Sample records for constitutively high levels

  1. Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity.

    PubMed

    Germain, Natacha; Viltart, Odile; Loyens, Anne; Bruchet, Céline; Nadin, Katia; Wolowczuk, Isabelle; Estour, Bruno; Galusca, Bogdan

    2016-01-01

    Interleukin-7 (IL-7) is a cytokine involved in energy homeostasis as demonstrated in rodents. Anorexia nervosa is characterized by restrained eating behavior despite adaptive orexigenic regulation profile including high ghrelin plasma levels. Constitutional thinness is a physiological condition of resistance to weight gain with physiological anorexigenic profile including high Peptide YY plasma level. Healthy obesity can be considered as a physiological state of resistance to weight loss with opposite appetite regulating profile to constitutional thinness including low Peptide YY plasma level. No studies in IL-7 are yet available in those populations. Therefore we evaluated circadian plasma levels of IL-7 in anorexia nervosa compared to constitutional thinness, healthy obese and control females. 10 restrictive-type anorexia nervosa women, 5 bingeing/purging anorexia nervosa woman, 5 recovered restrictive anorexia nervosa women, 4 bulimic females, 10 constitutional thinness women, 7 healthy obese females, and 10 normal weight women controls were enrolled in this cross-sectional study, performed in endocrinology unit and academic laboratory. Twelve-point circadian profiles of plasma IL-7 levels were measured in each subject. 24h mean IL-7 plasma levels (pg/ml, mean±SEM) were decreased in restrictive-type anorexia nervosa (123.4±14.4, p<0.0037), bingeing/purging anorexia nervosa (24.2±5.6, p<0.001), recovered restrictive anorexia nervosa (64.2±16.1, p = 0.01) and healthy obese patients (51±3.2, p<0.001) compared to controls (187.7±28.6). Bulimic patients (197.4±42.7) and constitutional thinness patients (264.3±35.8) were similar to controls. Low IL-7 is part of the adaptive profile in restrictive-type anorexia nervosa, confirming its difference with constitutional thinness. Healthy obesity, with low IL-7, is once again in mirror image of constitutional thinness with normal high IL-7.

  2. Antisense sequences of the nbl gene induce apoptosis in the human promyelocytic leukemia cell line HL-60.

    PubMed

    Naora, H; Nishida, T; Shindo, Y; Adachi, M; Naora, H

    1998-04-01

    Apoptosis is induced by the transcriptional inhibitor actinomycin D (Act D) in various cell types, particularly many leukemic cell lines such as HL-60. A common feature of these cell lines is their high constitutive expression level of the nbl gene, which was originally isolated by virtue of its abundance in a Namalwa Burkitt lymphoma cDNA library. In contrast, cell lines which constitutively express nbl at low levels appear not to undergo typical apoptotic death in response to Act D. Apoptotic induction by Act D in cells which normally express nbl at high levels was found in this study to be closely associated with a decline in nbl mRNA levels, raising the possibility that apoptosis could be induced by lowering nbl expression levels in such cells. Transient expression of nbl antisense sequences in HL-60 cells decreased cell viability, and induced typical apoptotic morphology such as cell shrinkage, chromatin condensation and nuclear fragmentation. Incubation with nbl antisense oligomers also induced similar features in HL-60 cells and in another high nb-expressing cell line, Jurkat, but had little effect in HepG2 cells which constitutively express nbl at low levels. These findings suggest that lowering constitutively high levels of nbl expression can induce apoptosis.

  3. Relationship between field resistance to Phytophthora ramorum and constitutive phenolic chemistry of coast live oak

    Treesearch

    A.M. Nagle; B.A. McPherson; D.L. Wood; M. Garbelotto; A.O. Conrad; S. Opiyo; P. Bonello

    2012-01-01

    Sudden oak death, caused by Phytophthora ramorum, has resulted in high levels of coast live oak (Quercus agrifolia Nee (CLO) mortality. However, some CLO survive in areas with high disease pressure and may thus be resistant. We tested the hypothesis that such field resistant trees contain constitutively higher levels of...

  4. We the People...The Citizen and the Constitution: Knowledge of and Support for Democratic Institutions and Processes by Participating Students. National Finals, 2000.

    ERIC Educational Resources Information Center

    Soule, Suzanne

    The "We the People...The Citizen and the Constitution" program is an instructional program on the history and principles of U.S. constitutional democracy for elementary, middle school, and high school students. At the high school level, classes may choose to enter a formal competition, advancing from congressional district and state…

  5. "We the People... The Citizen and the Constitution": Knowledge of and Support for Democratic Institutions and Processes by Participating Students. National Finals 2001.

    ERIC Educational Resources Information Center

    Soule, Suzanne

    The "We the People... The Citizen and the Constitution" program is an instructional program on the history and principles of U.S. constitutional democracy for elementary, middle, and high school students. The program is based on curricular materials developed by the Center for Civic Education. At the high school level, classes may choose…

  6. Judicious Discipline: A Constitutional Approach for Public High Schools.

    ERIC Educational Resources Information Center

    Grandmont, Richard P.

    2003-01-01

    Examines the practices in a large public high school where constitutional language and democratic citizenship education--judicious discipline--are introduced into the decision-making processes of the classroom. Data analysis suggests that a considerable number of students felt they possessed a high level of respect and responsibility as a result.…

  7. Detection of receptor ligands by monitoring selective stabilization of a Renilla luciferase-tagged, constitutively active mutant, G-protein-coupled receptor

    PubMed Central

    Ramsay, Douglas; Bevan, Nicola; Rees, Stephen; Milligan, Graeme

    2001-01-01

    The wild-type β2-adrenoceptor and a constitutively active mutant of this receptor were C-terminally tagged with luciferase from the sea pansy Renilla reniformis. C-terminal addition of Renilla luciferase did not substantially alter the levels of expression of either form of the receptor, the elevated constitutive activity of the mutant β2-adrenoceptor nor the capacity of isoprenaline to elevate cyclic AMP levels in intact cells expressing these constructs. Treatment of cells expressing constitutively active mutant β2-adrenoceptor-Renilla luciferase with antagonist/inverse agonist ligands resulted in upregulation of levels of this polypeptide which could be monitored by the elevated luciferase activity. The pEC50 for ligand-induced luciferase upregulation and ligand affinity to bind the receptor were highly correlated. Similar upregulation could be observed following sustained treatment with agonist ligands. These effects were only observed at a constitutively active mutant of the β2-adrenoceptor. Co-expression of the wild-type β2-adrenoceptor C-terminally tagged with the luciferase from Photinus pyralis did not result in ligand-induced upregulation of the levels of activity of this luciferase. Co-expression of the constitutively active mutant β2-adrenoceptor-Renilla luciferase and an equivalent mutant of the α1b-adrenoceptor C-terminally tagged with green fluorescent protein allowed pharmacological selectivity of adrenoceptor antagonists to be demonstrated. This approach offers a sensitive and convenient means, which is amenable to high throughput analysis, to monitor ligand binding to a constitutively active mutant receptor. As no prior knowledge of receptor ligands is required this approach may be suitable to identify ligands at orphan G protein-coupled receptors. PMID:11350868

  8. Underground herbivory and the costs of constitutive defense in tobacco

    NASA Astrophysics Data System (ADS)

    Preisser, Evan L.; Gibson, Sarah E.; Adler, Lynn S.; Lewis, Edwin E.

    2007-03-01

    Nicotine is both a constitutive and induced defense in cultivated tobacco ( Nicotiana tabacum). Nicotine is thought primarily to defend against above-ground herbivory; however, below-ground herbivores like the nematode Meloidogyne incognita can also damage plants. We evaluated the costs and benefits of constitutive nicotine production in four near-isogenic lines of N. tabacum differing in nicotine content. We exposed the four lines to levels of nematode infection below that found to induce nicotine synthesis, and measured nematode density and each line's response to nematode presence. Nematode density did not differ among lines and was not related to leaf nicotine content in any of the lines, suggesting that constitutive nicotine content did not affect nematode survival or reproduction. Most measures of plant performance were unaffected by nematodes; however, nematode infection decreased flowering in the high nicotine line relative to the other lines. Lines with less constitutive nicotine did not incur similar costs, suggesting a tradeoff between nicotine production and tolerance of low levels of herbivory. A cost of nicotine production is also suggested by the fact that flowering was inversely correlated with leaf nicotine content in all four lines. Although nicotine conferred no resistance to nematodes, high nicotine content reduced the plant's tolerance of low levels of nematode infection and was correlated with reduced flowering. In examining the costs and benefits of a constitutive plant defense, this work complements and extends previous research addressing the relationship between plant tolerance and induced defenses.

  9. A Drosophila heat shock response represents an exception rather than a rule amongst Diptera species.

    PubMed

    Zatsepina, O G; Przhiboro, A A; Yushenova, I A; Shilova, V; Zelentsova, E S; Shostak, N G; Evgen'ev, M B; Garbuz, D G

    2016-08-01

    Heat shock protein 70 (Hsp70) is the major player that underlies adaptive response to hyperthermia in all organisms studied to date. We investigated patterns of Hsp70 expression in larvae of dipteran species collected from natural populations of species belonging to four families from different evolutionary lineages of the order Diptera: Stratiomyidae, Tabanidae, Chironomidae and Ceratopogonidae. All investigated species showed a Hsp70 expression pattern that was different from the pattern in Drosophila. In contrast to Drosophila, all of the species in the families studied were characterized by high constitutive levels of Hsp70, which was more stable than that in Drosophila. When Stratiomyidae Hsp70 proteins were expressed in Drosophila cells, they became as short-lived as the endogenous Hsp70. Interestingly, three species of Ceratopogonidae and a cold-water species of Chironomidae exhibited high constitutive levels of Hsp70 mRNA and high basal levels of Hsp70. Furthermore, two species of Tabanidae were characterized by significant constitutive levels of Hsp70 and highly stable Hsp70 mRNA. In most cases, heat-resistant species were characterized by a higher basal level of Hsp70 than more thermosensitive species. These data suggest that different trends were realized during the evolution of the molecular mechanisms underlying the regulation of the responses of Hsp70 genes to temperature fluctuations in the studied families. © 2016 The Royal Entomological Society.

  10. Thermoviscoplastic nonlinear constitutive relationships for structural analysis of high temperature metal matrix composites

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.; Hopkins, D. A.

    1985-01-01

    A set of thermoviscoplastic nonlinear constitutive relationships (1VP-NCR) is presented. The set was developed for application to high temperature metal matrix composites (HT-MMC) and is applicable to thermal and mechanical properties. Formulation of the TVP-NCR is based at the micromechanics level. The TVP-NCR are of simple form and readily integrated into nonlinear composite structural analysis. It is shown that the set of TVP-NCR is computationally effective. The set directly predicts complex materials behavior at all levels of the composite simulation, from the constituent materials, through the several levels of composite mechanics, and up to the global response of complex HT-MMC structural components.

  11. Heat-shock protein 70 (Hsp70) expression in four limpets of the genus Lottia: interspecific variation in constitutive and inducible synthesis correlates with in situ exposure to heat stress.

    PubMed

    Dong, Yunwei; Miller, Luke P; Sanders, Jon G; Somero, George N

    2008-10-01

    Limpets of the genus Lottia occupy a broad vertical distribution on wave-exposed rocky shores, a range that encompasses gradients in the frequency and severity of thermal and desiccation stress brought on by aerial emersion. Using western blot analysis of levels of heat-shock protein 70 (Hsp70), we examined the heat-shock responses of four Lottia congeners: Lottia scabra and L. austrodigitalis, which occur in the high-intertidal zone, and L. pelta and L. scutum, which are restricted to the low- and mid-intertidal zones. Our results suggest distinct strategies of Hsp70 expression in limpets occupying different heights and orientations in the rocky intertidal zone. In freshly field-collected animals and in specimens acclimated at ambient temperature ( approximately 14 degrees C) for 14 days, the two high-intertidal species had higher constitutive levels of Hsp70 than the low- and mid-intertidal species. During aerial exposure to high temperatures, the two low-shore species and L. austrodigitalis exhibited an onset of Hsp70 expression at 28 degrees C; no induction of Hsp70 occurred in L. scabra. Our findings suggest that high-intertidal congeners of Lottia employ a "preparative defense" strategy involving maintenance of high constitutive levels of Hsp70 in their cells as a mechanism for protection against periods of extreme and unpredictable heat stress.

  12. Calculus Expectations: Comparisons by High School and College Faculty of What Constitutes Adequate Preparation

    ERIC Educational Resources Information Center

    Stroumbakis, Konstantinos

    2010-01-01

    Completion of higher level high school mathematics courses need not translate to success in introductory college level mathematics courses, which, in turn, may contribute to attrition from STEM programs. High school and college faculty rated online survey items, corresponding to content and pedagogy, with respect to importance for success in…

  13. Ionic regulation of the cardiac sodium-calcium exchanger.

    PubMed

    Reeves, John P; Condrescu, Madalina

    2008-01-01

    The Na(+)-Ca(2+) exchanger (NCX) links transmembrane movements of Ca(2+) ions to the reciprocal movement of Na(+) ions. It normally functions primarily as a Ca(2+) efflux mechanism in excitable tissues such as the heart, but it can also mediate Ca(2+) influx under certain conditions. Na(+) and Ca(2+) ions exert complex regulatory effects on NCX activity. Ca(2+) binds to two regulatory sites in the exchanger's central hydrophilic domain, and this interaction is normally essential for activation of exchange activity. High cytosolic Na(+) concentrations, however, can induce a constitutive activity that by-passes the need for allosteric Ca(2+) activation. Constitutive NCX activity can also be induced by high levels of phopshotidylinositol-4,5-bisphosphate (PIP₂) and by mutations affecting the regulatory calcium binding domains. In addition to promoting constitutive activity, high cytosolic Na(+) concentrations also induce an inactivated state of the exchanger (Na(+)-dependent inactivation) that becomes dominant when cytosolic pH and PIP₂ levels fall. Na(+)-dependent inactivation may provide a means of protecting cells from Ca(2+) overload due to NCX-mediated Ca(2+) influx during ischemia.

  14. Anthocyanin-rich Aronia melanocarpa extract improves body temperature maintenance in healthy women with a cold constitution.

    PubMed

    Sonoda, Keisuke; Aoi, Wataru; Iwata, Tomoaki; Li, Yanmei

    2013-01-01

    Specific anthocyanin-rich dietary factors have been shown to improve metabolic functions associated with thermogenesis in animal studies. Aronia melanocarpa, commonly known as wild chokeberry, contains a high level of anthocyanin that would be expected to maintain body temperature through thermogenesis. We here investigated the effects of Aronia melanocarpa extracts on body temperature and peripheral blood flow in healthy women with a cold constitution. A pre/post comparison trial was performed in 11 women with a cold constitution, who were taking Aronia melanocarpa extracts (150 mg/day) for 4 weeks. Physiological and biochemical parameters, along with psychological tests were examined. The subjects' body surface temperature was significantly higher in the post-trial than in the pre-trial. In psychological tests, factors related to cold were significantly improved by Aronia intake. On the other hand, peripheral blood flow was not affected by Aronia supplementation. Plasma noradrenalin level was significantly elevated by Aronia intake, and subjects with a higher level of 8-hydroxy-2'-deoxyguanosine in the pre-trial showed decreased levels in the post-trial. These data suggest that dietary Aronia melanocarpa extract improves the maintenance of body temperature in healthy women with a cold constitution, which may be mediated by noradrenalin and oxidative stress levels.

  15. A Study of the Environmental Risk Perceptions and Environmental Awareness Levels of High School Students

    ERIC Educational Resources Information Center

    Anilan, Burcu

    2014-01-01

    This descriptive research was conducted to determine the levels of environmental risk perceptions and environmental awareness of high school students in Eskisehir. High school students in the towns Tepebasi and Odunpazari in the 2010-2011 school years constitute the universe of the research. The sample of the research is composed of 413 high…

  16. Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice.

    PubMed

    Fernandez, Gimena; Cabral, Agustina; Andreoli, María F; Labarthe, Alexandra; M'Kadmi, Céline; Ramos, Jorge G; Marie, Jacky; Fehrentz, Jean-Alain; Epelbaum, Jacques; Tolle, Virginie; Perello, Mario

    2018-02-01

    Ghrelin is a potent orexigenic peptide hormone that acts through the growth hormone secretagogue receptor (GHSR), a G protein-coupled receptor highly expressed in the hypothalamus. In vitro studies have shown that GHSR displays a high constitutive activity, whose physiological relevance is uncertain. As GHSR gene expression in the hypothalamus is known to increase in fasting conditions, we tested the hypothesis that constitutive GHSR activity at the hypothalamic level drives the fasting-induced hyperphagia. We found that refed wild-type (WT) mice displayed a robust hyperphagia that continued for 5 days after refeeding and changed their food intake daily pattern. Fasted WT mice showed an increase in plasma ghrelin levels, as well as in GHSR expression levels and ghrelin binding sites in the hypothalamic arcuate nucleus. When fasting-refeeding responses were evaluated in ghrelin- or GHSR-deficient mice, only the latter displayed an ∼15% smaller hyperphagia, compared with WT mice. Finally, fasting-induced hyperphagia of WT mice was significantly smaller in mice centrally treated with the GHSR inverse agonist K-(D-1-Nal)-FwLL-NH2, compared with mice treated with vehicle, whereas it was unaffected in mice centrally treated with the GHSR antagonists D-Lys3-growth hormone-releasing peptide 6 or JMV2959. Taken together, genetic models and pharmacological results support the notion that constitutive GHSR activity modulates the magnitude of the compensatory hyperphagia triggered by fasting. Thus, the hypothalamic GHSR signaling system could affect the set point of daily food intake, independently of plasma ghrelin levels, in situations of negative energy balance. Copyright © 2018 Endocrine Society.

  17. Expression of endoglucanases in Pichia pastoris under control of the GAP promoter

    PubMed Central

    2014-01-01

    Background Plant-derived biomass is a potential alternative to fossil feedstocks for a greener economy. Enzymatic saccharification of biomass has been studied extensively and endoglucanases have been found to be a prerequisite for quick initial liquefaction of biomass under industrial conditions. Pichia pastoris, widely used for heterologous protein expression, can be utilized for fungal endoglucanase production. The recently marketed PichiaPink™ expression system allows for rapid clone selection, and employs the methanol inducible AOX1 promoter to ensure high protein expression levels. However, methanol is toxic and poses a fire hazard, issues which become more significant at an industrial scale. It is possible to eliminate these risks and still maintain high productivity by switching to the constitutive GAP promoter. Results In the present study, a plasmid carrying the constitutive GAP promoter was created for PichiaPink™. We then studied expression of two endoglucanases, AfCel12A from Aspergillus fumigatus and TaCel5A from Thermoascus aurantiacus, regulated by either the AOX1 promoter or the GAP promoter. Initial experiments in tubes and small bioreactors showed that the levels of AfCel12A obtained with the constitutive promoter were similar or higher, compared to the AOX1 promoter, whereas the levels of TaCel5A were somewhat lower. After optimization of cultivation conditions using a 15-l bioreactor, the recombinant P. pastoris strains utilizing the GAP promoter produced ca. 3–5 g/l of total secreted protein, with CMCase activity equivalent to 1200 nkat/ml AfCel12A and 170 nkat/ml TaCel5A. Conclusions We present a strategy for constitutive recombinant protein expression in the novel PichiaPink™ system. Both AfCel12A and TaCel5A were successfully expressed constitutively in P. pastoris under the GAP promoter. Reasonable protein levels were reached after optimizing cultivation conditions. PMID:24742273

  18. Expression of endoglucanases in Pichia pastoris under control of the GAP promoter.

    PubMed

    Várnai, Anikó; Tang, Campbell; Bengtsson, Oskar; Atterton, Andrew; Mathiesen, Geir; Eijsink, Vincent G H

    2014-04-18

    Plant-derived biomass is a potential alternative to fossil feedstocks for a greener economy. Enzymatic saccharification of biomass has been studied extensively and endoglucanases have been found to be a prerequisite for quick initial liquefaction of biomass under industrial conditions. Pichia pastoris, widely used for heterologous protein expression, can be utilized for fungal endoglucanase production. The recently marketed PichiaPink™ expression system allows for rapid clone selection, and employs the methanol inducible AOX1 promoter to ensure high protein expression levels. However, methanol is toxic and poses a fire hazard, issues which become more significant at an industrial scale. It is possible to eliminate these risks and still maintain high productivity by switching to the constitutive GAP promoter. In the present study, a plasmid carrying the constitutive GAP promoter was created for PichiaPink™. We then studied expression of two endoglucanases, AfCel12A from Aspergillus fumigatus and TaCel5A from Thermoascus aurantiacus, regulated by either the AOX1 promoter or the GAP promoter. Initial experiments in tubes and small bioreactors showed that the levels of AfCel12A obtained with the constitutive promoter were similar or higher, compared to the AOX1 promoter, whereas the levels of TaCel5A were somewhat lower. After optimization of cultivation conditions using a 15-l bioreactor, the recombinant P. pastoris strains utilizing the GAP promoter produced ca. 3-5 g/l of total secreted protein, with CMCase activity equivalent to 1200 nkat/ml AfCel12A and 170 nkat/ml TaCel5A. We present a strategy for constitutive recombinant protein expression in the novel PichiaPink™ system. Both AfCel12A and TaCel5A were successfully expressed constitutively in P. pastoris under the GAP promoter. Reasonable protein levels were reached after optimizing cultivation conditions.

  19. Petunia Floral Defensins with Unique Prodomains as Novel Candidates for Development of Fusarium Wilt Resistance in Transgenic Banana Plants

    PubMed Central

    Ghag, Siddhesh B.; Shekhawat, Upendra K. Singh; Ganapathi, Thumballi R.

    2012-01-01

    Antimicrobial peptides are a potent group of defense active molecules that have been utilized in developing resistance against a multitude of plant pathogens. Floral defensins constitute a group of cysteine-rich peptides showing potent growth inhibition of pathogenic filamentous fungi especially Fusarium oxysporum in vitro. Full length genes coding for two Petunia floral defensins, PhDef1 and PhDef2 having unique C- terminal 31 and 27 amino acid long predicted prodomains, were overexpressed in transgenic banana plants using embryogenic cells as explants for Agrobacterium–mediated genetic transformation. High level constitutive expression of these defensins in elite banana cv. Rasthali led to significant resistance against infection of Fusarium oxysporum f. sp. cubense as shown by in vitro and ex vivo bioassay studies. Transgenic banana lines expressing either of the two defensins were clearly less chlorotic and had significantly less infestation and discoloration in the vital corm region of the plant as compared to untransformed controls. Transgenic banana plants expressing high level of full-length PhDef1 and PhDef2 were phenotypically normal and no stunting was observed. In conclusion, our results suggest that high-level constitutive expression of floral defensins having distinctive prodomains is an efficient strategy for development of fungal resistance in economically important fruit crops like banana. PMID:22745785

  20. Constitutive Overexpression of Human Erythropoietin Protects the Mouse Retina against Induced But Not Inherited Retinal Degeneration

    PubMed Central

    Grimm, Christian; Wenzel, Andreas; Stanescu, Dinu; Samardzija, Marijana; Hotop, Svenja; Groszer, Mathias; Naash, Muna; Gassmann, Max; Remé, Charlotte

    2010-01-01

    Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application of recombinant human Epo (huEpo) protects the mouse retina against light-induced degeneration by inhibiting photoreceptor cell apoptosis. Because photoreceptor apoptosis is also the common path to cell loss in retinal dystrophies such as retinitis pigmentosa (RP), we tested whether high levels of huEpo would reduce apoptotic cell death in two mouse models of human RP. We combined the two respective mutant mouse lines with a transgenic line (tg6) that constitutively overexpresses huEpo mainly in neural tissues. Transgenic expression of huEpo caused constitutively high levels of Epo in the retina and protected photoreceptors against light-induced degeneration; however, the presence of high levels of huEpo did not affect the course or the extent of retinal degeneration in a light-independent (rd1) and a light-accelerated (VPP) mouse model of RP. Similarly, repetitive intraperitoneal injections of recombinant huEpo did not protect the retina in the rd1 and the VPP mouse. Lack of neuroprotection by Epo in the two models of inherited retinal degeneration was not caused by adaptational downregulation of Epo receptor. Our results suggest that apoptotic mechanisms during acute, light-induced photoreceptor cell death differ from those in genetically based retinal degeneration. Therapeutic intervention with cell death in inherited retinal degeneration may therefore require different drugs and treatments. PMID:15215287

  1. [Study on the distribution of Chinese medical constitutions of hypertension complicated diabetes patients].

    PubMed

    Han, Shu-Hui; Li, Kang-Zeng; Zheng, Jian-Ming; Zheng, Zhi-Xiong; Lin, Miao-Chun; Xu, Ming-Yuan; Yue, Zeng-Chang

    2013-02-01

    To investigate the distribution features of Chinese medical constitutions in hypertension complicated diabetes patients. Recruited were 251 primary hypertension inpatients at the Department of Neurology and the Department of Cardiology, Mindong Hospital of Ningde City from October 2010 to March 2011. They were assigned to two groups according to whether they were complicated with diabetes, i.e., the primary hypertension complicated diabetes (as the case group, 78 cases) and the primary hypertension without complicated diabetes (as the control group, 173 cases). The constitution types were investigated by questionnaire. The constitution type distribution was compared between the two groups. The data including gender, age, and the distribution of the constitution type were compared between the two groups. The levels of TG, TC, LDL-C, Hb, FPG, and ALB were detected on the 2nd day after admission. The levels of TG, TC, LDL-C, Hb, and ALB were compared be- tween the two groups in patients of yin deficiency constitution, phlegm dampness constitution, and qi deficiency constitution. There was no statistical difference in the hypertension grading, the disease course, and chronic disease complications between the two groups (P > 0.05). The main constitution types were yin deficiency (accounting for 26.0%), phlegm dampness (accounting for 19.1%), and qi deficiency (accounting for 19.1%) in the control group. The main constitution types were yin deficiency (accounting for 32.1%), phlegm dampness (accounting for 30.8%), and qi deficiency (accounting for 17.9%) in the case group. The ratio of phlegm dampness type in the case group was higher than that in the control group with statistical difference (P = 0.041). There was no statistical difference in the constitution distribution in the same gender between the two groups (P > 0.05). There was no statistical difference in the constitution distribution in those younger than 80 years between the two groups (P > 0.05). Compared with those older than 80 years in the control group, the ratio of phlegm dampness was higher, and the ratios of yang deficiency, yin deficiency, qi deficiency, and dampness heat were lower in the case group with statistical difference (P = 0.020). There was no statistical difference in the constitution distribution among different age stages in the case group (P > 0. 05). But there was statistical difference in the constitution distribution among different age stages in the control group (P < 0.05). The yin deficiency and qi deficiency constitutions were dominated in thinner patients of the control group, while yin deficiency constitution was dominated in thinner patients of the case group, showing no statistical difference between the two groups (P > 0.05). There was no statistical difference in the distribution of constitution type in overweight patients between the two groups (P = 0.458). Compared with those of gentle type constitution in the same group, the levels of TC and LDL-C increased in those of phlegm dampness constitution in the two groups (P < 0.05). The level of TC increased in those of qi deficiency constitution in the case group. The level of Hb decreased in those of qi deficiency constitution in the control group (P < 0.05). Compared with those of qi deficiency constitution in the same group, the levels of TC and Hb obviously increased in those of phlegm dampness constitution in the control group (P < 0.05). The level of ALB increased in those of yin deficiency constitution in the case group (P < 0. 05). Compared with the control group, the level of FPG of those of each constitution increased in the case group (P < 0.05) ,.and the level of TC increased in those of qi deficiency constitution (P = 0.007). The main constitution types of hypertension complicated diabetes patients were yin deficiency, phlegm dampness, and qi deficiency. The ratio of phlegm dampness was higher in hypertension complicated diabetes patients than hypertension without complicated diabetes patients. The levels of TC and LDL-C were higher in those of phlegm dampness constitution type. The level of TC was higher in hypertension complicated diabetes patients of qi deficiency constitution.

  2. Biaxial experiments supporting the development of constitutive theories for advanced high-temperature materials

    NASA Technical Reports Server (NTRS)

    Ellis, J. R.

    1988-01-01

    Complex states of stress and strain are introduced into components during service in engineering applications. It follows that analysis of such components requires material descriptions, or constitutive theories, which reflect the tensorial nature of stress and strain. For applications involving stress levels above yield, the situation is more complex in that material response is both nonlinear and history dependent. This has led to the development of viscoplastic constitutive theories which introduce time by expressing the flow and evolutionary equation in the form of time derivatives. Models were developed here which can be used to analyze high temperature components manufactured from advanced composite materials. In parallel with these studies, effort was directed at developing multiaxial testing techniques to verify the various theories. Recent progress in the development of constitutive theories from both the theoretical and experimental viewpoints are outlined. One important aspect is that material descriptions for advanced composite materials which can be implemented in general purpose finite element codes and used for practical design are verified.

  3. Human RON receptor tyrosine kinase induces complete epithelial-to-mesenchymal transition but causes cellular senescence

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

    Cote, Marceline; Miller, A. Dusty; Liu, Shan-Lu

    2007-08-17

    The RON receptor tyrosine kinase is a member of the MET proto-oncogene family and is important for cell proliferation, differentiation, and cancer development. Here, we created a series of Madin-Darby canine kidney (MDCK) epithelial cell clones that express different levels of RON, and have investigated their biological properties. While low levels of RON correlated with little morphological change in MDCK cells, high levels of RON expression constitutively led to morphological scattering or complete and stabilized epithelial-to-mesenchymal transition (EMT). Unexpectedly, MDCK clones expressing higher levels of RON exhibited retarded proliferation and senescence, despite increased motility and invasiveness. RON was constitutively tyrosine-phosphorylatedmore » in MDCK cells expressing high levels of RON and undergoing EMT, and the MAPK signaling pathway was activated. This study reveals for the first time that RON alone is sufficient to induce complete and stabilized EMT in MDCK cells, and overexpression of RON does not cause cell transformation but rather induces cell cycle arrest and senescence, leading to impaired cell proliferation.« less

  4. On finite element implementation and computational techniques for constitutive modeling of high temperature composites

    NASA Technical Reports Server (NTRS)

    Saleeb, A. F.; Chang, T. Y. P.; Wilt, T.; Iskovitz, I.

    1989-01-01

    The research work performed during the past year on finite element implementation and computational techniques pertaining to high temperature composites is outlined. In the present research, two main issues are addressed: efficient geometric modeling of composite structures and expedient numerical integration techniques dealing with constitutive rate equations. In the first issue, mixed finite elements for modeling laminated plates and shells were examined in terms of numerical accuracy, locking property and computational efficiency. Element applications include (currently available) linearly elastic analysis and future extension to material nonlinearity for damage predictions and large deformations. On the material level, various integration methods to integrate nonlinear constitutive rate equations for finite element implementation were studied. These include explicit, implicit and automatic subincrementing schemes. In all cases, examples are included to illustrate the numerical characteristics of various methods that were considered.

  5. Selection for low or high primary dormancy in Lolium rigidum Gaud seeds results in constitutive differences in stress protein expression and peroxidase activity

    PubMed Central

    Goggin, Danica E.; Powles, Stephen B.; Steadman, Kathryn J.

    2011-01-01

    Seed dormancy in wild Lolium rigidum Gaud (annual ryegrass) populations is highly variable and not well characterized at the biochemical level. To identify some of the determinants of dormancy level in these seeds, the proteomes of subpopulations selected for low and high levels of primary dormancy were compared by two-dimensional polyacrylamide gel electrophoresis of extracts from mature, dry seeds. High-dormancy seeds showed higher expression of small heat shock proteins, enolase, and glyoxalase I than the low-dormancy seeds. The functional relevance of these differences in protein expression was confirmed by the fact that high-dormancy seeds were more tolerant to high temperatures imposed at imbibition and had consistently higher glyoxalase I activity over 0–42 d dark stratification. Higher expression of a putative glutathione peroxidase in low-dormancy seeds was not accompanied by higher activity, but these seeds had a slightly more oxidized glutathione pool and higher total peroxidase activity. Overall, these biochemical and physiological differences suggest that L. rigidum seeds selected for low dormancy are more prepared for rapid germination via peroxidase-mediated cell wall weakening, whilst seeds selected for high dormancy are constitutively prepared to survive environmental stresses, even in the absence of stress during seed development. PMID:20974739

  6. Vectorized algorithms for spiking neural network simulation.

    PubMed

    Brette, Romain; Goodman, Dan F M

    2011-06-01

    High-level languages (Matlab, Python) are popular in neuroscience because they are flexible and accelerate development. However, for simulating spiking neural networks, the cost of interpretation is a bottleneck. We describe a set of algorithms to simulate large spiking neural networks efficiently with high-level languages using vector-based operations. These algorithms constitute the core of Brian, a spiking neural network simulator written in the Python language. Vectorized simulation makes it possible to combine the flexibility of high-level languages with the computational efficiency usually associated with compiled languages.

  7. The Effect of High-pressure Densification on Ballistic-penetration Resistance of a Soda-lime Glass

    DTIC Science & Technology

    2011-01-01

    equation of state and the strength constitutive laws of an existing material model for glass. This was fol- lowed by a set of transient non-linear... of irreversible densification. These relations are next used to upgrade the equation of state and the strength constitutive laws of an existing...its effect on the conti- nuum-level pressure versus degree- of -compression (the negative of volumetric strain) relation, also known as the

  8. Examining Gender Inequality in a High School Engineering Course

    ERIC Educational Resources Information Center

    Riegle-Crumb, Catherine; Moore, Chelsea

    2013-01-01

    This paper examines gender inequality within the context of an upper-level high school engineering course recently offered in Texas. Data was collected from six high schools that serve students from a variety of backgrounds. Among the almost two hundred students who enrolled in this challenge-based engineering course, females constituted a clear…

  9. Characterization of the mouse junD promoter--high basal level activity due to an octamer motif.

    PubMed Central

    de Groot, R P; Karperien, M; Pals, C; Kruijer, W

    1991-01-01

    The product of the junD gene belongs to the Jun/Fos family of nuclear DNA binding transcription factors. This family regulates the expression of TPA responsive genes by binding to the TPA responsive element (TRE). Unlike its counterparts c-jun and junB, junD expression is hardly inducible by growth factors and phorbol esters. In fact, junD is constitutively expressed at high levels in a wide variety of cells. To unravel the molecular mechanisms underlying constitutive junD expression, we have cloned and characterized the mouse junD promoter. We show that the high constitutive expression is caused by multiple cis-acting elements in its promoter, including an SP1 binding site, an octamer motif, a CAAT box, a Zif268 binding site and a TRE-like sequence. The octamer motif is the major determinant of junD promoter activity, while somewhat smaller contributions are made by the TRE and Zif268 binding site. The SP1 and CAAT box are shown to be of minor importance. The junD TRE is in its behavior indistinguishable from previously identified TREs. However, the junD promoter is not TPA inducible due to the presence of the octamer motif. Images PMID:1714380

  10. Transcription as a Threat to Genome Integrity.

    PubMed

    Gaillard, Hélène; Aguilera, Andrés

    2016-06-02

    Genomes undergo different types of sporadic alterations, including DNA damage, point mutations, and genome rearrangements, that constitute the basis for evolution. However, these changes may occur at high levels as a result of cell pathology and trigger genome instability, a hallmark of cancer and a number of genetic diseases. In the last two decades, evidence has accumulated that transcription constitutes an important natural source of DNA metabolic errors that can compromise the integrity of the genome. Transcription can create the conditions for high levels of mutations and recombination by its ability to open the DNA structure and remodel chromatin, making it more accessible to DNA insulting agents, and by its ability to become a barrier to DNA replication. Here we review the molecular basis of such events from a mechanistic perspective with particular emphasis on the role of transcription as a genome instability determinant.

  11. CHL1 is a dual-affinity nitrate transporter of Arabidopsis involved in multiple phases of nitrate uptake.

    PubMed Central

    Liu, K H; Huang, C Y; Tsay, Y F

    1999-01-01

    Higher plants have both high- and low-affinity nitrate uptake systems. These systems are generally thought to be genetically distinct. Here, we demonstrate that a well-known low-affinity nitrate uptake mutant of Arabidopsis, chl1, is also defective in high-affinity nitrate uptake. Two to 3 hr after nitrate induction, uptake activities of various chl1 mutants at 250 microM nitrate (a high-affinity concentration) were only 18 to 30% of those of wild-type plants. In these mutants, both the inducible phase and the constitutive phase of high-affinity nitrate uptake activities were reduced, with the inducible phase being severely reduced. Expressing a CHL1 cDNA driven by the cauliflower mosaic virus 35S promoter in a transgenic chl1 plant effectively recovered the defect in high-affinity uptake for the constitutive phase but not for the induced phase, which is consistent with the constitutive level of CHL1 expression in the transgenic plant. Kinetic analysis of nitrate uptake by CHL1-injected Xenopus oocytes displayed a biphasic pattern with a Michaelis-Menten Km value of approximately 50 microM for the high-affinity phase and approximately 4 mM for the low-affinity phase. These results indicate that in addition to being a low-affinity nitrate transporter, as previously recognized, CHL1 is also involved in both the inducible and constitutive phases of high-affinity nitrate uptake in Arabidopsis. PMID:10330471

  12. Analytical modeling of structure-soil systems for lunar bases

    NASA Technical Reports Server (NTRS)

    Macari-Pasqualino, Jose Emir

    1989-01-01

    The study of the behavior of granular materials in a reduced gravity environment and under low effective stresses became a subject of great interest in the mid 1960's when NASA's Surveyor missions to the Moon began the first extraterrestrial investigation and it was found that Lunar soils exhibited properties quite unlike those on Earth. This subject gained interest during the years of the Apollo missions and more recently due to NASA's plans for future exploration and colonization of Moon and Mars. It has since been clear that a good understanding of the mechanical properties of granular materials under reduced gravity and at low effective stress levels is of paramount importance for the design and construction of surface and buried structures on these bodies. In order to achieve such an understanding it is desirable to develop a set of constitutive equations that describes the response of such materials as they are subjected to tractions and displacements. This presentation examines issues associated with conducting experiments on highly nonlinear granular materials under high and low effective stresses. The friction and dilatancy properties which affect the behavior of granular soils with low cohesion values are assessed. In order to simulate the highly nonlinear strength and stress-strain behavior of soils at low as well as high effective stresses, a versatile isotropic, pressure sensitive, third stress invariant dependent, cone-cap elasto-plastic constitutive model was proposed. The integration of the constitutive relations is performed via a fully implicit Backward Euler technique known as the Closest Point Projection Method. The model was implemented into a finite element code in order to study nonlinear boundary value problems associated with homogeneous as well as nonhomogeneous deformations at low as well as high effective stresses. The effect of gravity (self-weight) on the stress-strain-strength response of these materials is evaluated. The calibration of the model is performed via three techniques: (1) physical identification, (2) optimized calibration at the constitutive level, and (3) optimized calibration at the finite element level (Inverse Identification). Activities are summarized in graphic and outline form.

  13. Constitutive expression of human pancreatic lipase-related protein 1 in Pichia pastoris.

    PubMed

    Aloulou, Ahmed; Grandval, Philippe; De Caro, Josiane; De Caro, Alain; Carrière, Frédéric

    2006-06-01

    High-level constitutive expression of the human pancreatic lipase-related protein 1 (HPLRP1) was achieved using the methylotrophic yeast Pichia pastoris. The HPLRP1 cDNA, including its original leader sequence, was subcloned into the pGAPZB vector and further integrated into the genome of P. pastoris X-33 under the control of the glyceraldehyde 3-phosphate dehydrogenase (GAP) constitutive promoter. A major protein with a molecular mass of 50 kDa was found to be secreted into the culture medium and was identified using anti-HPLRP1 polyclonal antibodies as HPLRP1 recombinant protein. The level of expression reached 100-120 mg of HPLRP1 per liter of culture medium after 40 h, as attested by specific and quantitative enzyme-linked immunosorbent assay. A single cation-exchange chromatography sufficed to obtain a highly purified recombinant HPLRP1 after direct batch adsorption onto S-Sepharose of the HPLRP1 present in the culture medium, at pH 5.5. N-terminal sequencing and mass spectrometry analysis were carried out to monitor the production of the mature protein and to confirm that its signal peptide was properly processed.

  14. Expression of endothelin-1 and constitutional nitric oxide synthase messenger RNA in saphenous vein endothelial cells exposed to arterial flow shear stress.

    PubMed

    Zhu, Z G; Li, H H; Zhang, B R

    1997-11-01

    It has long been speculated that increased blood flow shear stress might be one of the major factors affecting the patency of grafted saphenous vein in coronary artery bypass operations. The underlying cellular and molecular mechanisms for so-called "shear stress damage" have not yet been well elucidated. Endothelial cells harvested from human saphenous vein were cultured in vitro and then exposed to a high arterial level flow shear stress in the parallel flow chamber. The expression levels of endothelin-1 and constitutional nitric oxide synthase by the endothelial cells were evaluated semiquantitatively at the gene transcription (messenger RNA) level using reverse transcription polymerase chain reaction. After 7 hours of exposure to arterial level shear stress, the expression of constitutional nitric oxide synthase messenger RNA by saphenous vein endothelial cells was significantly reduced, whereas the expression of endothelin-1 messenger RNA was substantially increased. These changes were more predominant at 24 hours. Arterial level flow shear stress could cause important changes in the gene transcription level in saphenous vein endothelial cells within a short period of time. The functional alterations of saphenous vein endothelial cells, as manifested by the increased expression of endothelin-1 and decreased expression of nitric oxide synthase messenger RNA, might play a crucial role in the vein graft remodeling process.

  15. Genetic loci associated with changes in lipid levels leading to constitution-based discrepancy in Koreans

    PubMed Central

    2014-01-01

    Background Abnormal lipid concentrations are risk factors for atherosclerosis and cardiovascular disease. The pathological susceptibility to cardiovascular disease risks such as metabolic syndrome, diabetes mellitus, hypertension, insulin resistance, and so on differs between Sasang constitutional types. Methods We used multiple regression analyses to study the association between lipid-related traits and genetic variants from several genome-wide association studies according to Sasang constitutional types, considering that the Tae-Eum (TE) has predominant cardiovascular risk. Results By analyzing 26 variants of 20 loci in two Korean populations (8,597 subjects), we found that 12 and 5 variants, respectively, were replicably associated with lipid levels and dyslipidemia risk. By analyzing TE and non-TE type (each 2,664 subjects) populations classified on the basis of Sasang constitutional medicine, we found that the minor allele effects of three variants enriched in TE type had a harmful influence on lipid risk (near apolipoprotein A-V (APOA5)-APOA4-APOC3-APOA1 on increased triglyceride: p = 8.90 × 10-11, in APOE-APOC1-APOC4 on increased low-density lipoprotein cholesterol: p = 1.63 × 10-5, and near endothelial lipase gene on decreased high-density lipoprotein cholesterol: p = 4.28 × 10-3), whereas those of three variants (near angiopoietin-like 3 gene, APOA5-APOA4-APOC3-APOA1, and near lipoprotein lipase gene on triglyceride and high-density lipoprotein cholesterol) associated in non-TE type had neutral influences because of a compensating effect. Conclusions These results implied that the minor allele effects of lipid-associated variants may predispose TE type subjects to high cardiovascular disease risk because of their genetic susceptibility to lipid-related disorders. PMID:25005712

  16. A synthetic promoter library for constitutive gene expression in Lactobacillus plantarum.

    PubMed

    Rud, Ida; Jensen, Peter Ruhdal; Naterstad, Kristine; Axelsson, Lars

    2006-04-01

    A synthetic promoter library (SPL) for Lactobacillus plantarum has been developed, which generalizes the approach for obtaining synthetic promoters. The consensus sequence, derived from rRNA promoters extracted from the L. plantarum WCFS1 genome, was kept constant, and the non-consensus sequences were randomized. Construction of the SPL was performed in a vector (pSIP409) previously developed for high-level, inducible gene expression in L. plantarum and Lactobacillus sakei. A wide range of promoter strengths was obtained with the approach, covering 3-4 logs of expression levels in small increments of activity. The SPL was evaluated for the ability to drive beta-glucuronidase (GusA) and aminopeptidase N (PepN) expression. Protein production from the synthetic promoters was constitutive, and the most potent promoters gave high protein production with levels comparable to those of native rRNA promoters, and production of PepN protein corresponding to approximately 10-15 % of the total cellular protein. High correlation was obtained between the activities of promoters when tested in L. sakei and L. plantarum, which indicates the potential of the SPL for other Lactobacillus species. The SPL enables fine-tuning of stable gene expression for various applications in L. plantarum.

  17. Nonlinear Constitutive Relations for High Temperature Application, 1984

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Nonlinear constitutive relations for high temperature applications were discussed. The state of the art in nonlinear constitutive modeling of high temperature materials was reviewed and the need for future research and development efforts in this area was identified. Considerable research efforts are urgently needed in the development of nonlinear constitutive relations for high temperature applications prompted by recent advances in high temperature materials technology and new demands on material and component performance. Topics discussed include: constitutive modeling, numerical methods, material testing, and structural applications.

  18. Need of The Ministry of Health in Federal Democratic Republic of Nepal.

    PubMed

    Regmi, K; Upadhyay, M; Tarin, E; Chand, P B; Uprety, S R; Lekhak, S C

    2017-01-01

    The constitution of Nepal provides appointing a council of ministers both at federal and provincial levels without defining portfolios. There is a political agreement that MOH will be retained at the federal level. This article draws evidences around the world to meet health needs of Nepalese, the role of provincial ministry of health and coordinating structure at district/local level. The constitution emphasises on health and pronounced in 46 articles which provides guidance for the creation of federalized governance levels at federal, provincial and local levels. Retaining ministry of health at federal level without creating devolved structure at province and local levels in health sector will create difficulty in translating the spirit of the constitution and may not be effective in addressing health issues nationally and meeting global achievements like SDGs. It is suggested to establish an elaborate health system accordingly in Nepal to ensure constitutional mandate of health as a basic human right.

  19. Cosmic Rays with Portable Geiger Counters: From Sea Level to Airplane Cruise Altitudes

    ERIC Educational Resources Information Center

    Blanco, Francesco; La Rocca, Paola; Riggi, Francesco

    2009-01-01

    Cosmic ray count rates with a set of portable Geiger counters were measured at different altitudes on the way to a mountain top and aboard an aircraft, between sea level and cruise altitude. Basic measurements may constitute an educational activity even with high school teams. For the understanding of the results obtained, simulations of extensive…

  20. Controversial constitutive TSHR activity: patients, physiology, and in vitro characterization.

    PubMed

    Huth, S; Jaeschke, H; Schaarschmidt, J; Paschke, R

    2014-06-01

    G protein-coupled receptors constitute a large family of transmembrane receptors, which activate cellular responses by signal transmission and regulation of second messenger metabolism after ligand binding. For several of these receptors it is known that they also signal ligand-independently. The G protein-coupled thyroid stimulating hormone receptor (TSHR) is characterized by a high level of constitutive activity in the wild type state. However, little is known yet concerning the physiological relevance of the constitutive wild type TSHR activity. Certainly, knowledge of the physiological relevance of constitutive wild type receptor activity is necessary to better understand thyroid physiology and it is a prerequisite for the development of better therapies for nonautoimmune hyperthyroidism and thyroid cancer. Based on a literature search regarding all published TSHR mutations, this review covers several mutations which are clearly associated with a hyperthyroidism-phenotype, but interestingly show a lack of constitutive activity determined by in vitro characterization. Possible reasons for the observed discrepancies between clinical phenotypes and in vitro characterization results for constitutive TSHR activity are reviewed. All current in vitro characterization methods for constitutive TSHR mutations are "preliminary attempts" and may well be revised by more comprehensive and even better approaches. However, a standardized approach for the determination of constitutive activity can help to identify TSHR mutations for which the investigation of additional signaling mechanisms would be most interesting to find explanations for the current clinical phenotype/in vitro discrepancies and thereby also define suitable methods to explore the physiological relevance of constitutive wild type TSHR activity. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Kant on biological teleology: Towards a two-level interpretation.

    PubMed

    Quarfood, Marcel

    2006-12-01

    According to Kant's Critique of the power of judgment, teleological considerations are unavoidable for conceptualizing organisms. Does this mean that teleology is more than merely heuristic? Kant stresses the regulative status of teleological attributions, but sometimes he seems to treat teleology as a constitutive condition for biology. To clarify this issue, the concept of natural purpose and its role for biology are examined. I suggest that the concept serves an identificatory function: it singles out objects as natural purposes, whereby the special science of biology is constituted. This relative constitutivity of teleology is explicated by means of a distinction of levels: on the object level of biological science, teleology is taken as constitutive, though it is merely regulative on the philosophical meta level. This distinction also concerns the place of Aristotelian teleology in Kant: on the object level, the Aristotelian view is accepted, whereas on the meta level, an agnostic stance is taken concerning teleology.

  2. High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells

    PubMed Central

    Daniel, Jewel; Coulter, Jonathan; Woo, Ju-Hyung; Wilsbach, Kathleen; Gabrielson, Edward

    2011-01-01

    Most human cancers are aneuploid and have chromosomal instability, which contrasts to the inability of human cells to normally tolerate aneuploidy. Noting that aneuploidy in human breast cancer correlates with increased expression levels of the Mps1 checkpoint gene, we investigated whether these high levels of Mps1 contribute to the ability of breast cancer cells to tolerate this aneuploidy. Reducing Mps1 levels in cultured human breast cancer cells by RNAi resulted in aberrant mitoses, induction of apoptosis, and decreased ability of human breast cancer cells to grow as xenografts in nude mice. Remarkably, breast cancer cells that survive reductions in levels of Mps1 have relatively less aneuploidy, as measured by copies of specific chromosomes, compared with cells that have constitutively high levels of Mps1. Thus, high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy. PMID:21402910

  3. High levels of the Mps1 checkpoint protein are protective of aneuploidy in breast cancer cells.

    PubMed

    Daniel, Jewel; Coulter, Jonathan; Woo, Ju-Hyung; Wilsbach, Kathleen; Gabrielson, Edward

    2011-03-29

    Most human cancers are aneuploid and have chromosomal instability, which contrasts to the inability of human cells to normally tolerate aneuploidy. Noting that aneuploidy in human breast cancer correlates with increased expression levels of the Mps1 checkpoint gene, we investigated whether these high levels of Mps1 contribute to the ability of breast cancer cells to tolerate this aneuploidy. Reducing Mps1 levels in cultured human breast cancer cells by RNAi resulted in aberrant mitoses, induction of apoptosis, and decreased ability of human breast cancer cells to grow as xenografts in nude mice. Remarkably, breast cancer cells that survive reductions in levels of Mps1 have relatively less aneuploidy, as measured by copies of specific chromosomes, compared with cells that have constitutively high levels of Mps1. Thus, high levels of Mps1 in breast cancer cells likely contribute to these cells tolerating aneuploidy.

  4. Making the Constitution Meaningful.

    ERIC Educational Resources Information Center

    Pelow, Randall A.

    1989-01-01

    Describes learning activities based on the U.S. Constitution that enhance higher level thinking skills in elementary students. One activity proposes a hypothetical constitutional amendment banning Saturday cartoons; a second taxes children's earnings; and other activities focus on dramatizing events surrounding the Constitutional Convention. (LS)

  5. Suggestion of new possibilities in approaching individual variability in appetite through constitutional typology: a pilot study

    PubMed Central

    2012-01-01

    Background Appetite is intricately connected to eating behaviors and shows a high individual variability. In an attempt to approach the problem of gut hormone profiles, appetite, and eating behaviors at the individual level, we have adopted a constitutional typing system widely used in traditional East-Asian medicine, the Sasang constitutional typology, in order to determine the individual variations in appetite, eating behavior, and weight change. Methods This pilot study was designed to investigate the variability of appetite among individuals by tracking the gut hormone patterns across different constitutional types. Pre- and post-prandial concentrations of anorectic (peptide YY (PYY), glucagon-like peptide 1 (GLP-1)) and orexigenic (active ghrelin) gut hormones were measured in healthy, normal-weight (18.5 kg/m2 ≤BMI <23 kg/m2) male subjects aged 20–35 (Soyang (SY) (n = 9), Taeeum (TE) (n = 9), and Soeum (SE) (n = 10) constitutional types). Results Significant differences were found only in the PYY concentrations across the three groups (p = 0.031). The PYY concentration peaked at 30-min post-prandial in the SE group and was significantly higher compared to the other two groups (p = 0.004). The GLP-1 concentration peaked at 15-min post-prandial in the SE group (not significant). The ghrelin levels at 30-min pre-prandial were relatively lower in the TE group compared to the other groups (not significant). Conclusions In conclusion, although with weak statistical power, meaningful gut hormone patterns specific to each constitutional type were discovered in this pilot study, which could offer a new method of approaching the problem of appetite and eating behavior from the angle of individual variability in appetite. PMID:22889232

  6. Constitutive and inducible resistance to Atherigona soccata (Diptera: Muscidae) in Sorghum bicolor.

    PubMed

    Chamarthi, Siva K; Vijay, Peter M; Sharma, Hari C; Narasu, Lakshmi M

    2012-06-01

    Host plant resistance is one of the important components for minimizing the losses because of sorghum shoot fly, Atherigona soccata (Diptera: Muscidae) attack. Therefore, we studied the constitutive and inducible biochemical mechanisms of resistance to A. soccata in a diverse array of sorghum genotypes to identify lines with diverse mechanisms of resistance to this insect. Fifteen sorghum genotypes with different levels of resistance to A. soccata were evaluated. Methanol extracts of 10-d old damaged and undamaged sorghum seedlings were subjected to high-performance liquid chromatography analysis. Association between peak areas of the identified and unidentified compounds with parameters measuring A. soccata resistance was determined through correlation analysis. Amounts of p-hydroxy benzaldehyde and the unidentified compounds at RTs 24.38 and 3.70 min were associated with susceptibility to A. soccata. Genotypes exhibiting resistance to A. soccata were placed in four groups, and the lines showing constitutive and/or induced resistance to A. soccata with different combinations of biochemical factors potentially could be used for increasing the levels of resistance to A. soccata in sorghum.

  7. Studies on the psychosomatic functioning of ill-health according to eastern and Western medicine. 2. Anxiety-affinitive constitution associated with qi, blood, and body fluid--diagnostic and therapeutic methods.

    PubMed

    Takeichi, M; Sato, T; Takefu, M

    1999-01-01

    The objective of this investigation was to identify characteristics of psychosomatic function in medical students (N = 62, mean age, 23.3, SD, 1.7 years) whose ill-health was related to unbalanced qi, blood, and body fluid, and to develop a diagnosis and treatment method for these conditions. Our study revealed complicated characteristics. At the psychological level, these characteristics are stress-related emotional disturbances, including anxiety, insomnia and anergy, and the lowering of social function. At the physiological level, these characteristics are associated with high complexity of fractal dimension of eye (horizontal) and respiratory (thoracic) movements correlated to STA1-trait anxiety. Thus, the three psychosomatic characteristics related to unbalanced qi, blood, and body fluid suggest the concept of an anxiety-affinitive constitution, also described as the equivalent of ill-health. This indicates that diagnosis and treatment of this type of constitution has the potential to be useful for both the prevention of stress-related and life-style disease, and the treatment of current disease.

  8. Specific heat determination of plant barrier lipophilic components: biological implications.

    PubMed

    Casado, C G; Heredia, A

    2001-04-02

    The specific heat of isolated plant cuticles and their corresponding cuticular waxes have been measured for the physiological temperature in the range of 273-318 K at regular intervals. C(p) values ranged from 1.5 up to 4 J K(-1) g(-1) indicating a high cohesion, at the molecular level, of the molecular lipophilic components that constitute the plant cuticle. Second order phase transitions around 293 K, assigned to the cuticular matrix mainly constituted of the biopolyester cutin, have been detected and measured. Ecophysiological and physical implications of these thermodynamic data are discussed.

  9. Numerical simulation of the force generated by a superelastic NiTi orthodontic archwire during tooth alignment phase: comparison between different constitutive models

    NASA Astrophysics Data System (ADS)

    Gannoun, M.; Laroussi Hellara, M.; Bouby, C.; Ben Zineb, T.; Bouraoui, T.

    2018-04-01

    Nickel Titanium (NiTi) Superelastic (SE) Shape Memory Alloys (SMAs) are widely considered for applications that need high reversible strain or high recovery forces. In particular, the SE SMAs present a high interest for biomedical applications such as endodontic and orthodontic apparatus. They are available in a large variety of archwires exerting continuum forces to ensure the dental displacement. The purpose of this study is to report the clinical implications of NiTi SE wires for dental treatment in a given configuration. Three main constitutive models of the literature (Lagoudas and Boyd 1996 Int. J. Plast. 12 805–842, Auricchio and Petrini 2004 Int. J. Numer. Meth. Engng. 61 807–836 and Chemisky et al 2011 Mech. Mater. 68 361–376) are considered for the finite element (FE) numerical simulations of the SMA archwires response. Tensile tests had been carried out in order to identify the material parameters of these constitutive models. The FE numerical study allowed to predict the dental displacement and its corresponding orthodontic force level exerted by the wire in similar conditions to those in the oral environment. This work allows to predict the orthodontic generated load by a NiTi SE archwire with a 0.64 × 0.46 mm2 rectangular cross section under prescribed thermomechanical conditions. The effect of the temperature and the alveolar bone stiffness on the orthodontic load level and the tooth displacement degree has been investigated. The performed numerical simulations demonstrate that the orthodontic load is sensitive to the displacement magnitude, to the tooth stiffness and to the temperature variations. The obtained forces applied continuously and at a constant level are within the acceptable orthodontic force level range. Some directives are therefore provided to help orthodontists to select the optimal archwire.

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

    Roy, Ram Vinod; Pratheeshkumar, Poyil; Son, Yong-O

    Hexavalent chromium (Cr(VI)) is classified as a human carcinogen. Cr(VI) has been associated with adenocarcinomas and squamous cell carcinoma of the lung. The present study shows that acute Cr(VI) treatment in human bronchial epithelial cells (BEAS-2B) increased inflammatory responses (TNF-α, COX-2, and NF-кB/p65) and expression of Nrf2. Cr(VI)-induced generation of reactive oxygen species (ROS) are responsible for increased inflammation. Despite the fact that Nrf2 is a master regulator of response to oxidative stress, silencing of Nrf2 in the acute Cr(VI) treatment had no effect on Cr(VI)-induced inflammation. In contrast, in Cr(VI)-transformed (CrT) cells, Nrf2 is constitutively activated. Knock-down of thismore » protein resulted in decreased inflammation, while silencing of SOD2 and CAT had no effect in the expression of these inflammatory proteins. Results obtained from the knock-down of Nrf2 in CrT cells are very different from the results obtained in the acute Cr(VI) treatment. In BEAS-2B cells, knock-down of Nrf2 had no effect in the inflammation levels, while in CrT cells a decrease in the expression of inflammation markers was observed. These results indicate that before transformation, ROS plays a critical role while Nrf2 not in Cr(VI)-induced inflammation, whereas after transformation (CrT cells), Nrf2 is constitutively activated and this protein maintains inflammation while ROS not. Constitutively high levels of Nrf2 in CrT binds to the promoter regions of COX-2 and TNF-α, leading to increased inflammation. Collectively, our results demonstrate that before cell transformation ROS are important in Cr(VI)-induced inflammation and after transformation a constitutively high level of Nrf2 is important. - Highlights: • Cr(VI)-induced ROS increased inflammation, while Nrf2 had no effect. • In the CrT cells knock-down of Nrf2 resulted in decreased inflammation. • Mechanistic differences in regulating Cr(VI)-induced inflammation.« less

  11. Amino acids of Diclidophora merlangi (Monogenea).

    PubMed

    Arme, C; Whyte, A

    1975-02-01

    The level of free amino acids in Diclidophora merlangi is high, comprising over 500 mu moles/g ethanol extracted dry weight. A single amino acid, proline, constitutes some 70% of the total pool. Analysis of parasite protein and host blood and mucus revealed low proline levels, suggesting that the high free pool content was not related to a requirement for protein systhesis or to its abundance in the diet of the worm. Experiments revealed that proline was not involved specifically in osmoregulation, and the reasons for the large amounts present in Diclidophora remain unknown.

  12. Leadership: Underrepresentation of Women in Higher Education

    ERIC Educational Resources Information Center

    Krause, Susan Faye

    2017-01-01

    In 2014, statisticians at the Bureau of Labor Statistics found that women constitute 45% of the workforce. Women's participation in high-level organizational leadership roles remains low. In higher education, women's representation in top-ranking leadership roles is less than one-third at colleges and universities. The conceptual framework for…

  13. Professional Staff Carve out a New Space

    ERIC Educational Resources Information Center

    Szekeres, Judy

    2011-01-01

    A 2004 paper, "The invisible workers" by Szekeres, lamented the "invisibility" of professional staff in Australian higher education. Even then, professional staff constituted more than half the university workforce, but they were defined by what they were not (non-academic) and they experienced a high level of frustration in…

  14. Feminism, Budgeting and Gender Justice

    ERIC Educational Resources Information Center

    Misra, S. N.; Ghadai, Sanjaya Kumar

    2017-01-01

    The Fourth Conference on Women at Beijing (1995) underlined the importance of gender mainstreaming; spurring India to provide for separate Gender Budgeting in 2005-06. The Constitution tries to make fine balance between right to equality and positive discrimination for promoting gender justice in India. Yet high levels of Gender Inequality Index…

  15. Quality Measurement in Early Childhood Settings

    ERIC Educational Resources Information Center

    Zaslow, Martha, Ed.; Martinez-Beck, Ivelisse, Ed.; Tout, Kathryn, Ed.; Halle, Tamara, Ed.

    2011-01-01

    What constitutes quality in early childhood settings, and how can it best be measured with today's widely used tools and promising new approaches? Find authoritative answers in this book, a must-have for high-level administrators and policymakers as more and more states adopt early childhood Quality Rating and Improvement Systems. The most…

  16. Overexpression of pyruvate decarboxylase in the yeast Hansenula polymorpha results in increased ethanol yield in high-temperature fermentation of xylose.

    PubMed

    Ishchuk, Olena P; Voronovsky, Andriy Y; Stasyk, Oleh V; Gayda, Galina Z; Gonchar, Mykhailo V; Abbas, Charles A; Sibirny, Andriy A

    2008-11-01

    Improvement of xylose fermentation is of great importance to the fuel ethanol industry. The nonconventional thermotolerant yeast Hansenula polymorpha naturally ferments xylose to ethanol at high temperatures (48-50 degrees C). Introduction of a mutation that impairs ethanol reutilization in H. polymorpha led to an increase in ethanol yield from xylose. The native and heterologous (Kluyveromyces lactis) PDC1 genes coding for pyruvate decarboxylase were expressed at high levels in H. polymorpha under the control of the strong constitutive promoter of the glyceraldehyde-3-phosphate dehydrogenase gene (GAPDH). This resulted in increased pyruvate decarboxylase activity and improved ethanol production from xylose. The introduction of multiple copies of the H. polymorpha PDC1 gene driven by the strong constitutive promoter led to a 20-fold increase in pyruvate decarboxylase activity and up to a threefold elevation of ethanol production.

  17. Protein, carbohydrate, lipid concentrations and HSP 70-HSP 90 (stress protein) expression over an annual cycle: useful tools to detect feeding constraints in a benthic suspension feeder

    NASA Astrophysics Data System (ADS)

    Rossi, Sergio; Snyder, Mark J.; Gili, Josep-Marìa

    2006-03-01

    In the present paper we suggest an effect of seasonal variations in food availability on two ecophysiological parameters in a warm temperate benthic suspension feeder: the tissue concentrations of proteins, carbohydrates and lipids on the one hand, and the expression of stress proteins (HSP 70 and 90, inducible and/or constitutive) on the other hand. The concentrations of biomacromolecules have already been used to describe bentho-pelagic and reproductive processes, but this is the first time that stress protein expression is suggested to be directly related with food constraints in marine organisms. Paramuricea clavata (Cnidaria: Gorgonacea) express HSP 70 and 90 (constitutive and/or inducible) throughout the seasonal cycle, and HSP 70 levels are twice as high as the levels of HSP 90. In summer and autumn, when seston availability to suspension feeders was low, P. clavata showed low levels of carbohydrates and lipids, but high levels of HSPs expression. The levels of HSP 70 and 90 expression fit with negative exponential functions of carbohydrate and lipid concentrations. We suggest a direct effect of food availability on the studied ecophysiological parameters while the effect of temperature may be rather indirect. HSP expression as well as the tissue concentrations of carbohydrate and lipids may be used as biomarkers of environmental changes and seston availability to benthic suspension feeders.

  18. Over-expression of LeNCED1 in tomato (Solanum lycopersicum L.) with the rbcS3C promoter allows recovery of lines that accumulate very high levels of abscisic acid and exhibit severe phenotypes.

    PubMed

    Tung, Swee Ang; Smeeton, Rachel; White, Charlotte A; Black, Colin R; Taylor, Ian B; Hilton, Howard W; Thompson, Andrew J

    2008-07-01

    Previous work where 9-cis-epoxycarotenoid dioxygenase (NCED) was over-expressed using the constitutive Gelvin Superpromoter resulted in mild increases in abscisic acid (ABA) accumulation, accompanied by stomatal closure and increased water-use efficiency (WUE), but with apparently little impact on long-term biomass production. However, one of the negative effects of the over-expression of NCED using constitutive promoters in tomato was increased seed dormancy. Here we report the use of the rbcS3C promoter, from a gene encoding the small subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), to drive LeNCED1 transgene expression in tomato in a light-responsive and circadian manner. In comparison to the constitutive promoter, the rbcS3C promoter allowed the generation of transgenic plants with much higher levels of ABA accumulation in leaves and sap, but the effect on seed dormancy was diminished. These plants displayed the expected reductions in stomatal conductance and CO(2) assimilation, but they also exhibited a severe set of symptoms that included perturbed cotyledon release from the testa, increased photobleaching in young seedlings, substantially reduced chlorophyll and carotenoid content, interveinal leaf flooding, and greatly reduced growth. These symptoms illustrate adverse consequences of long-term, very high ABA accumulation. Only more moderate increases in ABA biosynthesis are likely to be useful in the context of agriculture. Implications are discussed for the design of transgenic 'high ABA' plants that exhibit increased WUE but have minimal negative phenotypic effects.

  19. Constitutional rights to health, public health and medical care: the status of health protections in 191 countries.

    PubMed

    Heymann, Jody; Cassola, Adèle; Raub, Amy; Mishra, Lipi

    2013-07-01

    United Nations (UN) member states have universally recognised the right to health in international agreements, but protection of this right at the national level remains incomplete. This article examines the level and scope of constitutional protection of specific rights to public health and medical care, as well as the broad right to health. We analysed health rights in the constitutions of 191 UN countries in 2007 and 2011. We examined how rights protections varied across the year of constitutional adoption; national income group and region; and for vulnerable groups within each country. A minority of the countries guaranteed the rights to public health (14%), medical care (38%) and overall health (36%) in their constitutions in 2011. Free medical care was constitutionally protected in 9% of the countries. Thirteen per cent of the constitutions guaranteed children's right to health or medical care, 6% did so for persons with disabilities and 5% for each of the elderly and the socio-economically disadvantaged. Valuable next steps include regular monitoring of the national protection of health rights recognised in international agreements, analyses of the impact of health rights on health outcomes and longitudinal multi-level studies to assess whether specific formulations of the rights have greater impact.

  20. Magneto-transport properties of a random distribution of few-layer graphene patches

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

    Iacovella, Fabrice; Mitioglu, Anatolie; Pierre, Mathieu

    In this study, we address the electronic properties of conducting films constituted of an array of randomly distributed few layer graphene patches and investigate on their most salient galvanometric features in the moderate and extreme disordered limit. We demonstrate that, in annealed devices, the ambipolar behaviour and the onset of Landau level quantization in high magnetic field constitute robust hallmarks of few-layer graphene films. In the strong disorder limit, however, the magneto-transport properties are best described by a variable-range hopping behaviour. A large negative magneto-conductance is observed at the charge neutrality point, in consistency with localized transport regime.

  1. Biometrics between opacity and transparency.

    PubMed

    Gutwirth, Serge

    2007-01-01

    The overall aim of the democratic constitutional state is to protect a social order in which the individual liberty of the citizen is a major concern. As a consequence the democratic constitutional state should guarantee simultaneously and paradoxically a high level of individual freedom and an order in which such freedom is made possible and guaranteed. Biometrics provide a strong and expressive example both of the necessity to address the issue of opacity and transparency and the complexity of the process. Indeed, the large scale use of biometrics does not only question the position of the individual in society, but it also alters the architecture or nature of this society as such.

  2. Plasmodium yoelii yoelii 17XNL constitutively expressing GFP throughout the life cycle.

    PubMed

    Ono, Takeshi; Tadakuma, Takushi; Rodriguez, Ana

    2007-03-01

    Plasmodium yoelii is a rodent parasite commonly used as a model to study malaria infection. It is the preferred model parasite for liver-stage immunological studies and is also widely used to study hepatocyte, erythrocyte and mosquito infection. We have generated a P. yoelii yoelii 17XNL line that is stably transfected with the green fluorescent protein (gfp) gene. This parasite line constitutively expresses high levels of GFP during the complete parasite life cycle including liver, blood and mosquito stages. These fluorescent parasites can be used in combination with fluorescence activated cell sorting or live microscopy for a wide range of experimental applications.

  3. Testing phenotypic trade-offs in the chemical defence strategy of Scots pine under growth-limiting field conditions.

    PubMed

    Villari, Caterina; Faccoli, Massimo; Battisti, Andrea; Bonello, Pierluigi; Marini, Lorenzo

    2014-09-01

    Plants protect themselves from pathogens and herbivores through fine-tuned resource allocation, including trade-offs among resource investments to support constitutive and inducible defences. However, empirical research, especially concerning conifers growing under natural conditions, is still scarce. We investigated the complexity of constitutive and induced defences in a natural Scots pine (Pinus sylvestris L.) stand under growth-limiting conditions typical of alpine environments. Phenotypic trade-offs at three hierarchical levels were tested by investigating the behaviour of phenolic compounds and terpenoids of outer bark and phloem. We tested resource-derived phenotypic correlations between (i) constitutive and inducible defences vs tree ring growth, (ii) different constitutive defence metabolites and (iii) constitutive concentration and inducible variation of individual metabolites. Tree ring growth was positively correlated only with constitutive concentration of total terpenoids, and no overall phenotypic trade-offs between different constitutive defensive metabolites were found. At the lowest hierarchical level tested, i.e., at the level of relationship between constitutive and inducible variation of individual metabolites, we found that different compounds displayed different behaviours; we identified five different defensive metabolite response types, based on direction and strength of the response, regardless of tree age and growth rate. Therefore, under growth-limiting field conditions, Scots pine appears to utilize varied and complex outer bark and phloem defence chemistry, in which only part of the constitutive specialized metabolism is influenced by tree growth, and individual components do not appear to be expressed in a mutually exclusive manner in either constitutive or inducible metabolism. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1-dependent phosphorylation of Cdc28CDK1.

    PubMed

    Maya Miles, Douglas; Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel; Simon, Marie-Noelle; Chavez, Sebastian; Geli, Vincent

    2018-03-27

    Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1 WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28 CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones. © 2018, Maya Miles et al.

  5. High levels of histones promote whole-genome-duplications and trigger a Swe1WEE1-dependent phosphorylation of Cdc28CDK1

    PubMed Central

    Peñate, Xenia; Sanmartín Olmo, Trinidad; Jourquin, Frederic; Muñoz Centeno, Maria Cruz; Mendoza, Manuel; Simon, Marie-Noelle; Chavez, Sebastian

    2018-01-01

    Whole-genome duplications (WGDs) have played a central role in the evolution of genomes and constitute an important source of genome instability in cancer. Here, we show in Saccharomyces cerevisiae that abnormal accumulations of histones are sufficient to induce WGDs. Our results link these WGDs to a reduced incorporation of the histone variant H2A.Z to chromatin. Moreover, we show that high levels of histones promote Swe1WEE1 stabilisation thereby triggering the phosphorylation and inhibition of Cdc28CDK1 through a mechanism different of the canonical DNA damage response. Our results link high levels of histones to a specific type of genome instability that is quite frequently observed in cancer and uncovers a new mechanism that might be able to respond to high levels of histones. PMID:29580382

  6. Avian influenza virus wild bird surveillance in the Azov and Black Sea regions of Ukraine

    USDA-ARS?s Scientific Manuscript database

    The Azov and Black Sea basins are transcontinental migration routes of wild birds from Northern Asia and Europe to the Mediterranean, Africa and Southwest Asia. These regions constitute an area of transit, stops during migration, and nesting of many migratory bird species with a very high level of ...

  7. Assured Optimism in a Scottish Girls' School: Habitus and the (Re)production of Global Privilege

    ERIC Educational Resources Information Center

    Forbes, Joan; Lingard, Bob

    2015-01-01

    This paper examines how high levels of social-cultural connectedness and academic excellence, inflected by gender and social class, constitute a particular school habitus of "assured optimism" at an elite Scottish girls' school. In Bourdieuian terms, Dalrymple is a "forcing ground" for the "intense cultivation" of a…

  8. Relating Stress of Mothers of Children with Developmental Disabilities to Family-School Partnerships

    ERIC Educational Resources Information Center

    Burke, Meghan M.; Hodapp, Robert M.

    2014-01-01

    Although mothers of children with intellectual and developmental disabilities (IDD) experience high levels of stress and schools constitute an important resource, the relation remains unknown between maternal stress and educational services. Responding to a national, web-based survey, 965 mothers of students with disabilities completed a 163-item…

  9. Adopted Children: A Question of Identity

    ERIC Educational Resources Information Center

    Mahmood, Samina; Visser, John

    2015-01-01

    This article draws upon a study completed in a specific school in Bangalore where most children enter at the pre-school level and continue till high school. While the particular children in the study constitute a small number--four--it was observed that questions of identity mainly arose when they started questioning the circumstances behind their…

  10. Neutrophil hyper-responsiveness in periodontitis.

    PubMed

    Matthews, J B; Wright, H J; Roberts, A; Ling-Mountford, N; Cooper, P R; Chapple, I L C

    2007-08-01

    Peripheral neutrophil hyper-responsiveness in chronic periodontitis leads to excessive reactive oxygen species (ROS) production. We aimed to determine whether neutrophil hyper-responsiveness was constitutive or reactive, and to discover the effect of non-surgical therapy. Peripheral blood neutrophils from patients (n = 19), before and 3 months after therapy, and matched control individuals were Fc gamma-receptor-stimulated with/without priming with P. gingivalis and F. nucleatum. Total and extracellular ROS were determined by luminol/isoluminol chemiluminescence. The high total ROS generation of patients' neutrophils compared with that of control individuals (P = 0.016) continued at a reduced level post-therapy (P = 0.059). Reduced activity post-therapy was also seen with priming. Unstimulated total ROS levels did not differ between patients and control individuals before or after therapy. However, the high unstimulated, extracellular ROS production by patients' neutrophils compared with control individuals (P < 0.05) continued post-therapy and was unaffected by priming. Therapy reduced Fc gamma-receptor-stimulated total ROS production, but not unstimulated extracellular radical release, suggesting that constitutive and reactive mechanisms underlie neutrophil hyper-responsiveness.

  11. Impacts of fishing low-trophic level species on marine ecosystems.

    PubMed

    Smith, Anthony D M; Brown, Christopher J; Bulman, Catherine M; Fulton, Elizabeth A; Johnson, Penny; Kaplan, Isaac C; Lozano-Montes, Hector; Mackinson, Steven; Marzloff, Martin; Shannon, Lynne J; Shin, Yunne-Jai; Tam, Jorge

    2011-08-26

    Low-trophic level species account for more than 30% of global fisheries production and contribute substantially to global food security. We used a range of ecosystem models to explore the effects of fishing low-trophic level species on marine ecosystems, including marine mammals and seabirds, and on other commercially important species. In five well-studied ecosystems, we found that fishing these species at conventional maximum sustainable yield (MSY) levels can have large impacts on other parts of the ecosystem, particularly when they constitute a high proportion of the biomass in the ecosystem or are highly connected in the food web. Halving exploitation rates would result in much lower impacts on marine ecosystems while still achieving 80% of MSY.

  12. Constitutive expression, purification and characterisation of pectin methylesterase from Aspergillus niger in Pichia pastoris for potential application in the fruit juice industry.

    PubMed

    Jiang, Xiuping; Chen, Peng; Yin, Maolu; Yang, Qing

    2013-01-01

    Pectin methylesterase (PME) catalyses the hydrolysis of the methyl ester of pectin, yielding free carboxyl groups and methanol. PME is widely used in the food, cosmetic and pharmaceutical industries. PME from Aspergillus niger was constitutively expressed to a high level in the yeast Pichia pastoris. The recombinant PME was purified by a combination of ammonium sulfate fractionation and ion exchange chromatography, giving an overall yield of 28.0%. It appeared as a single band in sodium dodecyl sulfate polyacrylamide gel electrophoresis, with a molecular mass of about 45 kDa. Optimal activity of the enzyme occurred at a temperature of 50 °C and a pH of 4.7. The K(m), V(max) and k(cat) values of the enzyme with respect to pectin were 8.6 mmol L⁻¹ [Formula: See Text], 1.376 mmol min⁻¹ mg⁻¹ and 8.26 × 10² s⁻¹ respectively. Cations such as K⁺, Mg²⁺, Ni²⁺, Mn²⁺ and Co²⁺ slightly inhibited its activity, whereas Na⁺ had no effect. PME from A. niger was constitutively expressed to a high level in P. pastoris without methanol induction. The recombinant PME was purified and characterised and shown to be a good candidate for potential application in the fruit juice industry. Copyright © 2012 Society of Chemical Industry.

  13. Defense traits in the long-lived Great Basin bristlecone pine and resistance to the native herbivore mountain pine beetle.

    PubMed

    Bentz, Barbara J; Hood, Sharon M; Hansen, E Matthew; Vandygriff, James C; Mock, Karen E

    2017-01-01

    Mountain pine beetle (MPB, Dendroctonus ponderosae) is a significant mortality agent of Pinus, and climate-driven range expansion is occurring. Pinus defenses in recently invaded areas, including high elevations, are predicted to be lower than in areas with longer term MPB presence. MPB was recently observed in high-elevation forests of the Great Basin (GB) region, North America. Defense and susceptibility in two long-lived species, GB bristlecone pine (Pinus longaeva) and foxtail pine (P. balfouriana), are unclear, although they are sympatric with a common MPB host, limber pine (P. flexilis). We surveyed stands with sympatric GB bristlecone-limber pine and foxtail-limber pine to determine relative MPB attack susceptibility and constitutive defenses. MPB-caused mortality was extensive in limber, low in foxtail and absent in GB bristlecone pine. Defense traits, including constitutive monoterpenes, resin ducts and wood density, were higher in GB bristlecone and foxtail than in limber pine. GB bristlecone and foxtail pines have relatively high levels of constitutive defenses which make them less vulnerable to climate-driven MPB range expansion relative to other high-elevation pines. Long-term selective herbivore pressure and exaptation of traits for tree longevity are potential explanations, highlighting the complexity of predicting plant-insect interactions under climate change. No claim to original US Government works. New Phytologist © 2016 New Phytologist Trust.

  14. Living Democracy: How Constitution High School Molds Better Citizens

    ERIC Educational Resources Information Center

    Brasof, Marc

    2009-01-01

    Philadelphia's Constitution High School (CHS) is committed both to the theory of education for democracy, and to its practice, as reflected by a school constitution, student elections, town hall meetings, and active student participation in school government. As its name indicates, CHS is a theme-based high school that focuses on history,…

  15. Constitutively Activated STAT3 Frequently Coexpresses with Epidermal Growth Factor Receptor in High-Grade Gliomas and Targeting STAT3 Sensitizes Them to Iressa and Alkylators

    PubMed Central

    Lo, Hui-Wen; Cao, Xinyu; Zhu, Hu; Ali-Osman, Francis

    2009-01-01

    Purpose The goals of this study are to elucidate the relationship of the oncogenic transcription factor signal transducer and activator of transcription 3(STAT3) with glioma aggressiveness and to understand the role of high STAT3 activity in the resistance of malignant gliomas and medulloblastomas to chemotherapy. Experimental Design Immunohistochemical staining and biochemical methods were used to examine the extent of STAT3 activation and EGFR expression in primary specimens and cell lines, respectively. Cellular response to drug treatments was determined using cell cytotoxicity and clonogenic growth assays. Results We found STAT3 to be constitutively activated in 60% of primary high-grade/malignant gliomas and the extent of activation correlated positively with glioma grade. High levels of activated/phosphorylated STAT3 were also present in cultured human malignant glioma and medulloblastoma cells. Three STAT3-activating kinases, Janus-activated kinase 2 (JAK2), EGFR, and EGFRvIII, contributed to STAT3 activation. An inhibitor toJAK2/STAT3, JSI-124, significantly reduced expression of STAT3 target genes, suppressed cancer cell growth, and induced apoptosis. Furthermore, we found that STAT3 constitutive activation coexisted with EGFR expression in 27.2% of primary high-grade/malignant gliomas and such coexpression correlated positively with glioma grade. Combination of an anti-EGFR agent Iressa and a JAK2/STAT3 inhibitor synergistically suppressed STAT3 activation and potently killed glioblastoma cell lines that expressed EGFR or EGFRvIII. JSI-124 also sensitized malignant glioma and medulloblastoma cells to temozolomide, 1,3-bis(2-chloroethyl)-1-nitrosourea, and cisplatin in which a synergism existed between JSI-124 and cisplatin. Conclusion STAT3 constitutive activation, alone and in concurrence with EGFR expression, plays an important role in high-grade/malignant gliomas and targeting STAT3/JAK2 sensitizes these tumors to anti-EGFR and alkylating agents. PMID:18829483

  16. Biogeochemical Relationships of a Subtropical Dry Forest on Karst

    Treesearch

    E. Medina; E. Cuevas; H. Marcano-Vega; E. Meléndez-Ackerman; E.H. Helmer

    2017-01-01

    Tropical dry forests on calcareous substrate constitute the main vegetation cover in many islands of the Caribbean. Dry climate and nutrient scarcity in those environments are ideal to investigate the potential role of high levels of soil calcium (Ca) in regulating plant selection and productivity. We analyzed the elemental composition of soil, loose litter, and leaf...

  17. School Violence and Its Effect on the Constitutionality of Public School Uniform Policies.

    ERIC Educational Resources Information Center

    Starr, Jennifer

    2000-01-01

    The Arizona Court of Appeals, in the first court decision regarding public school uniform policies, held that mandatory school uniforms do not violate students' First Amendment rights. Discusses the Arizona decision and its effect on the structuring of school uniform policies and their potential successful institution at the high school level. (31…

  18. Teachers' Adoptation Level of Student Centered Education Approach

    ERIC Educational Resources Information Center

    Arseven, Zeynep; Sahin, Seyma; Kiliç, Abdurrahman

    2016-01-01

    The aim of this study is to identify how far the student centered education approach is applied in the primary, middle and high schools in Düzce. Explanatory design which is one type of mixed research methods and "sequential mixed methods sampling" were used in the study. 685 teachers constitute the research sample of the quantitative…

  19. Accommodating Ontologies to Biological Reality—Top-Level Categories of Cumulative-Constitutively Organized Material Entities

    PubMed Central

    Vogt, Lars; Grobe, Peter; Quast, Björn; Bartolomaeus, Thomas

    2012-01-01

    Background The Basic Formal Ontology (BFO) is a top-level formal foundational ontology for the biomedical domain. It has been developed with the purpose to serve as an ontologically consistent template for top-level categories of application oriented and domain reference ontologies within the Open Biological and Biomedical Ontologies Foundry (OBO). BFO is important for enabling OBO ontologies to facilitate in reliably communicating and managing data and metadata within and across biomedical databases. Following its intended single inheritance policy, BFO's three top-level categories of material entity (i.e. ‘object’, ‘fiat object part’, ‘object aggregate’) must be exhaustive and mutually disjoint. We have shown elsewhere that for accommodating all types of constitutively organized material entities, BFO must be extended by additional categories of material entity. Methodology/Principal Findings Unfortunately, most biomedical material entities are cumulative-constitutively organized. We show that even the extended BFO does not exhaustively cover cumulative-constitutively organized material entities. We provide examples from biology and everyday life that demonstrate the necessity for ‘portion of matter’ as another material building block. This implies the necessity for further extending BFO by ‘portion of matter’ as well as three additional categories that possess portions of matter as aggregate components. These extensions are necessary if the basic assumption that all parts that share the same granularity level exhaustively sum to the whole should also apply to cumulative-constitutively organized material entities. By suggesting a notion of granular representation we provide a way to maintain the single inheritance principle when dealing with cumulative-constitutively organized material entities. Conclusions/Significance We suggest to extend BFO to incorporate additional categories of material entity and to rearrange its top-level material entity taxonomy. With these additions and the notion of granular representation, BFO would exhaustively cover all top-level types of material entities that application oriented ontologies may use as templates, while still maintaining the single inheritance principle. PMID:22253856

  20. Serum Levels of Stress Hormones and Oxidative Stress Biomarkers Differ according to Sasang Constitutional Type

    PubMed Central

    Kim, Hyeong Geug; Kim, Yoon Jung; Ahn, Yo Chan

    2015-01-01

    Objectives. This study investigated whether Sasang constitutional type is associated with differences in the serum levels of stress hormones and oxidative stress. Methods. A total of 236 participants (77 males and 159 females) were enrolled. The serum levels of cortisol, adrenaline, reactive oxygen species (ROS), and malondialdehyde (MDA) were analyzed. Results. The distribution of Sasang constitutional types was as follows: Taeumin, 35.6%; Soumin, 33.0%; and Soyangin, 31.4%. The serum cortisol levels of Taeumin were significantly lower than Soumin (p < 0.1 in both sexes) and Soyangin (p < 0.05 in males and p < 0.1 in females). The adrenaline levels were also significantly lower in Taeumin than in Soumin (p < 0.05 in males and p < 0.1 in females) and Soyangin (p < 0.1 in males). Serum ROS levels were significantly higher in Soyangin than in Taeumin and Soumin (p < 0.05 in males), whereas MDA levels were significantly lower in Taeumin compared with Soumin and Soyangin (p < 0.05 in males and p < 0.1 in females). Conclusion. Taeumin type may tolerate psychological or oxidative stress better than other types, which suggests a biological mechanism to explain the different pathophysiological features of Sasang constitutional types. PMID:26539232

  1. Hierarchical Levels of Abilities That Constitute Fraction Understanding at Elementary School

    ERIC Educational Resources Information Center

    Nicolaou, Aristoklis A.; Pitta-Pantazi, Demetra

    2016-01-01

    This article examines whether the 7 abilities found in a previous study carried out by the authors to constitute fraction understanding of sixth grade elementary school students determine hierarchical levels of fraction understanding. The 7 abilities were as follows: (a) fraction recognition, (b) definitions and mathematical explanations for…

  2. We the People: Elementary Pre-Service Teachers and Constitutional Readability

    ERIC Educational Resources Information Center

    Meier, Lori T.; Keith, Karin J.; Dwyer, Edward J.

    2014-01-01

    In light of increasing mandates to incorporate close reading of primary source historical documents at the elementary level, this study explored the reading difficulty level of the US Constitution with preservice elementary teachers using a traditional cloze assessment procedure. While best practice pedagogy of social studies has long included…

  3. Assessing the influence of biogeographical region and phylogenetic history on chemical defences and herbivory in Quercus species.

    PubMed

    Moreira, Xoaquín; Abdala-Roberts, Luis; Galmán, Andrea; Francisco, Marta; Fuente, María de la; Butrón, Ana; Rasmann, Sergio

    2018-06-07

    Biogeographical factors and phylogenetic history are key determinants of inter-specific variation in plant defences. However, few studies have conducted broad-scale geographical comparisons of plant defences while controlling for phylogenetic relationships, and, in doing so, none have separated constitutive from induced defences. This gap has limited our understanding of how historical or large-scale processes mediate biogeographical patterns in plant defences since these may be contingent upon shared evolutionary history and phylogenetic constraints. We conducted a phylogenetically-controlled experiment testing for differences in constitutive leaf chemical defences and their inducibility between Palearctic and Nearctic oak species (Quercus, total 18 species). We induced defences in one-year old plants by inflicting damage by gypsy moth larvae (Lymantria dispar), estimated the amount of leaf area consumed, and quantified various groups of phenolic compounds. There was no detectable phylogenetic signal for constitutive or induced levels of most defensive traits except for constitutive condensed tannins, as well as no phylogenetic signal in leaf herbivory. We did, however, find marked differences in defence levels between oak species from each region: Palearctic species had higher levels of constitutive condensed tannins, but less constitutive lignins and less constitutive and induced hydrolysable tannins compared with Nearctic species. Additionally, Palearctic species had lower levels of leaf damage compared with Nearctic species. These differences in leaf damage, lignins and hydrolysable (but not condensed) tannins were lost after accounting for phylogeny, suggesting that geographical structuring of phylogenetic relationships mediated biogeographical differences in defences and herbivore resistance. Together, these findings suggest that historical processes and large-scale drivers have shaped differences in allocation to constitutive defences (and in turn resistance) between Palearctic and Nearctic oaks. Moreover, although evidence of phylogenetic conservatism in the studied traits is rather weak, shared evolutionary history appears to mediate some of these biogeographical patterns in allocation to chemical defences. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Ligands raise the constraint that limits constitutive activation in G protein-coupled opioid receptors.

    PubMed

    Vezzi, Vanessa; Onaran, H Ongun; Molinari, Paola; Guerrini, Remo; Balboni, Gianfranco; Calò, Girolamo; Costa, Tommaso

    2013-08-16

    Using a cell-free bioluminescence resonance energy transfer strategy we compared the levels of spontaneous and ligand-induced receptor-G protein coupling in δ (DOP) and μ (MOP) opioid receptors. In this assay GDP can suppress spontaneous coupling, thus allowing its quantification. The level of constitutive activity was 4-5 times greater at the DOP than at the MOP receptor. A series of opioid analogues with a common peptidomimetic scaffold displayed remarkable inversions of efficacy in the two receptors. Agonists that enhanced coupling above the low intrinsic level of the MOP receptor were inverse agonists in reducing the greater level of constitutive coupling of the DOP receptor. Yet the intrinsic activities of such ligands are identical when scaled over the GDP base line of both receptors. This pattern is in conflict with the predictions of the ternary complex model and the "two state" extensions. According to this theory, the order of spontaneous and ligand-induced coupling cannot be reversed if a shift of the equilibrium between active and inactive forms raises constitutive activation in one receptor type. We propose that constitutive activation results from a lessened intrinsic barrier that restrains spontaneous coupling. Any ligand, regardless of its efficacy, must enhance this constraint to stabilize the ligand-bound complexed form.

  5. Genetic identification of a gene involved in constitutive, high-affinity nitrate transport in higher plants.

    PubMed Central

    Wang, R; Crawford, N M

    1996-01-01

    Two mutations have been found in a gene (NRT2) of Arabidopsis thaliana that specifically impair constitutive, high-affinity nitrate uptake. These mutants were selected for resistance to 0.1 mM chlorate in the absence of nitrate. Progency from one of the backcrossed mutants showed no constitutive uptake of nitrate below 0.5 mM at pH 7.0 in liquid culture (that is, within 30 min of initial exposure to nitrate). All other uptake activities measured (high-affinity phosphate and sulfate uptake, inducible high-affinity nitrate uptake, and constitutive low-affinity nitrate uptake) were present or nearly normal in the backcrossed mutant. Electrophysiological analysis of individual root cells showed that the nrt2 mutant showed little response to 0.25 mM of nitrate, whereas NRT2 wild-type cells showed an initial depolarization followed by recovery. At 10 mM of nitrate both the mutant and wild-type cells displayed similar, strong electrical responses. These results indicate that NRT2 is a critical and perhaps necessary gene for constitutive, high-affinity nitrate uptake in Arabidopsis, but not for inducible, high-affinity nor constitutive, low-affinity nitrate uptake. Thus, these systems are genetically distinct. PMID:8799195

  6. The Art of Athlete Leadership: Identifying High-Quality Athlete Leadership at the Individual and Team Level Through Social Network Analysis.

    PubMed

    Fransen, Katrien; Van Puyenbroeck, Stef; Loughead, Todd M; Vanbeselaere, Norbert; De Cuyper, Bert; Vande Broek, Gert; Boen, Filip

    2015-06-01

    This research aimed to introduce social network analysis as a novel technique in sports teams to identify the attributes of high-quality athlete leadership, both at the individual and at the team level. Study 1 included 25 sports teams (N = 308 athletes) and focused on athletes' general leadership quality. Study 2 comprised 21 sports teams (N = 267 athletes) and focused on athletes' specific leadership quality as a task, motivational, social, and external leader. The extent to which athletes felt connected with their leader proved to be most predictive for athletes' perceptions of that leader's quality on each leadership role. Also at the team level, teams with higher athlete leadership quality were more strongly connected. We conclude that social network analysis constitutes a valuable tool to provide more insight in the attributes of high-quality leadership both at the individual and at the team level.

  7. Interspecific variation within the genus Asclepias in response to herbivory by a phloem-feeding insect herbivore.

    PubMed

    Zehnder, Caralyn B; Hunter, Mark D

    2007-11-01

    Induced plant responses to leaf-chewing insects have been well studied, but considerably less is known about the effects of phloem-feedings insects on induction. In a set of laboratory experiments, we examined density-dependent induction by the milkweed-oleander aphid, Aphis nerii, of putative defenses in four milkweed species (Asclepias incarnata, Asclepias syriaca, Asclepias tuberosa, and Asclepias viridis). We hypothesized that high aphid density would lead to increased cardenolide expression in species with low constitutive levels of cardenolides (e.g., A. tuberosa), but that there would be no induction in high constitutive cardenolide species (e.g., A. viridis). Based on previous studies, we did not expect cardenolide induction in A. incarnata. Contrary to our predictions, we observed feeding-induced declines of cardenolide concentrations in A. viridis. Cardenolide concentrations did not respond to aphid feeding in the other three milkweed species. Aphids also caused reductions in biomass accumulation by two of four Asclepias species, A. viridis and A. incarnata. High aphid density led to a decrease in A. viridis foliar nitrogen concentration. However, aphids had no effect on the defensive chemistry, growth, or nutritional quality of either A. syriaca or A. tuberosa. Our results highlight that congeneric plant species may respond differently to the same levels of herbivore damage.

  8. Access to water

    NASA Astrophysics Data System (ADS)

    Stein, Robyn; Niklaas, Lindie

    This paper will examine the legal implications of the South African Constitutional judgement of Government of the Republic of South Africa and others vs Grootboom and others (2001(1) SA 46 (CC)) in view of the developing debate on socio-economic rights under the constitution on the constitutional right of access to sufficient water. It will look at the manner in which effect is being given to this right at municipal level through the provision of free water and the constitutional implications of an adequate basic minimum level set by the State and local authorities. The paper will also explore the implications of relevant legislation, which enables local authorities to cut off water supplies as well as the implications of the Grootboom decision for communities facing water cut-offs.

  9. Constitutive models for static and dynamic response of geotechnical materials

    NASA Astrophysics Data System (ADS)

    Nemat-Nasser, S.

    1983-11-01

    The objective of this research program has been to develop realistic macroscopic constitutive relations which describe static and dynamic properties of geotechnical materials (soils and rocks). To this end a coordinated theoretical and experimental activity has been followed. The theoretical work includes a balanced combination of statistical microscopic (at the grain size level) modeling and a nonclassical elasto-plastic macroscopic formulation. The latter includes the effects of internal friction, plastic compressibility, and pressure sensitivity, as well as anisotropy which is commonly observed in geotechnical materials. The following specific goals have been sought: (1) to develop three-dimensional constitutive relations under ordinary or high pressures (such as those induced by blasting or tectonic forces which may cause a large amount of densification by relative motion and possible crushing of grains); and (2) to examine and characterize the behavior of saturated granular materials under dynamic loading. The latter item includes characterization of possible liquefaction and subsidence which may be induced in granular materials under confining pressure by ground vibration or passage of waves. The theoretical work has been carefully coordinated with key experiments in order to: (1) understand the basic physics of the process, both at macroscopic and microscopic levels; (2) to verify the corresponding theoretical predictions; and (3) to establish relevant material parameters.

  10. Analysing Teachers' Operations When Teaching Students: What Constitutes Scientific Theories?

    ERIC Educational Resources Information Center

    Holmqvist, Mona O.; Olander, Clas

    2017-01-01

    The aim of the study is to analyse teachers' efforts to develop secondary school students' knowledge and argumentation skills of what constitutes scientific theories. The analysis is based on Leontiev's three-level structure of activity (activity, action, and operation), as these levels correspond to the questions why, what, and how content is…

  11. Novel regulatory mechanisms for generation of the soluble leptin receptor: implications for leptin action.

    PubMed

    Schaab, Michael; Kausch, Henriette; Klammt, Juergen; Nowicki, Marcin; Anderegg, Ulf; Gebhardt, Rolf; Rose-John, Stefan; Scheller, Juergen; Thiery, Joachim; Kratzsch, Juergen

    2012-01-01

    The adipokine leptin realizes signal transduction via four different membrane-anchored leptin receptor (Ob-R) isoforms in humans. However, the amount of functionally active Ob-R is affected by constitutive shedding of the extracellular domain via a so far unknown mechanism. The product of the cleavage process the so-called soluble leptin receptor (sOb-R) is the main binding protein for leptin in human blood and modulates its bioavailability. sOb-R levels are differentially regulated in metabolic disorders like type 1 diabetes mellitus or obesity and can, therefore, enhance or reduce leptin sensitivity. To describe mechanisms of Ob-R cleavage and to investigate the functional significance of differential sOb-R levels we established a model of HEK293 cells transiently transfected with different human Ob-R isoforms. Using siRNA knockdown experiments we identified ADAM10 (A Disintegrin And Metalloproteinase 10) as a major protease for constitutive and activated Ob-R cleavage. Additionally, the induction of lipotoxicity and apoptosis led to enhanced shedding shown by increased levels of the soluble leptin receptor (sOb-R) in cell supernatants. Conversely, high leptin concentrations and ER stress reduced sOb-R levels. Decreased amounts of sOb-R due to ER stress were accompanied by impaired leptin signaling and reduced leptin binding. Lipotoxicity and apoptosis increased Ob-R cleavage via ADAM10-dependent mechanisms. In contrast high leptin levels and ER stress led to reduced sOb-R levels. While increased sOb-R concentrations seem to directly block leptin action, reduced amounts of sOb-R may reflect decreased membrane expression of Ob-R. These findings could explain changes of leptin sensitivity which are associated with variations of serum sOb-R levels in metabolic diseases.

  12. Novel Regulatory Mechanisms for Generation of the Soluble Leptin Receptor: Implications for Leptin Action

    PubMed Central

    Schaab, Michael; Kausch, Henriette; Klammt, Juergen; Nowicki, Marcin; Anderegg, Ulf; Gebhardt, Rolf; Rose-John, Stefan; Scheller, Juergen; Thiery, Joachim; Kratzsch, Juergen

    2012-01-01

    Background The adipokine leptin realizes signal transduction via four different membrane-anchored leptin receptor (Ob-R) isoforms in humans. However, the amount of functionally active Ob-R is affected by constitutive shedding of the extracellular domain via a so far unknown mechanism. The product of the cleavage process the so-called soluble leptin receptor (sOb-R) is the main binding protein for leptin in human blood and modulates its bioavailability. sOb-R levels are differentially regulated in metabolic disorders like type 1 diabetes mellitus or obesity and can, therefore, enhance or reduce leptin sensitivity. Methodology/Principal Findings To describe mechanisms of Ob-R cleavage and to investigate the functional significance of differential sOb-R levels we established a model of HEK293 cells transiently transfected with different human Ob-R isoforms. Using siRNA knockdown experiments we identified ADAM10 (A Disintegrin And Metalloproteinase 10) as a major protease for constitutive and activated Ob-R cleavage. Additionally, the induction of lipotoxicity and apoptosis led to enhanced shedding shown by increased levels of the soluble leptin receptor (sOb-R) in cell supernatants. Conversely, high leptin concentrations and ER stress reduced sOb-R levels. Decreased amounts of sOb-R due to ER stress were accompanied by impaired leptin signaling and reduced leptin binding. Conclusions Lipotoxicity and apoptosis increased Ob-R cleavage via ADAM10-dependent mechanisms. In contrast high leptin levels and ER stress led to reduced sOb-R levels. While increased sOb-R concentrations seem to directly block leptin action, reduced amounts of sOb-R may reflect decreased membrane expression of Ob-R. These findings could explain changes of leptin sensitivity which are associated with variations of serum sOb-R levels in metabolic diseases. PMID:22545089

  13. From Confederation to Constitution: 1781-1789.

    ERIC Educational Resources Information Center

    Urofsky, Melvin I.; Cox, Nancy

    Students should achieve a higher level of understanding and appreciation of the evolving nature of the U.S. Constitution and its relevance to contemporary societal issues by studying historical documents from the period of time between the Articles of Confederation and the Constitution. This document begins with a history of that period and of the…

  14. A Sequenced Instructional Program in Physical Education for the Handicapped, Phase III. Producing and Disseminating Demonstration Packages. Final Report.

    ERIC Educational Resources Information Center

    Carr, Dorothy B.; Avance, Lyonel D.

    Presented is a sequenced instructional program in physical education which constitutes the third of a three-phase, 4-year project, funded by Title III, for handicapped children, preschool through high school levels, in the Los Angeles Unified School District. Described are the project setting and the following accomplishments: a curriculum guide…

  15. Private v. Public Rights (Grade Level: High School, 9-12)

    ERIC Educational Resources Information Center

    Fieth, Stacie; Deason, Neil

    2005-01-01

    Designed for grades 9-12, this lesson plan aims to let students learn how the Fifth Amendment to the Constitution relates to private property and how the power of eminent domain was defined in a recent Supreme Court case. Students will review summaries from Kelo v. New London to gain a better understanding of the case, which dealt with the limits…

  16. Stigma to Sage: Learning and Teaching Safer Sex Practices Among Canadian Sex Trade Workers. NALL Working Paper.

    ERIC Educational Resources Information Center

    Meaghan, Diane

    A study interviewed 37 Canadian sex workers in 4 cities to determine how they acquire a working knowledge of safer sex practices and what that knowledge constituted. Findings indicated the vast majority exhibited high levels of knowledge and efficacy regarding safer sex practices; sex workers took the initiative to obtain information and engage in…

  17. Interspecific comparison of constitutive ash phloem phenolic chemistry reveals compounds unique to manchurian ash, a species resistant to emerald ash borer.

    PubMed

    Whitehill, Justin G A; Opiyo, Stephen O; Koch, Jennifer L; Herms, Daniel A; Cipollini, Donald F; Bonello, Pierluigi

    2012-05-01

    The emerald ash borer (Agrilus planipennis, EAB) is an invasive wood-borer indigenous to Asia and is responsible for widespread ash (Fraxinus spp.) mortality in the U.S. and Canada. Resistance and susceptibility to EAB varies among Fraxinus spp., which is a result of their co-evolutionary history with the pest. We characterized constitutive phenolic profiles and lignin levels in the phloem of green, white, black, blue, European, and Manchurian ash. Phloem was sampled twice during the growing season, coinciding with phenology of early and late instar EAB. We identified 66 metabolites that displayed a pattern of variation, which corresponded strongly with phylogeny. Previously identified lignans and lignan derivatives were confirmed to be unique to Manchurian ash, and may contribute to its high level of resistance to EAB. Other compounds that had been considered unique to Manchurian ash, including hydroxycoumarins and the phenylethanoids calceolarioside A and B, were detected in closely related, but susceptible species, and thus are unlikely to contribute to EAB resistance of Manchurian ash. The distinct phenolic profile of blue ash may contribute to its relatively high resistance to EAB.

  18. Immunological Control of Viral Infections in Bats and the Emergence of Viruses Highly Pathogenic to Humans

    PubMed Central

    Schountz, Tony; Baker, Michelle L.; Butler, John; Munster, Vincent

    2017-01-01

    Bats are reservoir hosts of many important viruses that cause substantial disease in humans, including coronaviruses, filoviruses, lyssaviruses, and henipaviruses. Other than the lyssaviruses, they do not appear to cause disease in the reservoir bats, thus an explanation for the dichotomous outcomes of infections of humans and bat reservoirs remains to be determined. Bats appear to have a few unusual features that may account for these differences, including evidence of constitutive interferon (IFN) activation and greater combinatorial diversity in immunoglobulin genes that do not undergo substantial affinity maturation. We propose these features may, in part, account for why bats can host these viruses without disease and how they may contribute to the highly pathogenic nature of bat-borne viruses after spillover into humans. Because of the constitutive IFN activity, bat-borne viruses may be shed at low levels from bat cells. With large naive antibody repertoires, bats may control the limited virus replication without the need for rapid affinity maturation, and this may explain why bats typically have low antibody titers to viruses. However, because bat viruses have evolved in high IFN environments, they have enhanced countermeasures against the IFN response. Thus, upon infection of human cells, where the IFN response is not constitutive, the viruses overwhelm the IFN response, leading to abundant virus replication and pathology. PMID:28959255

  19. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence.

    PubMed

    Meuleman, Wouter; Peric-Hupkes, Daan; Kind, Jop; Beaudry, Jean-Bernard; Pagie, Ludo; Kellis, Manolis; Reinders, Marcel; Wessels, Lodewyk; van Steensel, Bas

    2013-02-01

    In metazoans, the nuclear lamina is thought to play an important role in the spatial organization of interphase chromosomes, by providing anchoring sites for large genomic segments named lamina-associated domains (LADs). Some of these LADs are cell-type specific, while many others appear constitutively associated with the lamina. Constitutive LADs (cLADs) may contribute to a basal chromosome architecture. By comparison of mouse and human lamina interaction maps, we find that the sizes and genomic positions of cLADs are strongly conserved. Moreover, cLADs are depleted of synteny breakpoints, pointing to evolutionary selective pressure to keep cLADs intact. Paradoxically, the overall sequence conservation is low for cLADs. Instead, cLADs are universally characterized by long stretches of DNA of high A/T content. Cell-type specific LADs also tend to adhere to this "A/T rule" in embryonic stem cells, but not in differentiated cells. This suggests that the A/T rule represents a default positioning mechanism that is locally overruled during lineage commitment. Analysis of paralogs suggests that during evolution changes in A/T content have driven the relocation of genes to and from the nuclear lamina, in tight association with changes in expression level. Taken together, these results reveal that the spatial organization of mammalian genomes is highly conserved and tightly linked to local nucleotide composition.

  20. A Potential Function Derivation of a Constitutive Equation for Inelastic Material Response

    NASA Technical Reports Server (NTRS)

    Stouffer, D. C.; Elfoutouh, N. A.

    1983-01-01

    Physical and thermodynamic concepts are used to develop a potential function for application to high temperature polycrystalline material response. Inherent in the formulation is a differential relationship between the potential function and constitutive equation in terms of the state variables. Integration of the differential relationship produces a state variable evolution equation that requires specification of the initial value of the state variable and its time derivative. It is shown that the initial loading rate, which is directly related to the initial hardening rate, can significantly influence subsequent material response. This effect is consistent with observed material behavior on the macroscopic and microscopic levels, and may explain the wide scatter in response often found in creep testing.

  1. [Unusually high level of chromosome variability in cultured human peripheral blood lymphocytes].

    PubMed

    Bochkov, N P; Popova, N A; Katosova, L D; Iakovleva, Iu S; Nazarenko, S A; Vasil'eva, E O; Platonova, V I; Chebotarev, A N

    1999-06-01

    A cytogenetic examination carried out in the inhabitants of Seversk (Tomsk oblast) and workers of the Siberian chemical industrial complex (a complex of nuclear-chemical and fuel plants), living in the same town, revealed unusually high level of spontaneous chromosomal variability both in control and industrial groups (total irradiation doses 1.8 to 3.7 and 9.3 to 15.7 Gy, respectively). The frequencies of cells with chromosomal aberrations (estimated per 100 cells) in control and industrial groups were 4.69, 6.04, and 6.64, respectively, and the total number of aberrations constituted 6.93, 8.47 and 12.06, respectively. These frequencies were several times higher compared to the summarized literature data on the control levels. The high average aberration level was caused by the elevated proportion of chromatid-type aberrations and paired fragments. The reasons for this are unclear. The levels of radioactive background and chemical air pollution in the town were not increased.

  2. Nonlinear Constitutive Relations for High Temperature Applications, 1986

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The purpose of the symposium was to review the state-of-the-art in nonlinear constitutive modeling of high temperature materials for aeronautics applications and to identify the need for future research and development efforts in this area. Through this symposium, it was recognized that considerable research efforts are urgently needed in the development of nonlinear constitutive relations for high temperature applications. In the aerospace industry this need is further prompted by recent advances in high temperature materials technology and new demands on material and component performance.

  3. A constitutive model and numerical simulation of sintering processes at macroscopic level

    NASA Astrophysics Data System (ADS)

    Wawrzyk, Krzysztof; Kowalczyk, Piotr; Nosewicz, Szymon; Rojek, Jerzy

    2018-01-01

    This paper presents modelling of both single and double-phase powder sintering processes at the macroscopic level. In particular, its constitutive formulation, numerical implementation and numerical tests are described. The macroscopic constitutive model is based on the assumption that the sintered material is a continuous medium. The parameters of the constitutive model for material under sintering are determined by simulation of sintering at the microscopic level using a micro-scale model. Numerical tests were carried out for a cylindrical specimen under hydrostatic and uniaxial pressure. Results of macroscopic analysis are compared against the microscopic model results. Moreover, numerical simulations are validated by comparison with experimental results. The simulations and preparation of the model are carried out by Abaqus FEA - a software for finite element analysis and computer-aided engineering. A mechanical model is defined by the user procedure "Vumat" which is developed by the first author in Fortran programming language. Modelling presented in the paper can be used to optimize and to better understand the process.

  4. Constitutional dynamic chemistry: bridge from supramolecular chemistry to adaptive chemistry.

    PubMed

    Lehn, Jean-Marie

    2012-01-01

    Supramolecular chemistry aims at implementing highly complex chemical systems from molecular components held together by non-covalent intermolecular forces and effecting molecular recognition, catalysis and transport processes. A further step consists in the investigation of chemical systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined functional supramolecular architectures by self-assembly from their components, thus behaving as programmed chemical systems. Supramolecular chemistry is intrinsically a dynamic chemistry in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibility, so as to allow a continuous change in constitution by reorganization and exchange of building blocks. These features define a Constitutional Dynamic Chemistry (CDC) on both the molecular and supramolecular levels.CDC introduces a paradigm shift with respect to constitutionally static chemistry. The latter relies on design for the generation of a target entity, whereas CDC takes advantage of dynamic diversity to allow variation and selection. The implementation of selection in chemistry introduces a fundamental change in outlook. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization with selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation.The merging of the features: -information and programmability, -dynamics and reversibility, -constitution and structural diversity, points to the emergence of adaptive and evolutive chemistry, towards a chemistry of complex matter.

  5. Cell cycle, differentiation and tissue-independent expression of ribosomal protein L37.

    PubMed

    Su, S; Bird, R C

    1995-09-15

    A unique human cDNA (hG1.16) that encodes a mRNA of 450 nucleotides was isolated from a subtractive library derived from HeLa cells. The relative expression level of hG1.16 during different cell-cycle phases was determined by Northern-blot analysis of cells synchronized by double-thymidine block and serum deprivation/refeeding. hG1.16 was constitutively expressed during all phases of the cell cycle, including the quiescent phase when even most constitutively expressed genes experience some suppression of expression. The expression level of hG1.16 did not change during terminal differentiation of myoblasts to myotubes, during which cells become permanently post-mitotic. Examination of other tissues revealed that the relative expression level of hG1.16 was constitutive in all embryonic mouse tissues examined, including brain, eye, heart, kidney, liver, lung and skeletal muscle. This was unusual in that expression was not down-modulated during differentiation and did not vary appreciably between tissue types. Analysis by inter-species Northern-blot analysis revealed that hG1.16 was highly conserved among all vertebrates studied (from fish to humans but not in insects). DNA sequence analysis of hG1.16 revealed a high level of similarity to rat ribosomal protein L37, identifying hG1.16 as a new member of this multigene family. The deduced amino acid sequence of hG1.16 was identical to rat ribosomal protein L37 that contained 97 amino acids, many of which are highly positively charged (15 arginine and 14 lysine residues with a predicted M(r) of 11,065). hG1.16 protein has a single C2-C2 zinc-finger-like motif which is also present in rat ribosomal protein L37. Using primers designed from the sequence of hG1.16, unique bovine and rat cDNAs were also isolated by 5'-rapid-amplification of cDNA ends. DNA sequences of bovine and rat G1.16, clones were 92.8% and 92.2% similar to human G1.16 while the deduced amino acid sequences derived from bovine and rat cDNAs each differed by a single amino acid from the sequence of hG1.16 and the published rat L37 sequence. Southern-blot analysis revealed that hG1.16 exists in multiple copies in human, rat and mouse genomes. These G1.16 clones encode unique human, rat and bovine members of the ribosomal protein L37 gene family, which are constitutively expressed even during transitions from quiescence to active cell proliferation or terminal differentiation, in all tissues and all vertebrates investigated.

  6. Effects of nutrient availabiiity on biomass allocation as well as constitutive and rapid induced herbivore resistance in poplar

    Treesearch

    Carolyn Glynn; Daniel A. Herms; Marie Egawa; Robert Hansen; William J. Mattson

    2003-01-01

    Many studies have examined effects of nutrient availability on constitutive herbivore resistance of plants, but few have addressed effects on expression of rapid induced resistance (RIR). We quantified effects of two levels of nutrient availability on growth, biomass allocation, photosynthesis, and constitutive secondary metabolism of black poplar (>i>Populus...

  7. Forum: Reconsidering the Supreme Court's "Rodriguez" Decision--Is There a Federal Constitutional Right to Education?

    ERIC Educational Resources Information Center

    Ogletree, Charles J., Jr.; Robinson, Kimberly Jenkins; Lindseth, Alfred A.; Testani, Rocco E.; Peifer, Lee A.

    2017-01-01

    Does the U.S. Constitution guarantee a right to education? The Supreme Court declared that it does not in "San Antonio Independent School District v. Rodriguez," a 1973 case alleging that disparities in spending levels among Texas school districts violated students' constitutional rights. This issue's forum contains two essays. The first…

  8. Thermotolerant desert lizards characteristically differ in terms of heat-shock system regulation.

    PubMed

    Zatsepina, O G; Ulmasov, K A; Beresten, S F; Molodtsov, V B; Rybtsov, S A; Evgen'ev, M B

    2000-03-01

    We compare the properties and activation of heat-shock transcription factor (HSF1) and the synthesis of a major family of heat-shock proteins (HSP70) in lizard species inhabiting ecological niches with strikingly different thermal parameters. Under normal non-heat-shock conditions, all desert-dwelling lizard species studied so far differ from a northern, non-desert species (Lacerta vivipara) in the electrophoretic mobility and content of proteins constitutively bound to the regulatory heat-shock elements in the heat-shock gene promoter. Under these conditions, levels of activated HSF1 and of both HSP70 mRNA and protein are higher in the desert species than in the non-desert species. Upon heat shock, HSF1 aggregates in all species studied, although in desert species HSF1 subsequently disaggregates more rapidly. Cells of the northern species have a lower thermal threshold for HSP expression than those of the desert species, which correlates with the relatively low constitutive level of HSPs and high basal content of HSF1 in their cells.

  9. Quarantine in times of emergency: the scope of s 51(ix) of the Constitution.

    PubMed

    Reynolds, Christopher

    2004-11-01

    This article explores the scope of s 51(ix) of the Constitution, the power of the Commonwealth to make laws with respect to "quarantine". While this power has sustained the Quarantine Act without a challenge since 1908, it may be that future national public health emergencies, such as epidemics or bioterrorism, will (as has happened in other countries) demand a level of federal preparedness that requires augmented public health powers at a national level. If so, will the scope of the quarantine power, as determined by the High Court, be wide enough allow the Commonwealth to implement these powers? While there is some advantage in a national approach, there is also some authority suggesting that the quarantine power could not extend to domestic public health controls. If there is uncertainty about the scope of the power, what are the options? Should there be another approach, with the States, Territories and the Commonwealth moving towards uniform legislation and co-operative arrangements?

  10. Constitutive and damage material modeling in a high pressure hydrogen environment

    NASA Technical Reports Server (NTRS)

    Russell, D. A.; Fritzemeier, L. G.

    1991-01-01

    Numerous components in reusable space propulsion systems such as the SSME are exposed to high pressure gaseous hydrogen environments. Flow areas and passages in the fuel turbopump, fuel and oxidizer preburners, main combustion chamber, and injector assembly contain high pressure hydrogen either high in purity or as hydrogen rich steam. Accurate constitutive and damage material models applicable to high pressure hydrogen environments are therefore needed for engine design and analysis. Existing constitutive and cyclic crack initiation models were evaluated only for conditions of oxidizing environments. The main objective is to evaluate these models for applicability to high pressure hydrogen environments.

  11. Who Said Learning about the Constitution Isn't Fun? Active Lessons on the U.S. Constitution for Junior and Senior High School Students. Lessons created by participants at "Congress and the Constitution: A Summer Institute for Teachers" (Ontario, California, 1988).

    ERIC Educational Resources Information Center

    Cramer, Elizabeth, Ed.; Hill, Margaret, Ed.

    Twenty-eight lesson plans developed by California teachers who attended a summer institute on Congress and the Constitution are presented in this document. Sample lesson plan titles are: (1) "Geopolitics and the Constitution," (2) "Judicial Review," (3) "Electoral College and the Constitution," (4) "First…

  12. Introducing mixotrophy into a biogeochemical model describing an eutrophied coastal ecosystem: The Southern North Sea

    NASA Astrophysics Data System (ADS)

    Ghyoot, Caroline; Lancelot, Christiane; Flynn, Kevin J.; Mitra, Aditee; Gypens, Nathalie

    2017-09-01

    Most biogeochemical/ecological models divide planktonic protists between phototrophs (phytoplankton) and heterotrophs (zooplankton). However, a large number of planktonic protists are able to combine several mechanisms of carbon and nutrient acquisition. Not representing these multiple mechanisms in biogeochemical/ecological models describing eutrophied coastal ecosystems can potentially lead to different conclusions regarding ecosystem functioning, especially regarding the success of harmful algae, which are often reported as mixotrophic. This modelling study investigates the implications for trophic dynamics of including 3 contrasting forms of mixotrophy, namely osmotrophy (using alkaline phosphatase activity, APA), non-constitutive mixotrophy (acquired phototrophy by microzooplankton) and also constitutive mixotrophy. The application is in the Southern North Sea, an ecosystem that faced, between 1985 and 2005, a significant increase in the nutrient supply N:P ratio (from 31 to 81 mol N:P). The comparison with a traditional model shows that, when the winter N:P ratio in the Southern North Sea is above 22 molN molP-1 (as occurred from mid-1990s), APA allows a 3-32% increase of annual gross primary production (GPP). In result of the higher GPP, the annual sedimentation increases as well as the bacterial production. By contrast, APA does not affect the export of matter to higher trophic levels because the increased GPP is mainly due to Phaeocystis colonies, which are not grazed by copepods. Under high irradiance, non-constitutive mixotrophy appreciably increases annual GPP, transfer to higher trophic levels, sedimentation, and nutrient remineralisation. In this ecosystem, non-constitutive mixotrophy is also observed to have an indirect stimulating effect on diatoms. Constitutive mixotrophy in nanoflagellates appears to have little influence on this ecosystem functioning. An important conclusion from this work is that contrasting forms of mixotrophy have different impacts on system dynamics and, due to the complex interactions in the ecosystem, their combined effect is not exactly the addition of the effects individually observed. It is thus important to describe such contrasting forms in an appropriate fashion.

  13. Characterizing the constitutive response and energy absorption of rigid polymeric foams subjected to intermediate-velocity impact

    DOE PAGES

    Koohbor, Behrad; Kidane, Addis; Lu, Wei-Yang

    2016-06-27

    As an optimum energy-absorbing material system, polymeric foams are needed to dissipate the kinetic energy of an impact, while maintaining the impact force transferred to the protected object at a low level. As a result, it is crucial to accurately characterize the load bearing and energy dissipation performance of foams at high strain rate loading conditions. There are certain challenges faced in the accurate measurement of the deformation response of foams due to their low mechanical impedance. In the present work, a non-parametric method is successfully implemented to enable the accurate assessment of the compressive constitutive response of rigid polymericmore » foams subjected to impact loading conditions. The method is based on stereovision high speed photography in conjunction with 3D digital image correlation, and allows for accurate evaluation of inertia stresses developed within the specimen during deformation time. In conclusion, full-field distributions of stress, strain and strain rate are used to extract the local constitutive response of the material at any given location along the specimen axis. In addition, the effective energy absorbed by the material is calculated. Finally, results obtained from the proposed non-parametric analysis are compared with data obtained from conventional test procedures.« less

  14. LentiPro26: novel stable cell lines for constitutive lentiviral vector production.

    PubMed

    Tomás, H A; Rodrigues, A F; Carrondo, M J T; Coroadinha, A S

    2018-03-27

    Lentiviral vectors (LVs) are excellent tools to promote gene transfer and stable gene expression. Their potential has been already demonstrated in gene therapy clinical trials for the treatment of diverse disorders. For large scale LV production, a stable producer system is desirable since it allows scalable and cost-effective viral productions, with increased reproducibility and safety. However, the development of stable systems has been challenging and time-consuming, being the selection of cells presenting high expression levels of Gag-Pro-Pol polyprotein and the cytotoxicity associated with some viral components, the main limitations. Hereby is described the establishment of a new LV producer cell line using a mutated less active viral protease to overcome potential cytotoxic limitations. The stable transfection of bicistronic expression cassettes with re-initiation of the translation mechanism enabled the generation of LentiPro26 packaging populations supporting high titers. Additionally, by skipping intermediate clone screening steps and performing only one final clone screening, it was possible to save time and generate LentiPro26-A59 cell line, that constitutively produces titers above 10 6 TU.mL -1 .day -1 , in less than six months. This work constitutes a step forward towards the development of improved LV producer cell lines, aiming to efficiently supply the clinical expanding gene therapy applications.

  15. American Focus on World Constitutions. Teacher's Guide.

    ERIC Educational Resources Information Center

    Holmes, Stanley T., III

    This curriculum project was designed to familiarize high school students with their own constitutional roots while gaining a better understanding of governmental systems developed by other nations. The project uses the U.S. Constitution as a baseline for analyzing the constitutions of other nations, and is intended to supplement courses in such…

  16. The wheat resistance gene Lr34 results in the constitutive induction of multiple defense pathways in transgenic barley.

    PubMed

    Chauhan, Harsh; Boni, Rainer; Bucher, Rahel; Kuhn, Benjamin; Buchmann, Gabriele; Sucher, Justine; Selter, Liselotte L; Hensel, Goetz; Kumlehn, Jochen; Bigler, Laurent; Glauser, Gaëtan; Wicker, Thomas; Krattinger, Simon G; Keller, Beat

    2015-10-01

    The wheat gene Lr34 encodes an ABCG-type transporter which provides durable resistance against multiple pathogens. Lr34 is functional as a transgene in barley, but its mode of action has remained largely unknown both in wheat and barley. Here we studied gene expression in uninfected barley lines transgenic for Lr34. Genes from multiple defense pathways contributing to basal and inducible disease resistance were constitutively active in seedlings and mature leaves. In addition, the hormones jasmonic acid and salicylic acid were induced to high levels, and increased levels of lignin as well as hordatines were observed. These results demonstrate a strong, constitutive re-programming of metabolism by Lr34. The resistant Lr34 allele (Lr34res) encodes a protein that differs by two amino acid polymorphisms from the susceptible Lr34sus allele. The deletion of a single phenylalanine residue in Lr34sus was sufficient to induce the characteristic Lr34-based responses. Combination of Lr34res and Lr34sus in the same plant resulted in a reduction of Lr34res expression by 8- to 20-fold when the low-expressing Lr34res line BG8 was used as a parent. Crosses with the high-expressing Lr34res line BG9 resulted in an increase of Lr34sus expression by 13- to 16-fold in progenies that inherited both alleles. These results indicate an interaction of the two Lr34 alleles on the transcriptional level. Reduction of Lr34res expression in BG8 crosses reduced the negative pleiotropic effects of Lr34res on barley growth and vigor without compromising disease resistance, suggesting that transgenic combination of Lr34res and Lr34sus can result in agronomically useful resistance. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  17. Initial characterisation of low and high seed dormancy populations of Lolium rigidum produced by repeated selection.

    PubMed

    Goggin, Danica E; Emery, R J Neil; Powles, Stephen B; Steadman, Kathryn J

    2010-10-15

    The physiological and biochemical bases of seed dormancy in Lolium rigidum (annual ryegrass) are largely unknown, and study of this process is complicated by the outcrossing nature of the species and the strong influence of environment on seed dormancy. In order to identify heritable biochemical factors contributing to seed dormancy in L. rigidum, seeds from a field-collected population were used to select sub-populations with consistently low or high seed dormancy over four generations. Low-dormancy seeds showed constitutive alpha-amylase activity prior to imbibition, higher concentrations of polyphenols and cis-zeatin, and lower abscisic acid and cis-zeatin riboside concentrations than high-dormancy seeds. Selection for high dormancy was associated with a reduction in response to dark-stratification for 21d at 20 degrees C (an effective means of releasing dormancy in the original, unselected population) over successive generations, but fluridone remained effective in breaking dormancy. Crossing of low- and high-dormancy populations indicated that dormancy level was not dependent upon the maternal genotype of the seed, and that the constitutive alpha-amylase activity and high seed anthocyanin concentrations characteristic of the low-dormancy populations were not correlated to high basal germination ability. Copyright (c) 2010 Elsevier GmbH. All rights reserved.

  18. Pharmacological targeting of the PI3K/mTOR pathway alters the release of angioregulatory mediators both from primary human acute myeloid leukemia cells and their neighboring stromal cells.

    PubMed

    Reikvam, Håkon; Nepstad, Ina; Bruserud, Øystein; Hatfield, Kimberley Joanne

    2013-06-01

    Acute myeloid leukemia (AML) is a heterogeneous and aggressive malignancy with poor overall survival. Constitutive as well as cytokine-initiated activation of PI3K/Akt/mTOR signaling is a common feature of AML patients, and inhibition of this pathway is considered as a possible therapeutic strategy in AML. Human AML cells and different stromal cell populations were cultured under highly standardized in vitro conditions. We investigated the effects of mTOR inhibitors (rapamycin and temsirolimus) and PI3K inhibitors (GDC-0941 and 3-methyladenin (3-MA)) on cell proliferation and the constitutive release of angioregulatory mediators by AML and stromal cells. Primary human AML cells were heterogeneous, though most patients showed high CXCL8 levels and detectable release of CXCL10, Ang-1, HGF and MMP-9. Hierarchical clustering analysis showed that disruption of PI3K/Akt/mTOR pathways decreased AML cell release of CXCL8-11 for a large subset of patients, whereas the effects on other mediators were divergent. Various stromal cells (endothelial cells, fibroblasts, cells with osteoblastic phenotype) also showed constitutive release of angioregulatory mediators, and inhibitors of both the PI3K and mTOR pathway had anti-proliferative effects on stromal cells and resulted in decreased release of these angioregulatory mediators. PI3K and mTOR inhibitors can decrease constitutive cytokine release both by AML and stromal cells, suggesting potential direct and indirect antileukemic effects.

  19. Pharmacological targeting of the PI3K/mTOR pathway alters the release of angioregulatory mediators both from primary human acute myeloid leukemia cells and their neighboring stromal cells

    PubMed Central

    Reikvam, Håkon; Nepstad, Ina; Bruserud, Øystein; Hatfield, Kimberley Joanne

    2013-01-01

    Acute myeloid leukemia (AML) is a heterogeneous and aggressive malignancy with poor overall survival. Constitutive as well as cytokine-initiated activation of PI3K/Akt/mTOR signaling is a common feature of AML patients, and inhibition of this pathway is considered as a possible therapeutic strategy in AML. Human AML cells and different stromal cell populations were cultured under highly standardized in vitro conditions. We investigated the effects of mTOR inhibitors (rapamycin and temsirolimus) and PI3K inhibitors (GDC-0941 and 3-methyladenin (3-MA)) on cell proliferation and the constitutive release of angioregulatory mediators by AML and stromal cells. Primary human AML cells were heterogeneous, though most patients showed high CXCL8 levels and detectable release of CXCL10, Ang-1, HGF and MMP-9. Hierarchical clustering analysis showed that disruption of PI3K/Akt/mTOR pathways decreased AML cell release of CXCL8-11 for a large subset of patients, whereas the effects on other mediators were divergent. Various stromal cells (endothelial cells, fibroblasts, cells with osteoblastic phenotype) also showed constitutive release of angioregulatory mediators, and inhibitors of both the PI3K and mTOR pathway had anti-proliferative effects on stromal cells and resulted in decreased release of these angioregulatory mediators. PI3K and mTOR inhibitors can decrease constitutive cytokine release both by AML and stromal cells, suggesting potential direct and indirect antileukemic effects. PMID:23919981

  20. Political legitimacy and European monetary union: contracts, constitutionalism and the normative logic of two-level games

    PubMed Central

    Bellamy, Richard; Weale, Albert

    2015-01-01

    ABSTRACT The crisis of the euro area has severely tested the political authority of the European Union (EU). The crisis raises questions of normative legitimacy both because the EU is a normative order and because the construction of economic and monetary union (EMU) rested upon a theory that stressed the normative value of the depoliticization of money. However, this theory neglected the normative logic of the two-level game implicit in EMU. It also neglected the need for an impartial and publically acceptable constitutional order to acknowledge reasonable disagreements. By contrast, we contend that any reconstruction of the EU's economic constitution has to pay attention to reconciling a European monetary order with the legitimacy of member state governance. The EU requires a two-level contract to meet this standard. Member states must treat each other as equals and be representative of and accountable to their citizens on an equitable basis. These criteria entail that the EU's political legitimacy requires a form of demoicracy that we call ‘republican intergovernmentalism’. Only rules that could be acceptable as the product of a political constitution among the peoples of Europe can ultimately meet the required standards of political legitimacy. Such a political constitution could be brought about through empowering national parliaments in EU decision-making. PMID:26924935

  1. Political legitimacy and European monetary union: contracts, constitutionalism and the normative logic of two-level games.

    PubMed

    Bellamy, Richard; Weale, Albert

    2015-02-07

    The crisis of the euro area has severely tested the political authority of the European Union (EU). The crisis raises questions of normative legitimacy both because the EU is a normative order and because the construction of economic and monetary union (EMU) rested upon a theory that stressed the normative value of the depoliticization of money. However, this theory neglected the normative logic of the two-level game implicit in EMU. It also neglected the need for an impartial and publically acceptable constitutional order to acknowledge reasonable disagreements. By contrast, we contend that any reconstruction of the EU's economic constitution has to pay attention to reconciling a European monetary order with the legitimacy of member state governance. The EU requires a two-level contract to meet this standard. Member states must treat each other as equals and be representative of and accountable to their citizens on an equitable basis. These criteria entail that the EU's political legitimacy requires a form of demoi cracy that we call 'republican intergovernmentalism'. Only rules that could be acceptable as the product of a political constitution among the peoples of Europe can ultimately meet the required standards of political legitimacy. Such a political constitution could be brought about through empowering national parliaments in EU decision-making.

  2. Distributions of zinc, copper, cadmium and lead in a tropical ultisol after long-term disposal of sewage sludge.

    PubMed

    Udom, B E; Mbagwu, J S C; Adesodun, J K; Agbim, N N

    2004-06-01

    Heavy metals present in soils constitute serious environmental hazards from the point of view of polluting the soils and adjoining streams and rivers. The distribution of heavy metals in a sandy Ultisol (Arenic Kandiustult) in south eastern Nigeria subjected to 40 years disposal of sewage wastes (sludge and effluents) was studied using two profile pits (S/NSK/1 and S/NSK/2) sited in the sewage disposal area and one profile pit (NS/NSK) sited in the non-sewage disposal area. Soil samples were collected in duplicate from these soil horizons and analyzed for their heavy metal contents. The mean concentrations of Zn, Cu, Cd and Pb in the top- and sub-soil horizons of sewage soil were 79.3, 32, 0.29 and 1.15 mg/kg, respectively. These levels were high enough to constitute health and phytotoxic risks. All the metal levels were much higher in the AB horizon in the sewage than in the non-sewage soil profile, but Pb and Cu contents were also high down to the Bt1 horizon, indicating their apparent relatively high mobility in this soil. There was a significant correlation between organic matter (OM) and Zn (r=0.818**), and between OM and Cd (0.864**) in the sewage soil. The high OM status of the sewage sludge, together with its corresponding low pH, might have favoured metal-OM complexation that could reduce heavy metal mobility and phytotoxicity in this soil.

  3. A test of life-history theories of immune defence in two ecotypes of the garter snake, Thamnophis elegans.

    PubMed

    Sparkman, Amanda Marie; Palacios, Maria Gabriela

    2009-11-01

    1. Life-history theorists have long observed that fast growth and high reproduction tend to be associated with short life span, suggesting that greater investment in such traits may trade off with self-maintenance. The immune system plays an integral role in self-maintenance and has been proposed as a mediator of life-history trade-offs. 2. Ecoimmunologists have predicted that fast-living organisms should rely more heavily on constitutive innate immunity than slow-living organisms, as constitutive innate defences are thought to be relatively inexpensive to develop and can provide a rapid, general response to pathogens. 3. We present the first study to examine this hypothesis in an ectothermic vertebrate, by testing for differences in three aspects of constitutive innate immunity in replicate populations of two life-history ecotypes of the garter snake Thamnophis elegans, one fast-living and one slow-living. 4. As predicted, free-ranging snakes from the fast-living ecotype had higher levels of all three measures of constitutive innate immunity than the slow-living ecotype. These differences in immunity were not explained by parasite loads measured. Furthermore, both ecotypes exhibited a positive relationship between innate immunity and body size/age, which we discuss in the context of ectotherm physiology and ecotype differences in developmental rates.

  4. Retention of mercury by salmon

    USGS Publications Warehouse

    Amend, Donald F.

    1970-01-01

    Consuming fish that have been exposed repeatedly to mercury derivatives is a potential public health hazard because fish can accumulate and retain mercury in their tissues (Rucker, 1968). Concern has been expressed in the United States because mercurials have been used extensively in industry and as prophylactic and therapeutic agents in fish hatcheries. Rucker and Amend (1969) showed that yearling rainbow trout (Salmo gairdneri) and chinook salmon (Oncorhynchus tshawytscha) exposed to mercurials accumulated excessive amounts of mercury in many tissues. Further, Rucker and Amend (1969) concluded that wild fish that ate mercury-contaminated fish also could contain high mercury levels. Although mercury was eliminated from most tissues within several months, substantial levels remained in the kidney for more than 33 weeks after the last exposure. Since high levels of mercury can be retained in the kidney for an undetermined time, it is possible that returning adult salmon exposed to mercurials as juveniles could constitute a potential hazard to public health. The purpose of this study was to determine whether such fish contained high residual levels of mercury.

  5. Consumption patterns and levels among households with HIV positive members and economic impoverishment due to medical spending in Pune city, India.

    PubMed

    Sharma, Varun; Krishnaswamy, Divya; Mulay, Sanjeevanee

    2015-01-01

    HIV infection poses a serious threat to the economy of a household. Out of pocket (OOP) health spending can be prohibitive and can drag households below poverty level. Based on the data collected from a cross-sectional survey of 401 households with HIV+ members in Pune city, India, this paper examines the consumption levels and patterns among households, and comments on the economic impoverishment resulting from OOP medical spending. Analysis reveals that households with HIV members spend a major portion of their monthly consumption expenditure on food items. Medical expenditure constitutes a large portion of their total consumption spending. Expenditure on children's education constitutes a minor proportion of total monthly spending. A high proportion of medical expenditure has a bearing on the economic condition of households with HIV members. Poverty increases by 20% among the studied HIV households when OOP health spending is adjusted. It increases 18% among male-headed households and 26% among female-headed households. The results reiterate the need of greater support from the government in terms of accessibility and affordability of health care to save households with HIV members from economic catastrophe.

  6. [The prevalence of hearing impairment in transport workers and peculiarities of management of occupational loss of hearing (as exemplified by the situation in the air and railway transport)].

    PubMed

    Pankova, V B; Skryabina, L Yu; Kas'kov, Yu N

    2016-01-01

    This article presents data on the prevalence of hearing impairment among the workers engaged in the main means of transportation(air and railway transport). They show that the relative frequency of occupational loss of hearing in the cockpit members of commercial aviation amounts to one third of all cases of analogous diseases in this country. The main professional groups of transport works suffering from hearing impairment are constituted by the representatives of the so-called elite specialities, such as flying crew personnel, locomotive engineers, and their assistants. This fact constitutes an important aspect (not only of medical but also of socio-economic significance) of the problem under consideration. The high prevalence of professional hearing impairment among the transport workers is attributable to the high noise level in the cabins of locomotives and aircraft cockpits as well as to the inadequate expert and diagnostic work or imperfection of the regulatory documentation.

  7. Season and light affect constitutive defenses of understory shrub species against folivorous insects

    NASA Astrophysics Data System (ADS)

    Karolewski, Piotr; Giertych, Marian J.; Żmuda, Michał; Jagodziński, Andrzej M.; Oleksyn, Jacek

    2013-11-01

    Understory shrubs contribute to overall species diversity, providing habitat and forage for animals, influence soil chemistry and forest microclimate. However, very little is known about the chemical defense of various shrub species against folivorous insects. Using six shrub species, we tested how seasonal changes and light conditions affect their constitutive defense to insect damage. We monitored leaf perforation, concentrations of total phenols, condensed tannins, nitrogen (N), and total nonstructural carbohydrates (TNC). Leaf damage caused by insects was low in Sambucus nigra, Cornus sanguinea, and Frangula alnus, intermediate in Corylus avellana and Prunus serotina, and high in Prunus padus. Leaves of all the species, when growing in high light conditions, had high concentrations of defense metabolites. Except for C. avellana, leaves of the other shrub species growing in full sun were less injured than those in shade. This may be due to higher concentrations of defense metabolites and lower concentrations of nitrogen. Similar patterns of the effects of light on metabolites studied and N were observed for leaves with varying location within the crown of individual shrubs (from the top of the south direction to the bottom of the north), as for leaves from shrubs growing in full sun and shrubs in the shade of canopy trees. A probable cause of the greater damage of more sunlit leaves of C. avellana was the fact that they were herbivorized mostly by Altica brevicollis, a specialist insect that prefers plant tissues with a high TNC level and is not very sensitive to a high level of phenolic compounds.

  8. A High-Resolution Comparative Chromosome Map of Cricetus cricetus and Peromyscus eremicus Reveals the Involvement of Constitutive Heterochromatin in Breakpoint Regions.

    PubMed

    Vieira-da-Silva, Ana; Louzada, Sandra; Adega, Filomena; Chaves, Raquel

    2015-01-01

    Compared to humans and other mammals, rodent genomes, specifically Muroidea species, underwent intense chromosome reshuffling in which many complex structural rearrangements occurred. This fact makes them preferential animal models for studying the process of karyotype evolution. Here, we present the first combined chromosome comparative maps between 2 Cricetidae species, Cricetus cricetus and Peromyscus eremicus, and the index species Mus musculus and Rattus norvegicus. Comparative chromosome painting was done using mouse and rat paint probes together with in silico analysis from the Ensembl genome browser database. Hereby, evolutionary events (inter- and intrachromosomal rearrangements) that occurred in C. cricetus and P. eremicus since the putative ancestral Muroidea genome could be inferred, and evolutionary breakpoint regions could be detected. A colocalization of constitutive heterochromatin and evolutionary breakpoint regions in each genome was observed. Our results suggest the involvement of constitutive heterochromatin in karyotype restructuring of these species, despite the different levels of conservation of the C. cricetus (derivative) and P. eremicus (conserved) genomes. © 2015 S. Karger AG, Basel.

  9. Effect of short-term, high-dose methylprednisolone on oxidative stress in children with acute immune thrombocytopenia.

    PubMed

    Cura, Musa; Koç, Ahmet; Aksoy, Nurten; Özdemir, Zeynep Canan

    2016-12-01

    Immune thrombocytopenia (ITP) is the most common cause of acquired childhood thrombocytopenia and is characterized by increased immune-mediated destruction of circulating thrombocytes. Oxidative damage may be involved in ITP pathogenesis; paraoxonase (PON) and arylesterase (ARE) enzymes are closely associated with the cellular antioxidant system. We investigated the effect of short-term high-dose methylprednisolone (HDMP) treatment on the total oxidant status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), and PON and ARE enzymatic activity in children with acute ITP. Thirty children with acute ITP constituted the study group and 30 healthy children constituted the control group. Children with acute ITP were treated with HDMP: 30 mg/kg for 3 days, then 20 mg/kg for 4 days. The TOS, TAC, OSI, PON, and ARE levels were determined before and after 7 days of HDMP treatment. The TAC level ( P <0.001), and PON ( P <0.001) and ARE (P=0.001) activities were lower and the TOS ( P =0.003) and OSI ( P <0.001) levels were higher in children with acute ITP than those in healthy children in the control group. We also observed statistically significant increases in the TAC ( P <0.01), PON ( P <0.001) and ARE levels ( P =0.001) and decreases in the TOS ( P <0.05) and OSI levels ( P <0.05) with 7 days of HDMP treatment compared to their values before treatment. Our study demonstrated increased oxidative stress (OSI and TOC) and decreased antioxidant capacity (TAC), PON, and ARE in ITP patients and that steroid treatment could be effective in reducing the oxidative stress.

  10. 77 FR 34404 - National Register of Historic Places; Notification of Pending Nominations and Related Actions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-11

    ... Constitution Ave., Hartford, 12000359 Kensington Grammar School--Jean E. Hooker High School, 462 Alling St..., 12000365 St. Johns County Constitution Obelisk, Plaza de la Constitution, St. Augustine, 12000364 NEW YORK...

  11. Enhanced constitutive invasion activity in human nontumorigenic keratinocytes exposed to a low level of barium for a long time.

    PubMed

    Thang, Nguyen D; Yajima, Ichiro; Ohnuma, Shoko; Ohgami, Nobutaka; Kumasaka, Mayuko Y; Ichihara, Gaku; Kato, Masashi

    2015-02-01

    We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion. © 2013 Wiley Periodicals, Inc.

  12. Characteristics of TCM constitutions of adult Chinese women in Hong Kong and identification of related influencing factors: a cross-sectional survey.

    PubMed

    Sun, Youzhi; Liu, Pei; Zhao, Yi; Jia, Lei; He, Yanhua; Xue, Steve An; Zheng, Xiao; Wang, Zhiyu; Wang, Neng; Chen, Jianping

    2014-05-21

    Traditional Chinese Medicine Constitution (TCMC) refers to an integrated, metastable and natural specialty of individual in morphosis, physiological functions and psychological conditions. It is formed on the basis of innate and acquired endowments in the human life process, which can be divided into normal constitution and unbalanced ones. The aim of this study was to investigate the distribution of TCMCs of Chinese women in Hong Kong and its acquired influencing factors. Local Chinese women between 30 to 65 years old, were recruited from 18 districts of Hong Kong (n=944), and were assessed using the Traditional Chinese Medicine Physical Constitution Scale for their TCMC types. Social-demographic, reproductive, lifestyle, systemic health and emotional status information were collected through structured questionnaire. The associations between different independent factors and each TCMC type, as well as the complex unbalanced TCMC types were tested individually. Significant factors related to unbalanced TCMC types were identified in final models using multiple factor analysis. A total of 764 (80.9%) participants were diagnosed with unbalanced TCMCs. The most common TCMC type was Qi-deficiency constitution (53.9%), followed by Phlegm-wetness (38.9%), Yang-deficiency (38.2%), Yin-deficiency (35.5), Blood-stasis (35.4) and Qi-depressed (31%) constitution. Six hundred and eleven participants (64.7%) had at least two types of combined and unbalanced constitutions. Stepwise logistic analysis indicated that poor systemic health condition (OR, 1.76-2.89), negative emotions (OR=1.39), overweight (OR=1.58), high educational level (OR=1.18) and mental work (OR=1.44) were significantly positively correlated with certain unbalanced TCMCs. Meanwhile, aging (OR, 0.59-0.73), exercise habit (OR, 0.61-0.79) and reproductive history (OR=0.72) showed inverse associations with unbalanced constitutions. In addition, systemic health condition and emotional status, exercise habit and age were significantly associated with the combined unbalanced TCMC types. The majority of middle-aged Chinese women in Hong Kong had unbalanced and complex TCMCs. Qi-deficiency, Phlegm-wetness and Yang-deficiency constitutions are the most common constitutions. Poor systemic health condition, less-than-satisfactory emotional life, overweight and mental work are associated with and may be contributors for the formation of unbalanced TCMCs, while regular physical exercise was found to be a potential protective factor for unbalanced TCMCs.

  13. The rcsA Promoter of Pantoea stewartii subsp. stewartii Features a Low-Level Constitutive Promoter and an EsaR Quorum-Sensing-Regulated Promoter

    PubMed Central

    Carlier, Aurelien L.; von Bodman, S. B.

    2006-01-01

    The upstream region of the Pantoea stewartii rcsA gene features two promoters, one for constitutive basal-level expression and a second autoregulated promoter for induced expression. The EsaR quorum-sensing repressor binds to a site centered between the two promoters, blocking transcription elongation from the regulated promoter under noninducing conditions. PMID:16740966

  14. A Framework for Translating a High Level Security Policy into Low Level Security Mechanisms

    NASA Astrophysics Data System (ADS)

    Hassan, Ahmed A.; Bahgat, Waleed M.

    2010-01-01

    Security policies have different components; firewall, active directory, and IDS are some examples of these components. Enforcement of network security policies to low level security mechanisms faces some essential difficulties. Consistency, verification, and maintenance are the major ones of these difficulties. One approach to overcome these difficulties is to automate the process of translation of high level security policy into low level security mechanisms. This paper introduces a framework of an automation process that translates a high level security policy into low level security mechanisms. The framework is described in terms of three phases; in the first phase all network assets are categorized according to their roles in the network security and relations between them are identified to constitute the network security model. This proposed model is based on organization based access control (OrBAC). However, the proposed model extend the OrBAC model to include not only access control policy but also some other administrative security policies like auditing policy. Besides, the proposed model enables matching of each rule of the high level security policy with the corresponding ones of the low level security policy. Through the second phase of the proposed framework, the high level security policy is mapped into the network security model. The second phase could be considered as a translation of the high level security policy into an intermediate model level. Finally, the intermediate model level is translated automatically into low level security mechanism. The paper illustrates the applicability of proposed approach through an application example.

  15. Research in the design of high-performance reconfigurable systems

    NASA Technical Reports Server (NTRS)

    Slotnick, D. L.; Mcewan, S. D.; Spry, A. J.

    1984-01-01

    An initial design for the Bit Processor (BP) referred to in prior reports as the Processing Element or PE has been completed. Eight BP's, together with their supporting random-access memory, a 64 k x 9 ROM to perform addition, routing logic, and some additional logic, constitute the components of a single stage. An initial stage design is given. Stages may be combined to perform high-speed fixed or floating point arithmetic. Stages can be configured into a range of arithmetic modules that includes bit-serial one or two-dimensional arrays; one or two dimensional arrays fixed or floating point processors; and specialized uniprocessors, such as long-word arithmetic units. One to eight BP's represent a likely initial chip level. The Stage would then correspond to a first-level pluggable module. As both this project and VLSI CAD/CAM progress, however, it is expected that the chip level would migrate upward to the stage and, perhaps, ultimately the box level. The BP RAM, consisting of two banks, holds only operands and indices. Programs are at the box (high-level function) and system level. At the system level initial effort has been concentrated on specifying the tools needed to evaluate design alternatives.

  16. Spectral Elements Analysis for Viscoelastic Fluids at High Weissenberg Number Using Logarithmic conformation Tensor Model

    NASA Astrophysics Data System (ADS)

    Jafari, Azadeh; Deville, Michel O.; Fiétier, Nicolas

    2008-09-01

    This study discusses the capability of the constitutive laws for the matrix logarithm of the conformation tensor (LCT model) within the framework of the spectral elements method. The high Weissenberg number problems (HWNP) usually produce a lack of convergence of the numerical algorithms. Even though the question whether the HWNP is a purely numerical problem or rather a breakdown of the constitutive law of the model has remained somewhat of a mystery, it has been recognized that the selection of an appropriate constitutive equation constitutes a very crucial step although implementing a suitable numerical technique is still important for successful discrete modeling of non-Newtonian flows. The LCT model formulation of the viscoelastic equations originally suggested by Fattal and Kupferman is applied for 2-dimensional (2D) FENE-CR model. The Planar Poiseuille flow is considered as a benchmark problem to test this representation at high Weissenberg number. The numerical results are compared with numerical solution of the standard constitutive equation.

  17. Comparison of lodgepole and jack pine resin chemistry: implications for range expansion by the mountain pine beetle, Dendroctonus ponderosae (Coleoptera: Curculionidae).

    PubMed

    Clark, Erin L; Pitt, Caitlin; Carroll, Allan L; Lindgren, B Staffan; Huber, Dezene P W

    2014-01-01

    The mountain pine beetle, Dendroctonus ponderosae, is a significant pest of lodgepole pine in British Columbia (BC), where it has recently reached an unprecedented outbreak level. Although it is native to western North America, the beetle can now be viewed as a native invasive because for the first time in recorded history it has begun to reproduce in native jack pine stands within the North American boreal forest. The ability of jack pine trees to defend themselves against mass attack and their suitability for brood success will play a major role in the success of this insect in a putatively new geographic range and host. Lodgepole and jack pine were sampled along a transect extending from the beetle's historic range (central BC) to the newly invaded area east of the Rocky Mountains in north-central Alberta (AB) in Canada for constitutive phloem resin terpene levels. In addition, two populations of lodgepole pine (BC) and one population of jack pine (AB) were sampled for levels of induced phloem terpenes. Phloem resin terpenes were identified and quantified using gas chromatography. Significant differences were found in constitutive levels of terpenes between the two species of pine. Constitutive α-pinene levels - a precursor in the biosynthesis of components of the aggregation and antiaggregation pheromones of mountain pine beetle - were significantly higher in jack pine. However, lower constitutive levels of compounds known to be toxic to bark beetles, e.g., 3-carene, in jack pine suggests that this species could be poorly defended. Differences in wounding-induced responses for phloem accumulation of five major terpenes were found between the two populations of lodgepole pine and between lodgepole and jack pine. The mountain pine beetle will face a different constitutive and induced phloem resin terpene environment when locating and colonizing jack pine in its new geographic range, and this may play a significant role in the ability of the insect to persist in this new host.

  18. Neighbourhood effects on body constitution-A case study of Hong Kong.

    PubMed

    Low, Chien Tat; Lai, Poh Chin; Li, Han Dong; Ho, Wai Kit; Wong, Paulina; Chen, Si; Wong, Wing Cheung

    2016-06-01

    Traditional Chinese Medicine (TCM) has long perceived environment as an integral part of the development of body constitution, which is a personal state of health closely related to disease presence. Despite of the ever-growing studies on the clinical effectiveness of TCM and the scientific linking between body constitution and diseases, the geographical influence on body constitution has yet remained an unexplored territory. This study sought to investigate whether the neighbourhood environment is relevant to the composition of body type of a population through statistical multilevel and Geographic Information Systems modelling. The analysis comprised 3277 participants who had completed their body type assessment between 2009 and 2012 inclusive. The multilevel analysis also took simultaneous accounts of both individual-level (gender, age, BMI, type of housing) and area-level (percent greenery, percent road surface, total road intersection, sky view factor, temperature, relative humidity, rainfall and social deprivation index) characteristics to explain geographical variation by body types. Significant random or place effects (p < 0.001) were identified in the multilevel models. The spatial variation of body constitution involved the dynamic interplay between individual and environmental factors. The findings amassed the first scientific indications to back the common belief that place does play a role in the development of body constitution and is worthy of further investigation. By considering spatial and personal attributes simultaneously, the study can yield valuable insights into the patterning of area variation in body constitution and disease presence. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Deployment of quasi-digital sensor for high temperature molten salt level measurement in pyroprocessing plants.

    PubMed

    Sanga, Ramesh; Agarwal, Sourabh; Sivaramakrishna, M; Rao, G Prabhakara

    2018-04-01

    Development of a liquid molten salt level sensor device that can detect the level of liquid molten salt in the process vessels of pyrochemical reprocessing of spent metallic fuels is detailed. It is proposed to apply a resistive-type pulsating sensor-based level measurement approach. There are no commercially available sensors due to limitations of high temperature, radiation, and physical dimensions. A compact, simple, rugged, low power, and high precise pulsating sensor-based level probe and simple instrumentation for the molten salt liquid level sensor to work in the extreme conditions has been indigenously developed, with high precision and accuracy. The working principle, design concept, and results have been discussed. This level probe is mainly composed of the variable resistor made up of ceramic rods. This resistor constitutes the part of resistance-capacitance-type Logic Gate Oscillator (LGO). A change in the molten salt level inside the tank causes a small change in the resistance which in turn changes the pulse frequency of the LGO. Thus the frequency, the output of the instrument that is displayed on the LCD of an embedded system, is a function of molten salt level. In the present design, the range of level measurement is about 10 mm. The sensitivity in position measurement up to 10 mm is ∼2.5 kHz/mm.

  20. Deployment of quasi-digital sensor for high temperature molten salt level measurement in pyroprocessing plants

    NASA Astrophysics Data System (ADS)

    Sanga, Ramesh; Agarwal, Sourabh; Sivaramakrishna, M.; Rao, G. Prabhakara

    2018-04-01

    Development of a liquid molten salt level sensor device that can detect the level of liquid molten salt in the process vessels of pyrochemical reprocessing of spent metallic fuels is detailed. It is proposed to apply a resistive-type pulsating sensor-based level measurement approach. There are no commercially available sensors due to limitations of high temperature, radiation, and physical dimensions. A compact, simple, rugged, low power, and high precise pulsating sensor-based level probe and simple instrumentation for the molten salt liquid level sensor to work in the extreme conditions has been indigenously developed, with high precision and accuracy. The working principle, design concept, and results have been discussed. This level probe is mainly composed of the variable resistor made up of ceramic rods. This resistor constitutes the part of resistance-capacitance-type Logic Gate Oscillator (LGO). A change in the molten salt level inside the tank causes a small change in the resistance which in turn changes the pulse frequency of the LGO. Thus the frequency, the output of the instrument that is displayed on the LCD of an embedded system, is a function of molten salt level. In the present design, the range of level measurement is about 10 mm. The sensitivity in position measurement up to 10 mm is ˜2.5 kHz/mm.

  1. Final Report

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

    Issen, Kathleen

    2017-06-05

    This project employed a continuum approach to formulate an elastic constitutive model for Castlegate sandstone. The resulting constitutive framework for high porosity sandstone is thermodynamically sound, (i.e., does not violate the 1st and 2nd law of thermodynamics), represents known material constitutive response, and is able to be calibrated using available mechanical response data. To authenticate the accuracy of this model, a series of validation criteria were employed, using an existing mechanical response data set for Castlegate sandstone. The resulting constitutive framework is applicable to high porosity sandstones in general, and is tractable for scientists and researchers endeavoring to solve problemsmore » of practical interest.« less

  2. CaMKII and CaMKIV mediate distinct prosurvival signaling pathways in response to depolarization in neurons

    PubMed Central

    Bok, Jinwoong; Wang, Qiong; Huang, Jie; Green, Steven H.

    2007-01-01

    By fusing the CaMKII inhibitory peptide AIP to GFP, we constructed a specific and effective CaMKII inhibitor, GFP-AIP. Expression of GFP-AIP and/or dominant-inhibitory CaMKIV in cultured neonatal rat spiral ganglion neurons (SGNs) shows that CaMKII and CaMKIV act additively and in parallel, to mediate the prosurvival effect of depolarization. Depolarization or expression of constitutively-active CaMKII functionally inactivates Bad, indicating that this is one means by which CaMKII promotes neuronal survival. CaMKIV, but not CaMKII, requires CREB to promote SGN survival, consistent with the exclusively nuclear localization of CaMKIV and indicating that the principal prosurvival function of CaMKIV is activation of CREB. Consistent with this, a constitutively-active CREB construct that provides a high level of CREB activity promotes SGN survival, although low levels of CREB activity did not do so. Also, in apoptotic SGNs, activation of CREB by depolarization is disabled, presumably as part of a cellular commitment to apoptosis. PMID:17651987

  3. Prevalence of latex hypersensitivity among health care workers in Malaysia.

    PubMed

    Shahnaz, M; Azizah, M R; Hasma, H; Mok, K L; Yip, E; Ganesapillai, T; Suraiya, H; Nasuruddin, B A

    1999-03-01

    Health care workers have been reported to constitute one of the few high-risk groups related to IgE-mediated hypersensitivity associated with the use of latex products. This paper describes the first ever study of prevalence carried out in Malaysia among these workers. One hundred and thirty health care personnel from Hospital Kuala Lumpur were skin tested. Extracts used were prepared from seven different brands of natural rubber latex gloves with varying levels of extractable protein (EPRRIM). Out of the 130 volunteers, 4 (3.1%) had positive skin test to latex with extracts with high levels of EPRRIM (> 0.7 mg/g). The prevalence among the Malaysian health care workers can be considered to be low in comparison to that of some consumer countries as the USA which reported a prevalence of as high as 16.9%.

  4. [Prediabetes, definition and treatment].

    PubMed

    Dolz, Manuel; Dhane, Yasmin

    2017-10-01

    Prediabetes corresponds to high levels of glycaemia on an empty stomach and/or lower tolerance to glucose. It is necessary to detect and treat it in order to prevent type 2 diabetes and its long-term morbidity-mortality. Several clinical trials, based notably on modifying the patient's lifestyle, have shown that prevention is possible. Bariatric surgery could constitute a favoured treatment option in prediabetic obese patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Generating new knowledge in cardiac interventions.

    PubMed

    Blackstone, Eugene H

    2013-06-01

    Cardiac interventions are among the most quantitatively studied therapies. It is important for all involved with cardiac interventions to understand how information generated from observations made during patient care is transformed into data suitable for analysis, to appreciate at a high level what constitutes appropriate analyses of those data, to effectively evaluate inferences drawn from those analyses, and to apply new knowledge to better care for individual patients. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. [Effect of electroacupuncture at Zhongwan(CV 12) on skin microcirculatory blood perfusion units along the conception vessel in yang-deficiency volunteers].

    PubMed

    Shen, Cimin; Xu, Jinsen; Zheng, Shuxia; Lin, Lijiao; Yang, Xiaomei; Liu, Chunlan

    2016-02-01

    To observe the effect of electroacupuncture(EA) at Zhongwan(CV 12) on the energy metabolism along the conception vessel(CV) in volunteers with yang-deficiency constitution,and to explore the relationship of electroacupuncture regulation and body constitution. Eighteen volunteers with mild constitution and 18 volunteers with yang-deficiency constitution were collected out of 200 students of Fujian University of TCM by body constitution questionnaire. Skin microcirculatory blood perfusion units (MBPU) at Danzhong (CV 17), Xiawan(CV 10) and Qihai(CV 6) of CV were measured by a laser Doppler flowmetry in the normal condition and after EA stimulation at Zhongwan(CV 12) for 20 min. (1)Before treatment, (1)MBPU values at Danzhong(CV 17), Xiawan(CV 10) and Qihai(CV 6) in the yang-deficiency constitution group were lower than those in the mild constitution group,but there was no statistical significance (both P>0. 05) except Danzhong(CV 17) (P<0. 01). (Z)As for the three acupoints in the mild constitution group, MBPU level of Danzhong(CV 17) was higher than that of Xiawan(CV 10) without statistical significance(P->0. 05),and MBPU values of Danzhong(CV 17) and Xiawan(CV 10) were higher than that of Qihai(CV 6) (both P<0. 01). (3About the three acupoints in the yang-deficiency constitution group, MBPU result of Danzhong(CV 17) was lower than the value of Xiawan(CV 10), but higher compared with Qihai(CV 6)(P<0. 05, P<0. 01). MBPU of Xiawan(CV 10) was higher than Qihai (CV 6) as well(P<0. 01). (2) MBPU values of Danzhong(CV 17), Xiawan(CV 10) and Qihai(CV 6) were increased apparently compared with those before treatment after EA stimulation at Zhongwan(CV 12) for 20 min in the two groups(all P<0. 01). (3) The rise rates of MBPU level about Danzhong(CV 17) and Qihai(CV 6) in the yang-deficiency constitution group were higher than those in the mild constitution group without statistical significance after EA at Zhongwan(CV 12) for 20 min(both P>0. 05). The energy metabolism in CV of volunteers with yang-deficiency constitution is declined, especially Danzhong(CV 17). EA can rise energy metabolism in CV of mild or yang-deficiency constitution volunteers through regulating MBPU along meridian.

  7. Zeaxanthin Accumulation in the Absence of a Functional Xanthophyll Cycle Protects Chlamydomonas reinhardtii from Photooxidative Stress

    PubMed Central

    Baroli, Irene; Do, An D.; Yamane, Tomoko; Niyogi, Krishna K.

    2003-01-01

    Xanthophylls participate in light harvesting and are essential in protecting the chloroplast from photooxidative damage. To investigate the roles of xanthophylls in photoprotection, we isolated and characterized extragenic suppressors of the npq1 lor1 double mutant of Chlamydomonas reinhardtii, which lacks zeaxanthin and lutein and undergoes irreversible photooxidative bleaching and cell death at moderate to high light intensities. Here, we describe three suppressor strains that carry point mutations in the coding sequence of the zeaxanthin epoxidase gene, resulting in the constitutive accumulation of zeaxanthin in a range of concentrations. The presence of zeaxanthin in these strains was sufficient to prevent photooxidative damage in the npq1 lor1 background. The size of the light-harvesting antenna in the suppressors decreased in high light in a manner that was proportional to the relative content of zeaxanthin, with the strain having the most zeaxanthin showing a severe reduction in levels of the major light-harvesting complex II proteins in high light. We show that the effect of constitutive zeaxanthin on light harvesting is not the main cause of increased photoprotection, because in the absence of zeaxanthin, a strain with a smaller light-harvesting antenna showed only minor protection against photobleaching in high light. Furthermore, the zeaxanthin-accumulating suppressors were able to tolerate higher levels of exogenous reactive oxygen than their parental strain under conditions that did not affect light harvesting. Our results are consistent with an antioxidant role of zeaxanthin in the quenching of singlet oxygen and/or free radicals in the thylakoid membrane in vivo. PMID:12671093

  8. Reconciling nature conservation and traditional farming practices: a spatially explicit framework to assess the extent of High Nature Value farmlands in the European countryside

    PubMed Central

    Lomba, Angela; Alves, Paulo; Jongman, Rob H G; McCracken, David I

    2015-01-01

    Agriculture constitutes a dominant land cover worldwide, and rural landscapes under extensive farming practices acknowledged due to high biodiversity levels. The High Nature Value farmland (HNVf) concept has been highlighted in the EU environmental and rural policies due to their inherent potential to help characterize and direct financial support to European landscapes where high nature and/or conservation value is dependent on the continuation of specific low-intensity farming systems. Assessing the extent of HNV farmland by necessity relies on the availability of both ecological and farming systems' data, and difficulties associated with making such assessments have been widely described across Europe. A spatially explicit framework of data collection, building out from local administrative units, has recently been suggested as a means of addressing such difficulties. This manuscript tests the relevance of the proposed approach, describes the spatially explicit framework in a case study area in northern Portugal, and discusses the potential of the approach to help better inform the implementation of conservation and rural development policies. Synthesis and applications: The potential of a novel approach (combining land use/cover, farming and environmental data) to provide more accurate and efficient mapping and monitoring of HNV farmlands is tested at the local level in northern Portugal. The approach is considered to constitute a step forward toward a more precise targeting of landscapes for agri-environment schemes, as it allowed a more accurate discrimination of areas within the case study landscape that have a higher value for nature conservation. PMID:25798221

  9. A step forward in laccase exploitation: Recombinant production and evaluation of techno-economic feasibility of the process.

    PubMed

    Pezzella, Cinzia; Giacobelli, Valerio Guido; Lettera, Vincenzo; Olivieri, Giuseppe; Cicatiello, Paola; Sannia, Giovanni; Piscitelli, Alessandra

    2017-10-10

    Protein heterologous production offers viable opportunities to tailor laccase properties to specific industrial needs. The high redox potential laccase POXA1b from Pleurotus ostreatus was chosen as case study of marketable enzyme, due to its desirable properties in terms of activity/stability profile, and already assessed applicability. POXA1b was heterologously produced in Pichia pastoris by investigating the effect of inducible and constitutive expression systems on both the yield and the cost of its production. System performances were first assessed in shaken-flasks and then scaled-up in bioreactor. The production level obtained in the inducible system is 42U/mL, while the activity value achieved with the constitutive one is 60U/mL, the highest obtained in constitutive systems so far. The economic feasibility of recombinant laccase production was simulated, describing the case of an Italian small-medium enterprise. Two scenarios were evaluated: Scenario (I) production based on methanol inducible system; Scenario (II) production based on the constitutive system, fed with glycerol. At all the scales the glycerol-based fermentation is more economic than the methanol-based one. The price forecast for rPOXA1b production is 0.34€kU -1 for glycerol-based process, and is very competitive with the current price of commercial laccase. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Integrated environmental policy: A review of economic analysis.

    PubMed

    Wiesmeth, Hans; Häckl, Dennis

    2017-04-01

    Holistic environmental policies, which emerged from a mere combination of technical activities in waste management some 40 years ago, constitute the most advanced level of environmental policies. These approaches to environmental policy, among them the policies in integrated waste management, attempt to guide economic agents to an environment-friendly behaviour. Nevertheless, current holistic policies in waste management, including policies on one-way drinks containers and waste electrical and electronic equipment, and implementations of extended producer responsibility with further applications to waste electrical and electronic equipment, reveal more or less severe deficiencies - despite some positive examples. This article relates these policy failures, which are not necessarily the result of an insufficient compliance with the regulations, to missing constitutive elements of what is going to be called an 'integrated environmental policy'. This article therefore investigates - mostly from a practical point of view - constitutive elements, which are necessary for a holistic policy to serve as a well-functioning allocation mechanism. As these constitutive elements result from a careful 'integration' of the environmental commodities into the economic allocation problems, we refer to these policies as 'integrated environmental policies'. The article also discusses and illustrates the main steps of designing such a policy - for waste electrical and electronic equipment and a (possible) ban of Glyphosat in agriculture. As these policies are dependent on economic and political stability with environmental awareness sufficiently developed, the article addresses mostly waste management policies in highly industrialised countries.

  11. Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

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

    Carpenter, Richard L.; Jiang, Yue; Jing, Yi

    2011-10-28

    Highlights: Black-Right-Pointing-Pointer Chronic exposure to arsenite induces cell proliferation and transformation. Black-Right-Pointing-Pointer Arsenite-induced transformation increases ROS production and downstream signalings. Black-Right-Pointing-Pointer Inhibition of ROS levels via catalase reduces arsenite-induced cell transformation. Black-Right-Pointing-Pointer Interruption of AKT, ERK, or p70S6K1 inhibits arsenite-induced cell transformation. -- Abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidencemore » suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.« less

  12. Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda.

    PubMed

    Prasher, Bhavana; Negi, Sapna; Aggarwal, Shilpi; Mandal, Amit K; Sethi, Tav P; Deshmukh, Shailaja R; Purohit, Sudha G; Sengupta, Shantanu; Khanna, Sangeeta; Mohammad, Farhan; Garg, Gaurav; Brahmachari, Samir K; Mukerji, Mitali

    2008-09-09

    Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates. Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types. Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types. Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine.

  13. Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda

    PubMed Central

    Prasher, Bhavana; Negi, Sapna; Aggarwal, Shilpi; Mandal, Amit K; Sethi, Tav P; Deshmukh, Shailaja R; Purohit, Sudha G; Sengupta, Shantanu; Khanna, Sangeeta; Mohammad, Farhan; Garg, Gaurav; Brahmachari, Samir K; Mukerji, Mitali

    2008-01-01

    Background Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates. Methods Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types. Results Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types. Conclusion Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine. PMID:18782426

  14. Guidelines for preparing high school psychology teachers: course-based and standards-based approaches.

    PubMed

    2013-01-01

    Psychology is one of the most popular elective high school courses. The high school psychology course provides the foundation for students to benefit from psychological perspectives on personal and contemporary issues and learn the rules of evidence and theoretical frameworks of the discipline. The guidelines presented here constitute the second of two reports in this issue of the American Psychologist (January 2013) representing recent American Psychological Association (APA) policies that support high-quality instruction in the teaching of high school psychology. These guidelines, aligned to the standards presented in the preceding report, describe models for the preparation of preservice psychology teachers. The two reports together demonstrate the rigor and competency that should be expected in psychology instruction at the high school level.

  15. An engineering, multiscale constitutive model for fiber-forming collagen in tension.

    PubMed

    Annovazzi, Lorella; Genna, Francesco

    2010-01-01

    This work proposes a nonlinear constitutive model for a single collagen fiber. Fiber-forming collagen can exhibit different hierarchies of basic units, called fascicles, bundles, fibrils, microfibrils, and so forth, down to the molecular (tropocollagen) level. Exploiting the fact that at each hierarchy level the microstructure can be seen, at least approximately, as that of a wavy, or crimped, extensible cable, the proposed stress-strain model considers a given number of levels, each of which contributes to the overall mechanical behavior according to its own geometrical features (crimp, or waviness), as well as to the basic mechanical properties of the tropocollagen. The crimp features at all levels are assumed to be random variables, whose statistical integration furnishes a stress-strain curve for a collagen fiber. The soundness of this model-the first, to the Authors' knowledge, to treat a single collagen fiber as a microstructured nonlinear structural element-is checked by its application to collagen fibers for which experimental results are available: rat tail tendon, periodontal ligament, and engineered ones. Here, no attempt is made to obtain a stress-strain law for generic collagenous tissues, which exhibit specific features, often much more complex than those of a single fiber. However, it is trivial to observe that the availability of a sound, microstructurally based constitutive law for a single collagen fiber (but applicable at any sub-level, or to any other material with a similar microstructure) is essential for assembling complex constitutive models for any collagenous fibrous tissue.

  16. Speciation and bioavailability of mercury in sediments impacted by gold mining in Colombia.

    PubMed

    Pinedo-Hernández, José; Marrugo-Negrete, José; Díez, Sergi

    2015-01-01

    Mercury (Hg) speciation and bioavailability were studied in surface sediments affected by artisanal and small-scale gold mining (ASGM) in the Mojana region of Colombia. The results demonstrated higher levels in sampling stations that receive water streams carrying Hg from mining areas. The T-Hg concentrations were slightly elevated with values between 196.2 and 1187.6 ng g(-1) dry weight (dw) (mean 524.2±256.8 ng g(-1) dw). The MeHg concentrations were significantly correlated with the T-Hg and organic matter (OM) and represent between 1.7% and 3.6% (mean: 2.6%) of the T-Hg. A five-step sequential extraction procedure shown that most of T-Hg in sediments occur primarily as organically bound Hg (Hg-o), which constitutes 48.4% of the T-Hg, followed by elemental Hg fraction (Hg-e) bound to amorphous compounds, such as Fe/Mn oxides with 26.5%, and the fraction bound to sulfur (Hg-s), which constitutes 18.7%. Exchangeable Hg (Hg-w; water-soluble Hg and stomach acid soluble mercury; Hg-h) represents between 1.7% and 4.7%. These fractions constitute a low percentage but exhibit a high level of risk when entering the water column, and they can bioaccumulate in organisms. The significant relationship between OM, T-Hg and MeHg suggests an important role in the control of the distribution, mobility and bioavailability of the Hg in the sediments. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. GPR3 Receptor, a Novel Actor in the Emotional-Like Responses

    PubMed Central

    Valverde, Olga; Célérier, Evelyne; Baranyi, Mária; Vanderhaeghen, Pierre; Maldonado, Rafael; Sperlagh, Beata; Vassart, Gilbert; Ledent, Catherine

    2009-01-01

    GPR3 is an orphan G protein-coupled receptor endowed with constitutive Gs signaling activity, which is expressed broadly in the central nervous system, with maximal expression in the habenula. We investigated the consequences of its genetic deletion in several behavioral paradigms and on neurotransmission. Compared to wild-type, hippocampal neurons from Gpr3−/− mice displayed lower basal intracellular cAMP levels, consistent with the strong constitutive activity of GPR3 in transiently transfected cells. Behavioral analyses revealed that Gpr3−/− mice exhibited a high level of avoidance of novel and unfamiliar environment, associated with increased stress reactivity in behavioral despair paradigms and aggressive behavior in the resident-intruder test. On the contrary, no deficit was found in the learning ability to avoid an aversive event in active avoidance task. The reduced ability of Gpr3 −/− mice to cope with stress was unrelated to dysfunction of the hypothalamic-pituitary-adrenal axis, with Gpr3−/− mice showing normal corticosterone production under basal or stressful conditions. In contrast, dramatic alterations of monoamine contents were found in hippocampus, hypothalamus and frontal cortex of Gpr3−/− mice. Our results establish a link between tonic stimulation of the cAMP signaling pathway by GPR3 and control of neurotransmission by monoamines throughout the forebrain. GPR3 qualifies as a new player in the modulation of behavioral responses to stress and constitutes a novel promising pharmacological target for treatment of emotional disorders. PMID:19259266

  18. Constitutive Expression of Mammalian Nitric Oxide Synthase in Tobacco Plants Triggers Disease Resistance to Pathogens

    PubMed Central

    Chun, Hyun Jin; Park, Hyeong Cheol; Koo, Sung Cheol; Lee, Ju Huck; Park, Chan Young; Choi, Man Soo; Kang, Chang Ho; Baek, Dongwon; Cheong, Yong Hwa; Yun, Dae-Jin; Chung, Woo Sik; Cho, Moo Je; Kim, Min Chul

    2012-01-01

    Nitric oxide (NO) is known for its role in the activation of plant defense responses. To examine the involvement and mode of action of NO in plant defense responses, we introduced calmodulin-dependent mammalian neuronal nitric oxide synthase (nNOS), which controls the CaMV35S promoter, into wild-type and NahG tobacco plants. Constitutive expression of nNOS led to NO production and triggered spontaneous induction of leaf lesions. Transgenic plants accumulated high amounts of H2O2, with catalase activity lower than that in the wild type. nNOS transgenic plants contained high levels of salicylic acid (SA), and they induced an array of SA-, jasmonic acid (JA)-, and/or ethylene (ET)-related genes. Consequently, NahG co-expression blocked the induction of systemic acquired resistance (SAR)-associated genes in transgenic plants, implying SA is involved in NO-mediated induction of SAR genes. The transgenic plants exhibited enhanced resistance to a spectrum of pathogens, including bacteria, fungi, and viruses. Our results suggest a highly ranked regulatory role for NO in SA-, JA-, and/or ET-dependent pathways that lead to disease resistance. PMID:23124383

  19. Genetic enhancement of oil content in potato tuber (Solanum tuberosum L.) through an integrated metabolic engineering strategy.

    PubMed

    Liu, Qing; Guo, Qigao; Akbar, Sehrish; Zhi, Yao; El Tahchy, Anna; Mitchell, Madeline; Li, Zhongyi; Shrestha, Pushkar; Vanhercke, Thomas; Ral, Jean-Philippe; Liang, Guolu; Wang, Ming-Bo; White, Rosemary; Larkin, Philip; Singh, Surinder; Petrie, James

    2017-01-01

    Potato tuber is a high yielding food crop known for its high levels of starch accumulation but only negligible levels of triacylglycerol (TAG). In this study, we evaluated the potential for lipid production in potato tubers by simultaneously introducing three transgenes, including WRINKLED 1 (WRI1), DIACYLGLYCEROL ACYLTRANSFERASE 1 (DGAT1) and OLEOSIN under the transcriptional control of tuber-specific (patatin) and constitutive (CaMV-35S) promoters. This coordinated metabolic engineering approach resulted in over a 100-fold increase in TAG accumulation to levels up to 3.3% of tuber dry weight (DW). Phospholipids and galactolipids were also found to be significantly increased in the potato tuber. The increase of lipids in these transgenic tubers was accompanied by a significant reduction in starch content and an increase in soluble sugars. Microscopic examination revealed that starch granules in the transgenic tubers had more irregular shapes and surface indentations when compared with the relatively smooth surfaces of wild-type starch granules. Ultrastructural examination of lipid droplets showed their close proximity to endoplasmic reticulum and mitochondria, which may indicate a dynamic interaction with these organelles during the processes of lipid biosynthesis and turnover. Increases in lipid levels were also observed in the transgenic potato leaves, likely due to the constitutive expression of DGAT1 and incomplete tuber specificity of the patatin promoter. This study represents an important proof-of-concept demonstration of oil increase in tubers and provides a model system to further study carbon reallocation during development of nonphotosynthetic underground storage organs. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  20. RF extraction issues in the relativistic klystron amplifiers

    NASA Astrophysics Data System (ADS)

    Serlin, Victor; Friedman, Moshe; Lampe, Martin; Hubbard, Richard F.

    1994-05-01

    Relativistic klystron amplifiers (RKAs) were successfully operated at NRL in several frequency regimes and power levels. In particular, an L-band RKA was optimized for high- power rf extraction into the atmosphere and an S-band RKA was operated, both in a two-beam and a single-beam configuration. At L-band the rf extraction at maximum power levels (>= 15 GW) was hindered by pulse shortening and poor repeatability. Preliminary investigation showed electron emission in the radiating horn, due to very high voltages associated with the multi-gigawatt rf power levels. This electron current constituted an electric load in parallel with the radiating antenna, and precipitated the rf pulse collapse. At S-band the peak extracted power reached 1.7 GW with power efficiency approximately 50%. However, pulse shortening limited the duration to approximately 50 nanoseconds. The new triaxial RKA promises to solve many of the existing problems.

  1. Effect of terbinafine on the biosynthetic pathway of isoprenoid compounds in carrot suspension cultured cells.

    PubMed

    Miras-Moreno, Begoña; Almagro, Lorena; Pedreño, María Angeles; Sabater-Jara, Ana Belén

    2018-07-01

    Terbinafine induced a significant increase of squalene production. Terbinafine increased the expression levels of squalene synthase. Cyclodextrins did not work as elicitors due to the gene expression levels obtained. Plant sterols are essential components of membrane lipids, which contributing to their fluidity and permeability. Besides their cholesterol-lowering properties, they also have anti-inflammatory, antidiabetic and anticancer activities. Squalene, which is phytosterol precursor, is widely used in medicine, foods and cosmetics due to its anti-tumor, antioxidant and anti-aging activities. Nowadays, vegetable oils constitute the main sources of phytosterols and squalene, but their isolation and purification involve complex extraction protocols and high costs. In this work, Daucus carota cell cultures were used to evaluate the effect of cyclodextrins and terbinafine on the production and accumulation of squalene and phytosterols as well as the expression levels of squalene synthase and cycloartenol synthase genes. D. carota cell cultures were able to produce high levels of extracellular being phytosterols in the presence of cyclodextrins (12 mg/L), these compounds able to increase both the secretion and accumulation of phytosterols in the culture medium. Moreover, terbinafine induced a significant increase in intracellular squalene production, as seen after 168 h of treatment (497.0 ± 23.5 µg g dry weight -1 ) while its extracellular production only increased in the presence of cyclodextrins.The analysis of sqs and cas gene expression revealed that cyclodextrins did not induce genes encoding enzymes involved in the phytosterol biosynthetic pathway since the expression levels of sqs and cas genes in cyclodextrin-treated cells were lower than in control cells. The results, therefore, suggest that cyclodextrins were only able to release phytosterols from the cells to the extracellular medium, thus contributing to their acumulation. To sum up, D. carota cell cultures treated with cyclodextrins or terbinafine were able to produce high levels of phytosterols and squalene, respectively, and, therefore, these suspension-cultured cells of carrot constitute an alternative biotechnological system, which is at the same time more sustainable, economic and ecological for the production of these bioactive compounds.

  2. Sasang constitutional types for the risk prediction of metabolic syndrome: a 14-year longitudinal prospective cohort study.

    PubMed

    Lee, Sunghee; Lee, Seung Ku; Kim, Jong Yeol; Cho, Namhan; Shin, Chol

    2017-09-02

    To examine whether the use of Sasang constitutional (SC) types, such as Tae-yang (TY), Tae-eum (TE), So-yang (SY), and So-eum (SE) types, increases the accuracy of risk prediction for metabolic syndrome. From 2001 to 2014, 3529 individuals aged 40 to 69 years participated in a longitudinal prospective cohort. The Cox proportional hazard model was utilized to predict the risk of developing metabolic syndrome. During the 14 year follow-up, 1591 incident events of metabolic syndrome were observed. Individuals with TE type had higher body mass indexes and waist circumferences than individuals with SY and SE types. The risk of developing metabolic syndrome was the highest among individuals with the TE type, followed by the SY type and the SE type. When the prediction risk models for incident metabolic syndrome were compared, the area under the curve for the model using SC types was significantly increased to 0.8173. Significant predictors for incident metabolic syndrome were different according to the SC types. For individuals with the TE type, the significant predictors were age, sex, body mass index (BMI), education, smoking, drinking, fasting glucose level, high-density lipoprotein (HDL) cholesterol level, systolic and diastolic blood pressure, and triglyceride level. For Individuals with the SE type, the predictors were sex, smoking, fasting glucose, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level, while the predictors in individuals with the SY type were age, sex, BMI, smoking, drinking, total cholesterol level, fasting glucose level, HDL cholesterol level, systolic and diastolic blood pressure, and triglyceride level. In this prospective cohort study among 3529 individuals, we observed that utilizing the SC types significantly increased the accuracy of the risk prediction for the development of metabolic syndrome.

  3. [Body composition and constitution: a constitutional syndrome (1st of 2 parts)].

    PubMed

    Terán Díaz, E

    1999-04-01

    Constitutional syndrome alters body constitution modifying (usually decreasing) two of its dimensions--weight and perimeters--by changing the composition of one, several or every body levels. Apart of the cause, the basic physiopathological process that characterizes this new syndrome is the amino acid mobilization from the muscle (proteolysis). As soon as fat loss has no consequence to the organism, proteolysis reduces the muscle mass and life is in danger. Actually, there is no effective treatment to improve the nitrogen balance by medication or hormones in speed catabolic states but it can also approach us to more proper therapeutics for these so frequent processes in clinic.

  4. [Effect of sibutramine (meridia) on body composition, peptide YY3-36 and serotonin levels in patients with exogenous constitutional obesity].

    PubMed

    Vlasova, Iu Iu; Ametov, A S

    2010-01-01

    To evaluate the impact of gradual weight loss and the positive effect of sibutramine on metabolic parameters and the levels of serotonin and neuropeptide YY3-36 levels in patients with exogenous constitutional obesity (ECO). The study included 36 patients (24 women and 12 men; mean age 37.56 +/- 0.9 years) with a verified diagnosis of ECO. The height, body weight, waist and hip circumference (WC and HC), and body mass index (BMI) were determined. Adipose tissue content was estimated by a bioimpedance method using an adipose mass analyzer. Serum peptide YY3-36 levels were measured by enzyme immunoassay and blood serotonin concentrations were estimated by high performance liquid chromatography with an electrochemical method. 12-week sibutramine therapy caused a significant reduction in body weight, WC, HC, and BMI (p < 0.05) in all the patients. At the same time they were found to have a considerable body composition change (total body and visceral fat was decreased, total body water increased, and systemic metabolism was lowered). The mean peptide YY3-36 level was significantly decreased. Sibutramine did not affect the serum content of total serotonin in the sera of patients. Sibutramine used in the combined therapy in patients with ECO contributes to an effective and steady-state weight loss. Sibutramine treatment causes a reduction in total neuropeptide YY3-36, systemic metabolism, and adipose tissue at the expense of the visceral depot.

  5. Persistence of Protective Immunity to Malaria Induced by DNA Priming and Poxvirus Boosting: Characterization of Effector and Memory CD8+-T-Cell Populations

    PubMed Central

    Sedegah, Martha; Brice, Gary T.; Rogers, William O.; Doolan, Denise L.; Charoenvit, Yupin; Jones, Trevor R.; Majam, Victoria F.; Belmonte, Arnel; Lu, Minh; Belmonte, Maria; Carucci, Daniel J.; Hoffman, Stephen L.

    2002-01-01

    The persistence of immunity to malaria induced in mice by a heterologous DNA priming and poxvirus boosting regimen was characterized. Mice were immunized by priming with DNA vaccine plasmids encoding the Plasmodium yoelii circumsporozoite protein (PyCSP) and murine granulocyte-macrophage colony-stimulating factor and boosting with recombinant vaccinia encoding PyCSP. BALB/c mice immunized with either high-dose (100 μg of p PyCSP plus 30 μg of pGM-CSF) or low-dose (1 μg of p PyCSP plus 1 μg of pGM-CSF DNA) priming were protected against challenge with 50 P. yoelii sporozoites. Protection 2 weeks after immunization was 70 to 100%, persisted at this level for at least 20 weeks, and declined to 30 to 40% by 28 weeks. Eight of eight mice protected at 20 weeks were still protected when rechallenged at 40 weeks. The antigen (Ag)-specific effector CD8+-T-cell population present 2 weeks after boosting had ex vivo Ag-specific cytolytic activity, expressed both gamma interferon (IFN-γ) and tumor necrosis factor alpha, and constituted 12 to 20% of splenic CD8+ T cells. In contrast, the memory CD8+-Ag-specific-cell population at 28 weeks lacked cytolytic activity and constituted only 6% of splenic CD8+ T cells, but at the single-cell level it produced significantly higher levels of IFN-γ than the effectors. High levels of Ag- or parasite-specific antibodies present 2 weeks after boosting had declined three- to sevenfold by 28 weeks. Low-dose priming was similarly immunogenic and as protective as high-dose priming against a 50-, but not a 250-, sporozoite challenge. These results demonstrate that a heterologous priming and boosting vaccination can provide lasting protection against malaria in this model system. PMID:12065488

  6. Satellite -Based Networks for U-Health & U-Learning

    NASA Astrophysics Data System (ADS)

    Graschew, G.; Roelofs, T. A.; Rakowsky, S.; Schlag, P. M.

    2008-08-01

    The use of modern Information and Communication Technologies (ICT) as enabling tools for healthcare services (eHealth) introduces new ways of creating ubiquitous access to high-level medical care for all, anytime and anywhere (uHealth). Satellite communication constitutes one of the most flexible methods of broadband communication offering high reliability and cost-effectiveness of connections meeting telemedicine communication requirements. Global networks and the use of computers for educational purposes stimulate and support the development of virtual universities for e-learning. Especially real-time interactive applications can play an important role in tailored and personalised services.

  7. Lack of correlation between minimal erythema dose and skin phototype in a Colombian scholar population.

    PubMed

    Sanclemente, Gloria; Zapata, José-F; García, José-J; Gaviria, Angela; Gómez, Luis-F; Barrera, Marcela

    2008-11-01

    Sun exposure and skin phototype are the most relevant risk factors for skin cancer. Colombia has high levels of ultraviolet radiation during the whole year, therefore, both, high UVI's and outdoor worker's daily activities, in our country are very important risk factors for the development of cutaneous cancer. To date no study has evaluated the usefulness of Fitzpatrick's skin phototype classification in Colombians and its correlation with the minimal erythema dose (MED) and constitutional skin color. Such information is gaining importance in other nations due to the fact that several country's population is becoming more ethnically diverse. To determine the skin phototype, accumulated sun exposure, sun protection behavior, MED and phenotype in a Colombian school population. Last year high school students from the western Antioquia were invited to participate by phone and letter through their respective school directors. A self-questionnaire was handled to each student. A representative sample of the universe was selected for a medical examination by a dermatologist in order to validate the results of the self-questionnaire. The constitutional skin color was determined with the chromameter CR 300 Minolta. The MED was defined as the minimal dose of UVB being able to induce erythema 24 h later. Eight schools of the area agreed to participate in the study, and a total of 911 students (58% girls and 42% boys) filled-out the self-questionnaire. Sun exposure in the majority of individuals was in a level between moderate and very high. Ninety percent of students do not use any sun protection device or cream. Only a 50% of concordance between self-assessed skin phototype vs. medical skin phototype was found, and the highest concordance corresponded to skin phototype II (82%). There was a marked difference in skin photosensitivity of Colombians compared with reports in Caucasians. We observed a marked overlapping in MED's and L* values in phototypes II and III. The Fitzpatrick's classification was not useful in Hispanic populations such as ours. Therefore, a new skin-phototype classification system is required. In our population the constitutional color was a good predictor of the MED but it did not correlate with skin phototype. The self-assessed questionnaire method was not useful to determine skin cancer risk in our population. The majority of this population has light skin phototypes and is highly exposed to solar UV radiation without proper protection.

  8. Near-Patient Sampling to Assist Infection Control—A Case Report and Discussion

    PubMed Central

    Tang, Julian W.; Hoyle, Elizabeth; Moran, Sammy; Pareek, Manish

    2018-01-01

    Air sampling as an aid to infection control is still in an experimental stage, as there is no consensus about which air samplers and pathogen detection methods should be used, and what thresholds of specific pathogens in specific exposed populations (staff, patients, or visitors) constitutes a true clinical risk. This case report used a button sampler, worn or held by staff or left free-standing in a fixed location, for environmental sampling around a child who was chronically infected by a respiratory adenovirus, to determine whether there was any risk of secondary adenovirus infection to the staff managing the patient. Despite multiple air samples taken on difference days, coinciding with high levels of adenovirus detectable in the child’s nasopharyngeal aspirates (NPAs), none of the air samples contained any detectable adenovirus DNA using a clinically validated diagnostic polymerase chain reaction (PCR) assay. Although highly sensitive, in-house PCR assays have been developed to detect airborne pathogen RNA/DNA, it is still unclear what level of specific pathogen RNA/DNA constitutes a true clinical risk. In this case, the absence of detectable airborne adenovirus DNA using a conventional diagnostic assay removed the requirement for staff to wear surgical masks and face visors when they entered the child’s room. No subsequent staff infections or outbreaks of adenovirus have so far been identified. PMID:29385031

  9. Temporal transcriptome analysis of the white-rot fungus Obba rivulosa shows expression of a constitutive set of plant cell wall degradation targeted genes during growth on solid spruce wood.

    PubMed

    Marinović, Mila; Aguilar-Pontes, Maria Victoria; Zhou, Miaomiao; Miettinen, Otto; de Vries, Ronald P; Mäkelä, Miia R; Hildén, Kristiina

    2018-03-01

    The basidiomycete white-rot fungus Obba rivulosa, a close relative of Gelatoporia (Ceriporiopsis) subvermispora, is an efficient degrader of softwood. The dikaryotic O. rivulosa strain T241i (FBCC949) has been shown to selectively remove lignin from spruce wood prior to depolymerization of plant cell wall polysaccharides, thus possessing potential in biotechnological applications such as pretreatment of wood in pulp and paper industry. In this work, we studied the time-course of the conversion of spruce by the genome-sequenced monokaryotic O. rivulosa strain 3A-2, which is derived from the dikaryon T241i, to get insight into transcriptome level changes during prolonged solid state cultivation. During 8-week cultivation, O. rivulosa expressed a constitutive set of genes encoding putative plant cell wall degrading enzymes. High level of expression of the genes targeted towards all plant cell wall polymers was detected at 2-week time point, after which majority of the genes showed reduced expression. This implicated non-selective degradation of lignin by the O. rivulosa monokaryon and suggests high variation between mono- and dikaryotic strains of the white-rot fungi with respect to their abilities to convert plant cell wall polymers. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. One-step purification of a functional, constitutively activated form of visual arrestin.

    PubMed

    Huang, Li; Mao, Xiang; Abdulaev, Najmoutin G; Ngo, Tony; Liu, Wei; Ridge, Kevin D

    2012-03-01

    Desensitization of agonist-activated G protein-coupled receptors (GPCRs) requires phosphorylation followed by the binding of arrestin, a ~48 kDa soluble protein. While crystal structures for the inactive, 'basal' state of various arrestins are available, the conformation of 'activated' arrestin adopted upon interaction with activated GPCRs remains unknown. As a first step towards applying high-resolution structural methods to study arrestin conformation and dynamics, we have utilized the subtilisin prodomain/Profinity eXact™ fusion-tag system for the high-level bacterial expression and one-step purification of wild-type visual arrestin (arrestin 1) as well as a mutant form (R175E) of the protein that binds to non-phosphorylated, light-activated rhodopsin (Rho∗). The results show that both prodomain/Profinity eXact™ fusion-tagged wild-type and R175E arrestins can be expressed to levels approaching 2-3 mg/l in Luria-Bertani media, and that the processed, tag-free mature forms can be purified to near homogeneity using a Bio-Scale™ Mini Profinity eXact™ cartridge on the Profinia™ purification system. Functional analysis of R175E arrestin generated using this approach shows that it binds to non-phosphorylated rhodopsin in a light-dependent manner. These findings should facilitate the structure determination of this 'constitutively activated' state of arrestin 1 as well as the monitoring of conformational changes upon interaction with Rho∗. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Human rights, health, and capital accumulation in the Third World.

    PubMed

    Chossudovsky, M

    1979-01-01

    This article examines the relationship between human rights and the pattern of capital accumulation in the Third World. The repressive authoritarian State increasingly constitutes the means for enforcing the intensive exploitation of labor in Third World industrial enclaves and commercial agriculture. While the development of center capitalism has evolved toward "the Welfare State" and a framework of liberal sociodemocracy, the "peripheral State" is generally characterized by nondemocratic forms of government. This bipolarity in the state structure between center and periphery is functionally related to the international division of labor and the unity of production and circulation on a world level. The programs and policies of the center Welfare State (health, education, social security, etc.) constitute an input of "human capital" into the high-technology center labor process. Moreover, welfare programs in center countries activate the process of circulation by sustaining high levels of consumer demand. In underdeveloped countries, the underlying vacuum in the social sectors and the important allocations to military expenditure support the requirements of the peripheral labor process. Programs in health in the center and periphery are related to the bipolarity (qualification/dequalification) in the international division of labor. The social and economic functions of health programs are intimately related to the organic structure of the State and the mechanics whereby the State allocates its financial surplus in support of both capitalist production and circulation.

  12. Characteristics of TCM constitutions of adult Chinese women in Hong Kong and identification of related influencing factors: a cross-sectional survey

    PubMed Central

    2014-01-01

    Background Traditional Chinese Medicine Constitution (TCMC) refers to an integrated, metastable and natural specialty of individual in morphosis, physiological functions and psychological conditions. It is formed on the basis of innate and acquired endowments in the human life process, which can be divided into normal constitution and unbalanced ones. The aim of this study was to investigate the distribution of TCMCs of Chinese women in Hong Kong and its acquired influencing factors. Methods Local Chinese women between 30 to 65years old, were recruited from 18 districts of Hong Kong (n = 944), and were assessed using the Traditional Chinese Medicine Physical Constitution Scale for their TCMC types. Social-demographic, reproductive, lifestyle, systemic health and emotional status information were collected through structured questionnaire. The associations between different independent factors and each TCMC type, as well as the complex unbalanced TCMC types were tested individually. Significant factors related to unbalanced TCMC types were identified in final models using multiple factor analysis. Results A total of 764 (80.9%) participants were diagnosed with unbalanced TCMCs. The most common TCMC type was Qi-deficiency constitution (53.9%), followed by Phlegm-wetness (38.9%), Yang-deficiency (38.2%), Yin-deficiency (35.5), Blood-stasis (35.4) and Qi-depressed (31%) constitution. Six hundred and eleven participants (64.7%) had at least two types of combined and unbalanced constitutions. Stepwise logistic analysis indicated that poor systemic health condition (OR, 1.76-2.89), negative emotions (OR = 1.39), overweight (OR = 1.58), high educational level (OR = 1.18) and mental work (OR = 1.44) were significantly positively correlated with certain unbalanced TCMCs. Meanwhile, aging (OR, 0.59-0.73), exercise habit (OR, 0.61-0.79) and reproductive history (OR = 0.72) showed inverse associations with unbalanced constitutions. In addition, systemic health condition and emotional status, exercise habit and age were significantly associated with the combined unbalanced TCMC types. Conclusion The majority of middle-aged Chinese women in Hong Kong had unbalanced and complex TCMCs. Qi-deficiency, Phlegm-wetness and Yang-deficiency constitutions are the most common constitutions. Poor systemic health condition, less-than-satisfactory emotional life, overweight and mental work are associated with and may be contributors for the formation of unbalanced TCMCs, while regular physical exercise was found to be a potential protective factor for unbalanced TCMCs. PMID:24886055

  13. Modeling of NiTiHf using finite difference method

    NASA Astrophysics Data System (ADS)

    Farjam, Nazanin; Mehrabi, Reza; Karaca, Haluk; Mirzaeifar, Reza; Elahinia, Mohammad

    2018-03-01

    NiTiHf is a high temperature and high strength shape memory alloy with transformation temperatures above 100oC. A constitutive model based on Gibbs free energy is developed to predict the behavior of this material. Two different irrecoverable strains including transformation induced plastic strain (TRIP) and viscoplastic strain (VP) are considered when using high temperature shape memory alloys (HTSMAs). The first one happens during transformation at high levels of stress and the second one is related to the creep which is rate-dependent. The developed model is implemented for NiTiHf under uniaxial loading. Finite difference method is utilized to solve the proposed equations. The material parameters in the equations are calibrated from experimental data. Simulation results are captured to investigate the superelastic behavior of NiTiHf. The extracted results are compared with experimental tests of isobaric heating and cooling at different levels of stress and also superelastic tests at different levels of temperature. More results are generated to investigate the capability of the proposed model in the prediction of the irrecoverable strain after full transformation in HTSMAs.

  14. Prevention of Surgical Site Infections: Decontamination With Mupirocin Based on Preoperative Screening for Staphylococcus aureus Carriers or Universal Decontamination?

    PubMed

    Hetem, David J; Bootsma, Martin C J; Bonten, Marc J M

    2016-03-01

    Perioperative decolonization of Staphylococcus aureus nasal carriers with mupirocin together with chlorhexidine body washing reduces the incidence of S. aureus surgical site infection. A targeted strategy, applied in S. aureus carriers only, is costly, and implementation may reduce effectiveness. Universal decolonization is more cost-effective but increases exposure of noncarriers to mupirocin and the risk of resistance to mupirocin in staphylococci. High-level mupirocin resistance in S. aureus can emerge through horizontal gene transfer originating from coagulase-negative staphylococci (CoNS) and through clonal transmission. The current evidence on the occurrence of high-level mupirocin resistance in S. aureus and CoNS, in combination with the results of mathematical modeling, strongly suggests that the increased selection of high-level mupirocin resistance in CoNS does not constitute an important risk for high-level mupirocin resistance in S. aureus. Compared with a targeted strategy, universal decolonization seems associated with an equally low risk of mupirocin resistance in S. aureus. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  15. IAOseq: inferring abundance of overlapping genes using RNA-seq data.

    PubMed

    Sun, Hong; Yang, Shuang; Tun, Liangliang; Li, Yixue

    2015-01-01

    Overlapping transcription constitutes a common mechanism for regulating gene expression. A major limitation of the overlapping transcription assays is the lack of high throughput expression data. We developed a new tool (IAOseq) that is based on reads distributions along the transcribed regions to identify the expression levels of overlapping genes from standard RNA-seq data. Compared with five commonly used quantification methods, IAOseq showed better performance in the estimation accuracy of overlapping transcription levels. For the same strand overlapping transcription, currently existing high-throughput methods are rarely available to distinguish which strand was present in the original mRNA template. The IAOseq results showed that the commonly used methods gave an average of 1.6 fold overestimation of the expression levels of same strand overlapping genes. This work provides a useful tool for mining overlapping transcription levels from standard RNA-seq libraries. IAOseq could be used to help us understand the complex regulatory mechanism mediated by overlapping transcripts. IAOseq is freely available at http://lifecenter.sgst.cn/main/en/IAO_seq.jsp.

  16. A Latent Class Analysis of Heterosexual Young Men’s Masculinities

    PubMed Central

    Masters, N. Tatiana; Beadnell, Blair; Wells, Elizabeth A.; Morrison, Diane M.; Hoppe, Marilyn J.

    2015-01-01

    Parallel bodies of research have described the diverse and complex ways that men understand and construct their masculine identities (often termed“masculinities”) and, separately, how adherence to traditional notions of masculinity places men at risk for negative sexual and health outcomes. The goal of this analysis was to bring together these two streams of inquiry. Using data from a national, online sample of 555 hetero-sexually active young men, we employed latent class analysis (LCA) to detect patterns of masculine identities based on men’s endorsement of behavioral and attitudinal indicators of“dominant” masculinity, including sexual attitudes and behaviors. LCA identified four conceptually distinct masculine identity profiles. Twogroups, termed the Normative and Normative/Male Activities groups, respectively, constituted 88 % of the sample and were characterized by low levels of adherence to attitudes, sexual scripts, and behaviors consistent with“dominant”masculinity, but differed in their levels of engagement in male-oriented activities (e.g., sports teams). Only eight percent of the sample comprised a masculinity profile consistent with “traditional” ideas about masculinity; this group was labeled Misogynistic because of high levels of sexual assault and violence toward female partners. The remaining four percent constituted a Sex-Focused group, characterized by high numbers of sexual partners, but relatively low endorsement of other indicators of traditional masculinity. Follow-up analyses showed a small number of differences across groups on sexual and substance use health indicators. Findings have implications for sexual and behavioral health interventions and suggest that very few young men embody or endorse rigidly traditional forms of masculinity. PMID:26496914

  17. A Latent Class Analysis of Heterosexual Young Men's Masculinities.

    PubMed

    Casey, Erin A; Masters, N Tatiana; Beadnell, Blair; Wells, Elizabeth A; Morrison, Diane M; Hoppe, Marilyn J

    2016-07-01

    Parallel bodies of research have described the diverse and complex ways that men understand and construct their masculine identities (often termed "masculinities") and, separately, how adherence to traditional notions of masculinity places men at risk for negative sexual and health outcomes. The goal of this analysis was to bring together these two streams of inquiry. Using data from a national, online sample of 555 heterosexually active young men, we employed latent class analysis (LCA) to detect patterns of masculine identities based on men's endorsement of behavioral and attitudinal indicators of "dominant" masculinity, including sexual attitudes and behaviors. LCA identified four conceptually distinct masculine identity profiles. Two groups, termed the Normative and Normative/Male Activities groups, respectively, constituted 88 % of the sample and were characterized by low levels of adherence to attitudes, sexual scripts, and behaviors consistent with "dominant" masculinity, but differed in their levels of engagement in male-oriented activities (e.g., sports teams). Only eight percent of the sample comprised a masculinity profile consistent with "traditional" ideas about masculinity; this group was labeled Misogynistic because of high levels of sexual assault and violence toward female partners. The remaining four percent constituted a Sex-Focused group, characterized by high numbers of sexual partners, but relatively low endorsement of other indicators of traditional masculinity. Follow-up analyses showed a small number of differences across groups on sexual and substance use health indicators. Findings have implications for sexual and behavioral health interventions and suggest that very few young men embody or endorse rigidly traditional forms of masculinity.

  18. The Fate of Teaching Constitutional Principles to Middle School Students.

    ERIC Educational Resources Information Center

    Wolf, Alvin

    1990-01-01

    Advocates teaching constitutional history and principles to middle school students in accordance with the 1988 California History-Social Science Framework. Reports findings of a survey of 118 California middle school and high school teachers that revealed a need for improved teacher knowledge about the U.S. Constitution. Recommends steps to ensure…

  19. Funding Florida's Schools: Adequacy, Costs, and the State Constitution. Policy Brief.

    ERIC Educational Resources Information Center

    Harris, Douglas N.

    2004-01-01

    In 1998, Florida voters passed a unique amendment to the state constitution requiring the state to make "adequate provision...for a uniform, efficient, safe, secure, and high quality system of free public schools." This brief examines how Florida courts are likely to interpret this constitutional amendment and whether Florida's funding system will…

  20. Variation in flooding-induced morphological traits in natural populations of white clover (Trifolium repens) and their effects on plant performance during soil flooding

    PubMed Central

    Huber, Heidrun; Jacobs, Elke; Visser, Eric J. W.

    2009-01-01

    Background and Aims Soil flooding leads to low soil oxygen concentrations and thereby negatively affects plant growth. Differences in flooding tolerance have been explained by the variation among species in the extent to which traits related to acclimation were expressed. However, our knowledge of variation within natural species (i.e. among individual genotypes) in traits related to flooding tolerance is very limited. Such data could tell us on which traits selection might have taken place, and will take place in future. The aim of the present study was to show that variation in flooding-tolerance-related traits is present among genotypes of the same species, and that both the constitutive variation and the plastic variation in flooding-induced changes in trait expression affect the performance of genotypes during soil flooding. Methods Clones of Trifolium repens originating from a river foreland were subjected to either drained, control conditions or to soil flooding. Constitutive expression of morphological traits was recorded on control plants, and flooding-induced changes in expression were compared with these constitutive expression levels. Moreover, the effect of both constitutive and flooding-induced trait expression on plant performance was determined. Key Results Constitutive and plastic variation of several morphological traits significantly affected plant performance. Even relatively small increases in root porosity and petiole length contributed to better performance during soil flooding. High specific leaf area, by contrast, was negatively correlated with performance during flooding. Conclusions The data show that different genotypes responded differently to soil flooding, which could be linked to variation in morphological trait expression. As flooded and drained conditions exerted different selection pressures on trait expression, the optimal value for constitutive and plastic traits will depend on the frequency and duration of flooding. These data will help us understanding the mechanisms affecting short- and long-term dynamics in flooding-prone ecosystems. PMID:18713824

  1. A multiresolutional approach to fuzzy text meaning: A first attempt

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

    Mehler, A.

    1996-12-31

    The present paper focuses on the connotative meaning aspect of language signs especially above the level of words. In this context the view is taken that texts can be defined as a kind of supersign, to which-in the same way as to other signs-a meaning can be assigned. A text can therefore be described as the result of a sign articulation which connects the material text sign with a corresponding meaning. For the constitution of the structural text meaning a kind of a semiotic composition principle is responsible, which leads to the emergence of interlocked levels of language units, demonstratingmore » different grades of resolution. Starting on the level of words, and going through the level of sentences this principle reaches finally the level of texts by aggregating step by step the meaning of a unit on a higher level out of the meanings of all components one level below, which occur within this unit. Besides, this article will elaborate the hypothesis that the meaning constitution as a two-stage process, corresponding to the syntagmatic and paradigmatic restrictions of language elements among each other, obtains equally on the level of texts. On text level this two-levelledness leads to the constitution of the connotative text meaning, whose constituents are determined on word level by the syntagmatic and paradigmatic relations of the words. The formalization of the text meaning representation occurs with the help of fuzzy set theory.« less

  2. Quality Audit in the Fastener Industry

    NASA Technical Reports Server (NTRS)

    Reagan, John R.

    1995-01-01

    Both the financial and quality communities rely on audits to verify customers records. The financial community is highly structured around three categories of risk, INHERENT RISK, CONTROL RISK, and DETECTION RISK. Combined, the product of these three categories constitute the AUDIT RISK. The financial community establishes CONTROL RISK based in large part on a systems level understanding of the process flow. This system level understanding is best expressed in a flowchart. The quality community may be able to adopt this structure and thereby reduce cost while maintaining and enhancing quality. The quality community should attempt to flowchart the systems level quality process before beginning substantive testing. This theory needs to be applied in several trial cases to prove or disprove this hypothesis

  3. Quality audit in the fastener industry

    NASA Astrophysics Data System (ADS)

    Reagan, John R.

    1995-09-01

    Both the financial and quality communities rely on audits to verify customers records. The financial community is highly structured around three categories of risk, INHERENT RISK, CONTROL RISK, and DETECTION RISK. Combined, the product of these three categories constitute the AUDIT RISK. The financial community establishes CONTROL RISK based in large part on a systems level understanding of the process flow. This system level understanding is best expressed in a flowchart. The quality community may be able to adopt this structure and thereby reduce cost while maintaining and enhancing quality. The quality community should attempt to flowchart the systems level quality process before beginning substantive testing. This theory needs to be applied in several trial cases to prove or disprove this hypothesis

  4. Characterisation of rebound depolarisation in mice deep dorsal horn neurons in vitro.

    PubMed

    Rivera-Arconada, Ivan; Lopez-Garcia, Jose A

    2015-09-01

    Spinal dorsal horn neurons constitute the first relay for pain processing and participate in the processing of other sensory, motor and autonomic information. At the cellular level, intrinsic excitability is a factor contributing to network function. In turn, excitability is set by the array of ionic conductance expressed by neurons. Here, we set out to characterise rebound depolarisation following hyperpolarisation, a feature frequently described in dorsal horn neurons but never addressed in depth. To this end, an in vitro preparation of the spinal cord from mice pups was used combined with whole-cell recordings in current and voltage clamp modes. Results show the expression of H- and/or T-type currents in a significant proportion of dorsal horn neurons. The expression of these currents determines the presence of rebound behaviour at the end of hyperpolarising pulses. T-type calcium currents were associated to high-amplitude rebounds usually involving high-frequency action potential firing. H-currents were associated to low-amplitude rebounds less prone to elicit firing or firing at lower frequencies. For a large proportion of neurons expressing both currents, the H-current constitutes a mechanism to ensure a faster response after hyperpolarisations, adjusting the latency of the rebound firing. We conclude that rebound depolarisation and firing are intrinsic factors to many dorsal horn neurons that may constitute a mechanism to integrate somatosensory information in the spinal cord, allowing for a rapid switch from inhibited-to-excited states.

  5. Differential requirements of arrestin-3 and clathrin for ligand-dependent and -independent internalization of human G protein-coupled receptor 40.

    PubMed

    Qian, Jing; Wu, Chun; Chen, Xiaopan; Li, Xiangmei; Ying, Guoyuan; Jin, Lili; Ma, Qiang; Li, Guo; Shi, Ying; Zhang, Guozheng; Zhou, Naiming

    2014-11-01

    G protein-coupled receptor 40 (GPR40) is believed to be an attractive target to enhance insulin secretion in patients with type 2 diabetes. GPR40 has been found to couple to Gq protein, leading to the activation of phospholipase C and subsequent increases in the intracellular Ca(2+) level. However, the underlying mechanisms that regulate the internalization and desensitization of GPR40 remain to be elucidated. In the present study, a construct of GPR40 fused with enhanced green fluorescent protein (EGFP) at its C-terminus was constructed for direct imaging of the localization and internalization of GPR40 by confocal microscopy. In stably transfected HEK-293 cells, GPR40 receptors underwent rapid agonist-induced internalization and constitutive ligand-independent internalization. Our data demonstrated that the agonist-mediated internalization of GPR40 was significantly blocked by hypertonic sucrose treatment and by siRNA mediated depletion of the heavy chain of clathrin. In contrast, constitutive GPR40 internalization was not affected by hypertonic sucrose or by knock-down of clathrin expression, but it was affected by treatment with methyl-β-cyclodextrin (MβCD) and nystatin. Furthermore, our results using an arrestin-3-EGFP redistribution assay and siRNA-mediated knock-down of arrestin-3 and GRK2 expression revealed that arrestin-3 and GRK2 play an essential role in the regulation of agonist-mediated GPR40 internalization, but are not involved in the regulation of constitutive GPR40 internalization. Additionally, our observation showed that upon activation by agonist, the internalized GPR40 receptors were rapidly recycled back to the plasma membrane via Rab4/Rab5 positive endosomes, whereas the constitutively internalized GPR40 receptors were recycled back to the cell surface through Rab5 positive endosomes. Because FFA receptors exhibit a high level of homology, our observations could be applicable to other members of this family. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Genetic requirements for high constitutive SOS expression in recA730 mutants of Escherichia coli.

    PubMed

    Vlašić, Ignacija; Šimatović, Ana; Brčić-Kostić, Krunoslav

    2011-09-01

    The RecA protein in its functional state is in complex with single-stranded DNA, i.e., in the form of a RecA filament. In SOS induction, the RecA filament functions as a coprotease, enabling the autodigestion of the LexA repressor. The RecA filament can be formed by different mechanisms, but all of them require three enzymatic activities essential for the processing of DNA double-stranded ends. These are helicase, 5'-3' exonuclease, and RecA loading onto single-stranded DNA (ssDNA). In some mutants, the SOS response can be expressed constitutively during the process of normal DNA metabolism. The RecA730 mutant protein is able to form the RecA filament without the help of RecBCD and RecFOR mediators since it better competes with the single-strand binding (SSB) protein for ssDNA. As a consequence, the recA730 mutants show high constitutive SOS expression. In the study described in this paper, we studied the genetic requirements for constitutive SOS expression in recA730 mutants. Using a β-galactosidase assay, we showed that the constitutive SOS response in recA730 mutants exhibits different requirements in different backgrounds. In a wild-type background, the constitutive SOS response is partially dependent on RecBCD function. In a recB1080 background (the recB1080 mutation retains only helicase), constitutive SOS expression is partially dependent on RecBCD helicase function and is strongly dependent on RecJ nuclease. Finally, in a recB-null background, the constitutive SOS expression of the recA730 mutant is dependent on the RecJ nuclease. Our results emphasize the importance of the 5'-3' exonuclease for high constitutive SOS expression in recA730 mutants and show that RecBCD function can further enhance the excellent intrinsic abilities of the RecA730 protein in vivo. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

  7. Effect of SOS-induced levels of imuABC on spontaneous and damage-induced mutagenesis in Caulobacter crescentus.

    PubMed

    Alves, Ingrid R; Lima-Noronha, Marco A; Silva, Larissa G; Fernández-Silva, Frank S; Freitas, Aline Luiza D; Marques, Marilis V; Galhardo, Rodrigo S

    2017-11-01

    imuABC (imuAB dnaE2) genes are responsible for SOS-mutagenesis in Caulobacter crescentus and other bacterial species devoid of umuDC. In this work, we have constructed operator-constitutive mutants of the imuABC operon. We used this genetic tool to investigate the effect of SOS-induced levels of these genes upon both spontaneous and damage-induced mutagenesis. We showed that constitutive expression of imuABC does not increase spontaneous or damage-induced mutagenesis, nor increases cellular resistance to DNA-damaging agents. Nevertheless, the presence of the operator-constitutive mutation rescues mutagenesis in a recA background, indicating that imuABC are the only genes required at SOS-induced levels for translesion synthesis (TLS) in C. crescentus. Furthermore, these data also show that TLS mediated by ImuABC does not require RecA, unlike umuDC-dependent mutagenesis in E. coli. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Endocytosis and Vacuolar Degradation of the Yeast Cell Surface Glucose Sensors Rgt2 and Snf3*

    PubMed Central

    Roy, Adhiraj; Kim, Jeong-Ho

    2014-01-01

    Sensing and signaling the presence of extracellular glucose is crucial for the yeast Saccharomyces cerevisiae because of its fermentative metabolism, characterized by high glucose flux through glycolysis. The yeast senses glucose through the cell surface glucose sensors Rgt2 and Snf3, which serve as glucose receptors that generate the signal for induction of genes involved in glucose uptake and metabolism. Rgt2 and Snf3 detect high and low glucose concentrations, respectively, perhaps because of their different affinities for glucose. Here, we provide evidence that cell surface levels of glucose sensors are regulated by ubiquitination and degradation. The glucose sensors are removed from the plasma membrane through endocytosis and targeted to the vacuole for degradation upon glucose depletion. The turnover of the glucose sensors is inhibited in endocytosis defective mutants, and the sensor proteins with a mutation at their putative ubiquitin-acceptor lysine residues are resistant to degradation. Of note, the low affinity glucose sensor Rgt2 remains stable only in high glucose grown cells, and the high affinity glucose sensor Snf3 is stable only in cells grown in low glucose. In addition, constitutively active, signaling forms of glucose sensors do not undergo endocytosis, whereas signaling defective sensors are constitutively targeted for degradation, suggesting that the stability of the glucose sensors may be associated with their ability to sense glucose. Therefore, our findings demonstrate that the amount of glucose available dictates the cell surface levels of the glucose sensors and that the regulation of glucose sensors by glucose concentration may enable yeast cells to maintain glucose sensing activity at the cell surface over a wide range of glucose concentrations. PMID:24451370

  9. Soluble Axl Is Generated by ADAM10-Dependent Cleavage and Associates with Gas6 in Mouse Serum†

    PubMed Central

    Budagian, Vadim; Bulanova, Elena; Orinska, Zane; Duitman, Erwin; Brandt, Katja; Ludwig, Andreas; Hartmann, Dieter; Lemke, Greg; Saftig, Paul; Bulfone-Paus, Silvia

    2005-01-01

    Axl receptor tyrosine kinase exists as a transmembrane protein and as a soluble molecule. We show that constitutive and phorbol 12-myristate 13-acetate-induced generation of soluble Axl (sAxl) involves the activity of disintegrin-like metalloproteinase 10 (ADAM10). Spontaneous and inducible Axl cleavage was inhibited by the broad-spectrum metalloproteinase inhibitor GM6001 and by hydroxamate GW280264X, which is capable of blocking ADAM10 and ADAM17. Furthermore, murine fibroblasts deficient in ADAM10 expression exhibited a significant reduction in constitutive and inducible Axl shedding, whereas reconstitution of ADAM10 restored sAxl production, suggesting that ADAM10-mediated proteolysis constitutes a major mechanism for sAxl generation in mice. Partially overlapping 14-amino-acid stretch deletions in the membrane-proximal region of Axl dramatically affected sAxl generation, indicating that these regions are involved in regulating the access of the protease to the cleavage site. Importantly, relatively high circulating levels of sAxl are present in mouse sera in a heterocomplex with Axl ligand Gas6. Conversely, two other family members, Tyro3 and Mer, were not detected in mouse sera and conditioned medium. sAxl is constitutively released by murine primary cells such as dendritic and transformed cell lines. Upon immobilization, sAxl promoted cell migration and induced the phosphorylation of Axl and phosphatidylinositol 3-kinase. Thus, ADAM10-mediated generation of sAxl might play an important role in diverse biological processes. PMID:16227584

  10. The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell alloantigen presentation to CD4+ T cells.

    PubMed

    Griffiths, C E; Railan, D; Gallatin, W M; Cooper, K D

    1995-12-01

    Intercellular adhesion molecule (ICAM)-3 is a recently described member of the immunoglobulin superfamily and, as such, is closely related to ICAM-1 and ICAM-2. All three ICAMS are cognate for the counter-receptor lymphocyte function associated antigen-1 (LFA-1, CD11a/CD18). Unlike ICAM-1 and ICAM-2, ICAM-3 is constitutively expressed at high levels on resting leucocytes. We investigated the expression and function of ICAM-3 in normal skin (n = 5), as well as its expression in psoriasis (n = 4), atopic eczema (n = 4), allergic (rhus) contact dermatitis (n = 3), and cutaneous T-cell lymphoma (CTCL, n = 2). Five-micrometre cryostat sections of skin were stained using monoclonal antibodies to ICAM-3 and a well characterized immunoperoxidase technique. In normal skin, ICAM-3 was expressed by all cutaneous leucocytes but most striking was the strong expression of ICAM-3 by Langerhans cells within both epidermis and dermis. This observation was confirmed by double-labelling with CD1a and negative staining with an IgG1 isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and CTCL, ICAM-3 was co-expressed on all CD1a+ cells, although, in psoriasis, the intensity of ICAM-3 expression was reduced. Functional blocking experiments were performed to determine whether the observed ICAM-3 expression on Langerhans cells was functionally important in antigen presentation. CD4+ T cells were prepared from peripheral blood and 10(5) CD4+ T cells combined with 10(5) epidermal cells harvested from keratome biopsies of normal skin of an individual allogeneic to the T-cell donor. Addition of 50 micrograms anti-ICAM-3 to the co-culture resulted in a consistent (50%) reduction in degree of alloantigen presentation by Langerhans cells to T cells. Inhibition was 77% of that produced by the addition of anti-LFA-1. These data indicate that ICAM-3 is constitutively expressed by Langerhans cells and is a major ligand for LFA-1 on CD4+ T cells during their response to Langerhans cells. Because fresh Langerhans cells constitutively express little ICAM-1, whereas ICAM-3 is constitutively expressed at high levels, it would appear that ICAM-3 is the dominant functional ICAM on in situ Langerhans cells in the normal epidermis.

  11. A Modified Constitutive Model for Tensile Flow Behaviors of BR1500HS Ultra-High-Strength Steel at Medium and Low Temperature Regions

    NASA Astrophysics Data System (ADS)

    Zhao, Jun; Quan, Guo-Zheng; Pan, Jia; Wang, Xuan; Wu, Dong-Sen; Xia, Yu-Feng

    2018-01-01

    Constitutive model of materials is one of the most requisite mathematical model in the finite element analysis, which describes the relationships of flow behaviors with strain, strain rate and temperature. In order to construct such constitutive relationships of ultra-high-strength BR1500HS steel at medium and low temperature regions, the true stress-strain data over a wide temperature range of 293-873 K and strain rate range of 0.01-10 s-1 were collected from a series of isothermal uniaxial tensile tests. The experimental results show that stress-strain relationships are highly non-linear and susceptible to three parameters involving temperature, strain and strain rate. By considering the impacts of strain rate and temperature on strain hardening, a modified constitutive model based on Johnson-Cook model was proposed to characterize flow behaviors in medium and low temperature ranges. The predictability of the improved model was also evaluated by the relative error (W(%)), correlation coefficient (R) and average absolute relative error (AARE). The R-value and AARE-value for modified constitutive model at medium and low temperature regions are 0.9915 & 1.56 % and 0.9570 & 5.39 %, respectively, which indicates that the modified constitutive model can precisely estimate the flow behaviors for BR1500HS steel in the medium and low temperature regions.

  12. We the People: Law-Related Lessons on Teaching the Constitution.

    ERIC Educational Resources Information Center

    Constitutional Rights Foundation, Chicago, IL.

    The Unites States Constitution and the Bill of Rights set forth the basic principles of the U.S. democratic constitutional order. It is from these documents that the fundamental political concepts of the United States are derived. The program presented here was developed for junior high school students and is intended to combat the apathy toward…

  13. Criminal Justice Majors' Basic Knowledge of U.S. Constitutional Rights and Pedagogical Implications

    ERIC Educational Resources Information Center

    Heuer, Janet; Coggins, Porter E.

    2017-01-01

    Criminal justice students preparing at the university level will be required to possess knowledge and understanding of applicable constitutional law, rights and responsibilities upon entering their profession to ensure the competent execution of the duties of which they will be entrusted to perform. Students majoring in the criminal justice field…

  14. The Constitution of the United States (Adapted). For Use in EMR Classes.

    ERIC Educational Resources Information Center

    Miller, Louise A.

    This special instructional handbook presents a unit of study on the United States Constitution for educable mentally retarded students at the secondary level. The adapted material explains the structure of the national government, and is designed to promote citizenship and patriotic values. Preliminary information includes a glossary of new words,…

  15. Hydrological states and the resilience of deltaic forested wetlands

    NASA Astrophysics Data System (ADS)

    Keim, R.; Allen, S. T.

    2017-12-01

    The flooding regime constitutes a set of chronic disturbances that are largely responsible for ecosystem structure. However, disturbances do not always constitute stresses to plants that survive because of adaptations to flooded conditions. We examine baldcypress-water tupelo forested wetlands in the delta of the Mississippi River as a case study in mechanisms by which hydrologic change shapes wetland ecosystem change, supported by experimental evidence from remote sensing, tree-ring and other field studies, and meta-analysis across the literature. Decreased hydrologic variability caused by water control structures has reduced the frequency of flood events that increase growth of baldcypress and favor its establishment by reducing competition from other species. Hydrologic modifications that lead to semi-permanent, stagnant flooding constitute semi-permanent disturbance that prevents regeneration of any trees, reduces growth of established trees, and reduces stand density by causing mortality of some trees. However, baldcypress trees in low-density stands appear to be generally adapted for long-term survival in stagnant conditions. Thus, initial decreases in stand density after impoundment do not necessarily portend continued conversion away from forest because reduced inter-tree competition is a negative feedback on mortality. Overall, a natural hydrologic regime with high variability in riverine flooding favors denser stands with greater diversity of tree species, and the present, controlled hydrologic regime that has largely eliminated riverine flooding favors open stands. Sea-level rise will increase salinity that quickly leads to forest conversion to marsh, but will also increase stagnant, freshwater flooding further inland. These drivers of hydrologic change reduce carbon assimilation by forests, both by reduced stand-level productivity and decreased forested area.

  16. Regulatory Subunit B′γ of Protein Phosphatase 2A Prevents Unnecessary Defense Reactions under Low Light in Arabidopsis1[W][OA

    PubMed Central

    Trotta, Andrea; Wrzaczek, Michael; Scharte, Judith; Tikkanen, Mikko; Konert, Grzegorz; Rahikainen, Moona; Holmström, Maija; Hiltunen, Hanna-Maija; Rips, Stephan; Sipari, Nina; Mulo, Paula; Weis, Engelbert; von Schaewen, Antje; Aro, Eva-Mari; Kangasjärvi, Saijaliisa

    2011-01-01

    Light is an important environmental factor that modulates acclimation strategies and defense responses in plants. We explored the functional role of the regulatory subunit B′γ (B′γ) of protein phosphatase 2A (PP2A) in light-dependent stress responses of Arabidopsis (Arabidopsis thaliana). The predominant form of PP2A consists of catalytic subunit C, scaffold subunit A, and highly variable regulatory subunit B, which determines the substrate specificity of PP2A holoenzymes. Mutant leaves of knockdown pp2a-b′γ plants show disintegration of chloroplasts and premature yellowing conditionally under moderate light intensity. The cell-death phenotype is accompanied by the accumulation of hydrogen peroxide through a pathway that requires CONSTITUTIVE EXPRESSION OF PR GENES5 (CPR5). Moreover, the pp2a-b′γ cpr5 double mutant additionally displays growth suppression and malformed trichomes. Similar to cpr5, the pp2a-b′γ mutant shows constitutive activation of both salicylic acid- and jasmonic acid-dependent defense pathways. In contrast to cpr5, however, pp2a-b′γ leaves do not contain increased levels of salicylic acid or jasmonic acid. Rather, the constitutive defense response associates with hypomethylation of DNA and increased levels of methionine-salvage pathway components in pp2a-b′γ leaves. We suggest that the specific B′γ subunit of PP2A is functionally connected to CPR5 and operates in the basal repression of defense responses under low irradiance. PMID:21571669

  17. A procedure for utilization of a damage-dependent constitutive model for laminated composites

    NASA Technical Reports Server (NTRS)

    Lo, David C.; Allen, David H.; Harris, Charles E.

    1992-01-01

    Described here is the procedure for utilizing a damage constitutive model to predict progressive damage growth in laminated composites. In this model, the effects of the internal damage are represented by strain-like second order tensorial damage variables and enter the analysis through damage dependent ply level and laminate level constitutive equations. The growth of matrix cracks due to fatigue loading is predicted by an experimentally based damage evolutionary relationship. This model is incorporated into a computer code called FLAMSTR. This code is capable of predicting the constitutive response and matrix crack damage accumulation in fatigue loaded laminated composites. The structure and usage of FLAMSTR are presented along with sample input and output files to assist the code user. As an example problem, an analysis of crossply laminates subjected to two stage fatigue loading was conducted and the resulting damage accumulation and stress redistribution were examined to determine the effect of variations in fatigue load amplitude applied during the first stage of the load history. It was found that the model predicts a significant loading history effect on damage evolution.

  18. Complexity of Multi-Dimensional Spontaneous EEG Decreases during Propofol Induced General Anaesthesia

    PubMed Central

    Schartner, Michael; Seth, Anil; Noirhomme, Quentin; Boly, Melanie; Bruno, Marie-Aurelie; Laureys, Steven; Barrett, Adam

    2015-01-01

    Emerging neural theories of consciousness suggest a correlation between a specific type of neural dynamical complexity and the level of consciousness: When awake and aware, causal interactions between brain regions are both integrated (all regions are to a certain extent connected) and differentiated (there is inhomogeneity and variety in the interactions). In support of this, recent work by Casali et al (2013) has shown that Lempel-Ziv complexity correlates strongly with conscious level, when computed on the EEG response to transcranial magnetic stimulation. Here we investigated complexity of spontaneous high-density EEG data during propofol-induced general anaesthesia. We consider three distinct measures: (i) Lempel-Ziv complexity, which is derived from how compressible the data are; (ii) amplitude coalition entropy, which measures the variability in the constitution of the set of active channels; and (iii) the novel synchrony coalition entropy (SCE), which measures the variability in the constitution of the set of synchronous channels. After some simulations on Kuramoto oscillator models which demonstrate that these measures capture distinct ‘flavours’ of complexity, we show that there is a robustly measurable decrease in the complexity of spontaneous EEG during general anaesthesia. PMID:26252378

  19. Unified constitutive models for high-temperature structural applications

    NASA Technical Reports Server (NTRS)

    Lindholm, U. S.; Chan, K. S.; Bodner, S. R.; Weber, R. M.; Walker, K. P.

    1988-01-01

    Unified constitutive models are characterized by the use of a single inelastic strain rate term for treating all aspects of inelastic deformation, including plasticity, creep, and stress relaxation under monotonic or cyclic loading. The structure of this class of constitutive theory pertinent for high temperature structural applications is first outlined and discussed. The effectiveness of the unified approach for representing high temperature deformation of Ni-base alloys is then evaluated by extensive comparison of experimental data and predictions of the Bodner-Partom and the Walker models. The use of the unified approach for hot section structural component analyses is demonstrated by applying the Walker model in finite element analyses of a benchmark notch problem and a turbine blade problem.

  20. Glutathione-S-transferase profiles in the emerald ash borer, Agrilus planipennis.

    PubMed

    Rajarapu, Swapna Priya; Mittapalli, Omprakash

    2013-05-01

    The emerald ash borer, Agrilus planipennis Fairmaire is a recently discovered invasive insect pest of ash, Fraxinus spp. in North America. Glutathione-S-transferases (GST) are a multifunctional superfamily of enzymes which function in conjugating toxic compounds to less toxic and excretable forms. In this study, we report the molecular characterization and expression patterns of different classes of GST genes in different tissues and developmental stages plus their specific activity. Multiple sequence alignment of all six A. planipennis GSTs (ApGST-E1, ApGST-E2, ApGST-E3, ApGST-O1, ApGST-S1 and ApGST-μ1) revealed conserved features of insect GSTs and a phylogenetic analysis grouped the GSTs within the epsilon, sigma, omega and microsomal classes of GSTs. Real time quantitative PCR was used to study field collected samples. In larval tissues high mRNA levels for ApGST-E1, ApGST-E3 and ApGST-O1 were obtained in the midgut and Malpighian tubules. On the other hand, ApGST-E2 and ApGST-S1 showed high mRNA levels in fat body and ApGST-μ1 showed constitutive levels in all the tissues assayed. During development, mRNA levels for ApGST-E2 were observed to be the highest in feeding instars, ApGST-S1 in prepupal instars; while the others showed constitutive patterns in all the developmental stages examined. At the enzyme level, total GST activity was similar in all the tissues and developmental stages assayed. Results obtained suggest that A. planipennis is potentially primed with GST-driven detoxification to metabolize ash allelochemicals. To our knowledge this study represents the first report of GSTs in A. planipennis and also in the family of wood boring beetles. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Longitudinal Examination of Links Between Risk Factors for the Metabolic Syndrome and Both Age and Fasting Glucose Levels in Nondiabetic Subjects.

    PubMed

    Preuss, Harry G; Kaats, Gilbert R; Mrvichin, Nate; Bagchi, Debasis; Swaroop, Anand

    2018-01-01

    Previous evaluations in nondiabetic subjects revealed statistically significant correlations between fasting blood glucose (FBG) levels used as an estimate of insulin resistance and many components constituting the metabolic syndrome. Similar significant correlations were not found employing chronological age as the independent variable in the same nondiabetic individuals. The major purpose here was to replicate as well as corroborate the previous cross-sectional observations, emphasizing results obtained from data collected longitudinally. Material was assessed from 99 nondiabetic volunteers who had undergone 2 separate baseline measurements carried out over a minimum of 5 and up to a maximum of 20 years. Findings from the starting baseline measurements mimicked many observations perceived in the earlier published cross-sectional material. The following correlations with elements constituting the metabolic syndrome using FBG as an independent variable were once more statistically significantly positive: scale weight, fat mass, circulating levels of triglycerides and high-sensitivity C-reactive protein (hsCRP). High-density lipoprotein (HDL) cholesterol was once again appropriately significant in a negative direction. In contrast, the same correlations were generally nonsignificant when age replaced FBG as the independent variable. Examining the 2 data sets over the 5-20-year intervals, FBG increased statistically significantly over time. However, the average increase clinically was relatively minor: -92.1 mg/dL ± 1.1 (SEM) vs 95.1 mg/dL ± 1.1 (SEM), p < 0.007. When the actual changes (delta) in the dependent parameters were correlated with the individual passages of time (intervals in years), only downward changes in aspartate aminotransferase (AST) levels were statistically significant. Fat-free mass showed a trend downward, whereas fat mass, trunk fat, and triglycerides merely demonstrated trends upward. Current findings gathered over years are consistent with the original hypothesis that maintaining relatively low, stable circulating glucose levels during aging retards the development and intensity of many common manifestations of the metabolic syndrome.

  2. [Somatic constitution and the ability to maintain dynamic body equilibrium in girls practicing rhythmic gymnastics].

    PubMed

    Poliszczuk, Tatiana; Broda, Daria

    2010-01-01

    The greatest similarities in body constitution were noted in competitors practising the same discipline. The similarities increase with the training level. A typical body constitution for a given discipline not only favourably affects athletic performance, but is also the factor preventing sportsrelated contusions. The ability to maintain body equilibrium, together with somatic constitution, are the basic selective criteria in rhythmic gymnastics. The objective of this paper was to determine somatotypes, to evaluate the ability to maintain dynamic body equilibrium in girls practicing rhythmic gymnastics and to develop model characteristics enabling early diagnosis of the disorders equilibrium system function. The sample comprised 19 girls aged 8-11 years, practising rhythmic gymnastics. For the evaluation of the competitors' somatotypes, the Heath-Carter method was used, based on the classic concept of Sheldon's body constitution components. Body equilibrium level was evaluated by means of posturography. The mean values of the endomorphic component I, mesomorphic component II and ectomorphic component III in the gymnasts were 2.65+/-1.29, 2.45+/-0.37 and 3.95+/-0.64 respectively. The mean body mass index (BMI) value for this cohort was 15.32, which means advanced slimness. The level of dynamic equilibrium is determined by the following mean values: the time of reaching the equilibrium, the way of reaching it and the duration of stay at the defined point. The model of above mentioned indicates was developed based on the analysis of it's best results. Body constitution type in the qualified gymnasts is characterised by the prevalence of the ectomorphic component. The study results indicate that female gymnasts are generally slim and lean. It is necessary to monitor BMI in order to exclude weight-related disorders and to observe the changes with age. The poorest result was found when the gymnasts bent in the backward direction as this body position is most difficult to assume and to maintain body equilibrium as compared to all other directions.

  3. E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte.

    PubMed

    Kusminski, Christine M; Gallardo-Montejano, Violeta I; Wang, Zhao V; Hegde, Vijay; Bickel, Perry E; Dhurandhar, Nikhil V; Scherer, Philipp E

    2015-10-01

    Type 2 diabetes remains a worldwide epidemic with major pathophysiological changes as a result of chronic insulin resistance. Insulin regulates numerous biochemical pathways related to carbohydrate and lipid metabolism. We have generated a novel mouse model that allows us to constitutively activate, in an inducible fashion, the distal branch of the insulin signaling transduction pathway specifically in adipocytes. Using the adenoviral 36 E4orf1 protein, we chronically stimulate locally the Ras-ERK-MAPK signaling pathway. At the whole body level, this leads to reduced body-weight gain under a high fat diet challenge. Despite overlapping glucose tolerance curves, there is a reduced requirement for insulin action under these conditions. The mice further exhibit reduced circulating adiponectin levels that ultimately lead to impaired lipid clearance, and inflamed and fibrotic white adipose tissues. Nevertheless, they are protected from diet-induced hepatic steatosis. As we observe constitutively elevated p-Akt levels in the adipocytes, even under conditions of low insulin levels, this pinpoints enhanced Ras-ERK-MAPK signaling in transgenic adipocytes as a potential alternative route to bypass proximal insulin signaling events. We conclude that E4orf1 expression in the adipocyte leads to enhanced baseline activation of the distal insulin signaling node, yet impaired insulin receptor stimulation in the presence of insulin, with important implications for the regulation of adiponectin secretion. The resulting systemic phenotype is complex, yet highlights the powerful nature of manipulating selective branches of the insulin signaling network within the adipocyte.

  4. Constitutive law for the densification of fused silica with applications in polishing and microgrinding

    NASA Astrophysics Data System (ADS)

    Lambropoulos, John C.; Fang, Tong; Xu, Su; Gracewski, Sheryl M.

    1995-09-01

    We discuss a constitutive model describing the permanent densification of fused silica under large applied pressures and shear stresses. The constitutive law is assumed to be rate- independent, and uses a yield function coupling hydrostatic pressure and shear stress, a flow rule describing the evolution of permanent strains after initial densification, and a hardening rule describing the dependence of the incremental densification on the levels of applied stresses. The constitutive law accounts for multiaxial states of stress, since during polishing and grinding operations complex stress states occur in a thin surface layer due to the action of abrasive particles. Due to frictional and other abrasive forces, large shear stresses are present near the surface during manufacturing. We apply the constitutive law in estimating the extent of the densified layer during the mechanical interaction of an abrasive grain and a flat surface.

  5. Utility of temporally distinct baculovirus promoters for constitutive and baculovirus-inducible transgene expression in transformed insect cells.

    PubMed

    Lin, Chi-Hung; Jarvis, Donald L

    2013-05-10

    Genetically transformed lepidopteran insect cell lines have biotechnological applications as constitutive recombinant protein production platforms and improved hosts for baculovirus-mediated recombinant protein production. Insect cell transformation is often accomplished with a DNA construct(s) encoding a foreign protein(s) under the transcriptional control of a baculovirus immediate early promoter, such as the ie1 promoter. However, the potential utility of increasingly stronger promoters from later baculovirus gene classes, such as delayed early (39K), late (p6.9), and very late (polh), has not been systematically assessed. Hence, we produced DNA constructs encoding secreted alkaline phosphatase (SEAP) under the transcriptional control of each of the four temporally distinct classes of baculovirus promoters, used them to transform insect cells, and compared the levels of SEAP RNA and protein production obtained before and after baculovirus infection. The ie1 construct was the only one that supported SEAP protein production by transformed insect cells prior to baculovirus infection, confirming that only immediate early promoters can be used to isolate transformed insect cells for constitutive recombinant protein production. However, baculovirus infection activated transgene expression by all four classes of baculovirus promoters. After infection, cells transformed with the very late (polh) and late (p6.9) promoter constructs produced the highest levels of SEAP RNA, but only low levels of SEAP protein. Conversely, cells transformed with the immediate early (ie1) and delayed early (39K) promoter constructs produced lower levels of RNA, but equal or higher levels of SEAP protein. Unexpectedly, the 39K promoter construct provided tightly regulated, baculovirus-inducible protein production at higher levels than the later promoter constructs. Thus, this study demonstrated the utility of the 39K promoter for insect cell engineering, particularly when one requires higher levels of effector protein production than obtained with ie1 and/or when constitutive transgene expression adversely impacts host cell fitness and/or genetic stability. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Epidermal Expression of Intercellular Adhesion Molecule 1 is Not a Primary Inducer of Cutaneous Inflammation in Transgenic Mice

    NASA Astrophysics Data System (ADS)

    Williams, Ifor R.; Kupper, Thomas S.

    1994-10-01

    Keratinocytes at sites of cutaneous inflammation have increased expression of intercellular adhesion molecule 1 (ICAM-1), a cytokine-inducible adhesion molecule which binds the leukocyte integrins LFA-1 and Mac-1. Transgenic mice were prepared in which the expression of mouse ICAM-1 was targeted to basal keratinocytes by using the human K14 keratin promoter. The level of constitutive expression attained in the transgenic mice exceeded the peak level of ICAM-1 expression induced on nontransgenic mouse keratinocytes in vitro by optimal combinations of interferon γ and tumor necrosis factor α or in vivo by proinflammatory stimuli such as phorbol 12-myristate 13-acetate. In vitro adhesion assays demonstrated that cultured transgenic keratinocytes were superior to normal keratinocytes as a substrate for the LFA-1-dependent binding of mouse T cells, confirming that the transgene-encoded ICAM-1 was expressed in a functional form. However, the high level of constitutive ICAM-1 expression achieved on keratinocytes in vivo in these transgenic mice did not result in additional recruitment of CD45^+ leukocytes into transgenic epidermis, nor did it elicit dermal inflammation. Keratinocyte ICAM-1 expression also did not potentiate contact-hypersensitivity reactions to epicutaneous application of haptens. The absence of a spontaneous phenotype in these transgenic mice was not the result of increased levels of soluble ICAM-1, since serum levels of soluble ICAM-1 were equal in transgenic mice and controls. We conclude that elevated ICAM-1 expression on keratinocytes cannot act independently to influence leukocyte trafficking and elicit cutaneous inflammation.

  7. Radiological incident preparedness: planning at the local level.

    PubMed

    Tan, Clive M; Barnett, Daniel J; Stolz, Adam J; Links, Jonathan M

    2011-03-01

    Radiological terrorism has been recognized as a probable scenario with high impact. Radiological preparedness planning at the federal and state levels has been encouraging, but translating complex doctrines into operational readiness at the local level has proved challenging. Based on the authors' experience with radiological response planning for the City of Baltimore, this article describes an integrated approach to municipal-level radiological emergency preparedness planning, provides information on resources that are useful for radiological preparedness planning, and recommends a step-by-step process toward developing the plan with relevant examples from the experience in Baltimore. Local governmental agencies constitute the first line of response and are critical to the success of the operation. This article is intended as a starting framework for local governmental efforts toward developing a response plan for radiological incidents in their communities.

  8. Food risks and consumer trust. Avian influenza and the knowing and non-knowing on UK shopping floors.

    PubMed

    de Krom, Michiel P M M; Mol, Arthur P J

    2010-12-01

    Irrespective of major food crises in the 2000s consumer trust in food seems to remain high in Western Europe. Transparent information provision to consumers on food risks is a central strategy of the EU, its Member States and private food providers to build food trust among consumers. But can the interpretation of such information by consumers explain high levels of trust in food safety? Following recent outbreaks of avian influenza in the UK, this paper investigates the constitution of food trust among UK poultry consumers by focusing on the place where consumer decisions are made: the shopping floor. In-store qualitative interviews with consumers of a variety of poultry products at different shops are used to reveal the use of information in constructing trust. Besides on knowledge inducted from information provision, trust depends as much on consumer strategies to handle non-knowing of food risks. Three main forms of trust relations are distinguished, which together at a system level result in high levels of consumer trust in food. Copyright © 2010 Elsevier Ltd. All rights reserved.

  9. Constitutional Reform and the Opportunity for Higher Education Access in Ecuador since 1950

    ERIC Educational Resources Information Center

    Post, David

    2011-01-01

    Ecuador's 2008 Constitution--and a subsequent law on higher education passed in its wake--effectively suspended student fees for public universities. The goal of this reform was to increase equality of opportunity. In this article I use newly-available individual-level retrospective information from the 2001 Census to explore gender and ethnic…

  10. University and Participative Democracy: Adoption, Perception and Impact--Case Study Universidad Politécnica Salesiana

    ERIC Educational Resources Information Center

    Buele, Irene; Pablo, Vidueira

    2016-01-01

    The Constitution of Ecuador was approved in 2008, and promotes the application of participatory processes for resource distribution at different levels of government. The ultimate aim of the Constitution of Ecuador is to promote sustainable development and equitable distribution of resources and wealth, and to access the "Buen Vivir."…

  11. No Time for Tea (Grade Level: Elementary Grades, 3-5)

    ERIC Educational Resources Information Center

    Social Education, 2005

    2005-01-01

    Designed for Grades 3-5, this lesson plan aims to let the students learn how the Constitution of the United States provided the framework for the country's democratic form of government. Students will learn how the Constitution provided for representation within the government. A short story about the Boston Tea Party gives the background related…

  12. We the People: A Secondary Level Student Text.

    ERIC Educational Resources Information Center

    Center for Civic Education, Calabasas, CA.

    This curriculum introduces secondary students to the study of constitutional government in the United States. It is designed to provide students with an understanding of how the Constitution came into existence, why it took the form it did, and how it has functioned for the past 200 years. Through the 31 lessons of the text, organized into six…

  13. [Relationship between Life Habits and Constitution Types of Chinese Medicine in the Senile Living at Home in Beijing Downtown].

    PubMed

    Shi, Mai; Liu, Zhao-lan; Xu, Mei-yan; Chen, Jie; Lin, Bing; Yu, Yong-chao; Ma, Xiao-tao

    2016-05-01

    To investigate the distribution of constitution types of Chinese medicine (CM) in the elderly living at home in Beijing downtown, and to explore its relationship with life habits. A total of 3894 senile more than 60 years old were enrolled in this study. Their constitution types of CM were typed using CM constitution questionnaire. Meanwhile, their demographic features, disease condition, diet habits, exercise habits, sleep habits, and so on were investigated. Multivariate Logistic regression analysis was used to evaluate the relationship between life habits and constitution types of CM. The number of mild type constitution senile was 1111 (28.53%) and the number of biased constitutions 2783 (71.47%). Biased constitutions of the top three were qi deficiency constitution (662, 17.00%), yang deficiency constitution (445, 11.43%), and blood stasis constitution (363, 9.32%). Univariate analysis showed that different habits of diet, exercise, and sleep exist among the senile of different constitutions (P < 0.05). By taking mild type constitution, multivariate Logistic regression analysis (except demographic indices and chronic history) showed that significantly positive correlation existed between qi deficiency constitution and favor for hot food (OR = 1.349, P = 0.015), yang deficiency constitution and favor for hot food (OR = 2.448, P < 0.01), phlegm-wetness constitution and favor for barbecue food (OR = 2.144, P = 0.003), wet-heat constitution and favor for sweet food (OR = 1.355, P = 0.032), wet-heat constitution and favor for tea (OR = 1.359, P = 0.047), blood stasis constitution and favor for hot food (OR = 1.422, P = 0.017), and qi depression constitution and favor for hot food (OR = 1.446, P = 0.031). Regular exercise had negative correlation with qi deficiency constitution (OR = 0.397, P < 0.01), yang deficiency constitution (OR = 0.522, P < 0.01) , phlegm-wetness constitution (OR = 0.475, P < 0.01), wet-heat constitution (OR = 0.647, P = 0.015), blood stasis constitution (OR = 0.608, P = 0.001), qi depression constitution (OR = 0.541, P = 0.001), and special diathesis constitution (OR = 0.466, P < 0.01). Early sleep and rise habit had negative with phlegm-wetness constitution (OR = 0.414, P < 0.01), wet-heat constitution (OR = 0.536, P = 0.015), blood stasis constitution (OR = 0.515, P = 0.004), and special diathesis constitution (OR = 0.526, P = 0.039). Different constitution types of CM might be highly related to specific life habits. Cultivating better life habits can improve biased constitutions of CM.

  14. Becoming Informed Citizens: Lessons on the Constitution for Junior High School Students.

    ERIC Educational Resources Information Center

    Wagner, Kenneth A.; And Others

    This document consists of lesson plans for teaching junior high school students about the U.S. Constitution. Lessons are derived from teaching methods that instructors have found useful and appropriate for the actual condition of the ordinary classroom, and account for the characteristics and needs of the early adolescent. The document includes a…

  15. Lessons on the Constitution. Supplements to High School Courses in American History, Government and Civics.

    ERIC Educational Resources Information Center

    Patrick, John J.; Remy, Richard C.

    These curriculum materials about various aspects of the United States Constitution are designed as supplements to high school courses in history, civics, and government. They include 60 original lessons for students, accompanied by lesson plans for teachers, and are divided into five chapters. Chapter I, "Documents of Freedom" includes…

  16. Hsc66 and Hsc20, a new heat shock cognate molecular chaperone system from Escherichia coli.

    PubMed

    Vickery, L E; Silberg, J J; Ta, D T

    1997-05-01

    The hscA and hscB genes of Escherichia coli encode novel chaperone and co-chaperone proteins, designated Hsc66 and Hsc20, respectively. We have overproduced and purified Hsc66 and Hsc20 in high yield in E. coli and describe their initial characterization including absorbance, fluorescence, and circular dichroism spectra. Immunoblot analyses of E. coli cultures using antisera to Hsc66 and Hsc20 raised in rabbits establish that Hsc66 and Hsc20 are constitutively expressed at levels corresponding to cell concentration approximately 20 microM and approximately 10 microM, respectively. The levels do not change appreciably following heat shock (44 degrees C), but a small increase in Hsc20 is observed following a shift to 10 degrees C. Purified Hsc66 exhibits a low intrinsic ATPase activity (approximately 0.6 min-1 at 37 degrees C), and Hsc20 was found to stimulate this activity up to 3.8-fold with half-maximal stimulation at a concentration approximately 5 microM. These findings suggest that Hsc66 and Hsc20 comprise a molecular chaperone system similar to the prokaryotic DnaK/DnaJ and eukaryotic hsp70/hsp40 systems. Sequence differences between Hsc66 and Hsc20 compared to other members of this chaperone family, however, suggest that the Hsc66/Hsc20 system will display different peptide binding specificity and that it is likely to be subject to different regulatory mechanisms. The high level of constitutive expression and the lack of a major response to temperature changes suggest that Hsc66 and Hsc20 play an important cellular role(s) under non-stress conditions.

  17. Hsc66 and Hsc20, a new heat shock cognate molecular chaperone system from Escherichia coli.

    PubMed Central

    Vickery, L. E.; Silberg, J. J.; Ta, D. T.

    1997-01-01

    The hscA and hscB genes of Escherichia coli encode novel chaperone and co-chaperone proteins, designated Hsc66 and Hsc20, respectively. We have overproduced and purified Hsc66 and Hsc20 in high yield in E. coli and describe their initial characterization including absorbance, fluorescence, and circular dichroism spectra. Immunoblot analyses of E. coli cultures using antisera to Hsc66 and Hsc20 raised in rabbits establish that Hsc66 and Hsc20 are constitutively expressed at levels corresponding to cell concentration approximately 20 microM and approximately 10 microM, respectively. The levels do not change appreciably following heat shock (44 degrees C), but a small increase in Hsc20 is observed following a shift to 10 degrees C. Purified Hsc66 exhibits a low intrinsic ATPase activity (approximately 0.6 min-1 at 37 degrees C), and Hsc20 was found to stimulate this activity up to 3.8-fold with half-maximal stimulation at a concentration approximately 5 microM. These findings suggest that Hsc66 and Hsc20 comprise a molecular chaperone system similar to the prokaryotic DnaK/DnaJ and eukaryotic hsp70/hsp40 systems. Sequence differences between Hsc66 and Hsc20 compared to other members of this chaperone family, however, suggest that the Hsc66/Hsc20 system will display different peptide binding specificity and that it is likely to be subject to different regulatory mechanisms. The high level of constitutive expression and the lack of a major response to temperature changes suggest that Hsc66 and Hsc20 play an important cellular role(s) under non-stress conditions. PMID:9144776

  18. Enhanced drought and heat stress tolerance of tobacco plants with ectopically enhanced cytokinin oxidase/dehydrogenase gene expression

    PubMed Central

    Macková, Hana; Hronková, Marie; Dobrá, Jana; Turečková, Veronika; Novák, Ondřej; Lubovská, Zuzana; Motyka, Václav; Haisel, Daniel; Hájek, Tomáš; Prášil, Ilja Tom; Gaudinová, Alena; Štorchová, Helena; Ge, Eva; Werner, Tomáš; Schmülling, Thomas; Vanková, Radomíra

    2013-01-01

    Responses to drought, heat, and combined stress were compared in tobacco (Nicotiana tabacum L.) plants ectopically expressing the cytokinin oxidase/dehydrogenase CKX1 gene of Arabidopsis thaliana L. under the control of either the predominantly root-expressed WRKY6 promoter or the constitutive 35S promoter, and in the wild type. WRKY6:CKX1 plants exhibited high CKX activity in the roots under control conditions. Under stress, the activity of the WRKY6 promoter was down-regulated and the concomitantly reduced cytokinin degradation coincided with raised bioactive cytokinin levels during the early phase of the stress response, which might contribute to enhanced stress tolerance of this genotype. Constitutive expression of CKX1 resulted in an enlarged root system, a stunted, dwarf shoot phenotype, and a low basal level of expression of the dehydration marker gene ERD10B. The high drought tolerance of this genotype was associated with a relatively moderate drop in leaf water potential and a significant decrease in leaf osmotic potential. Basal expression of the proline biosynthetic gene P5CSA was raised. Both wild-type and WRKY6:CKX1 plants responded to heat stress by transient elevation of stomatal conductance, which correlated with an enhanced abscisic acid catabolism. 35S:CKX1 transgenic plants exhibited a small and delayed stomatal response. Nevertheless, they maintained a lower leaf temperature than the other genotypes. Heat shock applied to drought-stressed plants exaggerated the negative stress effects, probably due to the additional water loss caused by a transient stimulation of transpiration. The results indicate that modulation of cytokinin levels may positively affect plant responses to abiotic stress through a variety of physiological mechanisms. PMID:23669573

  19. Elevated phthalates' exposure in children with constitutional delay of growth and puberty.

    PubMed

    Xie, Changming; Zhao, Yan; Gao, Lianlian; Chen, Jiao; Cai, Depei; Zhang, Yunhui

    2015-05-15

    Phthalates have been proven to be antiandrogenic, which may interfere with the timing of puberty. Children with Constitutional Delay of Growth and Puberty (CDGP) typically display short stature and pubertal delay. This study investigated whether phthalate's exposure was associated with CDGP, and evaluated the potential mediator role of testosterone. In this case-control study, a total of 167 boys, including 57 boys with CDGP (cases) and 110 controls were enrolled. We measured six major phthalate metabolites in urine samples using high-performance liquid chromatography and tandem mass spectrometry (LC-MS/MS). The serum testosterone level was determined by radioimmunoassay. Children in the CDGP group were determined to have significantly elevated urinary phthalates concentration compared with control subjects (total phthalates median: case, 107.00 ng/ml; control, 62.22 ng/ml, p = 0.001). After adjustment for BMI and other confounding factors: mono-n-butyl phthalate (MBP), monoethyl phthalate (MEP) and total phthalate concentrations were significantly negatively associated with serum testosterone level (MBP: β = -45.7, p = 0.017; MEP: β = -31.6, p = 0.022; total phthalates: β = -24.6, p = 0.011); MBP, MEP, mono (2-ethylhexyl) phthalate (MEHP) and total phthalates were significantly associated with CDGP (odds ratio: MBP: 8.30, p = 0.002; MEP: 5.43, p = 0.002; MEHP: 3.83, p = 0.017; total phthalates: 9.09, p = 0.001). Serum testosterone level acted as a mediator of the association between phthalates' exposure and CDGP (p = 0.002) (proportion mediated: 34.4%). In this case-control study, elevated phthalates' level was detected in children with CDGP in Shanghai, China and phthalate level was associated with CDGP, which appeared to be mediated by circulating testosterone level. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. A Polypyrimidine Tract Binding Protein, Pumpkin RBP50, Forms the Basis of a Phloem-Mobile Ribonucleoprotein Complex[W

    PubMed Central

    Ham, Byung-Kook; Brandom, Jeri L.; Xoconostle-Cázares, Beatriz; Ringgold, Vanessa; Lough, Tony J.; Lucas, William J.

    2009-01-01

    RNA binding proteins (RBPs) are integral components of ribonucleoprotein (RNP) complexes and play a central role in RNA processing. In plants, some RBPs function in a non-cell-autonomous manner. The angiosperm phloem translocation stream contains a unique population of RBPs, but little is known regarding the nature of the proteins and mRNA species that constitute phloem-mobile RNP complexes. Here, we identified and characterized a 50-kD pumpkin (Cucurbita maxima cv Big Max) phloem RNA binding protein (RBP50) that is evolutionarily related to animal polypyrimidine tract binding proteins. In situ hybridization studies indicated a high level of RBP50 transcripts in companion cells, while immunolocalization experiments detected RBP50 in both companion cells and sieve elements. A comparison of the levels of RBP50 present in vascular bundles and phloem sap indicated that this protein is highly enriched in the phloem sap. Heterografting experiments confirmed that RBP50 is translocated from source to sink tissues. Collectively, these findings established that RBP50 functions as a non-cell-autonomous RBP. Protein overlay, coimmunoprecipitation, and cross-linking experiments identified the phloem proteins and mRNA species that constitute RBP50-based RNP complexes. Gel mobility-shift assays demonstrated that specificity, with respect to the bound mRNA, is established by the polypyrimidine tract binding motifs within such transcripts. We present a model for RBP50-based RNP complexes within the pumpkin phloem translocation stream. PMID:19122103

  1. Sponge-associated bacteria mineralize arsenic and barium on intracellular vesicles

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

    Keren, Ray; Mayzel, Boaz; Lavy, Adi

    Arsenic and barium are ubiquitous environmental toxins that accumulate in higher trophic-level organisms. Whereas metazoans have detoxifying organs to cope with toxic metals, sponges lack organs but harbour a symbiotic microbiome performing various functions. Here we examine the potential roles of microorganisms in arsenic and barium cycles in the sponge Theonella swinhoei, known to accumulate high levels of these metals. We show that a single sponge symbiotic bacterium, Entotheonella sp., constitutes the arsenic- and barium-accumulating entity within the host. These bacteria mineralize both arsenic and barium on intracellular vesicles. Our results indicate that Entotheonella sp. may act as a detoxifyingmore » organ for its host.« less

  2. Sponge-associated bacteria mineralize arsenic and barium on intracellular vesicles

    DOE PAGES

    Keren, Ray; Mayzel, Boaz; Lavy, Adi; ...

    2017-02-24

    Arsenic and barium are ubiquitous environmental toxins that accumulate in higher trophic-level organisms. Whereas metazoans have detoxifying organs to cope with toxic metals, sponges lack organs but harbour a symbiotic microbiome performing various functions. Here we examine the potential roles of microorganisms in arsenic and barium cycles in the sponge Theonella swinhoei, known to accumulate high levels of these metals. We show that a single sponge symbiotic bacterium, Entotheonella sp., constitutes the arsenic- and barium-accumulating entity within the host. These bacteria mineralize both arsenic and barium on intracellular vesicles. Our results indicate that Entotheonella sp. may act as a detoxifyingmore » organ for its host.« less

  3. Constitutive BAK activation as a determinant of drug sensitivity in malignant lymphohematopoietic cells

    PubMed Central

    Dai, Haiming; Ding, Husheng; Meng, X. Wei; Peterson, Kevin L.; Schneider, Paula A.; Karp, Judith E.; Kaufmann, Scott H.

    2015-01-01

    Mitochondrial outer membrane permeabilization (MOMP), a key step in the intrinsic apoptotic pathway, is incompletely understood. Current models emphasize the role of BH3-only BCL2 family members in BAX and BAK activation. Here we demonstrate concentration-dependent BAK autoactivation under cell-free conditions and provide evidence that this autoactivation plays a key role in regulating the intrinsic apoptotic pathway in intact cells. In particular, we show that up to 80% of BAK (but not BAX) in lymphohematopoietic cell lines is oligomerized and bound to anti-apoptotic BCL2 family members in the absence of exogenous death stimuli. The extent of this constitutive BAK oligomerization is diminished by BAK knockdown and unaffected by BIM or PUMA down-regulation. Further analysis indicates that sensitivity of cells to BH3 mimetics reflects the identity of the anti-apoptotic proteins to which BAK is constitutively bound, with extensive BCLXL•BAK complexes predicting navitoclax sensitivity, and extensive MCL1•BAK complexes predicting A1210477 sensitivity. Moreover, high BAK expression correlates with sensitivity of clinical acute myelogenous leukemia to chemotherapy, whereas low BAK levels correlate with resistance and relapse. Collectively, these results inform current understanding of MOMP and provide new insight into the ability of BH3 mimetics to induce apoptosis without directly activating BAX or BAK. PMID:26494789

  4. GABAB-mediated rescue of altered excitatory-inhibitory balance, gamma synchrony and behavioral deficits following constitutive NMDAR-hypofunction.

    PubMed

    Gandal, M J; Sisti, J; Klook, K; Ortinski, P I; Leitman, V; Liang, Y; Thieu, T; Anderson, R; Pierce, R C; Jonak, G; Gur, R E; Carlson, G; Siegel, S J

    2012-07-17

    Reduced N-methyl-D-aspartate-receptor (NMDAR) signaling has been associated with schizophrenia, autism and intellectual disability. NMDAR-hypofunction is thought to contribute to social, cognitive and gamma (30-80 Hz) oscillatory abnormalities, phenotypes common to these disorders. However, circuit-level mechanisms underlying such deficits remain unclear. This study investigated the relationship between gamma synchrony, excitatory-inhibitory (E/I) signaling, and behavioral phenotypes in NMDA-NR1(neo-/-) mice, which have constitutively reduced expression of the obligate NR1 subunit to model disrupted developmental NMDAR function. Constitutive NMDAR-hypofunction caused a loss of E/I balance, with an increase in intrinsic pyramidal cell excitability and a selective disruption of parvalbumin-expressing interneurons. Disrupted E/I coupling was associated with deficits in auditory-evoked gamma signal-to-noise ratio (SNR). Gamma-band abnormalities predicted deficits in spatial working memory and social preference, linking cellular changes in E/I signaling to target behaviors. The GABA(B)-receptor agonist baclofen improved E/I balance, gamma-SNR and broadly reversed behavioral deficits. These data demonstrate a clinically relevant, highly translatable neural-activity-based biomarker for preclinical screening and therapeutic development across a broad range of disorders that share common endophenotypes and disrupted NMDA-receptor signaling.

  5. Application of activated barrier hopping theory to viscoplastic modeling of glassy polymers

    NASA Astrophysics Data System (ADS)

    Sweeney, J.; Spencer, P. E.; Vgenopoulos, D.; Babenko, M.; Boutenel, F.; Caton-Rose, P.; Coates, P. D.

    2018-05-01

    An established statistical mechanical theory of amorphous polymer deformation has been incorporated as a plastic mechanism into a constitutive model and applied to a range of polymer mechanical deformations. The temperature and rate dependence of the tensile yield of PVC, as reported in early studies, has been modeled to high levels of accuracy. Tensile experiments on PET reported here are analyzed similarly and good accuracy is also achieved. The frequently observed increase in the gradient of the plot of yield stress against logarithm of strain rate is an inherent feature of the constitutive model. The form of temperature dependence of the yield that is predicted by the model is found to give an accurate representation. The constitutive model is developed in two-dimensional form and implemented as a user-defined subroutine in the finite element package ABAQUS. This analysis is applied to the tensile experiments on PET, in some of which strain is localized in the form of shear bands and necks. These deformations are modeled with partial success, though adiabatic heating of the instability causes inaccuracies for this isothermal implementation of the model. The plastic mechanism has advantages over the Eyring process, is equally tractable, and presents no particular difficulties in implementation with finite elements.

  6. Application of activated barrier hopping theory to viscoplastic modeling of glassy polymers

    NASA Astrophysics Data System (ADS)

    Sweeney, J.; Spencer, P. E.; Vgenopoulos, D.; Babenko, M.; Boutenel, F.; Caton-Rose, P.; Coates, P. D.

    2017-10-01

    An established statistical mechanical theory of amorphous polymer deformation has been incorporated as a plastic mechanism into a constitutive model and applied to a range of polymer mechanical deformations. The temperature and rate dependence of the tensile yield of PVC, as reported in early studies, has been modeled to high levels of accuracy. Tensile experiments on PET reported here are analyzed similarly and good accuracy is also achieved. The frequently observed increase in the gradient of the plot of yield stress against logarithm of strain rate is an inherent feature of the constitutive model. The form of temperature dependence of the yield that is predicted by the model is found to give an accurate representation. The constitutive model is developed in two-dimensional form and implemented as a user-defined subroutine in the finite element package ABAQUS. This analysis is applied to the tensile experiments on PET, in some of which strain is localized in the form of shear bands and necks. These deformations are modeled with partial success, though adiabatic heating of the instability causes inaccuracies for this isothermal implementation of the model. The plastic mechanism has advantages over the Eyring process, is equally tractable, and presents no particular difficulties in implementation with finite elements.

  7. Motivation and Organizational Principles for Anatomical Knowledge Representation

    PubMed Central

    Rosse, Cornelius; Mejino, José L.; Modayur, Bharath R.; Jakobovits, Rex; Hinshaw, Kevin P.; Brinkley, James F.

    1998-01-01

    Abstract Objective: Conceptualization of the physical objects and spaces that constitute the human body at the macroscopic level of organization, specified as a machine-parseable ontology that, in its human-readable form, is comprehensible to both expert and novice users of anatomical information. Design: Conceived as an anatomical enhancement of the UMLS Semantic Network and Metathesaurus, the anatomical ontology was formulated by specifying defining attributes and differentia for classes and subclasses of physical anatomical entities based on their partitive and spatial relationships. The validity of the classification was assessed by instantiating the ontology for the thorax. Several transitive relationships were used for symbolically modeling aspects of the physical organization of the thorax. Results: By declaring Organ as the macroscopic organizational unit of the body, and defining the entities that constitute organs and higher level entities constituted by organs, all anatomical entities could be assigned to one of three top level classes (Anatomical structure, Anatomical spatial entity and Body substance). The ontology accommodates both the systemic and regional (topographical) views of anatomy, as well as diverse clinical naming conventions of anatomical entities. Conclusions: The ontology formulated for the thorax is extendible to microscopic and cellular levels, as well as to other body parts, in that its classes subsume essentially all anatomical entities that constitute the body. Explicit definitions of these entities and their relationships provide the first requirement for standards in anatomical concept representation. Conceived from an anatomical viewpoint, the ontology can be generalized and mapped to other biomedical domains and problem solving tasks that require anatomical knowledge. PMID:9452983

  8. Bt rice harbouring cry genes controlled by a constitutive or wound-inducible promoter: protection and transgene expression under Mediterranean field conditions.

    PubMed

    Breitler, Jean Christophe; Vassal, Jean Michel; del Mar Catala, Maria; Meynard, Donaldo; Marfà, Victoria; Melé, Enric; Royer, Monique; Murillo, Isabel; San Segundo, Blanca; Guiderdoni, Emmanuel; Messeguer, Joaquima

    2004-09-01

    Seven homozygous transgenic lines of two European commercial cultivars of rice (Ariete (A) and Senia (S)), harbouring the cry1B or cry1Aa Bacillus thuringiensis (Bt) delta-endotoxin genes, were field evaluated for protection from striped stem borer (SSB) (Chilo suppressalis) damage during the 2001 and 2002 summer crop seasons in the Delta de l'Ebre region, Spain. The plant codon-optimized toxin gene was placed under the control of the promoter of either the constitutive ubi1 gene or the wound-inducible mpi gene from maize. Stable, high-level, insecticidal protein accumulation was observed throughout root, leaf and seed tissues of field-grown plants harbouring the cry1B (lines A64.1, A33.1, A3.4 and S98.9) or cry1Aa (lines S05.1 and A19.14) genes under the control of the ubi1 promoter. Conversely, no toxin was detected in unwounded vegetative tissues of the A9.1 line harbouring the cry1B gene controlled by the mpi promoter, indicating that natural environmental stresses did not trigger the activity of the wound-inducible promoter. However, the toxin accumulated at 0.2% total soluble proteins in A9.1 sheath tissue exhibiting brown lesions resulting from SSB damage. The agronomical traits and performance of the transgenic lines were generally comparable with parental controls, except in the two lines accumulating Cry1Aa, which exhibited a high frequency of plants non-true to type. Natural infestation was assisted with manual infestations of L2/L3 SSB larvae in border control plants surrounding the experimental plots, which served as a reservoir for the second-cycle SSB population. The observation of damage (brown lesions and dead hearts) during the crop season and dissection of plants at harvest stage revealed a range of protection amongst the transgenic lines, which was highly consistent with the level of toxin accumulation and with previous experience in greenhouse assays. Lines A3.4 and S05.1 were found to exhibit stable and full protection against SSB attacks, mediated by the accumulation of Cry1B and Cry1Aa toxin, respectively, which was comparable with that afforded by the spraying of chemical insecticides on control plants. The wound-induced A9.1 line exhibited a satisfactory level of protection, with a notably low level of penetration of SSB larvae in the stems, but higher external symptoms than constitutive lines, probably due to the time lag to benefit from the protective effect of Cry1B.

  9. Modulating ectopic gene expression levels by using retroviral vectors equipped with synthetic promoters.

    PubMed

    Ferreira, Joshua P; Peacock, Ryan W S; Lawhorn, Ingrid E B; Wang, Clifford L

    2011-12-01

    The human cytomegalovirus and elongation factor 1α promoters are constitutive promoters commonly employed by mammalian expression vectors. These promoters generally produce high levels of expression in many types of cells and tissues. To generate a library of synthetic promoters capable of generating a range of low, intermediate, and high expression levels, the TATA and CAAT box elements of these promoters were mutated. Other promoter variants were also generated by random mutagenesis. Evaluation using plasmid vectors integrated at a single site in the genome revealed that these various synthetic promoters were capable of expression levels spanning a 40-fold range. Retroviral vectors were equipped with the synthetic promoters and evaluated for their ability to reproduce the graded expression demonstrated by plasmid integration. A vector with a self-inactivating long terminal repeat could neither reproduce the full range of expression levels nor produce stable expression. Using a second vector design, the different synthetic promoters enabled stable expression over a broad range of expression levels in different cell lines. The online version of this article (doi:10.1007/s11693-011-9089-0) contains supplementary material, which is available to authorized users.

  10. Significance of CEA and VEGF as Diagnostic Markers of Colorectal Cancer in Lebanese Patients.

    PubMed

    Dbouk, Hashem A; Tawil, Ayman; Nasr, Fahd; Kandakarjian, Loucine; Abou-Merhi, Raghida

    2007-11-08

    Carcinoembryonic antigen and vascular endothelial growth factors are among the most important prognostic markers of colorectal cancer. Testing for these markers independently has been of limited value in screening for this tumor. The aim of this study is to determine the importance of simultaneous blood CEA and VEGF level determinations in diagnosis of colorectal cancer. Thirty-six patients diagnosed with colorectal cancer along with eight healthy controls were tested by ELISA for CEA and VEGF levels in serum and plasma, respectively. The positive predictive value of these markers was 95.4% for CEA and 89.5% for VEGF, and for combined CEA and VEGF was also high at 88%. Combined CEA and VEGF blood level assay constitutes a useful panel in detecting patients with colorectal cancer. Positive results allow selection of a subgroup of patients with a high tumor risk; therefore, such tests comprise valuable tumor diagnostic tests to add to current detection methods.

  11. Irreversibly increased nitrogen fixation in Trichodesmium experimentally adapted to elevated carbon dioxide

    PubMed Central

    Hutchins, David A.; Walworth, Nathan G.; Webb, Eric A.; Saito, Mak A.; Moran, Dawn; McIlvin, Matthew R.; Gale, Jasmine; Fu, Fei-Xue

    2015-01-01

    Nitrogen fixation rates of the globally distributed, biogeochemically important marine cyanobacterium Trichodesmium increase under high carbon dioxide (CO2) levels in short-term studies due to physiological plasticity. However, its long-term adaptive responses to ongoing anthropogenic CO2 increases are unknown. Here we show that experimental evolution under extended selection at projected future elevated CO2 levels results in irreversible, large increases in nitrogen fixation and growth rates, even after being moved back to lower present day CO2 levels for hundreds of generations. This represents an unprecedented microbial evolutionary response, as reproductive fitness increases acquired in the selection environment are maintained after returning to the ancestral environment. Constitutive rate increases are accompanied by irreversible shifts in diel nitrogen fixation patterns, and increased activity of a potentially regulatory DNA methyltransferase enzyme. High CO2-selected cell lines also exhibit increased phosphorus-limited growth rates, suggesting a potential advantage for this keystone organism in a more nutrient-limited, acidified future ocean. PMID:26327191

  12. Irreversibly increased nitrogen fixation in Trichodesmium experimentally adapted to elevated carbon dioxide

    NASA Astrophysics Data System (ADS)

    Hutchins, David A.; Walworth, Nathan G.; Webb, Eric A.; Saito, Mak A.; Moran, Dawn; McIlvin, Matthew R.; Gale, Jasmine; Fu, Fei-Xue

    2015-09-01

    Nitrogen fixation rates of the globally distributed, biogeochemically important marine cyanobacterium Trichodesmium increase under high carbon dioxide (CO2) levels in short-term studies due to physiological plasticity. However, its long-term adaptive responses to ongoing anthropogenic CO2 increases are unknown. Here we show that experimental evolution under extended selection at projected future elevated CO2 levels results in irreversible, large increases in nitrogen fixation and growth rates, even after being moved back to lower present day CO2 levels for hundreds of generations. This represents an unprecedented microbial evolutionary response, as reproductive fitness increases acquired in the selection environment are maintained after returning to the ancestral environment. Constitutive rate increases are accompanied by irreversible shifts in diel nitrogen fixation patterns, and increased activity of a potentially regulatory DNA methyltransferase enzyme. High CO2-selected cell lines also exhibit increased phosphorus-limited growth rates, suggesting a potential advantage for this keystone organism in a more nutrient-limited, acidified future ocean.

  13. Effect of One Month Duration Ketogenic and non-Ketogenic High Fat Diets on Mouse Brain Bioenergetic Infrastructure

    PubMed Central

    Selfridge, J. Eva; Wilkins, Heather M.; Lezi, E; Carl, Steven M.; Koppel, Scott; Funk, Eric; Fields, Timothy; Lu, Jianghua; Tang, Ee Phie; Slawson, Chad; Wang, WenFang; Zhu, Hao; Swerdlow, Russell H.

    2014-01-01

    Diet composition may affect energy metabolism in a tissue-specific manner. Using C57Bl/6J mice, we tested the effect of ketosis-inducing and non-inducing high fat diets on genes relevant to brain bioenergetic infrastructures, and on proteins that constitute and regulate that infrastructure. At the end of a one-month study period the two high fat diets appeared to differentially affect peripheral insulin signaling, but brain insulin signaling was not obviously altered. Some bioenergetic infrastructure parameters were similarly impacted by both high fat diets, while other parameters were only impacted by the ketogenic diet. For both diets, mRNA levels for CREB, PGC1α, and NRF2 increased while NRF1, TFAM, and COX4I1 mRNA levels decreased. PGC1β mRNA increased and TNFα mRNA decreased only with the ketogenic diet. Brain mtDNA levels fell in both the ketogenic and non-ketogenic high fat diet groups, although TOMM20 and COX4I1 protein levels were maintained, and mRNA and protein levels of the mtDNA-encoded COX2 subunit were also preserved. Overall, the pattern of changes observed in mice fed ketogenic and non-ketogenic high fat diets over a one month time period suggests these interventions enhance some aspects of the brain’s aerobic infrastructure, and may enhance mtDNA transcription efficiency. Further studies to determine which diet effects are due to changes in brain ketone body levels, fatty acid levels, glucose levels, altered brain insulin signaling, or other factors such as adipose tissue-associated hormones are indicated. PMID:25104046

  14. Hydrocarbonoclastic bacteria isolated from petroleum contaminated sites in Tunisia: isolation, identification and characterization of the biotechnological potential.

    PubMed

    Mahjoubi, Mouna; Jaouani, Atef; Guesmi, Amel; Ben Amor, Sonia; Jouini, Ahlem; Cherif, Hanen; Najjari, Afef; Boudabous, Abdellatif; Koubaa, Nedra; Cherif, Ameur

    2013-09-25

    Petroleum hydrocarbons are important energy resources used by industry and in our daily life, whose production contributes highly to environmental pollution. To control such risk, bioremediation constitutes an environmentally friendly alternative technology that has been established and applied. It constitutes the primary mechanism for the elimination of hydrocarbons from contaminated sites by natural existing populations of microorganisms. In this work, a collection of 125 strains, adapted to grow on minimal medium supplemented with crude oil, was obtained from contaminated sediments and seawater from a refinery harbor of the Bizerte coast in the North of Tunisia. The diversity of the bacterial collection was analyzed by amplification of the internal transcribed spacers between the 16S and the 23S rRNA genes (ITS-PCR) and by 16S rRNA sequencing. A total of 36 distinct ITS haplotypes were detected on agarose matrix. Partial 16S rRNA gene sequencing performed on 50 isolates showed high level of identity with known sequences. Strains were affiliated to Ochrabactrum, Sphingobium, Acinetobacter, Gordonia, Microbacterium, Brevundimonas, Novosphingobium, Stenotrophomonas, Luteibacter, Rhodococcus, Agrobacterium, Achromobacter, Bacilllus, Kocuria and Pseudomonas genera. Acinetobacter and Stenotrophomons were found to be the most abundant species characterized by a marked microdiversity as shown through ITS typing. Culture-independent approach (DGGE) showed high diversity in the microbial community in all the studied samples with a clear correlation with the hydrocarbon pollution rate. Sequencing of the DGGE bands revealed a high proportion of Proteobacteria represented by the Alpha and Gamma subclasses. The predominant bacterial detected by both dependent and independent approaches were the Proteobacteria. The biotechnological potential of the isolates revealed a significant production of biosurfactants with important emulsification activities useful in bioremediation. The highest emulsification activity was detected in Pseudomonas geniculata with 52.77% of emulsification. Our overall results suggest that the obtained bacterial isolates may constitute potential candidates for bioremediation and can be useful for biotechnological applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Establishment of a quantitative PCR system for discriminating chitinase-like proteins: catalytically inactive breast regression protein-39 and Ym1 are constitutive genes in mouse lung.

    PubMed

    Ohno, Misa; Kida, Yuta; Sakaguchi, Masayoshi; Sugahara, Yasusato; Oyama, Fumitaka

    2014-10-08

    Mice and humans produce chitinase-like proteins (CLPs), which are highly homologous to chitinases but lack chitinolytic activity. Mice express primarily three CLPs, including breast regression protein-39 (BRP-39) [chitinase 3-like-1 (Chi3l1) or 38-kDa glycoprotein (gp38k)], Ym1 (Chi3l3) and Ym2 (Chi3l4). Recently, CLPs have attracted considerable attention due to their increased expression in a number of pathological conditions, including asthma, allergies, rheumatoid arthritis and malignant tumors. Although the exact functions of CLPs are largely unknown, the significance of their increased expression levels during pathophysiological states needs to be determined. The quantification of BRP-39, Ym1 and Ym2 is an important step in gaining insight into the in vivo regulation of the CLPs. We constructed a standard DNA for quantitative real-time PCR (qPCR) by containing three CLPs target fragments and five reference genes cDNA in a one-to-one ratio. We evaluated this system by analyzing the eight target cDNA sequences. Tissue cDNAs obtained by reverse transcription from total RNA from four embryonic stages and eight adult tissues were analyzed using the qPCR system with the standard DNA. We established a qPCR system detecting CLPs and comparing their expression levels with those of five reference genes using the same scale in mouse tissues. We found that BRP-39 and Ym1 were abundant in the mouse lung, whereas Ym2 mRNA was abundant in the stomach, followed by lung. The expression levels of BRP-39 and Ym1 in the mouse lung were higher than those of two active chitinases and were comparable to glyceraldehyde-3-phosphate dehydrogenase, a housekeeping gene which is constitutively expressed in all tissues. Our results indicate that catalytically inactive BRP-39 and Ym1 are constitutive genes in normal mouse lung.

  16. National Football League Skilled and Unskilled Positions Vary in Opportunity and Yield in Return to Play After an Anterior Cruciate Ligament Injury

    PubMed Central

    Yang, JaeWon; Hodax, Jonathan D.; Machan, Jason T.; Secrist, Eric S.; Durand, Wesley M.; Owens, Brett D.; Eltorai, Adam E.M.; Dodson, Christopher C.

    2017-01-01

    Background: Anterior cruciate ligament (ACL) injuries pose a significant risk to the careers of players in the National Football League (NFL). The relationships between draft round and position on return to play (RTP) among NFL players are not well understood, and the ability to return to preinjury performance levels remains unknown for most positions. Purpose: To test for differences in RTP rates and changes in performance after an ACL injury by position and draft round. We hypothesized that skilled positions would return at a lower rate compared to unskilled positions. We further hypothesized that early draft-round status would relate to a greater rate of RTP and that skilled positions and a lower draft round would correlate with decreased performance for players who return to sport. Study Design: Case-control study; Level of evidence, 3. Methods: Utilizing a previously established database of publicly available information regarding ACL tears among NFL players, athletes with ACL tears occurring between the 2010 and 2013 seasons were identified. Generalized linear models and Kaplan-Meier time-to-event models were used to test the study hypotheses. Results: The overall RTP rate was 61.7%, with skilled players and unskilled players returning at rates of 64.1% and 60.4%, respectively (P = .74). Early draft-round players and unskilled late draft-round players had greater rates of RTP compared to skilled late draft-round players and both unskilled and skilled undrafted free agents (UDFAs). Skilled early draft-round players constituted the only cohort that played significantly fewer games after an injury. Unskilled UDFAs constituted the only cohort to show a significant increase in the number of games started and ratio of games started to games played, starting more games in which they played, after an injury. Conclusion: Early draft-round and unskilled players were more likely to return compared to their later draft-round and skilled peers. Skilled early draft-round players, who displayed relatively high rates of RTP, constituted the only cohort to show a decline in performance. Unskilled UDFAs, who exhibited relatively low rates of RTP, constituted the only cohort to show an increase in performance. The significant effect of draft round and position type on RTP may be caused by a combination of differences in talent levels and in opportunities given to returning to play. PMID:28975136

  17. Enforced expression of the c-myc oncogene inhibits cell differentiation by precluding entry into a distinct predifferentiation state in G/sub 0//G/sub 1/

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

    Freytag, S.O.

    1988-04-01

    A broad base of data has implicated a role for the c-myc proto-oncogene in the control of the cell cycle and cell differentiation. To further define the role of myc in these processes, the authors examined the effect of enforced myc expression on several events that are thought to be important steps leading to the terminally differentiated state: (i) the ability to arrest growth in G/sub 0//G/sub 1/, (ii) the ability to replicate the genome upon initiation of the differentiation program, and (iii) the ability to loose responsiveness to mitogens and withdraw from the cell cycle. 3T3-L1 preadipocyte cell linesmore » expressing various levels of myc mRNA were established by transfection with a recombinant myc gene under the transcriptional control of the Rous sarcoma virus (RSV) promoter. Cells that expressed high constitutive levels of pRSV myc mRNA arrested in G/sub 0//G/sub 1/ at densities similar to those of normal cells at confluence. Upon initiation of the differentiation program, such cells traversed the cell cycle with kinetics similar to those of normal cells and subsequently arrested in G/sub 0//G/sub 1/. Thus, enforced expression of myc had no effect on the ability of cells to arrest growth in G/sub 0//G/sub 1/ or to replicate the genome upon initiation of the differentiation program. Cells were then tested for their ability to reenter the cell cycle upon exposure to high concentrations of serum and for their capacity to differentiate. In contrast to normal cells, cells expressing high constitutive levels of myc RNA reentered the cell cycle when challenged with 30% serum and failed to terminally differentiate.« less

  18. Depositional sequences and facies in the Torok Formation, National Petroleum Reserve, Alaska (NPRA)

    USGS Publications Warehouse

    Houseknecht, David W.; Schenk, Christopher J.

    2002-01-01

    Brookian turbidites (Cretaceous through Tertiary) have become oil exploration objectives on the NorthSlope of Alaska during the past decade, and it is likely this focus will extend into the National Petroleum Reserve-Alaska (NPRA). A regional grid of 2-D seismic data, sparse well control, and field work in the Brooks Range foothills provide constraints for an ongoing effort to establish a sequence stratigraphic framework for Brookian turbidites in the Torok Formation across NPRA. The Torok Formation and overlying Nanushuk Formation (both mostly Albian) display the overall seismic geometry of bottomset-clinoform-topset strata indicating northeastward migration of a shelf margin. Within bottomset and clinoform strata of the Torok, depositional sequences have been identified that represent four distinct phases of shelf-margin sedimentation. (1) Regression, representing low relative sea level, is characterized by the development of an erosional surface on the shelf and upper slope, and the deposition of turbidite channel deposits on the middle to lower slope and submarine fan deposits at the base of slope. These deposits constitute a lowstand systems tract (LST). (2) Transgression, representing rising relative sea level, is characterized by the deposition of a mudstone drape on the basin floor, slope, and outer shelf. This drape comprises relatively condensed facies that constitute a transgressive systems tract (TST). (3) Aggradation, representing high relative sea level, is characterized by the deposition of relatively thick strata on the outer shelf and moderately thick mudstones on the slope. (4) Progradation, also representing high relative sea level, is characterized by the deposition of relatively thin strata on the outer shelf and very thick mudstones on the slope. Together, deposits of the aggradation and progradation phases constitute a highstand systems tract (HST). Large scale geometries of Torok strata vary across the Colville basin. In southern NPRA, high rates of subsidence accommodated the deposition of a "foredeep clinoform wedge" that contains a high proportion of sand-rich LST deposits. In northern NPRA, lower rates of subsidence favored the accumulation of mud-rich HST deposits. The most favorable stratigraphic trapping geometries in the Torok Formation occur where amalgamated sandstones deposited in turbidite channels incised on the mid- to lower-slope and on the proximal parts of submarine fans during regression (LSTs) are capped by relatively condensed mudstone facies deposited during transgression (TSTs). Common successions observed in Torok cores include a spectrum of slope and turbidite facies. Upper slope facies comprise laminated mudstones and siltstones that locally display evidence of slumping, sliding, and chaotic failure. Lower slope facies comprise heterolithic turbidites at some locations and interlaminated mudstones and thin, very fine-grained sandstones at others. Torok turbidites include amalgamated sandstones deposited in channel systems as well as thin-bedded, widespread sandstones deposited by unconfined flows on lobes or in channel overbank settings. These turbidite facies likely occur in both channel-lobe systems and slope apron systems within the Torok.

  19. DNA methylation in inflammatory genes among children with obstructive sleep apnea.

    PubMed

    Kim, Jinkwan; Bhattacharjee, Rakesh; Khalyfa, Abdelnaby; Kheirandish-Gozal, Leila; Capdevila, Oscar Sans; Wang, Yang; Gozal, David

    2012-02-01

    Pediatric obstructive sleep apnea (OSA) leads to multiple end-organ morbidities that are mediated by the cumulative burden of oxidative stress and inflammation. Because not all children with OSA exhibit increased systemic inflammation, genetic and environmental factors may be affecting patterns of DNA methylation in genes subserving inflammatory functions. DNA from matched children with OSA with and without high levels of high-sensitivity C-reactive protein (hsCRP) were assessed for DNA methylation levels of 24 inflammatory-related genes. Primer-based polymerase chain reaction assays in a case-control setting involving 47 OSA cases and 31 control subjects were conducted to confirm the findings; hsCRP and myeloid-related protein (MRP) 8/14 levels were also assayed. Forkhead box P3 (FOXP3) and interferon regulatory factor 1 (IRF1) showed higher methylation in six children with OSA and high hsCRP levels compared with matched children with OSA and low hsCRP levels (P < 0.05). In the case-control cohort, children with OSA and high CRP levels had higher log FOXP3 DNA methylation levels compared with children with OSA and low CRP levels and control subjects. IRF1 did not exhibit significant differences. FOXP3 DNA methylation levels correlated with hsCRP and MRP 8/14 levels and with apnea-hypopnea index (AHI), BMI z score, and apolipoprotein B levels. A stepwise multiple regression model showed that AHI was independently associated with FOXP3 DNA methylation levels (P < 0.03). The FOXP3 gene, which regulates expression of T regulatory lymphocytes, is more likely to display increased methylation among children with OSA who exhibit increased systemic inflammatory responses. Thus, epigenetic modifications may constitute an important determinant of inflammatory phenotype in OSA, and FOXP3 DNA methylation levels may provide a potential biomarker for end-organ vulnerability.

  20. Evidence for a seismic activity mainly constituted of hybrid events at Cayambe volcano, Ecuador. Interpretation in a iced-domes volcano context

    NASA Astrophysics Data System (ADS)

    Guillier, Bertrand; Chatelain, Jean-Luc

    2006-06-01

    The high activity level of Hybrid Events (HE) detected beneath the Cayambe volcano since 1989 has been more thoroughly investigated with data from a temporary array. The unusual HE spectral content allows separating a high-frequency signal riding on a low-frequency one, with a probable single source. HEs are interpreted as high frequency VT events, produced by the interaction between magmatic heat and an underground water system fed by thaw water from the summital glacier, which trigger simultaneous low-frequency fluid resonance in the highly fractured adjacent medium. Pure VTs are interpreted as 'aborted' HEs occurring probably in the oldest and coldest part of the volcano complex. To cite this article: B. Guillier, J.-L. Chatelain, C. R. Geoscience 338 (2006).

  1. Materials with periodic internal structure: Computation based on homogenization and comparison with experiment

    NASA Technical Reports Server (NTRS)

    Jansson, S.; Leckie, F. A.; Onat, E. T.; Ranaweera, M. P.

    1990-01-01

    The combination of thermal and mechanical loading expected in practice means that constitutive equations of metal matrix composites must be developed which deal with time-independent and time-dependent irreversible deformation. Also, the internal state of composites is extremely complicated which underlines the need to formulate macroscopic constitutive equations with a limited number of state variables which represent the internal state at the micro level. One available method for calculating the macro properties of composites in terms of the distribution and properties of the constituent materials is the method of homogenization whose formulation is based on the periodicity of the substructure of the composite. A homogenization procedure was developed which lends itself to the use of the finite element procedure. The efficiency of these procedures, to determine the macroscopic properties of a composite system from its constituent properties, was demonstrated utilizing an aluminum plate perforated by directionally oriented slits. The selection of this problem is based on the fact that, extensive experimental results exist, the macroscopic response is highly anisotropic, and that the slits provide very high stress gradients which severely test the effectiveness of the computational procedures. Furthermore, both elastic and plastic properties were investigated so that the application to practical systems with inelastic deformation should be able to proceed without difficulty. The effectiveness of the procedures was rigorously checked against experimental results and with the predictions of approximate calculations. Using the computational results it is illustrated how macroscopic constitutive equations can be expressed in forms of the elastic and limit load behavior.

  2. Light responses in rods of vitamin A-deprived Xenopus.

    PubMed

    Solessio, Eduardo; Umino, Yumiko; Cameron, David A; Loew, Ellis; Engbretson, Gustav A; Knox, Barry E; Barlow, Robert B

    2009-09-01

    Accumulation of free opsin by mutations in rhodopsin or insufficiencies in the visual cycle can lead to retinal degeneration. Free opsin activates phototransduction; however, the link between constitutive activation and retinal degeneration is unclear. In this study, the photoresponses of Xenopus rods rendered constitutively active by vitamin A deprivation were examined. Unlike their mammalian counterparts, Xenopus rods do not degenerate. Contrasting phototransduction in vitamin A-deprived Xenopus rods with phototransduction in constitutively active mammalian rods may provide new understanding of the mechanisms that lead to retinal degeneration. The photocurrents of Xenopus tadpole rods were measured with suction electrode recordings, and guanylate cyclase activity was measured with the IBMX (3-isobutyl-1-methylxanthine) jump technique. The amount of rhodopsin in rods was determined by microspectrophotometry. The vitamin A-deprived rod outer segments were 60% to 70% the length and diameter of the rods in age-matched animals. Approximately 90% of its opsin content was in the free or unbound form. Analogous to bleaching adaptation, the photoresponses were desensitized (10- to 20-fold) and faster. Unlike bleaching adaptation, the vitamin A-deprived rods maintained near normal saturating (dark) current densities by developing abnormally high rates of cGMP synthesis. Their rate of cGMP synthesis in the dark (15 seconds(-1)) was twofold greater than the maximum levels attainable by control rods ( approximately 7 seconds(-1)). Preserving circulating current density and response range appears to be an important goal for rod homeostasis. However, the compensatory changes associated with vitamin A deprivation in Xenopus rods come at the high metabolic cost of a 15-fold increase in basal ATP consumption.

  3. Redundant mechanisms to form silent chromatin at pericentromeric regions rely on BEND3 and DNA methylation.

    PubMed

    Saksouk, Nehmé; Barth, Teresa K; Ziegler-Birling, Celine; Olova, Nelly; Nowak, Agnieszka; Rey, Elodie; Mateos-Langerak, Julio; Urbach, Serge; Reik, Wolf; Torres-Padilla, Maria-Elena; Imhof, Axel; Déjardin, Jérome; Simboeck, Elisabeth

    2014-11-20

    Constitutive heterochromatin is typically defined by high levels of DNA methylation and H3 lysine 9 trimethylation (H3K9Me3), whereas facultative heterochromatin displays DNA hypomethylation and high H3 lysine 27 trimethylation (H3K27Me3). The two chromatin types generally do not coexist at the same loci, suggesting mutual exclusivity. During development or in cancer, pericentromeric regions can adopt either epigenetic state, but the switching mechanism is unknown. We used a quantitative locus purification method to characterize changes in pericentromeric chromatin-associated proteins in mouse embryonic stem cells deficient for either the methyltransferases required for DNA methylation or H3K9Me3. DNA methylation controls heterochromatin architecture and inhibits Polycomb recruitment. BEND3, a protein enriched on pericentromeric chromatin in the absence of DNA methylation or H3K9Me3, allows Polycomb recruitment and H3K27Me3, resulting in a redundant pathway to generate repressive chromatin. This suggests that BEND3 is a key factor in mediating a switch from constitutive to facultative heterochromatin. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice.

    PubMed

    Masuyama, Hisashi; Hiramatsu, Yuji

    2012-07-15

    The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.

  5. Construing Morality at High versus Low Levels Induces Better Self-control, Leading to Moral Acts

    PubMed Central

    Wu, Chia-Chun; Wu, Wen-Hsiung; Chiou, Wen-Bin

    2017-01-01

    Human morality entails a typical self-control dilemma in which one must conform to moral rules or socially desirable norms while exerting control over amoral, selfish impulses. Extant research regarding the connection between self-control and level of construal suggest that, compared with a low-level, concrete construal (highlighting means and resources, e.g., answering ‘how’ questions), a high-level, abstract construal (highlighting central goals, e.g., answering ‘why’ questions) promotes self-control. Hence, construing morality at higher levels rather than lower levels should engender greater self-control and, it follows, promote a tendency to perform moral acts. We conducted two experiments to show that answering “why” (high-level construal) vs. “how” (low-level construal) questions regarding morality was associated with a situational state of greater self-control, as indexed by less Stroop interference in the Stroop color-naming task (Experiments 1 and 2). Participants exposed to “why” questions regarding morality displayed a greater inclination for volunteerism (Experiment 1), showed a lower tendency toward selfishness in a dictator game (Experiment 2), and were more likely to return undeserved money (Experiment 2) compared with participants exposed to “how” questions regarding morality. In both experiments, self-control mediated the effect of a high-level construal of morality on dependent measures. The current research constitutes a new approach to promoting prosociality and moral education. Reminding people to think abstractly about human morality may help them to generate better control over the temptation to benefit from unethical acts and make it more likely that they will act morally. PMID:28680415

  6. Construing Morality at High versus Low Levels Induces Better Self-control, Leading to Moral Acts.

    PubMed

    Wu, Chia-Chun; Wu, Wen-Hsiung; Chiou, Wen-Bin

    2017-01-01

    Human morality entails a typical self-control dilemma in which one must conform to moral rules or socially desirable norms while exerting control over amoral, selfish impulses. Extant research regarding the connection between self-control and level of construal suggest that, compared with a low-level, concrete construal (highlighting means and resources, e.g., answering 'how' questions), a high-level, abstract construal (highlighting central goals, e.g., answering 'why' questions) promotes self-control. Hence, construing morality at higher levels rather than lower levels should engender greater self-control and, it follows, promote a tendency to perform moral acts. We conducted two experiments to show that answering "why" (high-level construal) vs. "how" (low-level construal) questions regarding morality was associated with a situational state of greater self-control, as indexed by less Stroop interference in the Stroop color-naming task (Experiments 1 and 2). Participants exposed to "why" questions regarding morality displayed a greater inclination for volunteerism (Experiment 1), showed a lower tendency toward selfishness in a dictator game (Experiment 2), and were more likely to return undeserved money (Experiment 2) compared with participants exposed to "how" questions regarding morality. In both experiments, self-control mediated the effect of a high-level construal of morality on dependent measures. The current research constitutes a new approach to promoting prosociality and moral education. Reminding people to think abstractly about human morality may help them to generate better control over the temptation to benefit from unethical acts and make it more likely that they will act morally.

  7. School Attendance as a Civic Duty v. Home Education as a Human Right

    ERIC Educational Resources Information Center

    Reimer, Franz

    2010-01-01

    The article presents the legal situation of home education in Germany as a multi-level problem touching upon German constitutional law, State (Länder) constitutional law as well as administrative law, and the liberties of the European Convention of Human Rights. Whereas the parents' right to care for their children is explicitly granted by German…

  8. Can Embedded Annotations Help High School Students Perform Problem Solving Tasks Using a Web-Based Historical Document?

    ERIC Educational Resources Information Center

    Lee, John K.; Calandra, Brendan

    2004-01-01

    Two versions of a Web site on the United States Constitution were used by students in separate high school history classes to solve problems that emerged from four constitutional scenarios. One site contained embedded conceptual scaffolding devices in the form of textual annotations; the other did not. The results of our study demonstrated the…

  9. The Efficacy of "Catch-Up Programmes" in South African High Schools: A Legal Jinx

    ERIC Educational Resources Information Center

    Nyoni, Jabulani

    2013-01-01

    The South African State is mandated by Sections 28(2) and 29(1) of the South African Constitution to make provision for the education of a South African child in fulfilment of the child's constitutional rights. Teacher Unions (TUs) and provincial Departments of Basic Education (DBEs) have often promised South African high school student body, in…

  10. Teaching Free Speech Values to High School Students: Keys to Persevering Despite the Obstacles.

    ERIC Educational Resources Information Center

    Eveslage, Thomas

    To examine why citizens today do not understand the U.S. Constitution and its provisions, a survey was conducted among 153 high school social studies, journalism, and English teachers to examine, among other things, how they taught about constitutional rights and how they rated their students' knowledge of the subject compared to students'…

  11. Between demarcation and discretion: The medical-administrative boundary as a locus of safety in high-volume organisational routines.

    PubMed

    Grant, Suzanne; Guthrie, Bruce

    2018-04-01

    Patient safety is an increasing concern for health systems internationally. The majority of administrative work in UK general practice takes place in the context of organisational routines such as repeat prescribing and test results handling, where high workloads and increased clinician dependency on administrative staff have been identified as an emerging safety issue. Despite this trend, most research to date has focused on the redistribution of the clinical workload between doctors, nurses and allied health professionals within individual care settings. Drawing on Strauss's negotiated order perspective, we examine ethnographically the achievement of safety across the medical-administrative boundary in key high-volume routines in UK general practice. We focus on two main issues. First, GPs engaged in strategies of demarcation by defining receptionist work as routine, unspecialised and dependent upon GP clinical knowledge and oversight as the safety net to deal with complexity and risk. Receptionists consented to this 'social closure' when describing their role, thus reinforcing the underlying inter-occupational relationship of medical domination. Second, in everyday practice, GPs and receptionists engaged in informal boundary-blurring to safely accommodate the complexity of everyday high-volume routine work. This comprised additional informal discretionary spaces for receptionist decision-making and action that went beyond the routine safety work formally assigned to them. New restratified intra-occupational hierarchies were also being created between receptionists based on the complexity of the safety work that they were authorised to do at practice level, with specialised roles constituting a new form of administrative 'professional project'. The article advances negotiated order theory by providing an in-depth examination of the ways in which medical-administrative boundary-making and boundary-blurring constitute distinct modes of safety in high-volume routines. It also provides the basis for further research and safety improvement to maximise team-level understandings of the pivotal role of medical-administrative negotiations in achieving safety and mitigating risk. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Establishment and comparison of four constitutive relationships of PC/ABS from low to high uniaxial strain rates

    NASA Astrophysics Data System (ADS)

    Wang, Haitao; Zhang, Yun; Huang, Zhigao; Tang, Zhongbin; Wang, Yanpei; Zhou, Huamin

    2017-10-01

    The objective of this paper is to accurately predict the rate/temperature-dependent deformation of a polycarbonate (PC) and acrylonitrile-butadiene-styrene (ABS) blend at low, moderate, and high strain rates for various temperatures. Four constitutive models have been employed to predict stress-strain responses of PC/ABS under these conditions, including the DSGZ model, the original Mulliken-Boyce (M-B) model, the modified M-B model, and an adiabatic model named the Wang model. To more accurately capture the large deformation of PC/ABS under the high strain rate loading, the original M-B model is modified by allowing for the evolution of the internal shear strength. All of the four constitutive models above have been implemented in the finite element software ABAQUS/Explicit. A comparison of prediction accuracies of the four constitutive models over a wide range of strain rates and temperatures has been presented. The modified M-B model is observed to be more accurate in predicting the deformation of PC/ABS at high strain rates for various temperatures than the original M-B model, and the Wang model is demonstrated to be the most accurate in simulating the deformation of PC/ABS at low, moderate, and high strain rates for various temperatures.

  13. Distinguishing defensive characteristics in the phloem of ash species resistant and susceptible to emerald ash borer.

    PubMed

    Cipollini, Don; Wang, Qin; Whitehill, Justin G A; Powell, Jeff R; Bonello, Pierluigi; Herms, Daniel A

    2011-05-01

    We examined the extent to which three Fraxinus cultivars and a wild population that vary in their resistance to Emerald Ash Borer (EAB) could be differentiated on the basis of a suite of constitutive chemical defense traits in phloem extracts. The EAB-resistant Manchurian ash (F. mandshurica, cv. Mancana) was characterized by having a rapid rate of wound browning, a high soluble protein concentration, low trypsin inhibitor activities, and intermediate levels of peroxidase activity and total soluble phenolic concentration. The EAB-susceptible white ash (F. americana, cv. Autumn Purple) was characterized by a slow wound browning rate and low levels of peroxidase activity and total soluble phenolic concentrations. An EAB-susceptible green ash cultivar (F. pennsylvanica, cv. Patmore) and a wild accession were similar to each other on the basis of several chemical defense traits, and were characterized by high activities of peroxidase and trypsin inhibitor, a high total soluble phenolic concentration, and an intermediate rate of wound browning. Lignin concentration and polyphenol oxidase activities did not differentiate resistant and susceptible species. Of 33 phenolic compounds separated by HPLC and meeting a minimum criterion for analysis, nine were unique to Manchurian ash, five were shared among all species, and four were found in North American ashes and not in the Manchurian ash. Principal components analysis revealed clear separations between Manchurian, white, and green ashes on the basis of all phenolics, as well as clear separations on the basis of quantities of phenolics that all species shared. Variation in some of these constitutive chemical defense traits may contribute to variation in resistance to EAB in these species.

  14. Return to work, economic hardship, and women's postpartum health.

    PubMed

    Tucker, Jenna N; Grzywacz, Joseph G; Leng, Iris; Clinch, C Randall; Arcury, Thomas A

    2010-10-01

    This study followed a sample of 217 new mothers in a North Carolina county as they returned to work full-time, measuring their mental and physical health-related quality of life through 16 months postpartum. In general, working mothers of infants had mental health scores that were comparable to the general population of U.S. women, and physical health that was slightly better than women in general. Using ANCOVA and controlling for important demographic characteristics, health-related quality of life was compared between mothers experiencing low and high levels of economic hardship. Across the study period, women with high economic hardship, who constituted 30.7% of the sample, had levels of mental and physical health below those of women with low economic hardship. Mothers with high economic hardship also had less stable health trajectories than mothers with low economic hardship. The findings highlight the importance of reconsidering the traditionally accepted postpartum recovery period of six weeks and extending benefits, such as paid maternity and sick leave, as well as stable yet flexible work schedules.

  15. Risk profiles for poor treatment response to internet-delivered CBT in people with social anxiety disorder.

    PubMed

    Tillfors, Maria; Furmark, Tomas; Carlbring, Per; Andersson, Gerhard

    2015-06-01

    In social anxiety disorder (SAD) co-morbid depressive symptoms as well as avoidance behaviors have been shown to predict insufficient treatment response. It is likely that subgroups of individuals with different profiles of risk factors for poor treatment response exist. This study aimed to identify subgroups of social avoidance and depressive symptoms in a clinical sample (N = 167) with SAD before and after guided internet-delivered CBT, and to compare these groups on diagnostic status and social anxiety. We further examined individual movement between subgroups over time. Using cluster analysis we identified four subgroups, including a high-problem cluster at both time-points. Individuals in this cluster showed less remission after treatment, exhibited higher levels of social anxiety at both assessments, and typically remained in the high-problem cluster after treatment. Thus, in individuals with SAD, high levels of social avoidance and depressive symptoms constitute a risk profile for poor treatment response. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Nanophotonic Optical Isolator Controlled by the Internal State of Cold Atoms

    NASA Astrophysics Data System (ADS)

    Sayrin, Clément; Junge, Christian; Mitsch, Rudolf; Albrecht, Bernhard; O'Shea, Danny; Schneeweiss, Philipp; Volz, Jürgen; Rauschenbeutel, Arno

    2015-10-01

    The realization of nanophotonic optical isolators with high optical isolation even at ultralow light levels and low optical losses is an open problem. Here, we employ the link between the local polarization of strongly confined light and its direction of propagation to realize low-loss nonreciprocal transmission through a silica nanofiber at the single-photon level. The direction of the resulting optical isolator is controlled by the spin state of cold atoms. We perform our experiment in two qualitatively different regimes, i.e., with an ensemble of cold atoms where each atom is weakly coupled to the waveguide and with a single atom strongly coupled to the waveguide mode. In both cases, we observe simultaneously high isolation and high forward transmission. The isolator concept constitutes a nanoscale quantum optical analog of microwave ferrite resonance isolators, can be implemented with all kinds of optical waveguides and emitters, and might enable novel integrated optical devices for fiber-based classical and quantum networks.

  17. Arabidopsis thaliana phytochelatin synthase 2 is constitutively active in vivo and can rescue the growth defect of the PCS1-deficient cad1-3 mutant on Cd-contaminated soil.

    PubMed

    Kühnlenz, Tanja; Schmidt, Holger; Uraguchi, Shimpei; Clemens, Stephan

    2014-08-01

    Phytochelatins play a key role in the detoxification of metals in plants and many other eukaryotes. Their formation is catalysed by phytochelatin synthases (PCS) in the presence of metal excess. It appears to be common among higher plants to possess two PCS genes, even though in Arabidopsis thaliana only AtPCS1 has been demonstrated to confer metal tolerance. Employing a highly sensitive quantification method based on ultraperformance electrospray ionization quadrupole time-of-flight mass spectrometry, we detected AtPCS2-dependent phytochelatin formation. Overexpression of AtPCS2 resulted in constitutive phytochelatin accumulation, i.e. in the absence of metal excess, both in planta and in a heterologous system. This indicates distinct enzymatic differences between AtPCS1 and AtPCS2. Furthermore, AtPCS2 was able to partially rescue the Cd hypersensitivity of the AtPCS1-deficient cad1-3 mutant in a liquid seedling assay, and, more importantly, when plants were grown on soil spiked with Cd to a level that is close to what can be found in agricultural soils. No rescue was found in vertical-plate assays, the most commonly used method to assess metal tolerance. Constitutive AtPCS2-dependent phytochelatin synthesis suggests a physiological role of AtPCS2 other than metal detoxification. The differences observed between wild-type plants and cad1-3 on Cd soil demonstrated: (i) the essentiality of phytochelatin synthesis for tolerating levels of Cd contamination that can naturally be encountered by plants outside of metal-rich habitats, and (ii) a contribution to Cd accumulation under these conditions. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  18. A constitutive theory for shape memory polymers: coupling of small and large deformation

    NASA Astrophysics Data System (ADS)

    Tan, Qiao; Liu, Liwu; Liu, Yanju; Leng, Jinsong; Yan, Xiangqiao; Wang, Haifang

    2013-04-01

    At high temperatures, SMPs share attributes like rubber and exhibit long-range reversibility. In contrast, at low temperatures they become very rigid and are susceptible to plastic, only small strains are allowable. But there relatively little literature has considered the unique small stain (rubber phase) and large stain (glass phase) coupling in SMPs when developing the constitutive modeling. In this work, we present a 3D constitutive model for shape memory polymers in both low temperature small strain regime and high temperature large strain regime. The theory is based on the work of Liu et al. [15]. Four steps of SMP's thermomechanical loadings cycle are considered in the constitutive model completely. The linear elastic and hyperelastic effects of SMP in different temperatures are also fully accounted for in the proposed model by adopt the neo-Hookean model and the Generalized Hooke's laws.

  19. Predictors of weight gain: the biological-behavioural debate.

    PubMed

    Filozof, C; Gonzalez, C

    2000-05-01

    The rapidly increasing prevalence of obesity, in spite of an unchanged gene pool, makes it interesting to search for biological factors which increase the susceptibility at the individual level as well as searching for the responsible environmental factors. Among the identified metabolic factors is a low resting metabolic rate for given body size and composition, a high respiratory quotient (RQ) indicating a low fat oxidation and a low spontaneous physical activity, all factors which are regarded as being under substantial genetic influence. Among the environmental factors, it is low levels of physical activity, increasing inactivity and a high fat diet that are probably the most important ones. In this review we have focused on controversies in this area. Understanding the interaction between the constitutional biological factors and the environmentally determined lifestyle factors it is important to produce better options for both the prevention and treatment of obesity.

  20. Overexpression of monoubiquitin improves photosynthesis in transgenic tobacco plants following high temperature stress.

    PubMed

    Tian, Fengxia; Gong, Jiangfeng; Zhang, Jin; Feng, Yanan; Wang, Guokun; Guo, Qifang; Wang, Wei

    2014-09-01

    The ubiquitin/26S proteasome system (Ub/26S) is implicated in abiotic stress responses in plants. In this paper, transgenic tobacco plants overexpressing Ta-Ub2 from wheat were used to study the functions of Ub in the improvement of photosynthesis under high temperature (45°C) stress. We observed higher levels of Ub conjugates in transgenic plants under high temperature stress conditions compared to wild type (WT) as a result of the constitutive overexpression of Ta-Ub2, suggesting increased protein degradation by the 26S proteasome system under high temperature stress. Overexpressing Ub increased the photosynthetic rate (Pn) of transgenic tobacco plants, consistent with the improved ATPase activity in the thylakoid membrane and enhanced efficiency of PSII photochemistry. The higher D1 protein levels following high temperature stress in transgenic plants than WT were also observed. These findings imply that Ub may be involved in tolerance of photosynthesis to high temperature stress in plants. Compared with WT, the transgenic plants showed lower protein carbonylation and malondialdehyde (MDA) levels, less reactive oxygen species (ROS) accumulation, but higher antioxidant enzyme activity under high temperature stress. These findings suggest that the improved antioxidant capacity of transgenic plants may be one of the most important mechanisms underlying Ub-regulated high temperature tolerance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Inferring a dual-stream model of mentalizing from associative white matter fibres disconnection.

    PubMed

    Herbet, Guillaume; Lafargue, Gilles; Bonnetblanc, François; Moritz-Gasser, Sylvie; Menjot de Champfleur, Nicolas; Duffau, Hugues

    2014-03-01

    In the field of cognitive neuroscience, it is increasingly accepted that mentalizing is subserved by a complex frontotemporoparietal cortical network. Some researchers consider that this network can be divided into two distinct but interacting subsystems (the mirror system and the mentalizing system per se), which respectively process low-level, perceptive-based aspects and high-level, inference-based aspects of this sociocognitive function. However, evidence for this type of functional dissociation in a given neuropsychological population is currently lacking and the structural connectivities of the two mentalizing subnetworks have not been established. Here, we studied mentalizing in a large sample of patients (n = 93; 46 females; age range: 18-65 years) who had been resected for diffuse low-grade glioma-a rare tumour that migrates preferentially along associative white matter pathways. This neurological disorder constitutes an ideal pathophysiological model in which to study the functional anatomy of associative pathways. We mapped the location of each patient's resection cavity and residual lesion infiltration onto the Montreal Neurological Institute template brain and then performed multilevel lesion analyses (including conventional voxel-based lesion-symptom mapping and subtraction lesion analyses). Importantly, we estimated each associative pathway's degree of disconnection (i.e. the degree of lesion infiltration) and built specific hypotheses concerning the connective anatomy of the mentalizing subnetworks. As expected, we found that impairments in mentalizing were mainly related to the disruption of right frontoparietal connectivity. More specifically, low-level and high-level mentalizing accuracy were correlated with the degree of disconnection in the arcuate fasciculus and the cingulum, respectively. To the best of our knowledge, our findings constitute the first experimental data on the structural connectivity of the mentalizing network and suggest the existence of a dual-stream hodological system. Our results may lead to a better understanding of disorders that affect social cognition, especially in neuropathological conditions characterized by atypical/aberrant structural connectivity, such as autism spectrum disorders.

  2. Opposite nuclear level and binding activity of STAT5B and STAT3 proteins with rat haptoglobin gene under normal and turpentine induced acute phase conditions.

    PubMed

    Grigorov, I; Lazić, T; Cvetković, I; Milosavljević, T; Petrović, M

    2001-01-01

    Transcription of the rat gene encoding haptoglobin (Hp) is highly induced during acute phase (AP) response which has been previously shown to be mediated by inducible STAT3 member of the Signal Transducer and Activators of Transcription (STATs) family proteins. In this study, we observed that under normal but not in the turpentine induced AP conditions, another member of the STAT family proteins, STAT5b is expressed and binds to the hormone regulatory element (HRE) of the rat Hp gene. We found that the nuclear amounts of constitutively active STAT5b in rat liver decreased significantly with time of turpentine treatment as opposed to that of cytosol STAT5b, suggesting possible export of constitutive STAT5b from the nucleus. Nuclear accumulation and binding of inducible STAT3 proteins to the rat Hp gene HRE following turpentine treatment implicated that STAT5b negatively regulates Hp gene expression during normal conditions.

  3. The historical development and nutritional importance of olive and olive oil constituted an important part of the Mediterranean diet.

    PubMed

    Uylaşer, Vildan; Yildiz, Gökçen

    2014-01-01

    The olive tree (Olea europaea) is widely cultivated for the production of both oil and table olives and very significant because of its economic value. Olive and olive oil, a traditional food product with thousands of years of history, are the essential components of the Mediterranean diet and are largely consumed in the world. Beside of their economical contribution to national economy, these are an important food in terms of their nutritional value. Olive and olive oil may have a role in the prevention of coronary heart disease and certain cancers because of their high levels of monosaturated fatty acids and phenolic compounds. In addition, olives (Olea europaea L.) and olive oils provide a rich source of natural antioxidants. These make them both fairly stable against auto-oxidation and suitable for human health. The aim of this paper is to define the historical development and nutritional importance of olive and olive oil constituted an important part of the Mediterranean diet.

  4. Ring-like distribution of constitutive heterochromatin in bovine senescent cells.

    PubMed

    Pichugin, Andrey; Beaujean, Nathalie; Vignon, Xavier; Vassetzky, Yegor

    2011-01-01

    Cells that reach "Hayflick limit" of proliferation, known as senescent cells, possess a particular type of nuclear architecture. Human senescent cells are characterized by the presence of highly condensed senescent associated heterochromatin foci (SAHF) that can be detected both by immunostaining for histone H3 three-methylated at lysine 9 (H3K9me3) and by DAPI counterstaining. We have studied nuclear architecture in bovine senescent cells using a combination of immunofluorescence and 3D fluorescent in-situ hybridization (FISH). Analysis of heterochromatin distribution in bovine senescent cells using fluorescent in situ hybridization for pericentric chromosomal regions, immunostaining of H3K9me3, centromeric proteins CENP A/B and DNA methylation showed a lower level of heterochromatin condensation as compared to young cells. No SAHF foci were observed. Instead, we observed fibrous ring-like or ribbon-like heterochromatin patterns that were undetectable with DAPI counterstaining. These heterochromatin fibers were associated with nucleoli. Constitutive heterochromatin in bovine senescent cells is organized in ring-like structures.

  5. Constitutive modeling of intrinsic and oxygen-contaminated silicon monocrystals in easy glide

    NASA Astrophysics Data System (ADS)

    Cochard, J.; Yonenaga, I.; Gouttebroze, S.; M'Hamdi, M.; Zhang, Z. L.

    2010-11-01

    We generalize in this work the constitutive model for silicon crystals of Alexander and Haasen. Strain-rate and temperature dependency of the mechanical behavior of intrinsic crystals are correctly accounted for into stage I of hardening. We show that the steady-state of deformation in stage I is very well reproduced in a wide range of temperature and strain rate. The case of extrinsic crystals containing high levels of dissolved oxygen is examined. The introduction of an effective density of mobile dislocations dependent on the unlocking stress created by oxygen atoms gathered at the dislocation cores is combined to an alteration of the dislocation multiplication rate, due to pinning of the dislocation line by oxygen atoms. This increases the upper yield stress with the bulk oxygen concentration in agreement with experimental observations. The fraction of effectively mobile dislocations is found to decay exponentially with the unlocking stress. Finally, the influence of oxygen migration back onto the dislocations from the bulk on the stress distribution in silicon bars is investigated.

  6. Chemical composition and nutritional potential of yam bean seeds (Pachyrhizus erosus L. urban).

    PubMed

    Santos, A C; Cavalcanti, M S; Coelho, L C

    1996-01-01

    Pachyrhizus erosus seeds were analysed for proximate composition, minerals, protein fractions, antinutritional factors, and rotenoids. The seeds showed a high content of proteins, lipids, Fe and Ca, in comparison to other legumes. Glutelins constitute the highest protein fraction, followed by globulins. Antinutritional substances detected as tannins, hemagglutinating activity and trypsin inhibitory activity, were in low concentrations. Seeds were also processed to obtain a flour which showed proper characteristics, good in vitro digestibility, significant rotenoid reduction level and amino acid composition rich in essential amino acids, except methionine.

  7. Open airscrew VTOL concepts

    NASA Technical Reports Server (NTRS)

    Stepniewski, W. Z.; Tarczynski, T.

    1992-01-01

    The following concepts, based on using open airscrew(s) for VTOL maneuvers, are re-examined in light of current technology: (1) tip-driven helicopters, (2) compound helicopters; and (3) high-speed VTOL aircraft, represented by tiltrotors, tiltwings, retractoplanes and stoppable rotors. Criteria, permitting one to compare performance of aircraft using diverse lifting and propelling methods are established. Determination of currently possible performance, indication of near-future potentials, and comparison of those items with the baseline levels (as represented by contemporary shaft-driven helicopters, first generation tiltrotors, and commercial turboprop fixed-wind aircraft) constitutes bulk of this report.

  8. Multiplexing the Ethernet Interface Among VAX/VMS Users.

    DTIC Science & Technology

    1983-12-01

    Microcomputer Development Systems (MDS) and VAX/VPS sy’stemn were used for the implementation and testing of the project. The software is designed in such a...detailed design and .splesenta- toa of tie project. Is realLty chape: I constitutes the doee-.at os of the developed software. In soms instances, thisgs that...changes. 460i9n4t 4 provides a high level design of a virtual x $44 aletwock. alcag with some hints which may be useful So 44e W". who will work in this

  9. Constitutive Activation of NF-Kb in Prostate Carcinoma Cells through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (Ikki)

    DTIC Science & Technology

    2007-08-01

    mens retrieved from the two independent repositories. Overall, we evaluated GR expression in 35 high-grade prostatic intraepithelial neoplasia (HGPIN...NaCl, were incubated with AR antibody (1:500, BD Biosciences). DNA/protein complexes were isolated on salmon sperm DNA agarose and extracted with 1% SDS...NFjB is chiefly regulated via cytoplasmic retention by IjB-a. However, the IjB- a levels in the AR(1) cells showed only modest increase, after Dox

  10. Constitutive relationships of prestressed steel fiber concrete membrane elements

    NASA Astrophysics Data System (ADS)

    Hoffman, Norman S.

    Steel Fiber Concrete (SFC) displays certain tensile and shear characteristics which are beneficial for concrete that is loaded in a state of shear stress. For example, prestressed bridge beams carry shear load in their web by utilizing shear stirrups. If the properties of SFC can be better understood, then it may be possible to replace the shear stirrups with SFC. The first step in understanding this behavior is to develop a constitutive model for prestressed SFC. Two groups of full-scale prestressed steel fiber concrete (SFC) panels, with a nominal strength of 6 ksi, were tested in the Universal Element Testing machine at Thomas TC Hsu Structural Testing Laboratory to establish the effect of fiber and the level of prestress on the constitutive laws of fiber concrete and prestressing tendon. The specimens contained from 5 to 20 fully tensioned, low-relaxation grade 270 tendons. Fiber content ranged from 0.5% to 1.5% using high performance hooked end fibers. The first group of five panels, designated Group TEF, was used to determine the basic constitutive properties of prestressed SEC for use in the Softened Membrane Model (SMM). The constitutive model consists of smeared tensile and compressive stress strain relationships. An equation for softening with respect of both fiber content and tensile strain is presented. Also presented is a new equation for prestressed SFC in tension. It is notable that the behavior of prestressed SFC in tension displayed significant post-cracking tensile strength for fiber contents ranging from 0.5% to 1.5% by volume. Prior research on SFC using unreinforced dog-bone specimens, or prismatic specimens reinforced with only a single isolated tendon, are not capable of capturing SFC behavior afforded by the stress state, multiple load paths, and confinement situation available in full-scale panel assemblies. The second set of 5 test panels, designated Group TAF, was used to examine the properties of prestressed SFC under the conditions of pure shear. The constitutive model was incorporated into the softened membrane model framework and an analytic model was developed that was used to accurately predict the behavior of the specimens loaded in pure shear.

  11. Change in Thinking Demands for Students Across the Phases of a Science Task: An Exploratory Study

    NASA Astrophysics Data System (ADS)

    Tekkumru-Kisa, Miray; Schunn, Christian; Stein, Mary Kay; Reynolds, Bertha

    2017-08-01

    Science education communities around the world have increasingly emphasized engaging students in the disciplinary practices of science as they engage in high levels of reasoning about scientific ideas. Consistently, this is a critical moment in time in the USA as it goes through a new wave of science education reform within the context of Next Generation Science Standards (NGSS). We argue that the placement of high demands on students' thinking (i.e., a high level of thinking) in combination with positioning students to use disciplinary practices as they try to make sense of scientific ideas (i.e., a deep kind of thinking) constitute critical aspects of the reform. The main purpose of this paper is to identify and describe the kinds and levels of thinking in which students engage when they are invited to think and reason as demanded by NGSS-aligned curricular tasks. Our analysis of video records of classrooms in which an NGSS-aligned, cognitively demanding task was used, revealed many ways in which the aspirational level and kind of student thinking will not be met in many science classrooms. We propose a way of characterizing and labeling the differences among these kinds and levels of thinking during the implementation of a reform-based biology curriculum. These categories, which focus on two important features emphasized in the NGSS, can help us to better understand, diagnose, and communicate issues during the implementation of high-level tasks in science classrooms.

  12. Intraspecific variation in cadmium tolerance and accumulation of a high-biomass tropical tree Averrhoa carambola L.: implication for phytoextraction.

    PubMed

    Dai, Zi-yun; Shu, Wen-sheng; Liao, Bin; Wan, Cai-yun; Li, Jin-tian

    2011-06-01

    Averrhoa carambola L., a high-biomass tropical tree, has recently been shown to be a strong accumulator of cadmium (Cd) and has great potential for Cd phytoextraction. In the present study, field studies and a controlled-environment experiment were combined to establish the extent of variation in Cd tolerance and accumulation at the cultivar level using 14 to 19 cultivars of A. carambola. The results indicated that all cultivars tested could accumulate Cd at high but different levels, and that Cd tolerance also varied greatly between these cultivars. It is confirmed that the high Cd tolerance and accumulation capacity are species-level and constitutional traits in A. carambola. However, no correlation was detected between tolerance index and accumulation of Cd in different cultivars, suggesting that the two traits are independent in this woody Cd accumulator. More importantly, cultivar Wuchuan Sweet (WCT) was shown to have the highest Cd-extraction potential; it yielded a high shoot biomass of 30 t ha(-1) in 230 d, and extracted 330 g ha(-1) Cd in the aerial tissues grown in Cd-contaminated field soil, which accounted for 12.8% of the total soil Cd in the top 20 cm of the soil profile.

  13. Multiple Cytochrome P450 genes: their constitutive overexpression and permethrin induction in insecticide resistant mosquitoes, Culex quinquefasciatus.

    PubMed

    Liu, Nannan; Li, Ting; Reid, William R; Yang, Ting; Zhang, Lee

    2011-01-01

    Four cytochrome P450 cDNAs, CYP6AA7, CYP9J40, CYP9J34, and CYP9M10, were isolated from mosquitoes, Culex quinquefasciatus. The P450 gene expression and induction by permethrin were compared for three different mosquito populations bearing different resistance phenotypes, ranging from susceptible (S-Lab), through intermediate (HAmCq(G0), the field parental population) to highly resistant (HAmCq(G8), the 8(th) generation of permethrin selected offspring of HAmCq(G0)). A strong correlation was found for P450 gene expression with the levels of resistance and following permethrin selection at the larval stage of mosquitoes, with the highest expression levels identified in HAmCq(G8), suggesting the importance of CYP6AA7, CYP9J40, CYP9J34, and CYP9M10 in the permethrin resistance of larva mosquitoes. Only CYP6AA7 showed a significant overexpression in HAmCq(G8) adult mosquitoes. Other P450 genes had similar expression levels among the mosquito populations tested, suggesting different P450 genes may be involved in the response to insecticide pressure in different developmental stages. The expression of CYP6AA7, CYP9J34, and CYP9M10 was further induced by permethrin in resistant mosquitoes. Taken together, these results indicate that multiple P450 genes are up-regulated in insecticide resistant mosquitoes through both constitutive overexpression and induction mechanisms, thus increasing the overall expression levels of P450 genes.

  14. Predictive values of D-dimer assay, GRACE scores and TIMI scores for adverse outcome in patients with non-ST-segment elevation myocardial infarction

    PubMed Central

    Satilmisoglu, Muhammet Hulusi; Ozyilmaz, Sinem Ozbay; Gul, Mehmet; Ak Yildirim, Hayriye; Kayapinar, Osman; Gokturk, Kadir; Aksu, Huseyin; Erkanli, Korhan; Eksik, Abdurrahman

    2017-01-01

    Purpose To determine the predictive values of D-dimer assay, Global Registry of Acute Coronary Events (GRACE) and Thrombolysis in Myocardial Infarction (TIMI) risk scores for adverse outcome in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Patients and methods A total of 234 patients (mean age: 57.2±11.7 years, 75.2% were males) hospitalized with NSTEMI were included. Data on D-dimer assay, GRACE and TIMI risk scores were recorded. Logistic regression analysis was conducted to determine the risk factors predicting increased mortality. Results Median D-dimer levels were 349.5 (48.0–7,210.0) ng/mL, the average TIMI score was 3.2±1.2 and the GRACE score was 90.4±27.6 with high GRACE scores (>118) in 17.5% of patients. The GRACE score was correlated positively with both the D-dimer assay (r=0.215, P=0.01) and TIMI scores (r=0.504, P=0.000). Multivariate logistic regression analysis revealed that higher creatinine levels (odds ratio =18.465, 95% confidence interval: 1.059–322.084, P=0.046) constituted the only significant predictor of increased mortality risk with no predictive values for age, D-dimer assay, ejection fraction, glucose, hemoglobin A1c, sodium, albumin or total cholesterol levels for mortality. Conclusion Serum creatinine levels constituted the sole independent determinant of mortality risk, with no significant values for D-dimer assay, GRACE or TIMI scores for predicting the risk of mortality in NSTEMI patients. PMID:28408834

  15. E4orf1 induction in adipose tissue promotes insulin-independent signaling in the adipocyte

    PubMed Central

    Kusminski, Christine M.; Gallardo-Montejano, Violeta I.; Wang, Zhao V.; Hegde, Vijay; Bickel, Perry E.; Dhurandhar, Nikhil V.; Scherer, Philipp E.

    2015-01-01

    Background/Purpose Type 2 diabetes remains a worldwide epidemic with major pathophysiological changes as a result of chronic insulin resistance. Insulin regulates numerous biochemical pathways related to carbohydrate and lipid metabolism. Methods We have generated a novel mouse model that allows us to constitutively activate, in an inducible fashion, the distal branch of the insulin signaling transduction pathway specifically in adipocytes. Results Using the adenoviral 36 E4orf1 protein, we chronically stimulate locally the Ras-ERK-MAPK signaling pathway. At the whole body level, this leads to reduced body-weight gain under a high fat diet challenge. Despite overlapping glucose tolerance curves, there is a reduced requirement for insulin action under these conditions. The mice further exhibit reduced circulating adiponectin levels that ultimately lead to impaired lipid clearance, and inflamed and fibrotic white adipose tissues. Nevertheless, they are protected from diet-induced hepatic steatosis. As we observe constitutively elevated p-Akt levels in the adipocytes, even under conditions of low insulin levels, this pinpoints enhanced Ras-ERK-MAPK signaling in transgenic adipocytes as a potential alternative route to bypass proximal insulin signaling events. Conclusion We conclude that E4orf1 expression in the adipocyte leads to enhanced baseline activation of the distal insulin signaling node, yet impaired insulin receptor stimulation in the presence of insulin, with important implications for the regulation of adiponectin secretion. The resulting systemic phenotype is complex, yet highlights the powerful nature of manipulating selective branches of the insulin signaling network within the adipocyte. PMID:26500839

  16. The U.S. Constitution. A Teacher's Guide. Six 30-Minute Video Programs for Junior High and High School Students.

    ERIC Educational Resources Information Center

    Patrick, John J.

    This teacher's guide was designed to accompany six 30-minute video programs on the fundamental constitutional principles that form this nation's foundation. Each lesson in the guide contains an introduction to the main ideas of the program, a program summary, and suggested activities to carry out before and after the program. The topics emphasized…

  17. Misconceptions of High School Students Related to the Conceptions of Absolutism and Constitutionalism in History Courses

    ERIC Educational Resources Information Center

    Bal, Mehmet Suat

    2011-01-01

    The goal of this study is to analyze the 10th grade high school students' misconceptions related to the sense of ruling in the Ottoman State during the absolutist and constitutional periods and to investigate the causes of these misconceptions. The data were collected through eight open-ended questions related to the concepts of absolutism and…

  18. Reversible and Irreversible Time-Dependent Behavior of GRCop-84

    NASA Technical Reports Server (NTRS)

    Lerch, Bradley A.; Arnold, Steven M.; Ellis, David L.

    2017-01-01

    A series of mechanical tests were conducted on a high-conductivity copper alloy, GRCop-84, in order to understand the time dependent response of this material. Tensile, creep, and stress relaxation tests were performed over a wide range of temperatures, strain rates, and stress levels to excite various amounts of time-dependent behavior. At low applied stresses the deformation behavior was found to be fully reversible. Above a certain stress, termed the viscoelastic threshold, irreversible deformation was observed. At these higher stresses the deformation was observed to be viscoplastic. Both reversible and irreversible regions contained time dependent deformation. These experimental data are documented to enable characterization of constitutive models to aid in design of high temperature components.

  19. Oncogenic fusion proteins adopt the insulin-like growth factor signaling pathway.

    PubMed

    Werner, Haim; Meisel-Sharon, Shilhav; Bruchim, Ilan

    2018-02-19

    The insulin-like growth factor-1 receptor (IGF1R) has been identified as a potent anti-apoptotic, pro-survival tyrosine kinase-containing receptor. Overexpression of the IGF1R gene constitutes a typical feature of most human cancers. Consistent with these biological roles, cells expressing high levels of IGF1R are expected not to die, a quintessential feature of cancer cells. Tumor specific chromosomal translocations that disrupt the architecture of transcription factors are a common theme in carcinogenesis. Increasing evidence gathered over the past fifteen years demonstrate that this type of genomic rearrangements is common not only among pediatric and hematological malignancies, as classically thought, but may also provide a molecular and cytogenetic foundation for an ever-increasing portion of adult epithelial tumors. In this review article we provide evidence that the mechanism of action of oncogenic fusion proteins associated with both pediatric and adult malignancies involves transactivation of the IGF1R gene, with ensuing increases in IGF1R levels and ligand-mediated receptor phosphorylation. Disrupted transcription factors adopt the IGF1R signaling pathway and elicit their oncogenic activities via activation of this critical regulatory network. Combined targeting of oncogenic fusion proteins along with the IGF1R may constitute a promising therapeutic approach.

  20. Impact of constitutional copy number variants on biological pathway evolution.

    PubMed

    Poptsova, Maria; Banerjee, Samprit; Gokcumen, Omer; Rubin, Mark A; Demichelis, Francesca

    2013-01-23

    Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations.

  1. Impact of constitutional copy number variants on biological pathway evolution

    PubMed Central

    2013-01-01

    Background Inherited Copy Number Variants (CNVs) can modulate the expression levels of individual genes. However, little is known about how CNVs alter biological pathways and how this varies across different populations. To trace potential evolutionary changes of well-described biological pathways, we jointly queried the genomes and the transcriptomes of a collection of individuals with Caucasian, Asian or Yoruban descent combining high-resolution array and sequencing data. Results We implemented an enrichment analysis of pathways accounting for CNVs and genes sizes and detected significant enrichment not only in signal transduction and extracellular biological processes, but also in metabolism pathways. Upon the estimation of CNV population differentiation (CNVs with different polymorphism frequencies across populations), we evaluated that 22% of the pathways contain at least one gene that is proximal to a CNV (CNV-gene pair) that shows significant population differentiation. The majority of these CNV-gene pairs belong to signal transduction pathways and 6% of the CNV-gene pairs show statistical association between the copy number states and the transcript levels. Conclusions The analysis suggested possible examples of positive selection within individual populations including NF-kB, MAPK signaling pathways, and Alu/L1 retrotransposition factors. Altogether, our results suggest that constitutional CNVs may modulate subtle pathway changes through specific pathway enzymes, which may become fixed in some populations. PMID:23342974

  2. Microscopic molecular dynamics characterization of the second-order non-Navier-Fourier constitutive laws in the Poiseuille gas flow

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

    Rana, A.; Ravichandran, R.; Park, J. H.

    The second-order non-Navier-Fourier constitutive laws, expressed in a compact algebraic mathematical form, were validated for the force-driven Poiseuille gas flow by the deterministic atomic-level microscopic molecular dynamics (MD). Emphasis is placed on how completely different methods (a second-order continuum macroscopic theory based on the kinetic Boltzmann equation, the probabilistic mesoscopic direct simulation Monte Carlo, and, in particular, the deterministic microscopic MD) describe the non-classical physics, and whether the second-order non-Navier-Fourier constitutive laws derived from the continuum theory can be validated using MD solutions for the viscous stress and heat flux calculated directly from the molecular data using the statistical method.more » Peculiar behaviors (non-uniform tangent pressure profile and exotic instantaneous heat conduction from cold to hot [R. S. Myong, “A full analytical solution for the force-driven compressible Poiseuille gas flow based on a nonlinear coupled constitutive relation,” Phys. Fluids 23(1), 012002 (2011)]) were re-examined using atomic-level MD results. It was shown that all three results were in strong qualitative agreement with each other, implying that the second-order non-Navier-Fourier laws are indeed physically legitimate in the transition regime. Furthermore, it was shown that the non-Navier-Fourier constitutive laws are essential for describing non-zero normal stress and tangential heat flux, while the classical and non-classical laws remain similar for shear stress and normal heat flux.« less

  3. Stirling engine - Approach for long-term durability assessment

    NASA Technical Reports Server (NTRS)

    Tong, Michael T.; Bartolotta, Paul A.; Halford, Gary R.; Freed, Alan D.

    1992-01-01

    The approach employed by NASA Lewis for the long-term durability assessment of the Stirling engine hot-section components is summarized. The approach consists of: preliminary structural assessment; development of a viscoplastic constitutive model to accurately determine material behavior under high-temperature thermomechanical loads; an experimental program to characterize material constants for the viscoplastic constitutive model; finite-element thermal analysis and structural analysis using a viscoplastic constitutive model to obtain stress/strain/temperature at the critical location of the hot-section components for life assessment; and development of a life prediction model applicable for long-term durability assessment at high temperatures. The approach should aid in the provision of long-term structural durability and reliability of Stirling engines.

  4. State Constitutional Commitment to Health and Health Care and Population Health Outcomes: Evidence From Historical US Data

    PubMed Central

    2015-01-01

    Objectives. I investigated whether the introduction of health and health care provisions in US state constitutions can make health systems more equitable and improve health outcomes by urging state policymakers and administrative agencies to uphold their human rights obligations at state level. Methods. I constructed a panel of infant mortality rates from 50 US states over the period 1929 through 2000 to examine their association with the timing and details of introducing a constitutional right to health and health care provisions. Results. The introduction of a stronger constitutional commitment that obligates state legislature to provide health care was associated with a subsequent reduction in the infant mortality rate of approximately 7.8%. The introduction of provisions explicitly targeting the poor was also associated with a reduction in the infant mortality rate of 6.5%. These health benefits are primarily evident in non-White populations. Conclusions. This empirical result supports Elizabeth Leonard’s view that although state constitutional rights have been poorly enforced through the judiciary, a constitutional expression of health care duties has fueled the political and social process, ultimately allowing states to identify the best way to address citizens’ health inequality concerns. PMID:25905857

  5. State constitutional commitment to health and health care and population health outcomes: evidence from historical US data.

    PubMed

    Matsuura, Hiroaki

    2015-07-01

    I investigated whether the introduction of health and health care provisions in US state constitutions can make health systems more equitable and improve health outcomes by urging state policymakers and administrative agencies to uphold their human rights obligations at state level. I constructed a panel of infant mortality rates from 50 US states over the period 1929 through 2000 to examine their association with the timing and details of introducing a constitutional right to health and health care provisions. The introduction of a stronger constitutional commitment that obligates state legislature to provide health care was associated with a subsequent reduction in the infant mortality rate of approximately 7.8%. The introduction of provisions explicitly targeting the poor was also associated with a reduction in the infant mortality rate of 6.5%. These health benefits are primarily evident in non-White populations. This empirical result supports Elizabeth Leonard's view that although state constitutional rights have been poorly enforced through the judiciary, a constitutional expression of health care duties has fueled the political and social process, ultimately allowing states to identify the best way to address citizens' health inequality concerns.

  6. Inhibition of FUSCA3 degradation at high temperature is dependent on ABA signaling and is regulated by the ABA/GA ratio.

    PubMed

    Chiu, Rex Shun; Saleh, Yazan; Gazzarrini, Sonia

    2016-11-01

    During seed imbibition at supra-optimal temperature, an increase in the abscisic acid (ABA)/gibberellin (GA) ratio imposes secondary dormancy to prevent germination (thermoinhibition). FUSCA3 (FUS3), a positive regulator of seed dormancy, accumulates in seeds imbibed at high temperature and increases ABA levels to inhibit germination. Recently, we showed that ABA inhibits FUS3 degradation at high temperature, and that ABA and high temperature also inhibit the ubiquitin-proteasome system, by dampening both proteasome activity and protein polyubiquitination. Here, we investigated the role of ABA signaling components and the ABA antagonizing hormone, GA, in the regulation of FUS3 levels. We show that the ABA receptor mutant, pyl1-1, is less sensitive to ABA and thermoinhibition. In this mutant background, FUS3 degradation in vitro is faster. Similarly, GA alleviates thermoinhibition and also increases FUS3 degradation. These results indicate that inhibition of FUS3 degradation at high temperature is dependent on a high ABA/GA ratio and a functional ABA signaling pathway. Thus, FUS3 constitutes an important node in ABA-GA crosstalk during germination at supra-optimal temperature.

  7. Constitutive and Stability Behavior of Granular Materials Under Very Low Effective Stresses

    NASA Technical Reports Server (NTRS)

    Alshibli, Khalid A.; Sture, Stein; Costes, Nicholas C.; Batiste, Susan N.; Swanson, Roy A.; Lankton, Mark R.

    1999-01-01

    The study of the behavior of granular materials such as sand is of great importance to the understanding of the response of foundations resting on surface and near-surface soil deposits. A clear understanding of the behavior of such materials can also provide insights into other related issues where low effective stresses are encountered such as liquefaction. The main sources of the constitutive and stability properties of cohesionless granular materials is interparticle friction, which in turn under low confinement stress levels is strongly affected by gravitational body forces under terrestrial (1 gravity) conditions. Under moderate-to-high stress levels, the influence of gravity on the behavior of experiments may not be pronounced and therefore the test results in a terrestrial environment may be acceptable for engineering purposes. However, the conduct of experiments on granular materials under very low stress levels and under quasi-static conditions can only be performed in a microgravity environment. A series of displacement-controlled cyclic triaxial compression experiments were performed in a SPACEHAB module on the Space Shuttle during the STS-79 mission to Mir in September, 1996, and the STS-89 mission in January, 1998. The experiments were conducted on six right cylindrical specimens 75 mm in diameter and 150 mm long at effective confining pressures of 0.05, 0.52 and 1.30 kPa. The results show very high peak strength friction angles in the range of 47.6 to 70.0 degrees, which are mainly due to overconsolidation and grain interlocking effects. It was observed that the residual strength levels were in the same range as that observed at higher confining stress levels. The dilatancy angles were unusually high in the range of 30 to 31 degrees. All specimens display substantial initial stiffnesses and elastic moduli during unloading and reloading events, which are nearly an order of magnitude higher than conventional theories predict. A periodic instability phenomenon which appears to result from buckling of multiple internal arches and columnar systems, augmented by stick-slips was observed in the experiments. Computed Tomography (CT) measurements revealed valuable data about the internal fabric and the specimens deformation patterns. Uniform diffuse bifurcation with multiple radial shear bands was observed in the specimens tested in a microgravity environment. In the axial direction, two major conical surfaces were developed. Spatial nonsymmetrical deformations were observed in specimens tested in terrestrial laboratory.

  8. Multistate and phase change selection in constitutional multivalent systems.

    PubMed

    Barboiu, Mihail

    2012-01-01

    Molecular architectures and materials can be constitutionally self-sorted in the presence of different biomolecular targets or external physical stimuli or chemical effectors, thus responding to an external selection pressure. The high selectivity and specificity of different bioreceptors or self-correlated internal interactions may be used to describe the complex constitutional behaviors through multistate component selection from a dynamic library. The self-selection may result in the dynamic amplification of self-optimized architectures during the phase change process. The sol-gel resolution of dynamic molecular/supramolecular libraries leads to higher self-organized constitutional hybrid materials, in which organic (supramolecular)/inorganic domains are reversibily connected.

  9. Anisotropic constitutive model incorporating multiple damage mechanisms for multiscale simulation of dental enamel.

    PubMed

    Ma, Songyun; Scheider, Ingo; Bargmann, Swantje

    2016-09-01

    An anisotropic constitutive model is proposed in the framework of finite deformation to capture several damage mechanisms occurring in the microstructure of dental enamel, a hierarchical bio-composite. It provides the basis for a homogenization approach for an efficient multiscale (in this case: multiple hierarchy levels) investigation of the deformation and damage behavior. The influence of tension-compression asymmetry and fiber-matrix interaction on the nonlinear deformation behavior of dental enamel is studied by 3D micromechanical simulations under different loading conditions and fiber lengths. The complex deformation behavior and the characteristics and interaction of three damage mechanisms in the damage process of enamel are well captured. The proposed constitutive model incorporating anisotropic damage is applied to the first hierarchical level of dental enamel and validated by experimental results. The effect of the fiber orientation on the damage behavior and compressive strength is studied by comparing micro-pillar experiments of dental enamel at the first hierarchical level in multiple directions of fiber orientation. A very good agreement between computational and experimental results is found for the damage evolution process of dental enamel. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Even Lesbian Youths or Those Presumed to Be Lesbians Are Protected by the Constitution of Uganda--But to a Limited Extent: Rules the High Court

    ERIC Educational Resources Information Center

    Mujuzi, Jamil Ddamulira

    2009-01-01

    The Ugandan Penal Code criminalizes same-sex relationships. The author analyzes the Ugandan High Court decision where the judge relied on the Constitution and international human rights instruments to hold that law enforcement officers must respect the rights to privacy and human dignity even of those people presumed to be in same-sex…

  11. High Heregulin Expression Is Associated with Activated HER3 and May Define an Actionable Biomarker in Patients with Squamous Cell Carcinomas of the Head and Neck

    PubMed Central

    Shames, David S.; Carbon, Juliet; Walter, Kim; Jubb, Adrian M.; Kozlowski, Cleopatra; Januario, Tom; An, Do; Fu, Ling; Xiao, Yuanyuan; Raja, Rajiv; Jiang, Brittany; Malekafzali, Ashi; Stern, Howard; Settleman, Jeff; Wilson, Timothy R.; Hampton, Garret M.; Yauch, Robert L.; Pirzkall, Andrea; Amler, Lukas C.

    2013-01-01

    Purpose Tumors with oncogenic dependencies on the HER family of receptor tyrosine kinases (RTKs) often respond well to targeted inhibition. Our previous work suggested that many cell lines derived from squamous cell carcinomas of the head and neck (SCCHNs) depend on autocrine signaling driven by HER2/3 dimerization and high-level co-expression of HRG. Additionally, results from a Phase I trial of MEHD7495A, a dual-action antibody that blocks ligand binding to EGFR and HER3, suggest that high-level HRG expression was associated with clinical response in SCCHN patients. Here we explore the hypothesis that high-level HRG expression defines a subpopulation of SCCHNs with activated HER3. Experimental Design qRT-PCR expression profiling was performed on >750 tumors of diverse origin, including >150 therapy-naïve, primary, and recurrent SCCHNs. Activated HER3, defined by immunoprecipitation of phospho-HER3, was compared to HRG expression in SCCHN samples. Paracrine versus autocrine expression was evaluated using RNA-in situ hybridization. Results SCCHN tumors express the highest levels of HRG compared to a diverse collection of other tumor types. We show that high HRG expression is associated with activated HER3, whereas low HRG expression is associated with low HER3 activation in SCCHN tumors. Furthermore, HRG expression is higher in recurrent SCCHN compared to patient-matched therapy naïve specimens. Conclusions HRG expression levels define a biologically distinct subset of SCCHN patients. We propose that high-level expression of HRG is associated with constitutive activation of HER3 in SCCHN and thus defines an actionable biomarker for interventions targeting HER3. PMID:23468880

  12. Near East/South Asia Report.

    DTIC Science & Technology

    1985-10-08

    defunct Pakistan People’s Party [PPP] is currently divided into many fighting factions. After martial law had been imposed on the country, the ladies of...constitutional rule from Martial Law holding on national polls at the shortest possible time on the revival of the suspended Constitution, handing over of power...constitution re human rights and writ jurisdiction of the High Court. 101 JPRS-NEA-85-128 8 October 1985 The front called for winding up of Martial Law

  13. Detoxification of sewage sludge by natural attenuation and implications for its use as a fertilizer on agricultural soils.

    PubMed

    Mazzeo, Dânia Elisa Christofoletti; Casado, Marta; Piña, Benjamin; Marin-Morales, Maria Aparecida

    2016-12-01

    Sewage Sludges (SS) from wastewater treatment systems constitute a potential alternative to agricultural fertilizers. However, their use is limited by the presence of toxic substances that may represent significant hazards for the environment and for human health. To test the potential of natural processes to attenuate their putative toxic activities, actual SS samples from domestic sewage were buried in holes in a pollution-free environment for different periods of time, up to one year. Aqueous and organic extracts were obtained after each period of natural attenuation, and their respective toxicity was tested for estrogenic and dioxin-like activity by yeast-based bioassays (ER-RYA and AhR-RYA, respectively) and for general toxicity and teratogenicity in zebrafish embryos. Dioxin-like activity was also tested in zebrafish embryos by monitoring the induction of the marker gene cyp1a. Whereas the results showed essentially no estrogenic activity, both dioxin-like activity and embryotoxicity were observed in the initial samples, decreasing significantly after six months of attenuation. Chemical analysis of toxic SS samples showed the presence of low levels of dioxins and furans, and relatively high levels of m- and p-cresol, at concentrations that only partially justify the observed biological effects. Our data indicates the presence of largely uncharacterized hydrophilic compounds with high biological activity in SS, constituting a potential risk of groundwater pollution upon their disposal into the environment. It also shows that this potential impact may be significantly mitigated by attenuation protocols, as the one presented here. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. A Proposal for a Civics Study Program

    ERIC Educational Resources Information Center

    Marcus, Stuart Paul; Richman, Paul Jeffrey

    1978-01-01

    Two high school students recommend a civics study program which would include (1) a required course on governmental structure, responsibilities, and the U.S. Constitution, and (2) elective courses on crime, juvenile delinquency, state and local government, and history of constitutional law. (AV)

  15. A Venture in Constitutional Law.

    ERIC Educational Resources Information Center

    Cole, W. Graham; Dillon, Dorothy H.

    1980-01-01

    Senior high girls and boys from two single-sex schools undertook a study of a Supreme Court case that provided insight not only into constitutional law and history but also into how men and women can work together and relate in other ways than dating. (DS)

  16. Arabidopsis alcohol dehydrogenase expression in both shoots and roots is conditioned by root growth environment

    NASA Technical Reports Server (NTRS)

    Chung, H. J.; Ferl, R. J.

    1999-01-01

    It is widely accepted that the Arabidopsis Adh (alcohol dehydrogenase) gene is constitutively expressed at low levels in the roots of young plants grown on agar media, and that the expression level is greatly induced by anoxic or hypoxic stresses. We questioned whether the agar medium itself created an anaerobic environment for the roots upon their growing into the gel. beta-Glucuronidase (GUS) expression driven by the Adh promoter was examined by growing transgenic Arabidopsis plants in different growing systems. Whereas roots grown on horizontal-positioned plates showed high Adh/GUS expression levels, roots from vertical-positioned plates had no Adh/GUS expression. Additional results indicate that growth on vertical plates closely mimics the Adh/GUS expression observed for soil-grown seedlings, and that growth on horizontal plates results in induction of high Adh/GUS expression that is consistent with hypoxic or anoxic conditions within the agar of the root zone. Adh/GUS expression in the shoot apex is also highly induced by root penetration of the agar medium. This induction of Adh/GUS in shoot apex and roots is due, at least in part, to mechanisms involving Ca2+ signal transduction.

  17. Constitutive BAK activation as a determinant of drug sensitivity in malignant lymphohematopoietic cells.

    PubMed

    Dai, Haiming; Ding, Husheng; Meng, X Wei; Peterson, Kevin L; Schneider, Paula A; Karp, Judith E; Kaufmann, Scott H

    2015-10-15

    Mitochondrial outer membrane permeabilization (MOMP), a key step in the intrinsic apoptotic pathway, is incompletely understood. Current models emphasize the role of BH3-only BCL2 family members in BAX and BAK activation. Here we demonstrate concentration-dependent BAK autoactivation under cell-free conditions and provide evidence that this autoactivation plays a key role in regulating the intrinsic apoptotic pathway in intact cells. In particular, we show that up to 80% of BAK (but not BAX) in lymphohematopoietic cell lines is oligomerized and bound to anti-apoptotic BCL2 family members in the absence of exogenous death stimuli. The extent of this constitutive BAK oligomerization is diminished by BAK knockdown and unaffected by BIM or PUMA down-regulation. Further analysis indicates that sensitivity of cells to BH3 mimetics reflects the identity of the anti-apoptotic proteins to which BAK is constitutively bound, with extensive BCLXL•BAK complexes predicting navitoclax sensitivity, and extensive MCL1•BAK complexes predicting A1210477 sensitivity. Moreover, high BAK expression correlates with sensitivity of clinical acute myelogenous leukemia to chemotherapy, whereas low BAK levels correlate with resistance and relapse. Collectively, these results inform current understanding of MOMP and provide new insight into the ability of BH3 mimetics to induce apoptosis without directly activating BAX or BAK. © 2015 Dai et al.; Published by Cold Spring Harbor Laboratory Press.

  18. Generation of a stable cell line for constitutive miRNA expression.

    PubMed

    Lieber, Diana

    2013-01-01

    miRNAs have in recent years emerged as novel players in virus-host interactions. While individual miRNAs are capable of regulating many targets simultaneously, not much is known about the role of distinct host or viral miRNAs in the context of infection. Analysis of the function of a miRNA is often hampered by the complexity of virus-host interactions and the enormous changes in the host cell during infection. Many viral miRNAs as for example from Kaposi sarcoma-associated Herpesvirus (KSHV) are probably exclusively expressed in latent infection. This might lead to a steady-state situation with offense and defense mechanisms counteracting each other. Cellular miRNAs involved in defense against pathogens on the other hand might be suppressed in infection. A cell culture system allowing for constitutive expression of individual miRNAs at high levels is a useful tool to enhance miRNA-specific functions and to uncouple viral miRNA function from other infection-related mechanisms. Here, a protocol is described to generate stable cell lines for constitutive expression of single cellular or viral miRNA precursors in absence of infection. The procedure comprises cloning of the precursor sequence, generation of the lentiviral expression vector, transduction of the cells of interest, selection for polyclonal cell lines, and isolation of monoclonal cell lines by limiting dilution.

  19. Enhanced phosphorylation of STAT1 is dependent on PKR signaling in HLA-B27 expressing U937 monocytic cells

    PubMed Central

    Ruuska, Marja; Sahlberg, Anna S.; Colbert, Robert A.; Granfors, Kaisa; Penttinen, Markus A.

    2011-01-01

    Objective To study the phosphorylation of STAT1 in HLA-B27-transfected human monocytic cells and the role of signaling molecules PKR and p38 in STAT1 phosphorylation. Methods U937 human monocytic cell transfectants stably expressing wild type HLA-B27 or mutated HLA-B27 heavy chains (HC) with amino acid substitutions in the B pocket were prepared. Mock transfected cells were prepared using the antibiotic resistance vectors (pSV2neo or RSV5neo) alone. PMA differentiated cells were stimulated with LPS or infected with S. enteritidis. Western blotting and flow cytometry were used to detect the phosphorylation and expression levels of STAT1 protein. Specific inhibitors were added in cell culture to study the role of PKR and p38 on STAT1 phosphorylation. Results STAT1 is constitutively highly phosphorylated on tyrosine 701 residue in HLA-B27 positive monocytic cells when compared to control cells, even prior to stimulation with LPS or bacteria. This phenotype is associated with the expression of HLA-B27 HCs that misfold. In addition, phosphorylation of STAT1 is dependent on PKR. Conclusion Our results show that STAT1 tyrosine 701 is constitutively highly phosphorylated in HLA-B27 expressing monocyte-macrophage cell line. Since phosphorylation of tyrosine 701 on STAT1 is sufficient to induce interferon-dependent genes, constitutive activity of this phosphorylation site may lead to overexpression of interferon-dependent genes, as well as other STAT1-dependent genes, in HLA-B27 monocyte-macrophages. Our results offer a mechanism by which B27 expression alone, without any external trigger, is potentially capable of inducing activation of STAT1, a critical regulator of the inflammatory response. PMID:21968657

  20. Neuropeptide Y and α-MSH circadian levels in two populations with low body weight: anorexia nervosa and constitutional thinness.

    PubMed

    Galusca, Bogdan; Prévost, Gaëtan; Germain, Natacha; Dubuc, Isabelle; Ling, Yiin; Anouar, Youssef; Estour, Bruno; Chartrel, Nicolas

    2015-01-01

    Anorexia nervosa (AN) presents an adaptive appetite regulating profile including high levels of ghrelin and 26RFa (orexigenic) and low levels of leptin and PYY (anorexigenic). However, this adaptive mechanism is not effective in promoting food intake. The NPY/proopiomelanocortin (POMC) system plays a crucial role in the regulation of feeding behavior as NPY is the most potent orexigenic neuropeptide identified so far and as the POMC-derived peptide α-MSH drastically reduces food intake, and this peptidergic system has not been thoroughly studied in AN. The aim of the present study was thus to investigate whether a dysfunction of the NPY/POMC occurs in two populations with low body weight, AN and constitutional thinness (CT). This was a cross-sectional study performed in an endocrinological unit and in an academic laboratory. Three groups of age-matched young women were studied: 23 with AN (AN), 22 CT and 14 normal weight controls. Twelve-point circadian profiles of plasma NPY and α-MSH levels were measured in the three groups of investigated subjects. No significant circadian variation of NPY was detected between the three groups. Plasma α-MSH levels were significantly lower in AN (vs controls) all over the day. The CT group, compared to controls, presented lower levels of α-MSH in the morning and the evening, and an important rise during lunchtime. In AN patients, the NPY system is not up-regulated under chronic undernutrition suggesting that this may play a role in the inability of anorectic women to adapt food intake to their energy demand. In contrast, low circadian α-MSH levels integrate the adaptive profile of appetite regulation of this disease. Finally, in CT women, the important α-MSH peak detected during lunchtime could explain why these patients are rapidly food satisfied.

  1. Constitutive β-catenin activation in osteoblasts impairs terminal osteoblast differentiation and bone quality

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

    Bao, Quanwei; Chen, Sixu; Qin, Hao

    Accumulating evidence suggests that Wnt/β-catenin signaling plays a central role in controlling bone mass. We previously reported that constitutive activation of β-catenin (CA-β-catenin) in osteoblasts potentially has side effects on the bone growth and bone remodeling process, although it could increase bone mass. The present study aimed to observe the effects of osteoblastic CA-β-catenin on bone quality and to investigate possible mechanisms of these effects. It was found that CA-β-catenin mice exhibited lower mineralization levels and disorganized collagen in long bones as confirmed by von Kossa staining and sirius red staining, respectively. Also, bone strength decreased significantly in CA-β-catenin mice.more » Then the effect of CA-β-catenin on biological functions of osteoblasts were investigated and it was found that the expression levels of osteocalcin, a marker for the late differentiation of osteoblasts, decreased in CA-β-catenin mice, while the expression levels of osterix and alkaline phosphatase, two markers for the early differentiation of osteoblasts, increased in CA-β-catenin mice. Furthermore, higher proliferation rate were revealed in osteoblasts that were isolated from CA-β-catenin mice. The Real-time PCR and western blot examination found that the expression level of c-myc and cyclin D1, two G1 progression-related molecules, increased in osteoblasts that were isolated from the CA-β-catenin mice, and the expression levels of CDK14 and cyclin Y, two mitotic-related molecules that can accelerate cells entering into S and G2/M phases, increased in osteoblasts that were isolated from the CA-β-catenin mice. In summary, osteoblastic CA-β-catenin kept osteoblasts in high proliferative state and impaired the terminal osteoblast differentiation, and this led to changed bone structure and decreased bone strength. - Highlights: • Wnt/β-catenin signaling plays a central role in controlling bone mass. • CA-β-catenin has side effects on the bone strength and bone qulity. • CA-β-catenin kept osteoblasts in high proliferative state. • Osteoblastic CA-β-catenin impaired the terminal osteoblast differentiation.« less

  2. Maintenance of Mitochondrial Oxygen Homeostasis by Cosubstrate Compensation

    PubMed Central

    Kueh, Hao Yuan; Niethammer, Philipp; Mitchison, Timothy J.

    2013-01-01

    Mitochondria maintain a constant rate of aerobic respiration over a wide range of oxygen levels. However, the control strategies underlying oxygen homeostasis are still unclear. Using mathematical modeling, we found that the mitochondrial electron transport chain (ETC) responds to oxygen level changes by undergoing compensatory changes in reduced electron carrier levels. This emergent behavior, which we named cosubstrate compensation (CSC), enables the ETC to maintain homeostasis over a wide of oxygen levels. When performing CSC, our ETC models recapitulated a classic scaling relationship discovered by Chance [Chance B (1965) J. Gen. Physiol. 49:163-165] relating the extent of oxygen homeostasis to the kinetics of mitochondrial electron transport. Analysis of an in silico mitochondrial respiratory system further showed evidence that CSC constitutes the dominant control strategy for mitochondrial oxygen homeostasis during active respiration. Our findings indicate that CSC constitutes a robust control strategy for homeostasis and adaptation in cellular biochemical networks. PMID:23528093

  3. Constitutive and Stability Behavior of Soils in Microgravity Environment

    NASA Technical Reports Server (NTRS)

    Alshibli, Khalid A.; Sture, Stein; Costes, Nicholas

    2000-01-01

    All aspects of soil stability, bearing capacity, slope stability, the supporting capacity of deep foundations, and penetration resistance depend on soil strength. The stress-deformation and stress-deformation-time behavior of soils are of importance in any problem where ground movements are of interest. In most engineering materials, the strength is derived from internal chemical and physico-chemical forces of interaction, which bond the atoms, molecules, and particles together. In soils, the constitutive relations are mainly derived from interparticle friction between particles and particle groups and dilatancy, and to a lesser extent from particle bonding by weak electrostatic, physico-chemical, and coulomb forces. For engineering purposes, soils are classified as cohesive (clays and silts; typical particle sizes range from 10 nm to 10 micrometers) and cohesionless (sand and gravel; typical particle sizes range from 10 micrometers to 75 mm). The mechanical or constitutive properties of cohesionless soils or granular materials are highly fabric-dependent, highly non-linear, and non-conservative with engineering properties primarily depending on the effects of gravity through self-weight and on the tractions or forces applied to the soil mass. Under moderate-to-high stress levels, the influence of gravity on the behavior of laboratory test specimens may not be pronounced and, therefore, the test results in terrestrial (1-g) environment may be sufficiently conclusive. However at low interparticle stresses, which can result either from low applied (confining) stresses or from excess pore fluid pressures developed within the soil mass without corresponding changes in the applied stresses, the presence of gravitational body forces acting on solid particles and interstitial fluids exerts a pronounced influence on movement of individual particles or particle groups. Such motions, in turn, cause changes in soil fabric which results in significant changes in the interparticle friction forces contributing to the soil's strength and deformation characteristics.

  4. Supramolecular chemistry: from molecular information towards self-organization and complex matter

    NASA Astrophysics Data System (ADS)

    Lehn, Jean-Marie

    2004-03-01

    Molecular chemistry has developed a wide range of very powerful procedures for constructing ever more sophisticated molecules from atoms linked by covalent bonds. Beyond molecular chemistry lies supramolecular chemistry, which aims at developing highly complex chemical systems from components interacting via non-covalent intermolecular forces. By the appropriate manipulation of these interactions, supramolecular chemistry became progressively the chemistry of molecular information, involving the storage of information at the molecular level, in the structural features, and its retrieval, transfer, and processing at the supramolecular level, through molecular recognition processes operating via specific interactional algorithms. This has paved the way towards apprehending chemistry also as an information science. Numerous receptors capable of recognizing, i.e. selectively binding, specific substrates have been developed, based on the molecular information stored in the interacting species. Suitably functionalized receptors may perform supramolecular catalysis and selective transport processes. In combination with polymolecular organization, recognition opens ways towards the design of molecular and supramolecular devices based on functional (photoactive, electroactive, ionoactive, etc) components. A step beyond preorganization consists in the design of systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined supramolecular architectures by self-assembly from their components. Self-organization processes, directed by the molecular information stored in the components and read out at the supramolecular level through specific interactions, represent the operation of programmed chemical systems. They have been implemented for the generation of a variety of discrete functional architectures of either organic or inorganic nature. Self-organization processes also give access to advanced supramolecular materials, such as supramolecular polymers and liquid crystals, and provide an original approach to nanoscience and nanotechnology. In particular, the spontaneous but controlled generation of well-defined, functional supramolecular architectures of nanometric size through self-organization represents a means of performing programmed engineering and processing of nanomaterials. Supramolecular chemistry is intrinsically a dynamic chemistry, in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when a molecular entity contains covalent bonds that may form and break reversibly, so as to make possible a continuous change in constitution and structure by reorganization and exchange of building blocks. This behaviour defines a constitutional dynamic chemistry that allows self-organization by selection as well as by design at both the molecular and supramolecular levels. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization by selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation in a Darwinistic fashion. The merging of the features, information and programmability, dynamics and reversibility, constitution and structural diversity, points towards the emergence of adaptative and evolutionary chemistry. Together with the corresponding fields of physics and biology, it constitutes a science of informed matter, of organized, adaptative complex matter. This article was originally published in 2003 by the Israel Academy of Sciences and Humanities in the framework of its Albert Einstein Memorial Lectures series. Reprinted by permission of the Israel Academy of Sciences and Humanities.

  5. Isolation and functional characterization of a cotton ubiquitination-related promoter and 5'UTR that drives high levels of expression in root and flower tissues.

    PubMed

    Viana, Antonio A B; Fragoso, Rodrigo R; Guimarães, Luciane M; Pontes, Naiara; Oliveira-Neto, Osmundo B; Artico, Sinara; Nardeli, Sarah M; Alves-Ferreira, Marcio; Batista, João A N; Silva, Maria C M; Grossi-de-Sa, Maria F

    2011-11-24

    Cotton (Gossypium spp.) is an important crop worldwide that provides raw material to 40% of the textile fiber industry. Important traits have been studied aiming the development of genetically modified crops including resistance to insect and diseases, and tolerance to drought, cold and herbicide. Therefore, the characterization of promoters and regulatory regions is also important to achieve high gene expression and/or a specific expression pattern. Commonly, genes involved in ubiquitination pathways are highly and differentially expressed. In this study, we analyzed the expression of a cotton ubiquitin-conjugating enzyme (E2) family member with no previous characterization. Nucleotide analysis revealed high identity with cotton E2 homologues. Multiple alignment showed a premature stop codon, which prevents the encoding of the conserved cysteine residue at the E2 active site, and an intron that is spliced in E2 homologues, but not in GhGDRP85. The GhGDRP85 gene is highly expressed in different organs of cotton plants, and has high transcript levels in roots. Its promoter (uceApro2) and the 5'UTR compose a regulatory region named uceA1.7, and were isolated from cotton and studied in Arabidopsis thaliana. uceA1.7 shows strong expression levels, equaling or surpassing the expression levels of CaMV35S. The uceA1.7 regulatory sequence drives GUS expression 7-fold higher in flowers, 2-fold in roots and at similar levels in leaves and stems. GUS expression levels are decreased 7- to 15-fold when its 5'UTR is absent in uceApro2. uceA1.7 is a strong constitutive regulatory sequence composed of a promoter (uceApro2) and its 5'UTR that will be useful in genetic transformation of dicots, having high potential to drive high levels of transgene expression in crops, particularly for traits desirable in flower and root tissues.

  6. Isolation and functional characterization of a cotton ubiquitination-related promoter and 5'UTR that drives high levels of expression in root and flower tissues

    PubMed Central

    2011-01-01

    Background Cotton (Gossypium spp.) is an important crop worldwide that provides raw material to 40% of the textile fiber industry. Important traits have been studied aiming the development of genetically modified crops including resistance to insect and diseases, and tolerance to drought, cold and herbicide. Therefore, the characterization of promoters and regulatory regions is also important to achieve high gene expression and/or a specific expression pattern. Commonly, genes involved in ubiquitination pathways are highly and differentially expressed. In this study, we analyzed the expression of a cotton ubiquitin-conjugating enzyme (E2) family member with no previous characterization. Results Nucleotide analysis revealed high identity with cotton E2 homologues. Multiple alignment showed a premature stop codon, which prevents the encoding of the conserved cysteine residue at the E2 active site, and an intron that is spliced in E2 homologues, but not in GhGDRP85. The GhGDRP85 gene is highly expressed in different organs of cotton plants, and has high transcript levels in roots. Its promoter (uceApro2) and the 5'UTR compose a regulatory region named uceA1.7, and were isolated from cotton and studied in Arabidopsis thaliana. uceA1.7 shows strong expression levels, equaling or surpassing the expression levels of CaMV35S. The uceA1.7 regulatory sequence drives GUS expression 7-fold higher in flowers, 2-fold in roots and at similar levels in leaves and stems. GUS expression levels are decreased 7- to 15-fold when its 5'UTR is absent in uceApro2. Conclusions uceA1.7 is a strong constitutive regulatory sequence composed of a promoter (uceApro2) and its 5'UTR that will be useful in genetic transformation of dicots, having high potential to drive high levels of transgene expression in crops, particularly for traits desirable in flower and root tissues. PMID:22115195

  7. Development of a unified constitutive model for an isotropic nickel base superalloy Rene 80

    NASA Technical Reports Server (NTRS)

    Ramaswamy, V. G.; Vanstone, R. H.; Laflen, J. H.; Stouffer, D. C.

    1988-01-01

    Accurate analysis of stress-strain behavior is of critical importance in the evaluation of life capabilities of hot section turbine engine components such as turbine blades and vanes. The constitutive equations used in the finite element analysis of such components must be capable of modeling a variety of complex behavior exhibited at high temperatures by cast superalloys. The classical separation of plasticity and creep employed in most of the finite element codes in use today is known to be deficient in modeling elevated temperature time dependent phenomena. Rate dependent, unified constitutive theories can overcome many of these difficulties. A new unified constitutive theory was developed to model the high temperature, time dependent behavior of Rene' 80 which is a cast turbine blade and vane nickel base superalloy. Considerations in model development included the cyclic softening behavior of Rene' 80, rate independence at lower temperatures and the development of a new model for static recovery.

  8. Constitutional developments in Latin American abortion law.

    PubMed

    Bergallo, Paola; Ramón Michel, Agustina

    2016-11-01

    For most of the 20th Century, restrictive abortion laws were in place in continental Latin America. In recent years, reforms have caused a liberalizing shift, supported by constitutional decisions of the countries' high courts. The present article offers an overview of the turn toward more liberal rules and the resolution of abortion disputes by reference to national constitutions. For such purpose, the main legal changes of abortion laws in the last decade are first surveyed. Landmark decisions of the high courts of Argentina, Bolivia, Colombia, and Mexico are then analyzed. It is shown that courts have accepted the need to balance interests and competing rights to ground less restrictive laws. In doing so, they have articulated limits to protection of fetal interests, and basic ideas of women's dignity, autonomy, and equality. The process of constitutionalization has only just begun. Constitutional judgments are not the last word, but they are important contributions in reinforcing the legality of abortion. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  9. From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry.

    PubMed

    Lehn, Jean-Marie

    2007-02-01

    Supramolecular chemistry has developed over the last forty years as chemistry beyond the molecule. Starting with the investigation of the basis of molecular recognition, it has explored the implementation of molecular information in the programming of chemical systems towards self-organisation processes, that may occur either on the basis of design or with selection of their components. Supramolecular entities are by nature constitutionally dynamic by virtue of the lability of non-covalent interactions. Importing such features into molecular chemistry, through the introduction of reversible bonds into molecules, leads to the emergence of a constitutional dynamic chemistry, covering both the molecular and supramolecular levels. It considers chemical objects and systems capable of responding to external solicitations by modification of their constitution through component exchange or reorganisation. It thus opens the way towards an adaptive and evolutive chemistry, a further step towards the chemistry of complex matter.

  10. Advances in the study of mechanical properties and constitutive law in the field of wood research

    NASA Astrophysics Data System (ADS)

    Zhao, S.; Zhao, J. X.; Han, G. Z.

    2016-07-01

    This paper presents an overview of mechanical properties and constitutive law for wood. Current research on the mechanical properties of wood have mostly focused on density, grain, moisture, and other natural factors. It has been established that high density, dense grain, and high moisture lead to higher strength. In most literature, wood has been regarded as an anisotropic material because of its fiber. A microscopic view is used in research of wood today, in this way, which has allowed for clear observation of anisotropy. In general, wood has higher strength under a dynamic load, and no densification. The constitutive model is the basis of numerical analysis. An anisotropic model of porous and composite materials has been used for wood, but results were poor, and new constitutions have been introduced. According to the literature, there is no single theory that is widely accepted for the dynamic load. Research has shown that grain and moisture are key factors in wood strength, but there has not been enough study on dynamic loads so far. Hill law has been the most common method of simulation. Models that consider high strain rate are attracting more and more attention.

  11. Constitutive Equation with Varying Parameters for Superplastic Flow Behavior

    NASA Astrophysics Data System (ADS)

    Guan, Zhiping; Ren, Mingwen; Jia, Hongjie; Zhao, Po; Ma, Pinkui

    2014-03-01

    In this study, constitutive equations for superplastic materials with an extra large elongation were investigated through mechanical analysis. From the view of phenomenology, firstly, some traditional empirical constitutive relations were standardized by restricting some strain paths and parameter conditions, and the coefficients in these relations were strictly given new mechanical definitions. Subsequently, a new, general constitutive equation with varying parameters was theoretically deduced based on the general mechanical equation of state. The superplastic tension test data of Zn-5%Al alloy at 340 °C under strain rates, velocities, and loads were employed for building a new constitutive equation and examining its validity. Analysis results indicated that the constitutive equation with varying parameters could characterize superplastic flow behavior in practical superplastic forming with high prediction accuracy and without any restriction of strain path or deformation condition, showing good industrial or scientific interest. On the contrary, those empirical equations have low prediction capabilities due to constant parameters and poor applicability because of the limit of special strain path or parameter conditions based on strict phenomenology.

  12. A Modified Double Multiple Nonlinear Regression Constitutive Equation for Modeling and Prediction of High Temperature Flow Behavior of BFe10-1-2 Alloy

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Wang, Kuaishe; Shi, Jiamin; Wang, Wen; Liu, Yingying

    2018-01-01

    Constitutive analysis for hot working of BFe10-1-2 alloy was carried out by using experimental stress-strain data from isothermal hot compression tests, in a wide range of temperature of 1,023 1,273 K, and strain rate range of 0.001 10 s-1. A constitutive equation based on modified double multiple nonlinear regression was proposed considering the independent effects of strain, strain rate, temperature and their interrelation. The predicted flow stress data calculated from the developed equation was compared with the experimental data. Correlation coefficient (R), average absolute relative error (AARE) and relative errors were introduced to verify the validity of the developed constitutive equation. Subsequently, a comparative study was made on the capability of strain-compensated Arrhenius-type constitutive model. The results showed that the developed constitutive equation based on modified double multiple nonlinear regression could predict flow stress of BFe10-1-2 alloy with good correlation and generalization.

  13. Constitutive Behavior Modelling of AA1100-O AT Large Strain and High Strain Rates

    NASA Astrophysics Data System (ADS)

    Testa, Gabriel; Iannitti, Gianluca; Ruggiero, Andrew; Gentile, Domenico; Bonora, Nicola

    2017-06-01

    Constitutive behavior of AA1100-O, provided as extruded bar, was investigated. Microscopic observation showed that the cross-section has a peculiar microstructure consisting in the inner core with a large grain size surrounded by an external annulus with finer grains. Low and high strain rates tensile tests were carried out at different temperature ranging from -190 ° C to 100 ° C. Constitutive behavior was modelled using a modified version of Rusinek & Klepaczko model. Parameters were calibrated on tensile test results. Tests and numerical simulations of symmetric Taylor (RoR) and dynamic tensile extrusion (DTE) tests at different impact velocities were carried out in order to validate the model under complex deformation paths.

  14. Evolutionary Importance of the Intramolecular Pathways of Hydrolysis of Phosphate Ester Mixed Anhydrides with Amino Acids and Peptides

    NASA Astrophysics Data System (ADS)

    Liu, Ziwei; Beaufils, Damien; Rossi, Jean-Christophe; Pascal, Robert

    2014-12-01

    Aminoacyl adenylates (aa-AMPs) constitute essential intermediates of protein biosynthesis. Their polymerization in aqueous solution has often been claimed as a potential route to abiotic peptides in spite of a highly efficient CO2-promoted pathway of hydrolysis. Here we investigate the efficiency and relevance of this frequently overlooked pathway from model amino acid phosphate mixed anhydrides including aa-AMPs. Its predominance was demonstrated at CO2 concentrations matching that of physiological fluids or that of the present-day ocean, making a direct polymerization pathway unlikely. By contrast, the occurrence of the CO2-promoted pathway was observed to increase the efficiency of peptide bond formation owing to the high reactivity of the N-carboxyanhydride (NCA) intermediate. Even considering CO2 concentrations in early Earth liquid environments equivalent to present levels, mixed anhydrides would have polymerized predominantly through NCAs. The issue of a potential involvement of NCAs as biochemical metabolites could even be raised. The formation of peptide-phosphate mixed anhydrides from 5(4H)-oxazolones (transiently formed through prebiotically relevant peptide activation pathways) was also observed as well as the occurrence of the reverse cyclization process in the reactions of these mixed anhydrides. These processes constitute the core of a reaction network that could potentially have evolved towards the emergence of translation.

  15. Microbial community analysis of the hypersaline water of the Dead Sea using high-throughput amplicon sequencing.

    PubMed

    Jacob, Jacob H; Hussein, Emad I; Shakhatreh, Muhamad Ali K; Cornelison, Christopher T

    2017-10-01

    Amplicon sequencing using next-generation technology (bTEFAP ® ) has been utilized in describing the diversity of Dead Sea microbiota. The investigated area is a well-known salt lake in the western part of Jordan found in the lowest geographical location in the world (more than 420 m below sea level) and characterized by extreme salinity (approximately, 34%) in addition to other extreme conditions (low pH, unique ionic composition different from sea water). DNA was extracted from Dead Sea water. A total of 314,310 small subunit RNA (SSU rRNA) sequences were parsed, and 288,452 sequences were then clustered. For alpha diversity analysis, sample was rarefied to 3,000 sequences. The Shannon-Wiener index curve plot reached a plateau at approximately 3,000 sequences indicating that sequencing depth was sufficient to capture the full scope of microbial diversity. Archaea was found to be dominating the sequences (52%), whereas Bacteria constitute 45% of the sequences. Altogether, prokaryotic sequences (which constitute 97% of all sequences) were found to predominate. The findings expand on previous studies by using high-throughput amplicon sequencing to describe the microbial community in an environment which in recent years has been shown to hide some interesting diversity. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. Genotoxicity analysis of two halonitromethanes, a novel group of disinfection by-products (DBPs), in human cells treated in vitro

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

    Liviac, Danae; Creus, Amadeu; Marcos, Ricard

    Halonitromethanes (HNMs) constitute an emerging class of disinfection by-products (DBPs) produced when chlorine and/or ozone are used for water treatment. The HNMs are structurally similar to halomethanes, but have a nitro-group in place of hydrogen bonded to the central carbon atom. Since little information exists on the genotoxic potential of HNMs, a study has been carried out with two HNM compounds, namely trichloronitromethane (TCNM) and bromonitromethane (BNM) by using human cells. Primary damage induction has been measured with the Comet assay, which is used to determine both the repair kinetics of the induced damage and the proportion of induced oxidativemore » damage. In addition, the fixed DNA damage has been evaluated by using the micronucleus (MN) assay. The results obtained indicate that both compounds are genotoxic, inducing high levels of DNA breaks in the Comet assay, and that this DNA damage repairs well over time. In addition, oxidized bases constitute a high proportion of DNA-induced damage (50-75%). Contrarily, no positive effects were observed in the frequency of micronucleus, which measures both clastogenic and aneugenic effects, neither using TK6 cells nor peripheral blood lymphocytes. This lack of fixed genetic damage would minimize the potential mutagenic risk associated with HNMs exposure.« less

  17. Parental Effect of Long Acclimatization on Thermal Tolerance of Juvenile Sea Cucumber Apostichopus japonicus

    PubMed Central

    Dong, Yun-wei

    2015-01-01

    To evaluate the thermal resistance of marine invertebrates to elevated temperatures under scenarios of future climate change, it is crucial to understand parental effect of long acclimatization on thermal tolerance of offspring. To test whether there is parental effect of long acclimatization, adult sea cucumbers (Apostichopus japonicus) from the same broodstock were transplanted southward and acclimatized at high temperature in field mesocosms. Four groups of juvenile sea cucumbers whose parents experienced different durations of high temperature acclimatization were established. Upper thermal limits, oxygen consumption and levels of heat shock protein mRNA of juveniles was determined to compare thermal tolerance of individuals from different groups. Juvenile sea cucumbers whose parents experienced high temperature could acquire high thermal resistance. With the increase of parental exposure duration to high temperature, offspring became less sensitive to high temperature, as indicated by higher upper thermal limits (LT50), less seasonal variations of oxygen consumption, and stable oxygen consumption rates between chronic and acute thermal stress. The relatively high levels of constitutive expression of heat-shock proteins should contribute to the high thermal tolerance. Together, these results indicated that the existence of a parental effect of long acclimatization would increase thermal tolerance of juveniles and change the thermal sensitivity of sea cucumber to future climate change. PMID:26580550

  18. Parental Effect of Long Acclimatization on Thermal Tolerance of Juvenile Sea Cucumber Apostichopus japonicus.

    PubMed

    Wang, Qing-Lin; Yu, Shan-Shan; Dong, Yun-Wei

    2015-01-01

    To evaluate the thermal resistance of marine invertebrates to elevated temperatures under scenarios of future climate change, it is crucial to understand parental effect of long acclimatization on thermal tolerance of offspring. To test whether there is parental effect of long acclimatization, adult sea cucumbers (Apostichopus japonicus) from the same broodstock were transplanted southward and acclimatized at high temperature in field mesocosms. Four groups of juvenile sea cucumbers whose parents experienced different durations of high temperature acclimatization were established. Upper thermal limits, oxygen consumption and levels of heat shock protein mRNA of juveniles was determined to compare thermal tolerance of individuals from different groups. Juvenile sea cucumbers whose parents experienced high temperature could acquire high thermal resistance. With the increase of parental exposure duration to high temperature, offspring became less sensitive to high temperature, as indicated by higher upper thermal limits (LT50), less seasonal variations of oxygen consumption, and stable oxygen consumption rates between chronic and acute thermal stress. The relatively high levels of constitutive expression of heat-shock proteins should contribute to the high thermal tolerance. Together, these results indicated that the existence of a parental effect of long acclimatization would increase thermal tolerance of juveniles and change the thermal sensitivity of sea cucumber to future climate change.

  19. Thermo-hydrological and chemical (THC) modeling to support Field Test Design

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

    Stauffer, Philip H.; Jordan, Amy B.; Harp, Dylan Robert

    This report summarizes ongoing efforts to simulate coupled thermal-hydrological-chemical (THC) processes occurring within a hypothetical high-level waste (HLW) repository in bedded salt. The report includes work completed since the last project deliverable, “Coupled model for heat and water transport in a high level waste repository in salt”, a Level 2 milestone submitted to DOE in September 2013 (Stauffer et al., 2013). Since the last deliverable, there have been code updates to improve the integration of the salt module with the pre-existing code and development of quality assurance (QA) tests of constitutive functions and precipitation/dissolution reactions. Simulations of bench-scale experiments, bothmore » historical and currently in the planning stages have been performed. Additional simulations have also been performed on the drift-scale model that incorporate new processes, such as an evaporation function to estimate water vapor removal from the crushed salt backfill and isotopic fractionation of water isotopes. Finally, a draft of a journal paper on the importance of clay dehydration on water availability is included as Appendix I.« less

  20. Innate immunity in renal transplantation: the role of mannose-binding lectin.

    PubMed

    Ibernon, Meritxell; Moreso, Francesc; Serón, Daniel

    2014-01-01

    Innate immune system plays an important role in the modulation of the inflammatory response during infection and tissue injury/repair. Mannose-binding lectin (MBL) is a component of the innate immune system that activates complement via the lectin pathway. Different polymorphisms of the MBL gene are associated with MBL levels and MBL function. The relationship between MBL and disease is rather complex because MBL behaves as a double-edged sword. In the general population, low serum MBL levels are associated with higher risk of infection, type 2 diabetes, autoimmune and cardiovascular disease. However, in patients with diabetes or autoimmune disease, high MBL levels are associated with more severe renal and cardiovascular comorbidities. In renal transplantation, low MBL serum levels constitute a risk factor for infection, low grade inflammation, new onset diabetes after transplantation and subclinical rejection. Despite these associations suggest that low MBL levels should be associated with poorer renal allograft outcome, epidemiological studies evaluating the predictive value of MBL levels on graft survival are controversial. Taken together, these observations suggest that low MBL serum levels modulate chronic inflammatory response that may influence transplant outcome. © 2013.

  1. Smoking prevalence and associated attitudes among high school students in Turkey.

    PubMed

    Golbasi, Zehra; Kaya, Didem; Cetindag, Arzuhan; Capik, Emine; Aydogan, Semra

    2011-01-01

    This is a descriptive study to determine the smoking prevalence and attitudes with smoking among high school students in Sivas, Turkey. This study was carried out in 6 high schools located in Sivas, Turkey. The sample was constituted by 1050 students. The data of the study was obtained by a questionnaire which is developed by researchers. The x2 test was used in the statistical analyses. In this study, the rate of students who did not smoke or stopped smoking was found to be 79.6%, while the rate of occasionaly or daily smokers was 20.4%. Students with male gender, those whose fathers and mothers had a low educational level, and a smoking mother, father or sibling, had a higher frequency of smoking (p< 0.05). Students were found to have opposite attitudes to cigarette in general and rates of agreed to some attitude expressions were found to be higher in non-smoking students. The results demonstrated that the smoking prevalence among high school students was high and students with a smoking family member in particular, those with parents having low educational levels and of male gender should be regarded as a risk group for smoking.

  2. [Mental health in primary attention: needed constitution of competences].

    PubMed

    Neves, Hilton Giovani; Lucchese, Roselma; Munari, Denize Bouttelet

    2010-01-01

    The family/people integrally attention is one of health services and professionals challenges, creating spaces for metal health in the primary level health attention. The aim of this study is to reflect about the constitution necessity of new knowledges/dones to the mental health at the primary attention, taking as perspective the competence referential. Essay developed since the historical assumptions ascertains that contextualize the Family Health Strategy and its interfaces with the psychosocial principles and some nurse background implications since the competence development theoretical intentions. We consider that reality transformation, with the health attention improvement asks for knowledges/dones constitution that attends to the psychosocial attention and the Unique Health System rules.

  3. The Sad Case of the Columbine Tiles.

    ERIC Educational Resources Information Center

    Dowling-Sendor, Benjamin

    2003-01-01

    Analyzes free-speech challenge to school district's guidelines for acceptable expressions on ceramic tiles painted by Columbine High School students to express their feelings about the massacre. Tenth Circuit found that tile painting constituted school-sponsored speech and thus district had the constitutional authority under "Hazelwood School…

  4. Nonlinear piezoelectric effects—towards physics-based computational modelling of micro-cracking, fatigue, and switching

    NASA Astrophysics Data System (ADS)

    Menzel, A.; Utzinger, J.; Arockiarajan, A.

    2008-07-01

    Piezoelectric ceramics—as one widely commercialised group of smart materials—exhibit a great potential for various engineering applications. Their high-frequency capabilities are in particular attractive for actuator and sensor devices, which nowadays are present in daily-life-technologies such as cellular phones, fuel injection systems, and so forth. At high loading levels however, severely nonlinear behaviour of these materials is observed which, from the control point of view, must be further investigated in order to be able to precisely account for such effects within the design of intelligent systems. The reasons for these nonlinearities are manifold and, even investigated within the last decades, not fully understood. Nevertheless, two important sources for these observations are so-called micro-cracking, together with fatigue phenomena, as well as switching or rather phase transformations. Accordingly, the main goal of this contribution is to study these effects by means of developing related constitutive models that can be embedded into iterative algorithmic schemes such as the finite element method. One the one hand, the grain-structure of a piezoceramic specimen will be modelled via the direct incorporation of the grain-boundaries as so-called interface elements. The underlying cohesive-like constitutive law of this layer includes both degrees of freedom of the surrounding bulk material—or rather the jumps in these fields—namely displacements and the electric potential. Based on the resulting traction-separation-type relations, micro-cracking is directly accounted for on this microlevel. Moreover, the constitutive law of the interfacial layer is supplemented by additional variables that enable the formulation of fatigue under cyclic loading conditions. On the other hand, phase transformations—modelled in terms of an energy-based switching criterion—are discussed and embedded into an iterative finite element context. Symmetry relations of the underlying unit cells are directly included so that the switching model accounts for the micro-mechanical properties of the piezoelectric materials of interest. At this stage, representative numerical simulations of polycrystalline specimens are based on straightforward averaging-techniques, while the combination of the developed micro-cracking model (grain boundaries) with the proposed switching model (bulk) constitutes future research.

  5. To be or not to be "TALL"?

    PubMed

    Laron, Zvi

    2012-08-01

    Constitutional tall stature can be anticipated from neonatal length (1) and measurement at age 4 and 8 years (2). Mainly of genetic origin (3) it has been shown that tall children and parents have high normal or higher than normal serum hGH and/or IGF-I levels. (4-6). Also in a healthy adult population a significant (p<0.005) association between height and serum IGF-I has been reported (7). These within normal variations in "healthy" individuals should be distinguished from "gigantism" due to excessive GHR-H or hGH secretion (8, 9) and other pathological conditions leading to tall stature (3).

  6. Glass-(nAg, nCu) biocide coatings on ceramic oxide substrates.

    PubMed

    Esteban-Tejeda, Leticia; Malpartida, Francisco; Díaz, Luis Antonio; Torrecillas, Ramón; Rojo, Fernando; Moya, José Serafín

    2012-01-01

    The present work was focused on obtaining biocide coatings constituted by a glassy soda-lime matrix containing silver or copper nanoparticles on ceramic (alumina and zirconia based) substrates. Both glassy coatings showed a high biocide activity against Gram-, Gram+ bacteria and yeast, reducing cell numbers more than three logarithms. Silver nanoparticles had a significantly higher biocide activity than copper nanoparticles, since the lixiviation levels required to reduce cell numbers more than 3 logarithms was of almost 1-2 µg/cm(2) in the case of silver nanoparticles, and 10-15 µg/cm(2) for the copper nanoparticles.

  7. Evidence of constitutional MLH1 epimutation associated to transgenerational inheritance of cancer susceptibility.

    PubMed

    Crépin, Michel; Dieu, Marie-Claire; Lejeune, Sophie; Escande, Fabienne; Boidin, Denis; Porchet, Nicole; Morin, Gilles; Manouvrier, Sylvie; Mathieu, Michèle; Buisine, Marie-Pierre

    2012-01-01

    Constitutional epimutations of DNA mismatch repair (MMR) genes have been recently reported as a possible cause of Lynch syndrome. However, little is known about their prevalence, the risk of transmission through the germline and the risk for carriers to develop cancers. In this study, we evaluated the contribution of constitutional epimutations of MMR genes in Lynch syndrome. A cohort of 134 unrelated Lynch syndrome-suspected patients without MMR germline mutation was screened for constitutional epimutations of MLH1 and MSH2 by quantitative bisulfite pyrosequencing. Patients were also screened for the presence of EPCAM deletions, a possible cause of MSH2 methylation. Tumors from patients with constitutional epimutations were extensively analyzed. We identified a constitutional MLH1 epimutation in two proband patients. For one of them, we report for the first time evidence of transmission to two children who also developed early colonic tumors, indicating that constitutional MLH1 epimutations are associated to a real risk of transgenerational inheritance of cancer susceptibility. Moreover, a somatic BRAF mutation was detected in one affected child, indicating that tumors from patients carrying constitutional MLH1 epimutation can mimic MSI-high sporadic tumors. These findings may have important implications for future diagnostic strategies and genetic counseling. © 2011 Wiley Periodicals, Inc.

  8. Modified nonlinear amplifying loop mirror for mode-locked fibre oscillators with record-high energy and high-average-power pulsed output

    NASA Astrophysics Data System (ADS)

    Kobtsev, Sergey; Ivanenko, Alexey; Smirnov, Sergey; Kokhanovsky, Alexey

    2018-02-01

    The present work proposes and studies approaches for development of new modified non-linear amplifying loop mirror (NALM) allowing flexible and dynamic control of their non-linear properties within a relatively broad range of radiation powers. Using two independently pumped active media in the loop reflector constitutes one of the most promising approaches to development of better NALM with nonlinear properties controllable independently of the intra-cavity radiation power. This work reports on experimental and theoretical studies of the proposed redesigned NALM allowing both a higher level of energy parameters of output generated by mode-locked fibre oscillators and new possibilities of switching among different mode-locked regimes.

  9. Modeling a High Explosive Cylinder Experiment

    NASA Astrophysics Data System (ADS)

    Zocher, Marvin A.

    2017-06-01

    Cylindrical assemblies constructed from high explosives encased in an inert confining material are often used in experiments aimed at calibrating and validating continuum level models for the so-called equation of state (constitutive model for the spherical part of the Cauchy tensor). Such is the case in the work to be discussed here. In particular, work will be described involving the modeling of a series of experiments involving PBX-9501 encased in a copper cylinder. The objective of the work is to test and perhaps refine a set of phenomenological parameters for the Wescott-Stewart-Davis reactive burn model. The focus of this talk will be on modeling the experiments, which turned out to be non-trivial. The modeling is conducted using ALE methodology.

  10. Slit2 Modulates the Inflammatory Phenotype of Orbit-Infiltrating Fibrocytes in Graves' Disease.

    PubMed

    Fernando, Roshini; Grisolia, Ana Beatriz Diniz; Lu, Yan; Atkins, Stephen; Smith, Terry J

    2018-06-15

    Human CD34 + fibrocytes, circulating monocyte lineage progenitor cells, have recently been implicated in thyroid-associated ophthalmopathy (TAO), the ocular manifestation of Graves' disease (GD). Fibrocytes express constitutive MHC class II (MHC-2) and, surprisingly, thyroglobulin (Tg) and functional thyrotropin (TSH) receptor (TSHR). Underlying expression of these thyroid proteins is the autoimmune regulator protein (AIRE). Fibrocytes respond robustly to TSH and thyroid-stimulating Igs by generating extremely high levels of inflammatory cytokines, such as IL-6. In TAO, they appear to infiltrate the orbit, where they transition to CD34 + orbital fibroblasts (OF). There, they coexist with CD34 - OF as a mixed fibroblast population (GD-OF). In contrast to fibrocytes, GD-OF express vanishingly low levels of MHC-2, Tg, TSHR, and AIRE. Further, the amplitude of IL-6 induction by TSH in GD-OF is substantially lower. The molecular basis for this divergence between fibrocytes and CD34 + OF remains uncertain. In this article, we report that Slit2, an axon guidance glycoprotein, is constitutively expressed by the CD34 - OF subset of GD-OF. Culture conditioned medium (CM) generated by incubating with GD-OF and CD34 - OF substantially reduces levels of MHC-2, Tg, TSHR, and AIRE in fibrocytes. Expression can be restored by specifically depleting CM of Slit2. The effects of CD34 - OF CM are mimicked by recombinant human Slit2. TSH induces Slit2 levels in GD-OF by enhancing both Slit2 gene transcription and mRNA stability. These findings suggest that Slit2 represents a TSH-inducible factor within the TAO orbit that can modulate the inflammatory phenotype of CD34 + OF and therefore may determine the activity and severity of the disease. Copyright © 2018 by The American Association of Immunologists, Inc.

  11. Natural variation in resistance to desiccation and heat shock protein expression in the land snail Theba pisana along a climatic gradient.

    PubMed

    Mizrahi, Tal; Goldenberg, Shoshana; Heller, Joseph; Arad, Zeev

    2015-01-01

    Land snails frequently encounter desiccating conditions, and their survival depends on a suite of morphological, physiological, and molecular adaptations to the specific microhabitat. Strategies of survival can be determined by integrating information from various levels of biological organization. In this study, we used a combination of physiological parameters related to water economy and molecular factors (stress protein expression) to investigate the strategies of survival adopted by seven populations of the Mediterranean-type land snail Theba pisana from different habitats. We analyzed water compartmentalization during aestivation and used experimental desiccation to compare desiccation resistance. We also measured the endogenous levels of heat shock proteins (HSPs) Hsp72, Hsp74, and Hsp90 under nonstress conditions and analyzed the HSP response to desiccation in two populations that differed mostly in their resistance to desiccation. We revealed significant intraspecific differences in resistance to desiccation that seem to be determined by the speed of recruitment of the water-preserving mechanisms. The ability to cope with desiccating conditions was correlated with habitat temperature but not with the rainfall gradient, implying that in the coastal region, temperature is likely to have a major impact on desiccation resistance rather than precipitation. Also, higher desiccation resistance was correlated with higher constitutive levels of Hsp74 in the foot tissue. HSPs were upregulated during desiccation, but the response was delayed and was milder in the most resistant population compared to the most susceptible one. Our study suggests that T. pisana populations from warmer habitats were more resistant to desiccation and developed distinct strategies of HSP expression for survival, namely, the maintenance of high constitutive levels of Hsp70 together with a delayed and limited response to stress.

  12. High dietary levels of biotin and zinc to improve health of foot pads in broilers exposed experimentally to litter with critical moisture content.

    PubMed

    Abd El-Wahab, A; Radko, D; Kamphues, J

    2013-07-01

    Foot pad dermatitis (FPD) is a widespread problem in poultry production and constitutes a welfare issue. The objective of this study was to test potentially prophylactic effects of higher biotin and Zn levels in the diet of broilers exposed to critical litter moisture content (35% water) on the development of FPD. Two trials were performed in each 4 groups of 1-wk-old male broilers (Ross 708) during 33 d. The pens of all groups (25 birds in each) were littered with wood shavings of critical moisture content. Two groups were fed high levels of Zn as zinc-oxide (150 mg/kg of diet), with normal levels of biotin (300 µg/kg of diet) or high biotin (2,000 µg/kg of diet). The other 2 groups were fed Zn as zinc-methionine (150 mg/kg of diet), with normal levels of biotin (300 µg/kg of diet) or high biotin (2,000 µg/kg of diet). External assessment of foot pads and measurements the moisture contents of excreta and litter were performed weekly. The signs of foot pad lesions were recorded on a 7-point scale (0 = normal skin; 7 = more than half of the foot pad is necrotic). High biotin supplementation resulted in a reduction of 30 and 18% of cases of foot pad lesions in trials 1 and 2, respectively. The combination of Zn-methionine and high biotin supplementation led to a decreased severity of FPD in a range of about 50 and 30% in trials 1 and 2, respectively. In broilers fed the diet containing zinc-oxide and normal biotin levels about 28 and 24% of the birds had the scores of 6 and 7 (= high foot pad alterations), whereas in birds fed Zn-methionine and high biotin no high alterations (score = 7) in the foot pad (0%) occurred in either trial. The presented results suggest that it is advisable to combine the maximum levels of Zn (especially of Zn-methionine) and high levels of biotin when clinically relevant alterations in the foot pad occur.

  13. Life prediction and constitutive models for engine hot section anisotropic materials

    NASA Technical Reports Server (NTRS)

    Swanson, G. A.; Linask, I.; Nissley, D. M.; Norris, P. P.; Meyer, T. G.; Walker, K. P.

    1987-01-01

    The results are presented of a program designed to develop life prediction and constitutive models for two coated single crystal alloys used in gas turbine airfoils. The two alloys are PWA 1480 and Alloy 185. The two oxidation resistant coatings are PWA 273, an aluminide coating, and PWA 286, an overlay NiCoCrAlY coating. To obtain constitutive and fatigue data, tests were conducted on uncoated and coated specimens loaded in the CH76 100 CH110 , CH76 110 CH110 , CH76 111 CH110 and CH76 123 CH110 crystallographic directions. Two constitutive models are being developed and evaluated for the single crystal materials: a micromechanic model based on crystallographic slip systems, and a macroscopic model which employs anisotropic tensors to model inelastic deformation anisotropy. Based on tests conducted on the overlay coating material, constitutive models for coatings also appear feasible and two initial models were selected. A life prediction approach was proposed for coated single crystal materials, including crack initiation either in the coating or in the substrate. The coating initiated failures dominated in the tests at load levels typical of gas turbine operation. Coating life was related to coating stress/strain history which was determined from specimen data using the constitutive models.

  14. Proposing an amendment to the Constitution of the United States regarding the right of citizens of the United States to health care of equal high quality.

    THOMAS, 111th Congress

    Rep. Jackson, Jesse L., Jr. [D-IL-2

    2009-03-03

    House - 03/16/2009 Referred to the Subcommittee on the Constitution, Civil Rights, and Civil Liberties. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  15. High Crimes and Misdemeanors. Web Lesson.

    ERIC Educational Resources Information Center

    Constitutional Rights Foundation, Los Angeles, CA.

    This lesson presents an overview of the U. S. Constitution's provision of impeachment as the method for removing the president, vice president, federal judges, and other federal officials from office. The lesson outlines and discusses the impeachment process. It also offers historical background on the framing of the Constitution and on Presidents…

  16. Non-newtonian enhancement of both stability and permeability of liquid membranes for detoxifying wastewater. Report for 1 July 1991-30 September 1993

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

    Skelland, A.H.P.

    1995-06-01

    Emulsion liquid membrane processes constitute an emerging separations technology with widespread applications, including wastewater purification. However, they currently remain excessively vulnerable to one of more of four major problems. The difficulties lie in developing liquid membranes that combine high levels of both stability and permeability with acceptably low levels of swelling and ease of subsequent demulsification for membrane and solute recovery. This work provides a new technique for simultaneously overcoming the first three problems, while identifying physical indications that the proposed solution may have little adverse effect upon the fourth problem (demulsification) and may even alleviate it. The responsiveness ofmore » both aliphatic and aromatic membranes to the new technique has been demonstrated.« less

  17. You never think about my feelings: interpersonal dominance as a predictor of emotion decoding accuracy.

    PubMed

    Moeller, Sara K; Lee, Elizabeth A Ewing; Robinson, Michael D

    2011-08-01

    Dominance and submission constitute fundamentally different social interaction strategies that may be enacted most effectively to the extent that the emotions of others are relatively ignored (dominance) versus noticed (submission). On the basis of such considerations, we hypothesized a systematic relationship between chronic tendencies toward high versus low levels of interpersonal dominance and emotion decoding accuracy in objective tasks. In two studies (total N = 232), interpersonally dominant individuals exhibited poorer levels of emotion recognition in response to audio and video clips (Study 1) and facial expressions of emotion (Study 2). The results provide a novel perspective on interpersonal dominance, suggest its strategic nature (Study 2), and are discussed in relation to Fiske's (1993) social-cognitive theory of power. 2011 APA, all rights reserved

  18. Effectual Reasoning and Innovation among Entrepreneurial Science Teacher Leaders: a Correlational Study

    NASA Astrophysics Data System (ADS)

    Martin, Anita M.; Abd-El-Khalick, Fouad; Mustari, Elisa; Price, Ray

    2017-06-01

    This is one of the first studies to examine the educational entrepreneur in K-12 public schools and the first to present an instrument designed to measure entrepreneurial thinking among teachers using a type of reasoning, effectual reasoning, which has been proposed in the business literature on entrepreneurs. This study situates entrepreneurial thinking within the K-12 education arena and examines the relationship between high school and middle school teachers' use of effectual reasoning and their corresponding implementation of high, medium, or low levels of innovation in STEM areas within their classrooms, districts, or across districts. Our findings correlated higher use of effectual reasoning, a component of entrepreneurial thinking, with higher levels of implementation of innovations among teachers within an NSF grant, Entrepreneurial Leadership in STEM Teaching and learning, which centered on deeper content, reform-oriented pedagogies, and entrepreneurial thinking. We found that high innovators viewed uncertainty' differently than low innovators by associating it with more positive cognitive structures and that innovators at different levels hold distinct notions of what constitutes high and low risk innovations. Contrary to the common notion that entrepreneurs are high-risk takers, results reveal that the types of innovations perceived by high innovators as low risk are viewed as high risk by low innovators. Furthermore, the results are consistent with the idea that entrepreneurs do certain types of things to lower/manage the risk of innovations before and, if necessary, during the implementation of an innovation. NSF: Award 0831820

  19. Medical Geology in the Middle East: Potential Health Risks from Mineralized Dust Exposure

    NASA Astrophysics Data System (ADS)

    Lyles, M. B.; Fredrickson, H. L.; Bednar, A. J.; Fannin, H. B.; Griffin, D. W.; Sobecki, T. M.

    2012-04-01

    In the Middle East, dust and sand storms are a persistent problem delivering significant amounts of mineralized particulates via inhalation into the mouth, nasal pharynx, and lungs. The health risks of this dust inhalation are presently being studied but accurate characterization as to the potential health effects is still lacking. Experiments were designed to study the chemical composition, mineral content, and microbial flora of Kuwaiti and Iraqi dust particles for the potential to cause adverse human health effects both acute and chronic. Multiple site samples were collected and chemical and physical characterization including particle size distribution and inorganic analysis was conducted, followed by analysis and identification of biologic flora to include bacteria, fungi and viruses. Additionally, PM10 exposure data was collected hourly over a 12 day period (>10,000 ug/m3). Data indicates that the mineralized dust is composed of calcium carbonate and magnesium sulfate coating over a precipitated matrix of metallic silicate nanocrystals of various forms containing a variety of trace and heavy metals constituting ~3 % of the particles by weight. This includes ~ 1% by weight bioaccessible aluminum and reactive iron with the remaining 1% a mixture of bioaccessible trace and heavy metals. Microbial analysis reveals a significant biodiversity of bacteria of which ~25 % are known pathogens. Of the microbes identified, several have hemolytic properties and most have significant antibiotic resistance. Viral analysis indicates a tremendous amount of virons with a large percent of RNA viruses. The level of total suspended particle mass at PM10 constitutes an excessive exposure micro-particulates including PM 2.5 (~1,0000 ug/m3). Reported data on cell culture and animal studies have indicated a high level of toxicity to these dust particles. Taken together, these data suggest that at the level of dust exposure commonly found in the Middle East (i.e., Iraq, Kuwait, and Afghanistan), in addition to the microbial and metal content, mineralized dust constitutes a significant health risk, both acute and chronic, to deployed troops and native inhabitants.

  20. Middle East Desert Dust Exposure: Health Risks from Metals and Microbial Pathogens

    NASA Astrophysics Data System (ADS)

    Lyles, M. B.

    2014-12-01

    In the Middle East, dust and sand storms are a persistent problem and can deliver significant amounts of micro-particulates via inhalation into the mouth, nasal pharynx, & lungs due to the fine size and abundance of these micro-particulates. The chronic and acute health risks of this dust inhalation have not been well studied nor has the dust been effectively characterized as to its chemical composition, mineral content, or microbial flora. Scientific experiments were designed to study the Kuwaiti and Iraqi dust as to its physical, chemical, and biological characteristics and for its potential to cause adverse health effects. First, dust samples from different locations were collected and processed and exposure data collected. Initial chemical and physical characterization of each sample including particle size distribution and inorganic analysis was conducted, followed by characterization of biologic flora of the dust, including bacteria, fungi and viruses. Data indicates that the mineralized dust is composed of calcium carbonate over a matrix of metallic silicate nanocrystals containing a variety of trace and heavy metals constituting ~3 % of the PM10 particles by weight, of which ~1% is bioaccessible aluminum and reactive iron, each. The particles also consist of ~1% bioavailable aluminum and reactive iron each. Microbial analysis reveals a significant biodiversity of bacterial, fungi, and viruses of which ~30% are known pathogens. Of the microbes identified, several have hemolytic properties and most have significant antibiotic resistance. Viral analysis indicates a tremendous amount of virons with a large percent of RNA viruses. The level of total suspended particle mass at PM 10 along with environmental & physiological conditions present constitute an excessive exposure to micro-particulates including PM 2.5 and the potential for adverse health effects. Reported data on cell culture and animal studies have indicated a high level of toxicity to these dust particles. Taken together, these data suggest that at the level of dust exposure commonly found in the Middle East (i.e., Iraq, Kuwait, and Afghanistan), in addition to the microbial and metal content of the mineralized dust, constitutes a significant health risk, both acute and chronic, to deployed troops and native inhabitants.

  1. Origin of High Electronic Quality in Solar Cell Absorber CH3NH3PbI3

    NASA Astrophysics Data System (ADS)

    Yin, Wanjian; Shi, Tingting; Wei, Suhua; Yan, Yanfa

    Thin-film solar cells based on CH3NH3PbI3 halide perovskites have recently shown remarkable performance. First-principle calculations and molecular dynamic simulations show that the structure of pristine CH3NH3PbI3 is much more disordered than the inorganic archetypal thin-film semiconductor CdTe. However, the structural disorders from thermal fluctuation, point defects and grain boundaries introduce rare deep defect states within the bandgaps; therefore, the material has high electronic quality. We have further shown that this unusually high electronic quality is attributed to the unique electronic structures of halide perovskite: the strong coupling between cation lone-pair Pb s orbitals and anion p orbitals and the large atomic size of constitute cation atoms. We further found that although CH3NH3PbI3 GBs do not introduce a deep gap state, the defect level close to the VBM can still act as a shallow hole trap state. Cl and O can spontaneously segregate into GBs and passivate those defect levels and deactivate the trap state.

  2. Designing Peace and Conflict Exercises: Level of Analysis, Scenario, and Role Specification

    ERIC Educational Resources Information Center

    Bartels, Elizabeth; McCown, Margaret; Wilkie, Timothy

    2013-01-01

    Attentiveness to and transparency about the methodological implications of the level of analysis selected for peace and conflict exercises constitute essential elements of good game design. The article explores the impact of level of analysis choices in the context of two key portions of exercises, scenario construction and role specification. It…

  3. New alleles of FATB-1A to reduce palmitic acid levels in soybean

    USDA-ARS?s Scientific Manuscript database

    In wild-type soybeans, palmitic acid typically constitutes 10% of the total seed oil. Palmitic acid is a saturated fat linked to increased cholesterol levels, and reducing levels of saturated fats in soybean oil has been a breeding target. To identify novel and useful variation that could help in re...

  4. An Optimizing Compiler for Petascale I/O on Leadership Class Architectures

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

    Choudhary, Alok; Kandemir, Mahmut

    In high-performance computing systems, parallel I/O architectures usually have very complex hierarchies with multiple layers that collectively constitute an I/O stack, including high-level I/O libraries such as PnetCDF and HDF5, I/O middleware such as MPI-IO, and parallel file systems such as PVFS and Lustre. Our project explored automated instrumentation and compiler support for I/O intensive applications. Our project made significant progress towards understanding the complex I/O hierarchies of high-performance storage systems (including storage caches, HDDs, and SSDs), and designing and implementing state-of-the-art compiler/runtime system technology that targets I/O intensive HPC applications that target leadership class machine. This final report summarizesmore » the major achievements of the project and also points out promising future directions.« less

  5. Animal Fascioliasis: Perspectives from high altitudinal regions.

    PubMed

    Lyngdoh, Damanbha; Sharma, Sunil; Roy, Bishnupada; Tandon, Veena

    2016-12-15

    The parasitic flukes of the genus Fasciola (Platyhelminthes: Trematoda: Digenea) cause fascioliasis or liver-rot disease in ruminant livestock in tropical and sub-tropical regions of the world. Classically, two species of Fasciola- F. hepatica and F. gigantica, are universally recognized as taxonomically valid species. Our survey studies on ovid and bovid animals including yak and mithun from high altitudinal mountainous regions in Northeast India revealed the occurrence of Fasciola gigantica and also Fasciola sp.- an intermediate form, at altitudes between 5000 and 14,085 feet above sea level (asl). Two morphotypes- F. hepatica - like and F. gigantica - like, of Fasciola species were reported from the high altitudinal areas of Northeast India; most of these locales constitute new-locality and first records for the occurrence of these liver flukes. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Differential KrasV12 protein levels control a switch regulating lung cancer cell morphology and motility

    PubMed Central

    Schäfer, C.; Mohan, A.; Burford, W.; Driscoll, M. K.; Ludlow, A. T.; Wright, W. E.; Shay, J. W.; Danuser, G.

    2016-01-01

    Introduction Oncogenic Kras mutations are important drivers of lung cancer development and metastasis. They are known to activate numerous cellular signaling pathways implicated in enhanced proliferation, survival, tumorigenicity and motility during malignant progression. Objectives Most previous studies of Kras in cancer have focused on the comparison of cell states in the absence or presence of oncogenic Kras mutations. Here we show that differential expression of the constitutively active mutation KrasV12 has profound effects on cell morphology and motility that drive metastatic processes. Methods The study relies on lung cancer cell transformation models, patient-derived lung cancer cell lines, and human lung tumor sections combined with molecular biology techniques, live-cell imaging and staining methods. Results Our analysis shows two cell functional states driven by KrasV12 protein levels: a non-motile state associated with high KrasV12 levels and tumorigenicity, and a motile state associated with low KrasV12 levels and cell dissemination. Conversion between the states is conferred by differential activation of a mechano-sensitive double-negative feedback between KrasV12/ERK/Myosin II and matrix-adhesion signaling. KrasV12 expression levels change upon cues such as hypoxia and integrin-mediated cell-matrix adhesion, rendering KrasV12 levels an integrator of micro-environmental signals that translate into cellular function. By live cell imaging of tumor models we observe shedding of mixed high and low KrasV12 expressers forming multi-functional collectives with potentially optimal metastatic properties composed of a highly mobile and a highly tumorigenic unit. Discussion Together these data highlight previously unappreciated roles for the quantitative effects of expression level variation of oncogenic signaling molecules in conferring fundamental alterations in cell function regulation required for cancer progression. PMID:29057096

  7. Development of a novel HAC-based "gain of signal" quantitative assay for measuring chromosome instability (CIN) in cancer cells.

    PubMed

    Kim, Jung-Hyun; Lee, Hee-Sheung; Lee, Nicholas C O; Goncharov, Nikolay V; Kumeiko, Vadim; Masumoto, Hiroshi; Earnshaw, William C; Kouprina, Natalay; Larionov, Vladimir

    2016-03-22

    Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene ("loss of signal" assay). Using this system, anticancer drugs can be easily ranked on by their effect on HAC loss. However, it is problematic to covert this "loss of signal" assay into a high-throughput screen to identify drugs and mutations that increase CIN levels. To address this point, we re-designed the HAC-based assay. In this new system, the HAC carries a constitutively expressed shRNA against the EGFP transgene integrated into human genome. Thus, cells that inherit the HAC display no green fluorescence, while cells lacking the HAC do. We verified the accuracy of this "gain of signal" assay by measuring the level of CIN induced by known antimitotic drugs and added to the list of previously ranked CIN inducing compounds, two newly characterized inhibitors of the centromere-associated protein CENP-E, PF-2771 and GSK923295 that exhibit the highest effect on chromosome instability measured to date. The "gain of signal" assay was also sensitive enough to detect increase of CIN after siRNA depletion of known genes controlling mitotic progression through distinct mechanisms. Hence this assay can be utilized in future experiments to uncover novel human CIN genes, which will provide novel insight into the pathogenesis of cancer. Also described is the possible conversion of this new assay into a high-throughput screen using a fluorescence microplate reader to characterize chemical libraries and identify new conditions that modulate CIN level.

  8. MYBL1 rearrangements and MYB amplification in breast adenoid cystic carcinomas lacking the MYB-NFIB fusion gene.

    PubMed

    Kim, Jisun; Geyer, Felipe C; Martelotto, Luciano G; Ng, Charlotte Ky; Lim, Raymond S; Selenica, Pier; Li, Anqi; Pareja, Fresia; Fusco, Nicola; Edelweiss, Marcia; Kumar, Rahul; Gularte-Merida, Rodrigo; Forbes, Andre N; Khurana, Ekta; Mariani, Odette; Badve, Sunil; Vincent-Salomon, Anne; Norton, Larry; Reis-Filho, Jorge S; Weigelt, Britta

    2018-02-01

    Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer, has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression. A third AdCC harboured a high-level MYB amplification, which resulted in MYB overexpression at the mRNA and protein levels. RNA-sequencing and whole-genome sequencing revealed no definite alternative driver in the fourth AdCC studied, despite high levels of MYB expression and the activation of pathways similar to those activated in MYB-NFIB-positive AdCCs. In this case, a deletion encompassing the last intron and part of exon 15 of MYB, including the binding site of ERG-1, a transcription factor that may downregulate MYB, and the exon 15 splice site, was detected. In conclusion, we demonstrate that MYBL1 rearrangements and MYB amplification probably constitute alternative genetic drivers of breast AdCCs, functioning through MYBL1 or MYB overexpression. These observations emphasize that breast AdCCs probably constitute a convergent phenotype, whereby activation of MYB and MYBL1 and their downstream targets can be driven by the MYB-NFIB fusion gene, MYBL1 rearrangements, MYB amplification, or other yet to be identified mechanisms. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Development of a novel HAC-based “gain of signal” quantitative assay for measuring chromosome instability (CIN) in cancer cells

    PubMed Central

    Kim, Jung-Hyun; Lee, Hee-Sheung; Lee, Nicholas C. O.; Goncharov, Nikolay V.; Kumeiko, Vadim; Masumoto, Hiroshi; Earnshaw, William C.; Kouprina, Natalay; Larionov, Vladimir

    2016-01-01

    Accumulating data indicates that chromosome instability (CIN) common to cancer cells can be used as a target for cancer therapy. At present the rate of chromosome mis-segregation is quantified by laborious techniques such as coupling clonal cell analysis with karyotyping or fluorescence in situ hybridization (FISH). Recently, a novel assay was developed based on the loss of a non-essential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene (“loss of signal” assay). Using this system, anticancer drugs can be easily ranked on by their effect on HAC loss. However, it is problematic to covert this “loss of signal” assay into a high-throughput screen to identify drugs and mutations that increase CIN levels. To address this point, we re-designed the HAC-based assay. In this new system, the HAC carries a constitutively expressed shRNA against the EGFP transgene integrated into human genome. Thus, cells that inherit the HAC display no green fluorescence, while cells lacking the HAC do. We verified the accuracy of this “gain of signal” assay by measuring the level of CIN induced by known antimitotic drugs and added to the list of previously ranked CIN inducing compounds, two newly characterized inhibitors of the centromere-associated protein CENP-E, PF-2771 and GSK923295 that exhibit the highest effect on chromosome instability measured to date. The “gain of signal” assay was also sensitive enough to detect increase of CIN after siRNA depletion of known genes controlling mitotic progression through distinct mechanisms. Hence this assay can be utilized in future experiments to uncover novel human CIN genes, which will provide novel insight into the pathogenesis of cancer. Also described is the possible conversion of this new assay into a high-throughput screen using a fluorescence microplate reader to characterize chemical libraries and identify new conditions that modulate CIN level. PMID:26943579

  10. Nursing leadership in a chronic pain management group approach.

    PubMed

    Dysvik, Elin; Furnes, Bodil

    2012-03-01

    To explore and debate nursing leadership and challenges on organizational and group levels when conducting rehabilitation groups for people suffering from chronic pain. Group approaches based on cognitive behavioural therapy are generally described as effective. Leadership in group approaches offered to people suffering from chronic pain is a great challenge for nurses on an organizational as well as a group level. One overall leader and nine group leaders conducting 13 groups constituted the sample. Qualitative content analysis was used by identifying categories, subthemes and themes. The results from the content analysis revealed one main theme ('Complexity in nursing leadership') and three subthemes ('Challenges in leadership on organizational level', 'Challenges in leadership on teamwork level' and 'Challenges in leadership on group level'. The results show how important it is to have firm overall leadership and trained group leaders with a common purpose, interdependent roles and complementary skills, who are thus well prepared to prevent or deal with challenging group processes. The leaders of both levels, which are highly interrelated, should have a current theoretical understanding of pain theory, group leadership skills and a cognitive behavioural approach. © 2012 Blackwell Publishing Ltd.

  11. The Arabidopsis 14-3-3 Protein RARE COLD INDUCIBLE 1A Links Low-Temperature Response and Ethylene Biosynthesis to Regulate Freezing Tolerance and Cold Acclimation[C][W

    PubMed Central

    Catalá, Rafael; López-Cobollo, Rosa; Mar Castellano, M.; Angosto, Trinidad; Alonso, José M.; Ecker, Joseph R.; Salinas, Julio

    2014-01-01

    In plants, the expression of 14-3-3 genes reacts to various adverse environmental conditions, including cold, high salt, and drought. Although these results suggest that 14-3-3 proteins have the potential to regulate plant responses to abiotic stresses, their role in such responses remains poorly understood. Previously, we showed that the RARE COLD INDUCIBLE 1A (RCI1A) gene encodes the 14-3-3 psi isoform. Here, we present genetic and molecular evidence implicating RCI1A in the response to low temperature. Our results demonstrate that RCI1A functions as a negative regulator of constitutive freezing tolerance and cold acclimation in Arabidopsis thaliana by controlling cold-induced gene expression. Interestingly, this control is partially performed through an ethylene (ET)-dependent pathway involving physical interaction with different ACC SYNTHASE (ACS) isoforms and a decreased ACS stability. We show that, consequently, RCI1A restrains ET biosynthesis, contributing to establish adequate levels of this hormone in Arabidopsis under both standard and low-temperature conditions. We further show that these levels are required to promote proper cold-induced gene expression and freezing tolerance before and after cold acclimation. All these data indicate that RCI1A connects the low-temperature response with ET biosynthesis to modulate constitutive freezing tolerance and cold acclimation in Arabidopsis. PMID:25122152

  12. Molecular characterization of a CpTRIM35-like protein and its splice variants from whitespotted bamboo shark (Chiloscyllium plagiosum)

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

    Zhang, Xinshang, E-mail: sanmaosound@163.com; Zhao, Heng, E-mail: hengzhao2000@gmail.com; Chen, Yeyu, E-mail: cyyleaf@126.com

    2014-10-24

    Highlights: • A TRIM gene and three splice variants were firstly cloned from elasmobranch fish. • The genes were constitutively expressed with high levels in spleen and kidney. • The gene products were distributed in cytoplasm alone or cytoplasm and nucleus. • As E3 ubiquitin ligases, the proteins differed in immune responses to challenges. - Abstract: The tripartite motif (TRIM) proteins play important roles in a broad range of biological processes, including apoptosis, cell proliferation and innate immunity response. In this study, a TRIM gene and its three splice variants were cloned from an elasmobranch fish—whitespotted bamboo shark (Chiloscyllium plagiosummore » Bennett). Phylogenetic analysis indicated that the gene was closely related to TRIM35 homologs, thus termed CpTRIM35-like. Deduced CpTRIM35 has a RBCC-PRY/SPRY structure typical of TRIM proteins, and its splice variants (CpTRIM35-1–3) have different truncations at the C-terminus. The gene products were constitutively expressed in adult sharks with the highest levels in spleen and kidney. The different subcellular locations, upregulation upon LPS and poly I:C stimulation, and significant E3 ubiquitin ligase activities suggested their different roles in immune responses as an E3 ubiquitin ligase. This is the first TRIM protein ever characterized in elasmobranch fish.« less

  13. Involvement of overexpressed wild-type BRAF in the growth of malignant melanoma cell lines.

    PubMed

    Tanami, Hideaki; Imoto, Issei; Hirasawa, Akira; Yuki, Yasuhiro; Sonoda, Itaru; Inoue, Jun; Yasui, Kohichiro; Misawa-Furihata, Akiko; Kawakami, Yutaka; Inazawa, Johji

    2004-11-18

    Comparative genomic hybridization (CGH) using 40 cell lines derived from malignant melanomas (MMs) revealed frequent amplification at 7q33-q34 containing BRAF gene, which often is mutated in MM. We found this gene to be amplified to a remarkable degree in the MM cell lines that exhibited high-level gains at 7q33-q34 in CGH. Among 40 cell lines, the eight lines that revealed neither BRAF nor NRAS mutations showed even higher levels of BRAF mRNA expression than the 32 mutated lines, although DNA amplification at 7q33-q34 was not detected in every lines overexpressing BRAF. MM cells that carried wild-type BRAF and NRAS showed constitutive overexpression of B-Raf protein and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), even after serum starvation. Not only downregulation of the endogenously overexpressed wild-type B-Raf by antisense oligonucleotide but also a treatment with an inhibitor of mitogen-activated protein kinase kinase (MAPKK, MEK) reduced phosphorylated ERK1/2 and cell growth, whereas the exogenously expressed wild-type B-Raf promoted cell growth in MM cells. Our results provide the evidence that overexpression of wild-type B-Raf, in part but not always as a result of gene amplification, is one of the mechanisms underlying constitutive activation of the MAPK pathway that stimulates growth of MM cells.

  14. Sequence stratigraphy of the subaqueous Changjiang (Yangtze River) delta since the Last Glacial Maximum

    NASA Astrophysics Data System (ADS)

    Xu, Taoyu; Wang, Guoqing; Shi, Xuefa; Wang, Xin; Yao, Zhengquan; Yang, Gang; Fang, Xisheng; Qiao, Shuqing; Liu, Shengfa; Wang, Xuchen; Zhao, Quanhong

    2016-01-01

    This study focuses on sedimentary research at the subaqueous Changjiang (Yangtze River) delta, based on five high-resolution seismic profiles and seven borehole cores with accurate AMS 14C datings. Three distinct seismic units were identified from the seismic profiles according to seismic reflection characteristics, and five sedimentary facies were recognized from borehole cores. These facies constituted a fining upward sedimentary sequence in relation to postglacial sea-level transgression. Three sequence surfaces (sequence boundary (SB), transgressive surface (TS), and maximum flooding surface (MFS)) demarcate the boundaries between early transgressive system tract (E-TST), late transgressive system tract (L-TST), early highstand system tract (E-HST) and late highstand system tract (L-HST), which constitute the sixth order sequence. These system tracts were developed coevally with postglacial sea-level rise. E-TST (~ 19-12 ka BP) corresponds to an incised-valley infilling in the early stages of postglacial transgression whereas L-TST (~ 12-7.5 ka BP) was formed during the last stage of postglacial transgression. The progradational structure of L-TST reflected in seismic profiles is possibly related to the intensification of the East Asian summer monsoon. E-HST (~ 7.5-2 ka BP) was deposited in response to the highstand after maximum postglacial transgression was reached, while L-HST (~ 2 ka BP-present) was initiated by accelerated progradation of the Changjiang delta.

  15. Chicken interferon-inducible transmembrane protein 3 restricts influenza viruses and lyssaviruses in vitro.

    PubMed

    Smith, S E; Gibson, M S; Wash, R S; Ferrara, F; Wright, E; Temperton, N; Kellam, P; Fife, M

    2013-12-01

    Interferon-inducible transmembrane protein 3 (IFITM3) is an effector protein of the innate immune system. It confers potent, cell-intrinsic resistance to infection by diverse enveloped viruses both in vitro and in vivo, including influenza viruses, West Nile virus, and dengue virus. IFITM3 prevents cytosolic entry of these viruses by blocking complete virus envelope fusion with cell endosome membranes. Although the IFITM locus, which includes IFITM1, -2, -3, and -5, is present in mammalian species, this locus has not been unambiguously identified or functionally characterized in avian species. Here, we show that the IFITM locus exists in chickens and is syntenic with the IFITM locus in mammals. The chicken IFITM3 protein restricts cell infection by influenza A viruses and lyssaviruses to a similar level as its human orthologue. Furthermore, we show that chicken IFITM3 is functional in chicken cells and that knockdown of constitutive expression in chicken fibroblasts results in enhanced infection by influenza A virus. Chicken IFITM2 and -3 are constitutively expressed in all tissues examined, whereas IFITM1 is only expressed in the bursa of Fabricius, gastrointestinal tract, cecal tonsil, and trachea. Despite being highly divergent at the amino acid level, IFITM3 proteins of birds and mammals can restrict replication of viruses that are able to infect different host species, suggesting IFITM proteins may provide a crucial barrier for zoonotic infections.

  16. Brominated flame retardants and seafood safety: a review.

    PubMed

    Cruz, Rebeca; Cunha, Sara C; Casal, Susana

    2015-04-01

    Brominated flame retardants (BFRs), frequently applied to industrial and household products to make them less flammable, are highly persistent in the environment and cause multi-organ toxicity in human and wildlife. Based on the review of BFRs presence in seafood published from 2004 to 2014, it is clear that such pollutants are not ideally controlled as the surveys are too restricted, legislation inexistent for some classes, the analytical methodologies diversified, and several factors as food processing and eating habits are generally overlooked. Indeed, while a seafood rich diet presents plenty of nutritional benefits, it can also represent a potential source of these environmental contaminants. Since recent studies have shown that dietary intake constitutes a main route of human exposure to BFRs, it is of major importance to review and enhance these features, since seafood constitutes a chief pathway for human exposure and biomagnification of priority environmental contaminants. In particular, more objective studies focused on the variability factors behind contamination levels, and subsequent human exposure, are necessary to support the necessity for more restricted legislation worldwide. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Transcription of tandemly repetitive DNA: functional roles.

    PubMed

    Biscotti, Maria Assunta; Canapa, Adriana; Forconi, Mariko; Olmo, Ettore; Barucca, Marco

    2015-09-01

    A considerable fraction of the eukaryotic genome is made up of satellite DNA constituted of tandemly repeated sequences. These elements are mainly located at centromeres, pericentromeres, and telomeres and are major components of constitutive heterochromatin. Although originally satellite DNA was thought silent and inert, an increasing number of studies are providing evidence on its transcriptional activity supporting, on the contrary, an unexpected dynamicity. This review summarizes the multiple structural roles of satellite noncoding RNAs at chromosome level. Indeed, satellite noncoding RNAs play a role in the establishment of a heterochromatic state at centromere and telomere. These highly condensed structures are indispensable to preserve chromosome integrity and genome stability, preventing recombination events, and ensuring the correct chromosome pairing and segregation. Moreover, these RNA molecules seem to be involved also in maintaining centromere identity and in elongation, capping, and replication of telomere. Finally, the abnormal variation of centromeric and pericentromeric DNA transcription across major eukaryotic lineages in stress condition and disease has evidenced the critical role that these transcripts may play and the potentially dire consequences for the organism.

  18. Constitutively active mutation of ACVR1 in oral epithelium causes submucous cleft palate in mice.

    PubMed

    Noda, Kazuo; Mishina, Yuji; Komatsu, Yoshihiro

    2016-07-15

    Cleft palate is among the most common human birth defects. Submucous cleft palate (SMCP) is a subgroup of cleft palate, which may be as common as overt cleft palate. Despite the high frequency of SMCP in humans, only recently have several animal models of SMCP begun to provide insight into the mechanisms by which SMCP develops. In this study, we show that enhanced BMP signaling through constitutively active ACVR1 in palatal epithelium causes submucous cleft palate in mice. In these mutant mice, the fusion of both palatal mesenchyme in hard palate, and muscles in soft palate were hampered by epithelial tissue. During palatal fusion, enhanced SMAD-dependent BMP signaling impaired cell death and altered cell proliferation rate in medial edge epithelium (MEE), and resulted in MEE persistence. At the molecular level, downregulation of ΔNp63, which is crucial for normal palatal fusion, in MEE cells was impaired, leading to a reduction in caspase-3 activation. Our study provides a new insight into the etiology of SMCP caused by augmented BMP signaling. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Antioxidant supplement inhibits skeletal muscle constitutive autophagy rather than fasting-induced autophagy in mice.

    PubMed

    Qi, Zhengtang; He, Qiang; Ji, Liu; Ding, Shuzhe

    2014-01-01

    In this study, we tested the hypothesis that NAC administration leads to reduced oxidative stress and thus to decreased expression of autophagy markers in young mice. Our results reveal that NAC administration results in reduced muscle mRNA levels of several autophagy markers, including Beclin-1, Atg7, LC3, Atg9, and LAMP2. However, NAC supplement fails to block the activation of skeletal muscle autophagy in response to fasting, because fasting significantly increases the mRNA level of several autophagy markers and LC3 lipidation. We further examined the effects of NAC administration on mitochondrial antioxidant capacity in fed and 24-hour fasted mice. Our results clearly show that NAC administration depresses the expression of manganese superoxide dismutase (MnSOD) and TP53-induced glycolysis and apoptosis regulator (TIGAR), both of which play a predominant antioxidant role in mitochondria by reducing ROS level. In addition, we found no beneficial effect of NAC supplement on muscle mass but it can protect from muscle loss in response to fasting. Collectively, our findings indicate that ROS is required for skeletal muscle constitutive autophagy, rather than starvation-induced autophagy, and that antioxidant NAC inhibits constitutive autophagy by the regulation of mitochondrial ROS production and antioxidant capacity.

  20. Antioxidant Supplement Inhibits Skeletal Muscle Constitutive Autophagy rather than Fasting-Induced Autophagy in Mice

    PubMed Central

    Qi, Zhengtang; He, Qiang; Ji, Liu; Ding, Shuzhe

    2014-01-01

    In this study, we tested the hypothesis that NAC administration leads to reduced oxidative stress and thus to decreased expression of autophagy markers in young mice. Our results reveal that NAC administration results in reduced muscle mRNA levels of several autophagy markers, including Beclin-1, Atg7, LC3, Atg9, and LAMP2. However, NAC supplement fails to block the activation of skeletal muscle autophagy in response to fasting, because fasting significantly increases the mRNA level of several autophagy markers and LC3 lipidation. We further examined the effects of NAC administration on mitochondrial antioxidant capacity in fed and 24-hour fasted mice. Our results clearly show that NAC administration depresses the expression of manganese superoxide dismutase (MnSOD) and TP53-induced glycolysis and apoptosis regulator (TIGAR), both of which play a predominant antioxidant role in mitochondria by reducing ROS level. In addition, we found no beneficial effect of NAC supplement on muscle mass but it can protect from muscle loss in response to fasting. Collectively, our findings indicate that ROS is required for skeletal muscle constitutive autophagy, rather than starvation-induced autophagy, and that antioxidant NAC inhibits constitutive autophagy by the regulation of mitochondrial ROS production and antioxidant capacity. PMID:25028602

  1. Intensive herbicide use has selected for constitutively elevated levels of stress-responsive mRNAs and proteins in multiple herbicide-resistant Avena fatua L.

    PubMed

    Keith, Barbara K; Burns, Erin E; Bothner, Brian; Carey, Charles C; Mazurie, Aurélien J; Hilmer, Jonathan K; Biyiklioglu, Sezgi; Budak, Hikmet; Dyer, William E

    2017-11-01

    Intensive use of herbicides has led to the evolution of two multiple herbicide-resistant (MHR) Avena fatua (wild oat) populations in Montana that are resistant to members of all selective herbicide families available for A. fatua control in US small grain crops. We used transcriptome and proteome surveys to compare constitutive changes in MHR and herbicide-susceptible (HS) plants associated with non-target site resistance. Compared to HS plants, MHR plants contained constitutively elevated levels of differentially expressed genes (DEGs) with functions in xenobiotic catabolism, stress response, redox maintenance and transcriptional regulation that are similar to abiotic stress-tolerant phenotypes. Proteome comparisons identified similarly elevated proteins including biosynthetic and multifunctional enzymes in MHR plants. Of 25 DEGs validated by RT-qPCR assay, differential regulation of 21 co-segregated with flucarbazone-sodium herbicide resistance in F 3 families, and a subset of 10 of these were induced or repressed in herbicide-treated HS plants. Although the individual and collective contributions of these DEGs and proteins to MHR remain to be determined, our results support the idea that intensive herbicide use has selected for MHR populations with altered, constitutively regulated patterns of gene expression that are similar to those in abiotic stress-tolerant plants. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  2. Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion.

    PubMed

    Krtková, Jana; Thomas, Elizabeth B; Alas, Germain C M; Schraner, Elisabeth M; Behjatnia, Habib R; Hehl, Adrian B; Paredez, Alexander R

    2016-08-23

    Encystation of the common intestinal parasite Giardia lamblia involves the production, trafficking, and secretion of cyst wall material (CWM). However, the molecular mechanism responsible for the regulation of these sequential processes remains elusive. Here, we examined the role of GlRac, Giardia's sole Rho family GTPase, in the regulation of endomembrane organization and cyst wall protein (CWP) trafficking. Localization studies indicated that GlRac is associated with the endoplasmic reticulum (ER) and the Golgi apparatus-like encystation-specific vesicles (ESVs). Constitutive GlRac signaling increased levels of the ER marker PDI2, induced ER swelling, reduced overall CWP1 production, and promoted the early maturation of ESVs. Quantitative analysis of cells expressing constitutively active hemagglutinin (HA)-tagged GlRac (HA-Rac(CA)) revealed fewer but larger ESVs than control cells. Consistent with the phenotype of premature maturation of ESVs in HA-Rac(CA)-expressing cells, constitutive GlRac signaling resulted in increased CWP1 secretion and, conversely, morpholino depletion of GlRac blocked CWP1 secretion. Wild-type cells unexpectedly secreted large quantities of CWP1 into the medium, and free CWP1 was used cooperatively during cyst formation. These results, in part, could account for the previously reported observation that G. lamblia encysts more efficiently at high cell densities. These studies of GlRac show that it regulates encystation at several levels, and our findings support its coordinating role as a regulator of CWP trafficking and secretion. The central role of GlRac in regulating membrane trafficking and the cytoskeleton, both of which are essential to Giardia parasitism, further suggests its potential as a novel target for drug development to treat giardiasis. The encystation process is crucial for the transmission of giardiasis and the life cycle of many protists. Encystation for Giardia lamblia involves the assembly of a protective cyst wall via sequential production, trafficking, and secretion of cyst wall material. However, the regulatory pathways that coordinate cargo maturation and secretion remain unknown. Here, we asked whether the signaling activities of G. lamblia's single Rho family GTPase, GlRac, might have a regulatory role in the encystation process. We show that GlRac localizes to endomembranes and its signaling activities regulate the production of cyst wall protein 1 (CWP1), the maturation of encystation-specific vesicles (ESVs), and secretion of CWP1. We also show that secreted CWP1 is available for the development of cysts at the population level, a finding that in part could explain why Giardia encystation proceeds more efficiently at high cell densities. Copyright © 2016 Krtková et al.

  3. The 2011 United Nations high-level meeting on non-communicable diseases: the Africa agenda calls for a 5-by-5 approach.

    PubMed

    Mensah, G A; Mayosi, B M

    2012-11-08

    The High Level Meeting of the 66th Session of the United Nations General Assembly was held in September 2011. The Political Declaration issued at the meeting focused the attention of world leaders and the global health community on the prevention and control of noncommunicable diseases (NCDs). The four major NCDs (cardiovascular diseases, cancer, diabetes and chronic respiratory diseases) and their four risk factors (tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol) constitute the target of the '4-by-4' approach, which is also supported by national and international health organisations. We argue that while preventing these eight NCDs and risk factors is also important in Africa, it will not be enough. A '5-by-5' strategy is needed, addressing neuropsychiatric disorders as the fifth NCD; and transmissible agents that underlie the neglected tropical diseases and other NCDs as the fifth risk factor. These phenomena cause substantial preventable death and disability, and must therefore be prioritised.

  4. Genome Editing-Enabled HTS Assays Expand Drug Target Pathways for Charcot–Marie–Tooth Disease

    PubMed Central

    2015-01-01

    Copy number variation resulting in excess PMP22 protein causes the peripheral neuropathy Charcot–Marie–Tooth disease, type 1A. To broadly interrogate chemically sensitive transcriptional pathways controlling PMP22 protein levels, we used the targeting precision of TALEN-mediated genome editing to embed reporters within the genetic locus harboring the Peripheral Myelin Protein 22 (Pmp22) gene. Using a Schwann cell line with constitutively high endogenous levels of Pmp22, we obtained allelic insertion of secreted bioluminescent reporters with sufficient signal to enable a 1536-well assay. Our findings from the quantitative high-throughput screening (qHTS) of several thousand drugs and clinically investigated compounds using this assay design both overlapped and expanded results from a previous assay using a randomly inserted reporter gene controlled by a single regulatory element of the Pmp22 gene. A key difference was the identification of a kinase-controlled inhibitory pathway of Pmp22 transcription revealed by the activity of the Protein kinase C (PKC)-modulator bryostatin. PMID:25188731

  5. Laron syndrome. First report from Greece.

    PubMed

    Galli-Tsinopoulou, Assimina; Nousia-Arvanitakis, Sanda; Tsinopoulos, Ioannis; Bechlivanides, Christos; Shevah, Orit; Laron, Zvi

    2003-01-01

    Laron-type dwarfism is an autosomal recessive disorder caused by deletions or mutations of the growth hormone receptor gene. It is characterized by high circulating levels of growth hormone (GH) and low levels of insulin-like growth factor I (IGF-I). Patients are refractory to both endogenous and exogenous GH, and present severe growth retardation and obesity. Therapy with recombinant human insulin-like growth factor-I (rhIGF-I) accelerates linear growth. We describe a 2-year old girl with Laron syndrome, who presented with postnatal growth failure and hypoglycaemic seizures. Her evaluation disclosed high GH values during a glucagon test (peak GH value 170 ng/ml) and very low IGF I value (0.1 ng/ml) with no rise following GH administration. The growth velocity improved considerably with the administration of IGF I. Molecular analysis showed a heterozygous mutation on exon 4 of the GH receptor gene, inherited from the mother, a rather puzzling finding considering the clinical findings in mother and infant. This case constitutes the first report of Laron syndrome from Greece.

  6. Simultaneous saccharification and fermentation of Agave tequilana fructans by Kluyveromyces marxianus yeasts for bioethanol and tequila production.

    PubMed

    Flores, Jose-Axel; Gschaedler, Anne; Amaya-Delgado, Lorena; Herrera-López, Enrique J; Arellano, Melchor; Arrizon, Javier

    2013-10-01

    Agave tequilana fructans (ATF) constitute a substrate for bioethanol and tequila industries. As Kluyveromyces marxianus produces specific fructanases for ATF hydrolysis, as well as ethanol, it can perform simultaneous saccharification and fermentation. In this work, fifteen K. marxianus yeasts were evaluated to develop inoculums with fructanase activity on ATF. These inoculums were added to an ATF medium for simultaneous saccharification and fermentation. All the yeasts, showed exo-fructanhydrolase activity with different substrate specificities. The yeast with highest fructanase activity in the inoculums showed the lowest ethanol production level (20 g/l). Five K. marxianus strains were the most suitable for the simultaneous saccharification and fermentation of ATF. The volatile compounds composition was evaluated at the end of fermentation, and a high diversity was observed between yeasts, nevertheless all of them produced high levels of isobutyl alcohol. The simultaneous saccharification and fermentation of ATF with K. marxianus strains has potential for industrial application. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Rapid, quantitative analysis of ppm/ppb nicotine using surface-enhanced Raman scattering from polymer-encapsulated Ag nanoparticles (gel-colls).

    PubMed

    Bell, Steven E J; Sirimuthu, Narayana M S

    2004-11-01

    Rapid, quantitative SERS analysis of nicotine at ppm/ppb levels has been carried out using stable and inexpensive polymer-encapsulated Ag nanoparticles (gel-colls). The strongest nicotine band (1030 cm(-1)) was measured against d(5)-pyridine internal standard (974 cm(-1)) which was introduced during preparation of the stock gel-colls. Calibration plots of I(nic)/I(pyr) against the concentration of nicotine were non-linear but plotting I(nic)/I(pyr) against [nicotine](x)(x = 0.6-0.75, depending on the exact experimental conditions) gave linear calibrations over the range (0.1-10 ppm) with R(2) typically ca. 0.998. The RMS prediction error was found to be 0.10 ppm when the gel-colls were used for quantitative determination of unknown nicotine samples in 1-5 ppm level. The main advantages of the method are that the gel-colls constitute a highly stable and reproducible SERS medium that allows high throughput (50 sample h(-1)) measurements.

  8. Constitutive RET tyrosine kinase activation in hereditary medullary thyroid cancer: clinical opportunities.

    PubMed

    Machens, A; Lorenz, K; Dralle, H

    2009-07-01

    The ground-breaking discovery of genotype-phenotype relationships in hereditary medullary thyroid cancer has greatly facilitated early prophylactic thyroidectomy. Its timing depends not solely on a positive gene test but, more importantly, on the type of the REarranged during Transfection (RET) mutation and its underlying mode of RET receptor tyrosine kinase activation. In the past decade, the therapeutic corridor opened by molecular information has been defined down to a remarkable level of detail. Based on mutational risk profiles, preemptive thyroidectomy is recommended at 6 months of age for carriers of highest-risk mutations, before the age of 5 years for carriers of high-risk mutations, and before the age of 5 or 10 years for carriers of least-high-risk mutations. Additional lymph node dissection may not be needed in the absence of increased preoperative basal calcitonin levels. Better comprehension of RET function should enable the design of targeted therapies for RET carriers beyond surgical cure in whom the DNA-based 'window of opportunity' has been missed.

  9. Positive Affectivity is Dampened in Youths with Histories of Major Depression and Their Never-Depressed Adolescent Siblings

    PubMed Central

    Kovacs, Maria; Bylsma, Lauren M.; Yaroslavsky, Ilya; Rottenberg, Jonathan; George, Charles J.; Kiss, Enikő; Halas, Kitti; Benák, István; Baji, Ildiko; Vetro, Ágnes; Kapornai, Krisztina

    2015-01-01

    While hedonic capacity is diminished during clinical depression, it is unclear whether that deficit constitutes a risk factor and/or persists after depression episodes remit. To examine these issues, adolescents with current/past major depression (probands; n=218), never depressed biological siblings of probands (n=207), and emotionally-well controls (n=183) were exposed to several positively valenced probes. Across baseline and hedonic probe conditions, controls consistently reported higher levels of positive affect than high-risk siblings, and siblings reported higher levels of positive affect than probands (remitted and depressed probands' reports were similar). Extent of positive affect across the protocol predicted adolescents' self-reports of social support network and parental reports of offspring's use of various adaptive mood repair responses in daily life. Attenuated hedonic responding among youths remitted from depression offers partial support for anhedonia as a trait, while its presence among never depressed high-risk siblings argues for anhedonia as a potential diathesis for clinical depression. PMID:27747139

  10. Text Previews and Three Level Study Guides for Content Area Critical Reading.

    ERIC Educational Resources Information Center

    Bean, Thomas W.; Ericson, Bonnie O.

    1989-01-01

    Describes the integration of text previews (teacher-developed synopses of the text) and three-level study guides (encouraging factual, inferential, and problem solving responses). Claims a combination of these constitutes a powerful strategy for content area reading. (RS)

  11. Constitutive parameter de-embedding using inhomogeneously-filled rectangular waveguides with longitudinal section modes

    NASA Technical Reports Server (NTRS)

    Park, A.; Dominek, A. K.

    1990-01-01

    Constitutive parameter extraction from S parameter data using a rectangular waveguide whose cross section is partially filled with a material sample as opposed to being completely filled was examined. One reason for studying a partially filled geometry is to analyze the effect of air gaps between the sample and fixture for the extraction of constitutive parameters. Air gaps can occur in high temperature parameter measurements when the sample was prepared at room temperature. Single port and two port measurement approaches to parameter extraction are also discussed.

  12. Validation of the harmless acute pancreatitis score in predicting nonsevere course of acute pancreatitis.

    PubMed

    Oskarsson, V; Mehrabi, M; Orsini, N; Hammarqvist, F; Segersvärd, R; Andrén-Sandberg, A; Sadr Azodi, O

    2011-01-01

    The Harmless Acute Pancreatitis Score (HAPS) is a scoring algorithm to identify patients with nonsevere acute pancreatitis. The aim of this study was to evaluate the reproducibility of HAPS outside its original study setting. Baseline information of all hospitalized patients with acute pancreatitis at Karolinska University Hospital, Stockholm, Sweden, between 2004 and 2009 was collected. The parameters constituting HAPS were signs of peritonitis, hematocrit and serum creatinine levels. Since hematocrit was not available in all patients, complete sample analysis was performed by replacing hematocrit with hemoglobin (strongly correlated with hematocrit; r = 0.86). In total, 531 patients with a first-time or a recurrent attack of acute pancreatitis were included. Among 353 patients with complete information on parameters constituting HAPS, 79 patients were predicted to have a nonsevere course, of whom 1 patient developed severe acute pancreatitis. The specificity of HAPS in predicting a nonsevere course of acute pancreatitis was 96.3% (95% CI: 81.0-99.9) with a corresponding positive predictive value of 98.7% (95% CI: 93.1-100). Complete sample analysis replacing hematocrit with hemoglobin level predicted a nonsevere course in 182 patients, of whom 2 patients had severe acute pancreatitis (94.3% specificity and 98.9% positive predictive value). HAPS is a highly specific scoring algorithm that predicts a nonsevere course of acute pancreatitis. Therefore, HAPS might be an additional tool in the clinical assessment of acute pancreatitis where early screening is important to treat the patients at an optimal level of care. Copyright © 2011 S. Karger AG, Basel.

  13. Structure and regulation of the Yersinia pestis yscBCDEF operon.

    PubMed Central

    Haddix, P L; Straley, S C

    1992-01-01

    We have investigated the physical and genetic structure and regulation of the Yersinia pestis yscBCDEF region, previously called lcrC. DNA sequence analysis showed that this region is homologous to the corresponding part of the ysc locus of Yersinia enterocolitica and suggested that the yscBCDEF cistrons belong to a single operon on the low-calcium response virulence plasmid pCD1. Promoter activity measurements of ysc subclones indicated that yscBCDEF constitutes a suboperon of the larger ysc region by revealing promoter activity in a clone containing the 3' end of yscD, intact yscE and yscF, and part of yscG. These experiments also revealed an additional weak promoter upstream of yscD. Northern (RNA) analysis with a yscD probe showed that operon transcription is thermally induced and downregulated in the presence of Ca2+. Primer extension of operon transcripts suggested that two promoters, a moderate-level constitutive one and a stronger, calcium-downregulated one, control full-length operon transcription at 37 degrees C. Primer extension provided additional support for the proposed designation of a yscBCDEF suboperon by identifying a 5' end within yscF, for which relative abundances in the presence and absence of Ca2+ revealed regulation that is distinct from that for transcripts initiating farther upstream. YscB and YscC were expressed in Escherichia coli by using a high-level transcription system. Attempts to express YscD were only partially successful, but they revealed interesting regulation at the translational level. Images PMID:1624469

  14. An update on the constitutive relation of ligament tissues with the effects of collagen types.

    PubMed

    Wan, Chao; Hao, Zhixiu; Tong, Lingying; Lin, Jianhao; Li, Zhichang; Wen, Shizhu

    2015-10-01

    The musculoskeletal ligament is a kind of multiscale composite material with collagen fibers embedded in a ground matrix. As the major constituent in ligaments to bear external loads, collagens are composed mainly of two collagen contents with different mechanical properties, i.e., types I and III collagen. The constitutive relation of ligaments plays a critical role in the stability and normal function of human joints. However, collagen types have not been distinguished in the previous constitutive relations. In this paper a constitutive relation for ligament tissues was modified based on the previous constitutive relation by considering the effects of collagen types. Both the collagen contents and the mechanical properties of sixteen ligament specimens from four cadaveric human knee joints were measured for determining their material coefficients in the constitutive relation. The mechanical behaviors of ligaments were obtained from both the uniaxial tensile and simple shear tests. A linear regression between joint kinematic results from in vitro and in silico experiments was made to validate the accuracy of this constitutive relation. The high correlation coefficient (R(2)=0.93) and significance (P<0.0001) of the regression equation revealed that this modified constitutive relation of ligaments was accurate to be used in studying joint biomechanics. Another finite element analysis with collagen contents changing demonstrated that the effect of variations in collagen ratios on both joint kinematics and ligament biomechanics could be simulated by this constitutive relation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Constitutive Modelling and Deformation Band Angle Predictions for High Porosity Sandstones

    NASA Astrophysics Data System (ADS)

    Richards, M. C.; Issen, K. A.; Ingraham, M. D.

    2017-12-01

    The development of a field-scale deformation model requires a constitutive framework that is capable of representing known material behavior and able to be calibrated using available mechanical response data. This work employs the principle of hyperplasticity (e.g., Houlsby and Puzrin, 2006) to develop such a constitutive framework for high porosity sandstone. Adapting the works of Zimmerman et al. (1986) and Collins and Houlsby (1997), the mechanical data set of Ingraham et al. (2013 a, b) was used to develop a specific constitutive framework for Castlegate sandstone, a high porosity fluvial-deposited reservoir analog rock. Using the mechanical data set of Ingraham et al. (2013 a, b), explicit expressions and material parameters of the elastic moduli and strain tensors were obtained. With these expressions, analytical and numerical techniques were then employed to partition the total mechanical strain into elastic, coupled, and plastic strain components. With the partitioned strain data, yield surfaces in true-stress space, coefficients of internal friction, dilatancy factors, along with the theorectical predictions of the deformation band angles were obtained. These results were also evaluated against band angle values obtained from a) measurements on specimen jackets (Ingraham et al., 2013a), b) plane fits through located acoustic emissions (AE) events (Ingraham et al. 2013b), and c) X-ray micro-computed tomography (micro-CT) calculations.

  16. Hyperosmolarity induced by high glucose promotes senescence in human glomerular mesangial cells.

    PubMed

    del Nogal, Maria; Troyano, Nuria; Calleros, Laura; Griera, Mercedes; Rodriguez-Puyol, Manuel; Rodriguez-Puyol, Diego; Ruiz-Torres, María P

    2014-09-01

    Hyperglycemia is involved in the diabetic complication of different organs and can elevate serum osmolarity. Here, we tested whether hyperosmolarity promoted by high glucose levels induces cellular senescence in renal cells. We treated Wistar rats with streptozotocin to induce diabetes or with consecutive daily injections of mannitol to increase serum osmolarity and analyzed p53 and p16 genes in renal cortex by immunohistochemistry. Both diabetic and mannitol treated rats showed a significant increase in serum osmolarity, without significant signs of renal dysfunction, but associated with increased staining for p53 and p16 in the renal cortex. An increase in p53 and p16 expression was also found in renal cortex slices and glomeruli isolated from healthy rats, which were later treated with 30 mM glucose or mannitol. Intracellular mechanisms involved were analyzed in cultured human glomerular mesangial cells treated with 30 mM glucose or mannitol. After treatments, cells showed increased p53, p21 and p16 expression and elevated senescence-associated β-galactosidase activity. Senescence was prevented when myo-inositol was added before treatment. High glucose or mannitol induced constitutive activation of Ras and ERK pathways which, in turn, were activated by oxidative stress. In summary, hyperosmolarity induced renal senescence, particularly in glomerular mesangial cells, increasing oxidative stress, which constitutively activated Ras-ERK 1/2 pathway. Cellular senescence could contribute to the organ dysfunction associated with diabetes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Acute and constitutive increases in central serotonin levels reduce social play behaviour in peri-adolescent rats

    PubMed Central

    Schiepers, Olga J. G.; Schoffelmeer, Anton N. M.; Cuppen, Edwin; Vanderschuren, Louk J. M. J.

    2007-01-01

    Rationale Serotonin is an important modulator of social behaviour. Individual differences in serotonergic signalling are considered to be a marker of personality that is stable throughout lifetime. While a large body of evidence indicates that central serotonin levels are inversely related to aggression and sexual behaviour in adult rats, the relationship between serotonin and social behaviour during peri-adolescence has hardly been explored. Objective To study the effect of acute and constitutive increases in serotonin neurotransmission on social behaviour in peri-adolescent rats. Materials and methods Social behaviour in peri-adolesent rats (28–35 days old) was studied after genetic ablation of the serotonin transporter, causing constitutively increased extra-neuronal serotonin levels, and after acute treatment with the serotonin reuptake inhibitor fluoxetine or the serotonin releasing agent 3,4-methylenedioxymethamphetamine (MDMA). A distinction was made between social play behaviour that mainly occurs during peri-adolescence, and non-playful social interactions that are abundant during the entire lifespan of rats. Results In serotonin transporter knockout rats, social play behaviour was markedly reduced, while non-playful aspects of social interaction were unaffected. Acute treatment with fluoxetine or MDMA dose-dependently inhibited social play behaviour. MDMA also suppressed non-playful social interaction but at higher doses than those required to reduce social play. Fluoxetine did not affect non-playful social interaction. Conclusions These data show that both acute and constitutive increases in serotonergic neurotransmission reduce social play behaviour in peri-adolescent rats. Together with our previous findings of reduced aggressive and sexual behaviour in adult serotonin transporter knockout rats, these data support the notion that serotonin modulates social behaviour in a trait-like manner. PMID:17661017

  18. The Processing and Mechanical Properties of High Temperature/High Performance Composites. Book 3. Constituent Properties and Macroscopic Performance: MMCs

    DTIC Science & Technology

    1993-04-01

    re - expressed as, v .= hCSw (C3) Combining Eqns. (C2) and C3) yields, Se = - ’. S (C4...of vi( s ) or v ’( s ). Substituting eq. (B10) into eq. (25), one finds the finite element method expression for functional Ud [ v ] which is U, d [] = v , K...Measurements 1- D 2- D S ,_DL 4 Constitutive W Constitutive Laws Laws Matrix Cracking Labor Models Models Stress Redistribution Numerical Calculations

  19. Constitutive modelling of composite biopolymer networks.

    PubMed

    Fallqvist, B; Kroon, M

    2016-04-21

    The mechanical behaviour of biopolymer networks is to a large extent determined at a microstructural level where the characteristics of individual filaments and the interactions between them determine the response at a macroscopic level. Phenomena such as viscoelasticity and strain-hardening followed by strain-softening are observed experimentally in these networks, often due to microstructural changes (such as filament sliding, rupture and cross-link debonding). Further, composite structures can also be formed with vastly different mechanical properties as compared to the individual networks. In this present paper, we present a constitutive model presented in a continuum framework aimed at capturing these effects. Special care is taken to formulate thermodynamically consistent evolution laws for dissipative effects. This model, incorporating possible anisotropic network properties, is based on a strain energy function, split into an isochoric and a volumetric part. Generalisation to three dimensions is performed by numerical integration over the unit sphere. Model predictions indicate that the constitutive model is well able to predict the elastic and viscoelastic response of biological networks, and to an extent also composite structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Signature pathway expression of xylose utilization in the genetically engineered industrial yeast Saccharomyces cerevisiae.

    PubMed

    Feng, Quanzhou; Liu, Z Lewis; Weber, Scott A; Li, Shizhong

    2018-01-01

    Haploid laboratory strains of Saccharomyces cerevisiae are commonly used for genetic engineering to enable their xylose utilization but little is known about the industrial yeast which is often recognized as diploid and as well as haploid and tetraploid. Here we report three unique signature pathway expression patterns and gene interactions in the centre metabolic pathways that signify xylose utilization of genetically engineered industrial yeast S. cerevisiae NRRL Y-50463, a diploid yeast. Quantitative expression analysis revealed outstanding high levels of constitutive expression of YXI, a synthesized yeast codon-optimized xylose isomerase gene integrated into chromosome XV of strain Y-50463. Comparative expression analysis indicated that the YXI was necessary to initiate the xylose metabolic pathway along with a set of heterologous xylose transporter and utilization facilitating genes including XUT4, XUT6, XKS1 and XYL2. The highly activated transketolase and transaldolase genes TKL1, TKL2, TAL1 and NQM1 as well as their complex interactions in the non-oxidative pentose phosphate pathway branch were critical for the serial of sugar transformation to drive the metabolic flow into glycolysis for increased ethanol production. The significantly increased expression of the entire PRS gene family facilitates functions of the life cycle and biosynthesis superpathway for the yeast. The outstanding higher levels of constitutive expression of YXI and the first insight into the signature pathway expression and the gene interactions in the closely related centre metabolic pathways from the industrial yeast aid continued efforts for development of the next-generation biocatalyst. Our results further suggest the industrial yeast is a desirable delivery vehicle for new strain development for efficient lignocellulose-to-advanced biofuels production.

  1. Signature pathway expression of xylose utilization in the genetically engineered industrial yeast Saccharomyces cerevisiae

    PubMed Central

    Feng, Quanzhou; Weber, Scott A.; Li, Shizhong

    2018-01-01

    Haploid laboratory strains of Saccharomyces cerevisiae are commonly used for genetic engineering to enable their xylose utilization but little is known about the industrial yeast which is often recognized as diploid and as well as haploid and tetraploid. Here we report three unique signature pathway expression patterns and gene interactions in the centre metabolic pathways that signify xylose utilization of genetically engineered industrial yeast S. cerevisiae NRRL Y-50463, a diploid yeast. Quantitative expression analysis revealed outstanding high levels of constitutive expression of YXI, a synthesized yeast codon-optimized xylose isomerase gene integrated into chromosome XV of strain Y-50463. Comparative expression analysis indicated that the YXI was necessary to initiate the xylose metabolic pathway along with a set of heterologous xylose transporter and utilization facilitating genes including XUT4, XUT6, XKS1 and XYL2. The highly activated transketolase and transaldolase genes TKL1, TKL2, TAL1 and NQM1 as well as their complex interactions in the non-oxidative pentose phosphate pathway branch were critical for the serial of sugar transformation to drive the metabolic flow into glycolysis for increased ethanol production. The significantly increased expression of the entire PRS gene family facilitates functions of the life cycle and biosynthesis superpathway for the yeast. The outstanding higher levels of constitutive expression of YXI and the first insight into the signature pathway expression and the gene interactions in the closely related centre metabolic pathways from the industrial yeast aid continued efforts for development of the next-generation biocatalyst. Our results further suggest the industrial yeast is a desirable delivery vehicle for new strain development for efficient lignocellulose-to-advanced biofuels production. PMID:29621349

  2. Proposing an amendment to the Constitution of the United States regarding the right of all citizens of the United States to a public education of equal high quality.

    THOMAS, 111th Congress

    Rep. Jackson, Jesse L., Jr. [D-IL-2

    2009-03-03

    House - 03/16/2009 Referred to the Subcommittee on the Constitution, Civil Rights, and Civil Liberties. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  3. High Strain Rate Deformation Modeling of a Polymer Matrix Composite. Part 1; Matrix Constitutive Equations

    NASA Technical Reports Server (NTRS)

    Goldberg, Robert K.; Stouffer, Donald C.

    1998-01-01

    Recently applications have exposed polymer matrix composite materials to very high strain rate loading conditions, requiring an ability to understand and predict the material behavior under these extreme conditions. In this first paper of a two part report, background information is presented, along with the constitutive equations which will be used to model the rate dependent nonlinear deformation response of the polymer matrix. Strain rate dependent inelastic constitutive models which were originally developed to model the viscoplastic deformation of metals have been adapted to model the nonlinear viscoelastic deformation of polymers. The modified equations were correlated by analyzing the tensile/ compressive response of both 977-2 toughened epoxy matrix and PEEK thermoplastic matrix over a variety of strain rates. For the cases examined, the modified constitutive equations appear to do an adequate job of modeling the polymer deformation response. A second follow-up paper will describe the implementation of the polymer deformation model into a composite micromechanical model, to allow for the modeling of the nonlinear, rate dependent deformation response of polymer matrix composites.

  4. Female voice communications in high levels of aircraft cockpit noises--Part I: spectra, levels, and microphones.

    PubMed

    Nixon, C W; Morris, L J; McCavitt, A R; McKinley, R L; Anderson, T R; McDaniel, M P; Yeager, D G

    1998-07-01

    Female produced speech, although more intelligible than male speech in some noise spectra, may be more vulnerable to degradation by high levels of some military aircraft cockpit noises. The acoustic features of female speech are higher in frequency, lower in power, and appear more susceptible than male speech to masking by some of these military noises. Current military aircraft voice communication systems were optimized for the male voice and may not adequately accommodate the female voice in these high level noises. This applied study investigated the intelligibility of female and male speech produced in the noise spectra of four military aircraft cockpits at levels ranging from 95 dB to 115 dB. The experimental subjects used standard flight helmets and headsets, noise-canceling microphones, and military aircraft voice communications systems during the measurements. The intelligibility of female speech was lower than that of male speech for all experimental conditions; however, differences were small and insignificant except at the highest levels of the cockpit noises. Intelligibility for both genders varied with aircraft noise spectrum and level. Speech intelligibility of both genders was acceptable during normal cruise noises of all four aircraft, but improvements are required in the higher levels of noise created during aircraft maximum operating conditions. The intelligibility of female speech was unacceptable at the highest measured noise level of 115 dB and may constitute a problem for other military aviators. The intelligibility degradation due to the noise can be neutralized by use of an available, improved noise-canceling microphone, by the application of current active noise reduction technology to the personal communication equipment, and by the development of a voice communications system to accommodate the speech produced by both female and male aviators.

  5. Bayesian Correlation Analysis for Sequence Count Data

    PubMed Central

    Lau, Nelson; Perkins, Theodore J.

    2016-01-01

    Evaluating the similarity of different measured variables is a fundamental task of statistics, and a key part of many bioinformatics algorithms. Here we propose a Bayesian scheme for estimating the correlation between different entities’ measurements based on high-throughput sequencing data. These entities could be different genes or miRNAs whose expression is measured by RNA-seq, different transcription factors or histone marks whose expression is measured by ChIP-seq, or even combinations of different types of entities. Our Bayesian formulation accounts for both measured signal levels and uncertainty in those levels, due to varying sequencing depth in different experiments and to varying absolute levels of individual entities, both of which affect the precision of the measurements. In comparison with a traditional Pearson correlation analysis, we show that our Bayesian correlation analysis retains high correlations when measurement confidence is high, but suppresses correlations when measurement confidence is low—especially for entities with low signal levels. In addition, we consider the influence of priors on the Bayesian correlation estimate. Perhaps surprisingly, we show that naive, uniform priors on entities’ signal levels can lead to highly biased correlation estimates, particularly when different experiments have widely varying sequencing depths. However, we propose two alternative priors that provably mitigate this problem. We also prove that, like traditional Pearson correlation, our Bayesian correlation calculation constitutes a kernel in the machine learning sense, and thus can be used as a similarity measure in any kernel-based machine learning algorithm. We demonstrate our approach on two RNA-seq datasets and one miRNA-seq dataset. PMID:27701449

  6. Lynch syndrome associated with two MLH1 promoter variants and allelic imbalance of MLH1 expression.

    PubMed

    Hesson, Luke B; Packham, Deborah; Kwok, Chau-To; Nunez, Andrea C; Ng, Benedict; Schmidt, Christa; Fields, Michael; Wong, Jason W H; Sloane, Mathew A; Ward, Robyn L

    2015-06-01

    Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5'untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expression and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5'UTR in the pathogenesis of Lynch syndrome. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

  7. Lynch Syndrome Associated with Two MLH1 Promoter Variants and Allelic Imbalance of MLH1 Expression

    PubMed Central

    Hesson, Luke B; Packham, Deborah; Kwok, Chau-To; Nunez, Andrea C; Ng, Benedict; Schmidt, Christa; Fields, Michael; Wong, Jason WH; Sloane, Mathew A; Ward, Robyn L

    2015-01-01

    Lynch syndrome is a hereditary cancer syndrome caused by a constitutional mutation in one of the mismatch repair genes. The implementation of predictive testing and targeted preventative surveillance is hindered by the frequent finding of sequence variants of uncertain significance in these genes. We aimed to determine the pathogenicity of previously reported variants (c.-28A>G and c.-7C>T) within the MLH1 5′untranslated region (UTR) in two individuals from unrelated suspected Lynch syndrome families. We investigated whether these variants were associated with other pathogenic alterations using targeted high-throughput sequencing of the MLH1 locus. We also determined their relationship to gene expression and epigenetic alterations at the promoter. Sequencing revealed that the c.-28A>G and c.-7C>T variants were the only potentially pathogenic alterations within the MLH1 gene. In both individuals, the levels of transcription from the variant allele were reduced to 50% compared with the wild-type allele. Partial loss of expression occurred in the absence of constitutional epigenetic alterations within the MLH1 promoter. We propose that these variants may be pathogenic due to constitutional partial loss of MLH1 expression, and that this may be associated with intermediate penetrance of a Lynch syndrome phenotype. Our findings provide further evidence of the potential importance of noncoding variants in the MLH1 5′UTR in the pathogenesis of Lynch syndrome. PMID:25762362

  8. Triaxial constitutive model for plain and reinforced concrete behavior

    NASA Astrophysics Data System (ADS)

    Kang, Hong Duk

    Inelastic failure analysis of concrete structures has been one of the central issues in concrete mechanics. Especially, the effect of confinement has been of great importance to capture the transition from brittle to ductile fracture of concrete under triaxial loading scenarios. Moreover, it has been a difficult task to implement numerically material descriptions which are susceptible to loss of stability and localization. Consequently, it has been a challenge to develop comprehensive material formulations of concrete, which consider the full spectrum of loading histories which the material in a real structure is subjected to. A new triaxial constitutive model of concrete is presented that not only describes the hardening/softening behavior of concrete in tension and low confined compression, but also captures the transition from brittle to ductile failure under high confinement. The concrete model is based on a loading surface that is Csp1-continuous, and that closes smoothly in equitriaxial compression, while the deviatoric trace expands from a triangular to a circular shape with increasing confinement. The plastic potential has a different curvature from the plastic loading function for non-associativity in order to reduce excessive inelastic dilatancy. In the thesis, the results of deformation and localization analyses for various loading histories are presented in the constitutive study. In addition, studies of associativity and non-associativity, and two-invariant versus three-invariant formulations are performed. At the structural level the triaxial concrete model is used to predict the nonlinear response behavior of a reinforced concrete column subject to axial and lateral loadings.

  9. CopM is a novel copper-binding protein involved in copper resistance in Synechocystis sp. PCC 6803.

    PubMed

    Giner-Lamia, Joaquín; López-Maury, Luis; Florencio, Francisco J

    2015-02-01

    Copper resistance system in the cyanobacterium Synechocystis sp. PCC 6803 comprises two operons, copMRS and copBAC, which are expressed in response to copper in the media. copBAC codes for a heavy-metal efflux-resistance nodulation and division (HME-RND) system, while copMRS codes for a protein of unknown function, CopM, and a two-component system CopRS, which controls the expression of these two operons. Here, we report that CopM is a periplasmic protein able to bind Cu(I) with high affinity (KD ~3 × 10(-16) ). Mutants lacking copM showed a sensitive copper phenotype similar to mutants affected in copB, but lower than mutants of the two-component system CopRS, suggesting that CopBAC and CopM constitute two independent resistance mechanisms. Moreover, constitutive expression of copM is able to partially suppress the copper sensitivity of the copR mutant strain, pointing out that CopM per se is able to confer copper resistance. Furthermore, constitutive expression of copM was able to reduce total cellular copper content of the copR mutant to the levels determined in the wild-type (WT) strain. Finally, CopM was localized not only in the periplasm but also in the extracellular space, suggesting that CopM can also prevent copper accumulation probably by direct copper binding outside the cell. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  10. Safety mechanism assisted by the repressor of tetracycline (SMART) vaccinia virus vectors for vaccines and therapeutics.

    PubMed

    Grigg, Patricia; Titong, Allison; Jones, Leslie A; Yilma, Tilahun D; Verardi, Paulo H

    2013-09-17

    Replication-competent viruses, such as Vaccinia virus (VACV), are powerful tools for the development of oncolytic viral therapies and elicit superior immune responses when used as vaccine and immunotherapeutic vectors. However, severe complications from uncontrolled viral replication can occur, particularly in immunocompromised individuals or in those with other predisposing conditions. VACVs constitutively expressing interferon-γ (IFN-γ) replicate in cell culture indistinguishably from control viruses; however, they replicate in vivo to low or undetectable levels, and are rapidly cleared even in immunodeficient animals. In an effort to develop safe and highly effective replication-competent VACV vectors, we established a system to inducibly express IFN-γ. Our SMART (safety mechanism assisted by the repressor of tetracycline) vectors are designed to express the tetracycline repressor under a constitutive VACV promoter and IFN-γ under engineered tetracycline-inducible promoters. Immunodeficient SCID mice inoculated with VACVs not expressing IFN-γ demonstrated severe weight loss, whereas those given VACVs expressing IFN-γ under constitutive VACV promoters showed no signs of infection. Most importantly, mice inoculated with a VACV expressing the IFN-γ gene under an inducible promoter remained healthy in the presence of doxycycline, but exhibited severe weight loss in the absence of doxycycline. In this study, we developed a safety mechanism for VACV based on the conditional expression of IFN-γ under a tightly controlled tetracycline-inducible VACV promoter for use in vaccines and oncolytic cancer therapies.

  11. Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC).

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

    Schultz, Peter Andrew

    The objective of the U.S. Department of Energy Office of Nuclear Energy Advanced Modeling and Simulation Waste Integrated Performance and Safety Codes (NEAMS Waste IPSC) is to provide an integrated suite of computational modeling and simulation (M&S) capabilities to quantitatively assess the long-term performance of waste forms in the engineered and geologic environments of a radioactive-waste storage facility or disposal repository. Achieving the objective of modeling the performance of a disposal scenario requires describing processes involved in waste form degradation and radionuclide release at the subcontinuum scale, beginning with mechanistic descriptions of chemical reactions and chemical kinetics at the atomicmore » scale, and upscaling into effective, validated constitutive models for input to high-fidelity continuum scale codes for coupled multiphysics simulations of release and transport. Verification and validation (V&V) is required throughout the system to establish evidence-based metrics for the level of confidence in M&S codes and capabilities, including at the subcontiunuum scale and the constitutive models they inform or generate. This Report outlines the nature of the V&V challenge at the subcontinuum scale, an approach to incorporate V&V concepts into subcontinuum scale modeling and simulation (M&S), and a plan to incrementally incorporate effective V&V into subcontinuum scale M&S destined for use in the NEAMS Waste IPSC work flow to meet requirements of quantitative confidence in the constitutive models informed by subcontinuum scale phenomena.« less

  12. CopM is a novel copper-binding protein involved in copper resistance in Synechocystis sp. PCC 6803

    PubMed Central

    Giner-Lamia, Joaquín; López-Maury, Luis; Florencio, Francisco J

    2015-01-01

    Copper resistance system in the cyanobacterium Synechocystis sp. PCC 6803 comprises two operons, copMRS and copBAC, which are expressed in response to copper in the media. copBAC codes for a heavy-metal efflux–resistance nodulation and division (HME-RND) system, while copMRS codes for a protein of unknown function, CopM, and a two-component system CopRS, which controls the expression of these two operons. Here, we report that CopM is a periplasmic protein able to bind Cu(I) with high affinity (KD ∼3 × 10−16). Mutants lacking copM showed a sensitive copper phenotype similar to mutants affected in copB, but lower than mutants of the two-component system CopRS, suggesting that CopBAC and CopM constitute two independent resistance mechanisms. Moreover, constitutive expression of copM is able to partially suppress the copper sensitivity of the copR mutant strain, pointing out that CopM per se is able to confer copper resistance. Furthermore, constitutive expression of copM was able to reduce total cellular copper content of the copR mutant to the levels determined in the wild-type (WT) strain. Finally, CopM was localized not only in the periplasm but also in the extracellular space, suggesting that CopM can also prevent copper accumulation probably by direct copper binding outside the cell. PMID:25545960

  13. Construction and properties of a cell line constitutively expressing the herpes simplex virus glycoprotein B dependent on functional alpha 4 protein synthesis.

    PubMed Central

    Arsenakis, M; Hubenthal-Voss, J; Campadelli-Fiume, G; Pereira, L; Roizman, B

    1986-01-01

    We report the construction of a cell line constitutively expressing the glycoprotein B (gB) of herpes simplex virus (HSV) 1. The cell line was constructed in two steps. In the first, a baby hamster kidney cell line was transfected with the DNA of a plasmid containing the neomycin phosphotransferase gene that confers resistance to the antibiotic G418 and the gene specifying a temperature-sensitive (ts-) alpha 4 protein of HSV-1, the major viral regulatory protein. A clonal cell line, alpha 4/c113, selected for resistance to the antibiotic G418, expressed high levels of alpha 4 protein constitutively. Superinfection of these cells with HSV-2 resulted in twofold induction of the resident HSV-1 alpha 4 gene. In the second step, alpha 4/c113 cells were transfected with the DNA of a plasmid carrying the gB gene and the mouse methotrexate resistance dihydrofolate reductase gene. A clonal cell line, alpha 4/c113/gB, selected for methotrexate resistance expressed gB constitutively. Expression of both gB and alpha 4 continued unabated for at least 32 serial passages. Cells passaged serially in medium containing both methotrexate and G418 after passage 10 contained a higher copy number of the alpha 4 gene and produced larger amounts of both gB and alpha 4 proteins than did cells maintained in medium containing methotrexate alone. Expression of gB was dependent on the presence of functional alpha 4 protein inasmuch as expression of gB ceased on shift up to nonpermissive temperatures, when shifted to permissive temperatures, the cell line reinitiated expression of gB after a delay commensurate with the length of incubation at the nonpermissive temperature, and the cell-resident HSV-1 gB gene was expressed at the nonpermissive temperature in cells infected with a recombinant expressing a ts+ alpha 4 protein and an HSV-2 gB. The properties of the alpha 4/c113 cell line suggest that it may express other viral genes induced by alpha 4 protein constitutively, provided that the product is not toxic to the cells. Images PMID:3022001

  14. 40 CFR 761.123 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... decontamination levels set forth in this policy as constituting adequate cleanup of PCBs. (2) “Standards” refers to the numerical decontamination levels set forth in this policy. Residential/commercial areas means... designated agent (e.g., a facility manager or foreman). Soil means all vegetation, soils and other ground...

  15. Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: the role of GSK-3beta in the maintenance of steady-state levels of insulin receptor signaling molecules and Na(v)1.7 sodium channel in adrenal chromaffin cells.

    PubMed

    Nemoto, Takayuki; Yanagita, Toshihiko; Kanai, Tasuku; Wada, Akihiko

    2009-02-01

    Glycogen synthase kinase-3 (GSK-3) is constitutively active in nonstimulated cells, where the majority of its substrates undergo inactivation/proteolysis by phosphorylation. Extracellular stimuli (e.g., insulin) catalyze inhibitory Ser(9)-phosphorylation of GSK-3beta, turning on signaling and causing other biological consequences otherwise constitutively suppressed by GSK-3beta. Regulated and dysregulated activities of GSK-3beta are pivotal to health, disease, and therapeutics (e.g., insulin resistance, neurodegeneration, tumorigenesis, inflammation); however, the underlying mechanisms of multifunctional GSK-3beta remain elusive. In cultured bovine adrenal chromaffin cells, 1) constitutive and negatively-regulated activities of GSK-3beta up- and down-regulated insulin receptor, insulin receptor substrate-1 (IRS-1), IRS-2, and Akt levels via controlling proteasomal degradation and protein synthesis; 2) nicotinic receptor/protein kinase C-alpha (PKC-alpha)/extracellular signal-regulated kinase (ERK) pathway up-regulated IRS-1 and IRS-2 levels, enhancing insulin-induced the phosphoinositide 3-kinase (PI3K)/Akt/GSK-3beta pathway; 3) inhibition of calcineurin by cyclosporin A or FK506 down-regulated IRS-2 level, attenuating insulin-like growth factor-I (IGF-I)-induced ERK and GSK-3beta pathways; and 4) insulin, IGF-I or therapeutics (e.g., lithium) up-regulated the voltage-dependent Na(v)1.7 sodium channel.

  16. The Extracellular Loop 2 (ECL2) of the Human Histamine H4 Receptor Substantially Contributes to Ligand Binding and Constitutive Activity

    PubMed Central

    Wifling, David; Bernhardt, Günther; Dove, Stefan; Buschauer, Armin

    2015-01-01

    In contrast to the corresponding mouse and rat orthologs, the human histamine H4 receptor (hH4R) shows extraordinarily high constitutive activity. In the extracellular loop (ECL), replacement of F169 by V as in the mouse H4R significantly reduced constitutive activity. Stabilization of the inactive state was even more pronounced for a double mutant, in which, in addition to F169V, S179 in the ligand binding site was replaced by M. To study the role of the FF motif in ECL2, we generated the hH4R-F168A mutant. The receptor was co-expressed in Sf9 insect cells with the G-protein subunits Gαi2 and Gβ1γ2, and the membranes were studied in [3H]histamine binding and functional [35S]GTPγS assays. The potency of various ligands at the hH4R-F168A mutant decreased compared to the wild-type hH4R, for example by 30- and more than 100-fold in case of the H4R agonist UR-PI376 and histamine, respectively. The high constitutive activity of the hH4R was completely lost in the hH4R-F168A mutant, as reflected by neutral antagonism of thioperamide, a full inverse agonist at the wild-type hH4R. By analogy, JNJ7777120 was a partial inverse agonist at the hH4R, but a partial agonist at the hH4R-F168A mutant, again demonstrating the decrease in constitutive activity due to F168A mutation. Thus, F168 was proven to play a key role not only in ligand binding and potency, but also in the high constitutive activity of the hH4R. PMID:25629160

  17. Heterobimetallic porphyrin complexes displaying triple dynamics: coupled metal motions controlled by constitutional evolution.

    PubMed

    Le Gac, Stéphane; Fusaro, Luca; Roisnel, Thierry; Boitrel, Bernard

    2014-05-07

    A bis-strap porphyrin ligand (1), with an overhanging carboxylic acid group on each side of the macrocycle, has been investigated toward the formation of dynamic libraries of bimetallic complexes with Hg(II), Cd(II), and Pb(II). Highly heteroselective metalation processes occurred in the presence of Pb(II), with Hg(II) or Cd(II) bound out-of-plane to the N-core and "PbOAc" bound to a carboxylate group of a strap on the opposite side. The resulting complexes, 1(Hg)·PbOAc and 1(Cd)·PbOAc, display three levels of dynamics. The first is strap-level (interactional dynamics), where the PbOAc moiety swings between the left and right side of the strap owing to a second sphere of coordination with lateral amide functions. The second is ligand-level (motional dynamics), where 1(Hg)·PbOAc and 1(Cd)·PbOAc exist as two degenerate states in equilibrium controlled by a chemical effector (AcO(-)). The process corresponds to a double translocation of the metal ions according to an intramolecular migration of Hg(II) or Cd(II) through the N-core, oscillating between the two equivalent overhanging carbonyl groups, coupled to an intermolecular pathway for PbOAc exchanging between the two equivalent overhanging carboxylate groups (N-core(up) ⇆ N-core(down) coupled to strap(down) ⇆ strap(up), i.e., coupled motion #1 in the abstract graphic). The third is library-level (constitutional dynamics), where a dynamic constitutional evolution of the system was achieved by the successive addition of two chemical effectors (DMAP and then AcO(-)). It allowed shifting equilibrium forward and backward between 1(Hg)·PbOAc and the corresponding homobimetallic complexes 1(Hg2)·DMAP and 1(Pb)·PbOAc. The latter displays a different ligand-level dynamics, in the form of an intraligand coupled migration of the Pb(II) ions (N-core(up) ⇆ strap(up) coupled to strap(down) ⇆ N-core(down), i.e., coupled motion #2 in the abstract graphic). In addition, the neutral "bridged" complexes 1HgPb and 1CdPb, with the metal ions on opposite sides both bound to the N-core and to a carboxylate of a strap, were structurally characterized. These results establish an unprecedented approach in supramolecular coordination chemistry, by considering the reversible interaction of a metal ion with the porphyrin N-core as a new source of self-organization processes. This work should provide new inspirations for the design of innovative adaptative materials and devices.

  18. Rapid degradation of dominant-negative Rab27 proteins in vivo precludes their use in transgenic mouse models

    PubMed Central

    Ramalho, José S; Anders, Ross; Jaissle, Gesine B; Seeliger, Mathias W; Huxley, Clare; Seabra, Miguel C

    2002-01-01

    Background Transgenic mice have proven to be a powerful system to study normal and pathological gene functions. Here we describe an attempt to generate a transgenic mouse model for choroideremia (CHM), a slow-onset X-linked retinal degeneration caused by mutations in the Rab Escort Protein-1 (REP1) gene. REP1 is part of the Rab geranylgeranylation machinery, a modification that is essential for Rab function in membrane traffic. The loss of REP1 in CHM patients may trigger retinal degeneration through its effects on Rab proteins. We have previously reported that Rab27a is the Rab most affected in CHM lymphoblasts and hypothesised that the selective dysfunction of Rab27a (and possibly a few other Rab GTPases) plays an essential role in the retinal degenerative process. Results To investigate this hypothesis, we generated several lines of dominant-negative, constitutively-active and wild-type Rab27a (and Rab27b) transgenic mice whose expression was driven either by the pigment cell-specific tyrosinase promoter or the ubiquitous β-actin promoter. High levels of mRNA and protein were observed in transgenic lines expressing wild-type or constitutively active Rab27a and Rab27b. However, only modest levels of transgenic protein were expressed. Pulse-chase experiments suggest that the dominant-negative proteins, but not the constitutively-active or wild type proteins, are rapidly degraded. Consistently, no significant phenotype was observed in our transgenic lines. Coat-colour was normal, indicating normal Rab27a activity. Retinal function as determined by fundoscopy, angiography, electroretinography and histology was also normal. Conclusions We suggest that the instability of the dominant-negative mutant Rab27 proteins in vivo precludes the use of this approach to generate mouse models of disease caused by Rab27 GTPases. PMID:12401133

  19. Carbon Costs of Constitutive and Expressed Resistance to a Non-Native Pathogen in Limber Pine.

    PubMed

    Vogan, Patrick J; Schoettle, Anna W

    2016-01-01

    Increasing the frequency of resistance to the non-native fungus Cronartium ribicola (causative agent of white pine blister rust, WPBR) in limber pine populations is a primary management objective to sustain high-elevation forest communities. However, it is not known to what extent genetic disease resistance is costly to plant growth or carbon economy. In this study, we measured growth and leaf-level physiology in (1) seedling families from seed trees that have previously been inferred to carry or not carry Cr4, the dominant R gene allele conferring complete, gene-for-gene resistance to WPBR in limber pine, and (2) populations that were and were not infected with C. ribicola. We found that, in the absence of C. ribicola exposure, there was no significant difference in carbon relations between families born from seed trees that harbor the resistance allele compared to those that lack it, either to plant growth and phenology or leaf-level photosynthetic traits. However, post-infection with C. ribicola, growth was significantly reduced in inoculation survivors expressing complete resistance compared to uninoculated seedlings. Furthermore, inoculation survivors exhibited significant increases in a suite of traits including photosynthetic rate, respiration rate, leaf N, and stomatal conductance and a decrease in photosynthetic water-use efficiency. The lack of constitutive carbon costs associated with Cr4 resistance in non-stressed limber pine is consistent with a previous report that the R gene allele is not under selection in the absence of C. ribicola and suggests that host resistance may not bear a constitutive cost in pathosystems that have not coevolved. However, under challenge by C. ribicola, complete resistance to WPBR in limber pine has a significant cost to plant growth, though enhanced carbon acquisition post-infection may offset this somewhat. These costs and effects on performance further complicate predictions of this species' response in warmer future climates in the presence of WPBR.

  20. Carbon Costs of Constitutive and Expressed Resistance to a Non-Native Pathogen in Limber Pine

    PubMed Central

    2016-01-01

    Increasing the frequency of resistance to the non-native fungus Cronartium ribicola (causative agent of white pine blister rust, WPBR) in limber pine populations is a primary management objective to sustain high-elevation forest communities. However, it is not known to what extent genetic disease resistance is costly to plant growth or carbon economy. In this study, we measured growth and leaf-level physiology in (1) seedling families from seed trees that have previously been inferred to carry or not carry Cr4, the dominant R gene allele conferring complete, gene-for-gene resistance to WPBR in limber pine, and (2) populations that were and were not infected with C. ribicola. We found that, in the absence of C. ribicola exposure, there was no significant difference in carbon relations between families born from seed trees that harbor the resistance allele compared to those that lack it, either to plant growth and phenology or leaf-level photosynthetic traits. However, post-infection with C. ribicola, growth was significantly reduced in inoculation survivors expressing complete resistance compared to uninoculated seedlings. Furthermore, inoculation survivors exhibited significant increases in a suite of traits including photosynthetic rate, respiration rate, leaf N, and stomatal conductance and a decrease in photosynthetic water-use efficiency. The lack of constitutive carbon costs associated with Cr4 resistance in non-stressed limber pine is consistent with a previous report that the R gene allele is not under selection in the absence of C. ribicola and suggests that host resistance may not bear a constitutive cost in pathosystems that have not coevolved. However, under challenge by C. ribicola, complete resistance to WPBR in limber pine has a significant cost to plant growth, though enhanced carbon acquisition post-infection may offset this somewhat. These costs and effects on performance further complicate predictions of this species’ response in warmer future climates in the presence of WPBR. PMID:27706249

  1. Changing Trends of Skin Cancer: A Tertiary Care Hospital Study in Malwa Region of Punjab.

    PubMed

    Lal, Sonal Tina; Banipal, Raja Paramjeet Singh; Bhatti, Deepak John; Yadav, Hanuman Prasad

    2016-06-01

    Skin cancer constitutes a small but significant proportion of patients with cancer. Although the presence of eumelanin in dark skin is protective against the development of skin cancer, it is increasingly being diagnosed in the Indian population. To study the profile of skin cancer patients presenting to a tertiary hospital in Malwa area of Punjab, India. Retrospective study was done to analyse the profile of skin cancer patients who attended the institution over one year from 1(st) December 2013 to 30(th) November 2014. A comprehensive review of aetiology and related risk factors was done to correlate the environmental factors with high skin cancer prevalence in this region. Skin cancer constituted (3.18%) 84 out of 2638 patients registered with cancer of all types. The age of the patients was 62±14.2 years and ranged from 27 to 92 yrs. Basal cell carcinoma (BCC) was the most common histological type(46/84, 54.76%) followed by squamous cell carcinoma (SCC) (31/84, 36.91%) and malignant melanoma (MM) (7/84, 8.33%). Male: female ratio was found to be 0.79:1. BCC showed higher female preponderance (p<0.05). Head and Neck was the commonest site involved (p<0.05). Majority (88%) of patients were from rural area. 92% of patients were directly into the profession of agriculture with history of prolonged exposure to sunlight. Skin cancer constitutes a small but significant proportion of patients with cancers. This study highlights a paradoxically increasing trend of BCC and female preponderance. Head and neck is the most common site involved. Exposure to Ultra Violet B (UVB) radiation and higher levels of arsenic in drinking water has been reported to be associated with skin cancers. Limited studies show that levels of arsenic and pesticides were higher in the samples of drinking water in Malwa area of Punjab. Therefore a multipronged strategy to provide safe drinking water supply and discouraging the indiscriminate use of pesticides is recommended.

  2. Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.

    PubMed

    DeSmet, Marsha L; Fleet, James C

    2017-10-01

    High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH) 2 D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH) 2 D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. Young Adult Mouse Colon (YAMC) and Rat Intestinal Epithelial (RIE) cell lines with stable expression of mutant H-RAS had suppressed 1,25(OH) 2 D-mediated induction of CYP24A1 mRNA. The RAS effects were associated with lower Vitamin D receptor (VDR) mRNA and protein levels in YAMC and RIE cells and they could be partially reversed by VDR overexpression. RAS-mediated suppression of VDR levels was not due to either reduced VDR mRNA stability or increased VDR gene methylation. However, chromatin accessibility to the VDR gene at the proximal promoter (-300bp), an enhancer region at -6kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). These data show that constitutively active RAS signaling suppresses 1,25(OH) 2 D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription but the mechanism for this suppression is not yet known. These data suggest that cancers with RAS-activating mutations may be less responsive to vitamin D mediated treatment or chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Evaluation of constitutive iron reductase (AtFRO2) expression on mineral accumulation and distribution in soybean (Glycine max. L)

    PubMed Central

    Vasconcelos, Marta W.; Clemente, Thomas E.; Grusak, Michael A.

    2014-01-01

    Iron is an important micronutrient in human and plant nutrition. Adequate iron nutrition during crop production is central for assuring appropriate iron concentrations in the harvestable organs, for human food or animal feed. The whole-plant movement of iron involves several processes, including the reduction of ferric to ferrous iron at several locations throughout the plant, prior to transmembrane trafficking of ferrous iron. In this study, soybean plants that constitutively expressed the AtFRO2 iron reductase gene were analyzed for leaf iron reductase activity, as well as the effect of this transgene’s expression on root, leaf, pod wall, and seed mineral concentrations. High Fe supply, in combination with the constitutive expression of AtFRO2, resulted in significantly higher concentrations of different minerals in roots (K, P, Zn, Ca, Ni, Mg, and Mo), pod walls (Fe, K, P, Cu, and Ni), leaves (Fe, P, Cu, Ca, Ni, and Mg) and seeds (Fe, Zn, Cu, and Ni). Leaf and pod wall iron concentrations increased as much as 500% in transgenic plants, while seed iron concentrations only increased by 10%, suggesting that factors other than leaf and pod wall reductase activity were limiting the translocation of iron to seeds. Protoplasts isolated from transgenic leaves had three-fold higher reductase activity than controls. Expression levels of the iron storage protein, ferritin, were higher in the transgenic leaves than in wild-type, suggesting that the excess iron may be stored as ferritin in the leaves and therefore unavailable for phloem loading and delivery to the seeds. Also, citrate and malate levels in the roots and leaves of transgenic plants were significantly higher than in wild-type, suggesting that organic acid production could be related to the increased accumulation of minerals in roots, leaves, and pod walls, but not in the seeds. All together, these results suggest a more ubiquitous role for the iron reductase in whole-plant mineral accumulation and distribution. PMID:24765096

  4. Epidemiology of human leukocyte antigens among omani population.

    PubMed

    Al Salmi, Issa; Metry, Abdul Massiah; Al Ismaili, Faisal; Hola, Alan; Shaheen, Faissal; Fakhoury, Hana; Hannawi, Suad

    2017-01-01

    Oman is located on the Southeastern coast of the Arabian Peninsula, and its population has high levels of consanguinity. Human leukocytic antigen (HLA) typing analysis in human population holds unexploited potential for elucidating the genetic causes of human disease and possibly leads to personalized medicine. This is a retrospective, descriptive study evaluating HLA frequencies of Omani individuals who underwent workup for kidney transplantation at the Royal Hospital (RH) from 2005 to 2016. Data on 870 subjects were collected from the Oman kidney transplant registry at RH as well from electronic medical record system. The mean age (standard deviation) years for the cohort were 33.2 (13.0). Males constituted 56.3% (490) while females constituted 43.7% (380). Seven HLA-A alleles accounted for more than 70% of the total alleles. Of which, HLA-A2 contributed the highest frequency (24%), followed by HLA A11 (9.4%), and A32 (8.1%). Ten alleles accounted for 70% of HLA-B alleles. Of which, HLA-B51 was the most common (18.9%), followed by HLA-B-35 (13.6%), and HLA-B8 (7.9%). Seven HLA-DRB1 alleles accounted for more than 70% of the total HLA DRB1 alleles, of which HLA- DRB1*16 contributed the highest frequency (29.56%). This was followed by HLA-DRB1*03 (14.57%) and HLA-DRB1*11 (9.48%). While three alleles accounted for more than 75% of the total HLA DQB1alleles. Of which, HLA-DQB1*05 contributed the highest frequency (37.56%). This was followed by allele HLA-DQB1*02 (26.48%) and HLA-DQB1*03 (17.18%). This study showed considerable heterogeneity in both HLA Class I and Class II antigens, which reflects admixture of our population with rest of old world countries. Despite the high levels of consanguinity, this population is genetically highly heterogeneous. These findings may be useful for transplantation programs, noncommunicable diseases, epidemiology of HLA linked diseases, pharmacogenomics, and anthropology.

  5. Developing Critical Thinking through Socratic Questioning: An Action Research Study

    ERIC Educational Resources Information Center

    Sahamid, Husniah

    2016-01-01

    An action research study was conducted among 24 Form 4 level Malaysian students, aged 16. The duration of the study was five months and constituted 16 one-hour literature lessons (short stories from the secondary level Malaysian English Language Upper Secondary Level school syllabus). This paper describes my experience as a teacher-as-researcher…

  6. Exploring Factors Affecting Girls' Education at Secondary Level: A Case of Karak District, Pakistan

    ERIC Educational Resources Information Center

    Suleman, Qaiser; Aslam, Hassan Danial; Habib, Muhammad Badar; Yasmeen, Kausar; Jalalian, Mehrdad; Akhtar, Zaitoon; Akhtar, Basreen

    2015-01-01

    The study examined the factors that affect girls' education at secondary school level in Karak District, Khyber Pakhtunkhwa (Pakistan). All the female heads, teachers and students serving and studying at secondary school level in Karak District constituted the population of the study. The study was delimited to only 30 girls' secondary schools in…

  7. The co-occurrence of autistic traits and borderline personality disorder traits is associated to increased suicidal ideation in nonclinical young adults.

    PubMed

    Chabrol, Henri; Raynal, Patrick

    2018-04-01

    The co-occurrence of Autism Spectrum Disorder (ASD) and Borderline Personality Disorder (BPD) is not rare and has been linked to increased suicidality. Despite this significant comorbidity between ASD and BPD, no study had examined the co-occurrence of autistic traits and borderline personality disorder traits in the general population. The aim of the present study was to examine the co-occurrence of autistic and borderline traits in a non-clinical sample of young adults and its influence on the levels of suicidal ideation and depressive symptomatology. Participants were 474 college students who completed self-report questionnaires. Data were analysed using correlation and cluster analyses. Borderline personality traits and autistic traits were weakly correlated. However, cluster analysis yielded four groups: a low traits group, a borderline traits group, an autistic traits group, and a group characterized by high levels of both traits. Cluster analysis revealed that autistic and borderline traits can co-occur in a significant proportion of young adults. The high autistic and borderline traits group constituted 17% of the total sample and had higher level of suicidal ideation than the borderline traits group, despite similar levels of depressive symptoms. This result suggests that the higher suicidality observed in patients with comorbid ASD and BPD may extent to non-clinical individuals with high levels of co-occurrent autistic and borderline traits. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. The plastidial retrograde signal methyl erythritol cyclopyrophosphate is a regulator of salicylic acid and jasmonic acid crosstalk

    PubMed Central

    Lemos, Mark; Xiao, Yanmei; Bjornson, Marta; Wang, Jin-zheng; Hicks, Derrick; de Souza, Amancio; Wang, Chang-Quan; Yang, Panyu; Ma, Shisong; Dinesh-Kumar, Savithramma; Dehesh, Katayoon

    2016-01-01

    The exquisite harmony between hormones and their corresponding signaling pathways is central to prioritizing plant responses to simultaneous and/or successive environmental trepidations. The crosstalk between jasmonic acid (JA) and salicylic acid (SA) is an established effective mechanism that optimizes and tailors plant adaptive responses. However, the underlying regulatory modules of this crosstalk are largely unknown. Global transcriptomic analyses of mutant plants (ceh1) with elevated levels of the stress-induced plastidial retrograde signaling metabolite 2-C-methyl-D-erythritol cyclopyrophosphate (MEcPP) revealed robustly induced JA marker genes, expected to be suppressed by the presence of constitutively high SA levels in the mutant background. Analyses of a range of genotypes with varying SA and MEcPP levels established the selective role of MEcPP-mediated signal(s) in induction of JA-responsive genes in the presence of elevated SA. Metabolic profiling revealed the presence of high levels of the JA precursor 12-oxo-phytodienoic acid (OPDA), but near wild type levels of JA in the ceh1 mutant plants. Analyses of coronatine-insensitive 1 (coi1)/ceh1 double mutant plants confirmed that the MEcPP-mediated induction is JA receptor COI1 dependent, potentially through elevated OPDA. These findings identify MEcPP as a previously unrecognized central regulatory module that induces JA-responsive genes in the presence of high SA, thereby staging a multifaceted plant response within the environmental context. PMID:26733689

  9. [Determine and parallel analysis of three kinds of PAEs in serum for obese children].

    PubMed

    Li, Ping; Dai, Xingbi; Dan, Hong; Huang, Xiaohong

    2008-09-01

    To study the serum contents of the PAEs of obese children at the ages of 10 to 12 years, in order to estimate the harm of PAEs on obese children. The contents of three kinds PAEs(DEP, DBP and DEHP) in the serum for two groups of children, including 36 obese children and 36 normal weight children, were determined by the reversed phase high performance liquid chromatography (RP-HPLC) method And the average measure value of three kind PAEs between two groups of children were analysed. The median serum levels of PAEs were 0.0032 (DEP), 0.1649 (DBP) and 0.1680 (DEHP) in obese children. And the serum levels of PAEs were 0.0026 (DEP), 0.0359 (DBP) and 0.1063 (DEHP) in normal weight children. The differences of average measure value of DBP and DEHP in three kind PAEs between two groups of children were significant (P < 0.01). The amounts of obese children in high level were more than those of normal weight children, and the constitution ratios in three kinds of PAEs of obese children were higher than those of normal weight children. The differences between two groups of children were significant (P < 0.01). The average levels of DBP and DEHP in serum of obese children were more than those of serum of normal weight children. The amounts of obese children were higher than those of normal weight children in high level content of three kinds of PAEs.

  10. Constitutive expression of a putative high-affinity nitrate transporter in Nicotiana plumbaginifolia: evidence for post-transcriptional regulation by a reduced nitrogen source.

    PubMed

    Fraisier, V; Gojon, A; Tillard, P; Daniel-Vedele, F

    2000-08-01

    The NpNRT2.1 gene encodes a putative inducible component of the high-affinity nitrate (NO3-) uptake system in Nicotiana plumbaginifolia. Here we report functional and physiological analyses of transgenic plants expressing the NpNRT2.1 coding sequence fused to the CaMV 35S or rolD promoters. Irrespective of the level of NO3- supplied, NO3- contents were found to be remarkably similar in wild-type and transgenic plants. Under specific conditions (growth on 10 mM NO3-), the steady-state NpNRT2. 1 mRNA level resulting from the deregulated transgene expression was accompanied by an increase in 15NO3- influx measured in the low concentration range. This demonstrates for the first time that the NRT2.1 sequence codes a limiting element of the inducible high-affinity transport system. Both 15NO3- influx and mRNA levels decreased in the wild type after exposure to ammonium, in agreement with previous results from many species. Surprisingly, however, influx was also markedly decreased in transgenic plants, despite stable levels of transgene expression in independent transformants after ammonium addition. We conclude that the conditions associated with the supply of a reduced nitrogen source such as ammonium, or with the generation of a further downstream metabolite, probably exert a repressive effect on NO3- influx at both transcriptional and post-transcriptional levels.

  11. Construal-Level Theory of Psychological Distance

    PubMed Central

    Trope, Yaacov; Liberman, Nira

    2011-01-01

    People are capable of thinking about the future, the past, remote locations, another person’s perspective, and counterfactual alternatives. Without denying the uniqueness of each process, it is proposed that they constitute different forms of traversing psychological distance. Psychological distance is egocentric: Its reference point is the self in the here and now, and the different ways in which an object might be removed from that point—in time, in space, in social distance, and in hypotheticality—constitute different distance dimensions. Transcending the self in the here and now entails mental construal, and the farther removed an object is from direct experience, the higher (more abstract) the level of construal of that object. Supporting this analysis, research shows (a) that the various distances are cognitively related to each other, (b) that they similarly influence and are influenced by level of mental construal, and (c) that they similarly affect prediction, preference, and action. PMID:20438233

  12. Constitutive Law and Flow Mechanism in Diamond Deformation

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

    Yu, Xiaohui; Raterron, Paul; Zhang, Jianzhong

    2012-11-19

    Constitutive laws and crystal plasticity in diamond deformation have been the subjects of substantial interest since synthetic diamond was made in 1950's. To date, however, little is known quantitatively regarding its brittle-ductile properties and yield strength at high temperatures. In this paper, we report, for the first time, the strain-stress constitutive relations and experimental demonstration of deformation mechanisms under confined high pressure. The deformation at room temperature is essentially brittle, cataclastic, and mostly accommodated by fracturing on {111} plane with no plastic yielding at uniaxial strains up to 15%. At elevated temperatures of 1000°C and 1200°C diamond crystals exhibit significantmore » ductile flow with corresponding yield strength of 7.9 and 6.3 GPa, indicating that diamond starts to weaken when temperature is over 1000°C. Finally, at high temperature the plastic deformation and ductile flow is meditated by the <110>{111} dislocation glide and a very active {111} micro-twinning.« less

  13. Using constitutive activity to define appropriate high-throughput screening assays for orphan g protein-coupled receptors.

    PubMed

    Ngo, Tony; Coleman, James L J; Smith, Nicola J

    2015-01-01

    Orphan G protein-coupled receptors represent an underexploited resource for drug discovery but pose a considerable challenge for assay development because their cognate G protein signaling pathways are often unknown. In this methodological chapter, we describe the use of constitutive activity, that is, the inherent ability of receptors to couple to their cognate G proteins in the absence of ligand, to inform the development of high-throughput screening assays for a particular orphan receptor. We specifically focus on a two-step process, whereby constitutive G protein coupling is first determined using yeast Gpa1/human G protein chimeras linked to growth and β-galactosidase generation. Coupling selectivity is then confirmed in mammalian cells expressing endogenous G proteins and driving accumulation of transcription factor-fused luciferase reporters specific to each of the classes of G protein. Based on these findings, high-throughput screening campaigns can be performed on the already miniaturized mammalian reporter system.

  14. Multiscale Modeling of Dewetting Damage in Highly Filled Particulate Composites

    NASA Astrophysics Data System (ADS)

    Geubelle, P. H.; Inglis, H. M.; Kramer, J. D.; Patel, J. J.; Kumar, N. C.; Tan, H.

    2008-02-01

    Particle debonding or dewetting constitutes one of the key damage processes in highly filled particulate composites such as solid propellant and other energetic materials. To analyze this failure process, we have developed a multiscale finite element framework that combines, at the microscale, a nonlinear description of the binder response with a cohesive model of the damage process taking place in a representative periodic unit cell (PUC). To relate micro-scale damage to the macroscopic constitutive response of the material, we employ the mathematical theory of homogenization (MTH). After a description of the numerical scheme, we present the results of the damage response of a highly filled particulate composite subjected to a uniaxial macroscopic strain, and show the direct correlation between the complex damage processes taking place in the PUC and the nonlinear macroscopic constitutive response. We also present a detailed study of the PUC size and a comparison between the finite element MTH-based study and a micromechanics model of the dewetting process.

  15. [Consequences of the judgment of the Federal Constitutional Court on the fighting dog problem].

    PubMed

    Hülsenbusch, M

    2005-03-01

    The Federal Constitutional Court decided with its "Dangerous dog-judgment" about the constitutional complaint of 53 dog breeders on the federal act combating dangerous dogs. This judgment was a so-called Pyrrhic Victory for the appellants. The Court declared the legislative competence of the federal level in this issue for null and void. But the statutory prohibition for breeding Pitbull-Terrier-, American Staffordshire-Terrier-, Staffordshire-Bullterrier-, Bullterrier-races and cross breeding out of this dogs will be governed in police laws by the Laender finally. The Standing Conference of the Ministers for Internal Affairs declared an appropriate recommendation. The use of the category "race" was refused by experts in discussions as completely wrong and not acceptable. But the Federal Constitutional Court reasons that the legislator can use the category "race" within his scope of evaluation and prognostication in accordance with the Constitution for the ban of import of dangerous dogs. The Court demands--because of the weak data background - that the legislator monitors the legislation, to adjust it according to current developments. The Constitutional Court creates with the judgment "dangerous dogs" legal certainty. The jurisprudence of the administrative courts of the Laender and of the Federal Administrative Court based on the category "race" was approved as well as the police laws of the Laender dealing with dangerous dogs.

  16. Fear of negative evaluation modulates electrocortical and behavioral responses when anticipating social evaluative feedback.

    PubMed

    Van der Molen, Melle J W; Poppelaars, Eefje S; Van Hartingsveldt, Caroline T A; Harrewijn, Anita; Gunther Moor, Bregtje; Westenberg, P Michiel

    2013-01-01

    Cognitive models posit that the fear of negative evaluation (FNE) is a hallmark feature of social anxiety. As such, individuals with high FNE may show biased information processing when faced with social evaluation. The aim of the current study was to examine the neural underpinnings of anticipating and processing social-evaluative feedback, and its correlates with FNE. We used a social judgment paradigm in which female participants (N = 31) were asked to indicate whether they believed to be socially accepted or rejected by their peers. Anticipatory attention was indexed by the stimulus preceding negativity (SPN), while the feedback-related negativity and P3 were used to index the processing of social-evaluative feedback. Results provided evidence of an optimism bias in social peer evaluation, as participants more often predicted to be socially accepted than rejected. Participants with high levels of FNE needed more time to provide their judgments about the social-evaluative outcome. While anticipating social-evaluative feedback, SPN amplitudes were larger for anticipated social acceptance than for social rejection feedback. Interestingly, the SPN during anticipated social acceptance was larger in participants with high levels of FNE. None of the feedback-related brain potentials correlated with the FNE. Together, the results provided evidence of biased information processing in individuals with high levels of FNE when anticipating (rather than processing) social-evaluative feedback. The delayed response times in high FNE individuals were interpreted to reflect augmented vigilance imposed by the upcoming social-evaluative threat. Possibly, the SPN constitutes a neural marker of this vigilance in females with higher FNE levels, particularly when anticipating social acceptance feedback.

  17. High genetic diversity with moderate differentiation in Juniperus excelsa from Lebanon and the eastern Mediterranean region

    PubMed Central

    Douaihy, Bouchra; Vendramin, Giovanni G.; Boratyński, Adam; Machon, Nathalie; Bou Dagher-Kharrat, Magda

    2011-01-01

    Background and aims Juniperus excelsa is an important woody species in the high mountain ecosystems of the eastern Mediterranean Basin where it constitutes the only coniferous species found at the tree line. The genetic diversity within and among J. excelsa populations of the eastern Mediterranean Basin is studied in the light of their historical fragmentation. Methodology Nuclear microsatellites originally developed for Juniperus communis and J. przewalskii were tested on 320 individuals from 12 different populations originating from Lebanon, Turkey, Cyprus, Greece and the Ukraine. Principal results Among the 31 nuclear microsatellite primers tested, only three produced specific amplification products, with orthology confirmed by sequence analysis. They were then used for genetic diversity studies. The mean number of alleles and the expected heterozygosity means were Na=8.78 and He=0.76, respectively. The fixation index showed a significant deviation from Hardy–Weinberg equilibrium and an excess of homozygotes (FIS=0.27–0.56). A moderate level of genetic differentiation was observed among the populations (FST=0.075, P<0.001). The most differentiated populations corresponded to old vestigial stands found at the tree line (>2000 m) in Lebanon. These populations were differentiated from the other populations that are grouped into three sub-clusters. Conclusions High levels of genetic diversity were observed at species and population levels. The high level of differentiation in the high-mountain Lebanese populations reflects a long period of isolation or possibly a different origin. The admixture observed in other populations from Lebanon suggests a more recent separation from the Turkish–southeastern European populations. PMID:22476474

  18. High genetic diversity with moderate differentiation in Juniperus excelsa from Lebanon and the eastern Mediterranean region.

    PubMed

    Douaihy, Bouchra; Vendramin, Giovanni G; Boratyński, Adam; Machon, Nathalie; Bou Dagher-Kharrat, Magda

    2011-01-01

    Juniperus excelsa is an important woody species in the high mountain ecosystems of the eastern Mediterranean Basin where it constitutes the only coniferous species found at the tree line. The genetic diversity within and among J. excelsa populations of the eastern Mediterranean Basin is studied in the light of their historical fragmentation. Nuclear microsatellites originally developed for Juniperus communis and J. przewalskii were tested on 320 individuals from 12 different populations originating from Lebanon, Turkey, Cyprus, Greece and the Ukraine. Among the 31 nuclear microsatellite primers tested, only three produced specific amplification products, with orthology confirmed by sequence analysis. They were then used for genetic diversity studies. The mean number of alleles and the expected heterozygosity means were N(a)=8.78 and H(e)=0.76, respectively. The fixation index showed a significant deviation from Hardy-Weinberg equilibrium and an excess of homozygotes (F(IS)=0.27-0.56). A moderate level of genetic differentiation was observed among the populations (F(ST)=0.075, P<0.001). The most differentiated populations corresponded to old vestigial stands found at the tree line (>2000 m) in Lebanon. These populations were differentiated from the other populations that are grouped into three sub-clusters. High levels of genetic diversity were observed at species and population levels. The high level of differentiation in the high-mountain Lebanese populations reflects a long period of isolation or possibly a different origin. The admixture observed in other populations from Lebanon suggests a more recent separation from the Turkish-southeastern European populations.

  19. Comparative assessment of blood lead levels of automobile technicians in organised and roadside garages in Lagos, Nigeria.

    PubMed

    Saliu, Abdulsalam; Adebayo, Onajole; Kofoworola, Odeyemi; Babatunde, Ogunowo; Ismail, Abdussalam

    2015-01-01

    Occupational exposure to lead is common among automobile technicians and constitutes 0.9% of total global health burden with a majority of cases in developing countries. The aim of this study was to determine and compare the blood lead levels of automobile technicians in roadside and organised garages in Lagos State, Nigeria. This was a comparative cross-sectional study. Data were collected using interviewer-administered questionnaires. Physical examinations were conducted and blood was analysed for lead using atomic spectrophotometery. Statistical analyses were performed to compare the median blood lead levels of each group using the independent sample (Mann-Whitney U) test. Seventy-three (40.3%) of the organised compared to 59 (34.3%) of the roadside groups had high blood lead levels. The organised group had statistically significant higher median blood lead levels of, 66.0 µg/dL than the roadside 43.5 µg/dL (P < 0.05). There was also statistically significant association between high blood lead levels and abnormal discolouration of the mucosa of the mouth in the organised group. Automobile technicians in organised garages in Lagos have higher prevalence of elevated blood lead levels and higher median levels than the roadside group. Preventive strategies against lead exposures should be instituted by the employers and further actions should be taken to minimize exposures, improve work practices, implement engineering controls (e.g., proper ventilation), and ensure the use of personal protective equipment.

  20. Comparative Assessment of Blood Lead Levels of Automobile Technicians in Organised and Roadside Garages in Lagos, Nigeria

    PubMed Central

    Saliu, Abdulsalam; Adebayo, Onajole; Kofoworola, Odeyemi; Babatunde, Ogunowo; Ismail, Abdussalam

    2015-01-01

    Occupational exposure to lead is common among automobile technicians and constitutes 0.9% of total global health burden with a majority of cases in developing countries. The aim of this study was to determine and compare the blood lead levels of automobile technicians in roadside and organised garages in Lagos State, Nigeria. This was a comparative cross-sectional study. Data were collected using interviewer-administered questionnaires. Physical examinations were conducted and blood was analysed for lead using atomic spectrophotometery. Statistical analyses were performed to compare the median blood lead levels of each group using the independent sample (Mann-Whitney U) test. Seventy-three (40.3%) of the organised compared to 59 (34.3%) of the roadside groups had high blood lead levels. The organised group had statistically significant higher median blood lead levels of, 66.0 µg/dL than the roadside 43.5 µg/dL (P < 0.05). There was also statistically significant association between high blood lead levels and abnormal discolouration of the mucosa of the mouth in the organised group. Automobile technicians in organised garages in Lagos have higher prevalence of elevated blood lead levels and higher median levels than the roadside group. Preventive strategies against lead exposures should be instituted by the employers and further actions should be taken to minimize exposures, improve work practices, implement engineering controls (e.g., proper ventilation), and ensure the use of personal protective equipment. PMID:25759723

  1. A Fine Grain, High Mn Steel with Excellent Cryogenic Temperature Properties and Corresponding Constitutive Behaviour

    PubMed Central

    Wang, Yuhui; Shi, Baodong; He, Yanming; Zhang, Hongwang; Peng, Yan

    2018-01-01

    A Fe-34.5 wt % Mn-0.04 wt % C ultra-high Mn steel with a fully recrystallised fine-grained structure was produced by cold rolling and subsequent annealing. The steel exhibited excellent cryogenic temperature properties with enhanced work hardening rate, high tensile strength, and high uniform elongation. In order to capture the unique mechanical behaviour, a constitutive model within finite strain plasticity framework based on Hill-type yield function was established with standard Armstrong-Frederick type isotropic hardening. In particular, the evolution of isotropic hardening was determined by the content of martensite; thus, a relationship between model parameters and martensite content is built explicitly. PMID:29414840

  2. Relating stress of mothers of children with developmental disabilities to family-school partnerships.

    PubMed

    Burke, Meghan M; Hodapp, Robert M

    2014-02-01

    Although mothers of children with intellectual and developmental disabilities (IDD) experience high levels of stress and schools constitute an important resource, the relation remains unknown between maternal stress and educational services. Responding to a national, web-based survey, 965 mothers of students with disabilities completed a 163-item questionnaire about parent stress. We examined which child, parent, and parent-school characteristics correlated with maternal stress. Mothers with lower stress levels reported better parent-school relationships and low levels of parent advocacy. However, lower stress levels were predominantly shown by mothers with good-to-excellent parent-school relationships (vs. poor-to-fair partnerships) and who engaged in virtually no (vs. any) advocacy activities. Lower maternal stress levels were also noted when children had fewer behavior problems, Down syndrome, and did not have autism. Less stress was also reported by mothers who had not enacted procedural safeguards, were minorities, and rated themselves lower on neuroticism and were more extroverted, dependable, and open to new experiences. This study has important implications for practitioners and researchers.

  3. A High-Grade Chondrosarcoma of Calcaneum Mimicking as a Benign Pathology: Delayed Diagnosis and Management.

    PubMed

    Baba, Muzamil Ahmad; Nazir, Naila; Shabeer, Maajid; Mir, Bashir Ahmed; Kawoosa, Altaf Ahmad

    2016-10-01

    This case is presented to highlight a rare case of chondrosarcoma of calcaneum in a young adult mimicking as a benign pathology and to highlight the diagnosis and early management of such cases to prevent complications and even death. Chondrosarcoma constitutes less than 10% of all primary malignancies of bone and occurs mostly in proximal locations such as pelvis, proximal femur, and proximal humerus. We present a case of high-grade chondrosarcoma at a very rare site, calcaneum of a 40-year-old male that was mimicking as a benign pathology. This case report highlights the importance of proper clinical examination, evaluation, and suspicion for benign occurring lesions to prevent complications related to a delay in diagnosis. Therapeutic, Level IV: Case study. © 2016 The Author(s).

  4. Forming system of strategic innovation management at high-tech engineering enterprises

    NASA Astrophysics Data System (ADS)

    Ergunova, O. T.; Lizunkov, V. G.; Malushko, E. Yu; Marchuk, V. I.; Ignatenko, A. Yu

    2017-02-01

    The article considers the processes of forming the strategic system of innovative activity management at the enterprises of a high-tech mechanical engineering complex (MEC) that are traditionally decisive in shaping the economic base of Russia. The authors proposed a method of designing a strategic system of innovative activity management at the MEC’s enterprises of the region which is based on the consideration of means and opportunities of the enterprise to implement intellectual activity. The proposed methodology and the empirical results constituted a ground for developing a system of strategic innovation management when performing the state-guaranteed order at the hi-tech MEC enterprises. Its implementation will help to reduce the level of uncertainty throughout the entire life cycle of an innovative activity product.

  5. Governing University Strategy: Perceptions and Practice of Governance and Management Roles

    ERIC Educational Resources Information Center

    Rytmeister, Catherine

    2009-01-01

    Intertwined trends of massification, internationalisation and marketisation constitute and drive change in higher education at all levels. Consequences at the institutional level include: increased competition, adoption of corporate management forms, accrual of power to executive management, and greater emphasis on strategy. As Government policy…

  6. Effects of Recovery Behavior and Strain-Rate Dependence of Stress-Strain Curve on Prediction Accuracy of Thermal Stress Analysis During Casting

    NASA Astrophysics Data System (ADS)

    Motoyama, Yuichi; Shiga, Hidetoshi; Sato, Takeshi; Kambe, Hiroshi; Yoshida, Makoto

    2017-06-01

    Recovery behavior (recovery) and strain-rate dependence of the stress-strain curve (strain-rate dependence) are incorporated into constitutive equations of alloys to predict residual stress and thermal stress during casting. Nevertheless, few studies have systematically investigated the effects of these metallurgical phenomena on the prediction accuracy of thermal stress in a casting. This study compares the thermal stress analysis results with in situ thermal stress measurement results of an Al-Si-Cu specimen during casting. The results underscore the importance for the alloy constitutive equation of incorporating strain-rate dependence to predict thermal stress that develops at high temperatures where the alloy shows strong strain-rate dependence of the stress-strain curve. However, the prediction accuracy of the thermal stress developed at low temperatures did not improve by considering the strain-rate dependence. Incorporating recovery into the constitutive equation improved the accuracy of the simulated thermal stress at low temperatures. Results of comparison implied that the constitutive equation should include strain-rate dependence to simulate defects that develop from thermal stress at high temperatures, such as hot tearing and hot cracking. Recovery should be incorporated into the alloy constitutive equation to predict the casting residual stress and deformation caused by the thermal stress developed mainly in the low temperature range.

  7. Public health and the Australian Constitution.

    PubMed

    Reynolds, C

    1995-06-01

    The powers vested in the Commonwealth Government by the Constitution contain the basis of much public health law in Australia. Yet this is not often recognised; public health law is generally, and historically, seen as the states' responsibility. This article surveys the broad range of constitutional powers that the Commonwealth Government can rely upon to make public health laws. It considers areas of power specified in the Constitution, such as those with respect to external affairs and corporations. Decisions of the High Court have interpreted the various heads of power very broadly and have significantly enhanced the potential of the Commonwealth to pass detailed and far-reaching public health law. To this fact must be added the taxation arrangements in Australia and, with these, the very extensive control that the Commonwealth can exercise through its monopoly of major taxation sources. Its power to make financial arrangements can tie dependent states into specific policies (including public health policies) as a condition of the grants made to them. However, these broad powers may be limited in some important respects: the High Court is increasingly identifying rights and freedoms in the Constitution that may increasingly bring both state and Commonwealth public health law under challenge. Despite this possibility, the Commonwealth may prove to be our most significant source of public health law, and public health policy makers should recognise the full potential of its power to make such laws.

  8. Exploration to Constitution: Booklet 1. Critical Thinking in American History. Teacher's Guide and Source Envelope.

    ERIC Educational Resources Information Center

    O'Reilly, Kevin

    One of a series of curriculum materials in U.S. history designed to teach critical thinking skills systematically, this teacher's guide presents a series of supplementary ready-to-use lesson plans for teaching high school students about the exploration of early America, the colonies, the revolution, and the Constitution. The introduction presents…

  9. Exploration to Constitution: Booklet 1. Critical Thinking in American History. [Student Manual].

    ERIC Educational Resources Information Center

    O'Reilly, Kevin

    One of a series of curriculum materials in U.S. history designed to teach critical thinking skills systematically, this student booklet presents high school students with a series of supplementary lessons on the exploration of early America, the colonies, the revolution, and the Constitution. The booklet begins with a guide to critical thinking…

  10. Constitutive response of Rene 80 under thermal mechanical loads

    NASA Technical Reports Server (NTRS)

    Kim, K. S.; Cook, T. S.; Mcknight, R. L.

    1988-01-01

    The applicability of a classical constitutive model for stress-strain analysis of a nickel base superalloy, Rene' 80, in the gas turbine thermomechanical fatigue (TMF) environment is examined. A variety of tests were conducted to generate basic material data and to investigate the material response under cyclic thermomechanical loading. Isothermal stress-strain data were acquired at a variety of strain rates over the TMF temperature range. Creep curves were examined at 2 temperature ranges, 871 to 982 C and 760 to 871 C. The results provide optimism on the ability of the classical constitutive model for high temperature applications.

  11. Towards a magnetoresistive platform for neural signal recording

    NASA Astrophysics Data System (ADS)

    Sharma, P. P.; Gervasoni, G.; Albisetti, E.; D'Ercoli, F.; Monticelli, M.; Moretti, D.; Forte, N.; Rocchi, A.; Ferrari, G.; Baldelli, P.; Sampietro, M.; Benfenati, F.; Bertacco, R.; Petti, D.

    2017-05-01

    A promising strategy to get deeper insight on brain functionalities relies on the investigation of neural activities at the cellular and sub-cellular level. In this framework, methods for recording neuron electrical activity have gained interest over the years. Main technological challenges are associated to finding highly sensitive detection schemes, providing considerable spatial and temporal resolution. Moreover, the possibility to perform non-invasive assays would constitute a noteworthy benefit. In this work, we present a magnetoresistive platform for the detection of the action potential propagation in neural cells. Such platform allows, in perspective, the in vitro recording of neural signals arising from single neurons, neural networks and brain slices.

  12. [How to write an andrological paper: standardization, mechanics and techniques].

    PubMed

    Huang, Yu-Feng; Lu, Jin-Chun

    2010-12-01

    Andrological research papers not only reflect the current status and academic level of andrology, but also constitute an important communication platform for researchers and clinicians engaged in this field and contribute significantly to the development of andrology. It would be made easier to write a high-quality andrological paper once the author observes the basic requirements of research papers, adheres to the use of standard scientific terminology, knows the special writing mechanics, and equips himself with some essential writing techniques. Based on the long experience of editorship, we present a detailed introduction of the standardization, mechanics and techniques of writing an andrological paper.

  13. The importance of understanding individual differences in Down syndrome

    PubMed Central

    Karmiloff-Smith, Annette; Al-Janabi, Tamara; D'Souza, Hana; Groet, Jurgen; Massand, Esha; Mok, Kin; Startin, Carla; Fisher, Elizabeth; Hardy, John; Nizetic, Dean; Tybulewicz, Victor; Strydom, Andre

    2016-01-01

    In this article, we first present a summary of the general assumptions about Down syndrome (DS) still to be found in the literature. We go on to show how new research has modified these assumptions, pointing to a wide range of individual differences at every level of description. We argue that, in the context of significant increases in DS life expectancy, a focus on individual differences in trisomy 21 at all levels—genetic, cellular, neural, cognitive, behavioral, and environmental—constitutes one of the best approaches for understanding genotype/phenotype relations in DS and for exploring risk and protective factors for Alzheimer’s disease in this high-risk population. PMID:27019699

  14. Voluntariness of consent to HIV clinical research: A conceptual and empirical pilot study.

    PubMed

    Mamotte, Nicole; Wassenaar, Douglas

    2017-09-01

    Obtaining voluntary informed consent for research participation is an ethical imperative, yet there appears to be little consensus regarding what constitutes a voluntary consent decision. An instrument to assess influences on participants' consent decision and perceived voluntariness was developed and piloted in two South African HIV clinical trials. The pilot study found high levels of perceived voluntariness. The feeling of having no choice but to participate was significantly associated with lower perceived voluntariness. Overall the data suggest that it is possible to obtain voluntary and valid consent for research participants in ethically complex HIV clinical trials in a developing country context.

  15. Experiments of thermomechanical fatigue of SMAs

    NASA Astrophysics Data System (ADS)

    Lagoudas, Dimitris C.; Miller, David A.

    1999-07-01

    As SMA wires are gaining in popularity for use as actuators, one constitutive parameter that remain unknown is the thermomechanical fatigue life. Even though the effect of thermal cycles on the transformation characteristics of SMAs has been studied, these teste have not been extended to high number of cycles. In this study, a novel test frame developed to study the thermomechanical fatigue life of SMAs is described. Additionally, a testing protocol is discussed necessary to fully establish the fatigue characteristics of SMAs under various conditions. Initial results of the initial test show a substantial increase in the number of cycles to failure as the applied stress level reduces to approximately 100 MPa.

  16. Molecular determinants for the high constitutive activity of the human histamine H4 receptor: functional studies on orthologues and mutants

    PubMed Central

    Wifling, D; Löffel, K; Nordemann, U; Strasser, A; Bernhardt, G; Dove, S; Seifert, R; Buschauer, A

    2015-01-01

    Background and Purpose Some histamine H4 receptor ligands act as inverse agonists at the human H4 receptor (hH4R), a receptor with exceptionally high constitutive activity, but as neutral antagonists or partial agonists at the constitutively inactive mouse H4 receptor (mH4R) and rat H4 receptor (rH4R). To study molecular determinants of constitutive activity, H4 receptor reciprocal mutants were constructed: single mutants: hH4R-F169V, mH4R-V171F, hH4R-S179A, hH4R-S179M; double mutants: hH4R-F169V+S179A, hH4R-F169V+S179M and mH4R-V171F+M181S. Experimental Approach Site-directed mutagenesis with pVL1392 plasmids containing hH4 or mH4 receptors were performed. Wild-type or mutant receptors were co-expressed with Gαi2 and Gβ1γ2 in Sf9 cells. Membranes were studied in saturation and competition binding assays ([3H]-histamine), and in functional [35S]-GTPγS assays with inverse, partial and full agonists of the hH4 receptor. Key Results Constitutive activity decreased from the hH4 receptor via the hH4R-F169V mutant to the hH4R-F169V+S179A and hH4R-F169V+S179M double mutants. F169 alone or in concert with S179 plays a major role in stabilizing a ligand-free active state of the hH4 receptor. Partial inverse hH4 receptor agonists like JNJ7777120 behaved as neutral antagonists or partial agonists at species orthologues with lower or no constitutive activity. Some partial and full hH4 receptor agonists showed decreased maximal effects and potencies at hH4R-F169V and double mutants. However, the mutation of S179 in the hH4 receptor to M as in mH4 receptor or A as in rH4 receptor did not significantly reduce constitutive activity. Conclusions and Implications F169 and S179 are key amino acids for the high constitutive activity of hH4 receptors and may also be of relevance for other constitutively active GPCRs. Linked Articles This article is part of a themed issue on Histamine Pharmacology Update published in volume 170 issue 1. To view the other articles in this issue visit http://onlinelibrary.wiley.com/doi/10.1111/bph.2013.170.issue-1/issuetoc PMID:24903527

  17. Modeling the data systems role of the scientist (for the NEEDS Command and Control Task)

    NASA Technical Reports Server (NTRS)

    Hei, D. J., Jr.; Winter, W. J., Jr.; Brookes, R.; Locke, M.

    1981-01-01

    Research was conducted into the command and control activities of the scientists for five space missions: International Ultraviolet Explorer, Solar Maximum Mission, International Sun-Earth Explorer, High-Energy Astronomy Observatory 1, and Atmospheric Explorer 5. A basis for developing a generalized description of the scientists' activities was obtained. Because of this characteristic, it was decided that a series of flowcharts would be used. This set of flowcharts constitutes a model of the scientists' activities within the total data system. The model was developed through three levels of detail. The first is general and provides a conceptual framework for discussing the system. The second identifies major functions and should provide a fundamental understanding of the scientists' command and control activities. The third level expands the major functions into a more detailed description.

  18. Naturalness and interestingness of test images for visual quality evaluation

    NASA Astrophysics Data System (ADS)

    Halonen, Raisa; Westman, Stina; Oittinen, Pirkko

    2011-01-01

    Balanced and representative test images are needed to study perceived visual quality in various application domains. This study investigates naturalness and interestingness as image quality attributes in the context of test images. Taking a top-down approach we aim to find the dimensions which constitute naturalness and interestingness in test images and the relationship between these high-level quality attributes. We compare existing collections of test images (e.g. Sony sRGB images, ISO 12640 images, Kodak images, Nokia images and test images developed within our group) in an experiment combining quality sorting and structured interviews. Based on the data gathered we analyze the viewer-supplied criteria for naturalness and interestingness across image types, quality levels and judges. This study advances our understanding of subjective image quality criteria and enables the validation of current test images, furthering their development.

  19. Identification of a t(3;4)(p1.3;q1.5) translocation breakpoint in pigs using somatic cell hybrid mapping and high-resolution mate-pair sequencing

    PubMed Central

    Fève, Katia; Foissac, Sylvain; Pinton, Alain; Mompart, Florence; Esquerré, Diane; Faraut, Thomas; Yerle, Martine

    2017-01-01

    Reciprocal translocations are the most frequently occurring constitutional structural rearrangements in mammalian genomes. In phenotypically normal pigs, an incidence of 1/200 is estimated for such rearrangements. Even if constitutional translocations do not necessarily induce defects and diseases, they are responsible for significant economic losses in domestic animals due to reproduction failures. Over the last 30 years, advances in molecular and cytogenetic technologies have led to major improvements in the resolution of the characterization of translocation events. Characterization of translocation breakpoints helps to decipher the mechanisms that lead to such rearrangements and the functions of the genes that are involved in the translocation. Here, we describe the fine characterization of a reciprocal translocation t(3;4) (p1.3;q1.5) detected in a pig line. The breakpoint was identified at the base-pair level using a positional cloning and chromosome walking strategy in somatic cell hybrids that were generated from an animal that carries this translocation. We show that this translocation occurs within the ADAMTSL4 gene and results in a loss of expression in homozygous carriers. In addition, by taking this translocation as a model, we used a whole-genome next-generation mate-pair sequencing approach on pooled individuals to evaluate this strategy for high-throughput screening of structural rearrangements. PMID:29121641

  20. Learning to play the violin: motor control by freezing, not freeing degrees of freedom.

    PubMed

    Konczak, Jürgen; Vander Velden, Heidi; Jaeger, Lukas

    2009-05-01

    Playing a violin requires precise patterns of limb coordination that are acquired over years of practice. In the present study, the authors investigated how motion at proximal arm joints influenced the precision of bow movements in novice learners and experts. The authors evaluated the performances of 11 children (4-12 years old), 3 beginning-to-advanced level adult players, and 2 adult concert violinists, using a musical work that all had mastered as their first violin piece. The authors found that learning to play the violin was not associated with a release or freeing of joint degrees of freedom. Instead, learning was characterized by an experience-dependent suppression of sagittal shoulder motion, as documented by an observed reduction in joint angular amplitude. This reduction in the amplitude of shoulder flexion-extension correlated highly with a decrease of bow-movement variability. The remaining mechanical degrees of freedom at the elbow and shoulder showed patterns of neither suppression nor freeing. Only violinists with more than 700 practice hr achieved sagittal shoulder range of motion comparable to experts. The findings imply that restricting joint amplitude at selected joint degrees of freedom, while leaving other degrees of freedom unconstrained, constitutes an appropriate strategy for learning complex, high-precision motor patterns in children and adults. The findings also highlight that mastering even seemingly simple bowing movements constitutes a prolonged learning process.

  1. Highly Stereoselective Synthesis of Cyclopentanes bearing Four Stereocenters by a Rhodium Carbene–Initiated Domino Sequence

    PubMed Central

    Parr, Brendan T.; Davies, Huw M. L.

    2014-01-01

    Stereoselective synthesis of a cyclopentane nucleus by convergent annulations constitutes a significant challenge for synthetic chemists. Though a number of biologically relevant cyclopentane natural products are known, more often than not, the cyclopentane core is assembled in a stepwise fashion due to lack of efficient annulation strategies. Herein, we report the rhodium-catalyzed reactions of vinyldiazoacetates with (E)-1,3-disubstituted 2-butenols generate cyclopentanes, containing four new stereogenic centers with very high levels of stereoselectivity (99% ee, >97 : 3 dr). The reaction proceeds by a carbene–initiated domino sequence consisting of five distinct steps: rhodium–bound oxonium ylide formation, [2,3]-sigmatropic rearrangement, oxy-Cope rearrangement, enol–keto tautomerization, and finally an intramolecular carbonyl ene reaction. A systematic study is presented detailing how to control chirality transfer in each of the four stereo-defining steps of the cascade, consummating in the development of a highly stereoselective process. PMID:25082301

  2. Production of Japanese encephalitis virus-like particles in insect cells.

    PubMed

    Yamaji, Hideki; Konishi, Eiji

    2013-01-01

    Virus-like particles (VLPs) are composed of one or several recombinant viral surface proteins that spontaneously assemble into particulate structures without the incorporation of virus DNA or RNA. The baculovirus-insect cell system has been used extensively for the production of recombinant virus proteins including VLPs. While the baculovirus-insect cell system directs the transient expression of recombinant proteins in a batch culture, stably transformed insect cells allow constitutive production. In our recent study, a secretory form of Japanese encephalitis (JE) VLPs was successfully produced by Trichoplusia ni BTI-TN-5B1-4 (High Five) cells engineered to coexpress the JE virus (JEV) premembrane (prM) and envelope (E) proteins. A higher yield of E protein was attained with recombinant High Five cells than with the baculovirus-insect cell system. This study demonstrated that recombinant insect cells offer a promising approach to the high-level production of VLPs for use as vaccines and diagnostic antigens.

  3. Phenols, flame retardants and phthalates in water and wastewater - a global problem.

    PubMed

    Ayanda, Olushola Sunday; Olutona, Godwin Oladele; Olumayede, Emmanuel G; Akintayo, Cecilia O; Ximba, Bhekumusa J

    Organic pollutants in water and wastewater have been causing serious environmental problems. The arbitrary discharge of wastewater by industries, and handling, use, and disposal constitute a means by which phenols, flame retardants (FRs), phthalates (PAEs) and other toxic organic pollutants enter the ecosystem. Moreover, these organic pollutants are not completely removed during treatment processes and might be degraded into highly toxic derivatives, which has led to their occurrence in the environment. Phenols, FRs and PAEs are thus highly toxic, carcinogenic and mutagenic, and are capable of disrupting the endocrine system. Therefore, investigation to understand the sources, pathways, behavior, toxicity and exposure to phenols, FRs and PAEs in the environment is necessary. Formation of different by-products makes it difficult to compare the efficacy of the treatment processes, most especially when other organic matters are present. Hence, high levels of phenols, FRs and PAEs removal could be attained with in-line combined treatment processes.

  4. An Optimizing Compiler for Petascale I/O on Leadership-Class Architectures

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

    Kandemir, Mahmut Taylan; Choudary, Alok; Thakur, Rajeev

    In high-performance computing (HPC), parallel I/O architectures usually have very complex hierarchies with multiple layers that collectively constitute an I/O stack, including high-level I/O libraries such as PnetCDF and HDF5, I/O middleware such as MPI-IO, and parallel file systems such as PVFS and Lustre. Our DOE project explored automated instrumentation and compiler support for I/O intensive applications. Our project made significant progress towards understanding the complex I/O hierarchies of high-performance storage systems (including storage caches, HDDs, and SSDs), and designing and implementing state-of-the-art compiler/runtime system technology that targets I/O intensive HPC applications that target leadership class machine. This final reportmore » summarizes the major achievements of the project and also points out promising future directions Two new sections in this report compared to the previous report are IOGenie and SSD/NVM-specific optimizations.« less

  5. Coming of age: health-care challenges of an ageing population in Israel.

    PubMed

    Dwolatzky, Tzvi; Brodsky, Jenny; Azaiza, Faisal; Clarfield, A Mark; Jacobs, Jeremy M; Litwin, Howard

    2017-06-24

    Although Israel is still young in years, with relatively high birth rates and older people (individuals aged 65 years or older) constituting only about 11% of its population, the absolute number of older people is growing rapidly. Life expectancy is high, and increasing numbers of people are living to advanced old age (older than 85 years). A wide spectrum of geriatric care is provided within a universal system providing health services to all citizens. Community and institutional care is available, and many innovative programmes are being developed. The unique demographic characteristics of the ageing society in Israel reflect cultural and multiethnic diversity, in addition to a high rate of immigration of older people. To meet the growing challenges, address disparities, and search for innovation will require planning and development of adequate services at the highest level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. High throughput estimation of functional cell activities reveals disease mechanisms and predicts relevant clinical outcomes

    PubMed Central

    Hidalgo, Marta R.; Cubuk, Cankut; Amadoz, Alicia; Salavert, Francisco; Carbonell-Caballero, José; Dopazo, Joaquin

    2017-01-01

    Understanding the aspects of the cell functionality that account for disease or drug action mechanisms is a main challenge for precision medicine. Here we propose a new method that models cell signaling using biological knowledge on signal transduction. The method recodes individual gene expression values (and/or gene mutations) into accurate measurements of changes in the activity of signaling circuits, which ultimately constitute high-throughput estimations of cell functionalities caused by gene activity within the pathway. Moreover, such estimations can be obtained either at cohort-level, in case/control comparisons, or personalized for individual patients. The accuracy of the method is demonstrated in an extensive analysis involving 5640 patients from 12 different cancer types. Circuit activity measurements not only have a high diagnostic value but also can be related to relevant disease outcomes such as survival, and can be used to assess therapeutic interventions. PMID:28042959

  7. Caspian sea-level changes during the last millennium: historical and geological evidence from the south Caspian Sea

    NASA Astrophysics Data System (ADS)

    Naderi Beni, A.; Lahijani, H.; Mousavi Harami, R.; Arpe, K.; Leroy, S. A. G.; Marriner, N.; Berberian, M.; Andrieu-Ponel, V.; Djamali, M.; Mahboubi, A.; Reimer, P. J.

    2013-07-01

    Historical literature may constitute a valuable source of information to reconstruct sea-level changes. Here, historical documents and geological records have been combined to reconstruct Caspian sea-level (CSL) changes during the last millennium. In addition to a comprehensive literature review, new data from two short sediment cores were obtained from the south-eastern Caspian coast to identify coastal change driven by water-level changes and to compare the results with other geological and historical findings. The overall results indicate a high-stand during the Little Ice Age, up to -21 m (and extra rises due to manmade river avulsion), with a -28 m low-stand during the Medieval Climate Anomaly, while presently the CSL stands at -26.5 m. A comparison of the CSL curve with other lake systems and proxy records suggests that the main sea-level oscillations are essentially paced by solar irradiance. Although the major controller of the long-term CSL changes is driven by climatological factors, the seismicity of the basin creates local changes in base level. These local base-level changes should be considered in any CSL reconstruction.

  8. Caspian Sea level changes during the last millennium: historical and geological evidences from the south Caspian Sea

    NASA Astrophysics Data System (ADS)

    Naderi Beni, A.; Lahijani, H.; Mousavi Harami, R.; Arpe, K.; Leroy, S. A. G.; Marriner, N.; Berberian, M.; Andrieu-Ponel, V.; Djamali, M.; Mahboubi, A.

    2013-03-01

    Historical literature may constitute a valuable source of information to reconstruct sea level changes. Here, historical documents and geological records have been combined to reconstruct Caspian sea-level (CSL) changes during the last millennium. In addition to a literature survey, new data from two short sediment cores were obtained from the south-eastern Caspian coast to identify coastal change driven by water-level changes. Two articulated bivalve shells from the marine facies were radiocarbon dated and calibrated to establish a chronology and to compare them with historical findings. The overall results indicate a high-stand during the Little Ice Age, up to -19 m, with a -28 m low-stand during the Medieval Climate Anomaly, while presently the CSL stands at -26.5 m. A comparison of the CSL curve with other lake systems and proxy records suggests that the main sea-level oscillations are essentially paced by solar irradiance. Although the major controller of the long-term CSL changes is driven by climatological factors, the seismicity of the basin could create locally changes in base level. These local base-level changes should be considered in any CSL reconstruction.

  9. The burnout syndrome and associated personality disturbances. The study in three graduate programs in Dentistry at the University of Barcelona.

    PubMed

    Alemany Martínez, Aurelia; Berini Aytés, Leonardo; Gay Escoda, Cosme

    2008-07-01

    Determine the presence of "burnout" syndrome and characteristic personality patterns in the students and faculty of three graduate programs in Dentistry at the University of Barcelona: Department of Oral Surgery and Implantology, Department of Orthodontics and Department of Integrated Dentistry. The study was carried out in 78 dentists. The level of "burnout" was evaluated using the Maslach Burnout Inventory, socio-demographic variables and, finally, the personality test. Oral surgeons constituted the group of high-level "burnout". The profile of an individual with a propensity to "burn out" is a single man, with a median age of 27, that is in the first years of the graduate program and that combines studies with 30 hours of clinical practice and/or other work (p<0,05). Narcissistic and borderline are the types of personality most frequently found in the individuals that present "burnout" syndrome (p<0,05). In general, no high levels of "burnout" were registered in the studied population, only 2-3%, if applying strict definition of "burnout", and 10% if these criteria were amplified. We believe it is necessary to identify the individuals with a tendency towards "burnout", in order to establish preventive measures and avoid future negative behaviour at work as well as at the personal level.

  10. Phenotypic diversity, population structure and stress protein-based capacitoring in populations of Xeropicta derbentina, a heat-tolerant land snail species.

    PubMed

    Di Lellis, Maddalena A; Sereda, Sergej; Geißler, Anna; Picot, Adrien; Arnold, Petra; Lang, Stefanie; Troschinski, Sandra; Dieterich, Andreas; Hauffe, Torsten; Capowiez, Yvan; Mazzia, Christophe; Knigge, Thomas; Monsinjon, Tiphaine; Krais, Stefanie; Wilke, Thomas; Triebskorn, Rita; Köhler, Heinz-R

    2014-11-01

    The shell colour of many pulmonate land snail species is highly diverse. Besides a genetic basis, environmentally triggered epigenetic mechanisms including stress proteins as evolutionary capacitors are thought to influence such phenotypic diversity. In this study, we investigated the relationship of stress protein (Hsp70) levels with temperature stress tolerance, population structure and phenotypic diversity within and among different populations of a xerophilic Mediterranean snail species (Xeropicta derbentina). Hsp70 levels varied considerably among populations, and were significantly associated with shell colour diversity: individuals in populations exhibiting low diversity expressed higher Hsp70 levels both constitutively and under heat stress than those of phenotypically diverse populations. In contrast, population structure (cytochrome c oxidase subunit I gene) did not correlate with phenotypic diversity. However, genetic parameters (both within and among population differences) were able to explain variation in Hsp70 induction at elevated but non-pathologic temperatures. Our observation that (1) population structure had a high explanatory potential for Hsp70 induction and that (2) Hsp70 levels, in turn, correlated with phenotypic diversity while (3) population structure and phenotypic diversity failed to correlate provides empirical evidence for Hsp70 to act as a mediator between genotypic variation and phenotype and thus for chaperone-driven evolutionary capacitance in natural populations.

  11. The obesity-risk variant of FTO is inversely related with the So-Eum constitutional type: genome-wide association and replication analyses.

    PubMed

    Cha, Seongwon; Yu, Hyunjoo; Park, Ah Yeon; Oh, Soo A; Kim, Jong Yeol

    2015-04-15

    Body constitutional types described in the traditional Korean medicine system, Sasang constitutional medicine, are heritable, as has been revealed by twin and family studies. Thus, individuals with the same constitution type usually have similar pathophysiological and psychological traits. In several recent genome-wide association (GWA) analyses performed to identify constitution-associated variants, the association signals were not replicated due to small sample size and dissimilar, non-objective methods for classification of the constitutional types. We conducted GWA analysis and followed replication analysis in two large populations (5,490 subjects: 3,810 subjects at discovery stage and 1,680 subjects at replication stage) to identify the replicable constitution-associated variants, wherein subjects with the highest tertile of constitution probability values versus the reference with the lowest tertile of the values obtained from a recently developed constitution analysis tool were compared. We found that the obesity-risk variant in intron 1 of the fat mass and obesity-associated (FTO) gene was replicably inversely associated with the So-Eum (SE) type, characterized by reduced appetite, slim body, and cautious personality (rs7193144 in combined samples: odds ratio = 0.729, p = 1.47 × 10(-7)), and substantial association signal remained after controlling for body mass index (BMI). In contrast, the association of the variant with the Tae-Eum type, characterized by high body mass, disappeared after controlling BMI. In summary, the obesity-risk variant in FTO intron 1 was inversely associated with the SE type, independent of BMI, which corresponded well with the characteristics of the SE type, such as the lowest body mass and lowest susceptibility to metabolic disorders among the constitutional types. Therefore, the obesity-risk variant of FTO associated with body mass increase might be involved in the determination of body constitution type.

  12. Assessment of Hammocks (Petenes) Resilience to Sea Level Rise Due to Climate Change in Mexico

    PubMed Central

    Posada Vanegas, Gregorio; de Jong, Bernardus H. J.

    2016-01-01

    There is a pressing need to assess resilience of coastal ecosystems against sea level rise. To develop appropriate response strategies against future climate disturbances, it is important to estimate the magnitude of disturbances that these ecosystems can absorb and to better understand their underlying processes. Hammocks (petenes) coastal ecosystems are highly vulnerable to sea level rise linked to climate change; their vulnerability is mainly due to its close relation with the sea through underground drainage in predominantly karstic soils. Hammocks are biologically important because of their high diversity and restricted distribution. This study proposes a strategy to assess resilience of this coastal ecosystem when high-precision data are scarce. Approaches and methods used to derive ecological resilience maps of hammocks are described and assessed. Resilience models were built by incorporating and weighting appropriate indicators of persistence to assess hammocks resilience against flooding due to climate change at “Los Petenes Biosphere Reserve”, in the Yucatán Peninsula, Mexico. According to the analysis, 25% of the study area is highly resilient (hot spots), whereas 51% has low resilience (cold spots). The most significant hot spot clusters of resilience were located in areas distant to the coastal zone, with indirect tidal influence, and consisted mostly of hammocks surrounded by basin mangrove and floodplain forest. This study revealed that multi-criteria analysis and the use of GIS for qualitative, semi-quantitative and statistical spatial analyses constitute a powerful tool to develop ecological resilience maps of coastal ecosystems that are highly vulnerable to sea level rise, even when high-precision data are not available. This method can be applied in other sites to help develop resilience analyses and decision-making processes for management and conservation of coastal areas worldwide. PMID:27611802

  13. Assessment of Hammocks (Petenes) Resilience to Sea Level Rise Due to Climate Change in Mexico.

    PubMed

    Hernández-Montilla, Mariana C; Martínez-Morales, Miguel Angel; Posada Vanegas, Gregorio; de Jong, Bernardus H J

    2016-01-01

    There is a pressing need to assess resilience of coastal ecosystems against sea level rise. To develop appropriate response strategies against future climate disturbances, it is important to estimate the magnitude of disturbances that these ecosystems can absorb and to better understand their underlying processes. Hammocks (petenes) coastal ecosystems are highly vulnerable to sea level rise linked to climate change; their vulnerability is mainly due to its close relation with the sea through underground drainage in predominantly karstic soils. Hammocks are biologically important because of their high diversity and restricted distribution. This study proposes a strategy to assess resilience of this coastal ecosystem when high-precision data are scarce. Approaches and methods used to derive ecological resilience maps of hammocks are described and assessed. Resilience models were built by incorporating and weighting appropriate indicators of persistence to assess hammocks resilience against flooding due to climate change at "Los Petenes Biosphere Reserve", in the Yucatán Peninsula, Mexico. According to the analysis, 25% of the study area is highly resilient (hot spots), whereas 51% has low resilience (cold spots). The most significant hot spot clusters of resilience were located in areas distant to the coastal zone, with indirect tidal influence, and consisted mostly of hammocks surrounded by basin mangrove and floodplain forest. This study revealed that multi-criteria analysis and the use of GIS for qualitative, semi-quantitative and statistical spatial analyses constitute a powerful tool to develop ecological resilience maps of coastal ecosystems that are highly vulnerable to sea level rise, even when high-precision data are not available. This method can be applied in other sites to help develop resilience analyses and decision-making processes for management and conservation of coastal areas worldwide.

  14. Constitutive Modeling of High-Temperature Flow Behavior of an Nb Micro-alloyed Hot Stamping Steel

    NASA Astrophysics Data System (ADS)

    Zhang, Shiqi; Feng, Ding; Huang, Yunhua; Wei, Shizhong; Mohrbacher, Hardy; Zhang, Yue

    2016-03-01

    The thermal deformation behavior and constitutive models of an Nb micro-alloyed 22MnB5 steel were investigated by conducting isothermal uniaxial tensile tests at the temperature range of 873-1223 K with strain rates of 0.1-10 s-1. The results indicated that the investigated steel showed typical work hardening and dynamic recovery behavior during hot deformation, and the flow stress decreased with a decrease in strain rate and/or an increase in temperature. On the basis of the experimental data, the modified Johnson-Cook (modified JC), modified Norton-Hoff (modified NH), and Arrhenius-type (AT) constitutive models were established for the subject steel. However, the flow stress values predicted by these three models revealed some remarkable deviations from the experimental values for certain experimental conditions. Therefore, a new combined modified Norton-Hoff and Arrhenius-type constitutive model (combined modified NH-AT model), which accurately reflected both the work hardening and dynamic recovery behavior of the subject steel, was developed by introducing the modified parameter k ɛ. Furthermore, the accuracy of these constitutive models was assessed by the correlation coefficient, the average absolute relative error, and the root mean square error, which indicated that the flow stress values computed by the combined modified NH-AT model were highly consistent with the experimental values (R = 0.998, AARE = 1.63%, RMSE = 3.85 MPa). The result confirmed that the combined modified NH-AT model was suitable for the studied Nb micro-alloyed hot stamping steel. Additionally, the practicability of the new model was also verified using finite element simulations in ANSYS/LS-DYNA, and the results confirmed that the new model was practical and highly accurate.

  15. Identification of constitutional MLH1 epimutations and promoter variants in colorectal cancer patients from the Colon Cancer Family Registry

    PubMed Central

    Ward, Robyn L.; Dobbins, Timothy; Lindor, Noralane M.; Rapkins, Robert W.; Hitchins, Megan P.

    2013-01-01

    Purpose: Constitutional MLH1 epimutations manifest as promoter methylation and silencing of the affected allele in normal tissues, predisposing to Lynch syndrome–associated cancers. This study investigated their frequency and inheritance. Methods: A total of 416 individuals with a colorectal cancer showing loss of MLH1 expression and without deleterious germline mutations in MLH1 were ascertained from the Colon Cancer Family Registry (C-CFR). Constitutive DNA samples were screened for MLH1 methylation in all 416 subjects and for promoter sequence changes in 357 individuals. Results: Constitutional MLH1 epimutations were identified in 16 subjects. Of these, seven (1.7%) had mono- or hemi-allelic methylation and eight had low-level methylation (2%). In one subject the epimutation was linked to the c.-27C>A promoter variant. Testing of 37 relatives from nine probands revealed paternal transmission of low-level methylation segregating with a c.+27G>A variant in one case. Five additional probands had a promoter variant without an MLH1 epimutation, with three showing diminished promoter activity in functional assays. Conclusion: Although rare, sequence changes in the regulatory region of MLH1 and aberrant methylation may alone or together predispose to the development of cancer. Screening for these changes is warranted in individuals who have a negative germline sequence screen of MLH1 and loss of MLH1 expression in their tumor. PMID:22878509

  16. Individual consistency in exploratory behaviour and mating tactics in male guppies

    NASA Astrophysics Data System (ADS)

    Kelley, Jennifer L.; Phillips, Samuel C.; Evans, Jonathan P.

    2013-10-01

    While behavioural plasticity is considered an adaptation to fluctuating social and environmental conditions, many animals also display a high level of individual consistency in their behaviour over time or across contexts (generally termed ‘personality’). However, studies of animal personalities that include sexual behaviour, or functionally distinct but correlated traits, are relatively scarce. In this study, we tested for individual behavioural consistency in courtship and exploratory behaviour in male guppies ( Poecilia reticulata) in two light environments (high vs. low light intensity). Based on previous work on guppies, we predicted that males would modify their behaviour from sneak mating tactics to courtship displays under low light conditions, but also that the rank orders of courtship effort would remain unchanged (i.e. highly sexually active individuals would display relatively high levels of courtship under both light regimes). We also tested for correlations between courtship and exploratory behaviour, predicting that males that had high display rates would also be more likely to approach a novel object. Although males showed significant consistency in their exploratory and mating behaviour over time (1 week), we found no evidence that these traits constituted a behavioural syndrome. Furthermore, in contrast to previous work, we found no overall effect of the light environment on any of the behaviours measured, although males responded to the treatment on an individual-level basis, as reflected by a significant individual-by-environment interaction. The future challenge is to investigate how individual consistency across different environmental contexts relates to male reproductive success.

  17. Some Limits in Peer Assessment

    ERIC Educational Resources Information Center

    Domingo, Joan; Martinez, Herminio; Gomariz, Spartacus; Gámiz, Juan

    2014-01-01

    Nowadays, the educational methodology known as "peer assessment" constitutes one of the pillars of formative assessment at the different levels of the educational system, particularly at the University level. In fact, in recent years, it has been increasingly used to enhance students' meaningful learning, as it is considered to be an…

  18. Intonation and emotion: influence of pitch levels and contour type on creating emotions.

    PubMed

    Rodero, Emma

    2011-01-01

    Intonation is a vehicle for communication, which sometimes contributes greater meaning than the semantic content of speech itself. This prosodic element lends the message linguistic and paralinguistic meaning, which carries a highly significant communicative value when conveying emotional states. For this reason, this article analyses the use of intonation as an instrument for arousing various sensations in the listener. The aim was to verify which elements of intonation are more decisive to generate a specific sensation. Experimental research is conducted, in which certain pitch patterns (pitch levels and contour type) are assigned different emotions (joy, anxiety, sadness, and calmness) and are then listened to and assessed using a questionnaire with a bipolar scale of opposed pairs, by a sample audience comprising 100 individuals. The main conclusion drawn is that, although both the variables analyzed--pitch level and contour type--are representative of expressing emotions, contour type is more decisive. In all the models analyzed, contour type has been highly significant and constitutes the variable that has been determined as the final component for recognizing various emotions. Copyright © 2011 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  19. Firefly: an optical lithographic system for the fabrication of holographic security labels

    NASA Astrophysics Data System (ADS)

    Calderón, Jorge; Rincón, Oscar; Amézquita, Ricardo; Pulido, Iván.; Amézquita, Sebastián.; Bernal, Andrés.; Romero, Luis; Agudelo, Viviana

    2016-03-01

    This paper introduces Firefly, an optical lithography origination system that has been developed to produce holographic masters of high quality. This mask-less lithography system has a resolution of 418 nm half-pitch, and generates holographic masters with the optical characteristics required for security applications of level 1 (visual verification), level 2 (pocket reader verification) and level 3 (forensic verification). The holographic master constitutes the main core of the manufacturing process of security holographic labels used for the authentication of products and documents worldwide. Additionally, the Firefly is equipped with a software tool that allows for the hologram design from graphic formats stored in bitmaps. The software is capable of generating and configuring basic optical effects such as animation and color, as well as effects of high complexity such as Fresnel lenses, engraves and encrypted images, among others. The Firefly technology gathers together optical lithography, digital image processing and the most advanced control systems, making possible a competitive equipment that challenges the best technologies in the industry of holographic generation around the world. In this paper, a general description of the origination system is provided as well as some examples of its capabilities.

  20. The role of sugar-sweetened beverage consumption in adolescent obesity: a review of the literature.

    PubMed

    Harrington, Susan

    2008-02-01

    Soft drink consumption has increased by 300% in the past 20 years, and 56-85% of children in school consume at least one soft drink daily. The odds ratio of becoming obese among children increases 1.6 times for each additional can or glass of sugar-sweetened drink consumed beyond their usual daily intake of the beverage. Soft drinks currently constitute the leading source of added sugars in the diet and exceed the U.S. Department of Agriculture's recommended total sugar consumption for adolescents. With the increase in adolescent obesity and the concurrent increase in consumption of sugar-sweetened beverages (SSB), the assumption infers a relationship between the two variables. SSB, classified as high-glycemic index (GI) liquids, increase postprandial blood glucose levels and decrease insulin sensitivity. Additionally, high-GI drinks submit to a decreased satiety level and subsequent overeating. Low-GI beverages stimulate a delayed return of hunger, thereby prompting an increased flexibility in amounts and frequencies of servings. Single intervention manipulation, elimination, or marked reduction of SSB consumption may serve to decrease caloric intake, increase satiety levels, decrease tendencies towards insulin resistance, and simplify the process of weight management in this population.

  1. Refined energetic ordering for sulphate-water (n = 3-6) clusters using high-level electronic structure calculations

    NASA Astrophysics Data System (ADS)

    Lambrecht, Daniel S.; McCaslin, Laura; Xantheas, Sotiris S.; Epifanovsky, Evgeny; Head-Gordon, Martin

    2012-10-01

    This work reports refinements of the energetic ordering of the known low-energy structures of sulphate-water clusters ? (n = 3-6) using high-level electronic structure methods. Coupled cluster singles and doubles with perturbative triples (CCSD(T)) is used in combination with an estimate of basis set effects up to the complete basis set limit using second-order Møller-Plesset theory. Harmonic zero-point energy (ZPE), included at the B3LYP/6-311 + + G(3df,3pd) level, was found to have a significant effect on the energetic ordering. In fact, we show that the energetic ordering is a result of a delicate balance between the electronic and vibrational energies. Limitations of the ZPE calculations, both due to electronic structure errors, and use of the harmonic approximation, probably constitute the largest remaining errors. Due to the often small energy differences between cluster isomers, and the significant role of ZPE, deuteration can alter the relative energies of low-lying structures, and, when it is applied in conjunction with calculated harmonic ZPEs, even alters the global minimum for n = 5. Experiments on deuterated clusters, as well as more sophisticated vibrational calculations, may therefore be quite interesting.

  2. Arm Coordination and Performance Level in the 400-m Front Crawl

    ERIC Educational Resources Information Center

    Schnitzler, Christophe; Seifert, Ludovic; Chollet, Didier

    2011-01-01

    The purpose of this study was to determine whether the Index of Coordination (IdC) and the propulsive phase durations can differentiate performance level during a maximal 400-m front crawl swim trial. Sixteen male swimmers constituted two groups based on performance level (G1: experts; G2: recreational). All participants swam the 400-m front crawl…

  3. High-temperature viscoelastic creep constitutive equations for polymer composites: Homogenization theory and experiments

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

    Skontorp, A.; Wang, S.S.; Shibuya, Y.

    1994-12-31

    In this paper, a homogenization theory is developed to determine high-temperature effective viscoelastic constitutive equations for fiber-reinforced polymer composites. The homogenization theory approximates the microstructure of a fiber composite, and determine simultaneously effective macroscopic constitutive properties of the composite and the associated microscopic strain and stress in the heterogeneous material. The time-temperature dependent homogenization theory requires that the viscoelastic constituent properties of the matrix phase at elevated temperatures, the governing equations for the composites, and the boundary conditions of the problem be Laplace transformed to a conjugate problem. The homogenized effective properties in the transformed domain are determined, using amore » two-scale asymptotic expansion of field variables and an averaging procedure. Field solutions in the unit cell are determined from basic and first-order governing equations with the aid of a boundary integral method (BIM). Effective viscoelastic constitutive properties of the composite at elevated temperatures are determined by an inverse transformation, as are the microscopic stress and deformation in the composite. Using this method, interactions among fibers and between the fibers and the matrix can be evaluated explicitly, resulting in accurate solutions for composites with high-volume fraction of reinforcing fibers. Examples are given for the case of a carbon-fiber reinforced thermoplastic polyamide composite in an elevated temperature environment. The homogenization predictions are in good agreement with experimental data available for the composite.« less

  4. Fully Associative, Nonisothermal, Potential-Based Unified Viscoplastic Model for Titanium-Based Matrices

    NASA Technical Reports Server (NTRS)

    2005-01-01

    A number of titanium matrix composite (TMC) systems are currently being investigated for high-temperature air frame and propulsion system applications. As a result, numerous computational methodologies for predicting both deformation and life for this class of materials are under development. An integral part of these methodologies is an accurate and computationally efficient constitutive model for the metallic matrix constituent. Furthermore, because these systems are designed to operate at elevated temperatures, the required constitutive models must account for both time-dependent and time-independent deformations. To accomplish this, the NASA Lewis Research Center is employing a recently developed, complete, potential-based framework. This framework, which utilizes internal state variables, was put forth for the derivation of reversible and irreversible constitutive equations. The framework, and consequently the resulting constitutive model, is termed complete because the existence of the total (integrated) form of the Gibbs complementary free energy and complementary dissipation potentials are assumed a priori. The specific forms selected here for both the Gibbs and complementary dissipation potentials result in a fully associative, multiaxial, nonisothermal, unified viscoplastic model with nonlinear kinematic hardening. This model constitutes one of many models in the Generalized Viscoplasticity with Potential Structure (GVIPS) class of inelastic constitutive equations.

  5. Parameter optimization for the visco-hyperelastic constitutive model of tendon using FEM.

    PubMed

    Tang, C Y; Ng, G Y F; Wang, Z W; Tsui, C P; Zhang, G

    2011-01-01

    Numerous constitutive models describing the mechanical properties of tendons have been proposed during the past few decades. However, few were widely used owing to the lack of implementation in the general finite element (FE) software, and very few systematic studies have been done on selecting the most appropriate parameters for these constitutive laws. In this work, the visco-hyperelastic constitutive model of the tendon implemented through the use of three-parameter Mooney-Rivlin form and sixty-four-parameter Prony series were firstly analyzed using ANSYS FE software. Afterwards, an integrated optimization scheme was developed by coupling two optimization toolboxes (OPTs) of ANSYS and MATLAB for estimating these unknown constitutive parameters of the tendon. Finally, a group of Sprague-Dawley rat tendons was used to execute experimental and numerical simulation investigation. The simulated results showed good agreement with the experimental data. An important finding revealed that too many Maxwell elements was not necessary for assuring accuracy of the model, which is often neglected in most open literatures. Thus, all these proved that the constitutive parameter optimization scheme was reliable and highly efficient. Furthermore, the approach can be extended to study other tendons or ligaments, as well as any visco-hyperelastic solid materials.

  6. The distinction between key ideas in teaching school physics and key ideas in the discipline of physics

    NASA Astrophysics Data System (ADS)

    Deng, Zongyi

    2001-05-01

    The distinction between key ideas in teaching a high school science and key ideas in the corresponding discipline of science has been largely ignored in scholarly discourse about what science teachers should teach and about what they should know. This article clarifies this distinction through exploring how and why key ideas in teaching high school physics differ from key ideas in the discipline of physics. Its theoretical underpinnings include Dewey's (1902/1990) distinction between the psychological and the logical and Harré's (1986) epistemology of science. It analyzes how and why the key ideas in teaching color, the speed of light, and light interference at the high school level differ from the key ideas at the disciplinary level. The thesis is that key ideas in teaching high school physics can differ from key ideas in the discipline in some significant ways, and that the differences manifest Dewey's distinction. As a result, the article challenges the assumption of equating key ideas in teaching a high school science with key ideas in the corresponding discipline of science, and the assumption that having a college degree in science is sufficient to teach high school science. Furthermore, the article expands the concept of pedagogical content knowledge by arguing that key ideas in teaching high school physics constitute an essential component.

  7. An internal variable constitutive model for the large deformation of metals at high temperatures

    NASA Technical Reports Server (NTRS)

    Brown, Stuart; Anand, Lallit

    1988-01-01

    The advent of large deformation finite element methodologies is beginning to permit the numerical simulation of hot working processes whose design until recently has been based on prior industrial experience. Proper application of such finite element techniques requires realistic constitutive equations which more accurately model material behavior during hot working. A simple constitutive model for hot working is the single scalar internal variable model for isotropic thermal elastoplasticity proposed by Anand. The model is recalled and the specific scalar functions, for the equivalent plastic strain rate and the evolution equation for the internal variable, presented are slight modifications of those proposed by Anand. The modified functions are better able to represent high temperature material behavior. The monotonic constant true strain rate and strain rate jump compression experiments on a 2 percent silicon iron is briefly described. The model is implemented in the general purpose finite element program ABAQUS.

  8. Study on the surface constitute properties of high-speed end milling aluminum alloy

    NASA Astrophysics Data System (ADS)

    Huang, Xiaoming; Li, Hongwei; Yumeng, Ma

    2017-09-01

    The physical and mechanical properties of the metal surface will change after the metal cutting processing. The comprehensive study of the influence of machining parameters on surface constitute properties are necessary. A high-speed milling experiment by means of orthogonal method with four factors was conducted for aluminum alloy7050-T7451. The surface constitutive properties of the Al-Alloy surface were measured using SSM-B4000TM stress-strain microprobe system. Based on all the load-depth curves obtained, the characteristics parameters such as strain hardening exponent n and yield strength σy of the milling surface are calculated. The effect of cutting speed, feed rate, and width and depth of cut on n and σy was investigated using the ANOVA techniques. The affecting degree of milling parameters on n and σy was v>fz> ap < ae. The influence of milling parameters on n and σ y was described and discussed.

  9. Constitutive activity of the δ-opioid receptor expressed in C6 glioma cells: identification of non-peptide δ-inverse agonists

    PubMed Central

    Neilan, Claire L; Akil, Huda; Woods, James H; Traynor, John R

    1999-01-01

    G-protein coupled receptors can exhibit constitutive activity resulting in the formation of active ternary complexes in the absence of an agonist. In this study we have investigated constitutive activity in C6 glioma cells expressing either the cloned δ-(OP1) receptor (C6δ), or the cloned μ-(OP3) opioid receptor (C6μ).Constitutive activity was measured in the absence of Na+ ions to provide an increased signal. The degree of constitutive activity was defined as the level of [35S]-GTPγS binding that could be inhibited by pre-treatment with pertussis toxin (PTX). In C6δ cells the level of basal [35S]-GTPγS binding was reduced by 51.9±6.1 fmols mg−1 protein, whereas in C6μ and C6 wild-type cells treatment with PTX reduced basal [35S]-GTPγS binding by only 10.0±3.5 and 8.6±3.1 fmols mg−1 protein respectively.The δ-antagonists N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH (ICI 174,864), 7-benzylidenenaltrexone (BNTX) and naltriben (NTB), in addition to clocinnamox (C-CAM), acted as δ-opioid receptor inverse agonists. Naloxone, buprenorphine, and naltrindole were neutral antagonists. Furthermore, naltrindole blocked the reduction in [35S]-GTPγS binding caused by the inverse agonists. The inverse agonists did not inhibit basal [35S]-GTPγS binding in C6μ or C6 wild-type cell membranes.Competition binding assays in C6δ cell membranes revealed a leftward shift in the displacement curve of [3H]-naltrindole by ICI 174,864 and C-CAM in the presence of NaCl and the GTP analogue, GppNHp. There was no change in the displacement curve for BNTX or NTB under these conditions.These data confirm the presence of constitutive activity associated with the δ-opioid receptor and identify three novel, non-peptide, δ-opioid inverse agonists. PMID:10516632

  10. Existence of three subtypes of bradykinin B2 receptors in guinea pig.

    PubMed

    Seguin, L; Widdowson, P S; Giesen-Crouse, E

    1992-12-01

    We describe the binding of [3H]bradykinin to homogenates of guinea pig brain, lung, and ileum. Analysis of [3H]bradykinin binding kinetics in guinea pig brain, lung, and ileum suggests the existence of two binding sites in each tissue. The finding of two binding sites for [3H]bradykinin in ileum, lung, and brain was further supported by Scatchard analysis of equilibrium binding in each tissue. [3H]Bradykinin binds to a high-affinity site in brain, lung, and ileum (KD = 70-200 pM), which constitutes approximately 20% of the bradykinin binding, and to a second, lower-affinity site (0.63-0.95 nM), which constitutes the remaining 80% of binding. Displacement studies with various bradykinin analogues led us to subdivide the high- and lower-affinity sites in each tissue and to suggest the existence of three subtypes of B2 receptors in the guinea pig, which we classify as B2a, B2b, and B2c. Binding of [3H]bradykinin is largely to a B2b receptor subtype, which constitutes the majority of binding in brain, lung, and ileum and represents the lower-affinity site in our binding studies. Receptor subtype B2c constitutes approximately 20% of binding sites in the brain and lung and is equivalent to the high-affinity site in brain and lung. We suggest that a third subtype of B2 receptor (high-affinity site in ileum), B2a, is found only in the ileum. All three subtypes of B2 receptors display a high affinity for bradykinin, whereas they show different affinities for various bradykinin analogues displaying agonist or antagonist activities.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. Investigating the Influence Relationship Models for Stocks in Indian Equity Market: A Weighted Network Modelling Study

    PubMed Central

    Acharjee, Animesh

    2016-01-01

    The socio-economic systems today possess high levels of both interconnectedness and interdependencies, and such system-level relationships behave very dynamically. In such situations, it is all around perceived that influence is a perplexing power that has an overseeing part in affecting the dynamics and behaviours of involved ones. As a result of the force & direction of influence, the transformative change of one entity has a cogent aftereffect on the other entities in the system. The current study employs directed weighted networks for investigating the influential relationship patterns existent in a typical equity market as an outcome of inter-stock interactions happening at the market level, the sectorial level and the industrial level. The study dataset is derived from 335 constituent stocks of ‘Standard & Poor Bombay Stock Exchange 500 index’ and study period is 1st June 2005 to 30th June 2015. The study identifies the set of most dynamically influential stocks & their respective temporal pattern at three hierarchical levels: the complete equity market, different sectors, and constituting industry segments of those sectors. A detailed influence relationship analysis is performed for the sectorial level network of the construction sector, and it was found that stocks belonging to the cement industry possessed high influence within this sector. Also, the detailed network analysis of construction sector revealed that it follows scale-free characteristics and power law distribution. In the industry specific influence relationship analysis for cement industry, methods based on threshold filtering and minimum spanning tree were employed to derive a set of sub-graphs having temporally stable high-correlation structure over this ten years period. PMID:27846251

  12. Investigating the Influence Relationship Models for Stocks in Indian Equity Market: A Weighted Network Modelling Study.

    PubMed

    Bhattacharjee, Biplab; Shafi, Muhammad; Acharjee, Animesh

    2016-01-01

    The socio-economic systems today possess high levels of both interconnectedness and interdependencies, and such system-level relationships behave very dynamically. In such situations, it is all around perceived that influence is a perplexing power that has an overseeing part in affecting the dynamics and behaviours of involved ones. As a result of the force & direction of influence, the transformative change of one entity has a cogent aftereffect on the other entities in the system. The current study employs directed weighted networks for investigating the influential relationship patterns existent in a typical equity market as an outcome of inter-stock interactions happening at the market level, the sectorial level and the industrial level. The study dataset is derived from 335 constituent stocks of 'Standard & Poor Bombay Stock Exchange 500 index' and study period is 1st June 2005 to 30th June 2015. The study identifies the set of most dynamically influential stocks & their respective temporal pattern at three hierarchical levels: the complete equity market, different sectors, and constituting industry segments of those sectors. A detailed influence relationship analysis is performed for the sectorial level network of the construction sector, and it was found that stocks belonging to the cement industry possessed high influence within this sector. Also, the detailed network analysis of construction sector revealed that it follows scale-free characteristics and power law distribution. In the industry specific influence relationship analysis for cement industry, methods based on threshold filtering and minimum spanning tree were employed to derive a set of sub-graphs having temporally stable high-correlation structure over this ten years period.

  13. Stable Overexpression of the Constitutive Androstane Receptor Reduces the Requirement for Culture with Dimethyl Sulfoxide for High Drug Metabolism in HepaRG Cells.

    PubMed

    van der Mark, Vincent A; Rudi de Waart, D; Shevchenko, Valery; Elferink, Ronald P J Oude; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

    2017-01-01

    Dimethylsulfoxide (DMSO) induces cellular differentiation and expression of drug metabolic enzymes in the human liver cell line HepaRG; however, DMSO also induces cell death and interferes with cellular activities. The aim of this study was to examine whether overexpression of the constitutive androstane receptor (CAR, NR1I3), the nuclear receptor controlling various drug metabolism genes, would sufficiently promote differentiation and drug metabolism in HepaRG cells, optionally without using DMSO. By stable lentiviral overexpression of CAR, HepaRG cultures were less affected by DMSO in total protein content and obtained increased resistance to acetaminophen- and amiodarone-induced cell death. Transcript levels of CAR target genes were significantly increased in HepaRG-CAR cultures without DMSO, resulting in increased activities of cytochrome P450 (P450) enzymes and bilirubin conjugation to levels equal or surpassing those of HepaRG cells cultured with DMSO. Unexpectedly, CAR overexpression also increased the activities of non-CAR target P450s, as well as albumin production. In combination with DMSO treatment, CAR overexpression further increased transcript levels and activities of CAR targets. Induction of CYP1A2 and CYP2B6 remained unchanged, whereas CYP3A4 was reduced. Moreover, the metabolism of low-clearance compounds warfarin and prednisolone was increased. In conclusion, CAR overexpression creates a more physiologically relevant environment for studies on hepatic (drug) metabolism and differentiation in HepaRG cells without the utilization of DMSO. DMSO still may be applied to accomplish higher drug metabolism, required for sensitive assays, such as low-clearance studies and identification of (rare) metabolites, whereas reduced total protein content after DMSO culture is diminished by CAR overexpression. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  14. Peripheral muscle alterations in non-COPD smokers.

    PubMed

    Montes de Oca, Maria; Loeb, Eduardo; Torres, Sonia H; De Sanctis, Juan; Hernández, Noelina; Tálamo, Carlos

    2008-01-01

    Although tobacco smoke is the main cause of COPD, relatively little attention has been paid to its potential damage to skeletal muscle. This article addresses the effect of smoking on skeletal muscle. The vastus lateralis muscle was studied in 14 non-COPD smokers (FEV(1)/FVC, 78 +/- 5%) and 20 healthy control subjects (FEV(1)/FVC, 80 +/- 3%). Muscular structure, enzyme activity, constitutive and inducible nitric oxide (NO) synthases (endothelial NO oxide synthase [eNOS], neuronal NO synthase [nNOS] and inducible NO synthase [iNOS]), nitrites, nitrates, nitrotyrosine, and the presence of macrophages were analyzed. In smokers, type I muscle fibers cross-sectional area was decreased, and a similar trend was found in type IIa fibers. Lactate dehydrogenase levels and the percentage of fibers with low oxidative and high glycolytic capacity were increased in smokers. nNOS (96.9 +/- 11.7 vs 125.4 +/- 31.9 ng/mg protein; p < 0.01) and eNOS (38.9 +/- 11.0 vs 45.2 +/- 7.7 ng/mg protein [+/- SD]; p < 0.05) were lower in smokers, while fiber type distribution, capillarity measures, beta-hydroxy-acyl-CoA-dehydrogenase levels, iNOS, nitrite, nitrate, and nitrotyrosine levels, and macrophage number in the muscle tissue were similar to the nonsmoker subjects. Smokers presented some alterations of skeletal muscle such as oxidative fiber atrophy, increased glycolytic capacity, and reduced expression of the constitutive NO synthases (eNOS and nNOS). The findings support some muscular structural and metabolic damage but not the presence of local inflammation in the smokers. In addition, they suggest a possible effect of tobacco smoke impairing the normal process of NO generation.

  15. Quantitative proteomic analysis reveals effects of epidermal growth factor receptor (EGFR) on invasion-promoting proteins secreted by glioblastoma cells.

    PubMed

    Sangar, Vineet; Funk, Cory C; Kusebauch, Ulrike; Campbell, David S; Moritz, Robert L; Price, Nathan D

    2014-10-01

    Glioblastoma multiforme is a highly invasive and aggressive brain tumor with an invariably poor prognosis. The overexpression of epidermal growth factor receptor (EGFR) is a primary influencer of invasion and proliferation in tumor cells and the constitutively active EGFRvIII mutant, found in 30-65% of Glioblastoma multiforme, confers more aggressive invasion. To better understand how EGFR contributes to tumor aggressiveness, we investigated the effect of EGFR on the secreted levels of 65 rationally selected proteins involved in invasion. We employed selected reaction monitoring targeted mass spectrometry using stable isotope labeled internal peptide standards to quantity proteins in the secretome from five GBM (U87) isogenic cell lines in which EGFR, EGFRvIII, and/or PTEN were expressed. Our results show that cell lines with EGFR overexpression and constitutive EGFRvIII expression differ remarkably in the expression profiles for both secreted and intracellular signaling proteins, and alterations in EGFR signaling result in reproducible changes in concentrations of secreted proteins. Furthermore, the EGFRvIII-expressing mutant cell line secretes the majority of the selected invasion-promoting proteins at higher levels than other cell lines tested. Additionally, the intracellular and extracellular protein measurements indicate elevated oxidative stress in the EGFRvIII-expressing cell line. In conclusion, the results of our study demonstrate that EGFR signaling has a significant effect on the levels of secreted invasion-promoting proteins, likely contributing to the aggressiveness of Glioblastoma multiforme. Further characterization of these proteins may provide candidates for new therapeutic strategies and targets as well as biomarkers for this aggressive disease. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Constitutive androstane receptor upregulates Abcb1 and Abcg2 at the blood-brain barrier after CITCO activation.

    PubMed

    Lemmen, Julia; Tozakidis, Iasson E P; Bele, Prachee; Galla, Hans-Joachim

    2013-03-21

    ATP-driven efflux transporters are considered to be the major hurdle in the treatment of central nervous system (CNS) diseases. Abcb1 (P-glycoprotein) and Abcg2 (breast cancer resistance protein/brain multidrug resistance protein) belong to the best known ABC-transporters. These ABC-transporters limit the permeability of the blood-brain barrier and protect the brain against toxic compounds in the blood but on the other hand they also reduce the efficacy of CNS pharmacotherapy. Even after 40 years of extensive research, the regulatory mechanisms of these efflux transporters are still not completely understood. To unravel the efflux transporter regulation, we analyzed the effect of the nuclear receptor CAR (constitutive androstane receptor) on the expression of Abcb1 and Abcg2 in primary cultures of porcine brain capillary endothelial cells (PBCEC). CAR is a xenobiotic-activated transcription factor, which is, like the other important nuclear receptor pregnane X receptor (PXR), highly expressed in barrier tissue and known to be a positive regulator of ABC-transporters. We demonstrate that activation of porcine CAR by the human CAR (hCAR) ligand CITCO (6-(4-chlorophenyl)-imidazo[2,1-b]thiazole-5-carbaldehyde) leads to an up-regulation of both transporters, whereas the mouse-specific CAR ligand TCPOBOP (1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene) had no effect on transporter expression. The stimulation of PBCEC with CITCO caused a significant up-regulation of both efflux-transporters on RNA-level, protein level and transport level. Furthermore the additional application of a CAR inhibitor significantly decreased the transporter expression to control niveau. In conclusion our data prove CAR activation only by the human ligand CITCO leading to an increased ABC-transporter expression and transport activity. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Multi-scale Modeling of Plasticity in Tantalum.

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

    Lim, Hojun; Battaile, Corbett Chandler.; Carroll, Jay

    In this report, we present a multi-scale computational model to simulate plastic deformation of tantalum and validating experiments. In atomistic/ dislocation level, dislocation kink- pair theory is used to formulate temperature and strain rate dependent constitutive equations. The kink-pair theory is calibrated to available data from single crystal experiments to produce accurate and convenient constitutive laws. The model is then implemented into a BCC crystal plasticity finite element method (CP-FEM) model to predict temperature and strain rate dependent yield stresses of single and polycrystalline tantalum and compared with existing experimental data from the literature. Furthermore, classical continuum constitutive models describingmore » temperature and strain rate dependent flow behaviors are fit to the yield stresses obtained from the CP-FEM polycrystal predictions. The model is then used to conduct hydro- dynamic simulations of Taylor cylinder impact test and compared with experiments. In order to validate the proposed tantalum CP-FEM model with experiments, we introduce a method for quantitative comparison of CP-FEM models with various experimental techniques. To mitigate the effects of unknown subsurface microstructure, tantalum tensile specimens with a pseudo-two-dimensional grain structure and grain sizes on the order of millimeters are used. A technique combining an electron back scatter diffraction (EBSD) and high resolution digital image correlation (HR-DIC) is used to measure the texture and sub-grain strain fields upon uniaxial tensile loading at various applied strains. Deformed specimens are also analyzed with optical profilometry measurements to obtain out-of- plane strain fields. These high resolution measurements are directly compared with large-scale CP-FEM predictions. This computational method directly links fundamental dislocation physics to plastic deformations in the grain-scale and to the engineering-scale applications. Furthermore, direct and quantitative comparisons between experimental measurements and simulation show that the proposed model accurately captures plasticity in deformation of polycrystalline tantalum.« less

  18. Analysing teachers' operations when teaching students: what constitutes scientific theories?

    NASA Astrophysics Data System (ADS)

    Holmqvist, Mona O.; Olander, Clas

    2017-05-01

    The aim of the study is to analyse teachers' efforts to develop secondary school students' knowledge and argumentation skills of what constitutes scientific theories. The analysis is based on Leontiev's three-level structure of activity (activity, action, and operation), as these levels correspond to the questions why, what, and how content is taught. The unit of analysis was a school development project in science education, where design-based interventions were conducted. Data comprised notes and minutes from eight meetings, plans, and video recordings of the lessons, and a written teacher evaluation. The teachers' (n = 7) learning actions were analysed to identify (a) concept formation in science education, (b) expressions of agency, (c) discursive manifestations of contradictions, and (d) patterns of interaction during the science interventions. Three lessons on what constitutes scientific theories were implemented in three different student groups (n = 24, 23, 24), framed by planning and evaluation meetings for each lesson. The results describe (1) the ways in which teachers became more skilled at ensuring instruction met their students' needs and (2) the ways in which teachers' operations during instruction changed as a result of their developed knowledge of how to express the content based on theoretical assumptions.

  19. Functional reconstitution of an ATP-driven Ca sup 2+ -transport system from the plasma membrane of Commelina communis L

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

    Graef, P.; Weiler, E.W.

    1990-10-01

    The protein(s) that constitute(s) the ATP-driven Ca{sup 2+}-translocator of plasma membrane enriched vesicles obtained by aqueous two-phase partitioning from leaves of Commelina communis L. has/have been solubilized and reincorporated into tightly sealed liposomes. The reconstituted Ca{sup 2+}-transport system was studied using ATP-driven {sup 45}Ca{sup 2+} import into the proteoliposomes as a measure of activity. The detergent, 3- ((3-cholamidopropyl) dimethylammonio) -1-propane-sulfonate proved to be the most suitable and was used at 10 millimolar concentration, i.e. just above its critical micellar concentration. The presence of additional phospholipid and ATP improved the solubilization and/or reconstitution. The characteristics of the reconstituted system were similarmore » to those of the plasma membrane-bound activity, including the apparent K{sub m} for Ca{sup 2+} inhibition by relatively high levels of vanadate and lacking response to added calmodulin. The reconstituted transport system was very strongly inhibited by erythrosine B and had a low apparent K{sub m} for ATP levels of the Ca{sup 2+}-ionophore A 23187 instantaneously discharged 90% of the Ca{sup 2+} associated with the vesicles, proving that it had been accumulated in the intravesicular volume in soluble, freely exchangeable form. Ca{sup 2+}-transport in the reconstituted system was thus primary active, through a Ca{sup 2+}-translocating ATPase.« less

  20. Differential exposure and differential vulnerability as counteracting forces linking the psychosocial work environment to socioeconomic health differences.

    PubMed

    Vanroelen, C; Levecque, K; Louckx, F

    2010-10-01

    In this article, the link between (1) psychosocial working conditions (job demands, job autonomy, task variation, social support), (2) self-reported health (persistent fatigue, musculoskeletal complaints, emotional well-being) and (3) socioeconomic position (skill levels, occupational status) is explored. The two theoretical pathways linking the psychosocial work environment to socioeconomic differences in health are explored: differential exposure and differential vulnerability. Previously, the focus has often been on social inequalities in exposure to the stressors. The pathway of differential vulnerability in different socioeconomic positions is often neglected. In a representative cross-sectional sample of 11,099 Flemish (Belgian) wage earners, 16-65 years of age (47.5% women), logit modelling is applied. Higher exposure to psychosocial occupational stressors is associated with a higher prevalence of adverse health outcomes. Lower skill levels and subordinate occupational positions show a higher prevalence of musculoskeletal complaints, but not of persistent fatigue or emotional well-being. High demands, job strain and iso-strain are more common in higher-skilled, supervisory and managerial positions, but have the strongest health-damaging effects in lower socioeconomic positions. Low control is more prevalent in lower-skilled and subordinate positions, while having stronger adverse health effects in higher socioeconomic positions-the same holds for social support, although it has no clear socioeconomic distribution. Differential exposure and differential vulnerability constitute two counteracting forces in constituting the association between the psychosocial work environment and socioeconomic differences in self-reported health complaints among wage earners.

  1. Functional Characterization of a Strong Bi-directional Constitutive Plant Promoter Isolated from Cotton Leaf Curl Burewala Virus

    PubMed Central

    Khan, Zainul A.; Abdin, Malik Z.; Khan, Jawaid A.

    2015-01-01

    Cotton leaf curl Burewala virus (CLCuBuV), belonging to the genus Begomovirus, possesses single-stranded monopartite DNA genome. The bidirectional promoters representing Rep and coat protein (CP) genes of CLCuBuV were characterized and their efficacy was assayed. Rep and CP promoters of CLCuBuV and 35S promoter of Cauliflower mosaic virus (CaMV) were fused with β-glucuronidase (GUS) and green fluorescent protein (GFP) reporter genes. GUS activity in individual plant cells driven by Rep, CP and 35S promoters was estimated using real-time PCR and fluorometric GUS assay. Histochemical staining of GUS in transformed tobacco (Nicotiana tabacum cv. Xanthi) leaves showed highest expression driven by Rep promoter followed by 35S promoter and CP promoter. The expression level of GUS driven by Rep promoter in transformed tobacco plants was shown to be two to four-fold higher than that of 35S promoter, while the expression by CP promoter was slightly lower. Further, the expression of GFP was monitored in agroinfiltrated leaves of N. benthamiana, N. tabacum and cotton (Gossypium hirsutum) plants using confocal laser scanning microscopy. Rep promoter showed strong consistent transient expression in tobacco and cotton leaves as compared to 35S promoter. The strong constitutive CLCuBuV Rep promoter developed in this study could be very useful for high level expression of transgenes in a wide variety of plant cells. PMID:25799504

  2. Functional characterization of a strong bi-directional constitutive plant promoter isolated from cotton leaf curl Burewala virus.

    PubMed

    Khan, Zainul A; Abdin, Malik Z; Khan, Jawaid A

    2015-01-01

    Cotton leaf curl Burewala virus (CLCuBuV), belonging to the genus Begomovirus, possesses single-stranded monopartite DNA genome. The bidirectional promoters representing Rep and coat protein (CP) genes of CLCuBuV were characterized and their efficacy was assayed. Rep and CP promoters of CLCuBuV and 35S promoter of Cauliflower mosaic virus (CaMV) were fused with β-glucuronidase (GUS) and green fluorescent protein (GFP) reporter genes. GUS activity in individual plant cells driven by Rep, CP and 35S promoters was estimated using real-time PCR and fluorometric GUS assay. Histochemical staining of GUS in transformed tobacco (Nicotiana tabacum cv. Xanthi) leaves showed highest expression driven by Rep promoter followed by 35S promoter and CP promoter. The expression level of GUS driven by Rep promoter in transformed tobacco plants was shown to be two to four-fold higher than that of 35S promoter, while the expression by CP promoter was slightly lower. Further, the expression of GFP was monitored in agroinfiltrated leaves of N. benthamiana, N. tabacum and cotton (Gossypium hirsutum) plants using confocal laser scanning microscopy. Rep promoter showed strong consistent transient expression in tobacco and cotton leaves as compared to 35S promoter. The strong constitutive CLCuBuV Rep promoter developed in this study could be very useful for high level expression of transgenes in a wide variety of plant cells.

  3. Syndecan-1 alterations during the tumorigenic progression of human colonic Caco-2 cells induced by human Ha-ras or polyoma middle T oncogenes.

    PubMed Central

    Levy, P.; Munier, A.; Baron-Delage, S.; Di Gioia, Y.; Gespach, C.; Capeau, J.; Cherqui, G.

    1996-01-01

    The products of ras and src proto-oncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study we attempted to establish whether the tumorigenic progression induced by oncogenic activation of p21ras and pp60c-src in human colonic Caco-2 cells is associated with specific alterations of syndecan-1, a membrane-anchored proteoglycan playing a role in cell-matrix interaction and neoplastic growth control. To this end, we used Caco-2 cells made highly tumorigenic by transfection with an activated (Val 12) human Ha-ras gene or with the polyoma middle T (Py-MT) oncogene, a constitutive activator of pp60c-src tyrosine kinase activity. Compared with control vector-transfected Caco-2 cells, both oncogene-transfected cell lines (1) contained smaller amounts of membrane-anchored PGs; (2) exhibited decreased syndecan-1 expression at the protein but not the mRNA level; (3) synthesized 35S-labelled syndecan-1 with decreased specific activity; (4) produced a syndecan-1 ectodomain with a lower molecular mass and reduced GAG chain size and sulphation; and (5) expressed heparanase degradative activity. These results show that the dramatic activation of the tumorigenic potential induced by oncogenic p21ras or Py-MT/pp60c-src in Caco-2 cells is associated with marked alterations of syndecan-1 expression at the translational and post-translational levels. Images Figure 2 PMID:8695359

  4. Arsenic concentration in water and bovine milk in Cordoba, Argentina. Preliminary results.

    PubMed

    Pérez-Carrera, Alejo; Fernández-Cirelli, Alicia

    2005-02-01

    The Chaco Pampean Plain of central Argentina constitutes one of the largest regions of high arsenic (As) groundwaters known, covering around 1 x 10(6) km2 (Smedley & Kinniburg, 2002; Farías et al. 2004). The high-As groundwaters are from Quaternary deposits of loess (mainly silt) with intermixed rhyolitic or dacitic volcanic ash (Nicolli et al. 1989, Smedley et al. 1998,2002). Early in the last century an endemic disease due to contamination of drinking water with arsenic was recognised. This disease is called HACRE (Hidroarsenicismo Crónico Regional Endémico, Chronic Endemic Regional Hydroarsenism) and is connected with a particular type of skin cancer (Astolfi et al. 1981). One of the most affected region is the province of Cordoba, where Nicolli et al. (1989) reported As concentrations that exceed the maximun level permitted for drinking water of 50 microg/l for 82% of the groundwater samples (n=60) of a study area comprising approximately 10000 km2. The southeast of Cordoba is an important milk production zone in Argentina, where dairy product consumption is up to 192 equivalent milk l/inhabitant/year. As a secretion of the mammary gland, milk can carry numerous xenobiotic substances, which constitute a technological risk factor for dairy products and above all for the health of the consumer (Licata et al. 2004). Nevertheless no studies on the incidence of high-As livestock drinking water in livestock health and its transfer to milk have been performed in Argentina. The aim of the present study was the determination of arsenic content in livestock drinking water and milk from dairy farms located in an area of high-As groundwaters, to analyse the relation between As uptake through water and its transfer to milk.

  5. Constitutive Modeling of the Thermomechanical Behavior of Rock Salt

    NASA Astrophysics Data System (ADS)

    Hampel, A.

    2016-12-01

    For the safe disposal of heat-generating high-level radioactive waste in rock salt formations, highly reliable numerical simulations of the thermomechanical and hydraulic behavior of the host rock have to be performed. Today, the huge progress in computer technology has enabled experts to calculate large and detailed computer models of underground repositories. However, the big ad­van­ces in computer technology are only beneficial when the applied material models and modeling procedures also meet very high demands. They result from the fact that the evaluation of the long-term integrity of the geological barrier requires an extra­polation of a highly nonlinear deforma­tion behavior to up to 1 million years, while the underlying experimental investigations in the laboratory or in situ have a duration of only days, weeks or at most some years. Several advanced constitutive models were developed and continuously improved to describe the dependences of various deformation phenomena in rock salt on in-situ relevant boundary conditions: transient and steady-state creep, evolution of damage and dilatancy in the DRZ, failure, post-failure behavior, residual strength, damage and dilatancy reduction, and healing. In a joint project series between 2004 and 2016, fundamental features of the advanced models were investigated and compared in detail with benchmark calculations. The study included procedures for the determination of characteristic salt-type-specific model parameter values and for the performance of numerical calculations of underground structures. Based on the results of this work and on specific laboratory investigations, the rock mechanical modeling is currently developed further in a common research project of experts from Germany and the United States. In this presentation, an overview about the work and results of the project series is given and the current joint research project WEIMOS is introduced.

  6. Transplastomic expression of bacterial L-aspartate-alpha-decarboxylase enhances photosynthesis and biomass production in response to high temperature stress.

    PubMed

    Fouad, W M; Altpeter, F

    2009-10-01

    Metabolic engineering for beta-alanine over-production in plants is expected to enhance environmental stress tolerance. The Escherichia coli L-aspartate-alpha-decarboxylase (AspDC) encoded by the panD gene, catalyzes the decarboxylation of L-aspartate to generate beta-alanine and carbon dioxide. The constitutive E. coli panD expression cassette was co-introduced with the constitutive, selectable aadA expression cassette into the chloroplast genome of tobacco via biolistic gene transfer and homologous recombination. Site specific integration of the E. coli panD expression cassette into the chloroplast genome and generation of homotransplastomic plants were confirmed by PCR and Southern blot analysis, respectively, following plant regeneration and germination of seedlings on selective media. PanD expression was verified by assays based on transcript detection and in vitro enzyme activity. The AspDC activities in transplastomic plants expressing panD were drastically increased by high-temperature stress. beta-Alanine accumulated in transplastomic plants at levels four times higher than in wildtype plants. Analysis of chlorophyll fluorescence on plants subjected to severe heat stress at 45 degrees C under light verified that photosystem II (PSII) in transgenic plants had higher thermotolerance than in wildtype plants. The CO(2) assimilation of transplastomic plants expressing panD was more tolerant to high temperature stress than that of wildtype plants, resulting in the production of 30-40% more above ground biomass than wildtype control. The results presented indicate that chloroplast engineering of the beta-alanine pathway by over-expression of the E. coli panD enhances thermotolerance of photosynthesis and biomass production following high temperature stress.

  7. Cell survival under nutrient stress is dependent on metabolic conditions regulated by Akt and not by autophagic vacuoles.

    PubMed

    Bruno, P; Calastretti, A; Priulla, M; Asnaghi, L; Scarlatti, F; Nicolin, A; Canti, G

    2007-10-01

    Akt activation assists tumor cell survival and promotes resistance to chemotherapy. Here we show that constitutively active Akt (CA-Akt) cells are highly sensitized to cell death induced by nutrient and growth factor deprivation, whereas dominant-negative Akt (DN-Akt) cells have a high rate of survival. The content of autophagosomes in starved CA-Akt cells was high, while DN-Akt cells expressed autophagic vacuoles constitutively, independently of nutrition conditions. Thus Akt down-regulation and downstream events can induce autophagosomes which were not directly determinants of cell death. Biochemical analysis in Akt-mutated cells show that (i) Akt and mTOR proteins were degraded more rapidly than the housekeeping proteins, (ii) mTOR phosphorylation at position Thr(2446) was relatively high in DN-Akt and low in CA-Akt cells, induced by starvation in mock cells only, which suggests reduced autoregulation of these pathways in Akt-mutated cells, (iii) both protein synthesis and protein degradation were significantly higher in starved CA-Akt cells than in starved DN-Akt cells or mock cells. In conclusion, constitutively active Akt, unable to control synthesis and wasting of proteins, accelerates the death of starved cells.

  8. DUOX enzyme activity promotes AKT signalling in prostate cancer cells.

    PubMed

    Pettigrew, Christopher A; Clerkin, John S; Cotter, Thomas G

    2012-12-01

    Reactive oxygen species (ROS) and oxidative stress are related to tumour progression, and high levels of ROS have been observed in prostate tumours compared to normal prostate. ROS can positively influence AKT signalling and thereby promote cell survival. The aim of this project was to establish whether the ROS generated in prostate cancer cells positively regulate AKT signalling and enable resistance to apoptotic stimuli. In PC3 cells, dual oxidase (DUOX) enzymes actively generate ROS, which inactivate phosphatases, thereby maintaining AKT phosphorylation. Inhibition of DUOX by diphenylene iodium (DPI), intracellular calcium chelation and small-interfering RNA (siRNA) resulted in lower ROS levels, lower AKT and glycogen synthase kinase 3β (GSK3β) phosphorylation, as well as reduced cell viability and increased susceptibility to apoptosis stimulating fragment (FAS) induced apoptosis. This report shows that ROS levels in PC3 cells are constitutively maintained by DUOX enzymes, and these ROS positively regulate AKT signalling through inactivating phosphatases, leading to increased resistance to apoptosis.

  9. Intracellular calcium levels determine differential modulation of allosteric interactions within G protein-coupled receptor heteromers.

    PubMed

    Navarro, Gemma; Aguinaga, David; Moreno, Estefania; Hradsky, Johannes; Reddy, Pasham P; Cortés, Antoni; Mallol, Josefa; Casadó, Vicent; Mikhaylova, Marina; Kreutz, Michael R; Lluís, Carme; Canela, Enric I; McCormick, Peter J; Ferré, Sergi

    2014-11-20

    The pharmacological significance of the adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromer is well established and it is being considered as an important target for the treatment of Parkinson’s disease and other neuropsychiatric disorders. However, the physiological factors that control its distinctive biochemical properties are still unknown. We demonstrate that different intracellular Ca2+ levels exert a differential modulation of A2AR-D2R heteromer-mediated adenylyl-cyclase and MAPK signaling in striatal cells. This depends on the ability of low and high Ca2+ levels to promote a selective interaction of the heteromer with the neuronal Ca2+-binding proteins NCS-1 and calneuron-1, respectively. These Ca2+-binding proteins differentially modulate allosteric interactions within the A2AR-D2R heteromer, which constitutes a unique cellular device that integrates extracellular (adenosine and dopamine) and intracellular (Ca+2) signals to produce a specific functional response.

  10. Reducing DNA context dependence in bacterial promoters

    PubMed Central

    Carr, Swati B.; Densmore, Douglas M.

    2017-01-01

    Variation in the DNA sequence upstream of bacterial promoters is known to affect the expression levels of the products they regulate, sometimes dramatically. While neutral synthetic insulator sequences have been found to buffer promoters from upstream DNA context, there are no established methods for designing effective insulator sequences with predictable effects on expression levels. We address this problem with Degenerate Insulation Screening (DIS), a novel method based on a randomized 36-nucleotide insulator library and a simple, high-throughput, flow-cytometry-based screen that randomly samples from a library of 436 potential insulated promoters. The results of this screen can then be compared against a reference uninsulated device to select a set of insulated promoters providing a precise level of expression. We verify this method by insulating the constitutive, inducible, and repressible promotors of a four transcriptional-unit inverter (NOT-gate) circuit, finding both that order dependence is largely eliminated by insulation and that circuit performance is also significantly improved, with a 5.8-fold mean improvement in on/off ratio. PMID:28422998

  11. Psychological stress is associated with altered levels of myeloid-derived suppressor cells in breast cancer patients.

    PubMed

    Mundy-Bosse, Bethany L; Thornton, Lisa M; Yang, Hae-Chung; Andersen, Barbara L; Carson, William E

    2011-01-01

    Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stages II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 μg/dl vs. 9.74 μg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/ml vs. 97.16 pg/ml; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, vs. 27.3% in patients with low IES scores. Additional analyzes of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = 0.064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Psychological Stress is Associated with Altered Levels of Myeloid-Derived Suppressor cells in Breast Cancer Patients

    PubMed Central

    Mundy-Bosse, Bethany L.; Thornton, Lisa M.; Yang, Hae-Chung; Andersen, Barbara L.; Carson, William E.

    2011-01-01

    Our group has shown in a randomized clinical trial that psychological intervention to reduce stress in patients with stage II and III breast cancer led to enhanced immune function, fewer recurrences and improved overall survival. We hypothesized that patients with high levels of stress would have alterations in myeloid-derived suppressor cells (MDSC) compared to patients with lower stress. PBMC from 16 patients with high stress (n = 8) or with low stress (n = 8) after surgery as measured by the Impact of Event Scale (IES) questionnaire were evaluated for the presence of MDSC. Patients with higher IES scores had significantly elevated salivary cortisol levels (P = 0.013; 13 µg/dl vs. 9.74 µg/dl). Levels of IL-1Rα were also significantly elevated in the higher IES group (45.09 pg/mL vs. 97.16 pg/mL; P = 0.010). IP 10, G-CSF, and IL-6 were all higher in the high stress group although not to a significant degree. Flow cytometric analysis for CD33+/HLA-DR-neg/CD15+/CD11b+ MDSC revealed increased MDSC in patients with lower IES scores (P = 0.009). CD11b+/CD15+ cells constituted 9.4% of the CD33+/HLA DR-neg cell population in patients with high IES, versus 27.3% in patients with low IES scores. Additional analyses of the number of stressful events that affected the patients in addition to their cancer diagnosis revealed that this type of stress measure correlated with elevated levels of MDSC (P = .064). These data indicate the existence of a complex relationship between stress and immune function in breast cancer patients. PMID:21600570

  13. The determination of the constitutive parameters of a medium with application to a reinforced concrete pad

    NASA Technical Reports Server (NTRS)

    Poggio, A. J.; Burke, G. L.; Pennock, S. T.

    1995-01-01

    This report describes the experimental and analytical efforts performed to determine the constitutive parameters of a reinforced concrete pad on which an aircraft (the NASA Boeing 757) was parked while its internal electromagnetic environment was measured. This concrete pad is part of the Large Electromagnetic System-Level Illuminator (LESLI) test facility at the Phillips Laboratory, Kirtland Air Force Base, New Mexico. The relative dielectric constant, conductivity, index of refraction, and reflection coefficient have been determined over the frequency range of 0 to 300 MHz and are presented.

  14. N-acetyltransferase 2 activity and folate levels

    PubMed Central

    Cao, Wen; Strnatka, Diana; McQueen, Charlene A.; Hunter, Robert J.; Erickson, Robert P.

    2010-01-01

    Aims To determine whether increased N-acetyltransferase (NAT) activity might have a toxic effect during development and an influence on folate levels since previous work has shown that only low levels of exogenous NAT can be achieved in constitutionally transgenic mice (Cao, et al, 2005) Main Methods A human NAT1 tet-inducible construct was used that would not be expressed until the inducer was delivered. Human NAT1 cDNA was cloned into pTRE2 and injected into mouse oocytes. Two transgenic lines were crossed to mouse line TgN(rtTahCMV)4Uh containing the CMV promoted “teton.”Measurements of red blood cell folate levels in inbred strains of mice were performed. Key findings Only low levels of human NAT1 could be achieved in kidney (highly responsive in other studies) whether the inducer, doxycycline, was given by gavage or in drinking water.An inverse correlation of folate levels with Nat2 enzyme activity was found. Significance Since increasing NAT1 activity decrease folate in at least one tissue, the detrimental effect of expression of human NAT1 in combination with endogenous mouse Nat2 may be a consequence of increased catabolism of folate. PMID:19932120

  15. Passive control of rotorcraft high-speed impulsive noise

    NASA Astrophysics Data System (ADS)

    Szulc, O.; Doerffer, P.; Tejero, F.

    2016-10-01

    A strong, normal shock wave, terminating a local supersonic area located at the tip of a helicopter blade, not only limits the aerodynamic performance, but also constitutes an origin of the High-Speed Impulsive (HSI) noise. The application of a passive control device (a shallow cavity covered by a perforated plate) just beneath the interaction region weakens the compression level, thus reducing the main source of the HSI noise. The numerical investigation based on the URANS approach and Bohning/Doerffer (BD) transpiration law (SPARC code) confirms a large potential of the new method. Two exemplary implementations, adapted to model helicopter rotors tested at NASA Ames facility in transonic conditions: Caradonna-Tung (lifting, transonic hover) and Caradonna-Laub-Tung (non-lifting, high-speed forward flight), demonstrate the possible gains in terms of the reduction of acoustic pressure fluctuations in the near-field of the blade tip. The CFD results are validated against the experimental data obtained for the reference configurations (no control), while the analysis of the passive control arrangement is based on a purely numerical research. The normal shock wave is effectively eliminated by the wall ventilation exerting a positive impact on the generated level of the HSI noise.

  16. High level production of β-galactosidase exhibiting excellent milk-lactose degradation ability from Aspergillus oryzae by codon and fermentation optimization.

    PubMed

    Zhao, Qianqian; Liu, Fei; Hou, Zhongwen; Yuan, Chao; Zhu, Xiqiang

    2014-03-01

    A β-galactosidase gene from Aspergillus oryzae was engineered utilizing codon usage optimization to be constitutively and highly expressed in the Pichia pastoris SMD1168H strain in a high-cell-density fermentation. After fermentation for 96 h in a 50-L fermentor using glucose and glycerol as combined carbon sources, the recombinant enzyme in the culture supernatant had an activity of 4,239.07 U mL(-1) with o-nitrophenyl-β-D-galactopyranoside as the substrate, and produced a total of extracellular protein content of 7.267 g L(-1) in which the target protein (6.24 g L(-1)) occupied approximately 86 %. The recombinant β-galactosidase exhibited an excellent lactose hydrolysis ability. With 1,000 U of the enzyme in 100 mL milk, 92.44 % lactose was degraded within 24 h at 60 °C, and the enzyme could also accomplish the hydrolysis at low temperatures of 37, 25, and 10 °C. Thus, this engineered strain had significantly higher fermentation level of A. oryzae lactase than that before optimization and the β-galactosidase may have a good application potential in whey and milk industries.

  17. A new solution to emulsion liquid membrane problems by non-Newtonian conversion

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

    Skelland, A.H.P.; Meng, X.

    1996-02-01

    Surfactant-stabilized emulsion liquid membrane processes constitute an emerging separation technology that has repeatedly been shown to be highly suited for such diverse separation processes as metal recovery or removal from dilute aqueous solutions; separations in the food industry; removal of organic bases and acids from water; and separation of hydrocarbons. Emulsion liquid membrane separation processes remain excessively vulnerable to one or more of four major problems. Difficulties lie in developing liquid membranes that combine high levels of both stability and permeability with acceptably low levels of swelling and ease of subsequent demulsification for membrane and solute recovery. This article providesmore » a new technique for simultaneously overcoming the first three problems, while identifying physical indications that the proposed solution may have little adverse effect on the fourth problem (demulsification) and may even alleviate it. Numerous benefits of optimized conversion of the membrane phase into suitable non-Newtonian form are identified, their mechanisms outlined, and experimental verifications provided. These include increased stability, retained (or enhanced) permeability, reduced swelling, increased internal phase volume, and increased stirrer speeds. The highly favorable responsiveness of both aliphatic and aromatic membranes to the new technique is demonstrated.« less

  18. Bilateral breast keloids in an elderly woman associated with bilateral breast cancers and high concentration of serum tumor growth factor-β.

    PubMed

    Sakaguchi, Masanobu; Fukumoto, Takeshi; Fujishima, Fumiyoshi; Fukuda, Kaori; Kozaru, Takeshi; Ban, Masao; Oka, Masahiro

    2017-11-01

    We report a case of bilateral annular breast keloids in a 72-year-old woman who had been suffering from bilateral breast cancers. Histopathologically, the keloids showed unique distribution of α-SMA+, CD34- myofibroblasts and α-SMA-, CD34+ fibroblasts depending on the region. High serum levels of tumor growth factor-β were detected at 6 months after the development of the breast keloids, but not at 10 months. CD163-positive cells were abundantly detected in the skin of the elevated portion of the keloids. In contrast, these cells were considerably less numerous in the skin of the central healing portion compared with the skin of the elevated expanding portion. One interesting idea based on these results is that high levels of tumor growth factor-β released from CD163-positive cells played a crucial role in the formation of breast keloids through active induction of fibroblast differentiation into myofibroblasts. The present case strongly supports the previously proposed idea that keloids can form as a paraneoplastic phenomenon in breast cancer patients with keloid constitution. © 2017 Japanese Dermatological Association.

  19. Antimicrobial Resistance in Food Animals and the Environment in Nigeria: A Review.

    PubMed

    Oloso, Nurudeen Olalekan; Fagbo, Shamsudeen; Garbati, Musa; Olonitola, Steve O; Awosanya, Emmanuel Jolaoluwa; Aworh, Mabel Kamweli; Adamu, Helen; Odetokun, Ismail Ayoade; Fasina, Folorunso Oludayo

    2018-06-17

    Antimicrobial resistance (AMR) has emerged as a global health threat, which has elicited a high-level political declaration at the United Nations General Assembly, 2016. In response, member countries agreed to pay greater attention to the surveillance and implementation of antimicrobial stewardship. The Nigeria Centre for Disease Control called for a review of AMR in Nigeria using a “One Health approach”. As anecdotal evidence suggests that food animal health and production rely heavily on antimicrobials, it becomes imperative to understand AMR trends in food animals and the environment. We reviewed previous studies to curate data and evaluate the contributions of food animals and the environment (2000⁻2016) to the AMR burden in Nigeria using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart focused on three areas: Antimicrobial resistance, residues, and antiseptics studies. Only one of the 48 antimicrobial studies did not report multidrug resistance. At least 18 bacterial spp. were found to be resistant to various locally available antimicrobials. All 16 residue studies reported high levels of drug residues either in the form of prevalence or concentration above the recommended international limit. Fourteen different “resistotypes” were found in some commonly used antiseptics. High levels of residues and AMR were found in food animals destined for the human food chain. High levels of residues and antimicrobials discharged into environments sustain the AMR pool. These had evolved into potential public health challenges that need attention. These findings constitute public health threats for Nigeria’s teeming population and require attention.

  20. High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

    PubMed

    Roger, Thierry; Schneider, Anina; Weier, Manuela; Sweep, Fred C G J; Le Roy, Didier; Bernhagen, Jürgen; Calandra, Thierry; Giannoni, Eric

    2016-02-23

    The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.

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