Sample records for technical change nos

  1. 78 FR 23556 - Supplemental Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-19

    ...] Supplemental Notice of Technical Conference Docket Nos. Filing via the Internet RM07-16-000 Electronic Tariff... hold a technical conference on April 16, 2013 from 10:00 a.m. to 1:00 p.m. (EST) to demonstrate changes... there have been changes affecting the off-site broadcast of the technical conference. \\1\\ Notice of...

  2. 75 FR 13680 - Commutation of Sentence: Technical Change

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ... Sentence: Technical Change AGENCY: Bureau of Prisons, Justice. ACTION: Interim rule. SUMMARY: This document makes a minor technical change to the Bureau of Prisons (Bureau) regulations on sentence commutation to.... Commutation of Sentence: Technical Change This document makes a minor technical change to the Bureau...

  3. The Changing Nature of Technical Assistance.

    ERIC Educational Resources Information Center

    Noggle, Nelson L.

    The changing nature of technical assistance activities and evaluation for compensatory education programs was discussed. The emphasis is on the Education Consolidation and Improvement Act (ECIA) Chapter 1 Technical Assistance Centers (TAC) and their clients. Improvement of school practices demands that the technical assistance process be developed…

  4. Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution.

    PubMed

    Nozaki, Yuichi; Fujita, Koji; Wada, Koichiro; Yoneda, Masato; Shinohara, Yoshiyasu; Imajo, Kento; Ogawa, Yuji; Kessoku, Takaomi; Nakamuta, Makoto; Saito, Satoru; Masaki, Naohiko; Nagashima, Yoji; Terauchi, Yasuo; Nakajima, Atsushi

    2015-12-17

    Although many factors and molecules that are closely associated with non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) have been reported, the role of endothelial nitric oxide synthase (eNOS)-derived nitric oxide (NO) in the pathogenesis of NAFLD/NASH remains unclear. We therefore investigated the role of eNOS-derived NO in NAFLD pathogenesis using systemic eNOS-knockout mice fed a high-fat diet. eNOS-knockout and wild-type mice were fed a basal diet or a high-fat diet for 12 weeks. Lipid accumulation and inflammation were evaluated in the liver, and various factors that are closely associated with NAFLD/NASH and hepatic tissue blood flow were analyzed. Lipid accumulation and inflammation were more extensive in the liver and lipid accumulation was less extensive in the visceral fat tissue in eNOS-knockout mice, compared with wild-type mice, after 12 weeks of being fed a high-fat diet. While systemic insulin resistance was comparable between the eNOS-knockout and wild-type mice fed a high-fat diet, hepatic tissue blood flow was significantly suppressed in the eNOS-knockout mice, compared with the wild-type mice, in mice fed a high-fat diet. The microsomal triglyceride transfer protein activity was down-regulated in eNOS-knockout mice, compared with wild-type mice, in mice fed a high-fat diet. A deficiency of eNOS-derived NO may exacerbate the early-stage of NASH pathogenesis by changing the fat distribution in a mouse model via the regulation of hepatic tissue blood flow.

  5. Modeling technical change in climate analysis: evidence from agricultural crop damages.

    PubMed

    Ahmed, Adeel; Devadason, Evelyn S; Al-Amin, Abul Quasem

    2017-05-01

    This study accounts for the Hicks neutral technical change in a calibrated model of climate analysis, to identify the optimum level of technical change for addressing climate changes. It demonstrates the reduction to crop damages, the costs to technical change, and the net gains for the adoption of technical change for a climate-sensitive Pakistan economy. The calibrated model assesses the net gains of technical change for the overall economy and at the agriculture-specific level. The study finds that the gains of technical change are overwhelmingly higher than the costs across the agriculture subsectors. The gains and costs following technical change differ substantially for different crops. More importantly, the study finds a cost-effective optimal level of technical change that potentially reduces crop damages to a minimum possible level. The study therefore contends that the climate policy for Pakistan should consider the role of technical change in addressing climate impacts on the agriculture sector.

  6. Changes in eNOS phosphorylation contribute to increased arteriolar NO release during juvenile growth

    PubMed Central

    Kang, Lori S.; Nurkiewicz, Timothy R.; Wu, Guoyao

    2012-01-01

    Nitric oxide (NO) mediates a major portion of arteriolar endothelium-dependent dilation in adults, but indirect evidence has suggested that NO contributes minimally to these responses in the young. Isolated segments of arterioles were studied in vitro to verify this age-related increase in NO release and investigate the mechanism by which it occurs. Directly measured NO release induced by ACh or the Ca2+ ionophore A-23187 was five- to sixfold higher in gracilis muscle arterioles from 42- to 46-day-old (juvenile) rats than in those from 25- to 28-day-old (weanling) rats. There were no differences between groups in arteriolar endothelial NO synthase (eNOS) expression or tetrahydrobiopterin levels, and arteriolar l-arginine levels were lower in juvenile vessels than in weanling vessels (104 ± 6 vs.126 ± 3 pmol/mg). In contrast, agonist-induced eNOS Thr495 dephosphorylation and eNOS Ser1177 phosphorylation (events required for maximal activity) were up to 30% and 65% greater, respectively, in juvenile vessels. Juvenile vessels did not show increased expression of enzymes that mediate these events [protein phosphatases 1 and 2A and PKA and PKB (Akt)] or heat shock protein 90, which facilitates Ser1177 phosphorylation. However, agonist-induced colocalization of heat shock protein 90 with eNOS was 34–66% greater in juvenile vessels than in weanling vessels, and abolition of this difference with geldanamycin also abolished the difference in Ser1177 phosphorylation between groups. These findings suggest that growth-related increases in arteriolar NO bioavailability may be due at least partially to changes in the regulation of eNOS phosphorylation and increased signaling activity, with no change in the abundance of eNOS signaling proteins. PMID:22140037

  7. Balancing the health workforce: breaking down overall technical change into factor technical change for labour-an empirical application to the Dutch hospital industry.

    PubMed

    Blank, Jos L T; van Hulst, Bart L

    2017-02-17

    Well-trained, well-distributed and productive health workers are crucial for access to high-quality, cost-effective healthcare. Because neither a shortage nor a surplus of health workers is wanted, policymakers use workforce planning models to get information on future labour markets and adjust policies accordingly. A neglected topic of workforce planning models is productivity growth, which has an effect on future demand for labour. However, calculating productivity growth for specific types of input is not as straightforward as it seems. This study shows how to calculate factor technical change (FTC) for specific types of input. The paper first theoretically derives FTCs from technical change in a consistent manner. FTC differs from a ratio of output and input, in that it deals with the multi-input, multi-output character of the production process in the health sector. Furthermore, it takes into account substitution effects between different inputs. An application of the calculation of FTCs is given for the Dutch hospital industry for the period 2003-2011. A translog cost function is estimated and used to calculate technical change and FTC for individual inputs, especially specific labour inputs. The results show that technical change increased by 2.8% per year in Dutch hospitals during 2003-2011. FTC differs amongst the various inputs. The FTC of nursing personnel increased by 3.2% per year, implying that fewer nurses were needed to let demand meet supply on the labour market. Sensitivity analyses show consistent results for the FTC of nurses. Productivity growth, especially of individual outputs, is a neglected topic in workforce planning models. FTC is a productivity measure that is consistent with technical change and accounts for substitution effects. An application to the Dutch hospital industry shows that the FTC of nursing personnel outpaced technical change during 2003-2011. The optimal input mix changed, resulting in fewer nurses being needed to let

  8. Change in the Interstitial Cells of Cajal and nNOS Positive Neuronal Cells with Aging in the Stomach of F344 Rats

    PubMed Central

    Kwon, Yong Hwan; Kim, Nayoung; Nam, Ryoung Hee; Park, Ji Hyun; Lee, Sun Min; Kim, Sung Kook; Lee, Hye Seung; Kim, Yong Sung; Lee, Dong Ho

    2017-01-01

    The gastric accommodation reflex is an important mechanism in gastric physiology. However, the aging-associated structural and functional changes in gastric relaxation have not yet been established. Thus, we evaluated the molecular changes of interstitial cell of Cajal (ICC) and neuronal nitric oxide synthase (nNOS) and the function changes in the corpus of F344 rats at different ages (6-, 31-, 74-wk and 2-yr). The proportion of the c-Kit-positive area in the submucosal border (SMB) and myenteric plexus (MP) layer was significantly lower in the older rats, as indicated by immunohistochemistry. The density of the nNOS-positive immunoreactive area also decreased with age in the SMB, circular muscle (CM), and MP. Similarly, the percent of nNOS-positive neuronal cells per total neuronal cells and the proportion of nNOS immunoreactive area of MP also decreased in aged rats. In addition, the mRNA and protein expression of c-Kit and nNOS significantly decreased with age. Expression of stem cell factor (SCF) and the pan-neuronal marker PGP 9.5 mRNA was significantly lower in the older rats than in the younger rats. Barostat studies showed no difference depending on age. Instead, the change of volume was significantly decreased by L-NG63-nitroarginine methyl ester in the 2-yr-old rats compared with the 6-wk-old rats (P = 0.003). Taken together, the quantitative and molecular nNOS changes in the stomach might play a role in the decrease of gastric accommodation with age. PMID:28045993

  9. mNos2 deletion and human NOS2 replacement in Alzheimer disease models.

    PubMed

    Colton, Carol A; Wilson, Joan G; Everhart, Angela; Wilcock, Donna M; Puoliväli, Jukka; Heikkinen, Taneli; Oksman, Juho; Jääskeläinen, Olli; Lehtimäki, Kimmo; Laitinen, Teemu; Vartiainen, Nina; Vitek, Michael P

    2014-08-01

    Understanding the pathophysiologic mechanisms underlying Alzheimer disease relies on knowledge of disease onset and the sequence of development of brain pathologies. We present a comprehensive analysis of early and progressive changes in a mouse model that demonstrates a full spectrum of characteristic Alzheimer disease-like pathologies. This model demonstrates an altered immune redox state reminiscent of the human disease and capitalizes on data indicating critical differences between human and mouse immune responses, particularly in nitric oxide levels produced by immune activation of the NOS2 gene. Using the APPSwDI(+)/(+)mNos2(-/-) (CVN-AD) mouse strain, we show a sequence of pathologic events leading to neurodegeneration,which include pathologically hyperphosphorylated tau in the perforant pathway at 6 weeks of age progressing to insoluble tau, early appearance of β-amyloid peptides in perivascular deposits around blood vessels in brain regions known to be vulnerable to Alzheimer disease, and progression to damage and overt loss in select vulnerable neuronal populations in these regions. The role of species differences between hNOS2 and mNos2 was supported by generating mice in which the human NOS2 gene replaced mNos2. When crossed with CVN-AD mice, pathologic characteristics of this new strain (APPSwDI(+)/(-)/HuNOS2(tg+)/(+)/mNos2(-/-)) mimicked the pathologic phenotypes found in the CVN-AD strain.

  10. Technical Change in the North American Forestry Sector: A Review

    Treesearch

    Jeffery C. Stier; David N. Bengston

    1992-01-01

    Economists have examined the impact of technical change on the forest products sector using the historical, index number, and econometric approaches. This paper reviews econometric analyses of the rate and bias of technical change, examining functional form, factors included, and empirical results. Studies are classified as first- second-, or third-generation...

  11. Technical Assistance Model for Long-Term Systems Change: Three State Examples

    ERIC Educational Resources Information Center

    Kasprzak, Christina; Hurth, Joicey; Lucas, Anne; Marshall, Jacqueline; Terrell, Adriane; Jones, Elizabeth

    2010-01-01

    The National Early Childhood Technical Assistance Center (NECTAC) Technical Assistance (TA) Model for Long-Term Systems Change (LTSC) is grounded in conceptual frameworks in the literature on systems change and systems thinking. The NECTAC conceptual framework uses a logic model approach to change developed specifically for states' infant and…

  12. The Changing Role of Vocational and Technical Education and Training (VOTEC). Women in Vocational and Technical Education: Changes and Challenges.

    ERIC Educational Resources Information Center

    Organisation for Economic Cooperation and Development, Paris (France).

    Changes in the vocational and technical education (VTE) opportunities available for women in Organisation for Economic Cooperation Development (OECD) member countries in response to changing labor markets and job skill requirements were discussed at a June 1994 meeting of experts. The discussions focused on the following issues: gender differences…

  13. 77 FR 18716 - Transportation Security Administration Postal Zip Code Change; Technical Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... organizational changes and it has no substantive effect on the public. DATES: Effective March 28, 2012. FOR... No. 1572-9] Transportation Security Administration Postal Zip Code Change; Technical Amendment AGENCY: Transportation Security Administration, DHS. ACTION: Final rule. SUMMARY: This rule is a technical change to...

  14. Functional significance of differential eNOS translocation

    PubMed Central

    Sánchez, Fabiola A.; Savalia, Nirav B.; Durán, Ricardo G.; Lal, Brajesh K.; Boric, Mauricio P.; Durán, Walter N.

    2006-01-01

    Nitric oxide (NO) regulates flow and permeability. ACh and platelet-activating factor (PAF) lead to endothelial NO synthase (eNOS) phosphorylation and NO release. While ACh causes only vasodilation, PAF induces vasoconstriction and hyperpermeability. The key differential signaling mechanisms for discriminating between vasodilation and hyperpermeability are unknown. We tested the hypothesis that differential translocation may serve as a regulatory mechanism of eNOS to determine specific vascular responses. We used ECV-304 cells permanently transfected with eNOS-green fluorescent protein (ECVeNOS-GFP) and demonstrated that the agonists activate eNOS and reproduce their characteristic endothelial permeability effects in these cells. We evaluated eNOS localization by lipid raft analysis and immunofluorescence microscopy. After PAF and ACh, eNOS moves away from caveolae. eNOS distributes both in the plasma membrane and Golgi in control cells. ACh (10−5 M, 10−4 M) translocated eNOS preferentially to the trans-Golgi network (TGN) and PAF (10−7 M) preferentially to the cytosol. We suggest that PAF-induced eNOS translocation preferentially to cytosol reflects a differential signaling mechanism related to changes in permeability, whereas ACh-induced eNOS translocation to the TGN is related to vasodilation. PMID:16679407

  15. Technical change in forest sector models: the global forest products model approach

    Treesearch

    Joseph Buongiorno; Sushuai Zhu

    2015-01-01

    Technical change is developing rapidly in some parts of the forest sector, especially in the pulp and paper industry where wood fiber is being substituted by waste paper. In forest sector models, the processing of wood and other input into products is frequently represented by activity analysis (input–output). In this context, technical change translates in changes...

  16. The effect of high protein diet and exercise on irisin, eNOS, and iNOS expressions in kidney.

    PubMed

    Tastekin, Ebru; Palabiyik, Orkide; Ulucam, Enis; Uzgur, Selda; Karaca, Aziz; Vardar, Selma Arzu; Yilmaz, Ali; Aydogdu, Nurettin

    2016-08-01

    Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p < 0.05). Kidneys of exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p < 0.001). HPD-E group has not been observed to cause kidney damage and not have a significant effect on rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. İrisin, eNOS, and iNOS staining localizations should be supported with various research studies.

  17. Closing the Gap between Beliefs and Practice: Change of Pre-Service Chemistry Teachers' Orientations during a PCK-Based NOS Course

    ERIC Educational Resources Information Center

    Demirdögen, Betül; Uzuntiryaki-Kondakçi, Esen

    2016-01-01

    The purpose of this case study was to investigate how pre-service chemistry teachers' science teaching orientations change during a two-semester intervention designed to enhance their pedagogical content knowledge (PCK) for teaching the nature of science (NOS). Moreover, the way that pre-service chemistry teachers translated their change in…

  18. MGE-derived nNOS+ interneurons promote fear acquisition in nNOS-/- mice.

    PubMed

    Zhang, Lin; Yuan, Hong-Jin; Cao, Bo; Kong, Cheng-Cheng; Yuan, Fang; Li, Jun; Ni, Huan-Yu; Wu, Hai-Yin; Chang, Lei; Liu, Yan; Luo, Chun-Xia

    2017-12-02

    Neuronal nitric oxide synthase (nNOS) 1 , mainly responsible for NO release in central nervous system (CNS) 2 , plays a significant role in multiple physiological functions. However, the function of nNOS + interneurons in fear learning has not been much explored. Here we focused on the medial ganglionic eminences (MGE) 3 -derived nNOS + interneurons in fear learning. To determine the origin of nNOS + interneurons, we cultured neurons in vitro from MGE, cortex, lateral ganglionic eminence (LGE) 4 , caudal ganglionic eminences (CGE) 5 and preoptic area (POA) 6 . The results showed that MGE contained the most abundant precursors of nNOS + interneurons. Moreover, donor cells from E12.5 embryos demonstrated the highest positive rate of nNOS + interneurons compared with other embryonic periods (E11.5, E12, E13, E13.5 and E14). Additionally, these cells from E12.5 embryos showed long axonal and abundant dendritic arbors after 10 days culture, indicating the capability to disperse and integrate in host neural circuits after transplantation. To investigate the role of MGE-derived nNOS + interneurons in fear learning, donor MGE cells were transplanted into dentate gyrus (DG) 7 of nNOS knock-out (nNOS -/- ) or wild-type mice. Results showed that the transplantation of MGE cells promoted the acquisition of nNOS -/- but not the wild-type mice, suggesting the importance of nNOS + neurons in fear acquisition. Moreover, we transplanted MGE cells from nNOS -/- mice or wild-type mice into DG of the nNOS -/- mice and found that only MGE cells from wild-type mice but not the nNOS -/- mice rescued the deficit in acquisition of the nNOS -/- mice, further confirming the positive role of nNOS + neurons in fear learning. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Technical and Further Education (TAFE) Head Teachers: Their Changing Role

    ERIC Educational Resources Information Center

    Rice, Ann

    2005-01-01

    Change in Technical and Further Education (TAFE) in Australia is being driven by government initiatives that must be operationalised at the college level. Head teachers are the frontline managers in these colleges, who have to ensure their sections are responsive to the changes while also meeting the educational requirements of their traditional…

  20. Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions About Using History of Science to Teach NOS

    NASA Astrophysics Data System (ADS)

    Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

    2016-05-01

    A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing biology teachers' understanding of NOS, and their perceptions about using HOS to teach NOS. These teachers ( N = 8), enrolled in a professional development program in Chile are, according to the national curriculum, expected to teach NOS, but have no specific NOS and HOS training. Teachers' views of NOS were assessed using the VNOS-D+ questionnaire at the beginning and at the end of two modules about science instruction and NOS. Both the pre- and the post-test were accompanied by interviews, and in the second session we collected information about teachers' perceptions of which interventions had been more significant in changing their views on NOS. Finally, the teachers also had to prepare a lesson plan for teaching NOS that included HOS. Some of the most important study results were: significant improvements were observed in teachers' understanding of NOS, although they assigned different levels of importance to HOS in these improvements; and although the teachers improved their understanding of NOS, most had difficulties in planning lessons about NOS and articulating historical episodes that incorporated NOS. The relationship between teachers' improved understanding of NOS and their instructional NOS skills is also discussed.

  1. Rerouting the Pathway for the Biosynthesis of the Side Ring System of Nosiheptide: The Roles of NosI, NosJ, and NosK

    PubMed Central

    2017-01-01

    Nosiheptide (NOS) is a highly modified thiopeptide antibiotic that displays formidable in vitro activity against a variety of Gram-positive bacteria. In addition to a central hydroxypyridine ring, NOS contains several other modifications, including multiple thiazole rings, dehydro-amino acids, and a 3,4-dimethylindolic acid (DMIA) moiety. The DMIA moiety is required for NOS efficacy and is synthesized from l-tryptophan in a series of reactions that have not been fully elucidated. Herein, we describe the role of NosJ, the product of an unannotated gene in the biosynthetic operon for NOS, as an acyl carrier protein that delivers 3-methylindolic acid (MIA) to NosK. We also reassign the role of NosI as the enzyme responsible for catalyzing the ATP-dependent activation of MIA and MIA’s attachment to the phosphopantetheine moiety of NosJ. Lastly, NosK catalyzes the transfer of the MIA group from NosJ-MIA to a conserved serine residue (Ser102) on NosK. The X-ray crystal structure of NosK, solved to 2.3 Å resolution, reveals that the protein is an α/β-fold hydrolase. Ser102 interacts with Glu210 and His234 to form a catalytic triad located at the bottom of an open cleft that is large enough to accommodate the thiopeptide framework. PMID:28343381

  2. Folic acid modulates eNOS activity via effects on posttranslational modifications and protein–protein interactions☆

    PubMed Central

    Taylor, Sarah Y.; Dixon, Hannah M.; Yoganayagam, Shobana; Price, Natalie; Lang, Derek

    2013-01-01

    Folic acid enhances endothelial function and improves outcome in primary prevention of cardiovascular disease. The exact intracellular signalling mechanisms involved remain elusive and were therefore the subject of this study. Particular focus was placed on folic acid-induced changes in posttranslational modifications of endothelial nitric oxide synthase (eNOS). Cultured endothelial cells were exposed to folic acid in the absence or presence of phosphatidylinositol-3' kinase/Akt (PI3K/Akt) inhibitors. The phosphorylation status of eNOS was determined via western blotting. The activities of eNOS and PI3K/Akt were evaluated. The interaction of eNOS with caveolin-1, Heat-Shock Protein 90 and calmodulin was studied using co-immunoprecipitation. Intracellular localisation of eNOS was investigated using sucrose gradient centrifugation and confocal microscopy. Folic acid promoted eNOS dephosphorylation at negative regulatory sites, and increased phosphorylation at positive regulatory sites. Modulation of phosphorylation status was concomitant with increased cGMP concentrations, and PI3K/Akt activity. Inhibition of PI3K/Akt revealed specific roles for this kinase pathway in folic acid-mediated eNOS phosphorylation. Regulatory protein and eNOS protein associations were altered in favour of a positive regulatory effect in the absence of bulk changes in intracellular eNOS localisation. Folic acid-mediated eNOS activation involves the modulation of eNOS phosphorylation status at multiple residues and positive changes in important protein–protein interactions. Such intracellular mechanisms may in part explain improvements in clinical vascular outcome following folic acid treatment. PMID:23796957

  3. A review and update of the Health of the Nation Outcome Scales (HoNOS).

    PubMed

    James, Mick; Painter, Jon; Buckingham, Bill; Stewart, Malcolm W

    2018-04-01

    Aims and method The Health of the Nation Outcome Scales (HoNOS) and its older adults' version (HoNOS 65+) have been used widely for 20 years, but their glossaries have not been revised to reflect clinicians' experiences or changes in service delivery. The Royal College of Psychiatrists convened an international advisory board, with UK, Australian and New Zealand expertise, to identify desirable amendments. The aim was to improve rater experience by removing ambiguity and inconsistency in the glossary rather than more radical revision. Changes proposed to the HoNOS are reported. HoNOS 65+ changes will be reported separately. Based on the views and experience of the countries involved, a series of amendments were identified. Clinical implications While effective clinician training remains critically important, these revisions aim to improve intra- and interrater reliability and improve validity. Next steps will depend on feedback from HoNOS users. Reliability and validity testing will depend on funding. Declaration of interest None.

  4. 77 FR 62147 - Night Definition; Technical Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-12

    .... Nos. 1-1] Night Definition; Technical Amendment AGENCY: Federal Aviation Administration, DOT. ACTION... Canada. In 14 CFR 1.1 the definition of night refers to twilight times as published in the ``American Air... make the amendment effective in less than 30 days. List of Subjects in 14 CFR Part 1 Air transportation...

  5. The National Early Childhood Technical Assistance Center Model for Long-Term Systems Change

    ERIC Educational Resources Information Center

    Kahn, Lynne; Hurth, Joicey; Kasprzak, Christina M.; Diefendorf, Martha J.; Goode, Susan E.; Ringwalt, Sharon S.

    2009-01-01

    The National Early Childhood Technical Assistance Center was charged by the U.S. Department of Education's Office of Special Education Programs from October 2001 through September 2006 to develop, implement, and evaluate an approach to technical assistance (TA) that would result in sustainable systems change in state early intervention and…

  6. The Environment and Directed Technical Change.

    PubMed

    Acemoglu, Daron; Aghion, Philippe; Bursztyn, Leonardo; Hemous, David

    2012-02-01

    This paper introduces endogenous and directed technical change in a growth model with environmental constraints. The final good is produced from "dirty" and "clean" inputs. We show that: (i) when inputs are sufficiently substitutable, sustainable growth can be achieved with temporary taxes/subsidies that redirect innovation toward clean inputs; (ii) optimal policy involves both "carbon taxes" and research subsidies, avoiding excessive use of carbon taxes; (iii) delay in intervention is costly, as it later necessitates a longer transition phase with slow growth; and (iv) use of an exhaustible resource in dirty input production helps the switch to clean innovation under laissez-faire. (JEL O33, O44, Q30, Q54, Q56, Q58).

  7. Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation.

    PubMed

    Zhang, Jun-Xia; Qu, Xin-Liang; Chu, Peng; Xie, Du-Jiang; Zhu, Lin-Lin; Chao, Yue-Lin; Li, Li; Zhang, Jun-Jie; Chen, Shao-Liang

    2018-05-01

    Uncoupled endothelial nitric oxide synthase (eNOS) produces O 2 - instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O 2 - production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O 2 - burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O 2 - releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. 76 FR 35103 - Training and Qualification Requirements for Check Airmen and Flight Instructors; Technical Amendment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... which initial and transition flight training must include an in-flight element. Technical Amendment This.... 28471; Amendment Nos. 121-355 and 135-125] RIN 2120-AF08 Training and Qualification Requirements for Check Airmen and Flight Instructors; Technical Amendment AGENCY: Federal Aviation Administration (FAA...

  9. 75 FR 59261 - Mandatory Reliability Standards for the Bulk Power System; Supplemental Notice of Technical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. RM06-16-010; RM06-16-011] Mandatory Reliability Standards for the Bulk Power System; Supplemental Notice of Technical Conference September 17, 2010. On August 19, 2010 the Federal Energy Regulatory Commission announced that a Technical...

  10. 75 FR 57764 - Mandatory Reliability Standards for the Bulk Power System; Supplemental Notice of Technical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-22

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. RM06-16-010; RM06-16-011] Mandatory Reliability Standards for the Bulk Power System; Supplemental Notice of Technical Conference September 14, 2010. On August 19, 2010 the Federal Energy Regulatory Commission announced that a Technical...

  11. Characteristics of colonic migrating motor complexes in neuronal NOS (nNOS) knockout mice.

    PubMed

    Spencer, Nick J

    2013-01-01

    It is well established that the intrinsic pacemaker mechanism that generates cyclical colonic migrating motor complexes (CMMCs) does not require endogenous nitric oxide (NO). However, pharmacological blockade of endogenous NO production potently increases the frequency of CMMCs, suggesting that endogenous NO acts normally to inhibit the CMMC pacemaker mechanism. In this study, we investigated whether mice with a life long genetic deletion of the neuronal nitric oxide synthase (nNOS) gene would show similar CMMC characteristics as wild type mice that have endogenous NO production acutely inhibited. Intracellular electrophysiological and mechanical recordings were made from circular muscle cells of isolated whole mouse colon in wild type and nNOS knockout (KO) mice at 35°C. In wild type mice, the NOS inhibitor, L-NA (100 μM) caused a significant increase in CMMC frequency and a significant depolarization of the CM layer. However, unexpectedly, the frequency of CMMCs in nNOS KO mice was not significantly different from control mice. Also, the resting membrane potential of CM cells in nNOS KO mice was not depolarized compared to controls; and the amplitude of the slow depolarization phase underlying MCs was of similar amplitude between KO and wild type offspring. These findings show that in nNOS KO mice, the major characteristics of CMMCs and their electrical correlates are, at least in adult mice, indistinguishable from wild type control offspring. One possibility why the major characteristics of CMMCs were no different between both types of mice is that nNOS KO mice may compensate for their life long deletion of the nNOS gene, and their permanent loss of neuronal NO production. In this regard, we suggest caution should be exercised when assuming that data obtained from adult nNOS KO mice can be directly extrapolated to wild type mice, that have been acutely exposed to an inhibitor of NOS.

  12. A Meta-Analysis of Motivational Interviewing Process: Technical, Relational, and Conditional Process Models of Change

    PubMed Central

    Magill, Molly; Apodaca, Timothy R.; Borsari, Brian; Gaume, Jacques; Hoadley, Ariel; Gordon, Rebecca E.F.; Tonigan, J. Scott; Moyers, Theresa

    2018-01-01

    Objective In the present meta-analysis, we test the technical and relational hypotheses of Motivational Interviewing (MI) efficacy. We also propose an a priori conditional process model where heterogeneity of technical path effect sizes should be explained by interpersonal/relational (i.e., empathy, MI Spirit) and intrapersonal (i.e., client treatment seeking status) moderators. Method A systematic review identified k = 58 reports, describing 36 primary studies and 40 effect sizes (N = 3025 participants). Statistical methods calculated the inverse variance-weighted pooled correlation coefficient for the therapist to client and the client to outcome paths across multiple target behaviors (i.e., alcohol use, other drug use, other behavior change). Results Therapist MI-consistent skills were correlated with more client change talk (r = .55, p < .001) as well as more sustain talk (r = .40, p < .001). MI-inconsistent skills were correlated with more sustain talk (r = .16, p < .001), but not change talk. When these indicators were combined into proportions, as recommended in the Motivational Interviewing Skill Code, the overall technical hypothesis was supported. Specifically, proportion MI consistency was related to higher proportion change talk (r = .11, p = .004) and higher proportion change talk was related to reductions in risk behavior at follow up (r = −.16, p < .001). When tested as two independent effects, client change talk was not significant, but sustain talk was positively associated with worse outcome (r = .19, p < .001). Finally, the relational hypothesis was not supported, but heterogeneity in technical hypothesis path effect sizes was partially explained by inter- and intra-personal moderators. Conclusions This meta-analysis provides additional support for the technical hypothesis of MI efficacy; future research on the relational hypothesis should occur in the field rather than in the context of clinical trials. PMID:29265832

  13. A meta-analysis of motivational interviewing process: Technical, relational, and conditional process models of change.

    PubMed

    Magill, Molly; Apodaca, Timothy R; Borsari, Brian; Gaume, Jacques; Hoadley, Ariel; Gordon, Rebecca E F; Tonigan, J Scott; Moyers, Theresa

    2018-02-01

    In the present meta-analysis, we test the technical and relational hypotheses of Motivational Interviewing (MI) efficacy. We also propose an a priori conditional process model where heterogeneity of technical path effect sizes should be explained by interpersonal/relational (i.e., empathy, MI Spirit) and intrapersonal (i.e., client treatment seeking status) moderators. A systematic review identified k = 58 reports, describing 36 primary studies and 40 effect sizes (N = 3,025 participants). Statistical methods calculated the inverse variance-weighted pooled correlation coefficient for the therapist to client and the client to outcome paths across multiple target behaviors (i.e., alcohol use, other drug use, other behavior change). Therapist MI-consistent skills were correlated with more client change talk (r = .55, p < .001) as well as more sustain talk (r = .40, p < .001). MI-inconsistent skills were correlated with more sustain talk (r = .16, p < .001), but not change talk. When these indicators were combined into proportions, as recommended in the Motivational Interviewing Skill Code, the overall technical hypothesis was supported. Specifically, proportion MI consistency was related to higher proportion change talk (r = .11, p = .004) and higher proportion change talk was related to reductions in risk behavior at follow up (r = -.16, p < .001). When tested as two independent effects, client change talk was not significant, but sustain talk was positively associated with worse outcome (r = .19, p < .001). Finally, the relational hypothesis was not supported, but heterogeneity in technical hypothesis path effect sizes was partially explained by inter- and intrapersonal moderators. This meta-analysis provides additional support for the technical hypothesis of MI efficacy; future research on the relational hypothesis should occur in the field rather than in the context of clinical trials. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. Exploring Strengths of Career Technical Education Deans: Implementing Change within Community Colleges

    ERIC Educational Resources Information Center

    Davis, Maria

    2013-01-01

    The purpose of this qualitative study was to explore how career technical education (CTE) deans implement crucial changes in their programs to keep up with industry standards required by external agencies, the Perkins grant, and the advancements of technology. Deans must make top-down, lateral, as well as vertical change to implement improvements…

  15. The return of the Scarlet Pimpernel: cobalamin in inflammation II — cobalamins can both selectively promote all three nitric oxide synthases (NOS), particularly iNOS and eNOS, and, as needed, selectively inhibit iNOS and nNOS

    PubMed Central

    Wheatley, Carmen

    2007-01-01

    The up-regulation of transcobalamins [hitherto posited as indicating a central need for cobalamin (Cbl) in inflammation], whose expression, like inducible nitric oxide synthase (iNOS), is Sp1- and interferondependent, together with increased intracellular formation of glutathionylcobalamin (GSCbl), adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), may be essential for the timely promotion and later selective inhibition of iNOS and concordant regulation of endothelial and neuronal NOS (eNOS/nNOS.) Cbl may ensure controlled high output of nitric oxide (NO) and its safe deployment, because: (1) Cbl is ultimately responsible for the synthesis or availability of the NOS substrates and cofactors heme, arginine, BH4 flavin adenine dinucleotide/flavin mononucleotide (FAD/FMN) and NADPH, via the far-reaching effects of the two Cbl coenzymes, methionine synthase (MS) and methylmalonyl CoA mutase (MCoAM) in, or on, the folate, glutathione, tricarboxylic acid (TCA) and urea cycles, oxidative phosphorylation, glycolysis and the pentose phosphate pathway. Deficiency of any of theNOS substrates and cofactors results in ‘uncoupled’ NOS reactions, decreasedNO production and increased or excessive O2−, H2O2, ONOO− and other reactive oxygen species (ROS), reactive nitric oxide species (RNIS) leading to pathology. (2) Cbl is also the overlooked ultimate determinant of positive glutathione status, which favours the formation of more benign NO species, s-nitrosothiols, the predominant form in which NO is safely deployed. Cbl status may consequently act as a ‘back-up disc’ that ensures the active status of antioxidant systems, as well as reversing and modulating the effects of nitrosylation in cell signal transduction.New evidence shows that GSCbl can significantly promote iNOS/ eNOS NO synthesis in the early stages of inflammation, thus lowering high levels of tumour necrosis factor-a that normally result in pathology, while existing evidence shows that in extreme

  16. Expression profiles of eNOS, iNOS and microRNA-27b in the corpus cavernosum of rats submitted to chronic alcoholism and Diabetes mellitus.

    PubMed

    Cunha, Joao Paulo da; Lizarte, Fermino Sanches; Novais, Paulo Cezar; Gattas, Daniela; Carvalho, Camila Albuquerque Mello de; Tirapelli, Daniela Pretti da Cunha; Molina, Carlos Augusto Fernandes; Tirapelli, Luis Fernando; Tucci, Silvio

    2017-01-01

    To evaluate the expression of endothelial and inducible NOS in addition to the miRNA-27b in the corpus cavernosum and peripheral blood of healthy rats, diabetic rats, alcoholic rats and rats with both pathologies. Forty eight Wistar rats were divided into four groups: control (C), alcoholic (A), diabetic (D) and alcoholic-diabetic (AD). Samples of the corpus cavernosum were prepared to study protein expressions of eNOS and iNOS by immunohistochemistry and expression of miRNA-27b in the corpus cavernosum and peripheral blood. Immunohistochemistry for eNOS and iNOS showed an increase in cavernosal smooth muscle cells in the alcoholic, diabetic and alcoholic-diabetic groups when compared with the control group. Similarly, the mRNA levels for eNOS were increased in cavernosal smooth muscle (CSM) in the alcoholic, diabetic and alcoholic-diabetic groups and miRNA-27b were decreased in CSM in the alcoholic, diabetic and alcoholic-diabetic groups. The major new finding of our study was an impairment of relaxation of cavernosal smooth muscle in alcoholic, diabetic, and alcoholic-diabetic rats that involved a decrease in the nitric oxide pathway by endothelium-dependent mechanisms accompanied by a change in the corpus cavernosum contractile sensitivity.

  17. Expression analysis of NOS family and HSP genes during thermal stress in goat ( Capra hircus)

    NASA Astrophysics Data System (ADS)

    Yadav, Vijay Pratap; Dangi, Satyaveer Singh; Chouhan, Vikrant Singh; Gupta, Mahesh; Dangi, Saroj K.; Singh, Gyanendra; Maurya, Vijay Prakash; Kumar, Puneet; Sarkar, Mihir

    2016-03-01

    Approximately 50 genes other than heat shock protein (HSP) expression changes during thermal stress. These genes like nitric oxide synthase (NOS) need proper attention and investigation to find out their possible role in the adaptation to thermal stress in animals. So, the present study was undertaken to demonstrate the expressions of inducible form type II NOS (iNOS), endothelial type III NOS (eNOS), constitutively expressed enzyme NOS (cNOS), HSP70, and HSP90 in peripheral blood mononuclear cells (PBMCs) during different seasons in Barbari goats. Real-time polymerase chain reaction, western blot, and immunocytochemistry were applied to investigate messenger RNA (mRNA) expression, protein expression, and immunolocalization of examined factors. The mRNA and protein expressions of iNOS, eNOS, cNOS, HSP70, and HSP90 were significantly higher ( P < 0.05) during peak summer, and iNOS and eNOS expressions were also observed to be significantly higher ( P < 0.05) during peak winter season as compared with moderate season. The iNOS, eNOS, cNOS, HSP70, and HSP90 were mainly localized in plasma membrane and cytoplasm of PBMCs. To conclude, data generated in the present study indicate the possible involvement of the NOS family genes in amelioration of thermal stress so as to maintain cellular integrity and homeostasis in goats.

  18. Cardiovascular responses and neurotransmitter changes during static muscle contraction following blockade of inducible nitric oxide synthase (iNOS) within the ventrolateral medulla.

    PubMed

    Ally, Ahmmed; Phattanarudee, Siripan; Kabadi, Shruti; Patel, Maitreyee; Maher, Timothy J

    2006-05-23

    The enzyme nitric oxide synthase (NOS) which is necessary for the production of nitric oxide from L-arginine exists in three isoforms: neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Our previous studies have demonstrated the roles of nNOS and eNOS within the rostral (RVLM) and caudal ventrolateral medulla (CVLM) in modulating cardiovascular responses during static skeletal muscle contraction via altering localized glutamate and GABA levels (Brain Res. 977 (2003) 80-89; Neuroscience Res. 52 (2005) 21-30). In this study, we investigated the role of iNOS within the RVLM and CVLM on cardiovascular responses and glutamatergic/GABAergic neurotransmission during the exercise pressor reflex. Bilateral microdialysis of a selective iNOS antagonist, aminoguanidine (AGN; 1.0 microM), for 60 min into the RVLM attenuated increases in mean arterial pressure (MAP), heart rate (HR), and extracellular glutamate levels during a static muscle contraction. Levels of GABA within the RVLM were increased. After 120 min of discontinuation of the drug, MAP and HR responses and glutamate/GABA concentrations recovered to baseline values during a subsequent muscle contraction. In contrast, bilateral application of AGN (1.0 microM) into CVLM potentiated cardiovascular responses and glutamate concentration while attenuating levels of GABA during a static muscle contraction. All values recovered after 120 min of discontinuation of the drug. These results demonstrate that iNOS within the ventrolateral medulla plays an important role in modulating cardiovascular responses and glutamatergic/GABAergic neurotransmission that regulates the exercise pressor reflex.

  19. Endothelial dysfunction in children with obstructive sleep apnea is associated with epigenetic changes in the eNOS gene.

    PubMed

    Kheirandish-Gozal, Leila; Khalyfa, Abdelnaby; Gozal, David; Bhattacharjee, Rakesh; Wang, Yang

    2013-04-01

    Obstructive sleep apnea (OSA) is a highly prevalent disorder that has been associated with an increased risk for cardiovascular morbidity, even in children. However, not all children with OSA manifest alterations in endothelial postocclusive hyperemia, an endothelial nitric oxide synthase (eNOS)-dependent response. Since expression of the eNOS gene is regulated by epigenetic mechanisms and OSA may cause epigenetic modifications such as DNA hypermethylation, we hypothesized that epigenetic modifications in the eNOS gene may underlie the differential vascular phenotypes in pediatric OSA. Age-, sex-, ethnicity-, and BMI-matched prepubertal children with polysomnographically confirmed OSA and either normal (OSAn) or abnormal (OSAab) postocclusive hyperemic responses, assessed as the time to attain peak reperfusion flow (Tmax) by laser Doppler flowmetry, were recruited. Blood genomic DNA was assessed for epigenetic modifications in the eNOS gene using pyrosequencing. Children with no evidence of OSA or endothelial dysfunction served as a control group. The study comprised 36 children with OSA (11 with OSAab and 25 with OSAn) and 35 children in the control group. Overall, the mean age was 7.5 ± 2.4 years, 65% were boys, and 30% were obese; mean apnea-hypopnea index was 18 ± 8.6/h of sleep for the children with OSA. Tmax was 66.7 ± 8.8 s in the OSAab group and 30.1 ± 8.3 s in the OSAn group (P < .001). Pyrosequencing of the proximal promoter region of the eNOS gene revealed no significant differences in six of the seven CpG sites. However, a CpG site located at position -171 (relative to transcription start site), approximating important transcriptional elements, displayed significantly higher methylation levels in the OSAab group as compared with the OSAn or control groups (81.5% ± 3.5%, 74.8% ± 1.4%, and 74.5% ± 1.7%, respectively; P < .001). eNOS mRNA expression levels were assessed in a separate group of children and were significantly reduced in the

  20. Therapeutic effect of enhancing endothelial nitric oxide synthase (eNOS) expression and preventing eNOS uncoupling

    PubMed Central

    Förstermann, Ulrich; Li, Huige

    2011-01-01

    Nitric oxide (NO) produced by the endothelium is an important protective molecule in the vasculature. It is generated by the enzyme endothelial NO synthase (eNOS). Similar to all NOS isoforms, functional eNOS transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH), via the flavins flavin adenine dinucleotide and flavin mononucleotide in the carboxy-terminal reductase domain, to the heme in the amino-terminal oxygenase domain. Here, the substrate L-arginine is oxidized to L-citrulline and NO. Cardiovascular risk factors such as diabetes mellitus, hypertension, hypercholesterolaemia or cigarette smoking reduce bioactive NO. These risk factors lead to an enhanced production of reactive oxygen species (ROS) in the vessel wall. NADPH oxidases represent major sources of this ROS and have been found upregulated in the presence of cardiovascular risk factors. NADPH-oxidase-derived superoxide avidly reacts with eNOS-derived NO to form peroxynitrite (ONOO-). The essential NOS cofactor (6R-)5,6,7,8-tetrahydrobiopterin (BH4) is highly sensitive to oxidation by this ONOO-. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting NOS to a superoxide-producing enzyme. Among conventional drugs, compounds interfering with the renin-angiotensin-aldosterone system and statins can reduce vascular oxidative stress and increase bioactive NO. In recent years, we have identified a number of small molecules that have the potential to prevent eNOS uncoupling and, at the same time, enhance eNOS expression. These include the protein kinase C inhibitor midostaurin, the pentacyclic triterpenoids ursolic acid and betulinic acid, the eNOS enhancing compounds AVE9488 and AVE3085, and the polyphenolic phytoalexin trans-resveratrol. Such compounds enhance NO production from eNOS also under pathophysiological conditions and may thus have therapeutic potential. PMID:21198553

  1. Attenuation of smoke induced neuronal and physiological changes by bacoside rich extract in Wistar rats via down regulation of HO-1 and iNOS.

    PubMed

    Pandareesh, M D; Anand, T

    2014-01-01

    Bacopa monniera is well known herbal medicine for its neuropharmacological effects. It alleviates variety of disorders including neuronal and physiological changes. Crackers smoke is a potent risk factor that leads to free radical mediated oxidative stress in vivo. The aim of the current study is to evaluate the protective efficacy of B. monniera extract (BME) against crackers smoke induced neuronal and physiological changes via modulating inducible nitric oxide synthase (iNOS) and hemeoxygenase-1 (HO-1) expression in rats. Rats were exposed to smoke for 1h for a period of 3 weeks and consecutively treated with BME at three different dosages (i.e., 10, 20 and 40 mg/kg b.wt.). Our results elucidate that BME treatment ameliorates histopathalogical changes, reactive oxygen species levels, lipid peroxidation, acetylcholine esterase activity and brain neurotransmitter levels to normal. BME supplementation efficiently inhibited HO-1 expression and nitric oxide generation by down-regulating iNOS expression. Smoke induced depletion of antioxidant enzyme status, monoamine oxidase activity was also replenished by BME supplementation. Thus the present study indicates that BME ameliorates various impairments associated with neuronal and physiological changes in rats exposed to crackers smoke by its potent neuromodulatory, antioxidant and adaptogenic propensity. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Vascular endothelial dysfunction in Duchenne muscular dystrophy is restored by bradykinin through upregulation of eNOS and nNOS

    PubMed Central

    Dabiré, Hubert; Barthélémy, Inès; Blanchard-Gutton, Nicolas; Sambin, Lucien; Sampedrano, Carolina Carlos; Gouni, Vassiliki; Unterfinger, Yves; Aguilar, Pablo; Thibaud, Jean-Laurent; Ghaleh, Bijan; Bizé, Alain; Pouchelon, Jean-Louis; Blot, Stéphane; Berdeaux, Alain; Hittinger, Luc; Chetboul, Valérie; Su, Jin Bo

    2012-01-01

    Little is known about the vascular function and expression of endothelial and neuronal nitric oxide synthases (eNOS and nNOS) in Duchenne muscular dystrophy (DMD). Bradykinin is involved in the regulation of eNOS expression induced by angiotensin-converting enzyme inhibitors. We characterized the vascular function and eNOS and nNOS expression in a canine model of DMD and evaluated the effects of chronic bradykinin treatment. Vascular function was examined in conscious golden retriever muscular dystrophy (GRMD) dogs with left ventricular dysfunction (measured by echocardiography) and in isolated coronary arteries. eNOS and nNOS proteins in carotid arteries were measured by western blot and cyclic guanosine monophosphate (cGMP) content was analyzed by radioimmunoassay. Compared with controls, GRMD dogs had an impaired vasodilator response to acetylcholine. In isolated coronary artery, acetylcholine-elicited relaxation was nearly absent in placebo-treated GRMD dogs. This was explained by reduced nNOS and eNOS proteins and cGMP content in arterial tissues. Chronic bradykinin infusion (1 μg/min, 4 weeks) restored in vivo and in vitro vascular response to acetylcholine to the level of control dogs. This effect was NO-mediated through upregulation of eNOS and nNOS expression. In conclusion, this study is the first to demonstrate that DMD is associated with NO-mediated vascular endothelial dysfunction linked to an altered expression of eNOS and nNOS, which can be overcome by bradykinin. PMID:22193759

  3. Modulation of liver mitochondrial NOS is implicated in thyroid-dependent regulation of O(2) uptake.

    PubMed

    Carreras, M C; Peralta, J G; Converso, D P; Finocchietto, P V; Rebagliati, I; Zaninovich, A A; Poderoso, J J

    2001-12-01

    Changes in O(2) uptake at different thyroid status have been explained on the basis of the modulation of mitochondrial enzymes and membrane biophysical properties. Regarding the nitric oxide (NO) effects, we tested whether liver mitochondrial nitric oxide synthase (mtNOS) participates in the modulation of O(2) uptake in thyroid disorders. Wistar rats were inoculated with 400 microCi (131)I (hypothyroid group), 20 microg thyroxine (T(4))/100 g body wt administered daily for 2 wk (hyperthyroid group) or vehicle (control). Basal metabolic rate, mitochondrial function, and mtNOS activity were analyzed. Systemic and liver mitochondrial O(2) uptake and cytochrome oxidase activity were lower in hypothyroid rats with respect to controls; mitochondrial parameters were further decreased by L-arginine (-42 and -34%, P < 0.05), consistent with 5- to 10-fold increases in matrix NO concentration. Accordingly, mtNOS expression (75%) and activity (260%) were selectively increased in hypothyroidism and reverted by hormone replacement without changes in other nitric oxide isoforms. Moreover, mtNOS activity correlated with serum 3,5,3'-triiodothyronine (T(3)) and O(2) uptake. Increased mtNOS activity was also observed in skeletal muscle mitochondria from hypothyroid rats. Therefore, we suggest that modulation of mtNOS is a substantial part of thyroid effects on mitochondrial O(2) uptake.

  4. Imidacloprid exposure cause the histopathological changes, activation of TNF-α, iNOS, 8-OHdG biomarkers, and alteration of caspase 3, iNOS, CYP1A, MT1 gene expression levels in common carp (Cyprinus carpio L.).

    PubMed

    Özdemir, Selçuk; Altun, Serdar; Arslan, Harun

    2018-01-01

    Imidacloprid (IMI) is a neonicotinoid that is widely used for the protection of crops and carnivores from insects and parasites, respectively. It is well known that imidacloprid exposure has a harmful effect on several organisms. However, there is little information about imidacloprid toxicity in aquatic animals, particularly fish. Thus, in the current study, we assessed the histopathological changes; activation of iNOS, 8-OHdG and TNF-α; and expression levels of caspase 3, iNOS, CYP1A and MT1 genes in the common carp exposed to imidacloprid. For this purpose, fish were exposed to either a low dose (140 mg/L) or a high dose (280 mg/L) of imidacloprid for 24 h, 48 h, 72 h and 96 h. After IMI exposure, we detected hyperplasia of secondary lamellar cells and mucous cell hyperplasia in the gills, as well as hydropic degeneration in hepatocytes and necrosis in the liver. Moreover, 8-OHdG, iNOS and TNF-α activation was found particularly in the gills and liver but also moderately in the brain. Transcriptional analysis showed that caspase 3 expression was altered low dose and high doses of IMI for 72 h and 96 h exposure ( p <  0.05), iNOS expression was up-regulated with both low and high doses of IMI and in a time-dependent manner ( p <  0.05, p <  0.01, p <  0.001), CYP1A expression was not significantly changed regardless of the dose of IMI and exposure time ( p >  0.05) except with low and high doses of IMI for 96 h ( p <  0.05), and lastly, MT1 gene expression was up-regulated only in the brain with low doses of IMI for 96 h and high doses of IMI for 48 h, 72 h and 96 h exposure ( p <  0.05, p <  0.01). Our results indicated that acute IMI exposure moderately induce apoptosis in the brain but caused severe histopathological lesions, inflammation, and oxidative stress in the gills, liver, and brain of the common carp.

  5. Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.

    PubMed

    Li, Li-Li; Melero-Fernandez de Mera, Raquel M; Chen, Jia; Ba, Wei; Kasri, Nael Nadif; Zhang, Mingjie; Courtney, Michael J

    2015-05-13

    The protein NOS1AP/CAPON mediates signaling from a protein complex of NMDA receptor, PSD95 and nNOS. The only stroke trial for neuroprotectants that showed benefit to patients targeted this ternary complex. NOS1AP/nNOS interaction regulates small GTPases, iron transport, p38MAPK-linked excitotoxicity, and anxiety. Moreover, the nos1ap gene is linked to disorders from schizophrenia, post-traumatic stress disorder, and autism to cardiovascular disorders and breast cancer. Understanding protein interactions required for NOS1AP function, therefore, has broad implications for numerous diseases. Here we show that the interaction of NOS1AP with nNOS differs radically from the classical PDZ docking assumed to be responsible. The NOS1AP PDZ motif does not bind nNOS as measured by multiple methods. In contrast, full-length NOS1AP forms an unusually stable interaction with nNOS. We mapped the discrepancy between full-length and C-terminal PDZ motif to a novel internal region we call the ExF motif. The C-terminal PDZ motif, although neither sufficient nor necessary for binding, nevertheless promotes the stability of the complex. It therefore potentially affects signal transduction and suggests that functional interaction of nNOS with NOS1AP might be targetable at two distinct sites. We demonstrate that excitotoxic pathways can be regulated, in cortical neuron and organotypic hippocampal slice cultures from rat, either by the previously described PDZ ligand TAT-GESV or by the ExF motif-bearing region of NOS1AP, even when lacking the critical PDZ residues as long as the ExF motif is intact and not mutated. This previously unrecognized heterodivalent interaction of nNOS with NOS1AP may therefore provide distinct opportunities for pharmacological intervention in NOS1AP-dependent signaling and excitotoxicity. Copyright © 2015 the authors 0270-6474/15/357349-16$15.00/0.

  6. Assessing depression outcome in patients with moderate dementia: sensitivity of the HoNOS65+ scale.

    PubMed

    Canuto, Alessandra; Rudhard-Thomazic, Valérie; Herrmann, François R; Delaloye, Christophe; Giannakopoulos, Panteleimon; Weber, Kerstin

    2009-08-15

    To date, there is no widely accepted clinical scale to monitor the evolution of depressive symptoms in demented patients. We assessed the sensitivity to treatment of a validated French version of the Health of the Nation Outcome Scale (HoNOS) 65+ compared to five routinely used scales. Thirty elderly inpatients with ICD-10 diagnosis of dementia and depression were evaluated at admission and discharge using paired t-test. Using the Brief Psychiatric Rating Scale (BPRS) "depressive mood" item as gold standard, a receiver operating characteristic curve (ROC) analysis assessed the validity of HoNOS65+F "depressive symptoms" item score changes. Unlike Geriatric Depression Scale, Mini Mental State Examination and Activities of Daily Living scores, BPRS scores decreased and Global Assessment Functioning Scale score increased significantly from admission to discharge. Amongst HoNOS65+F items, "behavioural disturbance", "depressive symptoms", "activities of daily life" and "drug management" items showed highly significant changes between the first and last day of hospitalization. The ROC analysis revealed that changes in the HoNOS65+F "depressive symptoms" item correctly classified 93% of the cases with good sensitivity (0.95) and specificity (0.88) values. These data suggest that the HoNOS65+F "depressive symptoms" item may provide a valid assessment of the evolution of depressive symptoms in demented patients.

  7. 76 FR 33193 - Notice of Proposed Change to Section IV of the Virginia State Technical Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-08

    ... DEPARTMENT OF AGRICULTURE Natural Resources Conservation Service Notice of Proposed Change to....S. Department of Agriculture. ACTION: Notice of Availability of proposed changes in the Virginia... Conservationist for Virginia that changes must be made in the NRCS State Technical Guide specifically in practice...

  8. Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of oral squamous cell carcinoma

    PubMed Central

    Itoiz, María E.; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

    2014-01-01

    The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early carcinogenesis have been found in mucosa near carcinomas, which is considered a model to study field cancerization. The aim of the present study is to analyze NOS2 expression at the histologically normal margins of OSCC. Study Design: Eleven biopsy specimens of OSCC containing histologically normal margins (HNM) were analyzed. Ten biopsies of normal oral mucosa were used as controls. The activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi-squared test was applied. Results: Six out of the eleven HNM from carcinoma samples showed positive NOS2 activity whereas all the control group samples yielded negative (p=0.005). No statistically significant association between enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and nitrite was found. Conclusions: NOS2 expression would be an additional evidence of alterations that may occur in a state of field cancerization before the appearance of potentially malignant morphological changes. Key words:Field cancerization, oral squamous cell carcinoma, Nitric Oxide Synthase 2 (NOS2), malignity markers. PMID:24316703

  9. Neuronal NOS localises to human airway cilia.

    PubMed

    Jackson, Claire L; Lucas, Jane S; Walker, Woolf T; Owen, Holly; Premadeva, Irnthu; Lackie, Peter M

    2015-01-30

    Airway NO synthase (NOS) isoenzymes are responsible for rapid and localised nitric oxide (NO) production and are expressed in airway epithelium. We sought to determine the localisation of neuronal NOS (nNOS) in airway epithelium due to the paucity of evidence. Sections of healthy human bronchial tissue in glycol methacrylate resin and human nasal polyps in paraffin wax were immunohistochemically labelled and reproducibly demonstrated nNOS immunoreactivity, particularly at the proximal portion of cilia; this immunoreactivity was blocked by a specific nNOS peptide fragment. Healthy human epithelial cells differentiated at an air-liquid interface (ALI) confirmed the presence of all three NOS isoenzymes by immunofluorescence labelling. Only nNOS immunoreactivity was specific to the ciliary axonemeand co-localised with the cilia marker β-tubulin in the proximal part of the ciliary axoneme. We report a novel localisation of nNOS at the proximal portion of cilia in airway epithelium and conclude that its independent and local regulation of NO levels is crucial for normal cilia function. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Temporal Changes in Technical and Physical Performances During a Small-Sided Game in Elite Youth Soccer Players

    PubMed Central

    Moreira, Alexandre; Saldanha Aoki, Marcelo; Carling, Chris; Alan Rodrigues Lopes, Rafael; Felipe Schultz de Arruda, Ademir; Lima, Marcelo; Cesar Correa, Umberto; Bradley, Paul S

    2016-01-01

    Background There have been claims that small-sided games (SSG) may generate an appropriate environment to develop youth players’ technical performance associated to game-related problem solving. However, the temporal change in technical performance parameters of youth players during SSG is still unknown. Objectives The aim of this study was to examine temporal changes in technical and physical performances during a small-sided game (SSG) in elite soccer players. Methods Sixty elite youth players (age 14.8 ± 0.2 yr; stature 177 ± 5 cm; body mass 66.2 ± 4.7 kg) completed a 5 v 5 SSG using two repetitions of 8 minutes interspersed by 3 minutes of passive recovery. To evaluate temporal changes in performance, the data were analysed across 4 minutes quarters. Physical performance parameters included the total distance covered (TDC), the frequency of sprints (>18 km•h-1), accelerations and decelerations (> 2.0 m•s-2 and - 2.0 m•s-2), metabolic power (W•kg-1), training impulse (TRIMP), TDC: TRIMP, number of impacts, and body load. Technical performance parameters included goal attempts, total number of tackles, tackles and interceptions, total number of passes, and passes effectiveness. Results All physical performance parameters decreased from the first to the last quarter with notable declines in TDC, metabolic power and the frequency of sprints, accelerations and decelerations (P < 0.05; moderate to very large ES: 1.08 - 3.30). However, technical performance parameters did not vary across quarters (P > 0.05; trivial ES for 1st v 4th quarters: 0.15 - 0.33). Conclusions The data demonstrate that technical performance is maintained despite substantial declines in physical performance during a SSG in elite youth players. This finding may have implications for designing SSG’s for elite youth players to ensure physical, technical and tactical capabilities are optimized. Modifications in player number, pitch dimensions, rules, coach encouragement, for instance

  11. Temporal Changes in Technical and Physical Performances During a Small-Sided Game in Elite Youth Soccer Players.

    PubMed

    Moreira, Alexandre; Saldanha Aoki, Marcelo; Carling, Chris; Alan Rodrigues Lopes, Rafael; Felipe Schultz de Arruda, Ademir; Lima, Marcelo; Cesar Correa, Umberto; Bradley, Paul S

    2016-12-01

    There have been claims that small-sided games (SSG) may generate an appropriate environment to develop youth players' technical performance associated to game-related problem solving. However, the temporal change in technical performance parameters of youth players during SSG is still unknown. The aim of this study was to examine temporal changes in technical and physical performances during a small-sided game (SSG) in elite soccer players. Sixty elite youth players (age 14.8 ± 0.2 yr; stature 177 ± 5 cm; body mass 66.2 ± 4.7 kg) completed a 5 v 5 SSG using two repetitions of 8 minutes interspersed by 3 minutes of passive recovery. To evaluate temporal changes in performance, the data were analysed across 4 minutes quarters. Physical performance parameters included the total distance covered (TDC), the frequency of sprints (>18 km•h -1 ), accelerations and decelerations (> 2.0 m•s -2 and - 2.0 m•s -2 ), metabolic power (W•kg -1 ), training impulse (TRIMP), TDC: TRIMP, number of impacts, and body load. Technical performance parameters included goal attempts, total number of tackles, tackles and interceptions, total number of passes, and passes effectiveness. All physical performance parameters decreased from the first to the last quarter with notable declines in TDC, metabolic power and the frequency of sprints, accelerations and decelerations (P < 0.05; moderate to very large ES: 1.08 - 3.30). However, technical performance parameters did not vary across quarters (P > 0.05; trivial ES for 1st v 4th quarters: 0.15 - 0.33). The data demonstrate that technical performance is maintained despite substantial declines in physical performance during a SSG in elite youth players. This finding may have implications for designing SSG's for elite youth players to ensure physical, technical and tactical capabilities are optimized. Modifications in player number, pitch dimensions, rules, coach encouragement, for instance, should be included taking into account the

  12. The influence of authentic scientific research experiences on teachers' conceptions of the nature of science (NOS) and their NOS teaching practices

    NASA Astrophysics Data System (ADS)

    Moriarty, Meghan A.

    This study explored the influence of teachers' authentic scientific research experiences (ASREs) on teachers' conceptions of the nature of science (NOS) and teachers' NOS instruction. Twelve high school biology teachers participated in this study. Six of the participants had authentic scientific research experience (ASRE) and six had not participated in authentic scientific research. Data included background surveys, modified Views of the Nature of Science (VNOS) questionnaires, interviews, and teaching observations. Data was coded based on the eight NOS understandings outlined in 2013 in the Next Generation Science Standards (NGSS). Evidence from this study indicates participating in authentic scientific research as a member of a scientific community has dual benefits of enabling high school science teachers with informed understandings of the NOS and positioning them to teach with the NOS. However, these benefits do not always result from an ASRE. If the nature of the ASRE is limited, then it may limit teachers' NOS understandings and their NOS teaching practices. The results of this study suggest that participation in ASREs may be one way to improve teachers' NOS understandings and teaching practices if the experiences themselves offer a comprehensive view of the NOS. Because ASREs and other science learning experiences do not always offer such experiences, pre-service teacher education and professional development opportunities may engage science teachers in two ways: (1) becoming part of a scientific community may enable them to teach with NOS and (2) being reflective about what being a scientist means may improve teachers' NOS understandings and better position them to teach about NOS.. Keywords: nature of science, authentic scientific research experiences, Next Generation Science Standards, teaching about NOS, teaching with NOS.

  13. Nitric oxide synthase 2 (NOS2) expression in histologically normal margins of oral squamous cell carcinoma.

    PubMed

    Morelatto, Rosana; Itoiz, María-Elina; Guiñazú, Natalia; Piccini, Daniel; Gea, Susana; López-de Blanc, Silvia

    2014-05-01

    The activity of Nitric Oxide Synthase 2 (NOS2) was found in oral squamous cell carcinomas (OSCC) but not in normal mucosa. Molecular changes associated to early carcinogenesis have been found in mucosa near carcinomas, which is considered a model to study field cancerization. The aim of the present study is to analyze NOS2 expression at the histologically normal margins of OSCC. Eleven biopsy specimens of OSCC containing histologically normal margins (HNM) were analyzed. Ten biopsies of normal oral mucosa were used as controls. The activity of NOS2 was determined by immunohistochemistry. Salivary nitrate and nitrite as well as tobacco and alcohol consumption were also analyzed. The Chi-squared test was applied. Six out of the eleven HNM from carcinoma samples showed positive NOS2 activity whereas all the control group samples yielded negative (p=0.005). No statistically significant association between enzyme expression and tobacco and/or alcohol consumption and salivary nitrate and nitrite was found. NOS2 expression would be an additional evidence of alterations that may occur in a state of field cancerization before the appearance of potentially malignant morphological changes.

  14. 75 FR 33167 - Technical Amendment Language Change From “Wholly” to “Fully”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ... SOCIAL SECURITY ADMINISTRATION 20 CFR Parts 404, 405, 408, 416, and 418 [Docket No. SSA-2009-0062] RIN 0960-AH16 Technical Amendment Language Change From ``Wholly'' to ``Fully'' AGENCY: Social Security... these final rules, call Brian J. Rudick, Office of Regulations, Social Security Administration, 6401...

  15. Total Factor Productivity Growth, Technical Progress & Efficiency Change in Vietnam Coal Industry - Nonparametric Approach

    NASA Astrophysics Data System (ADS)

    Phuong, Vu Hung

    2018-03-01

    This research applies Data Envelopment Analysis (DEA) approach to analyze Total Factor Productivity (TFP) and efficiency changes in Vietnam coal mining industry from 2007 to 2013. The TFP of Vietnam coal mining companies decreased due to slow technological progress and unimproved efficiency. The decadence of technical efficiency in many enterprises proved that the coal mining industry has a large potential to increase productivity through technical efficiency improvement. Enhancing human resource training, technology and research & development investment could help the industry to improve efficiency and productivity in Vietnam coal mining industry.

  16. iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat

    PubMed Central

    Fujii, Naoto; Meade, Robert D.; Alexander, Lacy M.; Akbari, Pegah; Foudil-bey, Imane; Louie, Jeffrey C.; Boulay, Pierre

    2015-01-01

    Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P < 0.05). CVC at the eNOS-I site was lower than control in younger adults throughout the intermittent exercise protocol (all P < 0.05). In older adults, there were no differences between control and iNOS-I sites for sweating and CVC during both exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults. PMID:26586908

  17. iNOS-dependent sweating and eNOS-dependent cutaneous vasodilation are evident in younger adults, but are diminished in older adults exercising in the heat.

    PubMed

    Fujii, Naoto; Meade, Robert D; Alexander, Lacy M; Akbari, Pegah; Foudil-Bey, Imane; Louie, Jeffrey C; Boulay, Pierre; Kenny, Glen P

    2016-02-01

    Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilation during exercise in younger adults. We hypothesized that endothelial NOS (eNOS) and neuronal NOS (nNOS) mediate NOS-dependent sweating, whereas eNOS induces NOS-dependent cutaneous vasodilation in younger adults exercising in the heat. Further, aging may upregulate inducible NOS (iNOS), which may attenuate sweating and cutaneous vasodilator responses. We hypothesized that iNOS inhibition would augment sweating and cutaneous vasodilation in exercising older adults. Physically active younger (n = 12, 23 ± 4 yr) and older (n = 12, 60 ± 6 yr) adults performed two 30-min bouts of cycling at a fixed rate of metabolic heat production (400 W) in the heat (35°C). Sweat rate and cutaneous vascular conductance (CVC) were evaluated at four intradermal microdialysis sites with: 1) lactated Ringer (control), 2) nNOS inhibitor (nNOS-I, NPLA), 3) iNOS inhibitor (iNOS-I, 1400W), or 4) eNOS inhibitor (eNOS-I, LNAA). In younger adults during both exercise bouts, all inhibitors decreased sweating relative to control, albeit a lower sweat rate was observed at iNOS-I compared with eNOS-I and nNOS-I sites (all P < 0.05). CVC at the eNOS-I site was lower than control in younger adults throughout the intermittent exercise protocol (all P < 0.05). In older adults, there were no differences between control and iNOS-I sites for sweating and CVC during both exercise bouts (all P > 0.05). We show that iNOS and eNOS are the main contributors to NOS-dependent sweating and cutaneous vasodilation, respectively, in physically active younger adults exercising in the heat, and that iNOS inhibition does not alter sweating or cutaneous vasodilation in exercising physically active older adults. Copyright © 2016 the American Physiological Society.

  18. Decreased production of neuronal NOS-derived hydrogen peroxide contributes to endothelial dysfunction in atherosclerosis

    PubMed Central

    Capettini, LSA; Cortes, SF; Silva, JF; Alvarez-Leite, JI; Lemos, VS

    2011-01-01

    BACKGROUND AND PURPOSE Reduced NO availability has been described as a key mechanism responsible for endothelial dysfunction in atherosclerosis. We previously reported that neuronal NOS (nNOS)-derived H2O2 is an important endothelium-derived relaxant factor in the mouse aorta. The role of H2O2 and nNOS in endothelial dysfunction in atherosclerosis remains undetermined. We hypothesized that a decrease in nNOS-derived H2O2 contributes to the impaired vasodilatation in apolipoprotein E-deficient mice (ApoE−/−). EXPERIMENTAL APPROACH Changes in isometric tension were recorded on a myograph; simultaneously, NO and H2O2 were measured using carbon microsensors. Antisense oligodeoxynucleotides were used to knockdown eNOS and nNOS in vivo. Western blot and confocal microscopy were used to analyse the expression and localization of NOS isoforms. KEY RESULTS Aortas from ApoE−/− mice showed impaired vasodilatation paralleled by decreased NO and H2O2 production. Inhibition of nNOS with L-ArgNO2-L-Dbu, knockdown of nNOS and catalase, which decomposes H2O2 into oxygen and water, decreased ACh-induced relaxation by half, produced a small diminution of NO production and abolished H2O2 in wild-type animals, but had no effect in ApoE−/− mice. Confocal microscopy showed increased nNOS immunostaining in endothelial cells of ApoE−/− mice. However, ACh stimulation of vessels resulted in less phosphorylation on Ser852 in ApoE−/− mice. CONCLUSIONS AND IMPLICATIONS Our data show that endothelial nNOS-derived H2O2 production is impaired and contributes to endothelial dysfunction in ApoE−/− aorta. The present study provides a new mechanism for endothelial dysfunction in atherosclerosis and may represent a novel target to elaborate the therapeutic strategy for vascular atherosclerosis. PMID:21615722

  19. Post-translational regulation of endothelial nitric oxide synthase (eNOS) by estrogens in the rat vagina.

    PubMed

    Musicki, Biljana; Liu, Tongyun; Strong, Travis D; Lagoda, Gwen A; Bivalacqua, Trinity J; Burnett, Arthur L

    2010-05-01

    Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17beta (15 microg). Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement in the distal or proximal vagina. These results

  20. 75 FR 61478 - Mandatory Reliability Standards for the Bulk Power System; Notice Allowing Post-Technical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. RM06-16-010; RM06-16-011] Mandatory Reliability Standards for the Bulk Power System; Notice Allowing Post-Technical Conference Comments September 24, 2010. On September 23, 2010, the Federal Energy Regulatory Commission conducted a...

  1. NOS2 deficiency has no influence on the radiosensitivity of the hematopoietic system.

    PubMed

    Li, Chengcheng; Luo, Yi; Shao, Lijian; Meng, Aimin; Zhou, Daohong

    2018-01-01

    Previous studies have shown that inhibition of inducible NO synthase (NOS2 or iNOS) with an inhibitor can selectively protect several normal tissues against radiation during radiotherapy. However, the role of NOS2 in ionizing radiation (IR)-induced bone marrow (BM) suppression is unknown and thus was investigated in the present study using NOS2 - / - and wild-type mice 14 days after they were exposed to a sublethal dose of total body irradiation (TBI). The effects of different doses of IR (1, 2 and 4 Gy) on the apoptosis and colony-forming ability of bone marrow cells from wild-type (WT) and NOS2 - / - mice were investigated in vitro. In addition, we exposed NOS2 - / - mice and WT mice to 6-Gy TBI or sham irradiation. They were euthanized 14 days after TBI for analysis of peripheral blood cell counts and bone marrow cellularity. Colony-forming unit-granulocyte and macrophage, burst-forming unit-erythroid and CFU-granulocyte, erythroid, macrophage in bone marrow cells from the mice were determined to evaluate the function of hematopoietic progenitor cells (HPCs), and the ability of hematopoietic stem cells (HSCs) to self-renew was analysed by the cobblestone area forming cell assay. The cell cycling of HPCs and HSCs were measured by flow cytometry. Exposure to 2 and 4 Gy IR induced bone marrow cell apoptosis and inhibited the proliferation of HPCs in vitro. However, there was no difference between the cells from WT mice and NOS2 - / - mice in response to IR exposure in vitro. Exposure of WT mice and NOS2 - / - mice to 6 Gy TBI decreased the white blood cell, red blood cell, and platelet counts in the peripheral blood and bone marrow mononuclear cells, and reduced the colony-forming ability of HPCs (P < 0.05), damaged the clonogenic function of HSCs. However, these changes were not significantly different in WT and NOS2 - / - mice. These data suggest that IR induces BM suppression in a NOS2-independent manner.

  2. Impact of Research and Technical Change in Wildland Recreation: Evaluation Issues and Approaches

    Treesearch

    David N. Bengston; Zhi Xu

    1993-01-01

    The development and diffusion of new technologies have had tremendous impacts on wildland recreation in recent decades. This article examines the potential economic impacts of research and technical change in wildland recreation. Two evaluation models are presented, a cost-price approach and a research intensity model, which are intended to shed some light on the...

  3. Dryland ecohydrology and climate change: critical issues and technical advances

    NASA Astrophysics Data System (ADS)

    Wang, L.; D'Odorico, P.; Evans, J. P.; Eldridge, D.; McCabe, M. F.; Caylor, K. K.; King, E. G.

    2012-04-01

    Drylands cover about 40% of the terrestrial land surface and account for approximately 40% of global net primary productivity. Water is fundamental to the biophysical processes that sustain ecosystem function and food production, particularly in drylands, where a tight coupling exists between water resource availability and ecosystem productivity, surface energy balance, and biogeochemical cycles. Currently, drylands support at least 2 billion people and comprise both natural and managed ecosystems. In this synthesis, we identify some current critical issues in the understanding of dryland systems and discuss how arid and semiarid environments are responding to the changes in climate and land use. Specifically, we focus on dryland agriculture and food security, dryland population growth, desertification, shrub encroachment and dryland development issues as factors of change requiring increased understanding and management. We also review recent technical advances in the quantitative assessment of human versus climate change related drivers of desertification, evapotranspiration partitioning using field deployable stable water isotope systems and the remote sensing of key ecohydrological processes. These technological advances provide new tools that assist in addressing major critical issues in dryland ecohydrology under climate change

  4. Post-translational Regulation of Endothelial Nitric Oxide Synthase (eNOS) by Estrogens in the Rat Vagina

    PubMed Central

    Musicki, Biljana; Liu, Tongyun; Strong, Travis D.; Lagoda, Gwen A.; Bivalacqua, Trinity J.; Burnett, Arthur L.

    2010-01-01

    Introduction Estrogens control vaginal blood flow during female sexual arousal mostly through nitric oxide (NO). Although vascular effects of estrogens are attributed to an increase in endothelial NO production, the mechanisms of endothelial NO synthase (eNOS) regulation by estrogens in the vagina are largely unknown. Aims Our hypothesis was that estrogens regulate eNOS post-translationally in the vagina, providing a mechanism to affect NO bioavailability without changes in eNOS protein expression. Methods We measured eNOS phosphorylation and eNOS interaction with caveolin-1 and heat shock protein 90 (HSP90) in the distal and proximal vagina of female rats at diestrus, 7 days after ovariectomy and 2 days after replacement of ovariectomized rats with estradiol-17β (15 μg). Main Outcome Measures Molecular mechanisms of eNOS regulation by estrogen in the rat vagina. Results We localized phospho-eNOS (Ser-1177) immunohistochemically to the endothelium lining blood vessels and vaginal sinusoids. Estrogen withdrawal decreased phosphorylation of eNOS on its positive regulatory site (Ser-1177) and increased eNOS binding to its negative regulator caveolin-1 (without affecting eNOS/HSP90 interaction), and they were both normalized by estradiol replacement. Protein expressions of phosphorylated Akt (protein kinase B) and extracellular signal-regulated protein kinase 1/2 (ERK1/2) were not affected by estrogen status, suggesting that the effect of estrogens on eNOS (Ser-1177) phosphorylation was not mediated by activated AKT or ERK1/2. eNOS phosphorylation on its negative regulatory site (Ser-114) was increased in the vagina by estrogen withdrawal and normalized by estradiol replacement, implying that the maintenance of low phosphorylation of eNOS on this site by estradiol may limit eNOS interaction with caveolin-1 and preserve the enzyme's activity. Total eNOS, inducible NOS, caveolin-1, and HSP90 protein expressions were not affected by ovariectomy or estradiol replacement

  5. National climate assessment technical report on the impacts of climate and land use and land cover change

    Treesearch

    Thomas Loveland; Rezaul Mahmood; Toral Patel-Weynand; Krista Karstensen; Kari Beckendorf; Norman Bliss; Andrew Carleton

    2012-01-01

    This technical report responds to the recognition by the U.S. Global Change Research Program (USGCRP) and the National Climate Assessment (NCA) of the importance of understanding how land use and land cover (LULC) affects weather and climate variability and change and how that variability and change affects LULC. Current published, peer-reviewed, scientific literature...

  6. The Changing Role of Vocational and Technical Education and Training. Synthesis of Country Reports.

    ERIC Educational Resources Information Center

    Organisation for Economic Cooperation and Development, Paris (France).

    In preparation for a conference held in Paris, France, in November 1994, the Organisation for Economic Cooperation and Development (OECD) launched a 5-year program that involved 20 countries studying the changing role of vocational and technical education and training (VOTEC). This report synthesizes 18 country reports on major recent developments…

  7. Social media and nursing practice: changing the balance between the social and technical aspects of work.

    PubMed

    Casella, Evan; Mills, Jane; Usher, Kim

    2014-01-01

    Modern communication methods are drastically changing the way people interact with each other. Professions such as nursing need to evolve to remain relevant as social infrastructure changes. In the 1960s, researchers developed a sociotechnical theory that stated workers were more motivated and productive if there was a good balance between the social and technical aspects of their work. Today's technology is blurring the boundaries between the social and the technical thereby transforming human contact and communication into a multi-method process. In Australia, people are adept at utilising social media technology to become more efficient, creative and connected; Australian nurses also need to embrace changing technology to capitalise on the professional opportunities offered by social media. This paper imagines a world where nurses integrate social media into assessing, diagnosing, planning, implementing and evaluating care. Discussion draws on a combination of real-world examples of best-practice and blue-sky thinking to demonstrate that evidence-based care must be combined with the adoption of future-forward technology.

  8. Control of food intake and energy expenditure by Nos1 neurons of the paraventricular hypothalamus.

    PubMed

    Sutton, Amy K; Pei, Hongjuan; Burnett, Korri H; Myers, Martin G; Rhodes, Christopher J; Olson, David P

    2014-11-12

    The paraventricular nucleus of the hypothalamus (PVH) contains a heterogeneous cluster of Sim1-expressing cell types that comprise a major autonomic output nucleus and play critical roles in the control of food intake and energy homeostasis. The roles of specific PVH neuronal subtypes in energy balance have yet to be defined, however. The PVH contains nitric oxide synthase-1 (Nos1)-expressing (Nos1(PVH)) neurons of unknown function; these represent a subset of the larger population of Sim1-expressing PVH (Sim1(PVH)) neurons. To determine the role of Nos1(PVH) neurons in energy balance, we used Cre-dependent viral vectors to both map their efferent projections and test their functional output in mice. Here we show that Nos1(PVH) neurons project to hindbrain and spinal cord regions important for food intake and energy expenditure control. Moreover, pharmacogenetic activation of Nos1(PVH) neurons suppresses feeding to a similar extent as Sim1(PVH) neurons, and increases energy expenditure and activity. Furthermore, we found that oxytocin-expressing PVH neurons (OXT(PVH)) are a subset of Nos1(PVH) neurons. OXT(PVH) cells project to preganglionic, sympathetic neurons in the thoracic spinal cord and increase energy expenditure upon activation, though not to the same extent as Nos1(PVH) neurons; their activation fails to alter feeding, however. Thus, Nos1(PVH) neurons promote negative energy balance through changes in feeding and energy expenditure, whereas OXT(PVH) neurons regulate energy expenditure alone, suggesting a crucial role for non-OXT Nos1(PVH) neurons in feeding regulation. Copyright © 2014 the authors 0270-6474/14/3415306-13$15.00/0.

  9. JTPA Summer Youth Enrichment: A Change Agent Guide. A Technical Assistance and Training Series.

    ERIC Educational Resources Information Center

    Bruno, A. Lee; Meltzer, Ann S.

    This technical assistance guide is intended to aid teachers and trainers in Job Training Partnership Act Service Delivery Area (SDA) summer programs that are components of work force skill development programs for youths. It is aimed especially at SDAs that either are experiencing or anticipating resistance to change from their organizations,…

  10. Relationship between soil type and N₂O reductase genotype (nosZ) of indigenous soybean bradyrhizobia: nosZ-minus populations are dominant in Andosols.

    PubMed

    Shiina, Yoko; Itakura, Manabu; Choi, Hyunseok; Saeki, Yuichi; Hayatsu, Masahito; Minamisawa, Kiwamu

    2014-01-01

    Bradyrhizobium japonicum strains that have the nosZ gene, which encodes N2O reductase, are able to mitigate N2O emissions from soils (15). To examine the distribution of nosZ genotypes among Japanese indigenous soybean bradyrhizobia, we isolated bradyrhizobia from the root nodules of soybean plants inoculated with 32 different soils and analyzed their nosZ and nodC genotypes. The 1556 resultant isolates were classified into the nosZ+/nodC+ genotype (855 isolates) and nosZ-/nodC+ genotype (701 isolates). The 11 soil samples in which nosZ- isolates significantly dominated (P < 0.05; the χ(2) test) were all Andosols (a volcanic ash soil prevalent in agricultural fields in Japan), whereas the 17 soil samples in which nosZ+ isolates significantly dominated were mainly alluvial soils (non-volcanic ash soils). This result was supported by a principal component analysis of environmental factors: the dominance of the nosZ- genotype was positively correlated with total N, total C, and the phosphate absorption coefficient in the soils, which are soil properties typical of Andosols. Internal transcribed spacer sequencing of representative isolates showed that the nosZ+ and nosZ- isolates of B. japonicum fell mainly into the USDA110 (BJ1) and USDA6 (BJ2) groups, respectively. These results demonstrated that the group lacking nosZ was dominant in Andosols, which can be a target soil type for an N2O mitigation strategy in soybean fields. We herein discussed how the nosZ genotypes of soybean bradyrhizobia depended on soil types in terms of N2O respiration selection and genomic determinants for soil adaptation.

  11. Consistency of the Health of the Nation Outcome Scales (HoNOS) at inpatient-to-community transition.

    PubMed

    Luo, Wei; Harvey, Richard; Tran, Truyen; Phung, Dinh; Venkatesh, Svetha; Connor, Jason P

    2016-04-27

    The Health of the Nation Outcome Scales (HoNOS) are mandated outcome-measures in many mental-health jurisdictions. When HoNOS are used in different care settings, it is important to assess if setting specific bias exists. This article examines the consistency of HoNOS in a sample of psychiatric patients transitioned from acute inpatient care and community centres. A regional mental health service with both acute and community facilities. 111 psychiatric patients were transferred from inpatient care to community care from 2012 to 2014. Their HoNOS scores were extracted from a clinical database; Each inpatient-discharge assessment was followed by a community-intake assessment, with the median period between assessments being 4 days (range 0-14). Assessor experience and professional background were recorded. The difference of HoNOS at inpatient-discharge and community-intake were assessed with Pearson correlation, Cohen's κ and effect size. Inpatient-discharge HoNOS was on average lower than community-intake HoNOS. The average HoNOS was 8.05 at discharge (median 7, range 1-22), and 12.16 at intake (median 12, range 1-25), an average increase of 4.11 (SD 6.97). Pearson correlation between two total scores was 0.073 (95% CI -0.095 to 0.238) and Cohen's κ was 0.02 (95% CI -0.02 to 0.06). Differences did not appear to depend on assessor experience or professional background. Systematic change in the HoNOS occurs at inpatient-to-community transition. Some caution should be exercised in making direct comparisons between inpatient HoNOS and community HoNOS scores. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  12. Enhanced XOR activity in eNOS-deficient mice: Effects on the nitrate-nitrite-NO pathway and ROS homeostasis.

    PubMed

    Peleli, Maria; Zollbrecht, Christa; Montenegro, Marcelo F; Hezel, Michael; Zhong, Jianghong; Persson, Erik G; Holmdahl, Rikard; Weitzberg, Eddie; Lundberg, Jon O; Carlström, Mattias

    2016-10-01

    Xanthine oxidoreductase (XOR) is generally known as the final enzyme in purine metabolism and as a source of reactive oxygen species (ROS). In addition, this enzyme has been suggested to mediate nitric oxide (NO) formation via reduction of inorganic nitrate and nitrite. This NO synthase (NOS)-independent pathway for NO generation is of particular importance during certain conditions when NO bioavailability is diminished due to reduced activity of endothelial NOS (eNOS) or increased oxidative stress, including aging and cardiovascular disease. The exact interplay between NOS- and XOR-derived NO generation is not fully elucidated yet. The aim of the present study was to investigate if eNOS deficiency is associated with changes in XOR expression and activity and the possible impact on nitrite, NO and ROS homeostasis. Plasma levels of nitrate and nitrite were similar between eNOS deficient (eNOS -/- ) and wildtype (wt) mice. XOR activity was upregulated in eNOS -/- compared with wt, but not in nNOS -/- , iNOS -/- or wt mice treated with the non-selective NOS inhibitor L-NAME. Following an acute dose of nitrate, plasma nitrite increased more in eNOS -/- compared with wt, and this augmented response was abolished by the selective XOR inhibitor febuxostat. Livers from eNOS -/- displayed higher nitrite reducing capacity compared with wt, and this effect was attenuated by febuxostat. Dietary supplementation with nitrate increased XOR expression and activity, but concomitantly reduced superoxide generation. The latter effect was also seen in vitro after nitrite administration. Treatment with febuxostat elevated blood pressure in eNOS -/- , but not in wt mice. A high dose of dietary nitrate reduced blood pressure in naïve eNOS -/- mice, and again this effect was abolished by febuxostat. In conclusion, eNOS deficiency is associated with an upregulation of XOR facilitating the nitrate-nitrite-NO pathway and decreasing the generation of ROS. This interplay between XOR and eNOS

  13. Effect of Flooding and the nosZ Gene in Bradyrhizobia on Bradyrhizobial Community Structure in the Soil.

    PubMed

    Saeki, Yuichi; Nakamura, Misato; Mason, Maria Luisa T; Yano, Tsubasa; Shiro, Sokichi; Sameshima-Saito, Reiko; Itakura, Manabu; Minamisawa, Kiwamu; Yamamoto, Akihiro

    2017-06-24

    We investigated the effects of the water status (flooded or non-flooded) and presence of the nosZ gene in bradyrhizobia on the bradyrhizobial community structure in a factorial experiment that examined three temperature levels (20°C, 25°C, and 30°C) and two soil types (andosol and gray lowland soil) using microcosm incubations. All microcosms were inoculated with Bradyrhizobium japonicum USDA6 T , B. japonicum USDA123, and B. elkanii USDA76 T , which do not possess the nosZ gene, and then half received B. diazoefficiens USDA110 T wt (wt for the wild-type) and the other half received B. diazoefficiens USDA110ΔnosZ. USDA110 T wt possesses the nosZ gene, which encodes N 2 O reductase; 110ΔnosZ, a mutant variant, does not. Changes in the community structure after 30- and 60-d incubations were investigated by denaturing-gradient gel electrophoresis and an image analysis. USDA6 T and 76 T strains slightly increased in non-flooded soil regardless of which USDA110 T strain was present. In flooded microcosms with the USDA110 T wt strain, USDA110 T wt became dominant, whereas in microcosms with the USDA110ΔnosZ, a similar change in the community structure occurred to that in non-flooded microcosms. These results suggest that possession of the nosZ gene confers a competitive advantage to B. diazoefficiens USDA110 T in flooded soil. We herein demonstrated that the dominance of B. diazoefficiens USDA110 T wt within the soil bradyrhizobial population may be enhanced by periods of flooding or waterlogging systems such as paddy-soybean rotations because it appears to have the ability to thrive in moderately anaerobic soil.

  14. Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach.

    PubMed

    Zhai, Shiyan; Song, Genxin; Qin, Yaochen; Ye, Xinyue; Lee, Jay

    2017-01-01

    This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention.

  15. Modeling the impacts of climate change and technical progress on the wheat yield in inland China: An autoregressive distributed lag approach

    PubMed Central

    Qin, Yaochen; Lee, Jay

    2017-01-01

    This study aims to evaluate the impacts of climate change and technical progress on the wheat yield per unit area from 1970 to 2014 in Henan, the largest agricultural province in China, using an autoregressive distributed lag approach. The bounded F-test for cointegration among the model variables yielded evidence of a long-run relationship among climate change, technical progress, and the wheat yield per unit area. In the long run, agricultural machinery and fertilizer use both had significantly positive impacts on the per unit area wheat yield. A 1% increase in the aggregate quantity of fertilizer use increased the wheat yield by 0.19%. Additionally, a 1% increase in machine use increased the wheat yield by 0.21%. In contrast, precipitation during the wheat growth period (from emergence to maturity, consisting of the period from last October to June) led to a decrease in the wheat yield per unit area. In the short run, the coefficient of the aggregate quantity of fertilizer used was negative. Land size had a significantly positive impact on the per unit area wheat yield in the short run. There was no significant short-run or long-run impact of temperature on the wheat yield per unit area in Henan Province. The results of our analysis suggest that climate change had a weak impact on the wheat yield, while technical progress played an important role in increasing the wheat yield per unit area. The results of this study have implications for national and local agriculture policies under climate change. To design well-targeted agriculture adaptation policies for the future and to reduce the adverse effects of climate change on the wheat yield, climate change and technical progress factors should be considered simultaneously. In addition, adaptive measures associated with technical progress should be given more attention. PMID:28950027

  16. Light responses and morphology of bNOS-immunoreactive neurons in the mouse retina

    PubMed Central

    Pang, Ji-Jie; Gao, Fan; Wu, Samuel M.

    2010-01-01

    Nitric oxide (NO), produced by NO synthase (NOS), modulates the function of all retinal neurons and ocular blood vessels and participates in the pathogenesis of ocular diseases. To further understand the regulation of ocular NO release, we systematically studied the morphology, topography and light responses of NOS-containing amacrine cells (NOACs) in dark-adapted mouse retina. Immunohistological staining for neuronal NOS (bNOS), combined with retrograde labeling of ganglion cells (GCs) with Neurobiotin (NB, a gap junction permeable dye) and Lucifer yellow (LY, a less permeable dye), was used to identify NOACs. The light responses of ACs were recorded under whole-cell voltage clamp conditions and cell morphology was examined with a confocal microscope. We found that in dark-adapted conditions bNOS-immunoreactivity (IR) was present primarily in the inner nuclear layer and the ganglion cell layer. bNOS-IR somas were negative for LY, thus they were identified as ACs; nearly 6 % of the cells were labeled by NB but not by LY, indicating that they were dye-coupled with GCs. Three morphological subtypes of NOACs (NI, NII and displaced) were identified. The cell density, inter-cellular distance and the distribution of NOACs were studied in whole retinas. Light evoked depolarizing highly sensitive ON-OFF responses in NI cells and less sensitive OFF responses in NII cells. Frequent (1 to 2 Hz) or abrupt change of light-intensity evoked larger peak responses. The possibility for light to modify NO release from NOACs is discussed. PMID:20503422

  17. Relationship Between Soil Type and N2O Reductase Genotype (nosZ) of Indigenous Soybean Bradyrhizobia: nosZ-minus Populations are Dominant in Andosols

    PubMed Central

    Shiina, Yoko; Itakura, Manabu; Choi, Hyunseok; Saeki, Yuichi; Hayatsu, Masahito; Minamisawa, Kiwamu

    2014-01-01

    Bradyrhizobium japonicum strains that have the nosZ gene, which encodes N2O reductase, are able to mitigate N2O emissions from soils (15). To examine the distribution of nosZ genotypes among Japanese indigenous soybean bradyrhizobia, we isolated bradyrhizobia from the root nodules of soybean plants inoculated with 32 different soils and analyzed their nosZ and nodC genotypes. The 1556 resultant isolates were classified into the nosZ+/nodC+ genotype (855 isolates) and nosZ−/nodC+ genotype (701 isolates). The 11 soil samples in which nosZ− isolates significantly dominated (P < 0.05; the χ2 test) were all Andosols (a volcanic ash soil prevalent in agricultural fields in Japan), whereas the 17 soil samples in which nosZ+ isolates significantly dominated were mainly alluvial soils (non-volcanic ash soils). This result was supported by a principal component analysis of environmental factors: the dominance of the nosZ− genotype was positively correlated with total N, total C, and the phosphate absorption coefficient in the soils, which are soil properties typical of Andosols. Internal transcribed spacer sequencing of representative isolates showed that the nosZ+ and nosZ− isolates of B. japonicum fell mainly into the USDA110 (BJ1) and USDA6 (BJ2) groups, respectively. These results demonstrated that the group lacking nosZ was dominant in Andosols, which can be a target soil type for an N2O mitigation strategy in soybean fields. We herein discussed how the nosZ genotypes of soybean bradyrhizobia depended on soil types in terms of N2O respiration selection and genomic determinants for soil adaptation. PMID:25476067

  18. Pedagogical Reflections by Secondary Science Teachers at Different NOS Implementation Levels

    NASA Astrophysics Data System (ADS)

    Herman, Benjamin C.; Clough, Michael P.; Olson, Joanne K.

    2017-02-01

    This study investigated what 13 secondary science teachers at various nature of science (NOS) instruction implementation levels talked about when they reflected on their teaching. We then determined if differences exist in the quality of those reflections between high, medium, and low NOS implementers. This study sought to answer the following questions: (1) What do teachers talk about when asked general questions about their pedagogy and NOS pedagogy and (2) what qualitative differences, if any, exist within variables across teachers of varying NOS implementation levels? Evidence derived from these teachers' reflections indicated that self-efficacy and perceptions of general importance for NOS instruction were poor indicators of NOS implementation. However, several factors were associated with the extent that these teachers implemented NOS instruction, including the utility value they hold for NOS teaching, considerations of how people learn, understanding of NOS pedagogy, and their ability to accurately and deeply self-reflect about teaching. Notably, those teachers who effectively implemented the NOS at higher levels value NOS instruction for reasons that transcend immediate instructional objectives. That is, they value teaching NOS for achieving compelling ends realized long after formal schooling (e.g., lifelong socioscientific decision-making for civic reasons), and they deeply reflect about how to teach NOS by drawing from research about how people learn. Low NOS implementers' simplistic notions and reflections about teaching and learning appeared to be impeding factors to accurate and consistent NOS implementation. This study has implications for science teacher education efforts that promote NOS instruction.

  19. 76 FR 23970 - Notice of Proposed Changes to Section IV of the Virginia State Technical Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-29

    ... DEPARTMENT OF AGRICULTURE Natural Resources Conservation Service Notice of Proposed Changes to Section IV of the Virginia State Technical Guide AGENCY: Natural Resources Conservation Service (NRCS), U..., 395, Stream Habitat Improvement and Management, 422, Hedgerow Planting, 643, Restoration and...

  20. Exploring Elementary Science Methods Course Contexts to Improve Preservice Teachers' NOS of Science Conceptions and Understandings of NOS Teaching Strategies

    ERIC Educational Resources Information Center

    Akerson, Valarie L.; Weiland, Ingrid; Rogers, Meredith Park; Pongsanon, Khemmawaddee; Bilican, Kader

    2014-01-01

    We explored adaptations to an elementary science methods course to determine how varied contexts could improve elementary preservice teachers' conceptions of NOS as well as their ideas for teaching NOS to elementary students. The contexts were (a) NOS Theme in which the course focused on the teaching of science through the consistent teaching…

  1. Career and Technical Education in the Crossroads of Change

    ERIC Educational Resources Information Center

    Quailey, Janice

    2012-01-01

    Career and technical education (CTE) is faced with numerous forces that may impact its future. A variety of forces directly or indirectly affect CTE, ranging from the persisting stigma or negative image of career and technical education, the schools' curricular structure and requirements, along with federal laws such as No Child Left Behind (NCLB)…

  2. Lipopolysaccharide-induced overproduction of nitric oxide and overexpression of iNOS and interleukin-1β proteins in zinc-deficient rats.

    PubMed

    Miyazaki, Takashi; Takenaka, Tsuneo; Inoue, Tsutomu; Sato, Makiko; Miyajima, Yuka; Nodera, Makoto; Hanyu, Mayuko; Ohno, Yoichi; Shibazaki, Satomi; Suzuki, Hiromichi

    2012-03-01

    Zinc deficiency leads to decreased cellular immune responses. The overproduction of nitrogen species derived from inducible nitric oxide synthase (iNOS), its enzyme, and interleukine-1 beta (IL-1β), and inflammatory cytokine have been implicated in immune responses. The goal of this study was to investigate the effects of lipopolysaccharide (LPS)-induced changes in NO metabolites, iNOS, and IL-1β protein expression in the lungs of zinc-deficient rats. Male Sprague-Dawley rats (body weight, 100 g) were divided into two groups and were fed either a zinc-deficient diet (ZnD) or a zinc-containing diet (Cont). After 4 weeks on these diets, rats received a 10-mg/kg dose of LPS injected via the tail vein and were then maintained for an additional 72 h. To determine total NO concentrations in the blood, serum zinc concentration, iNOS protein expression, IL-1β, and iNOS immunohistochemistry, blood and lung samples were obtained at pre-LPS injection, 5, 24, and 72 h after injection. Total NO levels were significantly increased at 5, at 24, and at 72 h after LPS injection compared with pre-LPS injection level in ZnD group; significant changes in total NO levels was elevated at 5 h from at pre-LPS level but not significant changes from basal level at 24 and 72 h in the control group. Based on western blot analyses and immunohistochemistry, clear bands indicating iNOS and IL-1β protein expression and iNOS antibody-stained inflammatory cells were detected at 5 and 24 h in the ZnD group and 5 h in the Cont group, not observed at 24 and 72 h in the control group. These results suggest that zinc deficiency induces overexpression of iNOS and IL-1β proteins from inflammatory cells around the alveolar blood vessels, resulting in overproduction of total NO and persisted inflammatory response in the zinc-deficient rat lung. Taken together, overexpression of LPS-induced iNOS, overproduction of iNOS-derived NO, and overexpression of IL-1β may induce nitrosative and oxidative

  3. 76 FR 59382 - Notice of Proposed Change to Section IV of the Virginia State Technical Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... DEPARTMENT OF AGRICULTURE Natural Resources Conservation Service Notice of Proposed Change to Section IV of the Virginia State Technical Guide AGENCY: Natural Resources Conservation Service (NRCS), U... Harvest Management, 657, Wetland Restoration, 658, Wetland Creation, and 659, Wetland Enhancement. These...

  4. National policies for technical change: Where are the increasing returns to economic research?

    PubMed Central

    Pavitt, Keith

    1996-01-01

    Improvements over the past 30 years in statistical data, analysis, and related theory have strengthened the basis for science and technology policy by confirming the importance of technical change in national economic performance. But two important features of scientific and technological activities in the Organization for Economic Cooperation and Development countries are still not addressed adequately in mainstream economics: (i) the justification of public funding for basic research and (ii) persistent international differences in investment in research and development and related activities. In addition, one major gap is now emerging in our systems of empirical measurement—the development of software technology, especially in the service sector. There are therefore dangers of diminishing returns to the usefulness of economic research, which continues to rely completely on established theory and established statistical sources. Alternative propositions that deserve serious consideration are: (i) the economic usefulness of basic research is in the provision of (mainly tacit) skills rather than codified and applicable information; (ii) in developing and exploiting technological opportunities, institutional competencies are just as important as the incentive structures that they face; and (iii) software technology developed in traditional service sectors may now be a more important locus of technical change than software technology developed in “high-tech” manufacturing. PMID:8917481

  5. Multifaceted NOS Instruction: Contextualizing Nature of Science with Documentary Films

    ERIC Educational Resources Information Center

    Bloom, Mark; Binns, Ian C.; Koehler, Catherine

    2015-01-01

    This research focuses on inservice science teachers' conceptions of nature of science (NOS) before and after a two-week intensive summer professional development (PD). The PD combined traditional explicit NOS instruction, numerous interactive interventions that highlighted NOS aspects, along with documentary films that portrayed NOS in context of…

  6. nNOS expression in the brain of rats after burn and the effect of the ACE inhibitor captopril.

    PubMed

    Demiralay, Ebru; Saglam, Ibrahim Yaman; Ozdamar, Emine Nur; Sehirli, Ahmet Ozer; Sener, Goksel; Saglam, Esra

    2013-08-01

    To investigate the role of endogenous neuronal nitric oxide synthase (nNOS) on brain injury after burn and the effects of the captopril. Wistar albino rats (200-250 g) were exposed on the dorsal surface to 90°C (burn) or 25°C (sham) water for 10 s. The ACE group was treated with intraperitoneal 10 mg/kg captopril immediately after burn and this treatment was repeated twice daily. At the end of the 24 h brain samples were taken. nNOS was studied in brain areas by immunohistochemistry. There was no difference between the cerebellar and hypothalamic areas the nNOS expression of all groups. nNOS expression increased in the frontal cortex, striatum and midbrain in the burn group compared to the control group. In the frontal cortex, nNOS expression significantly decreased after ACE inhibitor treatment (p<0.05). The striatal nNOS of the ACE group significantly increased when compared to the control group (p=0.001). In the midbrain of the animals, nNOS decreased in the ACE group. Hippocampal nNOS expression did not change after burn and significantly increased after ACE inhibitor therapy (p<0.05). Our data showed that the pathophysiological events following burn appear to be related to an acute inflammatory reaction which is associated with nNOS in the frontal cortex, striatum and midbrain, and captopril treatment abrogates the nNOS response in the frontal cortex and midbrain. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

  7. 75 FR 34974 - Notice of Proposed Change to Section IV of the Virginia State Technical Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-21

    ... DEPARTMENT OF AGRICULTURE Natural Resources Conservation Service Notice of Proposed Change to Section IV of the Virginia State Technical Guide AGENCY: Natural Resources Conservation Service (NRCS), U... Road, Suite 209, Richmond, Virginia 23229-5014; Telephone number (804) 287-1691; Fax number (804) 287...

  8. 77 FR 55180 - Notice of Proposed Changes to Section IV of the Virginia State Technical Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-07

    ... DEPARTMENT OF AGRICULTURE Natural Resources Conservation Service Notice of Proposed Changes to Section IV of the Virginia State Technical Guide AGENCY: Natural Resources Conservation Service (NRCS), U..., Virginia 23229-5014; Telephone number (804) 287-1691 or [email protected] Copies of the practice...

  9. 75 FR 32858 - Medicare Program; Policy and Technical Changes to the Medicare Advantage and the Medicare...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-10

    ... Medicare Advantage and the Medicare Prescription Drug Benefit Programs; Corrections AGENCY: Centers for... Advantage and the Medicare Prescription Drug Benefit Programs'' which appeared in the April 15, 2010 Federal... and Technical Changes to the Medicare Advantage and the Medicare Prescription Drug Benefit Programs...

  10. Clinicopathological analysis in PTCL-NOS with CADM1 expression.

    PubMed

    Kato, Takeharu; Miyoshi, Hiroaki; Kobayashi, Seiichiro; Yoshida, Noriaki; Imaizumi, Yoshitaka; Seto, Masao; Uchimaru, Kaoru; Miyazaki, Yasushi; Ohshima, Koichi

    2017-11-01

    Peripheral T cell lymphoma, not otherwise specified (PTCL-NOS), is a heterogeneous disease with respect to clinicopathological features. Cell adhesion molecule 1 (CADM1) has been reported to be ectopically expressed in adult T cell leukaemia/lymphoma (ATLL). However, the frequency of CADM1 expression remains unknown in peripheral T cell lymphomas. In the current study, CADM1 expression was analysed in 88 PTCL-NOS patients. CADM1 was expressed in 14 of 88 (15.9%) PTCL-NOS cases, and its expression was associated with C-C chemokine receptor type 4 (CCR4) expression and nuclear atypia. CADM1-positive PTCL-NOS cases (10/74) had a significantly poorer prognosis than CADM1-negative cases (64/74) (P = 0.001). Multivariate analysis confirmed that CADM1 expression was an independent prognostic factor in PTCL-NOS. These findings suggest that CADM1 expression is a novel prognostic factor for PTCL-NOS.

  11. Identification of hamster inducible nitric oxide synthase (iNOS) promoter sequences that influence basal and inducible iNOS expression

    PubMed Central

    Saldarriaga, Omar A.; Travi, Bruno L.; Choudhury, Goutam Ghosh; Melby, Peter C.

    2012-01-01

    IFN-γ/LPS-activated hamster (Mesocricetus auratus) macrophages express significantly less iNOS (NOS2) than activated mouse macrophages, which contributes to the hamster's susceptibility to intracellular pathogens. We determined a mechanism responsible for differences in iNOS promoter activity in hamsters and mice. The HtPP (1.2 kb) showed low basal and inducible promoter activity when compared with the mouse, and sequences within a 100-bp region (−233 to −133) of the mouse and hamster promoters influenced this activity. Moreover, within this 100 bp, we identified a smaller region (44 bp) in the mouse promoter, which recovered basal promoter activity when swapped into the hamster promoter. The mouse homolog (100-bp region) contained a cis-element for NF-IL-6 (−153/−142), which was absent in the hamster counterpart. EMSA and supershift assays revealed that the hamster sequence did not support the binding of NF-IL-6. Introduction of a functional NF-IL-6 binding sequence into the hamster promoter or its alteration in the mouse promoter revealed the critical importance of this transcription factor for full iNOS promoter activity. Furthermore, the binding of NF-IL-6 to the iNOS promoter (−153/−142) in vivo was increased in mouse cells but was reduced in hamster cells after IFN-γ/LPS stimulation. Differences in the activity of the iNOS promoters were evident in mouse and hamster cells, so they were not merely a result of species-specific differences in transcription factors. Thus, we have identified unique DNA sequences and a critical transcription factor, NF-IL-6, which contribute to the overall basal and inducible expression of hamster iNOS. PMID:22517919

  12. Interaction between HSP 70 and iNOS in skeletal muscle injury and repair.

    PubMed

    Kim, Kijeong

    2015-10-01

    Muscle injuries are frequently occurred in various sports. The biological process and mechanism of muscle repair after injury are well known through the many studies. This study aimed at presenting heat shock protein and nitric oxide synthase are to respond to muscle damage and repair. This section discusses the results obtained through many articles. Heat shock proteins (HSPs) are considered to play an essential role in protecting cells from damage, preparing them to survive on new environmental challenges. In addition, exercise-induced changes such as heat shock, oxidative, metabolic, muscular, and cytokine stress seem to be responsible for the HSP response to exercise. Also, inducible nitric oxide synthase (iNOS) generates nitric oxide (NO) for prolonged period and causes pathophysiological effects. Furthermore, iNOS is involved in processes such as cell injury, wound repair, embryogenesis, tissue differentiation, and suppression of tumorigenesis. In conclusion, the inhibition of HSP 70 on caspase-3 and apoptosis is associated with its inhibition on iNOS that leads to less NO production.

  13. 75 FR 47259 - Notice of Proposed Change to Section IV of the Virginia State Technical Guide

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-05

    ... DEPARTMENT OF AGRICULTURE Natural Resources Conservation Service Notice of Proposed Change to Section IV of the Virginia State Technical Guide AGENCY: Natural Resources Conservation Service (NRCS), U..., Virginia 23229-5014; Telephone number (804) 287-1691; Fax number (804) 287-1737. Copies of the practice...

  14. St36 electroacupuncture activates nNOS, iNOS and ATP-sensitive potassium channels to promote orofacial antinociception in rats.

    PubMed

    Almeida, R T; Galdino, G; Perez, A C; Silva, G; Romero, T R; Duarte, I D

    2017-02-01

    Orofacial pain is pain perceived in the face and/or oral cavity, generally caused by diseases or disorders of regional structures, by dysfunction of the nervous system, or through referral from distant sources. Treatment of orofacial pain is mainly pharmacological, but it has increased the number of reports demonstrating great clinical results with the use of non-pharmacological therapies, among them electroacupuncture. However, the mechanisms involved in the electroacupuncture are not well elucidated. Thus, the present study investigate the involvement of the nitric oxide synthase (NOS) and ATP sensitive K + channels (KATP) in the antinociception induced by electroacupuncture (EA) at acupoint St36. Thermal nociception was applied in the vibrissae region of rats, and latency time for face withdrawal was measured. Electrical stimulation of acupoint St36 for 20 minutes reversed the thermal withdrawal latency and this effect was maintained for 150 min. Intraperitoneal administration of specific inhibitors of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and a KATP channels blocker reversed the antinociception induced by EA. Furthermore, nitrite concentration in cerebrospinal fluid (CSF) and plasma, increased 4 and 3-fold higher, respectively, after EA. This study suggests that NO participates of antinociception induced by EA by nNOS, iNOS and ATP-sensitive K + channels activation.

  15. Advancing the Perceptions of the Nature of Science (NOS): Integrating Teaching the NOS in a Science Content Course

    ERIC Educational Resources Information Center

    Aflalo, Ester

    2014-01-01

    Background: Understanding the nature of science (NOS) has been a key objective in teaching sciences for many years. Despite the importance of this goal it is, until this day, a complex challenge that we are far from achieving. Purpose: The study was conducted in order to further the understanding of the NOS amongst preservice teachers. It explores…

  16. eNOS-uncoupling in age-related erectile dysfunction

    PubMed Central

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  17. Zinc regulates iNOS-derived nitric oxide formation in endothelial cells.

    PubMed

    Cortese-Krott, Miriam M; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D; Suschek, Christoph V

    2014-01-01

    Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation.

  18. Zinc regulates iNOS-derived nitric oxide formation in endothelial cells

    PubMed Central

    Cortese-Krott, Miriam M.; Kulakov, Larissa; Opländer, Christian; Kolb-Bachofen, Victoria; Kröncke, Klaus-D.; Suschek, Christoph V.

    2014-01-01

    Aberrant production of nitric oxide (NO) by inducible NO synthase (iNOS) has been implicated in the pathogenesis of endothelial dysfunction and vascular disease. Mechanisms responsible for the fine-tuning of iNOS activity in inflammation are still not fully understood. Zinc is an important structural element of NOS enzymes and is known to inhibit its catalytical activity. In this study we aimed to investigate the effects of zinc on iNOS activity and expression in endothelial cells. We found that zinc down-regulated the expression of iNOS (mRNA+protein) and decreased cytokine-mediated activation of the iNOS promoter. Zinc-mediated regulation of iNOS expression was due to inhibition of NF-κB transactivation activity, as determined by a decrease in both NF-κB-driven luciferase reporter activity and expression of NF-κB target genes, including cyclooxygenase 2 and IL-1β. However, zinc did not affect NF-κB translocation into the nucleus, as assessed by Western blot analysis of nuclear and cytoplasmic fractions. Taken together our results demonstrate that zinc limits iNOS-derived high output NO production in endothelial cells by inhibiting NF-κB-dependent iNOS expression, pointing to a role of zinc as a regulator of iNOS activity in inflammation. PMID:25180171

  19. Gallic Acid Enriched Fraction of Phyllanthus emblica Potentiates Indomethacin-Induced Gastric Ulcer Healing via e-NOS-Dependent Pathway

    PubMed Central

    Chatterjee, Ananya; Chatterjee, Sirshendu; Biswas, Angshuman; Bhattacharya, Sayanti; Chattopadhyay, Subrata; Bandyopadhyay, Sandip K.

    2012-01-01

    The healing activity of gallic acid enriched ethanolic extract (GAE) of Phyllanthus emblica fruits (amla) against the indomethacin-induced gastric ulceration in mice was investigated. The activity was correlated with the ability of GAE to alter the cyclooxygenase- (COX-) dependent healing pathways. Histology of the stomach tissues revealed maximum ulceration on the 3rd day after indomethacin (18 mg/kg, single dose) administration that was associated with significant increase in inflammatory factors, namely, mucosal myeloperoxidase (MPO) activity and inducible nitric oxide synthase (i-NOS) expression. Proangiogenic parameters such as the levels of prostaglandin (PG) E2, vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), von Willebrand Factor VIII, and endothelial NOS (e-NOS) were downregulated by indomethacin. Treatment with GAE (5 mg/kg/day) and omeprazole (3 mg/kg/day) for 3 days led to effective healing of the acute ulceration, while GAE could reverse the indomethacin-induced proinflammatory changes of the designated biochemical parameters. The ulcer healing activity of GAE was, however, compromised by coadministration of the nonspecific NOS inhibitor, N-nitro-L-arginine methyl ester (L-NAME), but not the i-NOS-specific inhibitor, L-N6-(1-iminoethyl) lysine hydrochloride (L-NIL). Taken together, these results suggested that the GAE treatment accelerates ulcer healing by inducing PGE2 synthesis and augmenting e-NOS/i-NOS ratio. PMID:22966242

  20. Posttranscriptional regulation of human iNOS by the NO/cGMP pathway.

    PubMed

    Pérez-Sala, D; Cernuda-Morollón, E; Díaz-Cazorla, M; Rodríguez-Pascual, F; Lamas, S

    2001-03-01

    Nitric oxide (NO) and cGMP may exert positive or negative effects on inducible NO synthase (iNOS) expression. We have explored the influence of the NO/cGMP pathway on iNOS levels in human mesangial cells. Inhibition of NOS activity during an 8-h stimulation with IL-1beta plus tumor necrosis factor (TNF)-alpha reduced iNOS levels, while NO donors amplified iNOS induction threefold. However, time-course studies revealed a subsequent inhibitory effect of NO donors on iNOS protein and mRNA levels. This suggests that NO may contribute both to iNOS induction and downregulation. Soluble guanylyl cyclase (sGC) activation may be involved in these effects. Inhibition of sGC attenuated IL-1beta/TNF-alpha-elicited iNOS induction and reduced NO-driven amplification. Interestingly, cGMP analogs also modulated iNOS protein and mRNA levels in a biphasic manner. Inhibition of transcription unveiled a negative posttranscriptional modulation of the iNOS transcript by NO and cGMP at late times of induction. Supplementation with 8-bromo-cGMP (8-BrcGMP) reduced iNOS mRNA stability by 50%. These observations evidence a complex feedback regulation of iNOS expression, in which posttranscriptional mechanisms may play an important role.

  1. Technical assistance from state health departments for communities engaged in policy, systems, and environmental change: the ACHIEVE Program.

    PubMed

    Hefelfinger, Jenny; Patty, Alice; Ussery, Ann; Young, Walter

    2013-10-24

    This study assessed the value of technical assistance provided by state health department expert advisors and by the staff of the National Association of Chronic Disease Directors (NACDD) to community groups that participated in the Action Communities for Health, Innovation, and Environmental Change (ACHIEVE) Program, a CDC-funded health promotion program. We analyzed quantitative and qualitative data reported by community project coordinators to assess the nature and value of technical assistance provided by expert advisors and NACDD staff and the usefulness of ACHIEVE resources in the development and implementation of community action plans. A grounded theory approach was used to analyze and categorize phrases in text data provided by community coordinators. Open coding placed conceptual labels on text phrases. Frequency distributions of the quantitative data are described and discussed. The most valuable technical assistance and program support resources were those determined to be in the interpersonal domain (ie, interactions with state expert advisors, NACDD staff, and peer-to-peer support). The most valuable technical assistance events were action institutes, coaches' meetings, webinars, and technical assistance conference calls. This analysis suggests that ACHIEVE communities valued the management and training assistance provided by expert advisors and NACDD staff. State health department expert advisors provided technical guidance and support, including such skills or knowledge-based services as best-practice strategies, review and discussion of community assessment data, sustainability planning, and identification of possible funding opportunities. NACDD staff led development and implementation of technical assistance events.

  2. 9. "TEST STANDS NOS. 11, 13, & 15; CONCRETE STRUCTURAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. "TEST STANDS NOS. 1-1, 1-3, & 1-5; CONCRETE STRUCTURAL SECTIONS AND DETAILS." Specifications No. ENG 04-35350-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/13. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, no change; Date: 17 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

  3. 14. "TEST STANDS NOS. 11, 13, & 15; MISCELLANEOUS DETAILS." ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. "TEST STANDS NOS. 1-1, 1-3, & 1-5; MISCELLANEOUS DETAILS." Specifications No. OC12-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/22, Rev. D. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04-353 Eng. 177, Rev. D, no change; Date: 17 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

  4. Vocational-Technical Education; A Prospectus for Change.

    ERIC Educational Resources Information Center

    Schaefer, Carl J., Ed.; Kaufman, Jacob J., Ed.

    To seek resolution of problems in providing education for youth and adults oriented toward the world of work, the Massachusetts Advisory Council on Education (MACE) undertook a study of vocational-technical education as a major project. This publication contains the major papers and prepared reactions to these papers, which were presented at a…

  5. 75 FR 19677 - Medicare Program; Policy and Technical Changes to the Medicare Advantage and the Medicare...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-15

    ... Care and Network-Based Private Fee-for-Service Plans Under Part C (Sec. 422.112) 7. Deemable Program... Cost by HMO/CMP Cost Contractors and Health Care Prepayment Plans (HCPPs) (Sec. 417.564) 4. Calculation... and Other Technical Changes 1. Application of Subpart M to Health Care Prepayment Plans (Sec. 417.840...

  6. The Scientific Value and Technical Challenge of Chang'E-4 Landing on the Far-side of the Moon

    NASA Astrophysics Data System (ADS)

    Li, Fei; Zhang, He; Wu, Xueying; Ma, Jinan; Zhou, Wenyan

    2016-07-01

    The mission of Chang'E-4 probe is landing on the far-side of the moon for the first time in human history. Compared with the near-side, far-side landing has unique scientific value and more challenging technology implementation. The scientific significance of the exploration of far-side of the moon and the technical difficulties and solution approach of the Chang'E-4 were discussed in this paper. In science, the far-side of the Moon is an ideal scientific platform in that it is shielded from terrestrial radio-frequency interference. The terrane that records the formation of the primordial crust is located largely on the far-side hemisphere, and there is the largest and oldest recognized impact basin in our Solar System, the South Pole-Aitken basin. In technology, the difficulties mainly includes the analysis of the influence of lunar topography of far-side on the landing descent strategy, the study of relay orbit and operating modes for the relay satellite in the Earth-Moon L2(Lagrange point 2), and the requirement analysis of autonomous management due to the relay communication. It will provide the reference for landing exploration of the far-side of the moon.

  7. "Non alcoholic fatty liver disease and eNOS dysfunction in humans".

    PubMed

    Persico, Marcello; Masarone, Mario; Damato, Antonio; Ambrosio, Mariateresa; Federico, Alessandro; Rosato, Valerio; Bucci, Tommaso; Carrizzo, Albino; Vecchione, Carmine

    2017-03-07

    NAFLD is associated to Insulin Resistance (IR). IR is responsible for Endothelial Dysfunction (ED) through the impairment of eNOS function. Although eNOS derangement has been demonstrated in experimental models, no studies have directly shown that eNOS dysfunction is associated with NAFLD in humans. The aim of this study is to investigate eNOS function in NAFLD patients. Fifty-four NAFLD patients were consecutively enrolled. All patients underwent clinical and laboratory evaluation and liver biopsy. Patients were divided into two groups by the presence of NAFL or NASH. We measured vascular reactivity induced by patients' platelets on isolated mice aorta rings. Immunoblot assays for platelet-derived phosphorylated-eNOS (p-eNOS) and immunohistochemistry for hepatic p-eNOS have been performed to evaluate eNOS function in platelets and liver specimens. Flow-mediated-dilation (FMD) was also performed. Data were compared with healthy controls. Twenty-one (38, 8%) patients had NAFL and 33 (61, 7%) NASH. No differences were found between groups and controls except for HOMA and insulin (p < 0.0001). Vascular reactivity demonstrated a reduced function induced from NAFLD platelets as compared with controls (p < 0.001), associated with an impaired p-eNOS in both platelets and liver (p < 0.001). NAFL showed a higher impairment of eNOS phosphorylation in comparison to NASH (p < 0.01). In contrast with what observed in vitro, the vascular response by FMD was worse in NASH as compared with NAFL. Our data showed, for the first time in humans, that NAFLD patients show a marked eNOS dysfunction, which may contribute to a higher CV risk. eNOS dysfunction observed in platelets and liver tissue didn't match with FMD.

  8. iNOS expression in CD4+ T cells limits Treg induction by repressing TGFβ1: combined iNOS inhibition and Treg depletion unmask endogenous antitumor immunity.

    PubMed

    Jayaraman, Padmini; Alfarano, Matthew G; Svider, Peter F; Parikh, Falguni; Lu, Geming; Kidwai, Sarah; Xiong, Huabao; Sikora, Andrew G

    2014-12-15

    Expression of inducible nitric oxide synthase (iNOS) in different cellular compartments may have divergent effects on immune function. We used a syngeneic tumor model to functionally characterize the role of iNOS in regulation of CD4(+)FOXP3(+) regulatory T cells (Treg), and optimize the beneficial effects of iNOS inhibition on antitumor immunity. Wild-type (WT) or iNOS knockout mice bearing established MT-RET-1 melanoma were treated with the small-molecule iNOS inhibitor L-NIL and/or cyclophosphamide alone or in combination. The effect of iNOS inhibition or knockout on induction of Treg from mouse and human CD4(+) T cells in ex vivo culture was determined in parallel in the presence or absence of TGFβ1-depleting antibodies, and TGFβ1 levels were assessed by ELISA. Whereas intratumoral myeloid-derived suppressor cells (MDSC) were suppressed by iNOS inhibition or knockout, systemic and intratumoral FOXP3(+) Treg levels increased in tumor-bearing mice. iNOS inhibition or knockout similarly enhanced induction of Treg from activated cultured mouse splenocytes or purified human or mouse CD4(+) T cells in a TGFβ1-dependent manner. Although either iNOS inhibition or Treg depletion with low-dose cyclophosphamide alone had little effect on growth of established MT-RET1 melanoma, combination treatment potently inhibited MDSC and Treg, boosted tumor-infiltrating CD8(+) T-cell levels, and arrested tumor growth in an immune-dependent fashion. iNOS expression in CD4(+) T cells suppresses Treg induction by inhibiting TGFβ1 production. Our data suggest that iNOS expression has divergent effects on induction of myeloid and lymphoid-derived regulatory populations, and strongly support development of combinatorial treatment approaches that target these populations simultaneously. ©2014 American Association for Cancer Research.

  9. Principles and Procedures in Technical Assistance: An Approach to Educational Change

    ERIC Educational Resources Information Center

    Lillie, David L.; Black, Talbot

    1976-01-01

    The Technical Assistance Development System (TADS) has developed through the years a system for technical assistance and has identified some important principles that should be followed in the operation of organizational support systems. (Author/ER)

  10. 13. "TEST STANDS NOS. 11, 13, & 15; CONCRETE STRUCTURAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. "TEST STANDS NOS. 1-1, 1-3, & 1-5; CONCRETE STRUCTURAL SECTIONS AND DETAILS." Specifications No. OC12-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/18, Rev. D. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, Rev. D, no change; Date: 18 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

  11. 15. "TEST STANDS NOS. 11, 13, & 15; STRUCTURAL STEEL; ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. "TEST STANDS NOS. 1-1, 1-3, & 1-5; STRUCTURAL STEEL; PLAN & DETAILS." Specifications No. ENG 04-353-50-10; Drawing No. 60-09-04; no sheet number within title block. D.O. SERIES 1109/34, Rev. A. Stamped: RECORD DRAWING - AS CONSTRUCTED. Below stamp: Contract DA-04353 Eng. 177, Rev. A, no change; Date: 21 Dec. 1951. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Test Stand 1-5, Test Area 1-115, northwest end of Saturn Boulevard, Boron, Kern County, CA

  12. Technical Assistance From State Health Departments for Communities Engaged in Policy, Systems, and Environmental Change: The ACHIEVE Program

    PubMed Central

    Hefelfinger, Jenny; Patty, Alice; Ussery, Ann

    2013-01-01

    Introduction This study assessed the value of technical assistance provided by state health department expert advisors and by the staff of the National Association of Chronic Disease Directors (NACDD) to community groups that participated in the Action Communities for Health, Innovation, and Environmental Change (ACHIEVE) Program, a CDC-funded health promotion program. Methods We analyzed quantitative and qualitative data reported by community project coordinators to assess the nature and value of technical assistance provided by expert advisors and NACDD staff and the usefulness of ACHIEVE resources in the development and implementation of community action plans. A grounded theory approach was used to analyze and categorize phrases in text data provided by community coordinators. Open coding placed conceptual labels on text phrases. Frequency distributions of the quantitative data are described and discussed. Results The most valuable technical assistance and program support resources were those determined to be in the interpersonal domain (ie, interactions with state expert advisors, NACDD staff, and peer-to-peer support). The most valuable technical assistance events were action institutes, coaches’ meetings, webinars, and technical assistance conference calls. Conclusion This analysis suggests that ACHIEVE communities valued the management and training assistance provided by expert advisors and NACDD staff. State health department expert advisors provided technical guidance and support, including such skills or knowledge-based services as best-practice strategies, review and discussion of community assessment data, sustainability planning, and identification of possible funding opportunities. NACDD staff led development and implementation of technical assistance events. PMID:24157078

  13. Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum.

    PubMed

    Di Girolamo, G; Farina, M; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A M

    2003-07-01

    1. The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. 2. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. 3. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg(-1), i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. 4. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. 5. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. 6. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti-inflammatory effect of these NSAIDs and may also have importance in the prevention of NO-mediated neuronal injury.

  14. Effects of cyclooxygenase inhibitor pretreatment on nitric oxide production, nNOS and iNOS expression in rat cerebellum

    PubMed Central

    DiGirolamo, G; Farina, M; Riberio, M L; Ogando, D; Aisemberg, J; de los Santos, A R; Martí, M L; Franchi, A M

    2003-01-01

    The therapeutic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is thought to be due mainly to its inhibition of cyclooxygenase (COX) enzymes, but there is a growing body of research that now demonstrates a variety of NSAIDs effects on cellular signal transduction pathways other than those involving prostaglandins. Nitric oxide (NO) as a free radical and an agent that gives rise to highly toxic oxidants (peroxynitrile, nitric dioxide, nitron ion), becomes a cause of neuronal damage and death in some brain lesions such as Parkinson and Alzheimer disease, and Huntington's chorea. In the present study, the in vivo effect of three NSAIDs (lysine clonixinate (LC), indomethacine (INDO) and meloxicam (MELO)) on NO production and nitric oxide synthase expression in rat cerebellar slices was analysed. Rats were treated with (a) saline, (b) lipopolysaccharide (LPS) (5 mg kg−1, i.p.), (c) saline in combination with different doses of NSAIDs and (d) LPS in combination with different doses of NSAIDs and then killed 6 h after treatment. NO synthesis, evaluated by Bred and Snyder technique, was increased by LPS. This augmentation was inhibited by coadministration of the three NSAIDs assayed. None of the NSAIDs tested was able to modify control NO synthesis. Expression of iNOS and neural NOS (nNOS) was detected by Western blotting in control and LPS-treated rats. LC and INDO, but not MELO, were able to inhibit the expression of these enzymes. Therefore, reduction of iNOS and nNOS levels in cerebellum may explain, in part, the anti-inflammatory effect of these NSAIDs and may also have importance in the prevention of NO-mediated neuronal injury. PMID:12871835

  15. NOS3 gene polymorphisms and exercise hemodynamics in postmenopausal women.

    PubMed

    Hand, B D; McCole, S D; Brown, M D; Park, J J; Ferrell, R E; Huberty, A; Douglass, L W; Hagberg, J M

    2006-12-01

    We tested whether the G894T and T-786C NOS3 polymorphisms were associated with exercise cardiovascular (CV) hemodynamics in sedentary, physically active, and endurance-trained postmenopausal women. CV hemodynamic parameters including heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressures and cardiac output (Q), as determined by acetylene rebreathing, stroke volume (SV), arteriovenous oxygen difference (a-vO2 diff), and total peripheral resistance (TPR) were measured during submaximal (40, 60, 80 %) and maximal (approximately 100 % VO2max) exercise. NOS3 G894T genotype was not significantly associated, either independently or interactively with habitual physical activity (PA) level, with SBP, Q, TPR, or a-vO2 diff during submaximal or maximal exercise. However, NOS3 894T non-carriers had a higher submaximal exercise HR than NOS3 894T allele carriers (120 +/- 2 vs. 112 +/- 2 beats/min, p = 0.007). NOS3 894T allele carriers had a higher SV than 894T non-carriers (78 +/- 2 vs. 72 +/- 2 ml/beat, p = 0.03) during submaximal exercise. NOS3 894T non-carriers also had a higher maximal exercise HR averaged across habitual PA groups than T allele carrier women (165 +/- 2 vs. 158 +/- 2 beats/min, p = 0.04). NOS3 894T allele carriers also tended to have a higher SV during maximal exercise than 894T non-carriers (70 +/- 2 vs. 64 +/- 2 ml/beat, p = 0.08). NOS3 T-786C genotype was not significantly associated, either independently or interactively, with any of the CV hemodynamic measures during submaximal or maximal exercise. These results suggest an association of NOS3 G894T genotype with submaximal and maximal exercise CV hemodynamic responses, especially HR, in postmenopausal women.

  16. The protein inhibitor of nNOS (PIN/DLC1/LC8) binding does not inhibit the NADPH-dependent heme reduction in nNOS, a key step in NO synthesis

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

    Parhad, Swapnil S.; Jaiswal, Deepa; TIFR Centre for Interdisciplinary Sciences, 21 Brundavan Colony, Narsingi, Hyderabad 500075

    The neuronal nitric oxide synthase (nNOS) is an essential enzyme involved in the synthesis of nitric oxide (NO), a potent neurotransmitter. Although previous studies have indicated that the dynein light chain 1 (DLC1) binding to nNOS could inhibit the NO synthesis, the claim is challenged by contradicting reports. Thus, the mechanism of nNOS regulation remained unclear. nNOS has a heme-bearing, Cytochrome P450 core, and the functional enzyme is a dimer. The electron flow from NADPH to Flavin, and finally to the heme of the paired nNOS subunit within a dimer, is facilitated upon calmodulin (CaM) binding. Here, we show thatmore » DLC1 binding to nNOS-CaM complex does not affect the electron transport from the reductase to the oxygenase domain. Therefore, it cannot inhibit the rate of NADPH-dependent heme reduction in nNOS, which results in L-Arginine oxidation. Also, the NO release activity does not decrease with increasing DLC1 concentration in the reaction mix, which further confirmed that DLC1 does not inhibit nNOS activity. These findings suggest that the DLC1 binding may have other implications for the nNOS function in the cell. - Highlights: • The effect of interaction of nNOS with DLC1 has been debatable with contradicting reports in literature. • Purified DLC1 has no effect on electron transport between reductase and oxygenase domain of purified nNOS-CaM. • The NO release activity of nNOS was not altered by DLC1, supporting that DLC1 does not inhibit the enzyme. • These findings suggest that the DLC1 binding may have other implications for the nNOS function in the cell.« less

  17. iNOS inhibits hair regeneration in obese diabetic (ob/ob) mice.

    PubMed

    Sasaki, Mari; Shinozaki, Shohei; Morinaga, Hironobu; Kaneki, Masao; Nishimura, Emi; Shimokado, Kentaro

    2018-07-02

    Previous studies have shown that androgenic alopecia is associated with metabolic syndrome and diabetes. However, the detailed mechanism whereby diabetes causes alopecia still remains unclear. We focused on the inflammatory response that is caused by diabetes or obesity, given that inflammation is a risk factor for hair loss. Inducible nitric oxide synthase (iNOS) is known to be upregulated under conditions of acute or chronic inflammation. To clarify the potential role of iNOS in diabetes-related alopecia, we generated obese diabetic iNOS-deficient (ob/ob; iNOS-KO mice). We observed that ob/ob; iNOS-KO mice were potentiated for the transition from telogen (rest phase) to anagen (growth phase) in the hair cycle compared with iNOS-proficient ob/ob mice. To determine the effect of nitric oxide (NO) on the hair cycle, we administered an iNOS inhibitor intraperitoneally (compound 1400 W, 10 mg/kg) or topically (10% aminoguanidine) in ob/ob mice. We observed that iNOS inhibitors promoted anagen transition in ob/ob mice. Next, we administered an NO donor (S-nitrosoglutathione, GSNO), to test whether NO has the telogen elongation effects. The NO donor was sufficient to induce telogen elongation in wild-type mice. Together, our data indicate that iNOS-derived NO plays a role in telogen elongation under the inflammatory conditions associated with diabetes in mice. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Producing Scientific and Strategic Guidance for California's Department of Water Resources: The Climate Change Technical Advisory Group

    NASA Astrophysics Data System (ADS)

    Gyakum, J. R.; Austin, B. N.; Curtis, D. C.; Anderson, M.; Alpert, H.; Young, S.; Herson, A.; Schwarz, A.; Kavvas, M. L.; Langridge, R.; Lynn, E.; Anderson, J.; Redmond, K. T.; Dettinger, M. D.; Correa, M.; Franco, G.; Cayan, D.; Georgakakos, K.

    2015-12-01

    Diverse areas of expertise are needed to describe and assess a changing climate and provide guidance for the agency that runs the largest state-built, multi-purpose water project in the U.S. California's State Water Project provides: drinking water for more than 25 million people, flood control, power generation, recreation, fish and wildlife protection, and water quality improvements. Hydrologic impacts under a changing climate include rising seas, reduced ratio of snow to rain, earlier snowmelt and higher temperatures; all of which are being detected. To improve the scientific basis for decisions and enhance the consistency of climate change approaches, the California Department of Water Resources (DWR) empaneled a Climate Change Technical Advisory Group (CCTAG) for guidance on the scientific aspects of climate change, its impacts on water resources, the use and creation of planning approaches and analytical tools, and the development of adaptation responses. To carry out DWR's mission, incorporation of climate change into DWR's planning, projects, and other activities must be consistent, science-based, and continually improved through an iterative process. Hydrologists, academicians, modelers, planners, lawyers and practitioners convened regularly to tackle these complicated issues in water management policy, including climate change impacts on extreme events. Actions taken in response to the CCTAG recommendations will move California toward more sustainable management of water and related resources. DWR will release a technical report of CCTAG guidance and perspectives in 2015. The process to convene, collaborate and distribute the findings of this CCTAG will be the focus of this presentation. An academician and water resources practitioner will share their perspectives on the processes driving CCTAG's work.

  19. 78 FR 77563 - Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ... NATIONAL CREDIT UNION ADMINISTRATION 12 CFR Parts 700, 701, and 704 RIN 3133-AE33 Technical Amendments AGENCY: National Credit Union Administration (NCUA). ACTION: Final rule. SUMMARY: The NCUA Board... credit unions. The technical amendments conform the regulations to a recent policy change adopted by the...

  20. ET-1 Stimulates Superoxide Production by eNOS Following Exposure of Vascular Endothelial Cells to Endotoxin.

    PubMed

    Gopalakrishna, Deepak; Pennington, Samantha; Karaa, Amel; Clemens, Mark G

    2016-07-01

    It has been shown that microcirculation is hypersensitized to endothelin1 (ET-1) following endotoxin (lipopolysaccharide [LPS]) treatment leading to an increased vasopressor response. This may be related in part to decreased activation of endothelial nitric oxide synthase (eNOS) by ET-1. eNOS can also be uncoupled to produce superoxide (O2). This aberrant eNOS activity could further contribute to the hyperconstriction and injury caused by ET-1 following LPS. We therefore tested whether LPS affects ROS production by vascular endothelial cells and whether and how this effect is altered by ET-1. Human umbilical vein endothelial cells (HUVEC) or human microvascular endothelial cells (HMEC) were subjected to a 6-h treatment with LPS (250 ng/mL) or LPS and sepiapterin (100 μM) followed by a 30-min treatment with 100 μM L-Iminoethyl Ornithine (L-NIO) an irreversible eNOS inhibitor and 30-min treatment with ET-1 (10 nM). Conversion of [H]L-arginine to [H]L-citrulline was used to measure eNOS activity. Superoxide dismutase (SOD) inhibitable reduction of Cytochrome-C, dihydro carboxy fluorescein (DCF), and Mitosox was used to estimate ROS. LT-SDS PAGE was used to assess the degree of monomerization of the eNOS homodimer. Stimulation of HUVECs with ET-1 significantly increased NO synthesis by 1.4-fold (P < 0.05). ET-1 stimulation of LPS-treated HUVECs failed to increase NO production. Western blot for eNOS protein showed no change in eNOS protein levels. LPS alone resulted in an insignificant increase in ROS production as measured by cytochrome C that was increased 4.6-fold by ET-1 stimulation (P < 0.05). L-NIO significantly decreased ET-1-induced ROS production (P < 0.05). Sepiapterin significantly decreased ROS production in both; unstimulated and ET-1-stimulated LPS-treated groups, but did not restore NO production. DCF experiments confirmed intracellular ROS while Mitosox suggested a non-mitochondrial source. ET-1 treatment following a chronic LPS stress

  1. Nitrous oxide discretely up-regulates nNOS and p53 in neonatal rat brain.

    PubMed

    Cattano, D; Valleggi, S; Abramo, A; Forfori, F; Maze, M; Giunta, F

    2010-06-01

    Animal studies suggest that neuronal cell death often results from anesthetic administration during synaptogenesis. Volatile anesthetics are strongly involved in triggering neuronal apoptosis, whereas other inhalational agents (xenon) demonstrate protective effects. Nitrous oxide (N2O) has modest pro-apoptotic effects on its own and potent, synergistic toxic effects when combined with volatile agents. Recent findings suggest that, during periods of rapid brain development, the enhanced neurodegeneration triggered by anesthetic drugs may be caused by a compensatory increase in intracellular free calcium, a potent activator of neuronal nitric oxide synthase (nNOS). Anesthesia-induced neuro-apoptosis is also activated via the intrinsic and the extrinsic apoptotic pathways because both pathways involve p53, a key regulatory gene. The molecular events related to neuronal cell apoptosis are not completely understood. To gain further insight into the events underlying neuro-apoptosis, we analyzed the transcriptional consequences of N2O exposure on nNOS, iNOS and p53 mRNA levels. The study used 2 groups of postnatal day seven Sprague/Dawley rats (N=6 each) that were exposed for 120 minutes to air (75% N2, 25% O2) or N2O (75% N2O, 25% O2; this N2O concentration is commonly used to induce anesthesia and has been demonstrated to trigger neurodegeneration in postnatal day seven rats). Total RNA was isolated from each brain and expression analyses on iNOS and nNOS transcripts were performed using relative Real-Time C-reactive protein PCR (using G3PDH as a housekeeping gene). A semi-quantitative RT-PCR analysis was performed on the p53 transcript (using Ciclophylin A as a housekeeping gene). Statistical analysis (REST 2005) revealed a significant, 11-fold up-regulation (P=0.026) of the nNOS transcript but no significant changes in iNOS transcription. The p53 mRNA was up-regulated almost 2-fold (P=0.0002; Student's t-Test; GraphPad Prism 4.00) in N2O-treated samples relative to

  2. Correlation of technical surgical goals to the GDI and investigation of post-operative GDI change in children with cerebral palsy.

    PubMed

    Bickley, Christina; Linton, Judi; Scarborough, Nancy; Sullivan, Elroy; Mitchell, Katy; Barnes, Douglas

    2017-06-01

    The purpose of this study was to introduce a standardized set of surgical technical achievement goals (TAGs) as part of a comprehensive outcome assessment model for children with spastic cerebral palsy (CP) undergoing orthopaedic surgical intervention to improve gait. Examination of relationships of these surgical goals to the Gait Deviation Index (GDI) and use of two assessments in tandem provided a thorough picture of technical surgical outcomes. This study also investigated changes in GDI in children with spastic CP after surgery. Data from 269 participants with spastic CP, aged 4 to 19 years with Gross Motor Function Classification System (GMFCS) levels I, II, and III who underwent lower extremity orthopaedic surgical intervention to improve gait were retrospectively analyzed. Data were examined as one heterogeneous group and sub-grouped based on pattern of involvement and GMFCS level to determine change in GDI and relationships between GDI and TAGs. Differences in TAG achievement and GDI change by GMFCS level suggest a pairing of GDI with another technical measure to be beneficial. Analysis of the outcome tools individually revealed a significant difference between the pre-operative GDI and post-operative GDI mean for the entire group, as well as each of the subgroups. A significant difference in TAG achievement by GMFCS level was also noted. This paper provides evidence that lower extremity orthopedic intervention for the ambulatory child with spastic diplegic or hemiplegic CP improves gait and that a pairing of the GDI and TAGs system is beneficial to capture an accurate technical outcome assessment in both higher and lower functioning patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Gender, exercise training, and eNOS expression in porcine skeletal muscle arteries.

    PubMed

    Laughlin, M Harold; Welshons, Wade V; Sturek, Michael; Rush, James W E; Turk, James R; Taylor, Julia A; Judy, Barbara M; Henderson, Kyle K; Ganjam, V K

    2003-07-01

    Our purpose was to determine the effects of gender and exercise training on endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) protein content of porcine skeletal muscle arteries and to evaluate the role of 17beta-estradiol (E2) in these effects. We measured eNOS and SOD content with immunoblots and immunohistochemistry in femoral and brachial arteries of trained and sedentary male and female pigs and measured estrogen receptor (ER) mRNA and alpha-ER and beta-ER protein in aortas of male and female pigs. Results indicate that female arteries contain more eNOS than male arteries and that exercise training increases eNOS content independent of gender. Male and female pigs expressed similar levels of alpha-ER mRNA and protein and similar amounts beta-ER protein in their arteries. E2 concentrations as measured by RIA were 180 +/- 34 pg/ml in male sera and approximately 5 pg/ml in female sera, and neither was changed by training. However, bioassay indicated that biologically active estrogen equivalent to only 35 +/- 5 pg/ml was present in male sera. E2 in female pigs, whether measured by RIA or bioassay, was approximately 24 pg/ml at peak estrous and 2 pg/ml on day 5 diestrus. The free fraction of E2 in sera did not explain the low measurements, relative to RIA, of E2. We conclude that 1). gender has significant influence on eNOS and SOD content of porcine skeletal muscle arteries; 2). the effects of gender and exercise training vary among arteries of different anatomic origin; 3). male sera contains compounds that cause RIA to overestimate circulating estrogenic activity; and 4). relative to human men, the male pig is not biologically estrogenized by high levels of E2 reported by RIA, whereas in female pigs E2 levels are lower than in the blood of human women.

  4. Brain stem NOS and ROS in neural mechanisms of hypertension.

    PubMed

    Chan, Samuel H H; Chan, Julie Y H

    2014-01-01

    There is now compelling evidence to substantiate the notion that by depressing baroreflex regulation of blood pressure and augmenting central sympathetic outflow through their actions on the nucleus tractus solitarii (NTS) and rostral ventrolateral medulla (RVLM), brain stem nitric oxide synthase (NOS) and reactive oxygen species (ROS) are important contributing factors to neural mechanisms of hypertension. This review summarizes our contemporary views on the impact of NOS and ROS in the NTS and RVLM on neurogenic hypertension, and presents potential antihypertensive strategies that target brain stem NOS/ROS signaling. NO signaling in the brain stem may be pro- or antihypertensive depending on the NOS isoform that generates this gaseous moiety and the site of action. Elevation of the ROS level when its production overbalances its degradation in the NTS and RVLM underlies neurogenic hypertension. Interventional strategies with emphases on alleviating the adverse actions of these molecules on blood pressure regulation have been investigated. The pathological roles of NOS in the RVLM and NTS in neural mechanisms of hypertension are highly complex. Likewise, multiple signaling pathways underlie the deleterious roles of brain-stem ROS in neurogenic hypertension. There are recent indications that interactions between brain stem ROS and NOS may play a contributory role. Given the complicity of action mechanisms of brain-stem NOS and ROS in neural mechanisms of hypertension, additional studies are needed to identify the most crucial therapeutic target that is applicable not only in animal models but also in patients suffering from neurogenic hypertension.

  5. Detecting nitrous oxide reductase (NosZ) genes in soil metagenomes: method development and implications for the nitrogen cycle.

    PubMed

    Orellana, L H; Rodriguez-R, L M; Higgins, S; Chee-Sanford, J C; Sanford, R A; Ritalahti, K M; Löffler, F E; Konstantinidis, K T

    2014-06-03

    2). Until recently, consumption of N2O was attributed to bacteria encoding "typical" nitrous oxide reductase (NosZ). However, recent phylogenetic and physiological studies have shown that previously uncharacterized, functional, "atypical" NosZ proteins are encoded in genomes of diverse bacterial groups. The present study revealed that atypical nosZ genes outnumbered their typical counterparts, highlighting their potential role in N2O consumption in soils and possibly other environments. These findings advance our understanding of the diversity of microbes and functional genes involved in the nitrogen cycle and provide the means (e.g., gene sequences) to study N2O fluxes to the atmosphere and associated climate change. Copyright © 2014 Orellana et al.

  6. Sprint interval and endurance training are equally effective in increasing muscle microvascular density and eNOS content in sedentary males

    PubMed Central

    Cocks, Matthew; Shaw, Christopher S; Shepherd, Sam O; Fisher, James P; Ranasinghe, Aaron M; Barker, Thomas A; Tipton, Kevin D; Wagenmakers, Anton J M

    2013-01-01

    Sprint interval training (SIT) has been proposed as a time efficient alternative to endurance training (ET) for increasing skeletal muscle oxidative capacity and improving certain cardiovascular functions. In this study we sought to make the first comparisons of the structural and endothelial enzymatic changes in skeletal muscle microvessels in response to ET and SIT. Sixteen young sedentary males (age 21 ± SEM 0.7 years, BMI 23.8 ± SEM 0.7 kg m−2) were randomly assigned to 6 weeks of ET (40–60 min cycling at ∼65%, 5 times per week) or SIT (4–6 Wingate tests, 3 times per week). Muscle biopsies were taken from the m. vastus lateralis before and following 60 min cycling at 65% to measure muscle microvascular endothelial eNOS content, eNOS serine1177 phosphorylation, NOX2 content and capillarisation using quantitative immunofluorescence microscopy. Whole body insulin sensitivity, arterial stiffness and blood pressure were also assessed. ET and SIT increased skeletal muscle microvascular eNOS content (ET 14%; P < 0.05, SIT 36%; P < 0.05), with a significantly greater increase observed following SIT (P < 0.05). Sixty minutes of moderate intensity exercise increased eNOS ser1177 phosphorylation in all instances (P < 0.05), but basal and post-exercise eNOS ser1177 phosphorylation was lower following both training modes. All microscopy measures of skeletal muscle capillarisation (P < 0.05) were increased with SIT or ET, while neither endothelial nor sarcolemmal NOX2 was changed. Both training modes reduced aortic stiffness and increased whole body insulin sensitivity (P < 0.05). In conclusion, in sedentary males SIT and ET are effective in improving muscle microvascular density and eNOS protein content. PMID:22946099

  7. Impacts of climate change on biodiversity, ecosystems, and ecosystem services: technical input to the 2013 National Climate Assessment

    USGS Publications Warehouse

    Staudinger, Michelle D.; Grimm, Nancy B.; Staudt, Amanda; Carter, Shawn L.; Stuart, F. Stuart; Kareiva, Peter; Ruckelshaus, Mary; Stein, Bruce A.

    2012-01-01

    Ecosystems, and the biodiversity and services they support, are intrinsically dependent on climate. During the twentieth century, climate change has had documented impacts on ecological systems, and impacts are expected to increase as climate change continues and perhaps even accelerates. This technical input to the National Climate Assessment synthesizes our scientific understanding of the way climate change is affecting biodiversity, ecosystems, ecosystem services, and what strategies might be employed to decrease current and future risks. Building on past assessments of how climate change and other stressors are affecting ecosystems in the United States and around the world, we approach the subject from several different perspectives. First, we review the observed and projected impacts on biodiversity, with a focus on genes, species, and assemblages of species. Next, we examine how climate change is affecting ecosystem structural elements—such as biomass, architecture, and heterogeneity—and functions—specifically, as related to the fluxes of energy and matter. People experience climate change impacts on biodiversity and ecosystems as changes in ecosystem services; people depend on ecosystems for resources that are harvested, their role in regulating the movement of materials and disturbances, and their recreational, cultural, and aesthetic value. Thus, we review newly emerging research to determine how human activities and a changing climate are likely to alter the delivery of these ecosystem services. This technical input also examines two cross-cutting topics. First, we recognize that climate change is happening against the backdrop of a wide range of other environmental and anthropogenic stressors, many of which have caused dramatic ecosystem degradation already. This broader range of stressors interacts with climate change, and complicates our abilities to predict and manage the impacts on biodiversity, ecosystems, and the services they support. The

  8. Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats.

    PubMed

    Pakdeechote, Poungrat; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Prachaney, Parichat; Khrisanapant, Wilaiwan; Kukongviriyapan, Veerapol

    2014-01-16

    Asiatic acid is a triterpenoid isolated from Centella asiatica. The present study aimed to investigate whether asiatic acid could lessen the metabolic, cardiovascular complications in rats with metabolic syndrome (MS) induced by a high-carbohydrate, high-fat (HCHF) diet. Male Sprague-Dawley rats were fed with HCHF diet with 15% fructose in drinking water for 12 weeks to induce MS. MS rats were treated with asiatic acid (10 or 20 mg/kg/day) or vehicle for a further three weeks. MS rats had an impairment of oral glucose tolerance, increases in fasting blood glucose, serum insulin, total cholesterol, triglycerides, mean arterial blood pressure, heart rate, and hindlimb vascular resistance; these were related to the augmentation of vascular superoxide anion production, plasma malondialdehyde and tumor necrosis factor-alpha (TNF-α) levels (p<0.05). Plasma nitrate and nitrite (NOx) were markedly high with upregulation of inducible nitric oxide synthase (iNOS) expression, but dowregulation of endothelial nitric oxide synthase (eNOS) expression (p<0.05). Asiatic acid significantly improved insulin sensitivity, lipid profiles, hemodynamic parameters, oxidative stress markers, plasma TNF-α, NOx, and recovered abnormality of eNOS/iNOS expressions in MS rats (p<0.05). In conclusion, asiatic acid improved metabolic, hemodynamic abnormalities in MS rats that could be associated with its antioxidant, anti-inflammatory effects and recovering regulation of eNOS/iNOS expression.

  9. TurboTech Technical Evaluation Automated System

    NASA Technical Reports Server (NTRS)

    Tiffany, Dorothy J.

    2009-01-01

    TurboTech software is a Web-based process that simplifies and semiautomates technical evaluation of NASA proposals for Contracting Officer's Technical Representatives (COTRs). At the time of this reporting, there have been no set standards or systems for training new COTRs in technical evaluations. This new process provides boilerplate text in response to interview style questions. This text is collected into a Microsoft Word document that can then be further edited to conform to specific cases. By providing technical language and a structured format, TurboTech allows the COTRs to concentrate more on the actual evaluation, and less on deciding what language would be most appropriate. Since the actual word choice is one of the more time-consuming parts of a COTRs job, this process should allow for an increase in quantity of proposals evaluated. TurboTech is applicable to composing technical evaluations of contractor proposals, task and delivery orders, change order modifications, requests for proposals, new work modifications, task assignments, as well as any changes to existing contracts.

  10. Influence of coronary artery diameter on eNOS protein content

    NASA Technical Reports Server (NTRS)

    Laughlin, M. H.; Turk, J. R.; Schrage, W. G.; Woodman, C. R.; Price, E. M.

    2003-01-01

    The purpose of this study was to test the hypothesis that the content of endothelial nitric oxide synthase (eNOS) protein (eNOS protein/g total artery protein) increases with decreasing artery diameter in the coronary arterial tree. Content of eNOS protein was determined in porcine coronary arteries with immunoblot analysis. Arteries were isolated in six size categories from each heart: large arteries [301- to 2,500-microm internal diameter (ID)], small arteries (201- to 300-microm ID), resistance arteries (151- to 200-microm ID), large arterioles (101- to 150-microm ID), intermediate arterioles (51- to 100-microm ID), and small arterioles(<50-microm ID). To obtain sufficient protein for analysis from small- and intermediate-sized arterioles, five to seven arterioles 1-2 mm in length were pooled into one sample for each animal. Results establish that the number of smooth muscle cells per endothelial cell decreases from a number of 10 to 15 in large coronary arteries to 1 in the smallest arterioles. Immunohistochemistry revealed that eNOS is located only in endothelial cells in all sizes of coronary artery and in coronary capillaries. Contrary to our hypothesis, eNOS protein content did not increase with decreasing size of coronary artery. Indeed, the smallest coronary arterioles had less eNOS protein per gram of total protein than the large coronary arteries. These results indicate that eNOS protein content is greater in the endothelial cells of conduit arteries, resistance arteries, and large arterioles than in small coronary arterioles.

  11. Technical Assistance and Changes in Nutrition and Physical Activity Practices in the National Early Care and Education Learning Collaboratives Project, 2015-2016.

    PubMed

    Chiappone, Alethea; Smith, Teresa M; Estabrooks, Paul A; Rasmussen, Cristy Geno; Blaser, Casey; Yaroch, Amy L

    2018-04-26

    The National Early Care and Education Learning Collaboratives Project (ECELC) aims to improve best practices in early care and education (ECE) programs in topic areas of the Nutrition and Physical Activity Self-Assessment in Child Care (NAP SACC). Technical assistance is a component of the ECELC, yet its effect on outcomes is unclear. Beyond dose and duration of technical assistance, limited research exists on characteristics of technical assistance that contribute to outcomes. The objective of this study was to identify and describe technical assistance characteristics and explore associations with NAP SACC outcomes. We collected data from 10 collaboratives comprising 84 ECE programs in 2 states in 2015-2016. The objective of technical assistance was to support programs in improving best practices. Technical assistance was provided to programs via on-site, telephone, or email and was tailored to program needs. We used a mixed-methods design to examine associations between technical assistance and NAP SACC outcomes. We used multiple regression analysis to assess quantitative data and qualitative comparative analysis to determine necessary and sufficient technical assistance conditions supporting NAP SACC outcomes. We also conducted a document review to describe technical assistance that referred conditions identified by the qualitative comparative analysis. Regression analyses detected an inverse relationship between changes in NAP SACC scores and hours of technical assistance. No clear pattern emerged in the qualitative comparative analysis, leaving no necessary and sufficient conditions. However, the qualitative comparative analysis identified feedback as a potentially important component of technical assistance, whereas resource sharing and frequent email were characteristics that seemed to reduce the likelihood of improved outcomes. Email and resource sharing were considered primarily general information rather than tailored technical assistance. Technical

  12. The effectiveness of conceptual change texts and concept clipboards in learning the nature of science

    NASA Astrophysics Data System (ADS)

    Çil, Emine; Çepni, Salih

    2016-01-01

    Background: One of the most important goals of science education is to enable students to understand the nature of science (NOS). However, generally regular science teaching in classrooms does not help students improve informed NOS views. Purpose: This study investigated the influence of an explicit reflective conceptual change approach compared with an explicit reflective inquiry-oriented approach on seventh graders' understanding of NOS. Sample: The research was conducted with seventh grade students. A total of 44 students participated in the study. Design and method: The study was an interpretive study because this study focused on the meanings that students attach to target aspects of NOS. Participants were divided into two groups, each consisting of 22 students. One of the groups learned NOS with an explicit reflective conceptual change approach. The requirements of conceptual change were provided through the use of conceptual change texts and concept cartoons. The other group learned NOS with an explicit reflective inquiry-oriented approach. The data were collected through open-ended questionnaires and semi-structured interviews. These instruments were employed in a pre-test, a post-test and a delayed test. Students' views of the aspects of NOS were categorized as naive, transitional and informed. Results: The result of this study indicated that before receiving instruction, most of the participants had transitional views of the tentative, empirical and imaginative and creative aspects of the NOS, and they had naive understandings of the distinction between observation and inference. The instruction in the experimental group led to a 60% - a 25% increase in the number of students who possessed an informed understanding of the tentative, empirical, creative and observation and inference aspect of the NOS. The instruction in the control group led to a 30% - a 15% increase in the informed NOS views. Conclusion: The explicit reflective conceptual change approach

  13. Stromal cell-derived factor 2 is critical for Hsp90-dependent eNOS activation.

    PubMed

    Siragusa, Mauro; Fröhlich, Florian; Park, Eon Joo; Schleicher, Michael; Walther, Tobias C; Sessa, William C

    2015-08-18

    Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell-derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser(1177), a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser(1177) in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. Copyright © 2015, American Association for the Advancement of Science.

  14. Stromal cell–derived factor 2 is critical for Hsp90-dependent eNOS activation

    PubMed Central

    Siragusa, Mauro; Fröhlich, Florian; Park, Eon Joo; Schleicher, Michael; Walther, Tobias C.; Sessa, William C.

    2016-01-01

    Endothelial nitric oxide synthase (eNOS) catalyzes the conversion of l-arginine and molecular oxygen into l-citrulline and nitric oxide (NO), a gaseous second messenger that influences cardiovascular physiology and disease. Several mechanisms regulate eNOS activity and function, including phosphorylation at Ser and Thr residues and protein-protein interactions. Combining a tandem affinity purification approach and mass spectrometry, we identified stromal cell–derived factor 2 (SDF2) as a component of the eNOS macromolecular complex in endothelial cells. SDF2 knockdown impaired agonist-stimulated NO synthesis and decreased the phosphorylation of eNOS at Ser1177, a key event required for maximal activation of eNOS. Conversely, SDF2 overexpression dose-dependently increased NO synthesis through a mechanism involving Akt and calcium (induced with ionomycin), which increased the phosphorylation of Ser1177 in eNOS. NO synthesis by iNOS (inducible NOS) and nNOS (neuronal NOS) was also enhanced upon SDF2 overexpression. We found that SDF2 was a client protein of the chaperone protein Hsp90, interacting preferentially with the M domain of Hsp90, which is the same domain that binds to eNOS. In endothelial cells exposed to vascular endothelial growth factor (VEGF), SDF2 was required for the binding of Hsp90 and calmodulin to eNOS, resulting in eNOS phosphorylation and activation. Thus, our data describe a function for SDF2 as a component of the Hsp90-eNOS complex that is critical for signal transduction in endothelial cells. PMID:26286023

  15. The calcium channel blocker amlodipine promotes the unclamping of eNOS from caveolin in endothelial cells.

    PubMed

    Batova, Suzan; DeWever, Julie; Godfraind, Théophile; Balligand, Jean-Luc; Dessy, Chantal; Feron, Olivier

    2006-08-01

    in the absence of any detectable changes in intracellular calcium levels. The resulting increase in caveolin-free eNOS potentiates the NO production in response to agonists including VEGF and bradykinin. More generally, this work opens new avenues of treatment for drugs able to structurally alter signaling pathways concentrated in caveolae.

  16. 15 CFR Supplement Nos. 2-3 to Part... - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false [Reserved] Nos. Supplement Nos. 2-3 to Part 716 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS INITIAL...

  17. 15 CFR Supplement Nos. 2-3 to Part... - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false [Reserved] Nos. Supplement Nos. 2-3 to Part 716 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS INITIAL...

  18. Melatonin influences NO/NOS pathway and reduces oxidative and nitrosative stress in a model of hypoxic-ischemic brain damage.

    PubMed

    Blanco, Santos; Hernández, Raquel; Franchelli, Gustavo; Ramos-Álvarez, Manuel Miguel; Peinado, María Ángeles

    2017-01-30

    In this work, using a rat model combining ischemia and hypobaric hypoxia (IH), we evaluate the relationships between the antioxidant melatonin and the cerebral nitric oxide/nitric oxide synthase (NO/NOS) system seeking to ascertain whether melatonin exerts its antioxidant protective action by balancing this key pathway, which is highly involved in the cerebral oxidative and nitrosative damage underlying these pathologies. The application of the IH model increases the expression of the three nitric oxide synthase (NOS) isoforms, as well as nitrogen oxide (NOx) levels and nitrotyrosine (n-Tyr) impacts on the cerebral cortex. However, melatonin administration before IH makes nNOS expression response earlier and stronger, but diminishes iNOS and n-Tyr expression, while both eNOS and NOx remain unchanged. These results were corroborated by nicotine adenine dinucleotide phosphate diaphorase (NADPH-d) staining, as indicative of in situ NOS activity. In addition, the rats previously treated with melatonin exhibited a reduction in the oxidative impact evaluated by thiobarbituric acid reactive substances (TBARS). Finally, IH also intensified glial fibrillary acidic protein (GFAP) expression, reduced hypoxia-inducible factor-1alpha (HIF-1α), but did not change nuclear factor kappa B (NF-κB); meanwhile, melatonin did not significantly affect any of these patterns after the application of the IH model. The antioxidant melatonin acts on the NO/NOS system after IH injury balancing the release of NO, reducing peroxynitrite formation and protecting from nitrosative/oxidative damage. In addition, this paper raises questions concerning the classical role of some controversial molecules such as NO, which are of great consequence in the final fate of hypoxic neurons. We conclude that melatonin protects the brain from hypoxic/ischemic-derived damage in the first steps of the ischemic cascade, influencing the NO/NOS pathway and reducing oxidative and nitrosative stress. Copyright

  19. Daily cycling of nitric oxide synthase (NOS) in the hippocampus of pigeons (C. livia)

    PubMed Central

    2013-01-01

    Background Nitric oxide synthase (NOS) is essential for the synthesis of nitric oxide (NO), a non-conventional neurotransmitter with an important role in synaptic plasticity underlying processes of hippocampus-dependent memory and in the regulation of biological clocks and circadian rhythms. Many studies have shown that both the NOS cytosolic protein content and its enzymatic activity present a circadian variation in different regions of the rodent brain, including the hippocampus. The present study investigated the daily variation of NOS enzymatic activity and the cytosolic content of nNOS in the hippocampus of pigeons. Results Adult pigeons kept under a skeleton photoperiod were assigned to six different groups. Homogenates of the hippocampus obtained at six different times-of-day were used for NOS analyses. Both iNOS activity and nNOS cytosolic protein concentrations were highest during the subjective light phase and lowest in the subjective dark phase of the circadian period. ANOVA showed significant time differences for iNOS enzymatic activity (p < 0.05) and for nNOS protein content (p < 0.05) in the hippocampus. A significant daily rhythm for both iNOS and nNOS was confirmed by analysis with the Cosinor method (p < 0.05). The present findings indicate that the enzymatic activity of iNOS and content of nNOS protein in the hippocampus of pigeons exhibit a daily rhythm, with acrophase values occurring during the behavioral activity phase. Conclusions The data corroborate the reports on circadian variation of NOS in the mammalian hippocampus and can be considered indicative of a dynamic interaction between hippocampus-dependent processes and circadian clock mechanisms. PMID:24176048

  20. Technical writing versus technical writing

    NASA Technical Reports Server (NTRS)

    Dillingham, J. W.

    1981-01-01

    Two terms, two job categories, 'technical writer' and 'technical author' are discussed in terms of industrial and business requirements and standards. A distinction between 'technical writing' and technical 'writing' is made. The term 'technical editor' is also considered. Problems inherent in the design of programs to prepare and train students for these jobs are discussed. A closer alliance between industry and academia is suggested as a means of preparing students with competent technical communication skills (especially writing and editing skills) and good technical skills.

  1. 12. Railing Detail for Dam Nos. 3 and 4, Fence ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. Railing Detail for Dam Nos. 3 and 4, Fence Detail for Reservoir Nos. 3 and 4, Single Lamp Details, Triple Lamp Details - Washington Park Reservoirs, 2403 SW Jefferson Street, Portland, Multnomah County, OR

  2. Face and Emotion Recognition in MCDD versus PDD-NOS

    ERIC Educational Resources Information Center

    Herba, Catherine M.; de Bruin, Esther; Althaus, Monika; Verheij, Fop; Ferdinand, Robert F.

    2008-01-01

    Previous studies indicate that Multiple Complex Developmental Disorder (MCDD) children differ from PDD-NOS and autistic children on a symptom level and on psychophysiological functioning. Children with MCDD (n = 21) and PDD-NOS (n = 62) were compared on two facets of social-cognitive functioning: identification of neutral faces and facial…

  3. Organizational responses to a changing aid environment: the German Agency for Technical Cooperation (GTZ).

    PubMed

    Hill, Peter S

    2002-01-01

    As a major European donor, German government development assistance faces a series of challenges. Recent political changes have raised expectations for demonstrable health outcomes as a result of German development assistance; there has been a deepened commitment to collaboration with other bilateral and multilateral donors; and partner countries are increasingly open to new approaches to development. German development assistance also reflects a new ethos of partnership and the shift to programmatic and sector based development approaches. At the same time, its particular organizational structure and administrative framework highlight the extent of structural and systems reforms required of donors by changing development relationships, and the tensions created in responding to these. This paper examines organizational changes within the German Agency for Technical Cooperation (Deutsche Gesellschaft für Technische, Zusammenarbeit) (GTZ), aimed at increasing its Regional, Sectoral, Managerial and Process competence as they affect health and related sectors. These include the decentralization of GTZ, the trend to integration of projects, the increasing focus on policy and health systems reform, increased inter-sectoral collaboration, changes in recruitment and training, new perspectives in planning and evaluation and the introduction of a quality management programme.

  4. Urology technical and non-technical skills development: the emerging role of simulation.

    PubMed

    Rashid, Prem; Gianduzzo, Troy R J

    2016-04-01

    To review the emerging role of technical and non-technical simulation in urological education and training. A review was conducted to examine the current role of simulation in urology training. A PUBMED search of the terms 'urology training', 'urology simulation' and 'urology education' revealed 11,504 titles. Three hundred and fifty-seven abstracts were identified as English language, peer reviewed papers pertaining to the role of simulation in urology and related topics. Key papers were used to explore themes. Some cross-referenced papers were also included. There is an ongoing need to ensure that training time is efficiently utilised while ensuring that optimal technical and non-technical skills are achieved. Changing working conditions and the need to minimise patient harm by inadvertent errors must be taken into account. Simulation models for specific technical aspects have been the mainstay of graduated step-wise low and high fidelity training. Whole scenario environments as well as non-technical aspects can be slowly incorporated into the curriculum. Doing so should also help define what have been challenging competencies to teach and evaluate. Dedicated time, resources and trainer up-skilling are important. Concurrent studies are needed to help evaluate the effectiveness of introducing step-wise simulation for technical and non-technical competencies. Simulation based learning remains the best avenue of progressing surgical education. Technical and non-technical simulation could be used in the selection process. There are good economic, logistic and safety reasons to pursue the process of ongoing development of simulation co-curricula. While the role of simulation is assured, its progress will depend on a structured program that takes advantage of what can be delivered via this medium. Overall, simulation can be developed further for urological training programs to encompass technical and non-technical skill development at all stages, including

  5. KLF6 and iNOS regulates apoptosis during respiratory syncytial virus infection

    PubMed Central

    Mgbemena, Victoria; Segovia, Jesus; Chang, Te-Hung; Bose, Santanu

    2013-01-01

    Human respiratory syncytial virus (RSV) is a highly pathogenic lung-tropic virus that causes severe respiratory diseases. Enzymatic activity of inducible nitric oxide (iNOS) is required for NO generation. Although NO contributes to exaggerated lung disease during RSV infection, the role of NO in apoptosis during infection is not known. In addition, host trans-activator(s) required for iNOS gene expression during RSV infection is unknown. In the current study we have uncovered the mechanism of iNOS gene induction by identifying kruppel-like factor 6 (KLF6) as a critical transcription factor required for iNOS gene expression during RSV infection. Furthermore, we have also uncovered the role of iNOS as a critical host factor regulating apoptosis during RSV infection. PMID:23831683

  6. iNOS Activity Modulates Inflammation, Angiogenesis, and Tissue Fibrosis in Polyether-Polyurethane Synthetic Implants.

    PubMed

    Cassini-Vieira, Puebla; Araújo, Fernanda Assis; da Costa Dias, Filipi Leles; Russo, Remo Castro; Andrade, Silvia Passos; Teixeira, Mauro Martins; Barcelos, Luciola Silva

    2015-01-01

    There is considerable interest in implantation techniques and scaffolds for tissue engineering and, for safety and biocompatibility reasons, inflammation, angiogenesis, and fibrosis need to be determined. The contribution of inducible nitric oxide synthase (iNOS) in the regulation of the foreign body reaction induced by subcutaneous implantation of a synthetic matrix was never investigated. Here, we examined the role of iNOS in angiogenesis, inflammation, and collagen deposition induced by polyether-polyurethane synthetic implants, using mice with targeted disruption of the iNOS gene (iNOS(-/-)) and wild-type (WT) mice. The hemoglobin content and number of vessels were decreased in the implants of iNOS(-/-) mice compared to WT mice 14 days after implantation. VEGF levels were also reduced in the implants of iNOS(-/-) mice. In contrast, the iNOS(-/-) implants exhibited an increased neutrophil and macrophage infiltration. However, no alterations were observed in levels of CXCL1 and CCL2, chemokines related to neutrophil and macrophage migration, respectively. Furthermore, the implants of iNOS(-/-) mice showed boosted collagen deposition. These data suggest that iNOS activity controls inflammation, angiogenesis, and fibrogenesis in polyether-polyurethane synthetic implants and that lack of iNOS expression increases foreign body reaction to implants in mice.

  7. Crataegus Special Extract WS 1442 Effects on eNOS and microRNA 155.

    PubMed

    Wang, Xinwen; Liang, Yan; Shi, Jian; Zhu, Hao-Jie; Bleske, Barry E

    2018-04-16

    Increased expression of microRNA 155 (miR-155) results in a decrease in endothelial nitric oxide synthase (eNOS) expression and impaired endothelial function. Factors that have been shown to increase expression of miR-155 may be mitigated by WS 1442, an extract of hawthorn leaves and flowers ( Crataegus special extract) that contains a range of pharmacologically active substances including oligomeric proanthocyanidins and flavonoids. The purpose of this study is to determine the effect of WS 1442 on the expression of miR-155 and eNOS in the presence of tumor necrosis factor (TNF- α ). Human umbilical vein endothelial cells (HUVECs) were studied after the exposure to TNF- α , with or without simvastatin (positive control) and WS 1442. The expression levels of eNOS, phosphorylated eNOS, and miR-155 in the different HUVEC treatment groups were determined by western blot and quantitative real-time polymerase chain reaction, respectively. To evaluate the effect of WS 1442 on the eNOS activity, the medium and intracellular nitrate/nitrite (NO) concentrations were also analyzed using a colorimetric Griess assay kit. The results demonstrated that TNF- α upregulated miR-155 expression and decreased eNOS expression and NO concentrations. WS 1442 also increased miR-155 expression and decreased eNOS expression but, unlike TNF- α , increased phosphorylated eNOS expression and NO concentrations. Surprisingly, WS 1442 increased miR-155 expression; however, WS 1442 mitigated the overall negative effect of miR-155 on decreasing eNOS expression by increasing expression of phosphorylated eNOS and resulting in an increase in NO concentrations. In the setting where miR-155 may be expressed, WS 1442 may offer vascular protection by increasing the expression of phosphorylated eNOS. Georg Thieme Verlag KG Stuttgart · New York.

  8. Partial eNOS deficiency causes spontaneous thrombotic cerebral infarction, amyloid angiopathy and cognitive impairment.

    PubMed

    Tan, Xing-Lin; Xue, Yue-Qiang; Ma, Tao; Wang, Xiaofang; Li, Jing Jing; Lan, Lubin; Malik, Kafait U; McDonald, Michael P; Dopico, Alejandro M; Liao, Francesca-Fang

    2015-06-24

    Cerebral infarction due to thrombosis leads to the most common type of stroke and a likely cause of age-related cognitive decline and dementia. Endothelial nitric oxide synthase (eNOS) generates NO, which plays a crucial role in maintaining vascular function and exerting an antithrombotic action. Reduced eNOS expression and eNOS polymorphisms have been associated with stroke and Alzheimer's disease (AD), the most common type of dementia associated with neurovascular dysfunction. However, direct proof of such association is lacking. Since there are no reports of complete eNOS deficiency in humans, we used heterozygous eNOS(+/-) mice to mimic partial deficiency of eNOS, and determine its impact on cerebrovascular pathology and perfusion of cerebral vessels. Combining cerebral angiography with immunohistochemistry, we found thrombotic cerebral infarctions in eNOS(+/-) mice as early as 3-6 months of age but not in eNOS(+/+) mice at any age. Remarkably, vascular occlusions in eNOS(+/-) mice were found almost exclusively in three areas: temporoparietal and retrosplenial granular cortexes, and hippocampus this distribution precisely matching the hypoperfused areas identified in preclinical AD patients. Moreover, progressive cerebral amyloid angiopaphy (CAA), blood brain barrier (BBB) breakdown, and cognitive impairment were also detected in aged eNOS(+/-) mice. These data provide for the first time the evidence that partial eNOS deficiency results in spontaneous thrombotic cerebral infarctions that increase with age, leading to progressive CAA and cognitive impairments. We thus conclude that eNOS(+/-) mouse may represent an ideal model of ischemic stroke to address early and progressive damage in spontaneously-evolving chronic cerebral ischemia and thus, study vascular mechanisms contributing to vascular dementia and AD.

  9. Enterprise Planning for Change; Co-ordination of Manpower and Technical Planning. Industrial Relations Aspects of Manpower Policy, No. 5.

    ERIC Educational Resources Information Center

    Wedderburn, Dorothy

    Forty case studies made by research teams of independents or governmental agencies in Austria, Canada, France, Germany, Norway, Sweden, United Kingdom, and the United States were analyzed to provide managements and trade unions with illustrations of present systems of technical and manpower changes at the enterprise level and to describe the…

  10. Phenotyping of nNOS neurons in the postnatal and adult female mouse hypothalamus.

    PubMed

    Chachlaki, Konstantina; Malone, Samuel A; Qualls-Creekmore, Emily; Hrabovszky, Erik; Münzberg, Heike; Giacobini, Paolo; Ango, Fabrice; Prevot, Vincent

    2017-10-15

    Neurons expressing nitric oxide (NO) synthase (nNOS) and thus capable of synthesizing NO play major roles in many aspects of brain function. While the heterogeneity of nNOS-expressing neurons has been studied in various brain regions, their phenotype in the hypothalamus remains largely unknown. Here we examined the distribution of cells expressing nNOS in the postnatal and adult female mouse hypothalamus using immunohistochemistry. In both adults and neonates, nNOS was largely restricted to regions of the hypothalamus involved in the control of bodily functions, such as energy balance and reproduction. Labeled cells were found in the paraventricular, ventromedial, and dorsomedial nuclei as well as in the lateral area of the hypothalamus. Intriguingly, nNOS was seen only after the second week of life in the arcuate nucleus of the hypothalamus (ARH). The most dense and heavily labeled population of cells was found in the organum vasculosum laminae terminalis (OV) and the median preoptic nucleus (MEPO), where most of the somata of the neuroendocrine neurons releasing GnRH and controlling reproduction are located. A great proportion of nNOS-immunoreactive neurons in the OV/MEPO and ARH were seen to express estrogen receptor (ER) α. Notably, almost all ERα-immunoreactive cells of the OV/MEPO also expressed nNOS. Moreover, the use of EYFP Vglut2 , EYFP Vgat , and GFP Gad67 transgenic mouse lines revealed that, like GnRH neurons, most hypothalamic nNOS neurons have a glutamatergic phenotype, except for nNOS neurons of the ARH, which are GABAergic. Altogether, these observations are consistent with the proposed role of nNOS neurons in physiological processes. © 2017 Wiley Periodicals, Inc.

  11. Baclofen or nNOS inhibitor affect molecular and behavioral alterations evoked by traumatic spinal cord injury in rat spinal cord.

    PubMed

    Kisucká, Alexandra; Hricová, Ľudmila; Pavel, Jaroslav; Strosznajder, Joanna B; Chalimoniuk, Malgorzata; Langfort, Jozef; Gálik, Ján; Maršala, Martin; Radoňak, Jozef; Lukáčová, Nadežda

    2015-06-01

    The loss of descending control after spinal cord injury (SCI) and incessant stimulation of Ia monosynaptic pathway, carrying proprioceptive impulses from the muscles and tendons into the spinal cord, evoke exaggerated α-motoneuron activity leading to increased reflex response. Previous results from our laboratory have shown that Ia monosynaptic pathway is nitrergic. The aim of this study was to find out whether nitric oxide produced by neuronal nitric oxide synthase (nNOS) plays a role in setting the excitability of α-motoneurons after thoracic spinal cord transection. We tested the hypothesis that the inhibition of nNOS in α-motoneurons after SCI could have a neuroprotective effect on reflex response. Rats underwent spinal cord transection at Th10 level followed by 7, 10, and 14 days of survival. The animals were treated with Baclofen (a gamma aminobutyric acid B receptor agonist, 3 μg/two times per day/intrathecally) applied for 3 days from the seventh day after transection; N-nitro-l-arginine (NNLA) (nNOS blocator) applied for the first 3 days after injury (20 mg/kg per day, intramuscularly); NNLA and Baclofen; or NNLA (60 mg/kg/day, single dose) applied on the 10th day after transection. We detected the changes in the level of nNOS protein, nNOS messenger RNA, and nNOS immunoreactivity. To investigate the reflex response to heat-induced stimulus, tail-flick test was monitored in treated animals up to 16 days after SCI. Our data indicate that Baclofen therapy is more effective than the combined treatment with NNLA and Baclofen therapy. The single dose of NNLA (60 mg/kg) applied on the 10th day after SCI or Baclofen therapy reduced nNOS expression in α-motoneurons and suppressed symptoms of increased reflex activity. The results clearly show that increased nNOS expression in α-motoneurons after SCI may be pharmacologically modifiable with Baclofen or bolus dose of nNOS blocker. Copyright © 2015. Published by Elsevier Inc.

  12. Aucubin protects against pressure overload-induced cardiac remodelling via the β3 -adrenoceptor-neuronal NOS cascades.

    PubMed

    Wu, Qing-Qing; Xiao, Yang; Duan, Ming-Xia; Yuan, Yuan; Jiang, Xiao-Han; Yang, Zheng; Liao, Hai-Han; Deng, Wei; Tang, Qi-Zhu

    2018-05-01

    Aucubin, the predominant component of Eucommia ulmoides Oliv., has been shown to have profound effects on oxidative stress. As oxidative stress has previously been demonstrated to contribute to acute and chronic myocardial injury, we tested the effects of aucubin on cardiac remodelling and heart failure. Initially, H9c2 cardiomyocytes and neonatal rat cardiomyocytes pretreated with aucubin (1, 3, 10, 25 and 50 μM) were challenged with phenylephrine. Secondly, the transverse aorta was constricted in C57/B6 and neuronal NOS (nNOS)-knockout mice, then aucubin (1 or 5 mg·kg -1 body weight day -1 ) was injected i.p. for 25 days. Hypertrophy was evaluated by assessing morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers. Oxidative stress was evaluated by examining ROS generation, oxidase activity and NO generation. NOS expression was determined by Western blotting. Aucubin effectively suppressed cardiac remodelling; in mice, aucubin substantially inhibited pressure overload-induced cardiac hypertrophy, fibrosis and inflammation, whereas knocking out nNOS abolished these cardioprotective effects of aucubin. Blocking or knocking down the β 3 -adrenoceptor abolished the protective effects of aucubin in vitro. Furthermore, aucubin enhanced the protective effects of a β 3 -adrenoceptor agonist in vitro by increasing cellular cAMP levels, whereas treatment with an adenylate cyclase (AC) inhibitor abolished the cardioprotective effects of aucubin. Aucubin suppresses oxidative stress during cardiac remodelling by increasing the expression of nNOS in a process that requires activation of the β 3 -adrenoceptor/AC/cAMP pathway. These findings suggest that aucubin could have potential as a treatment for cardiac remodelling and heart failure. © 2018 The British Pharmacological Society.

  13. 49 CFR 173.187 - Pyrophoric solids, metals or alloys, n.o.s.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Pyrophoric solids, metals or alloys, n.o.s. 173... Class 1 and Class 7 § 173.187 Pyrophoric solids, metals or alloys, n.o.s. Packagings for pyrophoric solids, metals, or alloys, n.o.s. must conform to the requirements of part 178 of this subchapter at the...

  14. CPEB1 modulates lipopolysaccharide-mediated iNOS induction in rat primary astrocytes

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

    Kim, Ki Chan; Hyun Joo, So; Shin, Chan Young, E-mail: chanyshin@kku.ac.kr

    2011-06-17

    Highlights: {yields} Expression and phosphorylation of CPEB1 is increased by LPS stimulation in rat primary astrocytes. {yields} JNK regulates expression and phosphorylation of CPEB1 in reactive astrocytes. {yields} Down-regulation of CPEB1 using siRNA inhibits oxidative stress and iNOS induction by LPS stimulation. {yields} CPEB1 may play an important role in regulating inflammatory responses in reactive astrocytes induced by LPS. -- Abstract: Upon CNS damage, astrocytes undergo a series of biological changes including increased proliferation, production of inflammatory mediators and morphological changes, in a response collectively called reactive gliosis. This process is an essential part of the brains response to injury,more » yet much is unknown about the molecular mechanism(s) that induce these changes. In this study, we investigated the role of cytoplasmic polyadenylation element binding protein 1 (CPEB1) in the regulation of inflammatory responses in a model of reactive gliosis, lipopolysaccharide-stimulated astrocytes. CPEB1 is an mRNA-binding protein recently shown to be expressed in astrocytes that may play a role in astrocytes migration. After LPS stimulation, the expression and phosphorylation of CPEB1 was increased in rat primary astrocytes in a JNK-dependent process. siRNA-induced knockdown of CPEB1 expression inhibited the LPS-induced up-regulation of iNOS as well as NO and ROS production, a hallmark of immunological activation of astrocytes. The results from the study suggest that CPEB1 is actively involved in the regulation of inflammatory responses in astrocytes, which might provide new insights into the regulatory mechanism after brain injury.« less

  15. Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration.

    PubMed

    Ramalho, Joana; Ramalho, Miguel; AlObaidy, Mamdoh; Semelka, Richard C

    2016-12-01

    Over the last 2years several studies have been published regarding gadolinium deposition in brain structures in patients with normal renal function after repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the publications are magnetic resonance imaging (MRI) based retrospective studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes and gadolinium deposition was validated by human pathology studies. However, the variability of the MR equipment and parameters used across different publications, along with the inherent limitations of MRI to assess gadolinium in human tissues should be acknowledged when interpreting those studies. Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution knowledge. The aim of this paper is to overview current knowledge of technical aspects of T1 signal intensity evaluation by MRI and describe confounding factors, with the intention to achieve higher accuracy and maximize reproducibility. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Fashion, science and technical change: the history of the treatment of glue ear.

    PubMed

    Black, N A

    1985-02-01

    One reason for the current epidemic in the rate of surgery for glue ear in children is that a shift in treatment has taken place from non-surgical to surgical methods. An historical review of the treatment of this condition reveals the existence of previous 'surgical epidemics' and the importance of two particular factors-technical developments, such as the design of tympanostomy tubes and the introduction of antibacterial drugs; and the lure of panaceas such as ionizing radiation. In addition, it reveals how medical practice is, like most human behaviour, subject to fashion. Despite this, there is a constant desire by practitioners to be adjudged 'scientific' in their work, and definitions of science are equally susceptible to change over time.

  17. Exposure to diesel exhaust up-regulates iNOS expression in ApoE knockout mice

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

    Bai Ni; James Hogg Research Centre, Providence Heart and Lung Institute, St. Paul's Hospital, University of British Columbia, Vancouver, BC; Kido, Takashi

    Traffic related particulate matter air pollution is a risk factor for cardiovascular events; however, the biological mechanisms are unclear. We hypothesize that diesel exhaust (DE) inhalation induces up-regulation of inducible nitric oxide synthase (iNOS), which is known to contribute to vascular dysfunction, progression of atherosclerosis and ultimately cardiovascular morbidity and mortality. Methods: ApoE knockout mice (30-week) were exposed to DE (at 200 {mu}g/m{sup 3} of particulate matter) or filtered-air (control) for 7 weeks (6 h/day, 5 days/week). iNOS expression in the blood vessels and heart was evaluated by immunohistochemistry and western blotting analysis. To examine iNOS activity, thoracic aortae weremore » mounted in a wire myograph, and vasoconstriction stimulated by phenylephrine (PE) was measured with and without the presence of the specific inhibitor for iNOS (1400 W). NF-{kappa}B (p65) activity was examined by ELISA. The mRNA expression of iNOS and NF-{kappa}B (p65) was determined by real-time PCR. Results: DE exposure significantly enhanced iNOS expression in the thoracic aorta (4-fold) and heart (1.5 fold). DE exposure significantly attenuated PE-stimulated vasoconstriction by {approx} 20%, which was partly reversed by 1400 W. The mRNA expression of iNOS and NF-{kappa}B was significantly augmented after DE exposure. NF-{kappa}B activity was enhanced 2-fold after DE inhalation, and the augmented NF-{kappa}B activity was positively correlated with iNOS expression (R{sup 2} = 0.5998). Conclusions: We show that exposure to DE increases iNOS expression and activity possibly via NF-{kappa}B-mediated pathway. We suspect that DE exposure-caused up-regulation of iNOS contributes to vascular dysfunction and atherogenesis, which could ultimately lead to urban air pollution-associated cardiovascular morbidity and mortality. - Highlights: > Exposed ApoE knockout mice (30-week) to diesel exhaust (DE) for 7 weeks. > Examine iNOS expression and activity in

  18. Urinary tract infection in iNOS-deficient mice with focus on bacterial sensitivity to nitric oxide.

    PubMed

    Poljakovic, Mirjana; Persson, Katarina

    2003-01-01

    Inducible nitric oxide synthase (iNOS)-deficient mice were used to examine the role of iNOS in Escherichia coli-induced urinary tract infection (UTI). The toxicity of nitric oxide (NO)/peroxynitrite to bacteria and host was also investigated. The nitrite levels in urine of iNOS+/+ but not iNOS/ mice increased after infection. No differences in bacterial clearance or persistence were noted between the genotypes. In vitro, the uropathogenic E. coli 1177 was sensitive to 3-morpholinosydnonimine, whereas the avirulent E. coli HB101 was sensitive to both NO and 3-morpholinosydnonimine. E. coli HB101 was statistically (P < 0.05) more sensitive to peroxynitrite than E. coli 1177. Nitrotyrosine immunoreactivity was observed in infected bladders of both genotypes and in infected kidneys of iNOS+/+ mice. Myeloperoxidase, neuronal (n)NOS, and endothelial (e)NOS immunoreactivity was observed in inflammatory cells of both genotypes. Our results indicate that iNOS/ and iNOS+/+ mice are equally susceptible to E. coli-induced UTI and that the toxicity of NO to E. coli depends on bacterial virulence. Furthermore, myeloperoxidase and nNOS/eNOS may contribute to nitrotyrosine formation in the absence of iNOS.

  19. Climate Change 2014: Technical Summary

    USGS Publications Warehouse

    Field, Chrisopher B.; Barros, Vicente; Mach, Katherine; Mastrandrea, Michael; van Aalst, Maarten; Adger, Niel; Arent, Douglas J; Barnett, Jonathan; Betts, Richard; Bilir, Eren; Birkmann, Joern; Carmin, Joann; Chadee, Dave; Challinor, Andrew; Chaterjee, Monalisa; Cramer, Wolfgang; Davidson, Debra; Estrada, Yuka; Gatusso, Jean-Pierre; Hijioka, Yasuakai; Yohe, Gary; Hiza, Margaret; Hoegh-Guldberg, Ove; Huang, He-Qing; Insarov, Gregory; Jones, Roger; Kovats, Sari; Lankao, Patricia Romero; Larsen, Joan Nymand; Losada, Iñigo; Marengo, José; McLean, Roger; Mearns, Linda; Mechler, Reinhard; Morton, John; Niang, Isabelle; Oki, Taikan; Olwoch, Jane Mukarugwiza; Opondo, Maggie; Poloczanska, Elvira; Pörtner, Hans -O.; Reisinger, Andy; Revi, Aromar; Schmidt, Daniela; Shaw, Rebecca; Solecki, William; Stone, Dáithí; Stone, John; Strzepek, Ken; Suarez, Avelino G.; Tschakert, Petra; Valentini, Riccardo; Vicuna, Sebastian; Villamizar, Alicia; Vincent, Katharine; Warren, Rachel; White, Leslie; Wilbanks, Thomas; Wong, Poh Poh

    2014-01-01

    Human interference with the climate system is occurring (WGI AR5 SPM Section D.3; WGI AR5 Sections 2.2, 6.3, 10.3 to 10.6, 10.9). Climate change poses risks for human and natural systems. The assessment of impacts, adaptation, and vulnerability in the Working Group II contribution to the IPCC’s Fifth Assessment Report (WGII AR5) evaluates how patterns of risks and potential benefits are shifting due to climate change. It considers how impacts and risks related to climate change can be reduced and managed through adaptation and mitigation. The report assesses needs, options, opportunities, constraints, resilience, limits, and other aspects associated with adaptation. It recognizes that risks of climate change will vary across regions and populations, through space and time, dependent on myriad factors including the extent of adaptation and mitigation. For the past 2 decades, IPCC’s Working Group II has developed assessments of climate change impacts, adaptation, and vulnerability. The WGII AR5 builds from the WGII contribution to the IPCC’s Fourth Assessment Report (WGII AR4), published in 2007, and the Special Report on Managing the Risks of Extreme Events and Disasters to Advance Climate Change Adaptation (SREX), published in 2012. It follows the Working Group I contribution to the AR5. The WGII AR5 is presented in two parts (Part A: Global and Sectoral Aspects, and Part B: Regional Aspects), reflecting the expanded literature basis and multidisciplinary approach, increased focus on societal impacts and responses, and continued regionally comprehensive coverage. [1.1 to 1.3] The number of scientific publications available for assessing climate change impacts, adaptation, and vulnerability more than doubled between 2005 and 2010, with especially rapid increases in publications related to adaptation, allowing for a more robust assessment that supports policymaking (high confidence). The diversity of the topics and regions covered has similarly expanded, as has

  20. 15 CFR Supplement Nos.1-3 to Part 746 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false [Reserved] Nos.1 Supplement Nos.1-3 to Part 746 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE EXPORT ADMINISTRATION REGULATIONS EMBARGOES AND...

  1. Impact of technical and technological changes on energy efficiency of production company - case study

    NASA Astrophysics Data System (ADS)

    Szwedzka, K.; Gruszka, J.; Szafer, P.

    2016-08-01

    Improving energy efficiency is one of the strategic objectives of the European Union for rational energy economy. To make efforts to improve energy efficiency have been obliged both small and large end-users. This article aims to show the possibilities of improving energy efficiency by introducing technical and technological process changes of pine lumber drying. The object of the research is process of drying lumber implemented in a production company, which is a key supplier of large furniture manufacturer. Pine lumber drying chamber consume about 45% of total electricity in sawmill. According to various sources, drying of 1m3 of lumber uses about 3060kWh and is dependent of inter alia: the drying process itself, the factors affecting the processing time and the desired output moisture content of the timber. The article proposals for changes in the process of drying lumber pine have been positively validated in the company, and as a result their energy consumption per 1 m3 of product declined by 18%.

  2. Technical Assistance and Changes in Nutrition and Physical Activity Practices in the National Early Care and Education Learning Collaboratives Project, 2015–2016

    PubMed Central

    Smith, Teresa M.; Estabrooks, Paul A.; Rasmussen, Cristy Geno; Blaser, Casey; Yaroch, Amy L

    2018-01-01

    Purpose and Objectives The National Early Care and Education Learning Collaboratives Project (ECELC) aims to improve best practices in early care and education (ECE) programs in topic areas of the Nutrition and Physical Activity Self-Assessment in Child Care (NAP SACC). Technical assistance is a component of the ECELC, yet its effect on outcomes is unclear. Beyond dose and duration of technical assistance, limited research exists on characteristics of technical assistance that contribute to outcomes. The objective of this study was to identify and describe technical assistance characteristics and explore associations with NAP SACC outcomes. Intervention Approach We collected data from 10 collaboratives comprising 84 ECE programs in 2 states in 2015–2016. The objective of technical assistance was to support programs in improving best practices. Technical assistance was provided to programs via on-site, telephone, or email and was tailored to program needs. Evaluation Methods We used a mixed-methods design to examine associations between technical assistance and NAP SACC outcomes. We used multiple regression analysis to assess quantitative data and qualitative comparative analysis to determine necessary and sufficient technical assistance conditions supporting NAP SACC outcomes. We also conducted a document review to describe technical assistance that referred conditions identified by the qualitative comparative analysis. Results Regression analyses detected an inverse relationship between changes in NAP SACC scores and hours of technical assistance. No clear pattern emerged in the qualitative comparative analysis, leaving no necessary and sufficient conditions. However, the qualitative comparative analysis identified feedback as a potentially important component of technical assistance, whereas resource sharing and frequent email were characteristics that seemed to reduce the likelihood of improved outcomes. Email and resource sharing were considered primarily

  3. Voltage-dependent calcium channel involvement in NMDA-induced activation of NOS.

    PubMed

    Alagarsamy, S; Johnson, K M

    1995-11-13

    We have previously shown that N-methyl-D-aspartate (NMDA) increases nitric oxide synthase (NOS) activity in rat frontal cortex; however, the actual mechanism of this activation has not been addressed. Tetrodotoxin (TTX; 0.05 microM) inhibited NMDA-activated NOS, suggesting that TTX-sensitive Na+ channels are interposed between the NMDA receptors and the NOS cellular compartment. The NMDA response was also blocked by voltage-dependent Ca2+ channel (VDCC) blockers including Cd2+, Co2+, funnel web spider toxin (FTX) and omega-Aga IVa, but not by nifedipine or omega-conotoxin. These data suggest that Ca2+ flux through P- and/or Q-type VDCC subsequent to NMDA-induced depolarization may be at least as important for NOS activation as Ca2+ entry through the NMDA receptor.

  4. The Impact of the Social Norms of Education on Beginning Science Teachers' Understanding of NOS During their First Three Years in the Classroom

    NASA Astrophysics Data System (ADS)

    Firestone, Jonah B.

    An understanding of the Nature of Science (NOS) remains a fundamental goal of science education in the Unites States. A developed understanding of NOS provides a framework in which to situate science knowledge. Secondary science teachers play a critical role in providing students with an introduction to understanding NOS. Unfortunately, due to the high turnover rates of secondary science teachers in the United States, this critical role is often filled by relatively novice teachers. These beginning secondary science teachers make instructional decisions regarding science that are drawn from their emerging knowledge base, including a tentative understanding of NOS. This tentative knowledge can be affected by environment and culture of the classroom, school, and district in which beginning teachers find themselves. When examining NOS among preservice and beginning teachers the background and demographics of the teachers are often ignored. These teachers are treated as a homogenous block in terms of their initial understanding of NOS. This oversight potentially ignores interactions that may happen over time as teachers cross the border from college students, preservice teachers, and scientists into the classroom environment. Through Symbolic Interactionism we can explain how teachers change in order to adapt to their new surroundings and how this adaptation may be detrimental to their understanding of NOS and ultimately to their practice. 63 teachers drawn from a larger National Science Foundation (NSF) funded study were interviewed about their understanding of NOS over three years. Several demographic factors including college major, preservice program, number of History and Philosophy of Science classes, and highest academic degree achieve were shown to have an affect on the understanding of NOS over time. In addition, over time, the teachers tended to 'converge' in their understanding of NOS regardless of preservice experiences or induction support. Both the affect

  5. Circulating Blood eNOS Contributes to the Regulation of Systemic Blood Pressure and Nitrite Homeostasis

    PubMed Central

    Wood, Katherine C.; Cortese-Krott, Miriam M.; Kovacic, Jason C.; Noguchi, Audrey; Liu, Virginia B.; Wang, Xunde; Raghavachari, Nalini; Boehm, Manfred; Kato, Gregory J.; Kelm, Malte; Gladwin, Mark T.

    2013-01-01

    Objective Mice genetically deficient in endothelial nitric oxide synthase (eNOS−/−) are hypertensive with lower circulating nitrite levels, indicating the importance of constitutively produced nitric oxide (NO•) to blood pressure regulation and vascular homeostasis. While the current paradigm holds that this bioactivity derives specifically from expression of eNOS in endothelium, circulating blood cells also express eNOS protein. A functional red cell eNOS that modulates vascular NO• signaling has been proposed. Approach and Results To test the hypothesis that blood cells contribute to mammalian blood pressure regulation via eNOS-dependent NO• generation, we cross-transplanted WT and eNOS−/− mice, producing chimeras competent or deficient for eNOS expression in circulating blood cells. Surprisingly, we observed a significant contribution of both endothelial and circulating blood cell eNOS to blood pressure and systemic nitrite levels, the latter being a major component of the circulating NO• reservoir. These effects were abolished by the NOS inhibitor L-NAME and repristinated by the NOS substrate L-Arginine, and were independent of platelet or leukocyte depletion. Mouse erythrocytes were also found to carry an eNOS protein and convert 14C-Arginine into 14C-Citrulline in a NOS-dependent fashion. Conclusions These are the first studies to definitively establish a role for a blood borne eNOS, using cross transplant chimera models, that contributes to the regulation of blood pressure and nitrite homeostasis. This work provides evidence suggesting that erythrocyte eNOS may mediate this effect. PMID:23702660

  6. The mTOR kinase inhibitor rapamycin decreases iNOS mRNA stability in astrocytes

    PubMed Central

    2011-01-01

    Background Reactive astrocytes are capable of producing a variety of pro-inflammatory mediators and potentially neurotoxic compounds, including nitric oxide (NO). High amounts of NO are synthesized following up-regulation of inducible NO synthase (iNOS). The expression of iNOS is tightly regulated by complex molecular mechanisms, involving both transcriptional and post-transcriptional processes. The mammalian target of rapamycin (mTOR) kinase modulates the activity of some proteins directly involved in post-transcriptional processes of mRNA degradation. mTOR is a serine-threonine kinase that plays an evolutionarily conserved role in the regulation of cell growth, proliferation, survival, and metabolism. It is also a key regulator of intracellular processes in glial cells. However, with respect to iNOS expression, both stimulatory and inhibitory actions involving the mTOR pathway have been described. In this study the effects of mTOR inhibition on iNOS regulation were evaluated in astrocytes. Methods Primary cultures of rat cortical astrocytes were activated with different proinflammatory stimuli, namely a mixture of cytokines (TNFα, IFNγ, and IL-1β) or by LPS plus IFNγ. Rapamycin was used at nM concentrations to block mTOR activity and under these conditions we measured its effects on the iNOS promoter, mRNA and protein levels. Functional experiments to evaluate iNOS activity were also included. Results In this experimental paradigm mTOR activation did not significantly affect astrocyte iNOS activity, but mTOR pathway was involved in the regulation of iNOS expression. Rapamycin did not display any significant effects under basal conditions, on either iNOS activity or its expression. However, the drug significantly increased iNOS mRNA levels after 4 h incubation in presence of pro-inflammatory stimuli. This stimulatory effect was transient, since no differences in either iNOS mRNA or protein levels were detected after 24 h. Interestingly, reduced levels of iNOS

  7. Web-based technical assistance and training to promote community tobacco control policy change.

    PubMed

    Young, Walter F; Montgomery, Debbie; Nycum, Colleen; Burns-Martin, Lavon; Buller, David B

    2006-01-01

    In 1998 the tobacco industry was released of claims that provided monetary relief for states. A significant expansion of tobacco control activity in many states created a need to develop local capacity. Technical assistance and training for new and experienced staff became a significant challenge for tobacco control leadership. In Colorado, this challenge was addressed in part through the development of a technical assistance and training Web site designed for local tobacco control staff and coalition members. Researchers, technical Web site development specialists, state health agency, and state tobacco control coalition staff collaborated to develop, promote, and test the efficacy of this Web site. The work group embodied a range of skills including tobacco control, Web site technical development, marketing, training, and project management. Persistent marketing, updating of Web site content, and institutionalizing it as a principal source of information and training were key to use by community coalition members.

  8. Effects of AAV-mediated knockdown of nNOS and GPx-1 gene expression in rat hippocampus after traumatic brain injury.

    PubMed

    Boone, Deborah R; Leek, Jeanna M; Falduto, Michael T; Torres, Karen E O; Sell, Stacy L; Parsley, Margaret A; Cowart, Jeremy C; Uchida, Tatsuo; Micci, Maria-Adelaide; DeWitt, Douglas S; Prough, Donald S; Hellmich, Helen L

    2017-01-01

    Virally mediated RNA interference (RNAi) to knock down injury-induced genes could improve functional outcome after traumatic brain injury (TBI); however, little is known about the consequences of gene knockdown on downstream cell signaling pathways and how RNAi influences neurodegeneration and behavior. Here, we assessed the effects of adeno-associated virus (AAV) siRNA vectors that target two genes with opposing roles in TBI pathogenesis: the allegedly detrimental neuronal nitric oxide synthase (nNOS) and the potentially protective glutathione peroxidase 1 (GPx-1). In rat hippocampal progenitor cells, three siRNAs that target different regions of each gene (nNOS, GPx-1) effectively knocked down gene expression. However, in vivo, in our rat model of fluid percussion brain injury, the consequences of AAV-siRNA were variable. One nNOS siRNA vector significantly reduced the number of degenerating hippocampal neurons and showed a tendency to improve working memory. GPx-1 siRNA treatment did not alter TBI-induced neurodegeneration or working memory deficits. Nevertheless, microarray analysis of laser captured, virus-infected neurons showed that knockdown of nNOS or GPx-1 was specific and had broad effects on downstream genes. Since nNOS knockdown only modestly ameliorated TBI-induced working memory deficits, despite widespread genomic changes, manipulating expression levels of single genes may not be sufficient to alter functional outcome after TBI.

  9. Confronting Regulatory Cost and Quality Expectations. An Exploration of Technical Change in Minimum Efficiency Performance Standards

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

    Taylor, Margaret; Spurlock, C. Anna; Yang, Hung-Chia

    The dual purpose of this project was to contribute to basic knowledge about the interaction between regulation and innovation and to inform the cost and benefit expectations related to technical change which are embedded in the rulemaking process of an important area of national regulation. The area of regulation focused on here is minimum efficiency performance standards (MEPS) for appliances and other energy-using products. Relevant both to U.S. climate policy and energy policy for buildings, MEPS remove certain product models from the market that do not meet specified efficiency thresholds.

  10. Annual report of the National Advisory Committee for Aeronautics (5th).administrative report including Technical Reports nos. 51 to 82

    NASA Technical Reports Server (NTRS)

    1920-01-01

    Report includes the National Advisory Committee for Aeronautics letter of submittal to the President, Congressional report, summaries of the committee's activities and research accomplished, expenditures, and a compilation of technical reports produced.

  11. Quantitative Detection of the nosZ Gene, Encoding Nitrous Oxide Reductase, and Comparison of the Abundances of 16S rRNA, narG, nirK, and nosZ Genes in Soils

    PubMed Central

    Henry, S.; Bru, D.; Stres, B.; Hallet, S.; Philippot, L.

    2006-01-01

    Nitrous oxide (N2O) is an important greenhouse gas in the troposphere controlling ozone concentration in the stratosphere through nitric oxide production. In order to quantify bacteria capable of N2O reduction, we developed a SYBR green quantitative real-time PCR assay targeting the nosZ gene encoding the catalytic subunit of the nitrous oxide reductase. Two independent sets of nosZ primers flanking the nosZ fragment previously used in diversity studies were designed and tested (K. Kloos, A. Mergel, C. Rösch, and H. Bothe, Aust. J. Plant Physiol. 28:991-998, 2001). The utility of these real-time PCR assays was demonstrated by quantifying the nosZ gene present in six different soils. Detection limits were between 101 and 102 target molecules per reaction for all assays. Sequence analysis of 128 cloned quantitative PCR products confirmed the specificity of the designed primers. The abundance of nosZ genes ranged from 105 to 107 target copies g−1 of dry soil, whereas genes for 16S rRNA were found at 108 to 109 target copies g−1 of dry soil. The abundance of narG and nirK genes was within the upper and lower limits of the 16S rRNA and nosZ gene copy numbers. The two sets of nosZ primers gave similar gene copy numbers for all tested soils. The maximum abundance of nosZ and nirK relative to 16S rRNA was 5 to 6%, confirming the low proportion of denitrifiers to total bacteria in soils. PMID:16885263

  12. Expression of iNOS and NF-κB in melasma: an immunohistochemical study.

    PubMed

    Samaka, Rehab Monir; Bakry, Ola Ahmed; Shoeib, Mohamed Abd El Monaem; Zaaza, Marwa M

    2014-10-01

    To investigate the role of inducible nitric oxide synthases (iNOS) and nuclear factor-kappa B (NF-κB) in the pathogenesis of melasma through their immunohistochemical (IHC) co-localization in skin of melasma and to correlate their expression with the clinical and the histopathological data. This prospective case-control study was conducted on 34 female patients with melasma and 30 age- and gender-matched healthy subjects as a control group for evaluation of IHC expression of iNOS and NF-κB in melasma. There were significant differences between lesional and perilesional skin regarding iNOS intensity, iNOS histo-score (H-score), NF-κB intensity, and NF-κB H-score (p < 0.001 for all). There were significant associations between the higher values of H-scores for both iNOS and NF-κB and positive family history (p = 0.002 and p = 0.001, respectively) and very severe melasma areas and severity index score (p < 0.001 and p = 0.001, respectively). There was a positive correlation between H-score values of both iNOS and NF-κB (r = +0.604 and p < 0.001). The IHC co-localization and direct correlation of both iNOS and NF-κB in melasma could provide evidence about their role as co-players in melanogenesis and might provide new targets for a more efficient treatment for melasma.

  13. Investigating the Role of NOS2 in Breast Cancer | Center for Cancer Research

    Cancer.gov

    Inducible nitric oxide synthase (NOS2) is often elevated in breast tumors that lack expression of the estrogen receptor (ER) and predicts a poor prognosis for patients with these tumors. However, it is unclear whether NOS2 directly contributes to ER-negative breast cancer aggressiveness or how NOS2 expression is controlled within the tumor microenvironment. To tease apart the

  14. Annual Report of the National Advisory Committee for Aeronautics (1st). [Administrative Report Including Technical Reports Nos. 1 to 7

    NASA Technical Reports Server (NTRS)

    1916-01-01

    Report includes the National Advisory Committee for Aeronautics letter of submittal to the President, Congressional report, summaries of the committee's activities and research accomplished, expenditures, problems, recommendations, and a compilation of technical reports produced.

  15. Annual report of the National Advisory Committee for Aeronautics (4th).administrative report including Technical Reports nos. 24 to 50

    NASA Technical Reports Server (NTRS)

    1920-01-01

    Report includes the National Advisory Committee for Aeronautics letter of submittal to the President, Congressional report, summaries of the committee's activities and research accomplished, expenditures, problems, recommendations, and a compilation of technical reports produced.

  16. NOS1 mediates AP1 nuclear translocation and inflammatory response.

    PubMed

    Srivastava, Mansi; Baig, Mirza S

    2018-06-01

    A hallmark of the AP1 functioning is its nuclear translocation, which induces proinflammatory cytokine expression and hence the inflammatory response. After endotoxin shock AP1 transcription factor, which comprises Jun, ATF2, and Fos family of proteins, translocates into the nucleus and induces proinflammatory cytokine expression. In the current study, we found, NOS1 inhibition prevents nuclear translocation of the AP1 transcription factor subunits. Pharmacological inhibition of NOS1 impedes translocation of subunits into the nucleus, suppressing the transcription of inflammatory genes causing a diminished inflammatory response. In conclusion, the study shows the novel mechanism of NOS1- mediated AP1 nuclear translocation, which needs to be further explored. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. On the Necessity of Changes in the Strategy of Utilization Ship Boiler Technical Condition Maintenance in the Aspect of LNG Applied as Fuel

    NASA Astrophysics Data System (ADS)

    Adamkiewicz, Andrzej; Zeńczak, Wojciech

    2017-03-01

    Heavy oils (HFO fuels) used on ships play a part in degradation of technical condition of heat exchange surfaces of utilization boilers especially on the exhaust gas side. Presence of sulphur in these fuels is the main factor favouring degradation. The upper limit for sulphur content in the fuel used outside the SECA areas equal to 3.5% is currently in force, at least until the year 2020 or 2025. The recommended by classification societies overhauls of utilization boilers are, therefore characterized by a specially chosen strategy thanks to which it is possible to maintain their appropriate technical condition. The requirement to use fuels with low sulphur content (LSFO), which are significantly more expensive than MDO fuels, in the areas of controlled sulphur emissions also led to a further introduction of alternative fuels, such as methanol and above all liquefied natural gas (LNG), onto ships. That is especially valid for the ship owners whose vessels e.g. ferries sail mainly within SCECA This article analyses the consequences of the introduced fuel change on utilization boiler maintenance. A change in the technical condition maintenance strategy for utilization boilers has been suggested.

  18. 77 FR 12010 - Marine Mammals; File Nos. 1076-1789 and 14502

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-28

    ... Mammals; File Nos. 1076-1789 and 14502 AGENCY: National Marine Fisheries Service (NMFS), National Oceanic... 80208, have been issued minor amendments to Scientific Research Permit Nos. 1076-1789 and 14502.... 1076-1789: This permit, issued on March 13, 2007 (72 FR 13092), authorized the receipt, import and...

  19. 75 FR 10529 - Mail Classification Change

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-08

    ... POSTAL REGULATORY COMMISSION [Docket Nos. MC2010-19; Order No. 415] Mail Classification Change...-filed Postal Service request to make a minor modification to the Mail Classification Schedule. The.... concerning a change in classification which reflects a change in terminology from Bulk Mailing Center (BMC...

  20. microRNAs regulate nitric oxide release from endothelial cells by targeting NOS3.

    PubMed

    Qin, Ji-Zheng; Wang, Shao-Jie; Xia, Chun

    2018-06-13

    Endothelial nitric oxide synthase (eNOS) encoded by nitric oxide synthase 3 (NOS3), can generate nitric oxide (NO) which serves as an important deterrent to the pathogenesis of thrombosis by modulating the activation, adhesion and aggregate formation of platelets. Three serum miRNAs (miR-195, miR-532 and miR-582) have been suggested as biomarkers for the diagnosis of deep vein thrombosis (DVT), however their potential roles in DVT is not clear. The effect of miRNAs inhibiting the expression of NOS3 was evaluated in vitro. miR-195, miR-532 and miR-582 mimic, inhibitor, and control miRNAs were transfected into endothelial cells. The roles of miR-195, miR-532 and miR-582 regulating the expression of eNOS were evaluated by real-time quantitative PCR, Western Blotting and luciferase reporter assays. NO release was measured by Griess method. We confirmed NOS3 as a direct target of miR-195 and miR-582, which binds to the 3'-UTR of NOS3 mRNA in endothelial cells. A significantly inverse correlation between these two miRNAs and eNOS expression was detected. NO release from endothelial cells was decreased when the expression level of miR-195 and miR-582 was up-regulated. These findings indicated that miR-195 and miR-582 regulated NO release by targeting 3'-UTR of NOS3 post-transcriptionally in endothelial cells. Therefore, miR-195 and miR-582 might play an important role in maintaining endothelial NO bioavailability and could be a novel target for treatment of thrombotic diseases.

  1. Reliability Abstracts and Technical Reviews January - December 1970. Volume 10, Nos. 1-12; R70-14805 - R70-15438

    NASA Technical Reports Server (NTRS)

    1970-01-01

    Reliability Abstracts and Technical Reviews is an abstract and critical analysis service covering published and report literature on reliability. The service is designed to provide information on theory and practice of reliability as applied to aerospace and an objective appraisal of the quality, significance, and applicability of the literature abstracted.

  2. Better Jobs, Brighter Futures, a Stronger Washington. Washington's Community and Technical Colleges

    ERIC Educational Resources Information Center

    Washington State Board for Community and Technical Colleges, 2015

    2015-01-01

    The world is changing rapidly. With changes in technology, demographics, and workforce trends, Washington needs colleges to not only keep pace, but lead the way. Washington's 34 community and technical colleges answer that call. The community and technical colleges have proven uniquely positioned to adapt to, embrace, and ignite change. Community…

  3. Pedagogical Reflections by Secondary Science Teachers at Different NOS Implementation Levels

    ERIC Educational Resources Information Center

    Herman, Benjamin C.; Clough, Michael P.; Olson, Joanne K.

    2017-01-01

    This study investigated what 13 secondary science teachers at various nature of science (NOS) instruction implementation levels talked about when they reflected on their teaching. We then determined if differences exist in the quality of those reflections between high, medium, and low NOS implementers. This study sought to answer the following…

  4. Glu298Asp eNOS gene polymorphism causes attenuation in nonexercising muscle vasodilatation.

    PubMed

    Dias, Rodrigo G; Alves, Maria-Janieire N N; Pereira, Alexandre C; Rondon, Maria Urbana P B; Dos Santos, Marcelo R; Krieger, José E; Krieger, Marta H; Negrão, Carlos E

    2009-04-10

    The influence of Glu298Asp endothelial nitric oxide synthase (eNOS) polymorphism in exercise-induced reflex muscle vasodilatation is unknown. We hypothesized that nonexercising forearm blood flow (FBF) responses during handgrip isometric exercise would be attenuated in individuals carrying the Asp298 allele. In addition, these responses would be mediated by reduced eNOS function and NO-mediated vasodilatation or sympathetic vasoconstriction. From 287 volunteers previously genotyped, we selected 33 healthy individuals to represent three genotypes: Glu/Glu [n = 15, age 43 +/- 3 yr, body mass index (BMI) 22.9 +/- 0.3 kg/m(2)], Glu/Asp (n = 9, age 41 +/- 3 yr, BMI 23.7 +/- 1.0 kg/m(2)), and Asp/Asp (n = 9, age 40 +/- 4 yr, BMI 23.5 +/- 0.9 kg/m(2)). Heart rate (HR), mean blood pressure (MBP), and FBF (plethysmography) were recorded for 3 min at baseline and 3 min during isometric handgrip exercise. Baseline HR, MBP, FBF, and forearm vascular conductance (FVC) were similar among genotypes. FVC responses to exercise were significantly lower in Asp/Asp when compared with Glu/Asp and Glu/Glu (Delta = 0.07 +/- 0.14 vs. 0.64 +/- 0.20 and 0.57 +/- 0.09 units, respectively; P = 0.002). Further studies showed that intra-arterial infusion of NG-monomethyl-L-arginine (L-NMMA) did not change FVC responses to exercise in Asp/Asp, but significantly reduced FVC in Glu/Glu (Delta = 0.79 +/- 0.14 vs. 0.14 +/- 0.09 units). Thus the differences between Glu/Glu and Asp/Asp were no longer observed (P = 0.62). l-NMMA + phentolamine increased similarly FVC responses to exercise in Glu/Glu and Asp/Asp (P = 0.43). MBP and muscle sympathetic nerve activity increased significant and similarly throughout experimental protocols in Glu/Glu and Asp/Asp. Individuals who are homozygous for the Asp298 allele of the eNOS enzyme have attenuated nonexercising muscle vasodilatation in response to exercise. This genotype difference is due to reduced eNOS function and NO-mediated vasodilatation, but not

  5. Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications.

    PubMed

    Iqbal, Sana; Hayman, Erik G; Hong, Caron; Stokum, Jesse A; Kurland, David B; Gerzanich, Volodymyr; Simard, J Marc

    2016-01-01

    Aneurysmal subarachnoid hemorrhage (SAH) typically carries a poor prognosis. Growing evidence indicates that overabundant production of nitric oxide (NO) may be responsible for a large part of the secondary injury that follows SAH. Although SAH modulates the activity of all three isoforms of nitric oxide synthase (NOS), the inducible isoform, NOS-2, accounts for a majority of NO-mediated secondary injuries after SAH. Here, we review the indispensable physiological roles of NO that must be preserved, even while attempting to downmodulate the pathophysiologic effects of NO that are induced by SAH. We examine the effects of SAH on the function of the various NOS isoforms, with a particular focus on the pathological effects of NOS-2 and on the mechanisms responsible for its transcriptional upregulation. Finally, we review interventions to block NOS-2 upregulation or to counteract its effects, with an emphasis on the potential therapeutic strategies to improve outcomes in patients afflicted with SAH. There is still much to be learned regarding the apparently maladaptive response of NOS-2 and its harmful product NO in SAH. However, the available evidence points to crucial effects that, on balance, are adverse, making the NOS-2/NO/peroxynitrite axis an attractive therapeutic target in SAH.

  6. Up-regulation of the RhoA/Rho-kinase signaling pathway in corpus cavernosum from endothelial nitric-oxide synthase (NOS), but not neuronal NOS, null mice.

    PubMed

    Priviero, Fernanda B M; Jin, Li-Ming; Ying, Zhekang; Teixeira, Cleber E; Webb, R Clinton

    2010-04-01

    We tested the hypothesis that the basal release of nitric oxide (NO) from endothelial cells modulates contractile activity in the corpus cavernosum (CC) via inhibition of the RhoA/Rho-kinase signaling pathway. Cavernosal strips from wild-type (WT), endothelial nitric-oxide synthase knockout [eNOS(-/-)], and neuronal nitric-oxide synthase knockout [nNOS(-/-)] mice were mounted in myographs, and isometric force was recorded. mRNA and protein expression of key molecules in the RhoA/Rho-kinase pathway were analyzed by real-time polymerase chain reaction and Western blot, respectively. The cGMP levels were determined. The Rho-kinase inhibitors (R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide (Y-27632) and (S)-(+)-2-methyl-1-[(4-methyl-5-isoquinolinyl)sulfonyl] homopiperazine (H-1152) reduced cavernosal contractions evoked by phenylephrine or electrical field stimulation (EFS) in a concentration-dependent manner, although this inhibition was less effective in tissues from eNOS(-/-) mice. Y-27632 enhanced relaxations induced by sodium nitroprusside, EFS, and NO (administered as acidified NaNO2) without affecting the cGMP content of the cavernosal strips. This enhancement was less prominent in CC from eNOS(-/-). The protein expression of RhoA, Rho-guanine dissociation inhibitor, and Rho-kinase beta did not differ among the strains. However, in eNOS(-/-) CC, the protein expression of Rho-kinase alpha and both mRNA and protein expression of p115-Rho-associated guanine exchange factor (RhoGEF), PDZ-RhoGEF, and leukemia-associated RhoGEF were up-regulated. Phosphorylation of MYPT1 at Thr696 was higher in tissues from eNOS(-/-) mice. A high concentration of Y-27632 significantly enhanced NO release in CC stimulated by EFS. These results suggest a basal release of NO from endothelial cells, which inhibits contractions mediated by the RhoA/Rho-kinase pathway and modulates the expression of proteins related to this pathway in mouse CC. It indicates that

  7. Using a Professional Development Program for Enhancing Chilean Biology Teachers' Understanding of Nature of Science (NOS) and Their Perceptions about Using History of Science to Teach NOS

    ERIC Educational Resources Information Center

    Pavez, José M.; Vergara, Claudia A.; Santibañez, David; Cofré, Hernán

    2016-01-01

    A number of authors have recognized the importance of understanding the nature of science (NOS) for scientific literacy. Different instructional strategies such as decontextualized, hands-on inquiry, and history of science (HOS) activities have been proposed for teaching NOS. This article seeks to understand the contribution of HOS in enhancing…

  8. Investigating the Role of NOS2 in Breast Cancer | Center for Cancer Research

    Cancer.gov

    Inducible nitric oxide synthase (NOS2) is often elevated in breast tumors that lack expression of the estrogen receptor (ER) and predicts a poor prognosis for patients with these tumors. However, it is unclear whether NOS2 directly contributes to ER-negative breast cancer aggressiveness or how NOS2 expression is controlled within the tumor microenvironment. To tease apart the regulatory pathways upstream and downstream of NOS2, David Wink, Jr., Ph.D., Senior Investigator in CCR’s Radiation Biology Branch, along with colleagues from CCR’s Pediatric Oncology Branch, Laboratory of Human Carcinogenesis, and Laboratory of Experimental Immunology and from the Prostate Cancer Institute in Ireland, carried out studies in cell culture and mouse models.

  9. SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy

    PubMed Central

    Weng, Hongbo; Li, Xuezheng; Reece, E. Albert; Yang, Peixin

    2012-01-01

    Objectives Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression. Study Design iNOS-luciferase activities, nitrosylated protein, lipidperoxidation markers 4-HNE and MDA were determined in PYS-2 cells exposed to 5 mM glucose or high glucose (25 mM) with or without SOD1 (copper zinc superoxide dismutase 1) treatment. Levels of iNOS protein and mRNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1 overexpressing embryos from non-diabetic and diabetic dams. Results SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-HNE and MDA reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. in vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage. Conclusions We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy. PMID:22425406

  10. SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy.

    PubMed

    Weng, Hongbo; Li, Xuezheng; Reece, E Albert; Yang, Peixin

    2012-05-01

    Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression. iNOS-luciferase activities, nitrosylated protein, and lipid peroxidation markers 4-hydroxynonenal and malondialdehyde were determined in parietal yolk sac-2 cells exposed to 5 mmol/L glucose or high glucose (25 mmol/L) with or without copper zinc superoxide dismutase 1 (SOD1) treatment. Levels of iNOS protein and messenger RNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1-overexpressing embryos from nondiabetic and diabetic dams. SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-hydroxynonenal and malondialdehyde reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. In vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage. We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy. Copyright © 2012 Mosby, Inc. All rights reserved.

  11. Fluorination Effects on NOS Inhibitory Activity of Pyrazoles Related to Curcumin.

    PubMed

    Nieto, Carla I; Cabildo, María Pilar; Cornago, María Pilar; Sanz, Dionisia; Claramunt, Rosa M; Torralba, María Carmen; Torres, María Rosario; Elguero, José; García, José A; López, Ana; Acuña-Castroviejo, Darío

    2015-08-28

    A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (¹H, (13)C, (19)F and (15)N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure-activity analysis allowed the establishment of a correlation between the presence/ absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[β-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1H-pyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms.

  12. nNOS-positive minor-branches of the dorsal penile nerves is associated with erectile function in the bilateral cavernous injury model of rats.

    PubMed

    Chen, Yen-Lin; Chao, Ting-Ting; Wu, Yi-No; Chen, Meng-Chuan; Lin, Ying-Hung; Liao, Chun-Hou; Wu, Chien-Chih; Chen, Kuo-Chiang; Chou, Shang-Shing P; Chiang, Han-Sun

    2018-01-17

    The changes in neuronal nitric oxide synthases (nNOS) in the dorsal penile nerves (DPNs) are consistent with cavernous nerve (CN) injury in rat models. However, the anatomical relationship and morphological changes between the minor branches of the DPNs and the CNs after injury have never been clearly explored. There were forty 12 week old male Sprague-Dawley rats receiving bilateral cavernous nerve injury (BCNI). Erectile function of intracavernous pressure and mean arterial pressure were measured. The histology and ultrastructure with H&E stain, Masson's trichrome stain and immunohistochemical stains were applied on the examination of CNs and DPNs. We demonstrated communicating nerve branches between the DPNs and the CNs in rats. The greatest damage and lowest erectile function were seen in the 14 th day and partially recovered in the 28 th day after BCNI. The nNOS positive DPN minor branches' number was significantly correlated with erectile function. The sub-analysis of the number of nNOS positive DPN minor branches also matched with the time course of the erectile function after BCNI. We suggest the regeneration of the DPNs minor branches would ameliorate the erectile function in BCNI rats.

  13. 44 CFR 65.3 - Requirement to submit new technical data.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... available, a community shall notify the Administrator of the changes by submitting technical or scientific... IDENTIFICATION AND MAPPING OF SPECIAL HAZARD AREAS § 65.3 Requirement to submit new technical data. A community's...

  14. Technical change in US industry: A cross-industry analysis

    NASA Technical Reports Server (NTRS)

    Nelson, R. R. (Editor)

    1981-01-01

    The nature of the public policies which have influenced the pace and pattern of technical progress in a number of American industries is studied with the view of assessing the broad effects of these policies. The industries studied are agriculture, pharmaceuticals, semiconductors, computers, civil aircraft, automobiles and residential construction. The policies considered include research and development funding as well as government procurement, education, information dissemination, patent protection, licensing, regulations, and anti-trust policies.

  15. NOS-based biopolymers; towards novel thromboresistant NO-release materials

    NASA Astrophysics Data System (ADS)

    Abou Diwan, Charbel

    Nitric Oxide releasing biopolymers have the potential to prolong vascular graft and stent potency without adverse systemic vasodilation. It was reported in literature that eNOS-overexpressing endothelial cell seeding of synthetic small diameter vascular grafts decreased human platelet aggregation by 46% and bovine aortic smooth muscle cell proliferation by 67.2% in vitro. We hypothesized that incorporating the enzyme nitric oxide synthase (NOS) in biocompatible polymeric matrix will provide a source of NO that utilizes endogenous compounds to maintain an unlimited supply of NO. To test this hypothesis, we have incorporated the enzyme nitric oxide synthase into a polyethyleneimine film using a layer-by-layer electrostatic deposition. This approach will provide a source of NO that utilizes endogenous compounds available in the blood matrix to maintain a constant supply of NO at the blood/device interface. When coated onto the surface of various blood-contacting implantable medical devices, it will provide NO fluxes at levels equal or greater than the normal endothelial cells, and for extended time periods. This configuration will help solve the issues of both thrombosis and stenosis that occur as side effects for several types of biomedical implants. Our results indicate a proof of principle of a new approach for making antithrombotic coatings for medical devices and implants based on NO release. We have demonstrated that NOS-based polymetric films successfully generate NO under physiologic conditions at small levels equal to and higher than those observed for endothelial cells. The level of NO release can be fine-tuned through varying the number of NOS layers in the film buildup. We have shown that NO fluxes from our NOS-based PEI films are sustained for prolonged periods of time, which has the potential of producing efficient, short and long-term, antithrombotic coatings for medical devices and blood-contacting tools such as stents and catheters. We also show that

  16. Changes in Aspects of Students' Self-Reported Personal, Social and Technical Skills during a Six-Week Wilderness Expedition in Arctic Greenland

    ERIC Educational Resources Information Center

    Stott, Tim; Hall, Neil

    2003-01-01

    This investigation focuses on students' self-reported changes in personal, social and technical skills that took place during a six-week long expedition to East Greenland. A 105-item pre-and post-expedition questionnaire was completed by 60 young expeditioners aged 16 to 20. Before the expedition participants generally felt that they had high…

  17. National climate assessment technical report on the impacts of climate and land use and land cover change

    USGS Publications Warehouse

    Loveland, Thomas; Mahmood, Rezaul; Patel-Weynand, Toral; Karstensen, Krista; Beckendorf, Kari; Bliss, Norman; Carleton, Andrew

    2012-01-01

    This technical report responds to the recognition by the U.S. Global Change Research Program (USGCRP) and the National Climate Assessment (NCA) of the importance of understanding how land use and land cover (LULC) affects weather and climate variability and change and how that variability and change affects LULC. Current published, peer-reviewed, scientific literature and supporting data from both existing and original sources forms the basis for this report's assessment of the current state of knowledge regarding land change and climate interactions. The synthesis presented herein documents how current and future land change may alter environment processes and in turn, how those conditions may affect both land cover and land use by specifically investigating, * The primary contemporary trends in land use and land cover, * The land-use and land-cover sectors and regions which are most affected by weather and climate variability,* How land-use practices are adapting to climate change, * How land-use and land-cover patterns and conditions are affecting weather and climate, and * The key elements of an ongoing Land Resources assessment. These findings present information that can be used to better assess land change and climate interactions in order to better assess land management and adaptation strategies for future environmental change and to assist in the development of a framework for an ongoing national assessment.

  18. Nitrous Oxide Reductase (nosZ) Gene Fragments Differ between Native and Cultivated Michigan Soils

    PubMed Central

    Stres, Blaž; Mahne, Ivan; Avguštin, Gorazd; Tiedje, James M.

    2004-01-01

    The effect of standard agricultural management on the genetic heterogeneity of nitrous oxide reductase (nosZ) fragments from denitrifying prokaryotes in native and cultivated soil was explored. Thirty-six soil cores were composited from each of the two soil management conditions. nosZ gene fragments were amplified from triplicate samples, and PCR products were cloned and screened by restriction fragment length polymorphism (RFLP). The total nosZ RFLP profiles increased in similarity with soil sample size until triplicate 3-g samples produced visually identical RFLP profiles for each treatment. Large differences in total nosZ profiles were observed between the native and cultivated soils. The fragments representing major groups of clones encountered at least twice and four randomly selected clones with unique RFLP patterns were sequenced to verify nosZ identity. The sequence diversity of nosZ clones from the cultivated field was higher, and only eight patterns were found in clone libraries from both soils among the 182 distinct nosZ RFLP patterns identified from the two soils. A group of clones that comprised 32% of all clones dominated the gene library of native soil, whereas many minor groups were observed in the gene library of cultivated soil. The 95% confidence intervals of the Chao1 nonparametric richness estimator for nosZ RFLP data did not overlap, indicating that the levels of species richness are significantly different in the two soils, the cultivated soil having higher diversity. Phylogenetic analysis of deduced amino acid sequences grouped the majority of nosZ clones into an interleaved Michigan soil cluster whose cultured members are α-Proteobacteria. Only four nosZ sequences from cultivated soil and one from the native soil were related to sequences found in γ-Proteobacteria. Sequences from the native field formed a distinct, closely related cluster (Dmean = 0.16) containing 91.6% of the native clones. Clones from the cultivated field were more

  19. NOS1 ex1f-VNTR polymorphism influences prefrontal brain oxygenation during a working memory task.

    PubMed

    Kopf, Juliane; Schecklmann, Martin; Hahn, Tim; Dresler, Thomas; Dieler, Alica C; Herrmann, Martin J; Fallgatter, Andreas J; Reif, Andreas

    2011-08-15

    Nitric oxide (NO) synthase produces NO, which serves as first and second messenger in neurons, where the protein is encoded by the NOS1 gene. A functional variable number of tandem repeats (VNTR) polymorphism in the promoter region of the alternative first exon 1f of NOS1 is associated with various functions of human behavior, for example increased impulsivity, while another, non-functional variant was linked to decreased verbal working memory and a heightened risk for schizophrenia. We therefore investigated the influence of NOS1 ex 1f-VNTR on working memory function as reflected by both behavioral measures and prefrontal oxygenation. We hypothesized that homozygous short allele carriers exhibit altered brain oxygenation in task-related areas, namely the dorsolateral and ventrolateral prefrontal cortex and the parietal cortex. To this end, 56 healthy subjects were stratified into a homozygous long allele group and a homozygous short allele group comparable for age, sex and intelligence. All subjects completed a letter n-back task (one-, two-, and three-back), while concentration changes of oxygenated (O(2)Hb) hemoglobin in the prefrontal cortex were measured with functional near-infrared spectroscopy (fNIRS). We found load-associated O(2)Hb increases in the prefrontal and parts of the parietal cortex. Significant load-associated oxygenation differences between the two genotype groups could be shown for the dorsolateral prefrontal cortex and the parietal cortex. Specifically, short allele carriers showed a significantly larger increase in oxygenation in all three n-back tasks. This suggests a potential compensatory mechanism, with task-related brain regions being more active in short allele carriers to compensate for reduced NOS1 expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. De Novo Lipogenesis Maintains Vascular Homeostasis through Endothelial Nitric-oxide Synthase (eNOS) Palmitoylation*♦

    PubMed Central

    Wei, Xiaochao; Schneider, Jochen G.; Shenouda, Sherene M.; Lee, Ada; Towler, Dwight A.; Chakravarthy, Manu V.; Vita, Joseph A.; Semenkovich, Clay F.

    2011-01-01

    Endothelial dysfunction leads to lethal vascular complications in diabetes and related metabolic disorders. Here, we demonstrate that de novo lipogenesis, an insulin-dependent process driven by the multifunctional enzyme fatty-acid synthase (FAS), maintains endothelial function by targeting endothelial nitric-oxide synthase (eNOS) to the plasma membrane. In mice with endothelial inactivation of FAS (FASTie mice), eNOS membrane content and activity were decreased. eNOS and FAS were physically associated; eNOS palmitoylation was decreased in FAS-deficient cells, and incorporation of labeled carbon into eNOS-associated palmitate was FAS-dependent. FASTie mice manifested a proinflammatory state reflected as increases in vascular permeability, endothelial inflammatory markers, leukocyte migration, and susceptibility to LPS-induced death that was reversed with an NO donor. FAS-deficient endothelial cells showed deficient migratory capacity, and angiogenesis was decreased in FASTie mice subjected to hindlimb ischemia. Insulin induced FAS in endothelial cells freshly isolated from humans, and eNOS palmitoylation was decreased in mice with insulin-deficient or insulin-resistant diabetes. Thus, disrupting eNOS bioavailability through impaired lipogenesis identifies a novel mechanism coordinating nutritional status and tissue repair that may contribute to diabetic vascular disease. PMID:21098489

  1. Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner

    PubMed Central

    Hocher, Berthold; Haumann, Hannah; Rahnenführer, Jan; Reichetzeder, Christoph; Kalk, Philipp; Pfab, Thiemo; Tsuprykov, Oleg; Winter, Stefan; Hofmann, Ute; Li, Jian; Püschel, Gerhard P.; Lang, Florian; Schuppan, Detlef; Schwab, Matthias; Schaeffeler, Elke

    2016-01-01

    ABSTRACT Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood. PMID:27175980

  2. Impact of historical science short stories on students' attitudes and NOS understanding

    NASA Astrophysics Data System (ADS)

    Hall, Garrett

    This study examines the impact of historical short stories on upper and lower level high school chemistry students in the second semester of a two-semester course at a large Midwestern suburban school. Research focused on improved understanding of six fundamental nature of science (NOS) concepts made explicit in the stories, recollection of historical examples from the stories that supported student NOS thinking; student attitudes toward historical stories in comparison to traditional textbook readings as well as student attitudes regarding scientists and the development of science ideas. Data collection included surveys over six NOS concepts, attitudes towards science and reading, and semi-structured interviews. Analysis of the data collected in this study indicated significant increases in understanding for three of the six NOS concepts within the upper-level students and one of the six concepts for lower level students. Students were able to draw upon examples from the stories to defend their NOS views but did so more frequently when responding verbally in comparison to written responses on the surveys. The analysis also showed that students in both levels would rather utilize historical short stories over a traditional textbook and found value in learning about scientists and how scientific ideas are developed.

  3. PGC-1α dictates endothelial function through regulation of eNOS expression

    PubMed Central

    Craige, Siobhan M.; Kröller-Schön, Swenja; Li, Chunying; Kant, Shashi; Cai, Shenghe; Chen, Kai; Contractor, Mayur M.; Pei, Yongmei; Schulz, Eberhard; Keaney, John F.

    2016-01-01

    Endothelial dysfunction is a characteristic of many vascular related diseases such as hypertension. Peroxisome proliferator activated receptor gamma, coactivator 1α (PGC-1α) is a unique stress sensor that largely acts to promote adaptive responses. Therefore, we sought to define the role of endothelial PGC-1α in vascular function using mice with endothelial specific loss of function (PGC-1α EC KO) and endothelial specific gain of function (PGC-1α EC TG). Here we report that endothelial PGC-1α is suppressed in angiotensin-II (ATII)-induced hypertension. Deletion of endothelial PGC-1α sensitized mice to endothelial dysfunction and hypertension in response to ATII, whereas PGC-1α EC TG mice were protected. Mechanistically, PGC-1α promotes eNOS expression and activity, which is necessary for protection from ATII-induced dysfunction as mice either treated with an eNOS inhibitor (LNAME) or lacking eNOS were no longer responsive to transgenic endothelial PGC-1α expression. Finally, we determined that the orphan nuclear receptor, estrogen related receptor α (ERRα) is required to coordinate the PGC-1α -induced eNOS expression. In conclusion, endothelial PGC-1α expression protects from vascular dysfunction by promoting NO• bioactivity through ERRα induced expression of eNOS. PMID:27910955

  4. Aspirin prevents TNF-α-induced endothelial cell dysfunction by regulating the NF-κB-dependent miR-155/eNOS pathway: Role of a miR-155/eNOS axis in preeclampsia.

    PubMed

    Kim, Joohwan; Lee, Kyu-Sun; Kim, Ji-Hee; Lee, Dong-Keon; Park, Minsik; Choi, Seunghwan; Park, Wonjin; Kim, Suji; Choi, Yoon Kyung; Hwang, Jong Yun; Choe, Jongseon; Won, Moo-Ho; Jeoung, Dooil; Lee, Hansoo; Ryoo, Sungwoo; Ha, Kwon-Soo; Kwon, Young-Guen; Kim, Young-Myeong

    2017-03-01

    Preeclampsia is an inflammatory disease with endothelial cell dysfunction that occurs via decreased endothelial nitric oxide synthase/nitric oxide (eNOS/NO) activity. Aspirin reduces the incidence of hypertensive pregnancy complications. However, the underlying mechanism has not been clearly explained. Here, we found that tumor necrosis factor (TNF)-α, microRNA (miR)-155, and eNOS levels as well as endothelial redox phenotype were differentially regulated in preeclamptic patients, implying the involvement of TNF-α- and redox signal-mediated miR-155 biogenesis and eNOS downregulation in the pathogenesis of preeclampsia. Aspirin prevented the TNF-α-mediated increase in miR-155 biogenesis and decreases in eNOS expression and NO/cGMP production in cultured human umbilical vein endothelial cells (HUVECs). Similar effects of aspirin were also observed in HUVECs treated with H 2 O 2 . The preventive effects of aspirin was associated with the inhibition of nuclear factor-κB (NF-κB)-dependent MIR155HG (miR-155 host gene) expression. Aspirin recovered the TNF-α-mediated decrease in wild-type, but not mutant, eNOS 3'-untranslated region reporter activity, whose effect was blocked by miR-155 mimic. Moreover, aspirin prevented TNF-α-mediated endothelial cell dysfunction associated with impaired vasorelaxation, angiogenesis, and trophoblast invasion, and the preventive effects were blocked by miR-155 mimic or an eNOS inhibitor. Aspirin rescued TNF-α-mediated eNOS downregulation coupled with endothelial dysfunction by inhibiting NF-κB-dependent transcriptional miR-155 biogenesis. Thus, the redox-sensitive NF-κB/miR-155/eNOS axis may be crucial in the pathogenesis of vascular disorders including preeclampsia. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Lipopolysaccharide (LPS)-stimulated iNOS Induction Is Increased by Glucosamine under Normal Glucose Conditions but Is Inhibited by Glucosamine under High Glucose Conditions in Macrophage Cells*

    PubMed Central

    Hwang, Ji-Sun; Kwon, Mi-Youn; Kim, Kyung-Hong; Lee, Yunkyoung; Lyoo, In Kyoon; Kim, Jieun E.; Oh, Eok-Soo; Han, Inn-Oc

    2017-01-01

    We investigated the regulatory effect of glucosamine (GlcN) for the production of nitric oxide (NO) and expression of inducible NO synthase (iNOS) under various glucose conditions in macrophage cells. At normal glucose concentrations, GlcN dose dependently increased LPS-stimulated production of NO/iNOS. However, GlcN suppressed NO/iNOS production under high glucose culture conditions. Moreover, GlcN suppressed LPS-induced up-regulation of COX-2, IL-6, and TNF-α mRNAs under 25 mm glucose conditions yet did not inhibit up-regulation under 5 mm glucose conditions. Glucose itself dose dependently increased LPS-induced iNOS expression. LPS-induced MAPK and IκB-α phosphorylation did not significantly differ at normal and high glucose conditions. The activity of LPS-induced nuclear factor-κB (NF-κB) and DNA binding of c-Rel to the iNOS promoter were inhibited under high glucose conditions in comparison with no significant changes under normal glucose conditions. In addition, we found that the LPS-induced increase in O-GlcNAcylation as well as DNA binding of c-Rel to the iNOS promoter were further increased by GlcN under normal glucose conditions. However, both O-GlcNAcylation and DNA binding of c-Rel decreased under high glucose conditions. The NF-κB inhibitor, pyrrolidine dithiocarbamate, inhibited LPS-induced iNOS expression under high glucose conditions but it did not influence iNOS induction under normal glucose conditions. In addition, pyrrolidine dithiocarbamate inhibited NF-κB DNA binding and c-Rel O-GlcNAcylation only under high glucose conditions. By blocking transcription with actinomycin D, we found that stability of LPS-induced iNOS mRNA was increased by GlcN under normal glucose conditions. These results suggest that GlcN regulates inflammation by sensing energy states of normal and fuel excess. PMID:27927986

  6. Endothelial NOS-deficient mice reveal dual roles for nitric oxide during experimental autoimmune encephalomyelitis.

    PubMed

    Wu, Muzhou; Tsirka, Stella E

    2009-08-15

    Multiple sclerosis (MS) is a demyelinating autoimmune disease characterized by infiltration of T cells into the central nervous system (CNS) after compromise of the blood-brain barrier. A model used to mimic the disease in mice is experimental autoimmune encephalomyelitis (EAE). In this report, we examine the clinical and histopathological course of EAE in eNOS-deficient (eNOS-/-) mice to determine the role of nitric oxide (NO) derived from this enzyme in the disease progression. We find that eNOS-/- mice exhibit a delayed onset of EAE that correlates with delayed BBB breakdown, thus suggesting that NO production by eNOS underlies the T cell infiltration into the CNS. However, the eNOS-/- mice also eventually exhibit more severe EAE and delayed recovery, indicating that NO undertakes dual roles in MS/EAE, one proinflammatory that triggers disease onset, and the other neuroprotective that promotes recovery from disease exacerbation events.

  7. Looking Back, Moving Forward: Technical, Normative, and Political Dimensions of School Discipline

    ERIC Educational Resources Information Center

    Wiley, Kathryn E.; Anyon, Yolanda; Yang, Jessica L.; Pauline, Malina E.; Rosch, Alyssa; Valladares, Giovana; Downing, Barbara J.; Pisciotta, Lisa

    2018-01-01

    Purpose: School discipline reformers have presumed that such work is largely a technical task, emphasizing discrete changes to discipline policies and protocols. Yet prior theory and research suggest that emphasizing technical changes may overlook additional and important aspects of reform, namely, the normative and political dimensions within…

  8. Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury.

    PubMed

    Kan, Wen-Hong; Hsu, Jun-Te; Schwacha, Martin G; Choudhry, Mashkoor A; Raju, Raghavan; Bland, Kirby I; Chaudry, Irshad H

    2008-10-01

    Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of protein expression following trauma-hemorrhage. To investigate this, male Sprague-Dawley rats were subjected to midline laparotomy and hemorrhagic shock (mean blood pressure 35-40 mmHg for approximately 90 min) followed by fluid resuscitation. Animals were treated with either vehicle (DMSO) or 1400W (10 mg/kg body wt ip), or L-NAME (30 mg/kg iv), 30 min before resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation induced a marked hypotension and increase in markers of hepatic injury (i.e., plasma alpha-glutathione S-transferase, tissue myeloperoxidase activity, and nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor-1alpha, ICAM-1, IL-6, TNF-alpha, and neutrophil chemoattractant (cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein levels were also markedly increased following trauma-hemorrhage/resuscitation. Administration of the iNOS inhibitor 1400W significantly attenuated hypotension and expression of these mediators of hepatic injury induced by trauma-hemorrhage/resuscitation. However, administration of L-NAME could not attenuate hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it improved mean blood pressure as did 1400W. These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions.

  9. Technical and Vocational Education Transformation in Malaysia: Shaping the Future Leaders

    ERIC Educational Resources Information Center

    Sauffie, Nur Fatin Binti Mohd

    2015-01-01

    In accordance with the concept of lifelong education, the Technical and Vocational Education (TVE) system is one flaw of that is recognized or known as a system whose role is to develop individuals with high technical skills as desired by the industry nowadays. Changing times and technology development at this time require changes to the TVET…

  10. Identifying Technical Content Training Needs of Georgia Agriculture Teachers

    ERIC Educational Resources Information Center

    Peake, Jason B.; Duncan, Dennis W.; Ricketts, John C.

    2007-01-01

    The continuing trend toward increasing diversity of curriculum offered within secondary agricultural education programs is driving a change in pre-service and in-service technical training for agriculture teachers. This study looks at agriculture teachers' perceived importance of, and competence in, traditional technical competencies such as…

  11. Rethinking Technical Communication Pedagogy: A Poststructuralist View of Program and Course Design.

    ERIC Educational Resources Information Center

    Woolever, Kristin R.

    Technical communication specialists today really have to be technology experts as well as effective writers--even their titles have changed to "information designers, information engineers, or document developers." Teachers of technical communication should be up to date in the classroom to meet the changing needs of the workplace.…

  12. 77 FR 29703 - Product List Changes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... POSTAL REGULATORY COMMISSION [Docket Nos. MC2012-20 and CP2012-26; Order No. 1343] Product List Changes AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... proposed changes in the Mail Classification Schedule with the addition underlined; Attachment D--a...

  13. 77 FR 29393 - Product List Changes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-17

    ... POSTAL REGULATORY COMMISSION [Docket Nos. MC2012-18 and CP2012-24; Order No. 1341] Product List Changes AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... changes in the Mail Classification Schedule with the addition underlined; Attachment D--a Statement of...

  14. 77 FR 29702 - Product List Changes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... POSTAL REGULATORY COMMISSION [Docket Nos. MC2012-21 and CP2012-27; Order No. 1344] Product List Changes AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... proposed changes in the Mail Classification Schedule with the addition underlined; Attachment D--a...

  15. Constitutive NOS uncoupling and NADPH oxidase upregulation in the penis of type 2 diabetic men with erectile dysfunction

    PubMed Central

    Musicki, Biljana; Burnett, Arthur L.

    2016-01-01

    Erectile dysfunction (ED) associated with type 2 diabetes mellitus (T2DM) involves dysfunctional nitric oxide (NO) signaling and increased oxidative stress in the penis. However, the mechanisms of endothelial NO synthase (eNOS) and neuronal NO synthase (nNOS) dysregulation, and the sources of oxidative stress, are not well defined, particularly at the human level. The objective of this study was to define whether uncoupled eNOS and nNOS, and NADPH oxidase upregulation, contribute to the pathogenesis of ED in T2DM men. Penile erectile tissue was obtained from 9 T2DM patients with ED who underwent penile prosthesis surgery for ED, and from 6 control patients without T2DM or ED who underwent penectomy for penile cancer. The dimer-to-monomer protein expression ratio, an indicator of uncoupling for both eNOS and nNOS, total protein expressions of eNOS and nNOS, as well as protein expressions of NADPH oxidase catalytic subunit gp91phox (an enzymatic source of oxidative stress) and 4-hydroxy-2-nonenal [4-HNE] and nitrotyrosine (markers of oxidative stress) were measured by Western blot in this tissue. In the erectile tissue of T2DM men, eNOS and nNOS uncoupling and protein expressions of NADPH oxidase subunit gp91phox, 4-HNE- and nitrotyrosine-modified proteins were significantly (p<0.05) increased compared to control values. Total eNOS and nNOS protein expressions were not significantly different between the groups. In conclusion, mechanisms of T2DM-associated ED in the human penis may involve uncoupled eNOS and nNOS and NADPH oxidase upregulation. Our description of molecular factors contributing to the pathogenesis of T2DM-associated ED at the human level is relevant for advancing clinically therapeutic approaches to restore erectile function in T2DM patients. PMID:28076881

  16. NOS II inhibition attenuates post-suspension hypotension in Sprague-Dawley rats

    NASA Technical Reports Server (NTRS)

    Eatman, D.; Walton, M.; Socci, R. R.; Emmett, N.; Bayorh, M. A.

    2003-01-01

    The reduction in mean arterial pressure observed in astronauts may be related to the impairment of autonomic function and/or excessive production of endothelium-derived relaxing factors. Here, we examined the role of a nitric oxide synthase II (NOS II) inhibitor AMT (2-amino-dihydro-6-methyl-4H-1,3-thiazine) against the post-suspension reduction in mean arterial pressure (MAP) in conscious male Sprague-Dawley rats. Direct MAP and heart rate were determined prior to tail-suspension, daily during the 7-day suspension and every 2 hrs post-suspension. Prior to release from suspension and at 2 and 4 hrs post-suspension, AMT (0.1 mg/kg), or saline, were administered intravenously. During the 7-day suspension, MAP was not altered, nor were there significant changes in heart rate. The reduction in MAP post-suspension in saline-treated rats was associated with significant increases in plasma nitric oxide and prostacyclin. 2-Amino-dihydro-6-methyl4H-1,3-thiazine reduced plasma nitric oxide levels, but not those of prostacyclin, attenuated the observed post-suspension reduction in MAP and modified the baroreflex sensitivity for heart rate. Thus, the post suspension reduction in mean arterial pressure is due, in part, to overproduction of nitric oxide, via the NOS II pathway, and alteration in baroreflex activity.

  17. Central Role of eNOS in the Maintenance of Endothelial Homeostasis

    PubMed Central

    Rodriguez-Mateos, Ana; Kelm, Malte

    2015-01-01

    Abstract Significance: Disruption of endothelial function is considered a key event in the development and progression of atherosclerosis. Endothelial nitric oxide synthase (eNOS) is a central regulator of cellular function that is important to maintain endothelial homeostasis. Recent Advances: Endothelial homeostasis encompasses acute responses such as adaption of flow to tissue's demand and more sustained responses to injury such as re-endothelialization and sprouting of endothelial cells (ECs) and attraction of circulating angiogenic cells (CAC), both of which support repair of damaged endothelium. The balance and the intensity of endothelial damage and repair might be reflected by changes in circulating endothelial microparticles (EMP) and CAC. Flow-mediated vasodilation (FMD) is a generally accepted clinical read-out of NO-dependent vasodilation, whereas EMP are upcoming prognostically validated markers of endothelial injury and CAC are reflective of the regenerative capacity with both expressing a functional eNOS. These markers can be integrated in a clinical endothelial phenotype, reflecting the net result between damage from risk factors and endogenous repair capacity with NO representing a central signaling molecule. Critical Issues: Improvements of reproducibility and observer independence of FMD measurements and definitions of relevant EMP and CAC subpopulations warrant further research. Future Directions: Endothelial homeostasis may be a clinical therapeutic target for cardiovascular health maintenance. Antioxid. Redox Signal. 22, 1230–1242. PMID:25330054

  18. The Effect of Policy Changes of State Scholarship Programs on Enrollment and Financial Aid Awards to Students Attending Two-Year Technical Colleges in Georgia

    ERIC Educational Resources Information Center

    Whitlock, Tonya F.

    2013-01-01

    This dissertation is a policy evaluation of the HOPE Grant Program in the state of Georgia. It examines if the HOPE Grant policy change related to the shifts in enrollment and financial aid awards at two-year technical colleges in Georgia. It particularly focuses on the FY2011 policy change where the GPA was raised from a 2.0 to a 3.0 as a…

  19. Effect of iNOS inhibitor LNMMA along with antibiotics Chloramphenicol or Ofloxacin in murine peritoneal macrophages regulates S.aureus infection as well as inflammation: An in vitro study.

    PubMed

    Dey, Somrita; Bishayi, Biswadev

    2017-04-01

    Death due to sepsis by S. aureus is rapidly increasing because of their potent weaponries against macrophage mediated killing. Macrophages serve as intracellular reservoirs of S. aureus. Although significant resources have been invested during the last decade in new treatments for sepsis, only antibiotic therapy has failed to improve outcomes. Moreover the host pathogen interaction resulted in host cell death triggering inflammation. So, successful therapy requires amalgamation of therapies to delineate pathogen along with providing protection to host cell. With this idea, LNMMA, the iNOS inhibitor is used along with antibiotics Ofloxacin or Chloramphenicol on S. aureus infected mouse peritoneal macrophage. ROS like H 2 O 2 , O 2 - production has been measured. NO inhibition by iNOS inhibitor and antioxidant levels has been analysed. COX2, TLR2 and iNOS expression along with proinflammatory cytokine level was studied. It was found that the use of iNOS inhibitor LNMMA along with antibiotics not only enhances bacterial clearance but also decreases proinflammatory responses in Staphylococcus aureus infected macrophages. Inhibition of TLR2 as well as COX2 has also been found in combined treatment groups. The use of iNOS inhibitor LNMMA plus Ofloxacin or Chloramphenicol pretreatment enhanced bacterial clearance by increasing ROS. Decreases in NO protect the cell from harmful peroxynitril as well as inflammatory damage by changes in iNOS, COX2 activity along with reduced proinflammatory cytokines like TNFα, IFNγ, IL1-β etc. Changes in antioxidant level has been found. This in-vitro realm of augmented bacterial clearance and regulated inflammation may be considered as a novel and important therapeutic intervention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. 48 CFR 252.227-7015 - Technical data-Commercial items.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... support contractor means a contractor under a contract, the primary purpose of which is to furnish...) Form, fit, and function data means technical data that describes the required overall physical... another party; (ii) Are form, fit, and function data; (iii) Are a correction or change to technical data...

  1. 48 CFR 252.227-7015 - Technical data-Commercial items.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... support contractor means a contractor under a contract, the primary purpose of which is to furnish...) Form, fit, and function data means technical data that describes the required overall physical... another party; (ii) Are form, fit, and function data; (iii) Are a correction or change to technical data...

  2. 48 CFR 252.227-7015 - Technical data-Commercial items.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... support contractor means a contractor under a contract, the primary purpose of which is to furnish...) Form, fit, and function data means technical data that describes the required overall physical... another party; (ii) Are form, fit, and function data; (iii) Are a correction or change to technical data...

  3. The Akt1-eNOS axis illustrates the specificity of kinase-substrate relationships in vivo.

    PubMed

    Schleicher, Michael; Yu, Jun; Murata, Takahisa; Derakhshan, Berhad; Atochin, Dimitriy; Qian, Li; Kashiwagi, Satoshi; Di Lorenzo, Annarita; Harrison, Kenneth D; Huang, Paul L; Sessa, William C

    2009-08-04

    Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1(-/-) mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme "constitutively active" or "less active." The eNOS mutations did not influence several phenotypes in Akt1(-/-) mice; however, the defective postnatal angiogenesis characteristic of Akt1(-/-) mice was rescued by crossing the Akt1(-/-) mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant. This genetic rescue resulted in the stabilization of hypoxia-inducible factor 1alpha (HIF-1alpha) and increased production of HIF-1alpha-responsive genes in vivo and in vitro. Thus, Akt1 regulates angiogenesis largely through phosphorylation of eNOS and NO-dependent signaling.

  4. Interaction of nNOS with PSD-95 negatively controls regenerative repair after stroke.

    PubMed

    Luo, Chun-Xia; Lin, Yu-Hui; Qian, Xiao-Dan; Tang, Ying; Zhou, Hai-Hui; Jin, Xing; Ni, Huan-Yu; Zhang, Feng-Yun; Qin, Cheng; Li, Fei; Zhang, Yu; Wu, Hai-Yin; Chang, Lei; Zhu, Dong-Ya

    2014-10-01

    Stroke is a major public health concern. The lack of effective therapies heightens the need for new therapeutic targets. Mammalian brain has the ability to rewire itself to restore lost functionalities. Promoting regenerative repair, including neurogenesis and dendritic remodeling, may offer a new therapeutic strategy for the treatment of stroke. Here, we report that interaction of neuronal nitric oxide synthase (nNOS) with the protein postsynaptic density-95 (PSD-95) negatively controls regenerative repair after stroke in rats. Dissociating nNOS-PSD-95 coupling in neurons promotes neuronal differentiation of neural stem cells (NSCs), facilitates the migration of newborn cells into the injured area, and enhances neurite growth of newborn neurons and dendritic spine formation of mature neurons in the ischemic brain of rats. More importantly, blocking nNOS-PSD-95 binding during the recovery stage improves stroke outcome via the promotion of regenerative repair in rats. Histone deacetylase 2 in NSCs may mediate the role of nNOS-PSD-95 association. Thus, nNOS-PSD-95 can serve as a target for regenerative repair after stroke. Copyright © 2014 the authors 0270-6474/14/3413535-14$15.00/0.

  5. Annual report of the National Advisory Committee for Aeronautics (6th).administrative report including Technical Reports nos. 83 to 110

    NASA Technical Reports Server (NTRS)

    1921-01-01

    Report includes the National Advisory Committee for Aeronautics letter of submittal to the President, Congressional report, summaries of the committee's activities and research accomplished, expenditures, House of Representatives bill 14061, a copy of the bill introduced to the House of Representatives to regulate air navigation, and a compilation of technical reports produced.

  6. Reliability and Validity of the HoNOS-LD and HoNOS in a Sample of Individuals with Mild to Borderline Intellectual Disability and Severe Emotional and Behavior Disorders

    ERIC Educational Resources Information Center

    Tenneij, Nienke; Didden, Robert; Veltkamp, Eline; Koot, Hans M.

    2009-01-01

    In this study, psychometric properties of the Health of the Nation Outcome scales (HoNOS) and Health of the Nation Outcome Scales for People with Learning Disabilities (HoNOS-LD) were investigated in a sample (n = 79) of (young) adults with mild to borderline intellectual disability (ID) and severe behavior and mental health problems who were…

  7. Insights into the arginine paradox: evidence against the importance of subcellular location of arginase and eNOS

    PubMed Central

    Elms, Shawn; Chen, Feng; Wang, Yusi; Qian, Jin; Askari, Bardia; Yu, Yanfang; Pandey, Deepesh; Iddings, Jennifer; Caldwell, Ruth B.

    2013-01-01

    Reduced production of nitric oxide (NO) is one of the first indications of endothelial dysfunction and precedes overt cardiovascular disease. Increased expression of Arginase has been proposed as a mechanism to account for diminished NO production. Arginases consume l-arginine, the substrate for endothelial nitric oxide synthase (eNOS), and l-arginine depletion is thought to competitively reduce eNOS-derived NO. However, this simple relationship is complicated by the paradox that l-arginine concentrations in endothelial cells remain sufficiently high to support NO synthesis. One mechanism proposed to explain this is compartmentalization of intracellular l-arginine into distinct, poorly interchangeable pools. In the current study, we investigated this concept by targeting eNOS and Arginase to different intracellular locations within COS-7 cells and also BAEC. We found that supplemental l-arginine and l-citrulline dose-dependently increased NO production in a manner independent of the intracellular location of eNOS. Cytosolic arginase I and mitochondrial arginase II reduced eNOS activity equally regardless of where in the cell eNOS was expressed. Similarly, targeting arginase I to disparate regions of the cell did not differentially modify eNOS activity. Arginase-dependent suppression of eNOS activity was reversed by pharmacological inhibitors and absent in a catalytically inactive mutant. Arginase did not directly interact with eNOS, and the metabolic products of arginase or downstream enzymes did not contribute to eNOS inhibition. Cells expressing arginase had significantly lower levels of intracellular l-arginine and higher levels of ornithine. These results suggest that arginases inhibit eNOS activity by depletion of substrate and that the compartmentalization of l-arginine does not play a major role. PMID:23792682

  8. Hindlimb unweighting decreases endothelium-dependent dilation and eNOS expression in soleus not gastrocnemius

    NASA Technical Reports Server (NTRS)

    Woodman, C. R.; Schrage, W. G.; Rush, J. W.; Ray, C. A.; Price, E. M.; Hasser, E. M.; Laughlin, M. H.

    2001-01-01

    We tested the hypothesis that hindlimb unweighting (HLU) decreases endothelium-dependent vasodilation and expression of endothelial nitric oxide synthase (eNOS) and superoxide dismutase-1 (SOD-1) in arteries of skeletal muscle with reduced blood flow during HLU. Sprague-Dawley rats (300-350 g) were exposed to HLU (n = 15) or control (n = 15) conditions for 14 days. ACh-induced dilation was assessed in muscle with reduced [soleus (Sol)] or unchanged [gastrocnemius (Gast)] blood flow during HLU. eNOS and SOD-1 expression were measured in feed arteries (FA) and in first-order (1A), second-order (2A), and third-order (3A) arterioles. Dilation to infusion of ACh in vivo was blunted in Sol but not Gast. In arteries of Sol muscle, HLU decreased eNOS mRNA and protein content. eNOS mRNA content was significantly less in Sol FA (35%), 1A arterioles (25%) and 2A arterioles (18%). eNOS protein content was less in Sol FA (64%) and 1A arterioles (65%) from HLU rats. In arteries of Gast, HLU did not decrease eNOS mRNA or protein. SOD-1 mRNA expression was less in Sol 2A arterioles (31%) and 3A arterioles (29%) of HLU rats. SOD-1 protein content was less in Sol FA (67%) but not arterioles. SOD-1 mRNA and protein content were not decreased in arteries from Gast. These data indicate that HLU decreases endothelium-dependent vasodilation, eNOS expression, and SOD-1 expression primarily in arteries of Sol muscle where blood flow is reduced during HLU.

  9. Upregulation of endothelial nitric oxide synthase (eNOS) and its upstream regulators in Opisthorchis viverrini associated cholangiocarcinoma and its clinical significance.

    PubMed

    Suksawat, Manida; Techasen, Anchalee; Namwat, Nisana; Yongvanit, Puangrat; Khuntikeo, Narong; Titapun, Attapon; Koonmee, Supinda; Loilome, Watcharin

    2017-08-01

    Endothelial nitric oxide synthase (eNOS) is an isoform of the enzyme nitric oxide synthase (NOS) which is constitutively expressed in endothelial cells and plays important roles in vasodilation. We previously reported the importance of eNOS activation in cholangiocarcinoma (CCA) tissues and cell lines. The present study aims to investigate the relative abundance of eNOS and phosphorylated eNOS (P-eNOS) and their upstream regulators VEGFR3, VEGFC, EphA3 and ephrin-A1, in the Opisthorchis viverrini (Ov)/N-nitrosodimethylamine (NDMA)-induced hamster CCA model and in human CCA by semiquantitative immunohistochemical analysis of the relevant tissues. Results from the hamster model suggested an increase in eNOS and P-eNOS and upstream regulators during CCA genesis. In human CCA, high immunohistochemical staining intensity of all investigated proteins was associated with the presence of metastasis. A pairwise analysis of the staining data for eNOS and its upstream regulators showed that a concurrent increase in eNOS/VEGFR3, eNOS/ephrin-A1, eNOS/VEGFC and eNOS/EphA3 was significantly associated with metastasis. An increase in eNOS/VEGFR3, eNOS/ephrin-A1 was also associated with non-papillary type CCA. Additionally, an increase in eNOS and P-eNOS was significantly correlated with a high micro-vessel level (P=0.04). Our results indicate that the development of CCA involves upregulation of eNOS and P-eNOS and their regulators. This may drive angiogenesis and metastasis in CCA. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Activation of eNOS in endothelial cells exposed to ionizing radiation involves components of the DNA damage response pathway

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

    Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri

    2015-01-02

    Highlights: • eNOS activity is increased in BAECs exposed to X-rays. • ATM is involved in this increased eNOS activity. • HSP90 modulates the radiation-induced activation of ATM and eNOS. - Abstract: In this study, the involvement of ataxia telangiectasia mutated (ATM) kinase and heat shock protein 90 (HSP90) in endothelial nitric oxide synthase (eNOS) activation was investigated in X-irradiated bovine aortic endothelial cells. The activity of nitric oxide synthase (NOS) and the phosphorylation of serine 1179 of eNOS (eNOS-Ser1179) were significantly increased in irradiated cells. The radiation-induced increases in NOS activity and eNOS-Ser1179 phosphorylation levels were significantly reduced bymore » treatment with either an ATM inhibitor (Ku-60019) or an HSP90 inhibitor (geldanamycin). Geldanamycin was furthermore found to suppress the radiation-induced phosphorylation of ATM-Ser1181. Our results indicate that the radiation-induced eNOS activation in bovine aortic endothelial cells is regulated by ATM and HSP90.« less

  11. Suggesting a NOS Map for Nature of Science for Science Education Instruction

    ERIC Educational Resources Information Center

    Oh, Jun-Young

    2017-01-01

    The aims of this research are 1) to explore the inter-relationships within the individual elements or tenets of Nature of Science (NOS), based on the dimensions of scientific knowledge in science learning, and 2) to consider Kuhn's concept of how scientific revolution takes place. This study suggests that instruction according to our NOS Flowchart…

  12. Identification and molecular characterization of nitric oxide synthase (NOS) gene in the intertidal copepod Tigriopus japonicus.

    PubMed

    Jeong, Chang-Bum; Kang, Hye-Min; Seo, Jung Soo; Park, Heum Gi; Rhee, Jae-Sung; Lee, Jae-Seong

    2016-02-10

    In copepods, no information has been reported on the structure or molecular characterization of the nitric oxide synthase (NOS) gene. In the intertidal copepod Tigriopus japonicus, we identified a NOS gene that is involved in immune responses of vertebrates and invertebrates. In silico analyses revealed that nitric oxide (NO) synthase domains, such as the oxygenase and reductase domains, are highly conserved in the T. japonicus NOS gene. The T. japonicus NOS gene was highly transcribed in the nauplii stages, implying that it plays a role in protecting the host during the early developmental stages. To examine the involvement of the T. japonicus NOS gene in the innate immune response, the copepods were exposed to lipopolysaccharide (LPS) and two Vibrio sp. After exposure to different concentrations of LPS and Vibrio sp., T. japonicus NOS transcription was significantly increased over time in a dose-dependent manner, and the NO/nitrite concentration increased as well. Taken together, our findings suggest that T. japonicus NOS transcription is induced in response to an immune challenge as part of the conserved innate immunity. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Nosé-Thermostated Mechanical Systems on the n-Torus

    NASA Astrophysics Data System (ADS)

    Butler, Leo T.

    2018-02-01

    Let {H(q,p) = 1/2{allel p allel}^2 + V(q)} be an n-degree of freedom C r mechanical Hamiltonian on {T^{*}{T}^n} where {r > 2n+2}. When the metric {{allel \\cdot allel}} is flat, the Nosé-thermostated system associated to H is shown to have a positive-measure set of invariant tori near the infinite temperature limit. This is shown to be true for all variable mass thermostats similar to Nosé's, too. These results complement results of Bulter (Nonlinearity 11(29):3454-3463, 2016), Legoll et al. (Arch Ration Mech Anal 184(3):449-463, 2007, Nonlinearity 22(7):1673-1694, 2009).

  14. Evaluating the effectiveness of case method instruction in technical communication

    NASA Technical Reports Server (NTRS)

    Feinberg, S. G.

    1981-01-01

    The effectiveness of the case method as an instructional technique in improving technical writing was evaluated. The development of a self-report instrument that attempts to measure changes in attitude toward technical communication and the presentation results change are the purpose of this paper. Standards for developing a case set forth by Goldstein and Couture, were used to design an evaluation instrument to measure the effect instruction on student attitude toward technical communication. This self-report instrument is based on model developed and tested by Daly and Miller who studied writer attitude and apprehension toward writing. It was the most important objective of any evaluation is to provide information for improving the program.

  15. Regulation of iNOS function and cellular redox state by macrophage Gch1 reveals specific requirements for tetrahydrobiopterin in NRF2 activation

    PubMed Central

    McNeill, Eileen; Crabtree, Mark J.; Sahgal, Natasha; Patel, Jyoti; Chuaiphichai, Surawee; Iqbal, Asif J.; Hale, Ashley B.; Greaves, David R.; Channon, Keith M.

    2015-01-01

    Inducible nitric oxide synthase (iNOS) is a key enzyme in the macrophage inflammatory response, which is the source of nitric oxide (NO) that is potently induced in response to proinflammatory stimuli. However, the specific role of NO production, as distinct from iNOS induction, in macrophage inflammatory responses remains unproven. We have generated a novel mouse model with conditional deletion of Gch1, encoding GTP cyclohydrolase 1 (GTPCH), an essential enzyme in the biosynthesis of tetrahydrobiopterin (BH4) that is a required cofactor for iNOS NO production. Mice with a floxed Gch1 allele (Gch1fl/fl) were crossed with Tie2cre transgenic mice, causing Gch1 deletion in leukocytes (Gch1fl/flTie2cre). Macrophages from Gch1fl/flTie2cre mice lacked GTPCH protein and de novo biopterin biosynthesis. When activated with LPS and IFNγ, macrophages from Gch1fl/flTie2cre mice induced iNOS protein in a manner indistinguishable from wild-type controls, but produced no detectable NO, as judged by L-citrulline production, EPR spin trapping of NO, and by nitrite accumulation. Incubation of Gch1fl/flTie2cre macrophages with dihydroethidium revealed significantly increased production of superoxide in the presence of iNOS expression, and an iNOS-independent, BH4-dependent increase in other ROS species. Normal BH4 levels, nitric oxide production, and cellular redox state were restored by sepiapterin, a precursor of BH4 production by the salvage pathway, demonstrating that the effects of BH4 deficiency were reversible. Gch1fl/flTie2cre macrophages showed only minor alterations in cytokine production and normal cell migration, and minimal changes in basal gene expression. However, gene expression analysis after iNOS induction identified 78 genes that were altered between wild-type and Gch1fl/flTie2cre macrophages. Pathway analysis identified decreased NRF2 activation, with reduced induction of archetypal NRF2 genes (gclm, prdx1, gsta3, nqo1, and catalase) in BH4-deficient Gch1fl

  16. Morus alba extract modulates blood pressure homeostasis through eNOS signaling.

    PubMed

    Carrizzo, Albino; Ambrosio, Mariateresa; Damato, Antonio; Madonna, Michele; Storto, Marianna; Capocci, Luca; Campiglia, Pietro; Sommella, Eduardo; Trimarco, Valentina; Rozza, Francesco; Izzo, Raffaele; Puca, Annibale A; Vecchione, Carmine

    2016-10-01

    Morus alba is a promising phytomedicine cultivated in oriental countries that is extensively used to prevent and treat various cardiovascular problems. To date, despite its beneficial effects, the molecular mechanisms involved remain unclear. Thus, we investigate the vascular and haemodynamic effects of Morus alba extract in an experimental model focusing our attention on the molecular mechanisms involved. Through vascular reactivity studies, we demonstrate that Morus alba extract evokes endothelial vasorelaxation through a nitric oxide-dependent pathway. Our molecular analysis highlights an increase in endothelial nitric oxide synthase (eNOS) phosphorylation. In vivo administration of Morus alba extract reduces blood pressure levels exclusively in wild-type mice, whereas it fails to evoke any haemodynamic effects in eNOS-deficient mice. Molecular analyses revealed that its beneficial action on vasculature is mediated by the activation of two important proteins that act as stress sensors and chaperones: PERK and heat shock protein 90. Finally, Morus alba extract exerts antihypertensive action in an experimental model of arterial hypertension. Through its action on eNOS signaling, Morus alba extract could act as a food supplement for the regulation of cardiovascular system, mainly in clinical conditions characterized by eNOS dysfunction, such as arterial hypertension. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. The Akt1-eNOS Axis Illustrates the Specificity of Kinase-Substrate Relationships in Vivo

    PubMed Central

    Schleicher, Michael; Yu, Jun; Murata, Takahisa; Derakhshan, Berhad; Atochin, Dimitriy; Qian, Li; Kashiwagi, Satoshi; Lorenzo, Annarita Di; Harrison, Kenneth D.; Huang, Paul L.; Sessa, William C.

    2016-01-01

    Akt1 is critical for many in vivo functions; however, the cell-specific substrates responsible remain to be defined. Here, we examine the importance of endothelial nitric oxide synthase (eNOS) as an Akt1 substrate by generating Akt1-deficient mice (Akt1−/− mice) carrying knock-in mutations (serine to aspartate or serine to alanine substitutions) of the critical Akt1 phosphorylation site on eNOS (serine 1176) that render the enzyme “constitutively active” or “less active.” The eNOS mutations did not influence several phenotypes in Akt1−/− mice; however, the defective postnatal angiogenesis characteristic of Akt1−/− mice was rescued by crossing the Akt1−/− mice with mice carrying the constitutively active form of eNOS, but not by crossing with mice carrying the less active eNOS mutant. This genetic rescue resulted in the stabilization of hypoxia-inducible factor 1α (HIF-1α) and increased production of HIF-1α–responsive genes in vivo and in vitro. Thus, Akt1 regulates angiogenesis largely through phosphorylation of eNOS and NO-dependent signaling. PMID:19654415

  18. 1983-84 Evaluation Report of Vocational and Technical Education in South Carolina.

    ERIC Educational Resources Information Center

    South Carolina State Advisory Council on Vocational and Technical Education, Columbia.

    This evaluation report contains a series of articles on vocational and technical education encompassing the 1983-84 school year. The articles, collectively, are intended to give an overall picture of vocational and technical education programs in South Carolina. The lead article on technical education strongly urges several changes to bring about…

  19. Heat Shock Protein-70 Inducers and iNOS Inhibitors as Therapeutics to Ameliorate Hemorrhagic Shock

    DTIC Science & Technology

    2004-09-01

    downregulation of iNOS can limit tissue injury caused by ischemia / reperfusion or hemorrhage/resuscitation. In our laboratory, geldanamycin, a member of... ischemia / reperfusion [Charier 1999]. Mice deficient in inducible NO synthase (iNOS) also demonstrate limited hemorrhage/resuscitation-induced injury ...tissues and leukotriene B4 (LTB4) generation increases. In a hemorrhage/resuscitation-induced injury model, iNOS, cyclooxygenase- 2 , and CD14 are all

  20. Neuroanatomical Relationship of nNOS to GnRH and Kisspeptin Neurons in Adult Female Sheep and Primates.

    PubMed

    Bedenbaugh, Michelle; McCosh, Rick; Lopez, Justin; Connors, John; Goodman, Robert L; Hileman, Stan

    2018-06-21


    Background: Neuronal intermediates that communicate estrogen and progesterone feedback to gonadotropin-releasing hormone (GnRH) neurons are essential for modulating reproductive cyclicity. Individually, kisspeptin and nitric oxide (NO) influence GnRH secretion. However, it is possible these two neuronal intermediates interact with one another to affect reproductive cyclicity. We investigated the neuroanatomical relationship of one isoform of the enzyme that synthesizes NO, neuronal nitric oxide synthase (nNOS), to kisspeptin and GnRH in adult female rhesus monkeys and sheep using dual-label immunofluorescence. Additionally, we evaluated if the phase of the reproductive cycle would affect these relationships. Overall, no effect of stage of cycle was observed for any variable in this study. In the arcuate nucleus (ARC) of sheep, 98.8±3.5% of kisspeptin neurons colocalized with nNOS, and kisspeptin close-contacts were observed onto nNOS neurons. In contrast to ewes, no colocalization was observed between kisspeptin and nNOS in the infundibular arcuate nucleus (INF ARC) of primates, but kisspeptin fibers were apposed to nNOS neurons. In the preoptic area (POA) of ewes, 15.0±4.2% of GnRH neurons colocalized with nNOS. In primates, 38.8±10.1% of GnRH neurons in the mediobasal hypothalamus (MBH) colocalized with nNOS, and GnRH close-contacts were observed onto nNOS neurons in both sheep and primates. Although species differences were observed, this work establishes a neuroanatomical framework between nNOS and kisspeptin and nNOS and GnRH in adult female nonhuman primates and sheep.
    . ©2018S. Karger AG, Basel.

  1. INDOT Technical Training Plan : [Technical Summary

    DOT National Transportation Integrated Search

    2012-01-01

    A wide range of job classifications, increasing technical : performance expectations, licensing and certification requirements, : budget restrictions and frequent department : reorganization has made technical training of employees : more difficult, ...

  2. Beer elicits vasculoprotective effects through Akt/eNOS activation.

    PubMed

    Vilahur, Gemma; Casani, Laura; Mendieta, Guiomar; Lamuela-Raventos, Rosa M; Estruch, Ramon; Badimon, Lina

    2014-12-01

    There is controversy regarding the effect of alcohol beverage intake in vascular vasodilatory function in peripheral arteries. The effects of beer intake in coronary vasodilation remain unknown. We investigated whether regular beer intake (alcohol and alcohol-free) protects against hypercholesterolaemia-induced coronary endothelial dysfunction and the mechanisms behind this effect. Pigs were fed 10 days: (i) a Western-type hypercholesterolaemic diet (WD); (ii) WD+low-dose beer (12·5 g alcohol/day); (iii) WD+moderate-dose beer (25 g alcohol/day); or (iv) WD+moderate-dose alcohol-free-beer (0·0 g alcohol/day). Coronary responses to endothelium-dependent vasoactive drugs (acetylcholine: receptor mediated; calcium ionophore-A23189: nonreceptor mediated), endothelium-independent vasoactive drug (SNP) and L-NMMA (NOS-antagonist) were evaluated in the LAD coronary artery by flow Doppler. Coronary Akt/eNOS activation, MCP-1 expression, oxidative DNA damage and superoxide production were assessed. Lipid profile, lipoproteins resistance to oxidation and urinary isoxanthohumol concentration were evaluated. Alcoholic and nonalcoholic beer intake prevented WD-induced impairment of receptor- and non-receptor-operated endothelial-dependent coronary vasodilation. All animals displayed a similar vasodilatory response to SNP and L-NMMA blunted all endothelial-dependent vasorelaxation responses. Haemodynamic parameters remained unchanged. Coronary arteries showed lower DNA damage and increased Akt/eNOS axis activation in beer-fed animals. Animals taking beer showed HDL with higher antioxidant capacity, higher LDL resistance to oxidation and increased isoxanthohumol levels. Weight, lipids levels, liver enzymes and MCP-1 expression were not affected by beer intake. Non-alcoholic-related beer components protect against hyperlipemia-induced coronary endothelial dysfunction by counteracting vascular oxidative damage and preserving the Akt/eNOS pathway. Light-to-moderate beer

  3. 44 CFR 65.3 - Requirement to submit new technical data.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... technical data. 65.3 Section 65.3 Emergency Management and Assistance FEDERAL EMERGENCY MANAGEMENT AGENCY... IDENTIFICATION AND MAPPING OF SPECIAL HAZARD AREAS § 65.3 Requirement to submit new technical data. A community's base flood elevations may increase or decrease resulting from physical changes affecting flooding...

  4. 47 CFR 15.515 - Technical requirements for vehicular radar systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Technical requirements for vehicular radar... DEVICES Ultra-Wideband Operation § 15.515 Technical requirements for vehicular radar systems. (a..., changing gears, or engaging a turn signal. (b) The UWB bandwidth of a vehicular radar system operating...

  5. 47 CFR 15.515 - Technical requirements for vehicular radar systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Technical requirements for vehicular radar... DEVICES Ultra-Wideband Operation § 15.515 Technical requirements for vehicular radar systems. (a..., changing gears, or engaging a turn signal. (b) The UWB bandwidth of a vehicular radar system operating...

  6. The Technical Communicator as Corporate Spokesperson: A Public Relations Primer.

    ERIC Educational Resources Information Center

    Troester, Rod; Warburton, Terrence L.

    2001-01-01

    Examines the changing role of the technical communication professional in the rapidly evolving environment of organizational life. Presents five principles that serve as an initial step in laying a foundation for the preparation of technical communicators for the challenges and opportunities awaiting in contemporary organizations and the…

  7. 47 CFR 15.515 - Technical requirements for vehicular radar systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Technical requirements for vehicular radar... DEVICES Ultra-Wideband Operation § 15.515 Technical requirements for vehicular radar systems. (a..., changing gears, or engaging a turn signal. (b) The UWB bandwidth of a vehicular radar system operating...

  8. 47 CFR 15.515 - Technical requirements for vehicular radar systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Technical requirements for vehicular radar... DEVICES Ultra-Wideband Operation § 15.515 Technical requirements for vehicular radar systems. (a..., changing gears, or engaging a turn signal. (b) The UWB bandwidth of a vehicular radar system operating...

  9. 47 CFR 15.515 - Technical requirements for vehicular radar systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Technical requirements for vehicular radar... DEVICES Ultra-Wideband Operation § 15.515 Technical requirements for vehicular radar systems. (a..., changing gears, or engaging a turn signal. (b) The UWB bandwidth of a vehicular radar system operating...

  10. Enhancing eNOS activity with simultaneous inhibition of IKKβ restores vascular function in Ins2(Akita+/-) type-1 diabetic mice.

    PubMed

    Krishnan, Manickam; Janardhanan, Preethi; Roman, Linda; Reddick, Robert L; Natarajan, Mohan; van Haperen, Rien; Habib, Samy L; de Crom, Rini; Mohan, Sumathy

    2015-10-01

    The balance of nitric oxide (NO) versus superoxide generation has a major role in the initiation and progression of endothelial dysfunction. Under conditions of high glucose, endothelial nitric oxide synthase (eNOS) functions as a chief source of superoxide rather than NO. In order to improve NO bioavailability within the vessel wall in type-1 diabetes, we investigated treatment strategies that improve eNOS phosphorylation and NO-dependent vasorelaxation. We evaluated methods to increase the eNOS activity by (1) feeding Ins2(Akita) spontaneously diabetic (type-1) mice with l-arginine in the presence of sepiapterin, a precursor of tetrahydrobiopterin; (2) preventing eNOS/NO deregulation by the inclusion of inhibitor kappa B kinase beta (IKKβ) inhibitor, salsalate, in the diet regimen in combination with l-arginine and sepiapterin; and (3) independently increasing eNOS expression to improve eNOS activity and associated NO production through generating Ins2(Akita) diabetic mice that overexpress human eNOS predominantly in vascular endothelial cells. Our results clearly demonstrated that diet supplementation with l-arginine, sepiapterin along with salsalate improved phosphorylation of eNOS and enhanced vasorelaxation of thoracic/abdominal aorta in type-1 diabetic mice. More interestingly, despite the overexpression of eNOS, the in-house generated transgenic eNOS-GFP (TgeNOS-GFP)-Ins2(Akita) cross mice showed an unanticipated effect of reduced eNOS phosphorylation and enhanced superoxide production. Our results demonstrate that enhancement of endogenous eNOS activity by nutritional modulation is more beneficial than increasing the endogenous expression of eNOS by gene therapy modalities.

  11. Technical variations in low-input RNA-seq methodologies.

    PubMed

    Bhargava, Vipul; Head, Steven R; Ordoukhanian, Phillip; Mercola, Mark; Subramaniam, Shankar

    2014-01-14

    Recent advances in RNA-seq methodologies from limiting amounts of mRNA have facilitated the characterization of rare cell-types in various biological systems. So far, however, technical variations in these methods have not been adequately characterized, vis-à-vis sensitivity, starting with reduced levels of mRNA. Here, we generated sequencing libraries from limiting amounts of mRNA using three amplification-based methods, viz. Smart-seq, DP-seq and CEL-seq, and demonstrated significant technical variations in these libraries. Reduction in mRNA levels led to inefficient amplification of the majority of low to moderately expressed transcripts. Furthermore, noise in primer hybridization and/or enzyme incorporation was magnified during the amplification step resulting in significant distortions in fold changes of the transcripts. Consequently, the majority of the differentially expressed transcripts identified were either high-expressed and/or exhibited high fold changes. High technical variations ultimately masked subtle biological differences mandating the development of improved amplification-based strategies for quantitative transcriptomics from limiting amounts of mRNA.

  12. Imbalance of caveolin-1 and eNOS expression in the pulmonary vasculature of experimental diaphragmatic hernia.

    PubMed

    Hofmann, Alejandro; Gosemann, Jan-Hendrik; Takahashi, Toshiaki; Friedmacher, Florian; Duess, Johannes W; Puri, Prem

    2014-08-01

    Caveolin-1 (Cav-1) exerts major regulatory functions on intracellular signaling pathways originating at the plasma membrane. Cav-1 is a key regulator in adverse lung remodeling and the development of pulmonary hypertension (PH) regulating vasomotor tone through its ability to reduce nitric oxide (NO) production. This low-output endothelial NO synthase (eNOS) derived NO maintains normal pulmonary vascular homeostasis. Cav-1 deficiency leads to increased bioavailability of NO, which has been linked to increased nitrosative stress. Inhibition of eNOS reduced oxidant production and reversed PH, supporting the concept that Cav-1 regulation of eNOS activity is crucial to endothelial homeostasis in lungs. We designed this study to investigate the hypothesis that expression of Cav-1 is downregulated while eNOS expression is upregulated by the pulmonary endothelium in the nitrofen-induced congenital diaphragmatic hernia (CDH). Pregnant rats were exposed to nitrofen or vehicle on day 9.5 (D9.5). Fetuses were sacrificed on D21 and divided into nitrofen and control groups. Quantitative real-time polymerase chain reaction, Western blotting, and confocal immunofluorescence were performed to determine pulmonary gene expression levels and protein expression of Cav-1 and eNOS. Pulmonary Cav-1 gene expression levels were significantly decreased, while eNOS gene expression was significantly increased in nitrofen-induced CDH(+). Western blotting and confocal microscopy revealed decreased pulmonary Cav-1 protein expression, while eNOS protein expression was increased in CDH(+) compared to controls. The striking evidence of markedly decreased gene and protein expression of Cav-1 with concurrently increased eNOS gene and protein expression in the pulmonary vasculature suggests that activation of eNOS secondary to Cav-1 deficiency may play an important role in the pathogenesis of PH in the nitrofen-induced CDH. © 2014 Wiley Periodicals, Inc.

  13. p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity

    PubMed Central

    2014-01-01

    Background Endothelial nitric oxide synthase (eNOS)-uncoupling links obesity-associated insulin resistance and type-II diabetes to the increased incidence of cardiovascular disease. Studies have indicated that increased arginase is involved in eNOS-uncoupling through competing with the substrate L-arginine. Given that arginase-II (Arg-II) exerts some of its biological functions through crosstalk with signal transduction pathways, and that p38 mitogen-activated protein kinase (p38mapk) is involved in eNOS-uncoupling, we investigated here whether p38mapk is involved in Arg-II-mediated eNOS-uncoupling in a high fat diet (HFD)-induced obesity mouse model. Methods Obesity was induced in wild type (WT) and Arg-II-deficient (Arg-II-/-) mice on C57BL/6 J background by high-fat diet (HFD, 55% fat) for 14 weeks starting from age of 7 weeks. The entire aortas were isolated and subjected to 1) immunoblotting analysis of the protein level of eNOS, Arg-II and p38mapk activation; 2) arginase activity assay; 3) endothelium-dependent and independent vasomotor responses; 4) en face staining of superoxide anion and NO production with Dihydroethidium and 4,5-Diaminofluorescein Diacetate, respectively, to assess eNOS-uncoupling. To evaluate the role of p38mapk, isolated aortas were treated with p38mapk inhibitor SB203580 (10 μmol/L, 1 h) prior to the analysis. In addition, the role of p38mapk in Arg-II-induced eNOS-uncoupling was investigated in cultured human endothelial cells overexpressing Arg-II in the absence or presence of shRNA against p38mapk. Results HFD enhanced Arg-II expression/activity and p38mapk activity, which was associated with eNOS-uncoupling as revealed by decreased NO and enhanced L-NAME-inhibitable superoxide in aortas of WT obese mice. In accordance, WT obese mice revealed decreased endothelium-dependent relaxations to acetylcholine despite of higher eNOS protein level, whereas Arg-II-/- obese mice were protected from HFD-induced eNOS-uncoupling and

  14. Lactobacillus Fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling.

    PubMed

    Toral, Marta; Romero, Miguel; Rodríguez-Nogales, Alba; Jiménez, Rosario; Robles-Vera, Iñaki; Algieri, Francesca; Chueca-Porcuna, Natalia; Sánchez, Manuel; de la Visitación, Néstor; Olivares, Mónica; García, Federico; Pérez-Vizcaíno, Francisco; Gálvez, Julio; Duarte, Juan

    2018-05-30

    Our aim was to analyse whether the probiotic Lactobacillus fermentum CECT5716 (LC40) could prevent endothelial dysfunction and hypertension induced by tacrolimus in mice. Tacrolimus increased systolic blood pressure (SBP) and impaired endothelium-dependent relaxation to acetylcholine and these effects were partially prevented by LC40. Endothelial dysfunction induced by tacrolimus was related to both increased NADPH oxidase (NOX2) and uncoupled eNOS driven-superoxide production and Rho-kinase mediated eNOS inhibition. LC40 treatment prevented all the aortic changes induced by tacrolimus. LC40 restored the imbalance between T-helper 17 (Th17)/ regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and spleen. Tacrolimus induced gut dysbiosis, i.e. it decreased microbial diversity, increased Firmicutes/Bacteroidetes ratio and decreased acetate- and butyrate-producing bacteria and these effects were prevented by LC40. Fecal microbiota transplantation from LC40 treated mice to control mice prevented the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus. LC40 treatment prevented hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects were associated with a reduction in vascular oxidative stress, mainly through NOX2 down-regulation and prevention of eNOS-uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum.

    PubMed

    Combet, S; Ferrier, M L; Van Landschoot, M; Stoenoiu, M; Moulin, P; Miyata, T; Lameire, N; Devuyst, O

    2001-10-01

    Advanced glycation end products (AGE), growth factors, and nitric oxide contribute to alterations of the peritoneum during peritoneal dialysis (PD). These mediators are also involved in chronic uremia, a condition associated with increased permeability of serosal membranes. It is unknown whether chronic uremia per se modifies the peritoneum before PD initiation. A rat model of subtotal nephrectomy was used to measure peritoneal permeability after 3, 6, and 9 wk, in parallel with peritoneal nitric oxide synthase (NOS) isoform expression and activity and structural changes. Uremic rats were characterized by a higher peritoneal permeability for small solutes and an increased NOS activity due to the up-regulation of endothelial and neuronal NOS. The permeability changes and increased NOS activities correlated with the degree of renal failure. Focal areas of vascular proliferation and fibrosis were detected in uremic rats, in relation with a transient up-regulation of vascular endothelial growth factor and basic fibroblast growth factor, as well as vascular deposits of the AGE carboxymethyllysine and pentosidine. Correction of anemia with erythropoietin did not prevent the permeability or structural changes in uremic rats. Thus, in this rat model, uremia induces permeability and structural changes in the peritoneum, in parallel with AGE deposits and up-regulation of specific NOS isoforms and growth factors. These data suggest an independent contribution of uremia in the peritoneal changes during PD and offer a paradigm to better understand the modifications of serosal membranes in uremia.

  16. Endothelial CaMKII as a regulator of eNOS activity and NO-mediated vasoreactivity

    PubMed Central

    Murthy, Shubha; Koval, Olha M.; Ramiro Diaz, Juan M.; Kumar, Santosh; Nuno, Daniel; Scott, Jason A.; Allamargot, Chantal; Zhu, Linda J.; Broadhurst, Kim; Santhana, Velarchana; Kutschke, William J.; Irani, Kaikobad; Lamping, Kathryn G.; Grumbach, Isabella M.

    2017-01-01

    The multifunctional Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine kinase important in transducing intracellular Ca2+ signals. While in vitro data regarding the role of CaMKII in the regulation of endothelial nitric oxide synthase (eNOS) are contradictory, its role in endothelial function in vivo remains unknown. Using two novel transgenic models to express CaMKII inhibitor peptides selectively in endothelium, we examined the effect of CaMKII on eNOS activation, NO production, vasomotor tone and blood pressure. Under baseline conditions, CaMKII activation was low in the aortic wall. Consistently, systolic and diastolic blood pressure, heart rate and plasma NO levels were unaltered by endothelial CaMKII inhibition. Moreover, endothelial CaMKII inhibition had no significant effect on NO-dependent vasodilation. These results were confirmed in studies of aortic rings transduced with adenovirus expressing a CaMKII inhibitor peptide. In cultured endothelial cells, bradykinin treatment produced the anticipated rapid influx of Ca2+ and transient CaMKII and eNOS activation, whereas CaMKII inhibition blocked eNOS phosphorylation on Ser-1179 and dephosphorylation at Thr-497. Ca2+/CaM binding to eNOS and resultant NO production in vitro were decreased under CaMKII inhibition. Our results demonstrate that CaMKII plays an important role in transient bradykinin-driven eNOS activation in vitro, but does not regulate NO production, vasorelaxation or blood pressure in vivo under baseline conditions. PMID:29059213

  17. Women with TT genotype for eNOS gene are more responsive in lowering blood pressure in response to exercise.

    PubMed

    Sponton, Carlos H G; Rezende, Tiago M; Mallagrino, Pamella A; Franco-Penteado, Carla F; Bezerra, Marcos André C; Zanesco, Angelina

    2010-12-01

    The aim of this study was to investigate whether -786T>C endothelial nitric oxide synthase (eNOS) gene polymorphism might influence the effect of long-term exercise training (ET) on the blood pressure and its relationship with NO production in healthy postmenopausal women. Longitudinal study. Fifty-five postmenopausal women were studied in a double-blinded design. ET was performed for 3 days a week, each session consisting of 60 min during 6 months, in an intensity of 50-70% VO2max. After that, eNOS genotype analysis was performed and women were divided into two groups: TC+CC (n=41) and TT (n=14) genotype. No changes were found in the anthropometric parameters after ET in both the groups. Systolic and diastolic BP values were significantly reduced in both the groups, but women with TT genotype were more responsive in lowering BP as compared with those with TC+CC genotype. Plasma nitrite/nitrate concentrations were similar at baseline in both the groups, but the magnitude of increment in NO production in response to ET was higher in women with TT genotype as compared with those with TC+CC genotype. Our study shows clearly that women with or without eNOS gene polymorphism had no differences in NO production at basal conditions, but when physical exercise is applied an evident difference is detected showing that the presence of -786T>C eNOS gene polymorphism had a significant impact in the health-promoting effect of aerobic physical training on the blood pressure in postmenopausal women.

  18. Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans.

    PubMed

    Herrero, Pilar; Laforest, Richard; Shoghi, Kooresh; Zhou, Dong; Ewald, Gregory; Pfeifer, John; Duncavage, Eric; Krupp, Kitty; Mach, Robert; Gropler, Robert

    2012-06-01

    Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an (18)F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured (18)F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry. Two groups were studied-a kinetic analysis group and a dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic myocardial (18)F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial (18)F-NOS PET was assessed using volume of distribution; standardized uptake values at 10 min; area under the myocardial moment curve (AUMC); and mean resident time at 5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by immunohistochemistry. In the dosimetry group, the biodistribution and radiation dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12 OHT patients. The combined time-activity curves were used for residence time calculation, and organ doses were calculated with OLINDA. Both AUMC at 10 min (P < 0.05) and tissue iNOS (P < 0.0001) were higher in patients exhibiting rejection than in those without rejection. Moreover, the (18)F-NOS AUMC at 10 min correlated positively with tissue iNOS at 10 min (R(2) = 0.42, P < 0.05). (18)F-NOS activity was cleared by the hepatobiliary system. The critical organ was the bladder wall, with a dose of 95.3 μGy/MBq, and an effective dose of 15.9 μSv/MBq was calculated. Myocardial (18)F-NOS

  19. Time Talk: On Small Changes That Enact Infrastructural Mentoring for Undergraduate Women in Technical Fields

    ERIC Educational Resources Information Center

    Sullivan, Patricia; Moore, Kristen

    2013-01-01

    This article brings together the communication needs and positioning of women in technical areas, and asks "how can technical communication classes contribute to the mentoring of young women engineers at a time when many of those women want to be identified as engineers instead of being spotlighted as women in engineering?" Incorporating…

  20. TECHNICAL NOTE: Actuation displacement performance change of pre-stressed piezoelectric actuators attached to a flat surface

    NASA Astrophysics Data System (ADS)

    Goo, Nam Seo; Phuoc Phan, Van; Park, Hoon Cheol

    2009-03-01

    Pre-stressed piezoelectric actuators such as RAINBOW, THUNDER™, and LIPCA have a curvature due to a mismatch of the coefficient of thermal expansion, which inevitably exists during the manufacturing process. This technical note provides an answer to the question of how their actuation displacement performance changes when the curved pre-stressed piezoelectric actuators are attached to a flat surface. Finite element analysis with the ANSYS™ program was used to calculate the stress distribution inside a LIPCA, one of the pre-stressed piezoelectric actuators, after the LIPCA was cured and attached to the flat surface. The change of actuation displacement performance can be explained in terms of the relation between the piezoelectric strain constants and internal stress. As a result of the curing and attachment to a flat surface, the two-dimensional stress state inside the piezoceramic layer leads to an expected increase of around 51% for the longitudinal piezoelectric strain constant. To confirm this result, we reconsider the experimental results of the actuation moment measurement of the LIPCA and bare lead zirconium titanate.

  1. Deficiency of iNOS-derived NO accelerates lipid accumulation-independent liver fibrosis in non-alcoholic steatohepatitis mouse model.

    PubMed

    Nozaki, Yuichi; Fujita, Koji; Wada, Koichiro; Yoneda, Masato; Kessoku, Takaomi; Shinohara, Yoshiyasu; Imajo, Kento; Ogawa, Yuji; Nakamuta, Makoto; Saito, Satoru; Masaki, Naohiko; Nagashima, Yoji; Terauchi, Yasuo; Nakajima, Atsushi

    2015-04-01

    Although many of the factors and molecules closely associated with non-alcoholic steatohepatitis (NASH) have been reported, the role of inducible nitric oxide synthase (iNOS)-derived nitric oxide (NO) on the progression of NASH remains unclear. We therefore investigated the role of iNOS-derived NO in NASH pathogenesis with a long-term follow-up study using systemic iNOS-knockout mice under high-fat diet (HFD) conditions. iNOS-knockout and wild-type mice were fed a basal or HFD for 10 or 48 weeks. Lipid accumulation, fibrosis, and inflammation were evaluated, and various factors and molecules closely associated with NASH were analyzed. Marked fibrosis and inflammation (indicators of NASH) were observed in the livers of iNOS-knockout mice compared to wild-type mice after 48 weeks of a HFD; however, lipid accumulation in iNOS-knockout mice livers was less than in the wild-type. Increased expressions of various cytokines that are transcriptionally controlled by NF-kB in iNOS-deficient mice livers were observed during HFD conditions. iNOS-derived NO may play a protective role against the progression to NASH during an HFD by preventing fibrosis and inflammation, which are mediated by NF-kB activation in Kupffer cells. A lack of iNOS-derived NO accelerates progression to NASH without excessive lipid accumulation.

  2. Effects of Paracetamol on NOS, COX, and CYP Activity and on Oxidative Stress in Healthy Male Subjects, Rat Hepatocytes, and Recombinant NOS

    PubMed Central

    Trettin, Arne; Böhmer, Anke; Suchy, Maria-Theresia; Probst, Irmelin; Staerk, Ulrich; Stichtenoth, Dirk O.; Frölich, Jürgen C.

    2014-01-01

    Paracetamol (acetaminophen) is a widely used analgesic drug. It interacts with various enzyme families including cytochrome P450 (CYP), cyclooxygenase (COX), and nitric oxide synthase (NOS), and this interplay may produce reactive oxygen species (ROS). We investigated the effects of paracetamol on prostacyclin, thromboxane, nitric oxide (NO), and oxidative stress in four male subjects who received a single 3 g oral dose of paracetamol. Thromboxane and prostacyclin synthesis was assessed by measuring their major urinary metabolites 2,3-dinor-thromboxane B2 and 2,3-dinor-6-ketoprostaglandin F1α, respectively. Endothelial NO synthesis was assessed by measuring nitrite in plasma. Urinary 15(S)-8-iso-prostaglanding F2α was measured to assess oxidative stress. Plasma oleic acid oxide (cis-EpOA) was measured as a marker of cytochrome P450 activity. Upon paracetamol administration, prostacyclin synthesis was strongly inhibited, while NO synthesis increased and thromboxane synthesis remained almost unchanged. Paracetamol may shift the COX-dependent vasodilatation/vasoconstriction balance at the cost of vasodilatation. This effect may be antagonized by increasing endothelial NO synthesis. High-dosed paracetamol did not increase oxidative stress. At pharmacologically relevant concentrations, paracetamol did not affect NO synthesis/bioavailability by recombinant human endothelial NOS or inducible NOS in rat hepatocytes. We conclude that paracetamol does not increase oxidative stress in humans. PMID:24799980

  3. A Question of Trust: Predictive Conditions for Adaptive and Technical Leadership in Educational Contexts

    ERIC Educational Resources Information Center

    Daly, Alan J.; Chrispeels, Janet

    2008-01-01

    Recent studies have suggested that educational leaders enacting a balance of technical and adaptive leadership have an effect on increasing student achievement. Technical leadership focuses on problem-solving or first-order changes within existing structures and paradigms. Adaptive leadership involves deep or second-order changes that alter…

  4. Orbital debris: A technical assessment

    NASA Technical Reports Server (NTRS)

    Gleghorn, George; Asay, James; Atkinson, Dale; Flury, Walter; Johnson, Nicholas; Kessler, Donald; Knowles, Stephen; Rex, Dietrich; Toda, Susumu; Veniaminov, Stanislav

    1995-01-01

    To acquire an unbiased technical assessment of (1) the research needed to better understand the debris environment, (2) the necessity and means of protecting spacecraft against the debris environment, and (3) potential methods of reducing the future debris hazard, NASA asked the National Research Council to form an international committee to examine the orbital debris issue. The committee was asked to draw upon available data and analyses to: characterize the current debris environment, project how this environment might change in the absence of new measures to alleviate debris proliferation, examine ongoing alleviation activities, explore measures to address the problem, and develop recommendations on technical methods to address the problems of debris proliferation.

  5. Challenges and Changes: Developing Teachers' and Initial Teacher Education Students' Understandings of the Nature of Science

    NASA Astrophysics Data System (ADS)

    Ward, Gillian; Haigh, Mavis

    2017-12-01

    Teachers need an understanding of the nature of science (NOS) to enable them to incorporate NOS into their teaching of science. The current study examines the usefulness of a strategy for challenging or changing teachers' understandings of NOS. The teachers who participated in this study were 10 initial teacher education chemistry students and six experienced teachers from secondary and primary schools who were introduced to an explicit and reflective activity, a dramatic reading about a historical scientific development. Concept maps were used before and after the activity to assess teachers' knowledge of NOS. The participants also took part in a focus group interview to establish whether they perceived the activity as useful in developing their own understanding of NOS. Initial analysis led us to ask another group, comprising seven initial teacher education chemistry students, to take part in a modified study. These participants not only completed the same tasks as the previous participants but also completed a written reflection commenting on whether the activity and focus group discussion enhanced their understanding of NOS. Both Lederman et al.'s (Journal of Research in Science Teaching, 39(6), 497-521, 2002) concepts of NOS and notions of "naive" and "informed" understandings of NOS and Hay's (Studies in Higher Education, 32(1), 39-57, 2007) notions of "surface" and "deep" learning were used as frameworks to examine the participants' specific understandings of NOS and the depth of their learning. The ways in which participants' understandings of NOS were broadened or changed by taking part in the dramatic reading are presented. The impact of the data-gathering tools on the participants' professional learning is also discussed.

  6. 76 FR 80226 - Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-23

    ... final rule, effective upon publication. Generally, the Administrative Procedure Act (APA) requires a.... Additionally, the APA requires that a final rule must have a delayed effective date of 30 days from the date of... delayed effective date requirement under the APA. 5 U.S.C. 553(d)(3). Again the technical change conforms...

  7. 75 FR 58445 - Exelon Generation Company, LLC; Peach Bottom Atomic Power Station Unit Nos. 2 and 3...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-24

    ... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-277 AND 50-278; NRC-2010-0303] Exelon Generation Company, LLC; Peach Bottom Atomic Power Station Unit Nos. 2 and 3; Environmental Assessment and Finding of... Bottom Atomic Power Station (PBAPS), Unit Nos. 2 and 3, located in York and Lancaster Counties...

  8. nNOS inhibitors attenuate methamphetamine-induced dopaminergic neurotoxicity but not hyperthermia in mice.

    PubMed

    Itzhak, Y; Martin, J L; Ail, S F

    2000-09-11

    Methamphetamine (METH)-induced dopaminergic neurotoxicity is associated with hyperthermia. We investigated the effect of several neuronal nitric oxide synthase (nNOS) inhibitors on METH-induced hyperthermia and striatal dopaminergic neurotoxicity. Administration of METH (5 mg/kg; q. 3 h x 3) to Swiss Webster mice produced marked hyperthermia and 50-60% depletion of striatal dopaminergic markers 72 h after METH administration. Pretreatment with the nNOS inhibitors S-methylthiocitrulline (SMTC; 10 mg/kg) or 3-bromo-7-nitroindazole (3-Br-7-NI; 20 mg/kg) before each METH injection did not affect the persistent hyperthermia produced by METH, but afforded protection against the depletion of dopaminergic markers. A low dose (25 mg/kg) of the nNOS inhibitor 7-nitroindazole (7-NI) did not affect METH-induced hyperthermia, but a high dose (50 mg/kg) produced significant hypothermia. These findings indicate that low dose of selective nNOS inhibitors protect against METH-induced neurotoxicity with no effect on body temperature and support the hypothesis that nitric oxide (NO) and peroxynitrite have a major role in METH-induced dopaminergic neurotoxicity.

  9. Novel cellular targets of AhR underlie alterations in neutrophilic inflammation and iNOS expression during influenza virus infection

    PubMed Central

    Head Wheeler, Jennifer L.; Martin, Kyle C.; Lawrence, B. Paige

    2012-01-01

    The underlying reasons for variable clinical outcomes from respiratory viral infections remain uncertain. Several studies suggest that environmental factors contribute to this variation, but limited knowledge of cellular and molecular targets of these agents hampers our ability to quantify or modify their contribution to disease and improve public health. The aryl hydrocarbon receptor (AhR) is an environment sensing transcription factor that binds many anthropogenic and natural chemicals. The immunomodulatory properties of AhR ligands are best characterized with extensive studies of changes in CD4+ T cell responses. Yet, AhR modulates other aspects of immune function. We previously showed that during influenza virus infection, AhR activation modulates neutrophil accumulation in the lung, and this contributes to increased mortality in mice. Enhanced levels of inducible nitric oxide synthase (iNOS) in infected lungs are observed during the same timeframe as AhR-mediated increased pulmonary neutrophilia. In this study, we evaluated whether these two consequences of AhR activation are causally linked. Reciprocal inhibition of AhR-mediated elevations in iNOS and pulmonary neutrophilia reveal that, although they are contemporaneous, they are not causally related. We show using Cre/loxP technology that elevated iNOS levels and neutrophil number in the infected lung result from separate, AhR-dependent signaling in endothelial and respiratory epithelial cells, respectively. Studies using mutant mice further reveal that AhR-mediated alterations in these innate responses to infection require a functional nuclear localization signal and DNA binding domain. Thus, gene targets of AhR in non-hematopoietic cells are important new considerations for understanding AhR-mediated changes in innate anti-viral immunity. PMID:23233726

  10. NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans

    PubMed Central

    Velez, Digna Rosa; Hulme, William F.; Myers, Jamie L.; Weinberg, J. Brice; Levesque, Marc C.; Stryjewski, Martin E.; Abbate, Eduardo; Estevan, Rosa; Patillo, Sara G.; Gilbert, John R; Hamilton, Carol D.; Scott, William K.

    2010-01-01

    Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case-control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest associations were observed at rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23-2.77], p = 0.003) and rs7215373 (OR 1.67, 95% CI [1.17-2.37], p = 0.004), both of which passed a false discovery rate (FDR) correction for multiple comparisons (q*=0.20). The strongest gene-gene interactions were observed between NOS2A rs2248814 and IFNGR1 rs1327474 (p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 (p = 0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were observed in Caucasians. These results suggest that NOS2A variants may contribute to TB susceptibility, particularly in individuals of African descent, and may act synergistically with SNPs in TLR4 and IFNGR1. PMID:19575238

  11. Challenges and Changes: Developing Teachers' and Initial Teacher Education Students' Understandings of the Nature of Science

    ERIC Educational Resources Information Center

    Ward, Gillian; Haigh, Mavis

    2017-01-01

    Teachers need an understanding of the nature of science (NOS) to enable them to incorporate NOS into their teaching of science. The current study examines the usefulness of a strategy for challenging or changing teachers' understandings of NOS. The teachers who participated in this study were 10 initial teacher education chemistry students and six…

  12. Hemozoin Regulates iNOS Expression by Modulating the Transcription Factor NF-κB in Macrophages.

    PubMed

    Ranjan, Ravi; Karpurapu, Manjula; Rani, Asha; Chishti, Athar H; Christman, John W

    2016-01-01

    Hemozoin (Hz) is released from ruptured erythrocytes during malaria infection caused by Plasmodium sp., in addition the malaria infected individuals are prone to bacterial sepsis. The molecular interactions between Hz, bacterial components and macrophages remains poorly investigated. In this report, we investigated the combinatorial immune-modulatory effects of phagocytosed Hz, Interferon gamma (IFNγ) or lipopolysaccharide (LPS) in macrophages. Macrophages were treated with various concentrations of commercial synthetic Hz, and surprisingly it did not result in inducible nitric oxide synthase (iNOS) expression. However, when macrophages were pretreated with Hz and then challenged with IFNγ or LPS, there was a differential impact on iNOS expression. There was an increase in iNOS expression when macrophages were pre-treated with Hz and subsequently treated with IFNγ when compared to IFNγ alone. Whereas iNOS expression was reduced when Hz phagocytosed macrophages were stimulated with LPS compared to LPS alone. Furthermore, there was an increased activation of NF-κB in Hz phagocytosed macrophages that were challenged with IFNγ. The interaction between Hz and macrophages has an impact on iNOS expression.

  13. 75 FR 13600 - Virginia Electric and Power Company, North Anna Power Station, Unit Nos. 1 and 2, Surry Power...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-22

    ...- 2010-0116] Virginia Electric and Power Company, North Anna Power Station, Unit Nos. 1 and 2, Surry Power Station, Unit Nos. 1 and 2; Environmental Assessment and Finding of No Significant Impact The U.S... Anna Power Station, Unit Nos. 1 and 2 (NAPS), and Surry Power Station, Unit Nos. 1 and 2 (SPS), located...

  14. 75 FR 53984 - Virginia Electric and Power Company North Anna Power Station, Unit Nos. 1 and 2 Surry Power...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ...- 2010-0283] Virginia Electric and Power Company North Anna Power Station, Unit Nos. 1 and 2 Surry Power Station, Unit Nos. 1 and 2 Environmental Assessment and Finding of No Significant Impact The U.S. Nuclear... applications for North Anna Power Station, Unit Nos. 1 and 2 (NAPS), for Renewed Facility Operating License Nos...

  15. Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes

    PubMed Central

    Haaker, Jan; Glotzbach-Schoon, Evelyn; Schümann, Dirk; Andreatta, Marta; Mechias, Marie-Luise; Raczka, Karolina; Gartmann, Nina; Büchel, Christian; Mühlberger, Andreas; Pauli, Paul; Reif, Andreas; Kalisch, Raffael; Lonsdorf, Tina B.

    2016-01-01

    Abstract Being a complex phenotype with substantial heritability, anxiety and related phenotypes are characterized by a complex polygenic basis. Thereby, one candidate pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning processes. Using a multi-dimensional and -methodological replication approach, we investigated the impact of a functional promoter polymorphism (NOS1-ex1f-VNTR) on human anxiety-related phenotypes in a total of 1019 healthy controls in five different studies. Homozygous carriers of the NOS1-ex1f short-allele displayed enhanced trait anxiety, worrying and depression scores. Furthermore, short-allele carriers were characterized by increased anxious apprehension during contextual fear conditioning. While autonomous measures (fear-potentiated startle) provided only suggestive evidence for a modulatory role of NOS1-ex1f-VNTR on (contextual) fear conditioning processes, neural activation at the amygdala/anterior hippocampus junction was significantly increased in short-allele carriers during context conditioning. Notably, this could not be attributed to morphological differences. In accordance with data from a plethora of rodent studies, we here provide converging evidence from behavioral, subjective, psychophysiological and neuroimaging studies in large human cohorts that NOS-I plays an important role in anxious apprehension but provide only limited evidence for a role in (contextual) fear conditioning. PMID:26746182

  16. iNOS Activity Modulates Inflammation, Angiogenesis, and Tissue Fibrosis in Polyether-Polyurethane Synthetic Implants

    PubMed Central

    Cassini-Vieira, Puebla; Araújo, Fernanda Assis; da Costa Dias, Filipi Leles; Russo, Remo Castro; Andrade, Silvia Passos; Teixeira, Mauro Martins; Barcelos, Luciola Silva

    2015-01-01

    There is considerable interest in implantation techniques and scaffolds for tissue engineering and, for safety and biocompatibility reasons, inflammation, angiogenesis, and fibrosis need to be determined. The contribution of inducible nitric oxide synthase (iNOS) in the regulation of the foreign body reaction induced by subcutaneous implantation of a synthetic matrix was never investigated. Here, we examined the role of iNOS in angiogenesis, inflammation, and collagen deposition induced by polyether-polyurethane synthetic implants, using mice with targeted disruption of the iNOS gene (iNOS−/−) and wild-type (WT) mice. The hemoglobin content and number of vessels were decreased in the implants of iNOS−/− mice compared to WT mice 14 days after implantation. VEGF levels were also reduced in the implants of iNOS−/− mice. In contrast, the iNOS−/− implants exhibited an increased neutrophil and macrophage infiltration. However, no alterations were observed in levels of CXCL1 and CCL2, chemokines related to neutrophil and macrophage migration, respectively. Furthermore, the implants of iNOS−/− mice showed boosted collagen deposition. These data suggest that iNOS activity controls inflammation, angiogenesis, and fibrogenesis in polyether-polyurethane synthetic implants and that lack of iNOS expression increases foreign body reaction to implants in mice. PMID:26106257

  17. A central role of eNOS in the protective effect of wine against metabolic syndrome.

    PubMed

    Leighton, Federico; Miranda-Rottmann, Soledad; Urquiaga, Inés

    2006-01-01

    The positive health effects derived from moderate wine consumption are pleiotropic. They appear as improvements in cardiovascular risk factors such as plasma lipids, haemostatic mechanisms, endothelial function and antioxidant defences. The active principles would be ethanol and mainly polyphenols. Results from our and other laboratories support the unifying hypothesis that the improvements in risk factors after red wine consumption are mediated by endothelial nitric oxide synthase (eNOS). Many genes are involved, but the participation of eNOS would be a constant feature. The metabolic syndrome is a cluster of metabolic risk factors associated with high risk of cardiovascular disease (CVD). The National Cholesterol Education Programmmes Adult Treatment Panel III (NCEPATP III) clinical definition of the metabolic syndrome requires the presence of at least three risk factors, from among abdominal obesity, high plasma triacylglycerols, low plasma HDL, high blood pressure and high fasting plasma glucose. The molecular mechanisms responsible for the metabolic syndrome are not known. Since metabolic syndrome apparently affects 10-30% of the population in the world, research on its pathogenesis and control is needed. The recent finding that eNOS knockout mice present a cluster of cardiovascular risk factors comparable to those of the metabolic syndrome suggests that defects in eNOS function may cause human metabolic syndrome. These mice are hypertensive, insulin resistant and dyslipidemic. Further support for a pathogenic role of eNOS comes from the finding in humans that eNOS polymorphisms associate with insulin resistance and diabetes, with hypertension, with inflammatory and oxidative stress markers and with albuminuria. So, the data sustain the hypothesis that eNOS enhancement should reduce metabolic syndrome incidence and its consequences. Therefore red wine, since it enhances eNOS function, should be considered as a potential tool for the control of metabolic

  18. A meta-analysis of eNOS and ACE gene polymorphisms and risk of pre-eclampsia in women.

    PubMed

    Shaik, A P; Sultana, A; Bammidi, V K; Sampathirao, K; Jamil, K

    2011-10-01

    A meta-analyses of endothelial nitric oxide synthase (eNOS) and angiotensin-converting enzyme (ACE) gene polymorphisms in pre-eclampsia was performed. We shortlisted 33 studies (17 for ACE; 16 for eNOS gene polymorphisms), of which 29 articles (16 for ACE and 15 for eNOS) were analysed. Overall, 1,620 cases with pre-eclampsia and 2,158 controls were analysed for intron 16 insertion-deletion polymorphism in ACE gene. A total of 1,610 subjects with pre-eclampsia and 2,875 controls were analysed for the Glu298Asp in eNOS gene. Overall, the random-effects odds ratio (OR) with Glu298Asp in eNOS gene was 0.958 (95% confidence intervals, CI 0.747-1.228, p > 0.05), and for the insertion-deletion/ACE polymorphism was 0.987 (95% CI 0.698-1.395, p > 0.05). Significant heterogeneity was observed in the studies that evaluated polymorphisms in ACE (Q value = 55.6; I(2) = 73; p value = 0.000); and eNOS (Q value = 37.2; I(2) = 62.4; p value = 0.001) polymorphisms. No significant risk of pre-eclampsia was observed in both eNOS and ACE genes with these polymorphisms.

  19. Los Angeles County Poor Farm, Patient Ward Nos. 210 & ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Los Angeles County Poor Farm, Patient Ward Nos. 210 & 211 - Type B Plan, 7601 Imperial Highway; bounded by Esperanza Street, Laurel Street, Flores Street, and Descanso Street, Downey, Los Angeles County, CA

  20. Inducible NOS inhibitor 1400W reduces hypoxia/re-oxygenation injury in rat lung.

    PubMed

    Rus, Alma; Castro, Lourdes; Del Moral, Maria Luisa; Peinado, Angeles

    2010-01-01

    Nitric oxide (NO(*)) from inducible NO(*) synthase (iNOS) has been reported to either protect against, or contribute to, hypoxia/re-oxygenation lung injury. The present work aimed to clarify this double role in the hypoxic lung. With this objective, a follow-up study was made in Wistar rats submitted to hypoxia/re-oxygenation (hypoxia for 30 min; re-oxygenation of 0 h, 48 h, and 5 days), with or without prior treatment with the selective iNOS inhibitor 1400W (10 mg/kg). NO(*) levels (NOx), lipid peroxidation, apoptosis, and protein nitration were analysed. This is the first time-course study which investigates the effects of 1400W during hypoxia/re-oxygenation in the rat lung. The results showed that the administration of 1400W lowered NOx levels in all the experimental groups. In addition, lipid peroxidation, the percentage of apoptotic cells, and nitrated protein expression fell in the late post-hypoxia period (48 h and 5 days). Our results reveal that the inhibition of iNOS in the hypoxic lung reduced the damage observed before the treatment with 1400W, suggesting that iNOS-derived NO(*) may exert a negative effect on this organ during hypoxia/re-oxygenation. These findings are notable, since they indicate that any therapeutic strategy aimed at controlling excess generation of NO(*) from iNOS may be useful in alleviating NO(*)-mediated adverse effects in hypoxic lungs.

  1. Elementary school science teachers' reflection for nature of science: Workshop of NOS explicit and reflective on force and motion learning activity

    NASA Astrophysics Data System (ADS)

    Patho, Khanittha; Yuenyong, Chokchai; Chamrat, Suthida

    2018-01-01

    The nature of science has been part of Thailand's science education curriculum since 2008. However, teachers lack of understanding about the nature of science (NOS) and its teaching, particularly element school science teachers. In 2012, the Science Institute of Thailand MOE, started a project of Elementary Science Teacher Professional Development to enhance their thinking about the Nature of Science. The project aimed to enhance teachers' understanding of NOS, science teaching for explicit and reflective NOS, with the aim of extending their understanding of NOS to other teachers. This project selected 366 educational persons. The group was made up of a teacher and a teacher supervisor from 183 educational areas in 74 provinces all Thailand. The project provided a one week workshop and a year's follow up. The week-long workshop consisted of 11 activities of science teaching for explicit reflection on 8 aspects of NOS. Workshop of NOS explicit and reflective on force and motion learning activity is one of eight activities. This activity provided participants to learn force and motion and NOS from the traditional toy "Bang-Poh". The activity tried to enhance participants to explicit NOS for 5 aspects including empirical basis, subjectivity, creativity, observation and inference, and sociocultural embeddedness. The explicit NOS worksheet provided questions to ask participants to reflect their existing ideas about NOS. The paper examines elementary school science teachers' understanding of NOS from the force and motion learning activity which provided explicit reflection on 5 NOS aspects. An interpretive paradigm was used to analyse the teachers' reflections in a NOS worksheet. The findings indicated that majority of them could reflect about the empirical basis of science and creativity but few reflected on observation and inference, or sociocultural embeddedness. The paper will explain the teachers' NOS thinking and discuss the further enhancing of their understanding

  2. Neurological Outcome Scale for Traumatic Brain Injury: III. Criterion-Related Validity and Sensitivity to Change in the NABIS Hypothermia-II Clinical Trial

    PubMed Central

    Wilde, Elisabeth A.; Moretti, Paolo; MacLeod, Marianne C.; Pedroza, Claudia; Drever, Pamala; Fourwinds, Sierra; Frisby, Melisa L.; Beers, Sue R.; Scott, James N.; Hunter, Jill V.; Traipe, Elfrides; Valadka, Alex B.; Okonkwo, David O.; Zygun, David A.; Puccio, Ava M.; Clifton, Guy L.

    2013-01-01

    Abstract The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16–45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearman's rank-order correlations were calculated between the NOS-TBI and the Glasgow Outcome Scale (GOS), GOS-Extended (GOS-E), Disability Rating Scale (DRS), and Neurobehavioral Rating Scale-Revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxon's signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research. PMID:23617608

  3. Predictors of employer satisfaction: technical and non-technical skills.

    PubMed

    Danielson, Jared A; Wu, Tsui-Feng; Fales-Williams, Amanda J; Kirk, Ryan A; Preast, Vanessa A

    2012-01-01

    Employers of 2007-2009 graduates from Iowa State University College of Veterinary Medicine were asked to respond to a survey regarding their overall satisfaction with their new employees as well as their new employees' preparation in several technical and non-technical skill areas. Seventy-five responses contained complete data and were used in the analysis. Four technical skill areas (data collection, data interpretation, planning, and taking action) and five non-technical skill areas (interpersonal skills, ability to deal with legal issues, business skills, making referrals, and problem solving) were identified. All of the skill area subscales listed above had appropriate reliability (Cronbach's alpha>0.70) and were positively and significantly correlated with overall employer satisfaction. Results of two simultaneous regression analyses indicated that of the four technical skill areas, taking action is the most salient predictor of employer satisfaction. Of the five non-technical skill areas, interpersonal skills, business skills, making referrals, and problem solving were the most important skills in predicting employer satisfaction. Hierarchical regression analysis revealed that all technical skills explained 25% of the variation in employer satisfaction; non-technical skills explained an additional 42% of the variation in employer satisfaction.

  4. Differential response of nNOS knockout mice to MDMA ("ecstasy")- and methamphetamine-induced psychomotor sensitization and neurotoxicity.

    PubMed

    Itzhak, Yossef; Anderson, Karen L; Ali, Syed F

    2004-10-01

    It has been shown that mice deficient in neuronal nitric oxide synthase (nNOS) gene are resistant to cocaine-induced psychomotor sensitization and methamphetamine (METH)-induced dopaminergic neurotoxicity. The present study was undertaken to investigate the hypothesis that nNOS has a major role in dopamine (DA)- but not serotonin (5-hydroxytryptamine; 5-HT)-mediated effects of psychostimulants. The response of nNOS knockout (KO) and wild-type (WT) mice to the psychomotor-stimulating and neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") and METH were investigated. Repeated administration of MDMA for 5 days resulted in psychomotor sensitization in both WT and nNOS KO mice, while repeated administration of METH caused psychomotor sensitization in WT but not in KO mice. Sensitization to both MDMA and METH was persistent for 40 days in WT mice, but not in nNOS KO mice. These findings suggest that the induction of psychomotor sensitization to MDMA and METH is NO independent and NO dependent, respectively, while the persistence of sensitization to both drugs is NO dependent. For the neurochemical studies, a high dose of MDMA caused marked depletion of 5-HT in several brain regions of both WT and KO mice, suggesting that the absence of the nNOS gene did not afford protection against MDMA-induced depletion of 5-HT. Striatal dopaminergic neurotoxicity caused by high doses of MDMA and METH in WT mice was partially prevented in KO mice administered with MDMA, but it was fully precluded in KO mice administered with METH. The differential response of nNOS KO mice to the behavioral and neurotoxic effects of MDMA and METH suggests that the nNOS gene is required for the expression and persistence of DA-mediated effects of METH and MDMA, while 5-HT-mediated effects of MDMA (induction of sensitization and 5-HT depletion) are not dependent on nNOS.

  5. Sildenafil Promotes eNOS Activation and Inhibits NADPH Oxidase in the Transgenic Sickle Cell Mouse Penis

    PubMed Central

    Musicki, Biljana; Bivalacqua, Trinity J.; Champion, Hunter C.; Burnett, Arthur L.

    2014-01-01

    Introduction Sickle cell disease (SCD)-associated vasculopathy in the penis is characterized by aberrant nitric oxide and phosphodiesterase (PDE) 5 signaling, and by increased oxidative stress. Preliminary clinical trials show that continuous treatment with PDE5 inhibitor sildenafil unassociated with sexual activity decreases priapic activity in patients with SCD. However, the mechanism of its vasculoprotective effect in the penis remains unclear. Aims We evaluated whether continuous administration of PDE5 inhibitor sildenafil promotes eNOS function at posttranslational levels and decreases superoxide-producing enzyme NADPH oxidase activity in the sickle cell mouse penis. Methods SCD transgenic mice were used as an animal model of SCD. WT mice served as controls. Mice received treatment with the PDE5 inhibitor sildenafil (100 mg/kg/day) or vehicle for 3 weeks. eNOS phosphorylation on Ser-1177 (positive regulatory site), eNOS interactions with heat-shock protein 90 (HSP90) (positive regulator), phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser-1177), an NADPH oxidase catalytic subunit gp91(phox), and a marker of oxidative stress (4-hydroxy-2-nonenal [HNE]) were measured by Western blot. Main Outcome Measures Effect of continuous sildenafil treatment on eNOS posttranslational activation, NADPH oxidase catalytic subunit, and oxidative stress in the penis of the sickle cell mouse. Results Continuous treatment with sildenafil reversed (P < 0.05) the abnormalities in protein expressions of P-eNOS (Ser-1177), eNOS/HSP90 interaction, P-AKT, protein expression of gp91(phox), and 4-HNE, in the sickle cell mouse penis. Sildenafil treatment of WT mice did not affect any of these parameters. Conclusion Our findings that sildenafil enhances eNOS activation and inhibits NADPH oxidase function in the sickle cell mouse penis offers a vasculoprotective molecular basis for the therapeutic effect of sildenafil in the penis in association with SCD. PMID:24251665

  6. Sildenafil promotes eNOS activation and inhibits NADPH oxidase in the transgenic sickle cell mouse penis.

    PubMed

    Musicki, Biljana; Bivalacqua, Trinity J; Champion, Hunter C; Burnett, Arthur L

    2014-02-01

    Sickle cell disease (SCD)-associated vasculopathy in the penis is characterized by aberrant nitric oxide and phosphodiesterase (PDE) 5 signaling, and by increased oxidative stress. Preliminary clinical trials show that continuous treatment with PDE5 inhibitor sildenafil unassociated with sexual activity decreases priapic activity in patients with SCD. However, the mechanism of its vasculoprotective effect in the penis remains unclear. We evaluated whether continuous administration of PDE5 inhibitor sildenafil promotes eNOS function at posttranslational levels and decreases superoxide-producing enzyme NADPH oxidase activity in the sickle cell mouse penis. SCD transgenic mice were used as an animal model of SCD. WT mice served as controls. Mice received treatment with the PDE5 inhibitor sildenafil (100 mg/kg/day) or vehicle for 3 weeks. eNOS phosphorylation on Ser-1177 (positive regulatory site), eNOS interactions with heat-shock protein 90 (HSP90) (positive regulator), phosphorylated AKT (upstream mediator of eNOS phosphorylation on Ser-1177), an NADPH oxidase catalytic subunit gp91(phox), and a marker of oxidative stress (4-hydroxy-2-nonenal [HNE]) were measured by Western blot. Effect of continuous sildenafil treatment on eNOS posttranslational activation, NADPH oxidase catalytic subunit, and oxidative stress in the penis of the sickle cell mouse. Continuous treatment with sildenafil reversed (P < 0.05) the abnormalities in protein expressions of P-eNOS (Ser-1177), eNOS/HSP90 interaction, P-AKT, protein expression of gp91(phox), and 4-HNE, in the sickle cell mouse penis. Sildenafil treatment of WT mice did not affect any of these parameters. Our findings that sildenafil enhances eNOS activation and inhibits NADPH oxidase function in the sickle cell mouse penis offers a vasculoprotective molecular basis for the therapeutic effect of sildenafil in the penis in association with SCD. © 2013 International Society for Sexual Medicine.

  7. A conceptual change analysis of nature of science conceptions: The deep roots and entangled vines of a conceptual ecology

    NASA Astrophysics Data System (ADS)

    Johnston, Adam Thomas

    This research used theories of conceptual change to analyze learners' understandings of the nature of science (NOS). Ideas regarding the NOS have been advocated as vital aspects of science literacy, yet learners at many levels (students and teachers) have difficulty in understanding these aspects in the way that science literacy reforms advocate. Although previous research has shown the inadequacies in learners' NOS understandings and have documented ways by which to improve some of these understandings, little has been done to show how these ideas develop and why learners' preexisting conceptions of NOS are so resistant to conceptual change. The premise of this study, then, was to describe the nature of NOS conceptions and of the conceptual change process itself by deeply analyzing the conceptions of individual learners. Toward this end, 4 individuals enrolled in a physical science course designed for preservice elementary teachers were selected to participate in a qualitative research study. These individuals answered questionnaires, surveys, direct interview questions, and a variety of interview probes (e.g., critical incidents, responses to readings/videos, reflections on coursework, card sorting tasks, etc.) which were administered throughout the duration of a semester. By utilizing these in-depth, qualitative probes, learners' conceptions were not only assessed but also described in great detail, revealing the source of their conceptions as well as identifying many instances in which a learner's directly stated conception was contradictory to that which was reflected by more indirect probes. As a result of this research, implications regarding NOS conceptions and their development have been described. In addition, various descriptions of conceptual change have been further refined and informed. Especially notable, the influence of a learner's conceptual ecology and its extrarational influences on conceptual change have been highlighted. It is argued that

  8. Interaction of AR and iNOS in lens epithelial cell: A new pathogenesis and potential therapeutic targets of diabetic cataract.

    PubMed

    Li, Xue; Liu, Wenping; Huang, Xinduo; Xiong, Jianping; Wei, Xiaoyong

    2017-02-01

    Although there is significant interest in revealing the role of aldose reductase (AR) and inducible nitric oxide synthase (iNOS) in diabetic cataract (DC), the interaction of AR and iNOS remains unknown. The aim of this study is to investigate the pathogenesis mechanisms and explore as a new potential therapeutic targets for DC. This study investigated the interaction of AR-iNOS through the methods of enzyme kinetics, molecular docking and molecular dynamics simulation, co-immunoprecipitation and fluorescence resonance energy transfer (FRET). The IC50 of AR for inhibition of iNOS activity is 0.04 μM, and the IC50 of iNOS for inhibition of AR activity is 0.042 μM through enzyme kinetics; the interface showed that ARG99 on AR and GLU317 on iNOS played the key roles in the interaction of AR-iNOS predicted by molecular docking and molecular dynamics simulation. Co-immunoprecipitation of protein complexes in human lens epithelial cell (HLEC) demonstrated that AR could association with iNOS in cell; and the interaction distance of AR-iNOS was 6.50 ± 0.22 nm detected by FRET. This study exhibited a direct inhibition interaction between AR and iNOS in HLECs. It is the first report of inhibition interaction between AR and iNOS, suggesting a new pathophysiological mechanism and providing a new insight into the therapeutic mechanism of DC. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. l-Arginine normalizes NOS activity and zinc-MT homeostasis in the kidney of mice chronically exposed to inorganic mercury.

    PubMed

    Piacenza, Francesco; Malavolta, Marco; Cipriano, Catia; Costarelli, Laura; Giacconi, Robertina; Muti, Elisa; Tesei, Silvia; Pierpaoli, Sara; Basso, Andrea; Bracci, Massimo; Bonacucina, Viviana; Santarelli, Lory; Mocchegiani, Eugenio

    2009-09-28

    Inorganic mercury (HgCl2) exposure provokes damage in many organs, especially kidney. Inducible nitric oxide synthase (iNOS) expression, total NOS activity and the profiles of zinc (Zn), copper (Cu) and Hg as well as their distribution when bound to specific intracellular proteins, including metallothioneins (MT), were studied during HgCl2 exposure and after l-arginine treatment in C57BL/6 mouse kidney. HgCl2 exposure modulates differently iNOS expression and NOS activity, increasing iNOS expression but, conversely, decreasing total NOS activity in the mouse kidney. Moreover, during Hg exposure an increased MT production occurs. The kidney damage leads to a loss of urinary proteins, increased plasma creatinine and high Zn mobilization with consequent increased urinary Zn excretion. l-arginine treatment recovers NOS activity and induces a normalization of MT induction, plasma creatinine values and urinary proteins excretion, suggesting that l-arginine may limit kidney damages by Hg exposure.

  10. Adding Realism to Technical Drafting Programs

    ERIC Educational Resources Information Center

    Weaver, Gerald L.

    1976-01-01

    Suggestions for improved, relevant technical drafting programs are presented: (1) making realistic assignments, (2) viewing real projects, (3) duplicating industrial projects, (4) practicing lettering, (5) conducting research, (6) engaging in teamwork, (7) adapting to change, (8) learning to meet deadlines, and (9) stressing the importance of…

  11. 75 FR 5061 - Commission Information Collection Activities (FERC Form Nos. 6 and 6-Q); Comment Request; Extensions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-01

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. IC10-6-000 and IC10-6Q-000] Commission Information Collection Activities (FERC Form Nos. 6 and 6-Q); Comment Request; Extensions January... to Docket Nos. IC10-6-000 and IC10-6Q-000. For comments that only pertain to one of the collections...

  12. Managing change: an overview.

    PubMed

    Lorenzi, N M; Riley, R T

    2000-01-01

    As increasingly powerful informatics systems are designed, developed, and implemented, they inevitably affect larger, more heterogeneous groups of people and more organizational areas. In turn, the major challenges to system success are often more behavioral than technical. Successfully introducing such systems into complex health care organizations requires an effective blend of good technical and good organizational skills. People who have low psychological ownership in a system and who vigorously resist its implementation can bring a "technically best" system to its knees. However, effective leadership can sharply reduce the behavioral resistance to change-including to new technologies-to achieve a more rapid and productive introduction of informatics technology. This paper looks at four major areas-why information system failures occur, the core theories supporting change management, the practical applications of change management, and the change management efforts in informatics.

  13. Effects of NOS inhibition on the cardiopulmonary system and brain microvascular markers after intermittent hypoxia in rats.

    PubMed

    Barer, G R; Fairlie, J; Slade, J Y; Ahmed, S; Laude, E A; Emery, C J; Thwaites-Bee, D; Oakley, A E; Barer, D H; Kalaria, R N

    2006-07-07

    We previously demonstrated that rats subjected to intermittent hypoxia (IH) by exposure to 10% O(2) for 4 h daily for 56 days in a normobaric chamber, developed pulmonary hypertension, right ventricular hypertrophy and wall-thickening in pulmonary arterioles, compared with normoxic (N) controls. These changes were greater in rats subjected to continuous hypoxia (CH breathing 10% O(2) for 56 days). Cerebral angiogenesis was demonstrated by immunostaining with glucose transporter 1 (GLUT1) antibody, in viable vessels, in CH and to a lesser degree in IH. In this study, adult Wistar rats were subjected to the same hypoxic regimes and given the nitric oxide synthase (NOS) inhibitor N(6)-nitro-L-arginine methyl ester (L-NAME) in drinking water (NLN, IHLN and CHLN regimes) to induce hypertension. There was significant systemic hypertension in NLN and IHLN rats, compared with N and IH, but surprisingly not in CHLN compared with CH. Hematocrit rose in all hypoxic groups (up to 79% in CHLN). There was no significant pulmonary hypertension in IHLN versus NLN rats, although there was asymmetric wall thickening in pulmonary arterioles. Cerebral GLUT1 immunoreactivity increased with L-NAME, with or without hypoxia, especially in CHLN rats, but conspicuously there was no evidence of angiogenesis in brains of IHLN compared with NLN rats. NOS blockade may attenuate the cerebral and pulmonary vascular changes of IH while augmenting cerebral angiogenesis in continuous hypoxia. However, whether cerebral effects are due to systemic hypertension or changes in cerebral nitric oxide production needs to be evaluated.

  14. Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China

    PubMed Central

    Cheng, Zhaohui; Tao, Hongbing; Cai, Miao; Lin, Haifeng; Lin, Xiaojun; Shu, Qin; Zhang, Ru-ning

    2015-01-01

    Objectives Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. Setting and participants 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. Outcome measures Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. Results (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010–2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. Conclusions There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010–2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency

  15. Converging evidence for an impact of a functional NOS gene variation on anxiety-related processes.

    PubMed

    Kuhn, Manuel; Haaker, Jan; Glotzbach-Schoon, Evelyn; Schümann, Dirk; Andreatta, Marta; Mechias, Marie-Luise; Raczka, Karolina; Gartmann, Nina; Büchel, Christian; Mühlberger, Andreas; Pauli, Paul; Reif, Andreas; Kalisch, Raffael; Lonsdorf, Tina B

    2016-05-01

    Being a complex phenotype with substantial heritability, anxiety and related phenotypes are characterized by a complex polygenic basis. Thereby, one candidate pathway is neuronal nitric oxide (NO) signaling, and accordingly, rodent studies have identified NO synthase (NOS-I), encoded by NOS1, as a strong molecular candidate for modulating anxiety and hippocampus-dependent learning processes. Using a multi-dimensional and -methodological replication approach, we investigated the impact of a functional promoter polymorphism (NOS1-ex1f-VNTR) on human anxiety-related phenotypes in a total of 1019 healthy controls in five different studies. Homozygous carriers of the NOS1-ex1f short-allele displayed enhanced trait anxiety, worrying and depression scores. Furthermore, short-allele carriers were characterized by increased anxious apprehension during contextual fear conditioning. While autonomous measures (fear-potentiated startle) provided only suggestive evidence for a modulatory role of NOS1-ex1f-VNTR on (contextual) fear conditioning processes, neural activation at the amygdala/anterior hippocampus junction was significantly increased in short-allele carriers during context conditioning. Notably, this could not be attributed to morphological differences. In accordance with data from a plethora of rodent studies, we here provide converging evidence from behavioral, subjective, psychophysiological and neuroimaging studies in large human cohorts that NOS-I plays an important role in anxious apprehension but provide only limited evidence for a role in (contextual) fear conditioning. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. The Effects of Integrating On-Going Training for Technical Documentation Teams

    ERIC Educational Resources Information Center

    Catanio, Joseph T.; Catanio, Teri L.

    2010-01-01

    The tools and techniques utilized in the technical communications profession are constantly improving and changing. Information Technology (IT) organizations devote the necessary resources to equip and train engineering, marketing, and sales teams, but often fail to do so for technical documentation teams. Many IT organizations tend to view…

  17. TLR2 signal influences the iNOS/NO responses and worm development in C57BL/6J mice infected with Clonorchis sinensis.

    PubMed

    Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Shi, Yun-Liang; Wan, Xiao-Ling; Yang, Yi-Chao

    2017-08-07

    Although the responses of inducible nitric oxide synthase (iNOS) and associated cytokine after Clonorchis sinensis infection have been studied recently, their mechanisms remain incompletely understood. In this study, we investigated the effects of toll-like receptor 2 (TLR2) signals on iNOS/nitric oxide (NO) responses after C. sinensis infection. We also evaluated the correlations between iNOS responses and worm development, which are possibly regulated by TLR2 signal. TLR2 wild-type and mutant C57BL/6 J mice were infected with 60 C. sinensis metacercariae, and the samples were collected at 30, 60, 90 and 120 days post-infection (dpi). The total serum NO levels were detected using Griess reagent after nitrate was reduced to nitrite. Hepatic tissue samples from the infected mice were sliced and stained with hematoxylin and eosin (HE) to observe worm development in the intrahepatic bile ducts. The iNOS mRNA transcripts in the splenocytes were examined by real time reverse transcriptase polymerase chain reaction (qRT-PCR), and iNOS expression was detected by immunohistochemistry. Developing C. sinensis juvenile worms were more abundant in the intrahepatic bile ducts of TLR2 mutant mice than those of TLR2 wild-type mice. However, no eggs were found in the faeces of both mice samples. The serum levels of total NO significantly increased in TLR2 mutant mice infected with C. sinensis at 30 (t (5)  = 2.595, P = 0.049), 60 (t (5)  = 7.838, P = 0.001) and 90 dpi (t (5)  = 3.032, P = 0.029). Meanwhile, no changes occurred in TLR2 wild-type mice compared with uninfected controls during the experiment. The iNOS expression in splenocytes showed unexpected higher background levels in TLR2 mutant mice than those in TLR2 wild-type mice. Furthermore, the iNOS mRNA transcripts in splenocytes were significantly increased in the TLR2 wild-type mice infected with C. sinensis at 30 (t (5)  = 5.139, P = 0.004), 60 (t (5)  = 6.138, P = 0.002) and 90 dpi (t (5)  = 6

  18. Induction of expression of iNOS by N-nitrosodimethylamine (NDMA) in human leukocytes.

    PubMed

    Ratajczak-Wrona, Wioletta; Jablonska, Ewa; Jablonski, Jakub; Marcinczyk, Magdalena

    2009-01-01

    The aim of this study was to assess the influence of N-nitrosodimethylamine (NDMA) on expression of inducible nitric oxide synthase (iNOS), as well as production of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) by human neutrophils (PMN) and peripheral blood mononuclear cells (PBMC), and the participation of the p38 MAPK kinase in this process. Furthermore, the ability of neutrophils to release superoxide anion was determined. The influence of N-nitrosodimethylamine on iNOS expression was determined in isolated PMN and PBMC cells from peripheral blood of healthy individuals. The mononuclear cells showed higher sensitivity to NDMA. Moreover, cytotoxic effect of NDMA can be influenced in some way by the impact of this xenobiotic on nitric oxide and superoxide anion release from human leukocytes. Furthermore, increased generation of these radicals by human leukocytes suggest that neutrophils and mononuclear cells that are exposed to NDMA activity can play a key role in endogenous NDMA generation. However the relationship between iNOS expression and phospho-p38 MAPK in neutrophils and mononuclear cells shows that p38 MAPK pathway participates in induction of iNOS expression in the presence of NDMA.

  19. Changing Preservice Science Teachers' Views of Nature of Science: Why Some Conceptions May Be More Easily Altered than Others

    ERIC Educational Resources Information Center

    Mesci, Gunkut; Schwartz, Renee' S.

    2017-01-01

    The purpose of this study was to assess preservice teachers' views of Nature of Science (NOS), identify aspects that were challenging for conceptual change, and explore reasons why. This study particularly focused on why and how some concepts of NOS may be more easily altered than others. Fourteen preservice science teachers enrolled in a NOS and…

  20. Book Review: New Perspectives on Technical Editing

    NASA Astrophysics Data System (ADS)

    Murphy, A. J. (Ed.); Sterken, Christiaan

    2012-08-01

    New Perspectives on Technical Editing by Avon J. Murphy (ed.) ISBN : 978-0895033949 (2010) Baywood Publishing Company Inc, Hardcover, 210 pages, 35.5 GBP This book presents a collection of 10 chapters dealing with diverse aspects of technical editing (ie, editorial planning, and analysis and structural changes made to other people's technological documents): research in technical editing, trends and teaching of technical editing, copyediting, and technical journal editing. The role and function of the modern journal and book editor is also dealt with in detail. Each chapter is written by an expert in the field: senior editors, university professors in technical communication, technical writers and linguists. The ever-evolving role of the editor is clearly elucidated in several historical reviews, and in the descriptions of the expectations for the future. A very striking aspect of this book is its extensive collection of bibliographic resources: every chapter lists dozens of very useful references, and the closing chapter, and annotated bibliography, contain many not so well known references, and are most useful. All in all, the book is a treasure trove listing more than 400 references, in addition to numerous webpage URLs embedded in the texts. The book is designed to help the reader to understand current practices and norms in technical editing, and to help to take action in editing as well as in teaching and educating would-be editors. The audience for this book thus includes editors and teachers, but also writers, researchers and students. A deep reading of this book will result in a better understanding of the difference between full technical editing and its much narrower component so well known as copyediting, and will convince any prospective editor that editing should not be undertaken if the people involved do not master the art of precision and accuracy in technical (as well as in human) communication, do not possess the technical know how and computer

  1. Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer.

    PubMed

    Choi, Ji-Yeob; Lee, Kyoung-Mu; Noh, Dong-Young; Ahn, Sei-Hyun; Lee, Jong-Eun; Han, Wonshik; Jang, In-Jin; Shin, Sang-Goo; Yoo, Keun-Young; Hayes, Richard B; Kang, Daehee

    2006-11-01

    The endothelial cell-specific form of nitric oxide synthase (eNOS) may play an important role in tumor progression via angiogenesis or apoptosis. We studied eNOS -786T > C and 894G > T (Glu298Asp), two functionally significant SNPs, in relation to hazard of breast cancer recurrence or death in 873 women with incident, non-metastatic breast cancer, recruited from two teaching hospitals in Seoul, Korea, 1995-2002. Hazards were estimated by Cox proportional hazard models, in relation to genotype, adjusting for hormone receptor status, lymph node involvement, and tumor size. Women carriers of the eNOS -786C allele had significantly increased hazards of breast cancer recurrence or death, compared with women having the TT genotype (HR = 2.1, 95% CI = 1.03-4.33); risks increased up to 3-fold in ER positive cases (HR = 3.2, 95% CI = 0.95-10.50). The hazard was also increased in eNOS 894T carriers, however, it did not reach statistical significance (HR = 1.8, 95% CI = 0.85-3.93). The combined genotypes containing -786C or 894T was associated with a 2.5-fold risk, compared to the TT-GG genotypes, the most dominant genotype combination (95% CI = 1.29-4.68), with the greatest risks in ER positive cases (HR = 4.9, 95% CI = 1.31-18.36). These results indicate that the eNOS -786C polymorphism, and possibly the 894T polymorphism, are associated with breast cancer recurrence and death, particularly in women with ER positive tumors.

  2. Induction of iNOS in human monocytes infected with different Legionella species.

    PubMed

    Neumeister, B; Bach, V; Faigle, M; Northoff, H

    2001-08-07

    The contribution of nitric oxide (NO) radicals to the suppression of intracellular replication of Legionella has been well established in rodents but remained questionable in humans. Considering the fact that human monocytes do not exhibit a high-output NO production, we used sensitive methods such as detection of inducible NO synthase (iNOS) mRNA by reverse transcription-PCR and demonstration of iNOS protein expression by means of flow cytometry and Western blot to compare the levels of iNOS induced by Legionella species which, in accordance to their human prevalence, show different multiplication rates within human monocytic cells. The expression of iNOS in Mono Mac 6 (MM6) cells showed an only moderate inverse correlation to the intracellular replication rate of a given Legionella species in the protein expression assays. However, stimulation of host cells with 1,25-dihydroxyvitamin D(3) to enhance NO production and inhibition of NO production by treatment of host cells with N(G)-methyl-L-arginine were not able to modify the intracellular multiplication of legionellae within MM6 cells. Therefore, NO production does not seem to play a crucial role for the restriction of intracellular replication of Legionella bacteria within human monocytic cells. Rodent models in investigations which are supposed to clarify the involvement of NO radicals in defense mechanisms against Legionella infections in humans are of doubtful significance.

  3. NOS3 genotype-dependent correlation between blood pressure and physical activity.

    PubMed

    Kimura, Tomomi; Yokoyama, Tetsuji; Matsumura, Yasuhiro; Yoshiike, Nobuo; Date, Chigusa; Muramatsu, Masaaki; Tanaka, Heizo

    2003-02-01

    Endothelium-dependent vasorelaxation plays an important role in reduction of blood pressure and is mediated through release of nitric oxide (NO), which is generated by constitutively expressed endothelial nitric oxide synthase (NOS3). Exercise also augments NO release and has been recommended for primary prevention and improvement of hypertension, but individual responses are highly variable. We therefore postulated that genetic polymorphisms of NOS3 might interact with physical activity level to differentially influence blood pressure level. We genotyped 832 healthy Japanese (mean age of 54.4+/-8.6 years, 372 men and 460 women) for a polymorphism of NOS3 in intron 4 (ecNOS4a/b), using the polymerase chain reaction method, and scored their habitual physical activity level by using the rate of energy expenditure per resting metabolic rate through an interview according to a semiquantitative assessment method. Only in the subjects who had the rarer a allele (aa+ba type), systolic blood pressure was found to be inversely correlated with physical activity level (P for linear trend=0.0496, for interaction=0.0071). Eventually, this polymorphism was significantly associated with the prevalence of systolic hypertension only in the subjects who were in the lowest tertile of physical activity level (OR=2.4, 95% CI, 1.1 to 5.6, P for interaction=0.0474). In the present study, we found a significant interaction between the genotype and physical activity level on systolic blood pressure. These results might allow a better understanding of the mechanism to improve hypertension by exercise and to thereby reduce the risk of cardiovascular disease.

  4. Remote ischemic preconditioning protects liver ischemia-reperfusion injury by regulating eNOS-NO pathway and liver microRNA expressions in fatty liver rats.

    PubMed

    Duan, Yun-Fei; An, Yong; Zhu, Feng; Jiang, Yong

    2017-08-15

    Ischemic preconditioning (IPC) is a strategy to reduce ischemia-reperfusion (I/R) injury. The protective effect of remote ischemic preconditioning (RIPC) on liver I/R injury is not clear. This study aimed to investigate the roles of RIPC in liver I/R in fatty liver rats and the involvement of endothelial nitric oxide synthase-nitric oxide (eNOS-NO) pathway and microRNA expressions in this process. A total of 32 fatty rats were randomly divided into the sham group, I/R group, RIPC group and RIPC+I/R group. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and nitric oxide (NO) were measured. Hematoxylin-eosin staining was used to observe histological changes of liver tissues, TUNEL to detect hepatocyte apoptosis, and immunohistochemistry assay to detect heat shock protein 70 (HSP70) expression. Western blotting was used to detect liver inducible NOS (iNOS) and eNOS protein levels and real-time quantitative polymerase chain reaction to detect miR-34a, miR-122 and miR-27b expressions. Compared with the sham and RIPC groups, serum ALT, AST and iNOS in liver tissue were significantly higher in other two groups, while serum NO and eNOS in liver tissue were lower, and varying degrees of edema, degeneration and inflammatory cell infiltration were found. Cell apoptosis number was slightly lower in the RIPC+I/R group than that in I/R group. Compared with the sham group, HSP70 expressions were significantly increased in other three groups (all P<0.05). Compared with the sham and RIPC groups, elevated miR-34a expressions were found in I/R and RIPC+I/R groups (P<0.05). MiR-122 and miR-27b were found significantly decreased in I/R and RIPC+I/R groups compared with the sham and RIPC groups (all P<0.05). RIPC can reduce fatty liver I/R injury by affecting the eNOS-NO pathway and liver microRNA expressions. Copyright © 2017 The Editorial Board of Hepatobiliary & Pancreatic Diseases International. Published by Elsevier B.V. All rights reserved.

  5. The NosX and NirX Proteins of Paracoccus denitrificans Are Functional Homologues: Their Role in Maturation of Nitrous Oxide Reductase

    PubMed Central

    Saunders, Neil F. W.; Hornberg, Jorrit J.; Reijnders, Willem N. M.; Westerhoff, Hans V.; de Vries, Simon; van Spanning, Rob J. M.

    2000-01-01

    The nos (nitrous oxide reductase) operon of Paracoccus denitrificans contains a nosX gene homologous to those found in the nos operons of other denitrifiers. NosX is also homologous to NirX, which is so far unique to P. denitrificans. Single mutations of these genes did not result in any apparent phenotype, but a double nosX nirX mutant was unable to reduce nitrous oxide. Promoter-lacZ assays and immunoblotting against nitrous oxide reductase showed that the defect was not due to failure of expression of nosZ, the structural gene for nitrous oxide reductase. Electron paramagnetic resonance spectroscopy showed that nitrous oxide reductase in cells of the double mutant lacked the CuA center. A twin-arginine motif in both NosX and NirX suggests that the NosX proteins are exported to the periplasm via the TAT translocon. PMID:10960107

  6. NOS1-derived nitric oxide promotes NF-κB transcriptional activity through inhibition of suppressor of cytokine signaling-1

    PubMed Central

    Baig, Mirza Saqib; Zaichick, Sofia V.; Mao, Mao; de Abreu, Andre L.; Bakhshi, Farnaz R.; Hart, Peter C.; Saqib, Uzma; Deng, Jing; Chatterjee, Saurabh; Block, Michelle L.; Vogel, Stephen M.; Malik, Asrar B.; Consolaro, Marcia E.L.; Christman, John W.; Minshall, Richard D.

    2015-01-01

    The NF-κB pathway is central to the regulation of inflammation. Here, we demonstrate that the low-output nitric oxide (NO) synthase 1 (NOS1 or nNOS) plays a critical role in the inflammatory response by promoting the activity of NF-κB. Specifically, NOS1-derived NO production in macrophages leads to proteolysis of suppressor of cytokine signaling 1 (SOCS1), alleviating its repression of NF-κB transcriptional activity. As a result, NOS1−/− mice demonstrate reduced cytokine production, lung injury, and mortality when subjected to two different models of sepsis. Isolated NOS1−/− macrophages demonstrate similar defects in proinflammatory transcription on challenge with Gram-negative bacterial LPS. Consistently, we found that activated NOS1−/− macrophages contain increased SOCS1 protein and decreased levels of p65 protein compared with wild-type cells. NOS1-dependent S-nitrosation of SOCS1 impairs its binding to p65 and targets SOCS1 for proteolysis. Treatment of NOS1−/− cells with exogenous NO rescues both SOCS1 degradation and stabilization of p65 protein. Point mutation analysis demonstrated that both Cys147 and Cys179 on SOCS1 are required for its NO-dependent degradation. These findings demonstrate a fundamental role for NOS1-derived NO in regulating TLR4-mediated inflammatory gene transcription, as well as the intensity and duration of the resulting host immune response. PMID:26324446

  7. A noninhibitory mutant of the caveolin-1 scaffolding domain enhances eNOS-derived NO synthesis and vasodilation in mice

    PubMed Central

    Bernatchez, Pascal; Sharma, Arpeeta; Bauer, Philip M.; Marin, Ethan; Sessa, William C.

    2011-01-01

    Aberrant regulation of eNOS and associated NO release are directly linked with various vascular diseases. Caveolin-1 (Cav-1), the main coat protein of caveolae, is highly expressed in endothelial cells. Its scaffolding domain serves as an endogenous negative regulator of eNOS function. Structure-function analysis of Cav-1 has shown that phenylalanine 92 (F92) is critical for the inhibitory actions of Cav-1 toward eNOS. Herein, we show that F92A–Cav-1 and a mutant cell–permeable scaffolding domain peptide called Cavnoxin can increase basal NO release in eNOS-expressing cells. Cavnoxin reduced vascular tone ex vivo and lowered blood pressure in normal mice. In contrast, similar experiments performed with eNOS- or Cav-1–deficient mice showed that the vasodilatory effect of Cavnoxin is abolished in the absence of these gene products, which indicates a high level of eNOS/Cav-1 specificity. Mechanistically, biochemical assays indicated that noninhibitory F92A–Cav-1 and Cavnoxin specifically disrupted the inhibitory actions of endogenous Cav-1 toward eNOS and thereby enhanced basal NO release. Collectively, these data raise the possibility of studying the inhibitory influence of Cav-1 on eNOS without interfering with the other actions of endogenous Cav-1. They also suggest a therapeutic application for regulating the eNOS/Cav-1 interaction in diseases characterized by decreased NO release. PMID:21804187

  8. Phospho-eNOS Ser-1176 is associated with the nucleoli and the Golgi complex in C6 rat glioma cells.

    PubMed

    Klinz, Franz-Josef; Herberg, Natalie; Arnhold, Stefan; Addicks, Klaus; Bloch, Wilhelm

    2007-06-29

    Enzymatic activity of endothelial nitric oxide synthase (eNOS) is controlled by posttranslational modifications, protein-protein interactions, and subcellular localization. For example, N-terminal fatty acid modifications target eNOS to the Golgi complex where it becomes phosphorylated. We show here by immunofluorescence analysis that phospho-eNOS Ser-1176 is enriched in the perinuclear region of interphase C6 rat glioma cells. Confocal double immunofluorescence microscopy with the Golgi marker protein 58K revealed that phospho-eNOS Ser-1176 is associated with the Golgi complex. Surprisingly, we observed several spots in the nucleus of C6 cells that were positive for phospho-eNOS Ser-1176. Confocal double immunofluorescence analysis with the nucleolus marker protein fibrillarin revealed that within the nucleus phospho-eNOS Ser-1176 is exclusively associated with the nucleoli. It is known that in mitotic cells nucleoli are lost during prophase and rebuild during telophase. In agreement with this, we find no nucleoli-like distribution of phospho-eNOS Ser-1176 in metaphase and anaphase C6 glioma cells. Our finding that phospho-eNOS Ser-1176 is selectively associated with the nucleoli points to a so far unknown role for eNOS in interphase glioma cells.

  9. [Association of I/D and -786 Polymorphisms of ACE and NOS3 Genes With Features of the Course of Ischemic Heart Disease and Diabetes Mellitus Type 2].

    PubMed

    Afanasiev, S A; Muslimova, E F; Rebrov, T Y; Sergienko, T N; Repin, A N

    2016-09-01

    to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.

  10. Going beyond the Consensus View: Broadening and Enriching the Scope of NOS-Oriented Curricula

    ERIC Educational Resources Information Center

    Hodson, Derek; Wong, Siu Ling

    2017-01-01

    Nature of science (NOS) is now a well-established focus of science education and a key element in defining scientific literacy. In recent years, a particular specification of NOS, often described as "the consensus view," has become very influential and has gained ready acceptance in many countries around the world as a template for…

  11. VIEW OF NOS. 217 AND 219 WASHINGTON AVENUE LOOKING NORTHEAST, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF NOS. 217 AND 219 WASHINGTON AVENUE LOOKING NORTHEAST, SHOWING WEST FACADES - Apollo Iron & Steel Works, Company Housing, West of Washington & Lincoln Avenues, Vandergrift, Westmoreland County, PA

  12. Association of a NOS3 gene polymorphism with Behçet's disease but not with Vogt-Koyanagi-Harada syndrome in Han Chinese.

    PubMed

    Zhou, Yan; Yu, Hongsong; Hou, Shengping; Fang, Jing; Qin, Jieying; Yuan, Gangxiang; Kijlstra, Aize; Yang, Peizeng

    2016-01-01

    Previous studies have identified that nitric oxide synthase (NOS) genes are associated with several immune-mediated diseases. This study aimed to investigate whether NOS2 and NOS3 gene polymorphisms are associated with Behçet's disease (BD) and Vogt-Koyanagi-Harada (VKH) syndrome in a Han Chinese population. An association analysis of NOS2/rs4795067, NOS3/rs1799983 and NOS3/rs1800779 was performed in 733 patients with BD, 800 patients with VKH syndrome, and 1,359 controls using PCR restriction fragment length polymorphism (PCR-RFLP) assay. Statistical analysis was performed with the chi-square test followed by the Bonferroni correction. The result showed a decreased frequency of the NOS3/rs1799983 GG genotype and an increased frequency of NOS3/rs1799983 GT genotype in the patients with BD (Bonferroni correction test [Pc]=0.02, odds ratio [OR]=0.74; Pc=2.1×10(-3), OR=1.57, respectively). No significant association was found between rs1799983 and VKH syndrome. NOS2/ rs4795067 and NOS3/rs1800779 were not associated with either BD or VKH syndrome. Our findings suggest that a NOS3/rs1799983polymorphism is associated with susceptibility to BD in Han Chinese.

  13. Technical tips: Electrode application and preventing skin breakdown techniques.

    PubMed

    Berlin, Fira; Carlile, Jennifer A; de Burgo, Maria I; Rochon, Adrienne; Wagner, Esperanza E; Sellers, Martha C; Worrell, Amanda R; Andal, E Lauren C; Woods, Latina R

    2011-09-01

    The recording electrodes including their precise location, their ability to record during movements that can be intense during a convulsive seizure, and their capability to record for several days without causing skin breakdown are an integral part of long-term EEG recording. Many of the facets of EEG technology have changed dramatically with the introduction of digital EEG. But the electrode and the electrode/skin interface have not had many dramatic changes. The technologist still looks for ways to ensure correct electrode placement, good recording capabilities, and a patient with healthy skin when the electrodes are removed. This Technical Tips features ideas and experiences from several technologists. These technologists express suggestions and opinions which are accepted in Technical Tips.

  14. 78 FR 13478 - Compassionate Release; Technical Changes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-28

    ... (Bureau) makes a minor change to remove an administrative level of review from the processing of a... interim rule, the Bureau of Prisons (Bureau) makes a minor change to remove an administrative level of review from the processing of a Compassionate Release request packet. DATES: This rule is effective April...

  15. [Expressional change of nitric oxide synthases in dorsal root ganglia of cats after selective dorsal rhizotomy].

    PubMed

    Qin, Hua-li; Zhou, Xue; Zhang, Wei; Chen, Si-xiu

    2004-01-01

    To examine the expressional change of nitric oxide synthase (NOS) in the injured dorsal root ganglia (DRG) and the ipsilateral adjacent uninjured DRG after selective dorsal rhizotomy. Immunochemical ABC method was used to detect the distribution of immunoreaction complex of NOS isoforms--nNOS and eNOS, and quantitative analysis was conducted to get the number of nNOS-immunoreactivity (nNOS-IR) neurons in normal DRG, dorsal rhizotomized DRG and spared DRG from adult cats on the 6th day after operation. This operating model was made by rhizotomizing unilateral L1-L5 dorsal roots and leaving L6 as a spared root. nNOS-immunoreactants were mainly distributed in the small-sized neurons in the DRG of cat. The percentage of nNOS-expressing small-sized neurons increased in the deafferentated L5 DRG (29.74%) when compared with the contralateral DRG (19.35%), and it also increased in the spared DRG (24.22%), compared with the contralateral DRG (18.61%). eNOS-IR was not observed in the DRG of adult cats. nNOS/NO up-regulated in DRG neurons is involved in a wide variety of biological functions under physiological and lesion-induced pathophysiological conditions in nerve system.

  16. Interaction Between Neuronal NOS Signaling and Temperature Influences SR Ca2+ Leak:Role of Nitroso-Redox Balance

    PubMed Central

    Dulce, Raul A.; Mayo, Vera; Rangel, Erika B.; Balkan, Wayne; Hare, Joshua M.

    2014-01-01

    Rationale While nitric oxide (NO) signaling modulates cardiac function and excitation-contraction coupling, opposing results due to inconsistent experimental conditions, particularly with respect to temperature, confound the ability to elucidate NO signaling pathways. Here we show that temperature significantly modulates NO effects. Objective Test the hypothesis that temperature profoundly impacts nitroso-redox equilibrium, thereby affecting sarcomeric reticulum (SR) Ca2+ leak. Methods and Results We measured SR Ca2+ leak in cardiomyocytes from wild-type (WT), NO/redox imbalance (NOS1−/−), and hyper S-nitrosylation (GSNOR−/−) mice. In WT cardiomyocytes, SR Ca2+ leak increased as temperature decreased from 37°C to 23°C, whereas, in NOS1−/ −cells, the leak suddenly increased when the temperature surpassed 30°C. GSNOR−/ − cardiomyocytes exhibited low leak throughout the temperature range. Exogenously added NO had a biphasic effect on NOS1−/− cardiomyocytes; reducing leak at 37°C but increasing it at sub-physiologic temperatures. Oxypurinol and Tempol diminished the leak in NOS1−/ − cardiomyocytes. Cooling from 37° to 23°C increased ROS generation in WT but decreased it in NOS1−/− cardiomyocytes. Oxypurinol further reduced ROS generation. At 23°C in WT cells, leak was decreased by tetrahydrobiopterin, an essential NOS cofactor. Cooling significantly increased SR Ca2+ content in NOS1−/− cells but had no effect in WT or GSNOR−/−. Conclusions Ca2+ leak and temperature are normally inversely proportional, whereas NOS1 deficiency reverses this effect, increasing leak and elevating ROS production as temperature increases. Reduced denitrosylation (GSNOR deficiency) eliminates the temperature dependence of leak. Thus, temperature regulates the balance between NO and ROS which in turn has a major impact on SR Ca2+. PMID:25326127

  17. Does inducible NOS have a protective role against hypoxia/reoxygenation injury in rat heart?

    PubMed

    Rus, Alma; del Moral, Maria Luisa; Molina, Francisco; Peinado, Maria Angeles

    2011-01-01

    The present study analyzes the role of the nitric oxide (NO) derived from inducible NO synthase (iNOS) under cardiac hypoxia/reoxygenation situations. For this, we have designed a follow-up study of different parameters of cell and tissue damage in the heart of Wistar rats submitted for 30 min to acute hypobaric hypoxia, with or without prior treatment with the selective iNOS inhibitor N-(3-(aminomethyl)benzyl) acetamidine or 1400W (10 mg/kg). The rats were studied at 0 h, 12 h, and 5 days of reoxygenation, analyzing NO production (NOx), lipid peroxidation, apoptosis, and protein nitration expression and location. This is the first time-course study which analyzes the effects of the iNOS inhibition by 1400W during hypoxia/reoxygenation in the adult rat heart. The results show that when 1400W was administered before the hypoxic episode, NOx levels fell, while both the lipid peroxidation level and the percentage of apoptotic cells rose throughout the reoxygenation period. Levels of nitrated proteins expression fell only at 12 h post-hypoxia. The inhibition of iNOS raises the peroxidative and apoptotic level in the hypoxic heart indicating that this isoform may have a protective effect on this organ against hypoxia/reoxygenation injuries, and challenging the conventional wisdom that iNOS is deleterious under these conditions. These findings could help in the design of new treatments based on NO pharmacology against hypoxia/reoxygenation dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. The role of nNOS and PGC-1α in skeletal muscle cells.

    PubMed

    Baldelli, Sara; Lettieri Barbato, Daniele; Tatulli, Giuseppe; Aquilano, Katia; Ciriolo, Maria Rosa

    2014-11-15

    Neuronal nitric oxide synthase (nNOS) and peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α) are two fundamental factors involved in the regulation of skeletal muscle cell metabolism. nNOS exists as several alternatively spliced variants, each having a specific pattern of subcellular localisation. Nitric oxide (NO) functions as a second messenger in signal transduction pathways that lead to the expression of metabolic genes involved in oxidative metabolism, vasodilatation and skeletal muscle contraction. PGC-1α is a transcriptional coactivator and represents a master regulator of mitochondrial biogenesis by promoting the transcription of mitochondrial genes. PGC-1α can be induced during physical exercise, and it plays a key role in coordinating the oxidation of intracellular fatty acids with mitochondrial remodelling. Several lines of evidence demonstrate that NO could act as a key regulator of PGC-1α expression; however, the link between nNOS and PGC-1α in skeletal muscle remains only poorly understood. In this Commentary, we review important metabolic pathways that are governed by nNOS and PGC-1α, and aim to highlight how they might intersect and cooperatively regulate skeletal muscle mitochondrial and lipid energetic metabolism and contraction. © 2014. Published by The Company of Biologists Ltd.

  19. The decay of NASA's technical culture

    NASA Technical Reports Server (NTRS)

    Mccurdy, Howard E.

    1989-01-01

    Changes in the organization structure and technical research activities of NASA since 1970 are evaluated. The creation of NASA and the original organizational structure and operation of NASA are reviewed. The relationship between organization and advanced technology is discussed and suggestions are given for ways of maintaining NASA as a high reliability organization.

  20. Ischemic postconditioning provides cardioprotective and antiapoptotic effects against ischemia-reperfusion injury through iNOS inhibition in hyperthyroid rats.

    PubMed

    Zaman, Jalal; Jeddi, Sajad; Daneshpour, Maryam Sadat; Zarkesh, Maryam; Daneshian, Zahra; Ghasemi, Asghar

    2015-10-10

    Ischemic postconditioning (IPost) is a strategy to provide protection against ischemia-reperfusion (IR) injury. The cardioprotective effects of IPost in cases of ischemic heart disease along with co-morbidities like hyperthyroidism remain unknown. The aim of this study was to investigate the effects of IPost on expression of eNOS, iNOS, Bax, and Bcl-2 genes in hyperthyroid male rats, subjected to myocardial IR. Hyperthyroidism was induced by adding thyroxine to drinking water for a period of 21 days. Using the Langendorff device hearts were perfused, then subjected to a 30-minute global ischemia which was followed by 120 min of reperfusion; subsequently IPost was induced immediately after ischemia. Results indicated that following IR, expression of eNOS and Bcl-2 decreased, whereas expression of iNOS and Bax increased in both the control and hyperthyroid groups. In hyperthyroid animals, IPost significantly increased expression of eNOS by 3.19 fold and Bcl-2 by 3.66 fold; it also decreased expression of Bax by 51%, and reduced IR-induced DNA laddering pattern and infarct size (45.7 ± 1.82% vs. 59.3 ± 1.83%, p<0.05) in the presence of aminoguanidine (AG), a selective iNOS inhibitor. In conclusion, IPost per se could not provide cardioprotection against myocardial ischemia in hyperthyroid rats, a loss of which however was restored by the combination of IPost and iNOS inhibition that acts by a decrease in Bax and an increase in both eNOS and Bcl-2 expression. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Expression dynamics of HSP90 and nitric oxide synthase (NOS) isoforms during heat stress acclimation in Tharparkar cattle

    NASA Astrophysics Data System (ADS)

    Bharati, Jaya; Dangi, S. S.; Bag, S.; Maurya, V. P.; Singh, G.; Kumar, P.; Sarkar, M.

    2017-08-01

    Six male Tharparkar cattle of 2-3 years old were selected for the study. After 15-day acclimation at thermoneutral zone (TNZ) in psychrometric chamber, animals were exposed at 42 °C for 6 h up to 23 days followed by 12 days of recovery period. Blood samples were collected during control period at TNZ (days 1, 5, and 12), after heat stress exposure (day 1, immediate heat stress acclimation (IHSA); days 2 to 10, short-term heat stress acclimation (STHSA); days 15 to 23, long-term heat stress acclimation (LTHSA); days 7 and 12, recovery period), and peripheral blood mononuclear cells (PBMCs) were isolated for RNA and protein extraction. The messenger RNA (mRNA) and protein expression in PBMCs were determined by qPCR and western blot, respectively. Samples at TNZ were taken as control. The mRNA expression of HSP90, iNOS, and eNOS was significantly upregulated ( P < 0.05) on day 1 (ISHA) as compared to control, remained consistent during STHSA, again increased during LTHSA, and finally reduced to basal level during recovery period. The protein expression of HSP90, iNOS, and eNOS were akin to their transcript pattern. PBMC culture study was conducted to study transcriptional abundance of HSP90, iNOS, and eNOS at different temperature-time combinations. The present findings indicate that HSP90, iNOS, and eNOS could possibly play an important role in mitigating thermal insults and confer thermotolerance during long-term heat stress exposure in Tharparkar cattle.

  2. The Effectiveness of Conceptual Change Texts and Concept Clipboards in Learning the Nature of Science

    ERIC Educational Resources Information Center

    Çil, Emine; Çepni, Salih

    2016-01-01

    Background: One of the most important goals of science education is to enable students to understand the nature of science (NOS). However, generally regular science teaching in classrooms does not help students improve informed NOS views. Purpose: This study investigated the influence of an explicit reflective conceptual change approach compared…

  3. 75 FR 50884 - Navigation and Navigable Waters; Technical, Organizational, and Conforming Amendments, Sector...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-18

    ... 3 and 165 to reflect changes in Coast Guard internal organizational structure. Sector Portland and... 1625-ZA25 Navigation and Navigable Waters; Technical, Organizational, and Conforming Amendments, Sector... Waters; Technical, Organizational, and Conforming Amendments, Sector Columbia River.'' 2. On page 48564...

  4. Differential HIF and NOS responses to acute anemia: defining organ-specific hemoglobin thresholds for tissue hypoxia.

    PubMed

    Tsui, Albert K Y; Marsden, Philip A; Mazer, C David; Sled, John G; Lee, Keith M; Henkelman, R Mark; Cahill, Lindsay S; Zhou, Yu-Qing; Chan, Neville; Liu, Elaine; Hare, Gregory M T

    2014-07-01

    Tissue hypoxia likely contributes to anemia-induced organ injury and mortality. Severe anemia activates hypoxia-inducible factor (HIF) signaling by hypoxic- and neuronal nitric oxide (NO) synthase- (nNOS) dependent mechanisms. However, organ-specific hemoglobin (Hb) thresholds for increased HIF expression have not been defined. To assess organ-specific Hb thresholds for tissue hypoxia, HIF-α (oxygen-dependent degradation domain, ODD) luciferase mice were hemodiluted to mild, moderate, or severe anemia corresponding to Hb levels of 90, 70, and 50 g/l, respectively. HIF luciferase reporter activity, HIF protein, and HIF-dependent RNA levels were assessed. In the brain, HIF-1α was paradoxically decreased at mild anemia, returned to baseline at moderate anemia, and then increased at severe anemia. Brain HIF-2α remained unchanged at all Hb levels. Both kidney HIF-1α and HIF-2α increased earlier (Hb ∼70-90 g/l) in response to anemia. Liver also exhibited an early HIF-α response. Carotid blood flow was increased early (Hb ∼70, g/l), but renal blood flow remained relatively constant, only increased at Hb of 50 g/l. Anemia increased nNOS (brain and kidney) and endothelia NOS (eNOS) (kidney) levels. Whereas anemia-induced increases in brain HIFα were nNOS-dependent, our current data demonstrate that increased renal HIFα was nNOS independent. HIF-dependent RNA levels increased linearly (∼10-fold) in the brain. However, renal HIF-RNA responses (MCT4, EPO) increased exponentially (∼100-fold). Plasma EPO levels increased near Hb threshold of 90 g/l, suggesting that the EPO response is sensitive. Collectively, these observations suggest that each organ expresses a different threshold for cellular HIF/NOS hypoxia responses. This knowledge may help define the mechanism(s) by which the brain and kidney maintain oxygen homeostasis during anemia. Copyright © 2014 the American Physiological Society.

  5. iNOS-derived nitric oxide promotes glycolysis by inducing pyruvate kinase M2 nuclear translocation in ovarian cancer.

    PubMed

    Li, Linlin; Zhu, Lingqun; Hao, Bingtao; Gao, Wenwen; Wang, Qianli; Li, Keyi; Wang, Meng; Huang, Mengqiu; Liu, Zhengjun; Yang, Qiaohong; Li, Xiqing; Zhong, Zhuo; Huang, Wenhua; Xiao, Guanghui; Xu, Yang; Yao, Kaitai; Liu, Qiuzhen

    2017-05-16

    Aerobic glycolysis is essential for tumor growth and survival. Activation of multiple carcinogenic signals contributes to metabolism reprogramming during malignant transformation of cancer. Recently nitric oxide has been noted to promote glycolysis but the mechanism remains elusive. We report here the dual role of nitric oxide in glycolysis: low/physiological nitric oxide (≤ 100 nM) promotes glycolysis for ATP production, oxidative defense and cell proliferation of ovary cancer cells, whereas excess nitric oxide (≥ 500 nM) inhibits it. Nitric oxide has a positive effect on glycolysis by inducing PKM2 nuclear translocation in an EGFR/ERK2 signaling-dependent manner. Moreover, iNOS induced by mild inflammatory stimulation increased glycolysis and cell proliferation by producing low doses of nitric oxide, while hyper inflammation induced iNOS inhibited it by producing excess nitric oxide. Finally, iNOS expression is abnormally increased in ovarian cancer tissues and is correlated with PKM2 expression. Overexpression of iNOS is associated with aggressive phenotype and poor survival outcome in ovarian cancer patients. Our study indicated that iNOS/NO play a dual role of in tumor glycolysis and progression, and established a bridge between iNOS/NO signaling pathway and EGFR/ERK2/PKM2 signaling pathway, suggesting that interfering glycolysis by targeting the iNOS/NO/PKM2 axis may be a valuable new therapeutic approach of treating ovarian cancer.

  6. iNOS-derived nitric oxide promotes glycolysis by inducing pyruvate kinase M2 nuclear translocation in ovarian cancer

    PubMed Central

    Hao, Bingtao; Gao, Wenwen; Wang, Qianli; Li, Keyi; Wang, Meng; Huang, Mengqiu; Liu, Zhengjun; Yang, Qiaohong; Li, Xiqing; Zhong, Zhuo; Huang, Wenhua; Xiao, Guanghui; Xu, Yang; Yao, Kaitai; Liu, Qiuzhen

    2017-01-01

    Aerobic glycolysis is essential for tumor growth and survival. Activation of multiple carcinogenic signals contributes to metabolism reprogramming during malignant transformation of cancer. Recently nitric oxide has been noted to promote glycolysis but the mechanism remains elusive. We report here the dual role of nitric oxide in glycolysis: low/physiological nitric oxide (≤ 100 nM) promotes glycolysis for ATP production, oxidative defense and cell proliferation of ovary cancer cells, whereas excess nitric oxide (≥ 500 nM) inhibits it. Nitric oxide has a positive effect on glycolysis by inducing PKM2 nuclear translocation in an EGFR/ERK2 signaling-dependent manner. Moreover, iNOS induced by mild inflammatory stimulation increased glycolysis and cell proliferation by producing low doses of nitric oxide, while hyper inflammation induced iNOS inhibited it by producing excess nitric oxide. Finally, iNOS expression is abnormally increased in ovarian cancer tissues and is correlated with PKM2 expression. Overexpression of iNOS is associated with aggressive phenotype and poor survival outcome in ovarian cancer patients. Our study indicated that iNOS/NO play a dual role of in tumor glycolysis and progression, and established a bridge between iNOS/NO signaling pathway and EGFR/ERK2/PKM2 signaling pathway, suggesting that interfering glycolysis by targeting the iNOS/NO/PKM2 axis may be a valuable new therapeutic approach of treating ovarian cancer. PMID:28380434

  7. Quality Work, Quality Control in Technical Services.

    ERIC Educational Resources Information Center

    Horny, Karen L.

    1985-01-01

    Quality in library technical services is explored in light of changes produced by automation. Highlights include a definition of quality; new opportunities and shifting priorities; cataloging (fullness of records, heading consistency, accountability, local standards, automated checking); need for new skills (management, staff); and boons of…

  8. NF-kappaB mediates mitogen-activated protein kinase pathway-dependent iNOS expression in human melanoma.

    PubMed

    Uffort, Deon G; Grimm, Elizabeth A; Ellerhorst, Julie A

    2009-01-01

    Tumor expression of inducible nitric oxide synthase (iNOS) predicts poor outcomes for melanoma patients. We have reported the regulation of melanoma iNOS by the mitogen-activated protein kinase (MAPK) pathway. In this study, we test the hypothesis that NF-kappaB mediates this regulation. Western blotting of melanoma cell lysates confirmed the constitutive expression of iNOS. Western blot detected baseline levels of activated nuclear extracellular signal-regulated kinase and NF-kappaB. Indirect immunofluorescence confirmed the presence of NF-kappaB p50 and p65 in melanoma cell nuclei, with p50 being more prevalent. Electrophoretic mobility shift assay demonstrated baseline NF-kappaB activity, the findings confirmed by supershift analysis. Treatment of melanoma cells with the MEK inhibitor U0126 decreased NF-kappaB binding to its DNA recognition sequence, implicating the MAPK pathway in NF-kappaB activation. Two specific NF-kappaB inhibitors suppressed iNOS expression, demonstrating regulation of iNOS by NF-kappaB. Several experiments indicated the presence of p50 homodimers, which lack a transactivation domain and rely on the transcriptional coactivator Bcl-3 to carry out this function. Bcl-3 was detected in melanoma cells and co-immunoprecipitated with p50. These data suggest that the constitutively activated melanoma MAPK pathway stimulates activation of NF-kappaB hetero- and homodimers, which, in turn, drive iNOS expression and support melanoma tumorigenesis.

  9. Endothelial NOS-dependent activation of c-Jun NH(2)- terminal kinase by oxidized low-density lipoprotein

    NASA Technical Reports Server (NTRS)

    Go, Y. M.; Levonen, A. L.; Moellering, D.; Ramachandran, A.; Patel, R. P.; Jo, H.; Darley-Usmar, V. M.

    2001-01-01

    Oxidized low-density lipoprotein (oxLDL) is known to activate a number of signal transduction pathways in endothelial cells. Among these are the c-Jun NH(2)-terminal kinase (JNK), also known as stress-activated protein kinase, and extracellular signal-regulated kinase (ERK). These mitogen-activated protein kinases (MAP kinase) determine cell survival in response to environmental stress. Interestingly, JNK signaling involves redox-sensitive mechanisms and is activated by reactive oxygen and nitrogen species derived from both NADPH oxidases, nitric oxide synthases (NOS), peroxides, and oxidized low-density lipoprotein (oxLDL). The role of endothelial NOS (eNOS) in the activation of JNK in response to oxLDL has not been examined. Herein, we show that on exposure of endothelial cells to oxLDL, both ERK and JNK are activated through independent signal transduction pathways. A key role of eNOS activation through a phosphatidylinositol-3-kinase-dependent mechanism leading to phosphorylation of eNOS is demonstrated for oxLDL-dependent activation of JNK. Moreover, we show that activation of ERK by oxLDL is critical in protection against the cytotoxicity of oxLDL.

  10. Implications for Focusing Research in Career and Technical Education and Workforce Development

    ERIC Educational Resources Information Center

    Lambeth, Jeanea M.; Joerger, Richard M.; Elliot, Jack

    2009-01-01

    Education and educational research is shaped by philosophy, psychology, practice, and ever changing educational policies. Previous studies have expressed a need for a relevant and focused research agenda for career and technical education (CTE), workforce development education and career and technical education. A need for a relevant and timely…

  11. Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China.

    PubMed

    Cheng, Zhaohui; Tao, Hongbing; Cai, Miao; Lin, Haifeng; Lin, Xiaojun; Shu, Qin; Zhang, Ru-Ning

    2015-09-09

    Chinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors. 114 sample county hospitals were selected from Henan province, China, from 2010 to 2012. Data envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency. (1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010-2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency. There was considerable space for technical efficiency improvement in Henan county hospitals. During 2010-2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency. Published by the BMJ Publishing Group Limited. For permission to use (where

  12. Empowering Technical College Students in the Work Place.

    ERIC Educational Resources Information Center

    Lewis, Theodore; And Others

    The purpose of this report is to describe how Minnesota technical college students can be empowered through vocational education to be full participants in the labor force and to deal with the changes that they encounter in the workplace. Chapter 1 introduces the problem of keeping up with changes in the ways in which work is performed. Chapter 2…

  13. Changes in Pre-service Science Teachers' Understandings After Being Involved in Explicit Nature of Science and Socioscientific Argumentation Processes

    NASA Astrophysics Data System (ADS)

    Kutluca, A. Y.; Aydın, A.

    2017-08-01

    The study explored the changes in pre-service science teachers' understanding of the nature of science and their opinions about the nature of science, science teaching and argumentation after their participation in explicit nature of science (NOS) and socioscientific argumentation processes. The participants were 56 third-grade pre-service science teachers studying in a state university in Turkey. The treatment group comprised 27 participants, and there were 29 participants in the comparison group. The comparison group participants were involved in a student-centred science-teaching process, and the participants of the treatment group were involved in explicit NOS and socioscientific argumentation processes. In the study, which lasted a total of 11 weeks, a NOS-as-argumentation questionnaire was administered to all the participants to determine their understanding of NOS at the beginning and end of the data collection process, and six random participants of the treatment group participated in semi-structured interview questions in order to further understand their views regarding NOS, science teaching and argumentation. Qualitative and quantitative data analysis revealed that the explicit NOS and socioscientific argumentation processes had a significant effect on pre-service science teachers' NOS understandings. Furthermore, NOS, argumentation and science teaching views of the participants in the treatment group showed a positive change. The results of this study are discussed in light of the related literature, and suggestions are made within the context of contribution to science-teaching literature, improvement of education quality and education of pre-service teachers.

  14. Relationship between intraoperative non-technical performance and technical events in bariatric surgery.

    PubMed

    Fecso, A B; Kuzulugil, S S; Babaoglu, C; Bener, A B; Grantcharov, T P

    2018-03-30

    The operating theatre is a unique environment with complex team interactions, where technical and non-technical performance affect patient outcomes. The correlation between technical and non-technical performance, however, remains underinvestigated. The purpose of this study was to explore these interactions in the operating theatre. A prospective single-centre observational study was conducted at a tertiary academic medical centre. One surgeon and three fellows participated as main operators. All patients who underwent a laparoscopic Roux-en-Y gastric bypass and had the procedures captured using the Operating Room Black Box ® platform were included. Technical assessment was performed using the Objective Structured Assessment of Technical Skills and Generic Error Rating Tool instruments. For non-technical assessment, the Non-Technical Skills for Surgeons (NOTSS) and Scrub Practitioners' List of Intraoperative Non-Technical Skills (SPLINTS) tools were used. Spearman rank-order correlation and N-gram statistics were conducted. Fifty-six patients were included in the study and 90 procedural steps (gastrojejunostomy and jejunojejunostomy) were analysed. There was a moderate to strong correlation between technical adverse events (r s  = 0·417-0·687), rectifications (r s  = 0·380-0·768) and non-technical performance of the surgical and nursing teams (NOTSS and SPLINTS). N-gram statistics showed that after technical errors, events and prior rectifications, the staff surgeon and the scrub nurse exhibited the most positive non-technical behaviours, irrespective of operator (staff surgeon or fellow). This study demonstrated that technical and non-technical performances are related, on both an individual and a team level. Valuable data can be obtained around intraoperative errors, events and rectifications. © 2018 BJS Society Ltd Published by John Wiley & Sons Ltd.

  15. The influence of explicit versus implicit instructional approaches during a technology-based curriculum on students' understanding of nature of science (NOS)

    NASA Astrophysics Data System (ADS)

    Al-Saidi, Ahmed Mohammad

    The purpose of this study was to examine the effect of an explicit versus an implicit instructional approach during technology-based curriculum on students' understanding of the nature of science (NOS) within an introductory biology course. The study emphasized the inferential and tentative nature of science. The intervention or explicit group was involved in inquiry activities followed by discussions that were directly geared towards the target aspects of NOS. The implicit group was engaged in the same activities but received instruction devoid of direct reference to the NOS aspects. Students in both groups spent identical amount of time on task. Selected items of the Views of Nature of Science Questionnaire (VNOS) together with semi-structured interviews were used to evaluate students' NOS conceptions before and at the end of the intervention, which lasted two weeks. A quantitative analysis using chi-square of students' pre-intervention NOS views as provided by the VNOS questionnaires revealed that there was not a statistically significant difference between implicit and explicit groups in both targeted NOS aspects, with (p = 0.18) and (p = 0.34) for inferential and tentative NOS, respectively. However the same analysis indicated statistical significance difference for post-intervention between implicit and explicit groups, yielding (p < 0.02) and (p < 0.002) for both inferential and tentative NOS, respectively. A qualitative analysis of students' pre and post-intervention views of the target aspects of NOS as well as semi-structured interviews for both groups was also conducted. Before intervention, the number of informed NOS responses in both groups was not considerably different. However, analysis of post-intervention NOS views indicated that more students in the explicit group demonstrated informed views of the NOS aspects than in the implicit group. Therefore, the analysis of the data indicated that, in this particular study, engaging students in inquiry

  16. The Effect of Digital Publishing on Technical Services in University Libraries

    ERIC Educational Resources Information Center

    Hunter, Ben

    2013-01-01

    The past decade has brought enormous changes in scholarly communication, leading many libraries to undertake large-scale digital publishing initiatives. However, no study has investigated how technical services departments are changing to support these new services. Using change management as a theoretical framework, the investigator uses content…

  17. Characterization of Short Range DNA Looping in Endotoxin-mediated Transcription of the Murine Inducible Nitric-oxide Synthase (iNOS) Gene*

    PubMed Central

    Guo, Hongtao; Mi, Zhiyong; Kuo, Paul C.

    2008-01-01

    The local structural properties and spatial conformations of chromosomes are intimately associated with gene expression. The spatial associations of critical genomic elements in inducible nitric-oxide synthase (iNOS) transcription have not been previously examined. In this regard, the murine iNOS promoter contains 2 NF-κB binding sites (nt –86 and nt –972) that are essential for maximal transactivation of iNOS by LPS. Although AP-1 is commonly listed as an essential transcription factor for LPS-mediated iNOS transactivation, the relationship between AP-1 and NF-κB in this setting is not well studied. In this study using a model of LPS-stimulated ANA-1 murine macrophages, we demonstrate that short range DNA looping occurs at the iNOS promoter. This looping requires the presence of AP-1, c-Jun, NF-κB p65, and p300-associated acetyltransferase activity. The distal AP-1 binding site interacts via p300 with the proximal NF-κB binding site to create this DNA loop to participate in iNOS transcription. Other geographically distant AP-1 and NF-κB sites are certainly occupied, but selected sites are critical for iNOS transcription and the formation of the c-Jun, p65, and p300 transcriptional complex. In this “simplified” model of murine iNOS promoter, numerous transcription factors recognize and bind to various response elements, but these locales do not equally contribute to iNOS gene transcription. PMID:18596035

  18. Las Rocas Nos Cuentan (Rocks Tell Their Stories)

    ERIC Educational Resources Information Center

    Llerandi-Roman, Pablo A.

    2012-01-01

    Many Earth science lessons today still focus on memorizing the names of rocks and minerals. This led the author to develop a lesson that reveals the fascinating stories told by rocks through the study of their physical properties. He first designed the lesson for Puerto Rican teachers, hence its Spanish title: "Las Rocas Nos Cuentan Su Historia."…

  19. IL-10 and NOS2 Modulate Antigen-Specific Reactivity and Nerve Infiltration by T Cells in Experimental Leprosy

    PubMed Central

    Hagge, Deanna A.; Scollard, David M.; Ray, Nashone A.; Marks, Vilma T.; Deming, Angelina T.; Spencer, John S.; Adams, Linda B.

    2014-01-01

    Background Although immunopathology dictates clinical outcome in leprosy, the dynamics of early and chronic infection are poorly defined. In the tuberculoid region of the spectrum, Mycobacterium leprae growth is restricted yet a severe granulomatous lesion can occur. The evolution and maintenance of chronic inflammatory processes like those observed in the leprosy granuloma involve an ongoing network of communications via cytokines. IL-10 has immunosuppressive properties and IL-10 genetic variants have been associated with leprosy development and reactions. Methodology/Principal Findings The role of IL-10 in resistance and inflammation in leprosy was investigated using Mycobacterium leprae infection of mice deficient in IL-10 (IL-10−/−), as well as mice deficient in both inducible nitric oxide synthase (NOS2−/−) and IL-10 (10NOS2−/−). Although a lack of IL-10 did not affect M. leprae multiplication in the footpads (FP), inflammation increased from C57Bl/6 (B6)NOS2−/−<10NOS2−/−. While IL-10−/− mice exhibited modest FP induration compared to B6, NOS2−/− and 10NOS2−/− mice developed markedly enlarged FP marking distinct phases: early (1 month), peak (3–4 months), and chronic (8 months). IFN-γ-producing CD4+CD44+ cells responding to M. leprae cell wall, membrane, and cytosol antigens and ML2028 (Ag85B) were significantly increased in the evolved granuloma in NOS2−/− FP compared to B6 and IL-10−/− during early and peak phases. In 10NOS2−/− FP, CD4+CD44+ and especially CD8+CD44+ responses were augmented even further to these antigens as well as to ML0380 (GroES), ML2038 (bacterioferritin), and ML1877 (EF-Tu). Moreover, fragmented nerves containing CD4+ cells were present in 10NOS2−/− FP. Conclusions/Significance The 10NOS2−/− strain offers insight on the regulation of granuloma formation and maintenance by immune modulators in the resistant forms of leprosy and presents a new model for investigating the

  20. 36. ISLAND PLANT: Nos. 1 AND 2 TWENTYSIX INCH HORIZONTAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    36. ISLAND PLANT: Nos. 1 AND 2 TWENTY-SIX INCH HORIZONTAL SAMSON TURBINES - American Falls Water, Power & Light Company, Island Power Plant, Snake River, below American Falls Dam, American Falls, Power County, ID

  1. Antioxidative effects of cinnamomi cortex: A potential role of iNOS and COX-II

    PubMed Central

    Chung, Jin-Won; Kim, Jeong-Jun; Kim, Sung-Jin

    2011-01-01

    Background: Cinnamomi cortex has wide varieties of pharmacological actions such as anti-inflammatory action, anti-platelet aggregation, and improving blood circulation. In this study, we tested to determine whether the Cinnamomi cortex extract has antioxidant activities. Materials and Methods: Antioxidative actions were explored by measuring free radical scavenging activity, NO levels, and reducing power. The mechanism of antioxidative action of Cinnamomi cortex was determined by measuring iNOS and COX-II expression in lipopolysaccharide (LPS) stimulated Raw cells. Results: Seventy percent methanolic extract of Cinnamomi cortex exerted significant 1,1-diphenyl--2--picrylhydrazyl (DPPH) free radicals and NO scavenging activities in a dose-dependent manner. More strikingly, the Cinnamomi cortex extract exerted dramatic reducing power activity (13-fold over control). Production of iNOS induced by LPS was significantly inhibited by the Cinnamomi cortex extract, suggesting that it inhibits NO production by suppressing iNOS expression. Additionally, COX-2 induced by LPS was dramatically inhibited by the Cinnamomi cortex extract. Conclusion: These results suggest that 70% methanolic extract of Cinnamomi cortex exerts significant antioxidant activity via inhibiting iNOS and COX-II induction. PMID:22262934

  2. iNOS-Derived Nitric Oxide Stimulates Osteoclast Activity and Alveolar Bone Loss in Ligature-Induced Periodontitis in Rats

    PubMed Central

    Herrera, Bruno S.; Martins-Porto, Rodrigo; Maia-Dantas, Aline; Campi, Paula; Spolidorio, Luis C.; Costa, Soraia K.P.; Van Dyke, Thomas E.; Gyurko, Robert; Muscara, Marcelo N.

    2012-01-01

    Background Inflammatory stimuli activate inducible nitric oxide synthase (iNOS) in a variety of cell types, including osteoclasts (OC) and osteoblasts, resulting in sustained NO production. In this study, we evaluate the alveolar bone loss in rats with periodontitis under long-term iNOS inhibition, and the differentiation and activity of OC from iNOS-knockout (KO) mice in vitro. Methods Oral aminoguanidine (an iNOS inhibitor) or water treatment was started 2 weeks before induction of periodontitis. Rats were sacrificed 3, 7, or 14 days after ligature placement, and alveolar bone loss was evaluated. In vitro OC culture experiments were also performed to study the differentiation of freshly isolated bone marrow cells from both iNOS KO and wild-type C57BL/6 mice. OC were counted 6 days later after tartrate-resistant acid phosphatase staining (a marker of osteoclast identity), and bone resorption activity was assessed by counting the number of resorption pits on dentin disks. Results Rats with ligature showed progressive and significant alveolar bone loss compared to sham animals, and aminoguanidine treatment significantly inhibited ligature-induced bone loss at 7 and 14 days after the induction. In comparison to bone marrow cells from wild-type mice, cells from iNOS KO mice showed decreased OC growth and the resulting OC covered a smaller culture dish area and generated fewer resorption pit counts. Conclusion Our results demonstrate that iNOS inhibition prevents alveolar bone loss in a rat model of ligature-induced periodontitis, thus confirming that iNOS-derived NO plays a crucial role in the pathogenesis of periodontitis, probably by stimulating OC differentiation and activity. PMID:21417589

  3. Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added (18)F-Labelling Methods.

    PubMed

    Drerup, Christian; Ermert, Johannes; Coenen, Heinz H

    2016-09-01

    Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and (18)F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be (18)F-labelled in no-carrier-added (n.c.a.) form. For preparation of the (18)F-labelled nNOS-Inhibitor [(18)F]10 a "build-up" radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [(18)F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified "late-stage" (18)F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. (18)F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [(18)F]10 as probe for preclinical in vivo studies.

  4. Prodigiosin inhibits gp91{sup phox} and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia-ischemia

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

    Chang, Chia-Che; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Agricultural Biotechnology Center, National Chung-Hsing University, Taichung, Taiwan

    2011-11-15

    This study aimed to explore the mechanisms by which prodigiosin protects against hypoxia-induced oxidative/nitrosative brain injury induced by middle cerebral artery occlusion/reperfusion (MCAo/r) injury in mice. Hypoxia in vitro was modeled using oxygen-glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone MCAo/r injury with prodigiosin (10 and 100 {mu}g/kg, i.v.) at 1 h after hypoxia ameliorated MCAo/r-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. MCAo/r induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significantmore » increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (gp91{sup phox}), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b leukocytes due to breakdown of blood-brain barrier (BBB) by activation of nuclear factor-kappa B (NF-{kappa}B). All these changes were significantly diminished by prodigiosin. In BV-2 cells, OGD induced ROS and nitric oxide production by up-regulating gp91{sup phox} and iNOS via activation of the NF-{kappa}B pathway, and these changes were suppressed by prodigiosin. In conclusion, our results indicate that prodigiosin reduces gp91{sup phox} and iNOS expression possibly by impairing NF-{kappa}B activation. This compromises the activation of microglial and/or inflammatory cells, which then, in turn, mediates prodigiosin's protective effect in the MCAo/r mice. -- Highlights: Black-Right-Pointing-Pointer Prodigiosin ameliorated brain infarction and deficits. Black-Right-Pointing-Pointer Prodigiosin protected against hypoxia/reperfusion-induced brain injury. Black-Right-Pointing-Pointer Prodigiosin diminished oxidative/nitrosativestress and leukocytes infiltration. Black-Right-Pointing-Pointer Prodigiosin reduced BBB breakdown. Black

  5. Oxidative damage mediated iNOS and UCP-2 upregulation in rat brain after sub-acute cyanide exposure: dose and time-dependent effects.

    PubMed

    Bhattacharya, Rahul; Singh, Poonam; John, Jebin Jacob; Gujar, Niranjan L

    2018-04-03

    Cyanide-induced chemical hypoxia is responsible for pronounced oxidative damage in the central nervous system. The disruption of mitochondrial oxidative metabolism has been associated with upregulation of uncoupling proteins (UCPs). The present study addresses the dose- and time-dependent effect of sub-acute cyanide exposure on various non-enzymatic and enzymatic oxidative stress markers and their correlation with inducible-nitric oxide synthase (iNOS) and uncoupling protein-2 (UCP-2) expression. Animals received (oral) triple distilled water (vehicle control), 0.25 LD50 potassium cyanide (KCN) or 0.50 LD50 KCN daily for 21 d. Animals were sacrificed on 7, 14 and 21 d post-exposure to measure serum cyanide and nitrite, and brain malondialdehyde (MDA), reduced glutathione (GSH), glutathione disulfide (GSSG), cytochrome c oxidase (CCO), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CA) levels, together with iNOS and UCP-2 expression, and DNA damage. The study revealed that a dose- and time-dependent increase in cyanide concentration was accompanied by corresponding CCO inhibition and elevated MDA levels. Decrease in GSH levels was not followed by reciprocal change in GSSG levels. Diminution of SOD, GPx, GR and CA activity was congruent with elevated nitrite levels and upregulation of iNOS and UCP-2 expression, without any DNA damage. It was concluded that long-term cyanide exposure caused oxidative stress, accompanied by upregulation of iNOS. The upregulation of UCP-2 further sensitized the cells to cyanide and accentuated the oxidative stress, which was independent of DNA damage.

  6. (−)-Epicatechin induces calcium and translocation independent eNOS activation in arterial endothelial cells

    PubMed Central

    Ramirez-Sanchez, Israel; Maya, Lisandro; Ceballos, Guillermo

    2011-01-01

    The consumption of cacao-derived (i.e., cocoa) products provides beneficial cardiovascular effects in healthy subjects as well as individuals with endothelial dysfunction such as smokers, diabetics, and postmenopausal women. The vascular actions of cocoa are related to enhanced nitric oxide (NO) production. These actions can be reproduced by the administration of the cacao flavanol (−)-epicatechin (EPI). To further understand the mechanisms behind the vascular action of EPI, we investigated the effects of Ca2+ depletion on endothelial nitric oxide (NO) synthase (eNOS) activation/phosphorylation and translocation. Human coronary artery endothelial cells were treated with EPI or with bradykinin (BK), a well-known Ca2+-dependent eNOS activator. Results demonstrate that both EPI and BK induce increases in intracellular calcium and NO levels. However, under Ca2+-free conditions, EPI (but not BK) is still capable of inducing NO production through eNOS phosphorylation at serine 615, 633, and 1177. Interestingly, EPI-induced translocation of eNOS from the plasmalemma was abolished upon Ca2+ depletion. Thus, under Ca2+-free conditions, EPI can stimulate NO synthesis independent of calmodulin binding to eNOS and of its translocation into the cytoplasm. We also examined the effect of EPI on the NO/cGMP/vasodilator-stimulated phosphoprotein (VASP) pathway activation in isolated Ca2+-deprived canine mesenteric arteries. Results demonstrate that under these conditions, EPI induces the activation of this vasorelaxation-related pathway and that this effect is inhibited by pretreatment with nitro-l-arginine methyl ester, suggesting a functional relevance for this phenomenon. PMID:21209365

  7. Surgeons' and trainees' perceived self-efficacy in operating theatre non-technical skills.

    PubMed

    Pena, G; Altree, M; Field, J; Thomas, M J W; Hewett, P; Babidge, W; Maddern, G J

    2015-05-01

    An important factor that may influence an individual's performance is self-efficacy, a personal judgement of capability to perform a particular task successfully. This prospective study explored newly qualified surgeons' and surgical trainees' self-efficacy in non-technical skills compared with their non-technical skills performance in simulated scenarios. Participants undertook surgical scenarios challenging non-technical skills in two simulation sessions 6 weeks apart. Some participants attended a non-technical skills workshop between sessions. Participants completed pretraining and post-training surveys about their perceived self-efficacy in non-technical skills, which were analysed and compared with their performance in surgical scenarios in two simulation sessions. Change in performance between sessions was compared with any change in participants' perceived self-efficacy. There were 40 participants in all, 17 of whom attended the non-technical skills workshop. There was no significant difference in participants' self-efficacy regarding non-technical skills from the pretraining to the post-training survey. However, there was a tendency for participants with the highest reported self-efficacy to adjust their score downwards after training and for participants with the lowest self-efficacy to adjust their score upwards. Although there was significant improvement in non-technical skills performance from the first to second simulation sessions, a correlation between participants' self-efficacy and performance in scenarios in any of the comparisons was not found. The results suggest that new surgeons and surgical trainees have poor insight into their non-technical skills. Although it was not possible to correlate participants' self-belief in their abilities directly with their performance in a simulation, in general they became more critical in appraisal of their abilities as a result of the intervention. © 2015 BJS Society Ltd Published by John Wiley & Sons Ltd.

  8. Changing Preservice Science Teachers' Views of Nature of Science: Why Some Conceptions May be More Easily Altered than Others

    NASA Astrophysics Data System (ADS)

    Mesci, Gunkut; Schwartz, Renee'S.

    2017-04-01

    The purpose of this study was to assess preservice teachers' views of Nature of Science (NOS), identify aspects that were challenging for conceptual change, and explore reasons why. This study particularly focused on why and how some concepts of NOS may be more easily altered than others. Fourteen preservice science teachers enrolled in a NOS and Science Inquiry course participated in this study. Data were collected by using a pre/post format with the Views of Nature of Science questionnaire (VNOS-270), the Views of Scientific Inquiry questionnaire (VOSI-270), follow-up interviews, and classroom artifacts. The results indicated that most students initially held naïve views about certain aspects of NOS like tentativeness and subjectivity. By the end of the semester, almost all students dramatically improved their understanding about almost all aspects of NOS. However, several students still struggled with certain aspects like the differences between scientific theory and law, tentativeness, and socio-cultural embeddedness. Results suggested that instructional, motivational, and socio-cultural factors may influence if and how students changed their views about targeted NOS aspects. Students thought that classroom activities, discussions, and readings were most helpful to improve their views about NOS. The findings from the research have the potential to translate as practical advice for teachers, science educators, and future researchers.

  9. Substrate-Tuned Catalysis of the Radical S-Adenosyl-L-Methionine Enzyme NosL Involved in Nosiheptide Biosynthesis.

    PubMed

    Ji, Xinjian; Li, Yongzhen; Ding, Wei; Zhang, Qi

    2015-07-27

    NosL is a radical S-adenosyl-L-methionine (SAM) enzyme that converts L-Trp to 3-methyl-2-indolic acid, a key intermediate in the biosynthesis of a thiopeptide antibiotic nosiheptide. In this work we investigated NosL catalysis by using a series of Trp analogues as the molecular probes. Using a benzofuran substrate 2-amino-3-(benzofuran-3-yl)propanoic acid (ABPA), we clearly demonstrated that the 5'-deoxyadenosyl (dAdo) radical-mediated hydrogen abstraction in NosL catalysis is not from the indole nitrogen but likely from the amino group of L-Trp. Unexpectedly, the major product of ABPA is a decarboxylated compound, indicating that NosL was transformed to a novel decarboxylase by an unnatural substrate. Furthermore, we showed that, for the first time to our knowledge, the dAdo radical-mediated hydrogen abstraction can occur from an alcohol hydroxy group. Our study demonstrates the intriguing promiscuity of NosL catalysis and highlights the potential of engineering radical SAM enzymes for novel activities. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. 5. POWERHOUSE, PELTONFRANCIS TURBINES (GENERATORS) UNITS NOS. 1 AND 2 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    5. POWERHOUSE, PELTON-FRANCIS TURBINES (GENERATORS) UNITS NOS. 1 AND 2 WITH REGULATOR PANEL AT LEFT AND GATE VALVE IN CENTER FOREGROUND - Yosemite Hydroelectric Power Plant, Highways 120 & 140, Yosemite Village, Mariposa County, CA

  11. 76 FR 4391 - Calvert Cliffs Nuclear Power Plant, LLC, Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-25

    ... Nuclear Power Plant, LLC, Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2; Exemption 1.0 Background Calvert Cliffs Nuclear Power Plant, LLC, the licensee, is the holder of Facility Operating License Nos. DPR-53 and DPR-69 which authorizes operation of the Calvert Cliffs Nuclear Power Plant, Unit Nos. 1...

  12. Effects of Particulate Matter on Genomic DNA Methylation Content and iNOS Promoter Methylation

    PubMed Central

    Tarantini, Letizia; Bonzini, Matteo; Apostoli, Pietro; Pegoraro, Valeria; Bollati, Valentina; Marinelli, Barbara; Cantone, Laura; Rizzo, Giovanna; Hou, Lifang; Schwartz, Joel; Bertazzi, Pier Alberto; Baccarelli, Andrea

    2009-01-01

    Background Altered patterns of gene expression mediate the effects of particulate matter (PM) on human health, but mechanisms through which PM modifies gene expression are largely undetermined. Objectives We aimed at identifying short- and long-term effects of PM exposure on DNA methylation, a major genomic mechanism of gene expression control, in workers in an electric furnace steel plant with well-characterized exposure to PM with aerodynamic diameters < 10 μm (PM10). Methods We measured global genomic DNA methylation content estimated in Alu and long interspersed nuclear element-1 (LINE-1) repeated elements, and promoter DNA methylation of iNOS (inducible nitric oxide synthase), a gene suppressed by DNA methylation and induced by PM exposure in blood leukocytes. Quantitative DNA methylation analysis was performed through bisulfite PCR pyrosequencing on blood DNA obtained from 63 workers on the first day of a work week (baseline, after 2 days off work) and after 3 days of work (postexposure). Individual PM10 exposure was between 73.4 and 1,220 μg/m3. Results Global methylation content estimated in Alu and LINE-1 repeated elements did not show changes in postexposure measures compared with baseline. PM10 exposure levels were negatively associated with methylation in both Alu [β = −0.19 %5-methylcytosine (%5mC); p = 0.04] and LINE-1 [β = −0.34 %5mC; p = 0.04], likely reflecting long-term PM10 effects. iNOS promoter DNA methylation was significantly lower in postexposure blood samples compared with baseline (difference = −0.61 %5mC; p = 0.02). Conclusions We observed changes in global and gene specific methylation that should be further characterized in future investigations on the effects of PM. PMID:19270791

  13. β-Adrenergic induced SR Ca2+ leak is mediated by an Epac-NOS pathway.

    PubMed

    Pereira, Laëtitia; Bare, Dan J; Galice, Samuel; Shannon, Thomas R; Bers, Donald M

    2017-07-01

    Cardiac β-adrenergic receptors (β-AR) and Ca 2+ -Calmodulin dependent protein kinase (CaMKII) regulate both physiological and pathophysiological Ca 2+ signaling. Elevated diastolic Ca 2+ leak from the sarcoplasmic reticulum (SR) contributes to contractile dysfunction in heart failure and to arrhythmogenesis. β-AR activation is known to increase SR Ca 2+ leak via CaMKII-dependent phosphorylation of the ryanodine receptor. Two independent and reportedly parallel pathways have been implicated in this β-AR-CaMKII cascade, one involving exchange protein directly activated by cAMP (Epac2) and another involving nitric oxide synthase 1 (NOS1). Here we tested whether Epac and NOS function in a single series pathway to increase β-AR induced and CaMKII-dependent SR Ca 2+ leak. Leak was measured as both Ca 2+ spark frequency and tetracaine-induced shifts in SR Ca 2+ , in mouse and rabbit ventricular myocytes. Direct Epac activation by 8-CPT (8-(4-chlorophenylthio)-2'-O-methyl-cAMP) mimicked β-AR-induced SR Ca 2+ leak, and both were blocked by NOS inhibition. The same was true for myocyte CaMKII activation (assessed via a FRET-based reporter) and ryanodine receptor phosphorylation. Inhibitor and phosphorylation studies also implicated phosphoinositide 3-kinase (PI3K) and protein kinase B (Akt) downstream of Epac and above NOS activation in this pathway. We conclude that these two independently characterized parallel pathways function mainly via a single series arrangement (β-AR-cAMP-Epac-PI3K-Akt-NOS1-CaMKII) to mediate increased SR Ca 2+ leak. Thus, for β-AR activation the cAMP-PKA branch effects inotropy and lusitropy (by effects on Ca 2+ current and SR Ca 2+ -ATPase), this cAMP-Epac-NOS pathway increases pathological diastolic SR Ca 2+ leak. This pathway distinction may allow novel SR Ca 2+ leak therapeutic targeting in treatment of arrhythmias in heart failure that spare the inotropic and lusitropic effects of the PKA branch. Copyright © 2017 Elsevier Ltd. All

  14. 75 FR 23820 - Notice of Docketing of Amendment Request for Materials License No. SNM-2506; Northern States...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-04

    ... INFORMATION CONTACT: Pamela Longmire, Ph.D., Project Manager, Licensing Branch, Division of Spent Fuel Storage... Generating Plant (PINGP), Unit Nos. 1 and 2, site in Goodhue County, Minnesota. The TN-40 cask is currently..., higher burnup spent fuel used in the PINGP reactor as well as associated changes to the ISFSI's technical...

  15. Chronic Aerobic Exercise Associated to Dietary Modification Improve Endothelial Function and eNOS Expression in High Fat Fed Hamsters

    PubMed Central

    Boa, Beatriz C. S.; Souza, Maria das Graças C.; Leite, Richard D.; da Silva, Simone V.; Barja-Fidalgo, Thereza Christina; Kraemer-Aguiar, Luiz Guilherme; Bouskela, Eliete

    2014-01-01

    Obesity is epidemic in the western world and central adipose tissue deposition points to increased cardiovascular morbidity and mortality, independently of any association between obesity and other cardiovascular risk factors. Physical exercise has been used as non-pharmacological treatment to significantly reverse/attenuate obesity comorbidities. In this study we have investigated effects of exercise and/or dietary modification on microcirculatory function, body composition, serum glucose, iNOS and eNOS expression on 120 male hamsters treated for 12 weeks with high fat chow (HF, n = 30) starting on the 21st day of birth. From week 12 to 20, animals were randomly separated in HF (no treatment change), return to standard chow (HFSC, n = 30), high fat chow associated to an aerobic exercise training program (AET) (HFEX, n = 30) and return to standard chow+AET (HFSCEX, n = 30). Microvascular reactivity in response to acetylcholine and sodium nitroprusside and macromolecular permeability increase induced by 30 minutes ischemia followed by reperfusion were assessed on the cheek pouch preparation. Total body fat and aorta eNOS and iNOS expression by immunoblotting assay were evaluated on the experimental day. Compared to HFSC and HFSCEX groups, HF and HFEX ones presented increased visceral fat [(mean±SEM) (HF)4.9±1.5 g and (HFEX)4.7±0.9 g vs. (HFSC)*3.0±0.7 g and (HFSCEX)*1.9±0.4 g/100 g BW]; impaired endothelial-dependent vasodilatation [Ach 10−8 M (HF)87.9±2.7%; (HFSC)*116.7±5.9%; (HFEX)*109.1±4.6%; (HFSCEX)*105±2.8%; Ach10−6 M (HF)95.3±3.1%; (HFSC)*126±6.2%; (HFEX)*122.5±2.8%; (HFSCEX)*118.1±4.3% and Ach10−4 M (HF)109.5±4.8%; (HFSC)*149.6±6.6%; (HFEX)*143.5±5.4% and (HFSCEX)*139.4±5.2%], macromolecular permeability increase after ischemia/reperfusion [(HF)40.5±4.2; (HFSC)*19.0±1.6; (HFEX)*18.6±2.1 and (HFSCEX)* 21.5±3.7 leaks/cm2), decreased eNOS expression, increased leptin and glycaemic levels. Endothelial

  16. Final Technical Report

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

    Sobecky, Patricia A; Taillefert, Martial

    This final technical report describes results and findings from a research project to examine the role of microbial phosphohydrolase enzymes in naturally occurring subsurface microorganisms for the purpose of promoting the immobilization of the radionuclide uranium through the production of insoluble uranium phosphate minerals. The research project investigated the microbial mechanisms and the physical and chemical processes promoting uranium biomineralization and sequestration in oxygenated subsurface soils. Uranium biomineralization under aerobic conditions can provide a secondary biobarrier strategy to immobilize radionuclides should the metal precipitates formed by microbial dissimilatory mechanisms remobilize due to a change in redox state.

  17. Vault Area (original section), east corridor, looking north (Vault Nos. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Vault Area (original section), east corridor, looking north (Vault Nos. 1-9 - Fort McNair, Film Store House, Fort Lesley J. McNair, P Street between Third & Fourth Streets, Southwest, Washington, District of Columbia, DC

  18. Post-translational modifications of eNOS augment nitric oxide availability and facilitates hypoxia adaptation in Ladakhi women.

    PubMed

    Pooja; Ghosh, Dishari; Bhargava, Kalpana; Sethy, Niroj Kumar

    2018-06-09

    The lower inhaled oxygen per volume at high altitude poses an intimidating challenge for humans to survive and reproduce. Indigenous populations of the Himalayas reportedly exhibit higher microcirculatory blood flow accompanied by higher orders of magnitude of nitric oxide (NO) products in lung, plasma and red blood cells as a vascular adaptation strategy for hypobaric hypoxia. The precise mechanism of such observed higher NO metabolites for hypoxia adaptation remains elusive. Studying high altitude native Ladakhi women, we observed significant higher eNOS mRNA and protein in blood/plasma as compared to lowland women. We also observed higher level of plasma l-citrulline and NOx (nitrates and nitrites) with concomitant lower levels of arginase mRNA and protein further suggesting higher eNOS activity and NO bioavailability. Interestingly, middle aged postmenopausal Ladakhi women exhibited significantly higher level of eNOS activity, NOx and cGMP as compared to age matched lowland women. Preferential phosphorylation of eNOS on stimulatory Ser1177 and Ser615 as well as dephosphorylation of inhibitory Thr495 site contributed to higher NO availability in Ladakhi women irrespective of age. We also observed higher levels of eNOS activating humoral factors like bradykinin and estrogen in both young and middle-aged Ladakhi women. These results suggest that an altered phosphorylation status, together with an enhanced expression of eNOS and potential humoral endothelial activators, are involved in enhanced activation of the eNOS-NO-cGMP pathway in Ladakhi women irrespective of age, reinforcing the hypothesis that NO metabolites play a major role in Himalayan pattern of hypoxia adaptation. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. A non-synonymous SNP in the NOS2 associated with septic shock in patients with sepsis in Chinese populations.

    PubMed

    Wang, Zhifu; Feng, Kai; Yue, Maoxing; Lu, Xiaoguang; Zheng, Qihan; Zhang, Hongxing; Zhai, Yun; Li, Peiyao; Yu, Lixia; Cai, Mi; Zhang, Xiumei; Kang, Xin; Shi, Weihai; Xia, Xia; Chen, Xi; Cao, Pengbo; Li, Yuanfeng; Chen, Huipeng; Ling, Yan; Li, Yuxia; He, Fuchu; Zhou, Gangqiao

    2013-03-01

    Sepsis represents a systemic inflammatory response to infection and its sequelae include severe sepsis, septic shock, multiple organ dysfunction syndrome (MODS) and death. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS, NOS2) plays an important role in the development of sepsis and its sequelae. It was reported that several single nucleotide polymorphisms (SNPs) within NOS2 could influence the production or activity of NOS2. In this study, we assessed whether SNPs within NOS2 gene were associated with severity of sepsis in Chinese populations. A case-control study was conducted, which included 299 and 280 unrelated patients with sepsis recruited from Liaoning and Jiangsu provinces in China, respectively. Six SNPs within NOS2 were genotyped using Sequenom MassARRAY system. The associations between the SNPs and risk of sepsis complications were estimated by a binary logistic regression model adjusted for confounding factors. Functional assay was performed to assess the biological significance. The GA + AA genotype of a non-synonymous SNP in the exon 16 of NOS2 (rs2297518: G>A) was significantly associated with increased susceptibility to septic shock compared with GG genotype in Liaoning population (OR = 3.29, 95% CI = 1.40-7.72, P = 0.0047). This association was confirmed in the Jiangsu population (OR = 3.49, 95% CI = 1.57-7.79, P = 0.0019). Furthermore, the functional assay performed in the immortalized lymphocyte cell lines indicated that the at-risk GA genotype had a tendency of higher NOS2 activity than the GG genotype (P = 0.32). Our findings suggest that the NOS2 rs2297518 may play a role in mediating the susceptibility to septic shock in patients with sepsis in Chinese populations.

  20. [Effects of electroacupuncture on hippocampal nNOS expression in rats of post-traumatic stress disorder model].

    PubMed

    Hou, Liang-Qin; Liu, Song; Xiong, Ke-Ren

    2013-07-01

    To explore the mechanism of electroacupuncture (EA) in the treatment of post-traumatic stress disorder (PTSD). Thirty male Sprague-Dawley rats were randomly divided into a normal group, a model group and an electroacupuncture group. The single prolonged stress (SPS) method was used to set up the PTSD models in latter two groups. After SPS Stimulation, EA group was treated with 2Hz electroacupuncture at Baihui (GV 20) and Zusanli (ST 36) for 30 min, once a day for a week. Reverse transcriptase polymerase chain reaction (RT-PCR) and immuno-histochemistry were used to detect the mRNA and protein expression of nNOS in the hippocampus of rats in the each group. (1) The nNOS mRNA expression in hippocampus in model group was higher than that in normal group (P < 0.05). But the expression in EA group was lower significantly than that in model group (P < 0.05). (2) The nNOS protein expression in hippocampus CA1 and CA3 in model group was higher than that in normal group (P < 0.05). But after electroacupuncture treatment, its expression in EA group was lower significantly than that in model group (P < 0.05). The nNOS protein expression in hippocampal CA2 had no difference among all three groups. The elevated nNOS expression in hippocampus may be involved in the pathological process of PTSD. Electroacupuncture play a down-regulation effects in the hippocampal nNOS expression, which may be one mechanism of electroacupuncture for treatment of PTSD.

  1. Effect of aminoguanidine and albendazole on inducible nitric oxide synthase (iNOS) activity in T. spiralis-infected mice muscles.

    PubMed

    Zeromski, Jan; Boczoń, Krystyna; Wandurska-Nowak, Elzbieta; Mozer-Lisewska, Iwona

    2005-01-01

    The aim of this study was to provide evidence for the expression of iNOS in the cells of inflammatory infiltrates around larvae in skeletal muscles of T. spiralis infected mice. The BALB/c mice (n = 8) divided into subgroups, received either aminoguanidine (AMG)--a specific iNOS inhibitor or albendazole (ALB)--an antiparasitic drug of choice in trichinellosis treatment. Control animals (n = 2 in each subgroup) were either uninfected and treated or uninfected and untreated. Frozen sections of hind leg muscles from mice sacrificed at various time intervals after infection were cut and subjected to immunohistochemistry, using monoclonal anti-iNOS antibody. The ALB-treated mice revealed stronger iNOS staining in the infiltrating cells around larvae than the infected and untreated animals. On the contrary, in the AMG-treated animals, the infiltrating cells did not show any specific iNOS reaction. These data confirm the specificity of iNOS staining in the cellular infiltrates around T. spiralis larvae and shed some light on the role of nitric oxide during ALB treatment in experimental trichinellosis.

  2. Improving Secondary Career and Technical Education through Professional Development: Alternative Certification and Use of Technical Assessment Data

    ERIC Educational Resources Information Center

    National Research Center for Career and Technical Education, 2011

    2011-01-01

    Secondary career and technical education (CTE) is a field in transition. It is moving from a primary focus on preparing students for entry-level employment to preparing them for continuing education and training as well as employment. The rapid pace of change in technology and the global economy has created a demand for workers who are able to…

  3. 76 FR 64083 - Reliability Technical Conference; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-17

    ... Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory Commission will hold a Technical Conference on Tuesday, November 29, 2011, from 1 p.m. to 5 p.m. and... System. The conference will explore the progress made on the priorities for addressing risks to...

  4. A vast amount of various invariant tori in the Nosé-Hoover oscillator.

    PubMed

    Wang, Lei; Yang, Xiao-Song

    2015-12-01

    This letter restudies the Nosé-Hoover oscillator. Some new averagely conservative regions are found, each of which is filled with different sequences of nested tori with various knot types. Especially, the dynamical behaviors near the border of "chaotic region" and conservative regions are studied showing that there exist more complicated and thinner invariant tori around the boundaries of conservative regions bounded by tori. Our results suggest an infinite number of island chains in a "chaotic sea" for the Nosé-Hoover oscillator.

  5. A vast amount of various invariant tori in the Nosé-Hoover oscillator

    NASA Astrophysics Data System (ADS)

    Wang, Lei; Yang, Xiao-Song

    2015-12-01

    This letter restudies the Nosé-Hoover oscillator. Some new averagely conservative regions are found, each of which is filled with different sequences of nested tori with various knot types. Especially, the dynamical behaviors near the border of "chaotic region" and conservative regions are studied showing that there exist more complicated and thinner invariant tori around the boundaries of conservative regions bounded by tori. Our results suggest an infinite number of island chains in a "chaotic sea" for the Nosé-Hoover oscillator.

  6. Technical interventions to increase adenoma detection rate in colonoscopy.

    PubMed

    Rondonotti, Emanuele; Andrealli, Alida; Amato, Arnaldo; Paggi, Silvia; Conti, Clara Benedetta; Spinzi, Giancarlo; Radaelli, Franco

    2016-12-01

    Adenoma detection rate (ADR) is the most robust colonoscopy quality metric and clinical studies have adopted it as the ideal method to assess the impact of technical interventions. Areas covered: We reviewed papers focusing on the impact of colonoscopy technical issues on ADR, including withdrawal time and technique, second evaluation of the right colon, patient positional changes, gastrointestinal assistant participation during colonoscopy, water-aided technique, optimization of bowel preparation and antispasmodic administration. Expert commentary: Overall, technical interventions are inexpensive, available worldwide and easy to implement. Some of them, such as the adoption of split dose regimen and slow scope withdrawal to allow a careful inspection, have been demonstrated to significantly improve ADR. Emerging data support the use of water-exchange colonoscopy. According to published studies, other technical interventions seem to provide only marginal benefit to ADR. Unfortunately, the available evidence has methodological limitations, such as small sample sizes, the inclusion of expert endoscopists only and the evaluation of single technical interventions. Additionally, larger studies are needed to clarify whether these interventions might have a higher benefit on low adenoma detectors and whether the implementation of a bundle of them, instead of a single technical maneuver, might have a greater impact on ADR.

  7. 10. VIEW OF GENERATING ROOM, POWERHOUSE, SHOWING ORIGINAL GENERATORS NOS. ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. VIEW OF GENERATING ROOM, POWERHOUSE, SHOWING ORIGINAL GENERATORS NOS. 1 THROUGH 4, WITH NO. 4 GENERATOR IN FOREGROUND - Nine Mile Hydroelectric Development, Powerhouse, State Highway 291 along Spokane River, Nine Mile Falls, Spokane County, WA

  8. 37. ISLAND PLANT: Nos. 1 AND 2 TWENTYSIX INCH SPECIAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    37. ISLAND PLANT: Nos. 1 AND 2 TWENTY-SIX INCH SPECIAL HORIZONTAL SAMSON TURBINE (RIVITED CASE) - American Falls Water, Power & Light Company, Island Power Plant, Snake River, below American Falls Dam, American Falls, Power County, ID

  9. [Change management: An analysis of actors; perceptions about technical assistance in the Democratic Republic of Congo].

    PubMed

    Ribesse, Nathalie; Iyeti, Alain; Macq, Jean

    2015-01-01

    Technical assistance (TA) is a common component of health system strengthening interventions. This type of intervention is too often designed and evaluated according to a logic that fails to take into account social complexity. Actors' perceptions are one element of this complexity. This article presents a study conducted in the Democratic Republic of Congo designed to identify perceptions concerning two types of technical support providers for health system strengthening: long-term technical assistants (agents of development agencies) and provincial technical advisors (agents of the Ministry of Health). Interviews were conducted with an innovative tool inspired by the principles of systems thinking. Interviewees were actors involved in a TA intervention in the province of Bandundu. Their expectations regarding TA providers were identified in terms of personal characteristics (knowledge, know-how and interpersonal skills), roles, and styles of interaction for capacity building ("interventionist/ prescriptive axes"). Interviewees emphasized the importance of mutual learning and the quality of interactions, which depends on TA provider's interpersonal skills and mutual willingness. Perceptions of TA provider's characteristics tend to be similar, but several differences were observed concerning the expectations about the roles of TAs, and the style that should be adopted for capacity building. Ignoring these differences in expectations may be a threat to the effectiveness of TA.

  10. miR-708-5p and miR-34c-5p are involved in nNOS regulation in dystrophic context.

    PubMed

    Guilbaud, Marine; Gentil, Christel; Peccate, Cécile; Gargaun, Elena; Holtzmann, Isabelle; Gruszczynski, Carole; Falcone, Sestina; Mamchaoui, Kamel; Ben Yaou, Rabah; Leturcq, France; Jeanson-Leh, Laurence; Piétri-Rouxel, France

    2018-04-27

    Duchenne (DMD) and Becker (BMD) muscular dystrophies are caused by mutations in the DMD gene coding for dystrophin, a protein being part of a large sarcolemmal protein scaffold that includes the neuronal nitric oxide synthase (nNOS). The nNOS was shown to play critical roles in a variety of muscle functions and alterations of its expression and location in dystrophic muscle fiber leads to an increase of the muscle fatigability. We previously revealed a decrease of nNOS expression in BMD patients all presenting a deletion of exons 45 to 55 in the DMD gene (BMDd45-55), impacting the nNOS binding site of dystrophin. Since several studies showed deregulation of microRNAs (miRNAs) in dystrophinopathies, we focused on miRNAs that could target nNOS in dystrophic context. By a screening of 617 miRNAs in BMDd45-55 muscular biopsies using TLDA and an in silico study to determine which one could target nNOS, we selected four miRNAs. In order to select those that targeted a sequence of 3'UTR of NOS1, we performed luciferase gene reporter assay in HEK393T cells. Finally, expression of candidate miRNAs was modulated in control and DMD human myoblasts (DMDd45-52) to study their ability to target nNOS. TLDA assay and the in silico study allowed us to select four miRNAs overexpressed in muscle biopsies of BMDd45-55 compared to controls. Among them, only the overexpression of miR-31, miR-708, and miR-34c led to a decrease of luciferase activity in an NOS1-3'UTR-luciferase assay, confirming their interaction with the NOS1-3'UTR. The effect of these three miRNAs was investigated on control and DMDd45-52 myoblasts. First, we showed a decrease of nNOS expression when miR-708 or miR-34c were overexpressed in control myoblasts. We then confirmed that DMDd45-52 cells displayed an endogenous increased of miR-31, miR-708, and miR-34c and a decreased of nNOS expression, the same characteristics observed in BMDd45-55 biopsies. In DMDd45-52 cells, we demonstrated that the inhibition of miR-708

  11. Near infrared radiation protects against oxygen-glucose deprivation-induced neurotoxicity by down-regulating neuronal nitric oxide synthase (nNOS) activity in vitro.

    PubMed

    Yu, Zhanyang; Li, Zhaoyu; Liu, Ning; Jizhang, Yunneng; McCarthy, Thomas J; Tedford, Clark E; Lo, Eng H; Wang, Xiaoying

    2015-06-01

    Near infrared radiation (NIR) has been shown to be neuroprotective against neurological diseases including stroke and brain trauma, but the underlying mechanisms remain poorly understood. In the current study we aimed to investigate the hypothesis that NIR may protect neurons by attenuating oxygen-glucose deprivation (OGD)-induced nitric oxide (NO) production and modulating cell survival/death signaling. Primary mouse cortical neurons were subjected to 4 h OGD and NIR was applied at 2 h reoxygenation. OGD significantly increased NO level in primary neurons compared to normal control, which was significantly ameliorated by NIR at 5 and 30 min post-NIR. Neither OGD nor NIR significantly changed neuronal nitric oxide synthase (nNOS) mRNA or total protein levels compared to control groups. However, OGD significantly increased nNOS activity compared to normal control, and this effect was significantly diminished by NIR. Moreover, NIR significantly ameliorated the neuronal death induced by S-Nitroso-N-acetyl-DL-penicillamine (SNAP), a NO donor. Finally, NIR significantly rescued OGD-induced suppression of p-Akt and Bcl-2 expression, and attenuated OGD-induced upregulation of Bax, BAD and caspase-3 activation. These results suggest NIR may protect against OGD at least partially through reducing NO production by down-regulating nNOS activity, and modulating cell survival/death signaling.

  12. "I Don't Know Where to Find the Careers Adviser … He Has Disappeared": The Impact of Changes to Careers Advice on 14-16 Year Olds in University Technical Colleges and Schools

    ERIC Educational Resources Information Center

    Acquah, Daniel K.; Limmer, Hayley; Malpass, Debra

    2017-01-01

    Recent policies in England have enacted significant changes to careers information advice and guidance (CIAG) and work-related learning (WRL). This paper offers insight into these changes from the perspective of young people studying engineering at University Technical Colleges (UTCs) as well as "comprehensive" schools. Face-to-face CIAG…

  13. Awakening the Scientist Inside: Global Climate Change and the Nature of Science in an Elementary Science Methods Course

    NASA Astrophysics Data System (ADS)

    Matkins, Juanita Jo; Bell, Randy L.

    2007-04-01

    This investigation assessed the impact of situating explicit nature of science (NOS) instruction within the issues surrounding global climate change and global warming (GCC/GW). Participants in the study were 15 preservice elementary teachers enrolled in a science methods course. The instructional intervention included explicit NOS instruction combined with explicit GCC/GW instruction situated within the normal elementary science methods curriculum. Participants’ conceptions of NOS and GCC/GW were assessed with pre- and postadministrations of open-ended questionnaires and interviews. Results indicated that participants’ conceptions of NOS and GCC/GW improved over the course of the semester. Furthermore, participants were able to apply their conceptions to decision making about socioscientific issues. The results provide support for context-based NOS instruction in an elementary science methods course.

  14. The nature of science and the preservice elementary teacher: Changes in understanding and practice

    NASA Astrophysics Data System (ADS)

    Rivas, Michael Gerald

    This action research project studies preservice elementary teachers in a science methods course. The purpose of this research project was to enhance preservice teachers' understanding of specific nature of science (NOS) tenets so as to promote equity and access within the elementary science classroom. In particular, I chose five NOS tenets that were listed in the first chapter of the AAAS (1989) document titled, "The Nature of Science," and connected them to equitable educational goals and practices. The theoretical framework guiding this study came from bodies of scholarship relating to the NOS, social constructivism, and action research. This study addressed the following three questions: (1) What opportunities were provided the preservice teachers so that they could enhance their understandings of the NOS? (2) What were the changes in preservice teachers' understanding of the NOS as a result? (3) How did the prospective teachers' understandings of the NOS translate into their classroom practice? The analysis revealed that the science methods course's operational curriculum consisted of implicit and explicit teaching of the NOS, as well as intended and untended NOS tenets. The prospective teachers initially held a limited view of the NOS, but by the end of the course their view had been enhanced. In addition, the participants made direct connections between their new understandings of the NOS and equity and access in the science classroom. In their teaching, the preservice teachers as a group implicitly taught all five of the NOS tenets. In fact, a majority taught three of the five intended tenets. Explicitly, only one tenet was taught, but it was taught with a direct connection to making the science classroom more inclusive. The findings of this study indicate that preservice teachers can have their views of the NOS enhanced even though they may have experienced years of deficient science instruction. They pointed out that this enhanced view of the NOS can be

  15. 78 FR 39018 - Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 2 and 3

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-28

    ... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-247 and 50-286; NRC-2008-0672] Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 2 and 3 AGENCY: Nuclear Regulatory Commission... Renewal of Nuclear Plants; issuance. SUMMARY: Notice is hereby given that the U.S. Nuclear Regulatory...

  16. [Influence of hepatocyte growth factor on iNOS, NO and IL-1β in the cerebrum during cerebral ischemia/reperfusion in rats].

    PubMed

    He, Fang; Ye, Bei; Chen, Jianzhen; Sun, Xiaoyan; Li, Chang

    2014-01-01

    To explore the effect of hepatocyte growth factor (HGF) on inducible nitric oxide synthase (iNOS), NO and interleukin-1β (IL-1β) in the cerebrum of rats subjected to cerebral ischemia/reperfusion (I/R). Sprague-Dawley rats were randomly divided into 5 groups: a sham group, an I/R group,an HGF1 group, an HGF2 group, and an HGF3 group. The latter 3 groups were respectively injected 15, 30 and 60 μg/kg HGF. The focal cerebral I/R model was established by sutureoccluded method. After 1.5 h ischemia followed by 24 h reperfusion, the iNOS activity and NO content in the ischemic cerebral tissue were assessed. The expression of iNOS mRNA and IL-1β mRNA was detected. The level of iNOS protein and IL-1β content were determined. In addition, cultured cerebral cortical neurons in vitro were exposed to I/R. Then the expression of iNOS and IL-1β protein in the neurons was detected, and NO content was assessed. The iNOS activity and NO content in the ischemic cerebral tissue were increased. The expression of iNOS mRNA and IL-1β mRNA was upregulated. The level of iNOS protein and IL- 1β content were increased. Administration of HGF decreased the iNOS activity and NO content, and downregulated the expression of iNOS mRNA, IL-1β mRNA, iNOS protein and IL-1β content in the ischemic cerebral tissue. HGF decreased the expression of IL-1β, iNOS protein and NO content in the cortical neurons exposed to I/R in vitro. HGF can inhibit the expression of IL-1β and decrease the expression of iNOS and content of NO, which is probably one of the mechanisms mediating the protection of HGF against cerebral ischemia injury.

  17. Effects of atorvastatin and T-786C polymorphism of eNOS gene on plasma metabolic lipid parameters.

    PubMed

    Zago, Vanessa Helena de Souza; Santos, José Eduardo Tanus dos; Danelon, Mirian Regina Gardin; Silva, Roger Marcelo Mesquita da; Panzoldo, Natália Baratella; Parra, Eliane Soler; Alexandre, Fernanda; Virgínio, Vítor Wilson de Moura; Quintão, Eder Carlos Rocha; Faria, Eliana Cotta de

    2013-01-01

    Endothelial nitric oxide synthase (eNOS) activity may be modulated by high-density lipoprotein cholesterol (HDL-C), statins or polymorphisms, such as the T-786C of eNOS. This study aimed at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile, on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP). Thirty male volunteers, asymptomatic, aged between 18 and 56 years were genotyped and classified according to absence (TT, n = 15) or presence (CC, n = 15) of the polymorphism. They were randomly selected for the use of placebo or atorvastatin (10 mg/day/14 days). After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer protein (CETP) activity, metabolites of NO and hsCRP were evaluated. The comparisons between genotypes after placebo showed an increase in CETP activity in a polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments indicated that atorvastatin has an effect on cholesterol, LDL, nitrite and lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline decrease in CETP, but with no effect on Lp(a). HsCRP showed no alteration. These results suggest that statin treatment may be relevant for primary prevention of atherosclerosis in patients with the T-786C polymorphism of eNOS, considering the effects on lipid metabolism.

  18. Computerising the Salesforce: The Introduction of Technical Change in a Non-Union Workforce.

    ERIC Educational Resources Information Center

    Newell, Helen; Lloyd, Caroline

    1998-01-01

    Results of interviews with 13 pharmaceutical sales representatives, five sales managers, and six human-resource managers and 47 survey responses showed that introduction of information technology was seen as purely technical; human-resources departments played no role; and informal communication procedures enabled management to ignore individual…

  19. A vast amount of various invariant tori in the Nosé-Hoover oscillator

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

    Wang, Lei; Department of Mathematics and Physics, Hefei University, Hefei 230601; Yang, Xiao-Song, E-mail: yangxs@hust.edu.cn

    2015-12-15

    This letter restudies the Nosé-Hoover oscillator. Some new averagely conservative regions are found, each of which is filled with different sequences of nested tori with various knot types. Especially, the dynamical behaviors near the border of “chaotic region” and conservative regions are studied showing that there exist more complicated and thinner invariant tori around the boundaries of conservative regions bounded by tori. Our results suggest an infinite number of island chains in a “chaotic sea” for the Nosé-Hoover oscillator.

  20. Inducible nitric oxide synthase (iNOS) in gingival tissues of chronic periodontitis with and without diabetes: immunohistochemistry and RT-PCR study.

    PubMed

    Shaker, Olfat; Ghallab, Noha A; Hamdy, Ebtehal; Sayed, Safinaz

    2013-10-01

    There is few data concerning the pathogenesis and contribution of inducible nitric oxide synthase (iNOS) in the inflammatory reactions of the periodontium in the course of diabetes. This study evaluated the expression of iNOS in the gingival biopsies of periodontitis patients with and without type 2 diabetes. 80 subjects were evaluated in four groups: patients with chronic periodontitis and diabetes, patients with chronic periodontitis, periodontally healthy patients with diabetes, and systemically and periodontally healthy control subjects. Gingival biopsies were subjected to immunohistochemistry as well as reverse transcription polymerase chain reaction (RT-PCR) for determination of iNOS. All diseased gingival tissues had a significant increase in iNOS expression by immunohistochemistry (P<0.001) compared to controls. There was no significant difference observed between patients with both diabetes and periodontitis and diabetic patients regarding iNOS(+) cells. Meanwhile, these two groups had significantly increased iNOS(+) cells when compared to periodontitis patients (P<0.001). There are significantly higher levels of iNOS mRNA expression of all patient groups compared to controls (P<0.0001). In addition, samples from patients with diabetes and periodontitis showed significantly higher levels of iNOS mRNA expression compared to samples from periodontitis patients and diabetic patients (P<0.0001) yet, without noting statistically significant differences between the latter two groups. Although iNOS expression was prominent in the gingiva of patients with diabetes and periodontitis, periodontitis patients and diabetic patients, the higher mRNA for iNOS observed in diabetes and periodontitis may indicate a possible involvement of this mediator in the periodontal destruction of type 2 diabetes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Awakening the Scientist Inside: Global Climate Change and the Nature of Science in an Elementary Science Methods Course

    ERIC Educational Resources Information Center

    Matkins, Juanita Jo; Bell, Randy L.

    2007-01-01

    This investigation assessed the impact of situating explicit nature of science (NOS) instruction within the issues surrounding global climate change and global warming (GCC/GW). Participants in the study were 15 preservice elementary teachers enrolled in a science methods course. The instructional intervention included explicit NOS instruction…

  2. Inhibitory effect of baicalin on iNOS and NO expression in intestinal mucosa of rats with acute endotoxemia.

    PubMed

    Feng, Aiwen; Zhou, Guangrong; Yuan, Xiaoming; Huang, Xinli; Zhang, Zhengyuan; Zhang, Ti

    2013-01-01

    The mechanism by which baicalin modulated the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the mucosa of distal ileum was investigated in a rat model of acute endo-toxemia induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). The experiment demonstrated that LPS upregulated iNOS mRNA and protein expression as well as NO produc-tion (measured as the stable degradation production, nitrites). LPS not only increased toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor gamma (PPARγ) content, but also activated p38 and activating transcription factor 2 (ATF2) and inactivated PPARγ via phosphorylation. Inhibition of p38 signalling pathway by chemical inhibitor SB202190 and small interfering RNA (siRNA) ameliorated LPS-induced iNOS generation, while suppression of PPARγ pathway by SR-202 boosted LPS-elicited iNOS expression. Baicalin treatment (I) attenuated LPS-induced iNOS mRNA and protein as well as nitrites generation, and (II) ameliorated LPS-elicited TLR4 and PPARγ production, and (III) inhibited p38/ATF2 phosphorylation leading to suppression of p38 signalling, and (IV) prevented PPARγ from phosphorylation contributing to maintainence of PPARγ bioactivity. However, SR-202 co-treatment (I) partially abrogated the inhibitory effect of baicalin on iNOS mRNA expression, and (II) partially reversed baicalin-inhibited p38 phosphorylation. In summary, baicalin could ameliorate LPS-induced iNOS and NO overproduction in mucosa of rat terminal ileum via inhibition of p38 signalling cascade and activation of PPARγ pathway. There existed a interplay between the two signalling pathways.

  3. 77 FR 74524 - Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-14

    ... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-68394; File No. SR-BX-2012-073] Self-Regulatory Organizations; NASDAQ OMX BX, Inc.; Notice of Filing and Immediate Effectiveness of Proposed Rule Change With Respect to the Authority of the Exchange or Nasdaq Options Services LLC (``NOS'') To Cancel Options Orders When a Technical or System Issu...

  4. Resveratrol protects rats from Aβ-induced neurotoxicity by the reduction of iNOS expression and lipid peroxidation.

    PubMed

    Huang, Tai-Chun; Lu, Kwok-Tung; Wo, Yu-Yuan Peter; Wu, Yao-Ju; Yang, Yi-Ling

    2011-01-01

    Alzheimer disease (AD) is an age-dependent neurodegenerative disease characterized by the formation of β-amyloid (Aβ)-containing senile plaque. The disease could be induced by the administration of Aβ peptide, which was also known to upregulate inducible nitric oxide synthase (iNOS) and stimulate neuronal apoptosis. The present study is aimed to elucidate the cellular effect of resveratrol, a natural phytoestrogen with neuroprotective activities, on Aβ-induced hippocampal neuron loss and memory impairment. On adult Sprague-Dawley rats, we found the injection of Aβ could result in a significant impairment in spatial memory, a marked increase in the cellular level of iNOS and lipid peroxidation, and an apparent decrease in the expression of heme oxygenase-1 (HO-1). By combining the treatment with Aβ, resveratrol was able to confer a significant improvement in spatial memory, and protect animals from Aβ-induced neurotoxicity. These neurological protection effects of resveratrol were associated with a reduction in the cellular levels of iNOS and lipid peroxidation and an increase in the production of HO-1. Moreover, the similar neurological and cellular response were also observed when Aβ treatment was combined with the administration of a NOS inhibitor, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME). These findings strongly implicate that iNOS is involved in the Aβ-induced lipid peroxidation and HO-1 downregulation, and resveratrol protects animals from Aβ-induced neurotoxicity by suppressing iNOS production.

  5. Resveratrol Protects Rats from Aβ-induced Neurotoxicity by the Reduction of iNOS Expression and Lipid Peroxidation

    PubMed Central

    Wo, Yu-Yuan Peter; Wu, Yao-Ju; Yang, Yi-Ling

    2011-01-01

    Alzheimer disease (AD) is an age-dependent neurodegenerative disease characterized by the formation of β–amyloid (Aβ)-containing senile plaque. The disease could be induced by the administration of Aβ peptide, which was also known to upregulate inducible nitric oxide synthase (iNOS) and stimulate neuronal apoptosis. The present study is aimed to elucidate the cellular effect of resveratrol, a natural phytoestrogen with neuroprotective activities, on Aβ-induced hippocampal neuron loss and memory impairment. On adult Sprague-Dawley rats, we found the injection of Aβ could result in a significant impairment in spatial memory, a marked increase in the cellular level of iNOS and lipid peroxidation, and an apparent decrease in the expression of heme oxygenase-1 (HO-1). By combining the treatment with Aβ, resveratrol was able to confer a significant improvement in spatial memory, and protect animals from Aβ-induced neurotoxicity. These neurological protection effects of resveratrol were associated with a reduction in the cellular levels of iNOS and lipid peroxidation and an increase in the production of HO-1. Moreover, the similar neurological and cellular response were also observed when Aβ treatment was combined with the administration of a NOS inhibitor, N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME). These findings strongly implicate that iNOS is involved in the Aβ-induced lipid peroxidation and HO-1 downregulation, and resveratrol protects animals from Aβ-induced neurotoxicity by suppressing iNOS production. PMID:22220203

  6. [Association of Schizophrenia and its Clinical Implications with the NOS1AP Gene in the Colombian Population].

    PubMed

    Valencia, Jenny García; Duarte, Ana Victoria Valencia; Vila, Ana Lucía Páez; Kremeyer, Bárbara; Montoya, María Patricia Arbeláez; Linares, Andrés Ruiz; Acosta, Carlos Alberto Palacio; Duque, Jorge Ospina; Berrío, Gabriel Bedoya

    2012-06-01

    The nitric oxide synthase 1 adaptor protein (NOS1AP) gene is possibly implicated in schizophrenia etiopathogenesis. To determine the association of NOS1AP gene variants with schizophrenia and the relationship of variants with the clinical dimensions of the disorder in the Colombian population. It is a case-control study with 255 subjects per group. Markers within the NOS1AP gene were typified as well as other informative material of genetic origin so as to adjust by population stratification. A factorial analysis of the main components for each item in the Scales for Evaluating Negative Symptoms (SENS) together with the Scales for Evaluating Positive Symptoms (SEPS) to determine clinical dimensions. Association between the C/C genotype of the rs945713 marker with schizophrenia (OR = 1.79, 95% CI: 1.13 - 2.84) was found. The C/C genotype of the rs945713 was related to higher scores in the "affective flattening and alogia" dimension; and the A/A genotype of the rs4657181 marker was associated to lower scores in the same dimension. Significant associations of markers inside the NOS1AP gene with schizophrenia and the "affective flattening and alogia" clinical dimension were found. These results are consistent with previous studies and support the possibility that NOS1AP influences schizophrenia susceptibility. Furthermore, NOS1AP might be a modifier of schizophrenia clinical characteristics. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  7. New Findings in eNOS gene and Thalidomide Embryopathy Suggest pre-transcriptional effect variants as susceptibility factors

    PubMed Central

    Kowalski, Thayne Woycinck; Fraga, Lucas Rosa; Tovo-Rodrigues, Luciana; Sanseverino, Maria Teresa Vieira; Hutz, Mara Helena; Schuler-Faccini, Lavínia; Vianna, Fernanda Sales Luiz

    2016-01-01

    Antiangiogenic properties of thalidomide have created an interest in the use of the drug in treatment of cancer. However, thalidomide is responsible for thalidomide embryopathy (TE). A lack of knowledge regarding the mechanisms of thalidomide teratogenesis acts as a barrier in the aim to synthesize a safer analogue of thalidomide. Recently, our group detected a higher frequency of alleles that impair the pro-angiogenic mechanisms of endothelial nitric oxide synthase (eNOS), coded by the NOS3 gene. In this study we evaluated variable number tandem repeats (VNTR) functional polymorphism in intron 4 of NOS3 in individuals with TE (38) and Brazilians without congenital anomalies (136). Haplotypes were estimated for this VNTR with previously analyzed polymorphisms, rs2070744 (−786C > T) and rs1799983 (894T > G), in promoter region and exon 7, respectively. Haplotypic distribution was different between the groups (p = 0.007). Alleles −786C (rs2070744) and 4b (VNTR), associated with decreased NOS3 expression, presented in higher frequency in TE individuals (p = 0.018; OR = 2.57; IC = 1.2–5.8). This association was not identified with polymorphism 894T > G (p = 0.079), which influences eNOS enzymatic activity. These results suggest variants in NOS3, with pre-transcriptional effects as susceptibility factors, influencing the risk TE development. This finding generates insight for a new approach to research that pursues a safer analogue. PMID:27004986

  8. Zeb1-Hdac2-eNOS circuitry identifies early cardiovascular precursors in naive mouse embryonic stem cells.

    PubMed

    Cencioni, Chiara; Spallotta, Francesco; Savoia, Matteo; Kuenne, Carsten; Guenther, Stefan; Re, Agnese; Wingert, Susanne; Rehage, Maike; Sürün, Duran; Siragusa, Mauro; Smith, Jacob G; Schnütgen, Frank; von Melchner, Harald; Rieger, Michael A; Martelli, Fabio; Riccio, Antonella; Fleming, Ingrid; Braun, Thomas; Zeiher, Andreas M; Farsetti, Antonella; Gaetano, Carlo

    2018-03-29

    Nitric oxide (NO) synthesis is a late event during differentiation of mouse embryonic stem cells (mESC) and occurs after release from serum and leukemia inhibitory factor (LIF). Here we show that after release from pluripotency, a subpopulation of mESC, kept in the naive state by 2i/LIF, expresses endothelial nitric oxide synthase (eNOS) and endogenously synthesizes NO. This eNOS/NO-positive subpopulation (ESNO+) expresses mesendodermal markers and is more efficient in the generation of cardiovascular precursors than eNOS/NO-negative cells. Mechanistically, production of endogenous NO triggers rapid Hdac2 S-nitrosylation, which reduces association of Hdac2 with the transcriptional repression factor Zeb1, allowing mesendodermal gene expression. In conclusion, our results suggest that the interaction between Zeb1, Hdac2, and eNOS is required for early mesendodermal differentiation of naive mESC.

  9. TECHNICAL REPORTS DATABASE

    EPA Science Inventory

    The Defense Technical Information Center (DTIC?) is the central facility for the collection and dissemination of scientific and technical information for the Department of Defense (DoD). Much of this information is made available by DTIC in the form of technical reports about com...

  10. Galilean-invariant Nosé-Hoover-type thermostats.

    PubMed

    Pieprzyk, S; Heyes, D M; Maćkowiak, Sz; Brańka, A C

    2015-03-01

    A new pairwise Nosé-Hoover type thermostat for molecular dynamics (MD) simulations which is similar in construction to the pair-velocity thermostat of Allen and Schmid, [Mol. Simul. 33, 21 (2007)] (AS) but is based on the configurational thermostat is proposed and tested. Both thermostats generate the canonical velocity distribution, are Galilean invariant, and conserve linear and angular momentum. The unique feature of the pairwise thermostats is an unconditional conservation of the total angular momentum, which is important for thermalizing isolated systems and those nonequilibrium bulk systems manifesting local rotating currents. These thermostats were benchmarked against the corresponding Nosé-Hoover (NH) and Braga-Travis prescriptions, being based on the kinetic and configurational definitions of temperature, respectively. Some differences between the shear-rate-dependent shear viscosity from Sllod nonequilibrium MD are observed at high shear rates using the different thermostats. The thermostats based on the configurational temperature produced very similar monotically decaying shear viscosity (shear thinning) with increasing shear rate, while the NH method showed discontinuous shear thinning into a string phase, and the AS method produced a continuous increase of viscosity (shear thickening), after a shear thinning region at lower shear rates. Both pairwise additive thermostats are neither purely kinetic nor configurational in definition, and possible directions for further improvement in certain aspects are discussed.

  11. Galilean-invariant Nosé-Hoover-type thermostats

    NASA Astrophysics Data System (ADS)

    Pieprzyk, S.; Heyes, D. M.; Maćkowiak, Sz.; Brańka, A. C.

    2015-03-01

    A new pairwise Nosé-Hoover type thermostat for molecular dynamics (MD) simulations which is similar in construction to the pair-velocity thermostat of Allen and Schmid, [Mol. Simul. 33, 21 (2007), 10.1080/08927020601052856] (AS) but is based on the configurational thermostat is proposed and tested. Both thermostats generate the canonical velocity distribution, are Galilean invariant, and conserve linear and angular momentum. The unique feature of the pairwise thermostats is an unconditional conservation of the total angular momentum, which is important for thermalizing isolated systems and those nonequilibrium bulk systems manifesting local rotating currents. These thermostats were benchmarked against the corresponding Nosé-Hoover (NH) and Braga-Travis prescriptions, being based on the kinetic and configurational definitions of temperature, respectively. Some differences between the shear-rate-dependent shear viscosity from Sllod nonequilibrium MD are observed at high shear rates using the different thermostats. The thermostats based on the configurational temperature produced very similar monotically decaying shear viscosity (shear thinning) with increasing shear rate, while the NH method showed discontinuous shear thinning into a string phase, and the AS method produced a continuous increase of viscosity (shear thickening), after a shear thinning region at lower shear rates. Both pairwise additive thermostats are neither purely kinetic nor configurational in definition, and possible directions for further improvement in certain aspects are discussed.

  12. eNOS uncoupling in cardiovascular diseases--the role of oxidative stress and inflammation.

    PubMed

    Karbach, Susanne; Wenzel, Philip; Waisman, Ari; Munzel, Thomas; Daiber, Andreas

    2014-01-01

    Many cardiovascular diseases and drug-induced complications are associated with - or even based on - an imbalance between the formation of reactive oxygen and nitrogen species (RONS) and antioxidant enzymes catalyzing the break-down of these harmful oxidants. According to the "kindling radical" hypothesis, the formation of RONS may trigger in certain conditions the activation of additional sources of RONS. According to recent reports, vascular dysfunction in general and cardiovascular complications such as hypertension, atherosclerosis and coronary artery diseases may be connected to inflammatory processes. The present review is focusing on the uncoupling of endothelial nitric oxide synthase (eNOS) by different mechanisms involving so-called "redox switches". The oxidative depletion of tetrahydrobiopterin (BH4), oxidative disruption of the dimeric eNOS complex, S-glutathionylation and adverse phosphorylation as well as RONS-triggered increases in levels of asymmetric dimethylarginine (ADMA) will be discussed. But also new concepts of eNOS uncoupling and state of the art detection of this process will be described. Another part of this review article will address pharmaceutical interventions preventing or reversing eNOS uncoupling and thereby normalize vascular function in a given disease setting. We finally turn our attention to the inflammatory mechanisms that are also involved in the development of endothelial dysfunction and cardiovascular disease. Inflammatory cell and cytokine profiles as well as their interactions, which are among the kindling mechanisms for the development of vascular dysfunction will be discussed on the basis of the current literature.

  13. West Hackberry Tertiary Project. Quarterly technical progress report, July 1--September 30, 1995

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

    NONE

    The goal of the West Hackberry Tertiary Project is to demonstrate the technical and economic feasibility of combining air injection with the Double Displacement Process for tertiary oil recovery. The Double Displacement Process is the gas displacement of a water invaded oil column for the purpose of recovering oil through gravity drainage. The novel aspect of this project is the use of air as the injection fluid. The target reservoir for the project is the Camerina C-1,2,3 Sand located on the West Flank of West Hackberry Field in Cameron Parish, Louisiana. If successful, this project will demonstrate that the usemore » of air injection in the Double Displacement Process can economically recover oil in reservoirs where tertiary oil recovery is presented uneconomic. During this quarter, the West Hackberry Tertiary Project completed the first ten months of air injection operations. Plots of air injection rates and cumulative air injected are included in this report as attachments. The following events are reviewed in this quarter`s technical progress report: (1) successful workovers on the Gulf Land D Nos. 44, 45 and 51 and the Watkins No. 3; (2) the unsuccessful repair attempt on the Watkins No. 16; (3) gathering of additional bottom hole pressure data; (4) air compressor operations and repairs; and (5) technology transfer activities.« less

  14. High Technology Training at Greenville Technical College.

    ERIC Educational Resources Information Center

    Barton, Thomas E.; And Others

    These three papers focus on various aspects of high technology training at Greenville Technical College (GTC). First, "High Technology and the Community College," by Thomas E. Barton, discusses what high technology should mean to educators and argues that changes in the nature of industrial production require that community colleges not only keep…

  15. Proton pump inhibitors suppress iNOS-dependent DNA damage in Barrett's esophagus by increasing Mn-SOD expression

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

    Thanan, Raynoo; Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507; Ma, Ning

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Inflammation by Barrett's esophagus (BE) is a risk factor of its adenocarcinoma (BEA). Black-Right-Pointing-Pointer 8-Nitroguanine and 8-oxodG are inflammation-related DNA lesions. Black-Right-Pointing-Pointer DNA lesions and iNOS expression were higher in the order, BEA > BE > normal tissues. Black-Right-Pointing-Pointer Proton pump inhibitors suppress DNA damage by increasing Mn-SOD via Nrf2 activation. Black-Right-Pointing-Pointer DNA lesions can be useful biomarkers to predict risk of BEA in BE patients. -- Abstract: Barrett's esophagus (BE), an inflammatory disease, is a risk factor for Barrett's esophageal adenocarcinoma (BEA). Treatment of BE patients with proton pump inhibitors (PPIs) is expected to reduce the riskmore » of BEA. We performed an immunohistochemical study to examine the formation of nitrative and oxidative DNA lesions, 8-nitroguanine and 8-oxo-7,8-dihydro-2 Prime -deoxygaunosine (8-oxodG), in normal esophageal, BE with pre- and post-treatment by PPIs and BEA tissues. We also observed the expression of an oxidant-generating enzyme (iNOS) and its transcription factor NF-{kappa}B, an antioxidant enzyme (Mn-SOD), its transcription factor (Nrf2) and an Nrf2 inhibitor (Keap1). The immunoreactivity of DNA lesions was significantly higher in the order of BEA > BE > normal tissues. iNOS expression was significantly higher in the order of BEA > BE > normal tissues, while Mn-SOD expression was significantly lower in the order of BEA < BE < normal tissues. Interestingly, Mn-SOD expression and the nuclear localization of Nrf2 were significantly increased, and the formation of DNA lesions was significantly decreased in BE tissues after PPIs treatment for 3-6 months. Keap1 and iNOS expression was not significantly changed by the PPIs treatment in BE tissues. These results indicate that 8-nitroguanine and 8-oxodG play a role in BE-derived BEA. Additionally, PPIs treatment may trigger the activation and nuclear

  16. Disrupting nNOS-PSD-95 coupling in the hippocampal dentate gyrus promotes extinction memory retrieval.

    PubMed

    Li, Jun; Han, Zhou; Cao, Bo; Cai, Cheng-Yun; Lin, Yu-Hui; Li, Fei; Wu, Hai-Ying; Chang, Lei; Luo, Chun-Xia; Zhu, Dong-Ya

    2017-11-04

    Granule cells in the dentate gyrus regenerate constantly in adult hippocampus and then integrate into neural circuits in the hippocampus thereby providing the neural basis for learning and memory. Promoting the neurogenesis in the hippocampus facilitates learning and memory such as spatial learning, object identification, and extinction learning. The interaction between neuronal nitric oxide synthase (nNOS) and postsynaptic density protein-95 (PSD-95) is reported to negatively regulate neurogenesis in brain, so we hypothesized that disrupting this interaction might facilitate the neurogenesis in the dentate gyrus (DG) and thus enhance the extinction memory retrieval of fear learning. We found that uncoupling the nNOS-PSD-95 complex in remote contextual fear condition promoted both neuronal proliferation and survival in the DG, contributing to an enhanced retrieval of the extinction memory. Moreover, the nNOS-PSD-95 uncoupling-induced neurogenesis may be mediated by the extracellular signal-regulated kinase (ERK) as the phosphorylation level of ERK1/2 was increased after uncoupling. These findings suggest that the nNOS-PSD-95 complex may serve as a novel target for the treatment of post-traumatic stress disorder (PTSD). Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Recreational technical diving part 1: an introduction to technical diving methods and activities.

    PubMed

    Mitchell, Simon J; Doolette, David J

    2013-06-01

    Technical divers use gases other than air and advanced equipment configurations to conduct dives that are deeper and/or longer than typical recreational air dives. The use of oxygen-nitrogen (nitrox) mixes with oxygen fractions higher than air results in longer no-decompression limits for shallow diving, and faster decompression from deeper dives. For depths beyond the air-diving range, technical divers mix helium, a light non-narcotic gas, with nitrogen and oxygen to produce 'trimix'. These blends are tailored to the depth of intended use with a fraction of oxygen calculated to produce an inspired oxygen partial pressure unlikely to cause cerebral oxygen toxicity and a nitrogen fraction calculated to produce a tolerable degree of nitrogen narcosis. A typical deep technical dive will involve the use of trimix at the target depth with changes to gases containing more oxygen and less inert gas during the decompression. Open-circuit scuba may be used to carry and utilise such gases, but this is very wasteful of expensive helium. There is increasing use of closed-circuit 'rebreather' devices. These recycle expired gas and potentially limit gas consumption to a small amount of inert gas to maintain the volume of the breathing circuit during descent and the amount of oxygen metabolised by the diver. This paper reviews the basic approach to planning and execution of dives using these methods to better inform physicians of the physical demands and risks.

  18. Staff Considerations in Technical Services: The Chameleon Approach.

    ERIC Educational Resources Information Center

    Foster, Constance L.

    1988-01-01

    Discusses the need to cope effectively with technological transitions in library technical services and to plan for successful staff development. The areas discussed include changing job skills, financial planning, ergonomics, innovative partnerships, training, and an emphasis on human resources development. (21 references) (Author/CLB)

  19. 75 FR 41237 - Public Land Order No. 7745; Partial Revocation of Power Site Reserve Nos. 510 and No. 515; Montana

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-15

    ... MTM 41534] Public Land Order No. 7745; Partial Revocation of Power Site Reserve Nos. 510 and No. 515... of public lands withdrawn for Power Site Reserve Nos. 510 and 515. This order also opens the lands to... INFORMATION: The Bureau of Land Management has determined that portions of Power Site Reserve Nos. 510 and 515...

  20. Groundwater technical procedures of the U.S. Geological Survey

    USGS Publications Warehouse

    Cunningham, William L.; Schalk, Charles W.

    2011-01-01

    A series of groundwater technical procedures documents (GWPDs) has been released by the U.S. Geological Survey, Water-Resources Discipline, for general use by the public. These technical procedures were written in response to the need for standardized technical procedures of many aspects of groundwater science, including site and measuring-point establishment, measurement of water levels, and measurement of well discharge. The techniques are described in the GWPDs in concise language and are accompanied by necessary figures and tables derived from cited manuals, reports, and other documents. Because a goal of this series of procedures is to remain current with the state of the science, and because procedures change over time, this report is released in an online format only. As new procedures are developed and released, they will be linked to this document.

  1. Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content

    PubMed Central

    Harvey, Nicholas C.; Lillycrop, Karen A.; Garratt, Emma; Sheppard, Allan; McLean, Cameron; Burdge, Graham; Slater-Jefferies, Jo; Rodford, Joanne; Crozier, Sarah; Inskip, Hazel; Emerald, Bright Starling; Gale, Catharine R; Hanson, Mark; Gluckman, Peter; Godfrey, Keith; Cooper, Cyrus

    2013-01-01

    Aim Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year old children. Methods We used Sequenom MassARRAY to assess the methylation status of 2 CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Results Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553+, after taking account of age and sex there was a strong positive association between methylation status and the child’s whole body bone area (r=0.28,p=0.02), bone mineral content (r=0.34,p=0.005) and areal bone mineral density (r=0.34,p=0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Conclusions Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development. PMID:22159788

  2. Inhibitory Effect of Baicalin on iNOS and NO Expression in Intestinal Mucosa of Rats with Acute Endotoxemia

    PubMed Central

    Yuan, Xiaoming; Huang, Xinli; Zhang, Zhengyuan; Zhang, Ti

    2013-01-01

    The mechanism by which baicalin modulated the expression of inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in the mucosa of distal ileum was investigated in a rat model of acute endo-toxemia induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). The experiment demonstrated that LPS upregulated iNOS mRNA and protein expression as well as NO produc-tion (measured as the stable degradation production, nitrites). LPS not only increased toll-like receptor 4 (TLR4) and peroxisome proliferator-activated receptor gamma (PPARγ) content, but also activated p38 and activating transcription factor 2 (ATF2) and inactivated PPARγ via phosphorylation. Inhibition of p38 signalling pathway by chemical inhibitor SB202190 and small interfering RNA (siRNA) ameliorated LPS-induced iNOS generation, while suppression of PPARγ pathway by SR-202 boosted LPS-elicited iNOS expression. Baicalin treatment (I) attenuated LPS-induced iNOS mRNA and protein as well as nitrites generation, and (II) ameliorated LPS-elicited TLR4 and PPARγ production, and (III) inhibited p38/ATF2 phosphorylation leading to suppression of p38 signalling, and (IV) prevented PPARγ from phosphorylation contributing to maintainence of PPARγ bioactivity. However, SR-202 co-treatment (I) partially abrogated the inhibitory effect of baicalin on iNOS mRNA expression, and (II) partially reversed baicalin-inhibited p38 phosphorylation. In summary, baicalin could ameliorate LPS-induced iNOS and NO overproduction in mucosa of rat terminal ileum via inhibition of p38 signalling cascade and activation of PPARγ pathway. There existed a interplay between the two signalling pathways. PMID:24312512

  3. Habitual energy expenditure modifies the association between NOS3 gene polymorphisms and blood pressure.

    PubMed

    Vimaleswaran, Karani S; Franks, Paul W; Barroso, Inês; Brage, Soren; Ekelund, Ulf; Wareham, Nicholas J; Loos, Ruth J F

    2008-03-01

    The endothelial nitric-oxide synthase (NOS3) gene encodes the enzyme (eNOS) that synthesizes the molecule nitric oxide, which facilitates endothelium-dependent vasodilation in response to physical activity. Thus, energy expenditure may modify the association between the genetic variation at NOS3 and blood pressure. To test this hypothesis, we genotyped 11 NOS3 polymorphisms, capturing all common variations, in 726 men and women from the Medical Research Council (MRC) Ely Study (age (mean +/- s.d.): 55 +/- 10 years, body mass index: 26.4 +/- 4.1 kg/m(2)). Habitual/non-resting energy expenditure (NREE) was assessed via individually calibrated heart rate monitoring over 4 days. The intronic variant, IVS25+15 [G-->A], was significantly associated with blood pressure; GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (-2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (-1.9 mm Hg; P = 0.018) than A-allele carriers. The interaction between NREE and IVS25+15 was also significant for both DBP (P = 0.006) and SBP (P = 0.026), in such a way that the effect of the GG-genotype on blood pressure was stronger in individuals with higher NREE (DBP: -4.9 mm Hg, P = 0.02. SBP: -3.8 mm Hg, P= 0.03 for the third tertile). Similar results were observed when the outcome was dichotomously defined as hypertension. In summary, the NOS3 IVS25+15 is directly associated with blood pressure and hypertension in white Europeans. However, the associations are most evident in the individuals with the highest NREE. These results need further replication and have to be ideally tested in a trial before being informative for targeted disease prevention. Eventually, the selection of individuals for lifestyle intervention programs could be guided by knowledge of genotype.

  4. Context view, Building Nos. 2728, looking north from a spot ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Context view, Building Nos. 27-28, looking north from a spot south of Building No. 28 - U.S. Veterans Hospital, Jefferson Barracks, Medical Officer in Charge Residence, VA Medical Center, Jefferson Barracks Division 1 Jefferson Barracks Drive, Saint Louis, Independent City, MO

  5. Donkey milk kefir induces apoptosis and suppresses proliferation of Ehrlich ascites carcinoma by decreasing iNOS in mice.

    PubMed

    Esener, Obb; Balkan, B M; Armutak, E I; Uvez, A; Yildiz, G; Hafizoglu, M; Yilmazer, N; Gurel-Gurevin, E

    2018-04-12

    Donkey milk and donkey milk kefir exhibit antiproliferative, antimutagenic and antibacterial effects. We investigated the effects of donkey milk and donkey milk kefir on oxidative stress, apoptosis and proliferation in Ehrlich ascites carcinoma (EAC) in mice. Thirty-four adult male Swiss albino mice were divided into four groups as follows: group 1, administered 0.5 ml water; group 2, administered 0.5 ml water + EAC cells; group 3, administered 0.5 ml donkey milk + EAC cells; group 4, administered 0.5 ml donkey milk kefir + EAC cells. We introduced 2.5 x 10 6 EAC cells into each animal by subcutaneous injection. Tap water, donkey milk and donkey milk kefir were administered by gavage for 10 days. Animals were sacrificed on day 11. After measuring the short and long diameters of the tumors, tissues were processed for histology. To determine oxidative stress, cell death and proliferation iNOS and eNOS, active caspase-3 and proliferating cell nuclear antigen were assessed using immunohistochemistry. A TUNEL assay also was used to detect apoptosis. Tumor volume decreased in the donkey milk kefir group compared to the control and donkey milk groups. Tumor volume increased in the donkey milk group compared to the control group. Proliferating cell nuclear antigen levels were higher in the donkey milk kefir group compared to the control and donkey milk groups. The number of apoptotic cells was less in the donkey milk group, compared to the control, whereas it was highest in the donkey milk kefir group. Donkey milk administration increased eNOS levels and decreased iNOS levels, compared to the control group. In the donkey milk kefir group, iNOS levels were significantly lower than those of the control and donkey milk groups, while eNOS levels were similar to the control group. Donkey milk kefir induced apoptosis, suppressed proliferation and decreased co-expression of iNOS and eNOS. Donkey milk promoted development of the tumors. Therefore, donkey milk kefir appears to

  6. Projections for Changes in Natural and Technical Snow Reliability of a Major Turkish Ski Resort by Using RegCM4.3.5

    NASA Astrophysics Data System (ADS)

    Ozturk, Tugba; Cenk Demiroglu, O.; Tufan Turp, M.; Türkeş, Murat; Kurnaz, M. Levent

    2014-05-01

    Climate change has been and increasingly will be a major threat to the ski tourism industry whose survival is highly dependent on existence of snow cover of sufficient depth and duration. The common knowledge requires that in order for a ski resort to be viable, it has to perform operations for at least 100 days in seven out of ten winters. For this matter, it is now even more usual for the ski resorts to adapt to this issue by technical snowmaking. In this study, projected future changes for the period of 2010-2040, 2040-2070, and 2070-2100 in air temperature, relative humidity, and snow depth climatology and variability with respect to the control period of 1970-2000 were assessed for the domain of a major ski resort in Turkey. Regional Climate Model (RegCM4.3.5) of ICTP (International Centre for Theoretical Physics) was used for projections of future and present climate conditions. HadGEM2 global climate model of the Met Office Hadley Centre, MPI-ESM-MR of the Max Planck Institute for Meteorology, GFDL-ESM2M of the National Oceanic and Atmospheric Administration Geophysical Fluid Dynamics Laboratory were downscaled to 10 km for the resort and its surrounding region. Both the projections and the downscaling were realized according to the RCP4.5 and the RCP8.5 emission scenarios of the IPCC. The outputs on snow depth were used for a count of the changes on snow cover duration sufficient for skiing actitivies, signaling natural snow-reliability, whereas the outputs on air temperature and relative humidity were utilized for determination of wet-bulb temperatures. The latter measure was used to interpret the changes in the snowmaking capacity, in other words; technical snow-reliability, of the resort. This work was supported by the BU Reasearch Fund under the project number 7362. One of the authors (MLK) was partially supported by Mercator-IPC Fellowship Program.

  7. NOS2 expression in glioma cell lines and glioma primary cell cultures: correlation with neurosphere generation and SOX-2 expression.

    PubMed

    Palumbo, Paola; Miconi, Gianfranca; Cinque, Benedetta; Lombardi, Francesca; La Torre, Cristina; Dehcordi, Soheila Raysi; Galzio, Renato; Cimini, Annamaria; Giordano, Antonio; Cifone, Maria Grazia

    2017-04-11

    Nitric oxide has been implicated in biology and progression of glioblastoma (GBM) being able to influence the cellular signal depending on the concentration and duration of cell exposure. NOS2 (inducible nitric oxide synthase) have been proposed as a component of molecular profile of several tumors, including glioma, one of the most aggressive primary brain tumor featuring local cancer stem cells responsible for enhanced resistance to therapies and for tumor recurrence. Here, we investigated the NOS2 mRNA expression by reverse transcription-PCR in human glioma primary cultures at several grade of malignancy and glioma stem cell (GSC) derived neurospheres. Glioma cell lines were used as positive controls both in terms of stemness marker expression that of capacity of generating neurospheres. NOS2 expression was detected at basal levels in cell lines and primary cultures and appeared significantly up-regulated in cultures kept in the specific medium for neurospheres. The immunofluorescence analysis of all cell cultures to evaluate the levels of SOX-2, a stemness marker aberrantly up-regulated in GBM, was also performed. The potential correlation between NOS2 expression and ability to generate neurospheres and between NOS2 and SOX-2 levels was also verified. The results show that the higher NOS2 expression is detected in all primary cultures able to arise neurosphere. A high and significant correlation between NOS2 expression and SOX-2 positive cells (%) in all cell cultures maintained in standard conditions has been observed. The results shed light on the potential relevance of NOS2 as a prognostic factor for glioma malignancy and recurrence.

  8. EDUCATIONAL STABILITY IN AN UNSTABLE TECHNICAL SOCIETY.

    ERIC Educational Resources Information Center

    LESSINGER, LEON

    CURRENT OPINION REGARDING THE ROLE OF THE HIGH SCHOOL IN PROFESSIONAL, TECHNICAL, AND VOCATIONAL EDUCATION IS THAT CHANGES IN TECHNOLOGY MAKE IT IMPOSSIBLE FOR SCHOOLS TO DO ANY TRAINING OTHER THAN GENERAL EDUCATION, OR THAT YOUTH SHOULD BE TRAINED WITH ONLY IMMEDIATE SALEABLE SKILLS BECAUSE THEY WILL HAVE SEVERAL CAREERS BEFORE RETIRING AND WILL…

  9. Qualification and Development Needs for Technical Education.

    ERIC Educational Resources Information Center

    El Tell, Khalaf; Al-Maaitah, Ayman

    Vast and rapid changes in global technologies have made development of a sound and efficient system of technical education (TE) critical for Oman and the other Arab Gulf countries. Producing TE graduates with the skills needed for success in today's global economy requires TE teachers with the following qualifications: mastery of the core skills…

  10. Characterization and gene expression analysis of pacu (Piaractus mesopotamicus) inducible nitric oxide synthase (iNOS) following Aeromonas dhakensis infection.

    PubMed

    Carriero, Mateus M; Henrique-Silva, Flávio; Caetano, Alexandre Rodrigues; Lobo, Francisco Pereira; Alves, Anderson Luis; Varela, Eduardo Sousa; Del Collado, Maite; Moreira, Gabriel S A; Maia, Antonio A M

    2018-03-01

    Nitric oxide (NO) is an important effector molecule which is involved in a myriad of biological processes, including immune responses against pathogens such as parasites, virus and bacteria. During the inflammatory processes in vertebrates, NO is produced by the inducible nitric oxide synthase (iNOS) enzyme in practically all nucleated cells to suppress or kill intracellular pathogens. The aim of the present study was to characterize the full coding region of the iNOS gene of pacu (Piaractus mesopotamicus), an economically and ecologically important South American fish species, and to analyze mRNA expression levels following intraperitoneal infection with the pathogenic bacterium Aeromonas dhakensis by means of quantitative real time PCR (qPCR). The results showed that the pacu iNOS transcript is 3237 bp in length, encoding a putative protein composed of 1078 amino acid residues. The amino acid sequence showed similarities ranging from 69.03% to 94.34% with other teleost fish and 57.70% with the human iNOS, with all characteristic domains and cofactor binding sites of the enzyme detected. Phylogenetic analysis showed that the iNOS from the red-bellied piranha, another South American characiform, was the closest related sequence to the pacu iNOS. iNOS transcripts were constitutively detected in the liver, spleen and head kidney, and there was a significant upregulation in the liver and spleen at 12, 24 and 48 h after infection with A. dhakensis. No significant variations were observed in the head kidney during the periods analyzed. These results show that iNOS expression was induced by A. dhakensis infection and suggest that this enzyme may be involved in the response to this bacterium in pacu. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Service building. Cross section thru dry dock nos. 4 & ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Service building. Cross section thru dry dock nos. 4 & 5 showing service bldg & 20-75-150 ton cranes (dry dock associates, May 23, 1941). In files of Cushman & Wakefield, building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

  12. Legitimizing Technical Communication in English Departments: Carolyn Miller's "Humanistic Rationale for Technical Writing"

    ERIC Educational Resources Information Center

    Moore, Patrick

    2006-01-01

    Carolyn Miller's oft-cited "Humanistic Rationale for Technical Writing," published in 1979, tries to give technical communication faculty more cultural capital in English departments controlled by literature professors. Miller replaces a positivistic emphasis in technical communication pedagogy with rhetoric. She shows how technical knowledge is…

  13. Wisconsin Technical College Presidential Perspectives on Leading Organizational Change

    ERIC Educational Resources Information Center

    Borowicz, Laurie S.

    2012-01-01

    This qualitative study examines leadership perceptions of attributes needed for effectively leading organizations within and through change. Current change forces substantiate the need for higher educational institutions to change in order to fulfill their missions. Creating a culture of organizational change presents a leadership challenge. The…

  14. Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism

    NASA Technical Reports Server (NTRS)

    Boo, Yong Chool; Hwang, Jinah; Sykes, Michelle; Michell, Belinda J.; Kemp, Bruce E.; Lum, Hazel; Jo, Hanjoong

    2002-01-01

    Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli.

  15. Contrasting effects of exercise and NOS inhibition on tissue-specific fatty acid and glucose uptake in mice.

    PubMed

    Rottman, Jeffrey N; Bracy, Deanna; Malabanan, Carlo; Yue, Zou; Clanton, Jeff; Wasserman, David H

    2002-07-01

    Isotopic techniques were used to test the hypothesis that exercise and nitric oxide synthase (NOS) inhibition have distinct effects on tissue-specific fatty acid and glucose uptakes in a conscious, chronically catheterized mouse model. Uptakes were measured using the radioactive tracers (125)I-labeled beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) and deoxy-[2-(3)H]glucose (DG) during treadmill exercise with and without inhibition of NOS. [(125)I]BMIPP uptake at rest differed substantially among tissues with the highest levels in heart. With exercise, [(125)I]BMIPP uptake increased in both heart and skeletal muscles. In sedentary mice, NOS inhibition induced by nitro-L-arginine methyl ester (L-NAME) feeding increased heart and soleus [(125)I]BMIPP uptake. In contrast, exercise, but not L-NAME feeding, resulted in increased heart and skeletal muscle [2-(3)H]DG uptake. Significant interactions were not observed in the effects of combined exercise and L-NAME feeding on [(125)I]BMIPP and [2-(3)H]DG uptakes. In the conscious mouse, exercise and NOS inhibition produce distinct patterns of tissue-specific fatty acid and glucose uptake; NOS is not required for important components of exercise-associated metabolic signaling, or other mechanisms compensate for the absence of this regulatory mechanism.

  16. Expanding the Chemistry of the Class C Radical SAM Methyltransferase NosN by Using an Allyl Analogue of SAM.

    PubMed

    Ji, Xinjian; Mandalapu, Dhanaraju; Cheng, Jinduo; Ding, Wei; Zhang, Qi

    2018-03-30

    The radical S-adenosylmethionine (SAM) superfamily enzymes cleave SAM reductively to generate a highly reactive 5'-deoxyadenosyl (dAdo) radical, which initiates remarkably diverse reactions. Unlike most radical SAM enzymes, the class C radical SAM methyltransferase NosN binds two SAMs in the active site, using one SAM to produce a dAdo radical and the second as a methyl donor. Here, we report a mechanistic investigation of NosN in which an allyl analogue of SAM (allyl-SAM) was used. We show that NosN cleaves allyl-SAM efficiently and the resulting dAdo radical can be captured by the olefin moieties of allyl-SAM or 5'-allylthioadenosine (ATA), the latter being a derivative of allyl-SAM. Remarkably, we found that NosN produced two distinct sets of products in the presence and absence of the methyl acceptor substrate, thus suggesting substrate-triggered production of ATA from allyl-SAM. We also show that NosN produces S-adenosylhomocysteine from 5'-thioadenosine and homoserine lactone. These results support the idea that 5'-methylthioadenosine is the direct methyl donor in NosN reactions, and demonstrate great potential to modulate radical SAM enzymes for novel catalytic activities. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Electronic inventory systems and barcode technology: impact on pharmacy technical accuracy and error liability.

    PubMed

    Oldland, Alan R; Golightly, Larry K; May, Sondra K; Barber, Gerard R; Stolpman, Nancy M

    2015-01-01

    To measure the effects associated with sequential implementation of electronic medication storage and inventory systems and product verification devices on pharmacy technical accuracy and rates of potential medication dispensing errors in an academic medical center. During four 28-day periods of observation, pharmacists recorded all technical errors identified at the final visual check of pharmaceuticals prior to dispensing. Technical filling errors involving deviations from order-specific selection of product, dosage form, strength, or quantity were documented when dispensing medications using (a) a conventional unit dose (UD) drug distribution system, (b) an electronic storage and inventory system utilizing automated dispensing cabinets (ADCs) within the pharmacy, (c) ADCs combined with barcode (BC) verification, and (d) ADCs and BC verification utilized with changes in product labeling and individualized personnel training in systems application. Using a conventional UD system, the overall incidence of technical error was 0.157% (24/15,271). Following implementation of ADCs, the comparative overall incidence of technical error was 0.135% (10/7,379; P = .841). Following implementation of BC scanning, the comparative overall incidence of technical error was 0.137% (27/19,708; P = .729). Subsequent changes in product labeling and intensified staff training in the use of BC systems was associated with a decrease in the rate of technical error to 0.050% (13/26,200; P = .002). Pharmacy ADCs and BC systems provide complementary effects that improve technical accuracy and reduce the incidence of potential medication dispensing errors if this technology is used with comprehensive personnel training.

  18. Electronic Inventory Systems and Barcode Technology: Impact on Pharmacy Technical Accuracy and Error Liability

    PubMed Central

    Oldland, Alan R.; May, Sondra K.; Barber, Gerard R.; Stolpman, Nancy M.

    2015-01-01

    Purpose: To measure the effects associated with sequential implementation of electronic medication storage and inventory systems and product verification devices on pharmacy technical accuracy and rates of potential medication dispensing errors in an academic medical center. Methods: During four 28-day periods of observation, pharmacists recorded all technical errors identified at the final visual check of pharmaceuticals prior to dispensing. Technical filling errors involving deviations from order-specific selection of product, dosage form, strength, or quantity were documented when dispensing medications using (a) a conventional unit dose (UD) drug distribution system, (b) an electronic storage and inventory system utilizing automated dispensing cabinets (ADCs) within the pharmacy, (c) ADCs combined with barcode (BC) verification, and (d) ADCs and BC verification utilized with changes in product labeling and individualized personnel training in systems application. Results: Using a conventional UD system, the overall incidence of technical error was 0.157% (24/15,271). Following implementation of ADCs, the comparative overall incidence of technical error was 0.135% (10/7,379; P = .841). Following implementation of BC scanning, the comparative overall incidence of technical error was 0.137% (27/19,708; P = .729). Subsequent changes in product labeling and intensified staff training in the use of BC systems was associated with a decrease in the rate of technical error to 0.050% (13/26,200; P = .002). Conclusions: Pharmacy ADCs and BC systems provide complementary effects that improve technical accuracy and reduce the incidence of potential medication dispensing errors if this technology is used with comprehensive personnel training. PMID:25684799

  19. 75 FR 21623 - Commission Information Collection Activities (FERC Form Nos. 6 and 6-Q); Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-26

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket Nos. IC10-6-001 and IC10-6Q-001] Commission Information Collection Activities (FERC Form Nos. 6 and 6-Q); Comment Request; Submitted for OMB... (75FR5061, 2/1/ 2010) requesting public comments. FERC received one comment on the FERC Form No. 6 and FERC...

  20. Loss of nNOS inhibits compensatory muscle hypertrophy and exacerbates inflammation and eccentric contraction-induced damage in mdx mice

    PubMed Central

    Froehner, Stanley C.; Reed, Sarah M.; Anderson, Kendra N.; Huang, Paul L.; Percival, Justin M.

    2015-01-01

    Approaches targeting nitric oxide (NO) signaling show promise as therapies for Duchenne and Becker muscular dystrophies. However, the mechanisms by which NO benefits dystrophin-deficient muscle remain unclear, but may involve nNOSβ, a newly discovered enzymatic source of NO in skeletal muscle. Here we investigate the impact of dystrophin deficiency on nNOSβ and use mdx mice engineered to lack nNOSμ and nNOSβ to discern how the loss of nNOS impacts dystrophic skeletal muscle pathology. In mdx muscle, nNOSβ was mislocalized and its association with the Golgi complex was reduced. nNOS depletion from mdx mice prevented compensatory skeletal muscle cell hypertrophy, decreased myofiber central nucleation and increased focal macrophage cell infiltration, indicating exacerbated dystrophic muscle damage. Reductions in muscle integrity in nNOS-null mdx mice were accompanied by decreases in specific force and increased susceptibility to eccentric contraction-induced muscle damage compared with mdx controls. Unexpectedly, muscle fatigue was unaffected by nNOS depletion, revealing a novel latent compensatory mechanism for the loss of nNOS in mdx mice. Together with previous studies, these data suggest that localization of both nNOSμ and nNOSβ is disrupted by dystrophin deficiency. They also indicate that nNOS has a more complex role as a modifier of dystrophic pathology and broader therapeutic potential than previously recognized. Importantly, these findings also suggest nNOSβ as a new drug target and provide a new conceptual framework for understanding nNOS signaling and the benefits of NO therapies in dystrophinopathies. PMID:25214536

  1. Platelet Activating Factor-Induced Ceramide Micro-Domains Drive Endothelial NOS Activation and Contribute to Barrier Dysfunction

    PubMed Central

    Predescu, Sanda; Knezevic, Ivana; Bardita, Cristina; Neamu, Radu Florin; Brovcovych, Viktor; Predescu, Dan

    2013-01-01

    The spatial and functional relationship between platelet activating factor-receptor (PAF-R) and nitric oxide synthase (eNOS) in the lateral plane of the endothelial plasma membrane is poorly characterized. In this study, we used intact mouse pulmonary endothelial cells (ECs) as well as endothelial plasma membrane patches and subcellular fractions to define a new microdomain of plasmalemma proper where the two proteins colocalize and to demonstrate how PAF-mediated nitric oxide (NO) production fine-tunes ECs function as gatekeepers of vascular permeability. Using fluorescence microscopy and immunogold labeling electron microscopy (EM) on membrane patches we demonstrate that PAF-R is organized as clusters and colocalizes with a subcellular pool of eNOS, outside recognizable vesicular profiles. Moreover, PAF-induced acid sphingomyelinase activation generates a ceramide-based microdomain on the external leaflet of plasma membrane, inside of which a signalosome containing eNOS shapes PAF-stimulated NO production. Real-time measurements of NO after PAF-R ligation indicated a rapid (5 to 15 min) increase in NO production followed by a > 45 min period of reduction to basal levels. Moreover, at the level of this new microdomain, PAF induces a dynamic phosphorylation/dephosphorylation of Ser, Thr and Tyr residues of eNOS that correlates with NO production. Altogether, our findings establish the existence of a functional partnership PAF-R/eNOS on EC plasma membrane, at the level of PAF-induced ceramide plasma membrane microdomains, outside recognized vesicular profiles. PMID:24086643

  2. Ambient ultrafine particles reduce endothelial nitric oxide production via S-glutathionylation of eNOS.

    PubMed

    Du, Yunfeng; Navab, Mohamad; Shen, Melody; Hill, James; Pakbin, Payam; Sioutas, Constantinos; Hsiai, Tzung K; Li, Rongsong

    2013-07-05

    Exposure to airborne particulate pollutants is intimately linked to vascular oxidative stress and inflammatory responses with clinical relevance to atherosclerosis. Particulate matter (PM) has been reported to induce endothelial dysfunction and atherosclerosis. Here, we tested whether ambient ultrafine particles (UFP, diameter <200 nm) modulate eNOS activity in terms of nitric oxide (NO) production via protein S-glutathionylation. Treatment of human aortic endothelial cells (HAEC) with UFP significantly reduced NO production. UFP-mediated reduction in NO production was restored in the presence of JNK inhibitor (SP600125), NADPH oxidase inhibitor (Apocynin), anti-oxidant (N-acetyl cysteine), and superoxide dismutase mimetics (Tempol and MnTMPyP). UFP exposure increased the GSSG/GSH ratio and eNOS S-glutathionylation, whereas over-expression of Glutaredoxin-1 (to inhibit S-glutathionylation) restored UFP-mediated reduction in NO production by nearly 80%. Thus, our findings suggest that eNOS S-glutathionylation is a potential mechanism underlying ambient UFP-induced reduction of NO production. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Ambient ultrafine particles reduce endothelial nitric oxide production via S-glutathionylation of eNOS

    PubMed Central

    Du, Yunfeng; Navab, Mohamad; Shen, Melody; Hill, James; Pakbin, Payam; Sioutas, Constantinos; Hsiai, Tzung; Li, Rongsong

    2013-01-01

    Exposure to airborne particulate pollutants is intimately linked to vascular oxidative stress and inflammatory responses with clinical relevance to atherosclerosis. Particulate matter (PM) has been reported to induce endothelial dysfunction and atherosclerosis. Here, we tested whether ambient ultrafine particles (UFP, diameter < 200 nm) modulate eNOS activity in terms of nitric oxide (NO) production via protein S-glutathionylation. Treatment of human aortic endothelial cells (HAEC) with UFP significantly reduced NO production. UFP-mediated reduction in NO production was restored in the presence of JNK inhibitor (SP600125), NADPH oxidase inhibitor (Apocynin), anti-oxidant (N-acetyl cysteine), and superoxide dismutase mimetics (Tempol and MnTMPyP). UFP exposure increased the GSSG/GSH ratio and eNOS S-glutathionylation, whereas over-expression of Glutaredoxin-1 (to inhibit S-glutathionylation) restored UFP-mediated reduction in NO production by nearly 80%. Thus, our findings suggest that eNOS S-glutathionylation is a potential mechanism underlying ambient UFP-induced reduction of NO production. PMID:23751346

  4. The flavinyl transferase ApbE of Pseudomonas stutzeri matures the NosR protein required for nitrous oxide reduction.

    PubMed

    Zhang, Lin; Trncik, Christian; Andrade, Susana L A; Einsle, Oliver

    2017-02-01

    The copper-containing enzyme nitrous oxide reductase (N 2 OR) catalyzes the transformation of nitrous oxide (N 2 O) to dinitrogen (N 2 ) in microbial denitrification. Several accessory factors are essential for assembling the two copper sites Cu A and Cu Z , and for maintaining the activity. In particular, the deletion of either the transmembrane iron-sulfur flavoprotein NosR or the periplasmic protein NosX, a member of the ApbE family, abolishes N 2 O respiration. Here we demonstrate through biochemical and structural studies that the ApbE protein from Pseudomonas stutzeri, where the nosX gene is absent, is a monomeric FAD-binding protein that can serve as the flavin donor for NosR maturation via covalent flavinylation of a threonine residue. The flavin transfer reaction proceeds both in vivo and in vitro to generate post-translationally modified NosR with covalently bound FMN. Only FAD can act as substrate and the reaction requires a divalent cation, preferably Mg 2+ that was also present in the crystal structure. In addition, the reaction is species-specific to a certain extent. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI): II. Reliability and Convergent Validity

    PubMed Central

    Wilde, Elisabeth A.; Kelly, Tara M.; Weyand, Annie M.; Yallampalli, Ragini; Waldron, Eric J.; Pedroza, Claudia; Schnelle, Kathleen P.; Boake, Corwin; Levin, Harvey S.; Moretti, Paolo

    2010-01-01

    Abstract A standardized measure of neurological dysfunction specifically designed for TBI currently does not exist and the lack of assessment of this domain represents a substantial gap. To address this, the Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) was developed for TBI outcomes research through the addition to and modification of items specifically relevant to patients with TBI, based on the National Institutes of Health Stroke Scale. In a sample of 50 participants (mean age = 33.3 years, SD = 12.9) ≤18 months (mean = 3.1, SD = 3.2) following moderate (n = 8) to severe (n = 42) TBI, internal consistency of the NOS-TBI was high (Cronbach's alpha = 0.942). Test-retest reliability also was high (ρ = 0.97, p < 0.0001), and individual item kappas between independent raters were excellent, ranging from 0.83 to 1.0. Overall inter-rater agreement between independent raters (Kendall's coefficient of concordance) for the NOS-TBI total score was excellent (W = 0.995). Convergent validity was demonstrated through significant Spearman rank-order correlations between the NOS-TBI and the concurrently administered Disability Rating Scale (ρ = 0.75, p < 0.0001), Rancho Los Amigos Scale (ρ = −0.60, p < 0.0001), Supervision Rating Scale (ρ = 0.59, p < 0.0001), and the FIM™ (ρ = −0.68, p < 0.0001). These results suggest that the NOS-TBI is a reliable and valid measure of neurological functioning in patients with moderate to severe TBI. PMID:20210595

  6. Technical Support Document for Version 3.6.1 of the COMcheck Software

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

    Bartlett, Rosemarie; Connell, Linda M.; Gowri, Krishnan

    2009-09-29

    This technical support document (TSD) is designed to explain the technical basis for the COMcheck software as originally developed based on the ANSI/ASHRAE/IES Standard 90.1-1989 (Standard 90.1-1989). Documentation for other national model codes and standards and specific state energy codes supported in COMcheck has been added to this report as appendices. These appendices are intended to provide technical documentation for features specific to the supported codes and for any changes made for state-specific codes that differ from the standard features that support compliance with the national model codes and standards.

  7. 50. INTERIOR OF BRIDGE SUSPENSION STRUCTURE ABOVE BRIDGE NOS. 10 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    50. INTERIOR OF BRIDGE SUSPENSION STRUCTURE ABOVE BRIDGE NOS. 10 AND 9 SHOWING CABLE COUNTERWEIGHT SYSTEM AND SCREW-TYPE VERTICAL ADJUSTMENT MACHINERY (LIFTING SCREWS). LOOKING NORTH. - Greenville Yard, Transfer Bridge System, Port of New York/New Jersey, Upper New York Bay, Jersey City, Hudson County, NJ

  8. The U.S. government technical report and the transfer of federally funded aerospace R & D

    NASA Technical Reports Server (NTRS)

    Pinelli, Thomas E.; Barclay, Rebecca O.; Kennedy, John M.

    1993-01-01

    This article discusses the U.S. government technical report and the transfer of federally funded aerospace research and development in a conceptual framework of the federal government as a producer of scientific and technical information. The article summarizes current literature and research and discusses U.S. government technical report use and the importance of using data obtained from the NASA/DoD Aerospace Knowledge Diffusion Research Project. The authors make a case for changing existing U.S. technology policy and present a research agenda for the U.S. government technical report.

  9. Regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord.

    PubMed

    Jing, Y; Fleete, M S; Collie, N D; Zhang, H; Liu, P

    2013-11-12

    Accumulating evidence suggests that the metabolism of l-arginine, a metabolically versatile amino acid, is critically involved in the aging process. The present study compared the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of l-arginine and its eight down-stream metabolites in the brain stem (pons and medulla) and the cervical spinal cord in 3- (young) and 22- (aged) month-old male Sprague-Dawley rats. Total NOS activity was significantly reduced with age in the spinal cord (but not brain stem), and there were no age-related changes in arginase activity in both regions. Western blot revealed decreased protein expression of endothelial NOS, but not neuronal NOS, with age in both regions. Furthermore, there were significantly decreased l-arginine, glutamate, GABA and spermine levels and increased putrescine and spermidine levels with age in both regions. Although the absolute concentrations of l-arginine and six metabolites were significantly different between the brain stem and spinal cord in both age groups, there were similar clusters between l-arginine and its three main metabolites (l-citrulline, l-ornithine and agmatine) in both regions, which changed as a function of age. These findings, for the first time, demonstrate the regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord. Future research is required to understand the functional significance of these changes and the underlying mechanisms. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. Problems of Technical Electrodynamics (Selected Articles),

    DTIC Science & Technology

    1984-04-11

    copy available. ii DC 83143001 PAGE 1 PROBLEMS OF TECHNICAL ELECTRODYNAMICS. DOC - 83143001 PAGE 2 In the collector /collection are connected the...composite/ compound reliable in mechanical sense forgings of rotors with a weight of 250 t and it is more and rotor binding bands. These K forgings must be...go - calculated coefficient, which considers the character of temperature field. With a linear change in temperature .=1, with parabolic =3

  11. Nos2 inactivation promotes the development of medulloblastoma in Ptch1(+/-) mice by deregulation of Gap43-dependent granule cell precursor migration.

    PubMed

    Haag, Daniel; Zipper, Petra; Westrich, Viola; Karra, Daniela; Pfleger, Karin; Toedt, Grischa; Blond, Frederik; Delhomme, Nicolas; Hahn, Meinhard; Reifenberger, Julia; Reifenberger, Guido; Lichter, Peter

    2012-01-01

    Medulloblastoma is the most common malignant brain tumor in children. A subset of medulloblastoma originates from granule cell precursors (GCPs) of the developing cerebellum and demonstrates aberrant hedgehog signaling, typically due to inactivating mutations in the receptor PTCH1, a pathomechanism recapitulated in Ptch1(+/-) mice. As nitric oxide may regulate GCP proliferation and differentiation, we crossed Ptch1(+/-) mice with mice lacking inducible nitric oxide synthase (Nos2) to investigate a possible influence on tumorigenesis. We observed a two-fold higher medulloblastoma rate in Ptch1(+/-) Nos2(-/-) mice compared to Ptch1(+/-) Nos2(+/+) mice. To identify the molecular mechanisms underlying this finding, we performed gene expression profiling of medulloblastomas from both genotypes, as well as normal cerebellar tissue samples of different developmental stages and genotypes. Downregulation of hedgehog target genes was observed in postnatal cerebellum from Ptch1(+/+) Nos2(-/-) mice but not from Ptch1(+/-) Nos2(-/-) mice. The most consistent effect of Nos2 deficiency was downregulation of growth-associated protein 43 (Gap43). Functional studies in neuronal progenitor cells demonstrated nitric oxide dependence of Gap43 expression and impaired migration upon Gap43 knock-down. Both effects were confirmed in situ by immunofluorescence analyses on tissue sections of the developing cerebellum. Finally, the number of proliferating GCPs at the cerebellar periphery was decreased in Ptch1(+/+) Nos2(-/-) mice but increased in Ptch1(+/-) Nos2(-/) (-) mice relative to Ptch1(+/-) Nos2(+/+) mice. Taken together, these results indicate that Nos2 deficiency promotes medulloblastoma development in Ptch1(+/-) mice through retention of proliferating GCPs in the external granular layer due to reduced Gap43 expression. This study illustrates a new role of nitric oxide signaling in cerebellar development and demonstrates that the localization of pre-neoplastic cells during

  12. Case Study on Technical and Vocational Education in Japan. Case Studies on Technical and Vocational Education in Asia and the Pacific.

    ERIC Educational Resources Information Center

    Iwamoto, Muneharu

    In the course of Japan's economic progress, remarkable changes have occurred in the structure of industry and employment. Workers are in extremely short supply in such occupations as mining, manufacturing and construction, services, transportation and communication, sales, and professional and technical. On the basis of recommendations of the…

  13. 75 FR 64751 - Braidwood Station, Units 1 and 2 and Byron Station, Unit Nos. 1 and 2; Notice of Withdrawal of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-20

    ...- 2010-0329] Braidwood Station, Units 1 and 2 and Byron Station, Unit Nos. 1 and 2; Notice of Withdrawal... NPF-77 for Braidwood Station, Units 1 and 2, respectively, located in Will County, Illinois, and to Facility Operating License Nos. NPF-37 and NPF-66 for Byron Station, Unit Nos. 1 and 2, respectively...

  14. 78 FR 5755 - Change in Terminology: “Mental Retardation” to “Intellectual Disability”

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-28

    ... SOCIAL SECURITY ADMINISTRATION 20 CFR Parts 404 and 416 [Docket No. SSA-2012-0066] RIN 0960-AH52 Change in Terminology: ``Mental Retardation'' to ``Intellectual Disability'' AGENCY: Social Security... non- substantive change requests. (Catalog of Federal Domestic Program Nos. 96.001, Social Security...

  15. Employment Shifts in the Technical and Further Education Workforce in Victoria.

    ERIC Educational Resources Information Center

    Shah, Chandra

    2003-01-01

    Analyzes changes in Technical and Further Education (TAFE) work force in Victoria, Australia, that occurred during the period 1993-98. Main changes include increased participation of women, significant growth in part-time employment, decline in full-time (mainly male) employment, and an increased use of seasonal teachers. (Includes 10 figures and…

  16. 76 FR 31416 - Federal Acquisition Regulation; Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... ADMINISTRATION 48 CFR Parts 52 and 53 [FAC 2005-52; Item VI; Docket 2011-0078; Sequence 2] Federal Acquisition... publication schedules. Please cite FAC 2005-52, Technical Amendments. SUPPLEMENTARY INFORMATION: In order to update certain elements in 48 CFR parts 52 and 53, this document makes editorial changes to the Federal...

  17. NOS2-deficient mice with hypoxic necrotizing lung lesions predict outcomes of tuberculosis chemotherapy in humans.

    PubMed

    Gengenbacher, Martin; Duque-Correa, Maria A; Kaiser, Peggy; Schuerer, Stefanie; Lazar, Doris; Zedler, Ulrike; Reece, Stephen T; Nayyar, Amit; Cole, Stewart T; Makarov, Vadim; Barry Iii, Clifton E; Dartois, Véronique; Kaufmann, Stefan H E

    2017-08-18

    During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used in TB drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We found that Nos2 -/- mice incapable of NO-production in immune cells as microbial defence uniformly develop hypoxic necrotizing lung lesions, widely observed in human TB. To study the impact of hypoxic necrosis on the efficacy of antimycobacterials and drug candidates, we subjected Nos2 -/- mice with TB to monotherapy before or after establishment of human-like pathology. Isoniazid induced a drug-tolerant persister population only when necrotic lesions were present. Rifapentine was more potent than rifampin prior to development of human-like pathology and equally potent thereafter, in agreement with recent clinical trials. Pretomanid, delamanid and the pre-clinical candidate BTZ043 were bactericidal independent of pulmonary pathology. Linezolid was bacteriostatic in TB-infected Nos2 -/- mice but significantly improved lung pathology. Hypoxic necrotizing lesions rendered moxifloxacin less active. In conclusion, Nos2 -/- mice are a predictive TB drug development tool owing to their consistent development of human-like pathology.

  18. The Development of Scientific Literacy through Nature of Science (NoS) within Inquiry Based Learning Approach

    NASA Astrophysics Data System (ADS)

    Widowati, A.; Widodo, E.; Anjarsari, P.; Setuju

    2017-11-01

    Understanding of science instructional leading to the formation of student scientific literacy, seems not yet fully understood well by science teachers. Because of this, certainly needs to be reformed because science literacy is a major goal in science education for science education reform. Efforts of development science literacy can be done by help students develop an information conception of the Nature of Science (NoS) and apply inquiry approach. It is expected that students’ science literacy can develop more optimal by combining NoS within inquiry approach. The purpose of this research is to produce scientific literacy development model of NoS within inquiry-based learning. The preparation of learning tools will be maked through Research and Development (R & D) following the 4-D model (Define, Design, Develop, and Disseminate) and Borg & Gall. This study is a follow-up of preliminary research results about the inquiry profile of junior high school students indicating that most categories are quite good. The design of the model NoS within inquiry approach for developing scientific literacy is using MER Model in development educational reconstruction. This research will still proceed to the next stage that is Develop.

  19. Retinoic acid-induced nNOS expression depends on a novel PI3K/Akt/DAX1 pathway in human TGW-nu-I neuroblastoma cells.

    PubMed

    Nagl, Florian; Schönhofer, Katrin; Seidler, Barbara; Mages, Jörg; Allescher, Hans-Dieter; Schmid, Roland M; Schneider, Günter; Saur, Dieter

    2009-11-01

    Neuronal nitric oxide synthase (nNOS)-derived nitric oxide (NO) acts as a neurotransmitter and intracellular signaling molecule in the central and peripheral nervous system. NO regulates multiple processes like neuronal development, plasticity, and differentiation and is a mediator of neurotoxicity. The nNOS gene is highly complex with 12 alternative first exons, exon 1a-1l, transcribed from distinct promoters, leading to nNOS variants with different 5'-untranslated regions. Transcriptional control of the nNOS gene is not understood in detail. To investigate regulation of nNOS gene expression by retinoic acid (RA), we used the human neuroblastoma cell line TGW-nu-I as a model system. We show that RA induces nNOS transcription in a protein synthesis-dependent fashion. We identify the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and the atypical orphan nuclear receptor DAX1 (NR0B1) as critical mediators involved in RA-induced nNOS gene transcription. RA treatment increases DAX1 expression via PI3K/Akt signaling. Upregulation of DAX1 expression in turn induces nNOS transcription in response to RA. These results identify nNOS as a target gene of a novel RA/PI3K/Akt/DAX1-dependent pathway in human neuroblastoma cells and stress the functional importance of the transcriptional regulator DAX1 for nNOS gene expression in response to RA treatment.

  20. REM sleep deprivation induces endothelial dysfunction and hypertension in middle-aged rats: Roles of the eNOS/NO/cGMP pathway and supplementation with L-arginine.

    PubMed

    Jiang, Jiaye; Gan, Zhongyuan; Li, Yuan; Zhao, Wenqi; Li, Hanqing; Zheng, Jian-Pu; Ke, Yan

    2017-01-01

    Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes. The results showed that REM sleep deprivation decreased body weight, increased blood pressure, and impaired endothelial function of the aortas in middle-aged rats but not young rats. Moreover, nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) concentrations as well as endothelial NO synthase (eNOS) phosphorylation in the aorta were decreased by REM sleep deprivation. Supplementation with L-arginine could protect against REM sleep deprivation-induced hypertension, endothelial dysfunction, and damage to the eNOS/NO/cGMP signaling pathway. The results of the present study suggested that REM sleep deprivation caused endothelial dysfunction and hypertension in middle-aged rats via the eNOS/NO/cGMP pathway and that these pathological changes could be inhibited via L-arginine supplementation. The present study provides a new strategy to inhibit the signaling pathways involved in insomnia-induced or insomnia-enhanced cardiovascular diseases.

  1. NASA Technical Standards Program and Implications for Lessons Learned and Technical Standard Integration

    NASA Technical Reports Server (NTRS)

    Gill, Paul S.; Garcia, Danny; Vaughan, William W.; Parker, Nelson C. (Technical Monitor)

    2002-01-01

    The National Aeronautics and Space Agency consists of fourteen Facilities throughout the United States. They are organized to support the Agency's principal Enterprises: (1) Space Science, (2) Earth Science, (3) Aerospace Technology, (4) Human Exploration and Development of Space, and (5) Biological and Physical Research. Technical Standards are important to the activities of each Enterprise and have been an integral part in the development and operation of NASA Programs and Projects since the Agency was established in 1959. However, for years each Center was responsible for its own standards development and selection of non-NASA technical standards that met the needs of Programs and Projects for which they were responsible. There were few Agencywide applicable Technical Standards, mainly those in area of safety. Department of Defense Standards and Specifications were the foundation and main source for Technical Standards used by the Agency. This process existed until about 1997 when NASA embarked on a Program to convert NASA's Center-developed Technical Standards into Agencywide endorsed NASA Preferred Technical Standards. In addition, action was taken regarding the formal adoption of non-NASA Technical Standards (DOD, SAE, ASTM, ASME, IEEE, etc.) as NASA Preferred Technical Standards.

  2. AP-1 Inhibition by SR 11302 Protects Human Hepatoma HepG2 Cells from Bile Acid-Induced Cytotoxicity by Restoring the NOS-3 Expression

    PubMed Central

    González-Rubio, Sandra; Linares, Clara I.; Aguilar-Melero, Patricia; Rodríguez-Perálvarez, Manuel; Montero-Álvarez, José L.

    2016-01-01

    The harmful effects of bile acid accumulation occurring during cholestatic liver diseases have been associated with oxidative stress increase and endothelial nitric oxide synthase (NOS-3) expression decrease in liver cells. We have previously reported that glycochenodeoxycholic acid (GCDCA) down-regulates gene expression by increasing SP1 binding to the NOS-3 promoter in an oxidative stress dependent manner. In the present study, we aimed to investigate the role of transcription factor (TF) AP-1 on the NOS-3 deregulation during GCDCA-induced cholestasis. The cytotoxic response to GCDCA was characterized by 1) the increased expression and activation of TFs cJun and c-Fos; 2) a higher binding capability of these at position -666 of the NOS-3 promoter; 3) a decrease of the transcriptional activity of the promoter and the expression and activity of NOS-3; and 4) the expression increase of cyclin D1. Specific inhibition of AP-1 by the retinoid SR 11302 counteracted the cytotoxic effects induced by GCDCA while promoting NOS-3 expression recovery and cyclin D1 reduction. NOS activity inhibition by L-NAME inhibited the protective effect of SR 11302. Inducible NOS isoform was no detected in this experimental model of cholestasis. Our data provide direct evidence for the involvement of AP-1 in the NOS-3 expression regulation during cholestasis and define a critical role for NOS-3 in regulating the expression of cyclin D1 during the cell damage induced by bile acids. AP-1 appears as a potential therapeutic target in cholestatic liver diseases given its role as a transcriptional repressor of NOS-3. PMID:27490694

  3. Expressive/Exploratory Technical Writing (XTW) in Engineering: Shifting the Technical Writing Curriculum

    ERIC Educational Resources Information Center

    Warnock, Scott; Kahn, Michael

    2007-01-01

    While the importance of "expressive writing," or informal, self-directed writing, has been well established, teachers underutilize it, particularly in technical writing courses. We introduce the term expressive/exploratory technical writing (XTW), which is the use of informal, self-directed writing to problem-solve in technical fields. We describe…

  4. 15. Dry Dock No. 4. Longitudinal Section. Subdivision Nos. I ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. Dry Dock No. 4. Longitudinal Section. Subdivision Nos. I and II (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

  5. 16. Dry Dock No. 4. Longitudinal Section. Subdivision Nos. III ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    16. Dry Dock No. 4. Longitudinal Section. Subdivision Nos. III and IV (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

  6. Involvement of PI3K, Akt, and RhoA in oestradiol regulation of cardiac iNOS expression.

    PubMed

    Zafirovic, Sonja; Sudar-Milovanovic, Emina; Obradovic, Milan; Djordjevic, Jelena; Jasnic, Nebojsa; Borovic, Milica Labudovic; Isenovic, Esma R

    2018-02-12

    Oestradiol is an important regulatory factor with several positive effects on the cardiovascular (CV) system. We evaluated the molecular mechanism of the in vivo effects of oestradiol on the regulation of cardiac inducible nitric oxide (NO) synthase (iNOS) expression and activity. Male Wistar rats were treated with oestradiol (40 mg/kg, intraperitoneally) and after 24 h the animals were sacrificed. The concentrations of NO and L-Arginine (L-Arg) were determined spectrophotometrically. For protein expressions of iNOS, p65 subunit of nuclear factor-κB (NFκB-p65), Ras homolog gene family-member A (RhoA), angiotensin II receptor type 1 (AT1R), insulin receptor substrate 1 (IRS-1), p85, p110 and protein kinase B (Akt), Western blot method was used. Co-immunoprecipitation was used for measuring the association of IRS-1 with the p85 subunit of phosphatidylinositol-3-kinase (PI3K). The expression of iNOS messenger ribonucleic acid (mRNA) was measured with the quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemical analysis of the tissue was used to detect localization and expression of iNOS in heart tissue. Oestradiol treatment reduced L-Arg concentration (p<0.01), iNOS mRNA (p<0.01) and protein (p<0.001) expression, level of RhoA (p<0.05) and AT1R (p<0.001) protein. In contrast, plasma NO (p<0.05), Akt phosphorylation at Thr308 (p<0.05) and protein level of p85 (p<0.001) increased after oestradiol treatment. Our results suggest that oestradiol in vivo regulates cardiac iNOS expression via the PI3K/Akt signaling pathway, through attenuation of RhoA and AT1R. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. 75 FR 14639 - Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 1, 2, and 3...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-26

    ... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-003, 50-247, and 50-286; NRC-2010-0137] Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 1, 2, and 3; Environmental Assessment and Finding of No Significant Impact The U.S. Nuclear Regulatory Commission (NRC) is considering issuance of an exemption, pursuant to Title 10 of...

  8. Ergodicity of the Stochastic Nosé-Hoover Heat Bath

    NASA Astrophysics Data System (ADS)

    Wei Chung Lo,; Baowen Li,

    2010-07-01

    We numerically study the ergodicity of the stochastic Nosé-Hoover heat bath whose formalism is based on the Markovian approximation for the Nosé-Hoover equation [J. Phys. Soc. Jpn. 77 (2008) 103001]. The approximation leads to a Langevin-like equation driven by a fluctuating dissipative force and multiplicative Gaussian white noise. The steady state solution of the associated Fokker-Planck equation is the canonical distribution. We investigate the dynamics of this method for the case of (i) free particle, (ii) nonlinear oscillators and (iii) lattice chains. We derive the Fokker-Planck equation for the free particle and present approximate analytical solution for the stationary distribution in the context of the Markovian approximation. Numerical simulation results for nonlinear oscillators show that this method results in a Gaussian distribution for the particles velocity. We also employ the method as heat baths to study nonequilibrium heat flow in one-dimensional Fermi-Pasta-Ulam (FPU-β) and Frenkel-Kontorova (FK) lattices. The establishment of well-defined temperature profiles are observed only when the lattice size is large. Our results provide numerical justification for such Markovian approximation for classical single- and many-body systems.

  9. Hypercholesterolemia-induced erectile dysfunction: endothelial nitric oxide synthase (eNOS) uncoupling in the mouse penis by NAD(P)H oxidase

    PubMed Central

    Musicki, Biljana; Liu, Tongyun; Lagoda, Gwen A.; Strong, Travis D.; Sezen, Sena F.; Johnson, Justin M.; Burnett, Arthur L.

    2010-01-01

    INTRODUCTION Hypercholesterolemia induces erectile dysfunction (ED) mostly by increasing oxidative stress and impairing endothelial function in the penis, but the mechanisms regulating reactive oxygen species (ROS) production in the penis are not understood. AIMS We evaluated whether hypercholesterolemia activates nicotinamide adenine dinucleotide phosphate (NAD[P]H) oxidase in the penis, providing an initial source of ROS to induce endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction resulting in ED. METHODS Low-density-lipoprotein receptor (LDLR)–null mice were fed Western diet for 4 weeks to induce early-stage hyperlipidemia. Wild type (WT) mice fed regular chow served as controls. Mice received NAD(P)H oxidase inhibitor apocynin (10 mM in drinking water) or vehicle. Erectile function was assessed in response to cavernous nerve electrical stimulation. Markers of endothelial function (phospho [P]-vasodilator-stimulated-protein [VASP]-Ser-239), oxidative stress (4-hydroxy-2-nonenal [HNE]), sources of ROS (eNOS uncoupling and NAD[P]H oxidase subunits p67phox, p47phox, and gp91phox), P-eNOS-Ser-1177, and eNOS were measured by Western blot in penes. MAIN OUTCOME MEASURES Molecular mechanisms of ROS generation and endothelial dysfunction in hypercholesterolemia-induced ED. RESULTS Erectile response was significantly (P<0.05) reduced in hypercholesterolemic LDLR-null mice compared to WT mice. Relative to WT mice, hypercholesterolemia increased (P<0.05) protein expressions of NAD(P)H oxidase subunits p67phox, p47phox and gp91phox, eNOS uncoupling, and 4-HNE-modified proteins, and reduced (P<0.05) P-VASP-Ser-239 expression in the penis. Apocynin treatment of LDLR-null mice preserved (P<0.05) maximal intracavernosal pressure, and reversed (P < 0.05) the abnormalities in protein expressions of gp67phox and gp47phox, 4-HNE, P-VASP-Ser-239, and eNOS uncoupling in the penis. Apocynin treatment of WT mice did not affect any of these parameters

  10. Dissemination of technical information from the oil-shale program

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

    Not Available

    1980-09-03

    Auditors found cause to believe that DOE was not receiving technical information from a jointly financed demonstration project in Colorado to produce shale oil means of the modified in-situ process. The governments right to use and disseminate technical information developed under the Cooperative Agreement is seen a a contractual right spelled out in the Agreement for cost sharing. Enforcement is necessary to lessen vulnerability to charges of subsidy of private research and development without adequate benefits to the public. This final report was prepared after sending the draft report to the Assistant Secretaries of Fossil Energy (FE) and of Resourcemore » Applications (RA) for comments. IG still takes issue with some of the comments by FE, which are attached. Comments by IR, also appended, point out operational changes at the DOE Technical Information Center, Oak Ridge, TN that will improve, its publication operations time.« less

  11. Organizational Routines as Coupling Mechanisms: Policy, School Administration, and the Technical Core

    ERIC Educational Resources Information Center

    Spillane, James P.; Parise, Leigh Mesler; Sherer, Jennifer Zoltners

    2011-01-01

    The institutional environment of America's schools has changed substantially as government regulation has focused increasingly on the core technical work of schools--instruction. The authors explore the school administrative response to this changing environment, describing how government regulation becomes embodied in the formal structure of four…

  12. Neuronal nitric oxide synthase (NOS1) polymorphisms interact with financial hardship to affect depression risk.

    PubMed

    Sarginson, Jane E; Deakin, J F William; Anderson, Ian M; Downey, Darragh; Thomas, Emma; Elliott, Rebecca; Juhasz, Gabriella

    2014-11-01

    There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression.

  13. Neuronal Nitric Oxide Synthase (NOS1) Polymorphisms Interact with Financial Hardship to Affect Depression Risk

    PubMed Central

    Sarginson, Jane E; Deakin, JF William; Anderson, Ian M; Downey, Darragh; Thomas, Emma; Elliott, Rebecca; Juhasz, Gabriella

    2014-01-01

    There is increasing evidence that genetic factors have a role in differential susceptibility to depression in response to severe or chronic adversity. Studies in animals suggest that nitric oxide (NO) signalling has a key role in depression-like behavioural responses to stress. This study investigated whether genetic variation in the brain-expressed nitric oxide synthase gene NOS1 modifies the relationship between psychosocial stress and current depression score. We recruited a population sample of 1222 individuals who provided DNA and questionnaire data on symptoms and stress. Scores on the List of Life-Threatening Experiences (LTE) questionnaire for the last year and self-rated current financial hardship were used as measures of recent/ongoing psychosocial stress. Twenty SNPs were genotyped. Significant associations between eight NOS1 SNPs, comprising two regional haplotypes, and current depression score were identified that survived correction for multiple testing when current financial hardship was used as the interaction term. A smaller three-SNP haplotypes (rs10507279, rs1004356 and rs3782218) located in a regulatory region of NOS1 showed one of the strongest effects, with the A-C-T haplotype associating with higher depression scores at low adversity levels but lower depression scores at higher adversity levels (p=2.3E-05). These results suggest that NOS1 SNPs interact with exposure to economic and psychosocial stressors to alter individual's susceptibility to depression. PMID:24917196

  14. 2013 Technical Roundtable

    EPA Pesticide Factsheets

    On December 9, 2013, EPA reconvened the study’s Technical Roundtable. Subject-matter experts discussed the outcomes of the 2013 Technical Workshops, stakeholder engagement, and plans for draft assessment report.

  15. Lymphatic endothelial cells efferent to inflamed joints produce iNOS and inhibit lymphatic vessel contraction and drainage in TNF-induced arthritis in mice.

    PubMed

    Liang, Qianqian; Ju, Yawen; Chen, Yan; Wang, Wensheng; Li, Jinlong; Zhang, Li; Xu, Hao; Wood, Ronald W; Schwarz, Edward M; Boyce, Brendan F; Wang, Yongjun; Xing, Lianping

    2016-03-12

    In this study, we sought to determine the cellular source of inducible nitric oxide synthase (iNOS) induced in lymphatic endothelial cells (LECs) in response to tumor necrosis factor (TNF), the effects of iNOS on lymphatic smooth muscle cell (LSMC) function and on the development of arthritis in TNF-transgenic (TNF-Tg) mice, and whether iNOS inhibitors improve lymphatic function and reduce joint destruction in inflammatory erosive arthritis. We used quantitative polymerase chain reactions, immunohistochemistry, histology, and near-infrared imaging to examine (1) iNOS expression in podoplanin + LECs and lymphatic vessels from wild-type (WT) and TNF-Tg mice, (2) iNOS induction by TNF in WT LECs, (3) the effects of iNOS inhibitors on expression of functional muscle genes in LSMCs, and (4) the effects of iNOS inhibitors on lymphatic vessel contraction and drainage, as well as the severity of arthritis, in TNF-Tg mice. LECs from TNF-Tg mice had eight fold higher iNOS messenger RNA levels than WT cells, and iNOS expression was confirmed immunohistochemically in podoplanin + LECs in lymphatic vessels from inflamed joints. TNF (0.1 ng/ml) increased iNOS levels 40-fold in LECs. LSMCs cocultured with LECs pretreated with TNF had reduced expression of functional muscle genes. This reduction was prevented by ferulic acid, which blocked nitric oxide production. Local injection of L-N(6)-(1-iminoethyl)lysine 5-tetrazole-amide into inflamed paws of TNF-Tg mice resulted in recovery of lymphatic vessel contractions and drainage. Treatment of TNF-Tg mice with ferulic acid reduced synovial inflammation as well as cartilage and bone erosion, and it also restored lymphatic contraction and drainage. iNOS is produced primarily by LECs in lymphatic vessel efferent from inflamed joints of TNF-Tg mice in response to TNF and inhibits LSMC contraction and lymph drainage. Ferulic acid represents a potential new therapy to restore lymphatic function and thus improve inflammatory

  16. Grape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS.

    PubMed

    Anselm, Eric; Chataigneau, Marta; Ndiaye, Mamadou; Chataigneau, Thierry; Schini-Kerth, Valérie B

    2007-01-15

    An enhanced endothelial formation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), is thought to contribute to the protective effect of moderate consumption of red wine on coronary diseases. The present study has characterized endothelium-dependent relaxations to Concord grape juice (CGJ), a non-alcoholic rich source of grape-derived polyphenols, in the coronary artery. Porcine coronary artery rings were suspended in organ chambers for the measurement of changes in isometric tension in the presence of indomethacin. NO formation was assessed by electron spin resonance spectroscopy, and the phosphorylation of Src, Akt and endothelial NO synthase (eNOS) by Western blot analysis in cultured endothelial cells. Endothelium-dependent relaxations to CGJ were slightly but significantly reduced by L-NA, not affected by charybdotoxin (CTX) plus apamin (APA, two inhibitors of EDHF-mediated responses) whereas the combination of L-NA, CTX plus APA reduced maximal relaxation to about 50%. In the presence of CTX plus APA, relaxations to CGJ were markedly reduced by the membrane permeant mimetic of superoxide dismutase (SOD), MnTMPyP, the membrane permeant analogue of catalase polyethyleneglycol-catalase (PEG-catalase), PP2, an inhibitor of Src kinase, and by wortmannin, an inhibitor of the PI3-kinase. CGJ stimulated the formation of reactive oxygen species and the N(omega)-nitro-L-arginine-, PP2- and wortmannin-sensitive formation of NO in endothelial cells. The formation of NO was associated with a redox-sensitive and time-dependent phosphorylation of Src, Akt and eNOS. CGJ induces endothelium-dependent relaxations of coronary arteries, which involve a NO-mediated component and also, to a minor extent, an EDHF-mediated component. In addition, CGJ-induced NO formation is due to the redox-sensitive activation of Src kinase with the subsequent PI3-kinase/Akt-dependent phosphorylation of eNOS.

  17. Organizational change: Incentives and resistance

    NASA Technical Reports Server (NTRS)

    Bishop, Peter C.

    1992-01-01

    Topics concerning Space Exploration Initiative technical interchange are presented in viewgraph form and include the following: models of change, elements of the current period, the signs of change, leaders' contribution, paradigms - our worldview, paradigm change, the effects of revealing paradigms, a checklist for change, and organizational control.

  18. Necessity of creating digital tools to ensure efficiency of technical means

    NASA Astrophysics Data System (ADS)

    Rakov, V. I.; Zakharova, O. V.

    2018-05-01

    The authors estimated the problems of functioning of technical objects. The article notes that the increasing complexity of automation systems may lead to an increase of the redundant resource in proportion to the number of components and relationships in the system, and to the need of the redundant resource constant change that can make implementation of traditional structures with redundancy unnecessarily costly (Standby System, Fault Tolerance, High Availability). It proposes the idea of creating digital tools to ensure efficiency of technical facilities.

  19. The Role of Career and Technical Education in Iowa Community Colleges

    ERIC Educational Resources Information Center

    Laanan, Frankie Santos; Compton, Jonathan I.; Friedel, Janice Nahra

    2006-01-01

    This scholarly paper describes and analyzes the role of career and technical education (CTE) in Iowa community colleges. Iowa's community colleges are doing a good job of responding to the changing workforce needs of the state and providing smooth career pathways. However, changes in the population and economy of the state will call for further…

  20. Context view, Building Nos. 2729, with Building No. 28 in ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Context view, Building Nos. 27-29, with Building No. 28 in the center, looking west at front of buildings, from a spot south of Building No. 29 - U.S. Veterans Hospital, Jefferson Barracks, Medical Officer in Charge Residence, VA Medical Center, Jefferson Barracks Division 1 Jefferson Barracks Drive, Saint Louis, Independent City, MO

  1. Pyridoxine inhibits endothelial NOS uncoupling induced by oxidized low-density lipoprotein via the PKCα signalling pathway in human umbilical vein endothelial cells

    PubMed Central

    Xie, Liping; Liu, Zhen; Lu, Hui; Zhang, Wen; Mi, Qiongyu; Li, Xiaozhen; Tang, Yan; Chen, Qi; Ferro, Albert; Ji, Yong

    2012-01-01

    BACKGROUND AND PURPOSE One key mechanism for endothelial dysfunction is endothelial NOS (eNOS) uncoupling, whereby eNOS generates superoxide (O2•−) rather than NO. We explored the effect of pyridoxine on eNOS uncoupling induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism. EXPERIMENTAL APPROACH HUVECs were incubated with ox-LDL with/without pyridoxine, NG-nitro-L-arginine methylester (L-NAME), chelerythrine chloride (CHCI) or apocynin. Endothelial O2•− was measured using lucigenin chemiluminescence, and O2•−-sensitive fluorescent dye dihydroethidium (DHE). NO levels were measured by chemiluminescence, PepTag Assay for non-radioactive detection of PKC activity, depletion of PKCα and p47phox by siRNA silencing and the states of phospho-eNOS Thr495, total-eNOS, phospho-PKCα/βII, total PKC, phospho-PKCα, total PKCα and p47phox were measured by Western blot. KEY RESULTS Ox-LDL significantly increased O2•− production and reduced NO levels released from HUVECs; an effect reversed by eNOS inhibitor, L-NAME. Pyridoxine pretreatment significantly inhibited ox-LDL-induced O2•− generation and preserved NO levels. Pyridoxine also prevented the ox-LDL-induced reduction in phospho-eNOS Thr495 and PKC activity. These protective effects of pyridoxine were abolished by the PKC inhibitor, CHCI, or siRNA silencing of PKCα. However, depletion of p47phox or treatment with the NADPH oxidase inhibitor, apocynin, had no influence on these effects. Also, cytosol p47phox expression was unchanged by the different treatments. CONCLUSIONS AND IMPLICATIONS Pyridoxine mitigated eNOS uncoupling induced by ox-LDL. This protectant effect was related to phosphorylation of eNOS Thr495 stimulated by PKCα, not via NADPH oxidase. These results provide support for the use of pyridoxine in ox-LDL-related vascular endothelial dysfunction. PMID:21797845

  2. Changing the attitudes and practices of professional developers through a constructivist model: The Technical Assistance Academy for Mathematics and Science Services

    NASA Astrophysics Data System (ADS)

    Charles, Karen Jungblut

    For much of this century, mathematics and science have been taught in a didactic manner that is characterized by a passive student and a lecturing teacher. Since the late eighties national standards have encouraged professional developers specializing in mathematics and science education to deliver the messages of inquiry-based learning, active student engagement, and learner-constructed knowledge to the teachers they support. Follow-up studies of professional development programs, however, found that telling teachers was no more effective than telling students. Information transmitted in a passive setting was not transferring into effective classroom practices. This phenomenological case study was conducted to determine the effects of a constructivist-oriented professional development experience, the Technical Assistance Academy, in changing the practices and attitudes of mathematics and science professional developers regarding the use of constructivist strategies in workshop design. This study focused on 45 professional developers who participated in the Technical Assistance Academy. Data from a 2 1/2 year period were collected from session evaluations, journal reflections, a follow-up interview, and site visits that included observations and collaborative planning. Content analysis procedures were used to find common themes among the data. Use of new skills developed as a result of participation in the Technical Assistance Academy was determined using the Concerns-Based Adoption Model Levels of Use framework (Hall & Hord, 1987). Changes in attitude were determined by examining participants' journal reflections related to common constructivist themes such as those discussed by Fosnot (1996c): learning is developmental, disequilibrium and reflection facilitate learning, and the construction of "big ideas" results from the opportunity to struggle with new information. Results verified that all 45 participants demonstrated some level of use, and that most were in

  3. 76 FR 59745 - Virginia Electric and Power Company; North Anna Power Station, Unit Nos. 1 and 2; Exemption

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-27

    ... hours. After the high wind conditions pass, wind damage to the plant and surrounding area might preclude... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-338 and 50-339] Virginia Electric and Power Company; North Anna Power Station, Unit Nos. 1 and 2; Exemption 1.0 Background Virginia Electric Power Company...

  4. 48 CFR 252.227-7015 - Technical data-Commercial items.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) under a contract, the primary purpose of which is to furnish independent and impartial advice or... Government-Furnished Information Marked with Restrictive Legends. (3) Form, fit, and function data means..., fit, and function data; (iii) Are a correction or change to technical data furnished to the Contractor...

  5. The β3 Adrenergic Receptor Agonist BRL37344 Exacerbates Atrial Structural Remodeling Through iNOS Uncoupling in Canine Models of Atrial Fibrillation.

    PubMed

    Wang, Xiaobing; Wang, Ruifeng; Liu, Guangzhong; Dong, Jingmei; Zhao, Guanqi; Tian, Jingpu; Sun, Jiayu; Jia, Xiuyue; Wei, Lin; Wang, Yuping; Li, Weimin

    2016-01-01

    The role of the β3-adrenergic receptor (β3-AR) agonist BRL37344 in atrial fibrillation (AF) structural remodeling and the underlying mechanisms as a therapeutic target were investigated. Four groups of dogs were evaluated: sham, pacing, β3-AR agonist BRL37344 (β3-AGO), and β3-AR antagonist L748337 (β3-ANT) groups. Dogs in the pacing, β3-AGO and β3-ANT groups were subjected to rapid atrial pacing for four weeks. Atrial structure and function, AF inducibility and duration, atrial myocyte apoptosis and interstitial fibrosis were assessed. Atrial superoxide anions were evaluated by fluorescence microscopy and colorimetric assays. Cardiac nitrate+nitrite levels were used to assess nitric oxide (NO) production. Protein and mRNA expression of β3-AR, neuronal NO synthase (nNOS), inducible NO synthase (iNOS), endothelial NO synthase (eNOS) and guanosine triphosphate cyclohydrolase-1 (GCH-1) as well as tetrahydrobiopterin (BH4) levels were measured. β3-AR was up-regulated in AF. Stimulation of β3-AR significantly increased atrial myocyte apoptosis, fibrosis and atrial dilatation, resulting in increased AF induction and prolonged duration. These effects were attenuated by β3-ANT. Moreover, β3-AGO reduced BH4 and NO production and increased superoxide production, which was inhibited by the specific iNOS inhibitor, 1400w β3-AGO also increased iNOS but decreased eNOS and had no effect on nNOS expression in AF. β3-AR stimulation resulted in atrial structural remodeling by increasing iNOS uncoupling and related oxidative stress. β3-AR up-regulation and iNOS uncoupling might be underlying AF therapeutic targets. © 2016 The Author(s) Published by S. Karger AG, Basel.

  6. Modulation of NO and ROS production by AdiNOS transduced vascular cells through supplementation with L-Arg and BH4: implications for gene therapy of restenosis.

    PubMed

    Forbes, Scott P; Alferiev, Ivan S; Chorny, Michael; Adamo, Richard F; Levy, Robert J; Fishbein, Ilia

    2013-09-01

    Gene therapy with viral vectors encoding for NOS enzymes has been recognized as a potential therapeutic approach for the prevention of restenosis. Optimal activity of iNOS is dependent on the intracellular availability of L-Arg and BH4 via prevention of NOS decoupling and subsequent ROS formation. Herein, we investigated the effects of separate and combined L-Arg and BH4 supplementation on the production of NO and ROS in cultured rat arterial smooth muscle and endothelial cells transduced with AdiNOS, and their impact on the antirestenotic effectiveness of AdiNOS delivery to balloon-injured rat carotid arteries. Supplementation of AdiNOS transduced endothelial and vascular smooth muscle cells with L-Arg (3.0 mM), BH4 (10 μM) and especially their combination resulted in a significant increase in NO production as measured by nitrite formation in media. Formation of ROS was dose-dependently increased following transduction with increasing MOIs of AdiNOS. Exposure of RASMC to AdiNOS tethered to meshes via a hydrolyzable cross-linker, modeling viral delivery from stents, resulted in increased ROS production, which was decreased by supplementation with BH4 but not L-Arg or L-Arg/BH4. Enhanced cell death, caused by AdiNOS transduction, was also preventable with BH4 supplementation. In the rat carotid model of balloon injury, intraluminal delivery of AdiNOS in BH4-, L-Arg-, and especially in BH4 and L-Arg supplemented animals was found to significantly enhance the antirestenotic effects of AdiNOS-mediated gene therapy. Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced vasculature augments the therapeutic potential of gene therapy with iNOS for the prevention of restenosis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  7. Modulation of NO and ROS production by AdiNOS transduced vascular cells through supplementation with L-Arg and BH4: Implications for gene therapy of restenosis

    PubMed Central

    Forbes, Scott P.; Alferiev, Ivan S.; Chorny, Michael; Adamo, Richard F.; Levy, Robert J.; Fishbein, Ilia

    2013-01-01

    Objective Gene therapy with viral vectors encoding for NOS enzymes has been recognized as a potential therapeutic approach for the prevention of restenosis. Optimal activity of iNOS is dependent on the intracellular availability of L-Arg and BH4 via prevention of NOS decoupling and subsequent ROS formation. Herein, we investigated the effects of separate and combined L-Arg and BH4 supplementation on the production of NO and ROS in cultured rat arterial smooth muscle and endothelial cells transduced with AdiNOS, and their impact on the antirestenotic effectiveness of AdiNOS delivery to balloon-injured rat carotid arteries. Methods and Results Supplementation of AdiNOS transduced endothelial and vascular smooth muscle cells with L-Arg (3.0 mM), BH4 (10 μM) and especially their combination resulted in a significant increase in NO production as measured by nitrite formation in media. Formation of ROS was dose-dependently increased following transduction with increasing MOIs of AdiNOS. Exposure of RASMC to AdiNOS tethered to meshes via a hydrolysable cross-linker, modeling viral delivery from stents, resulted in increased ROS production, which was decreased by supplementation with BH4 but not L-Arg or L-Arg/BH4. Enhanced cell death, caused by AdiNOS transduction, was also preventable with BH4 supplementation. In the rat carotid model of balloon injury, intraluminal delivery of AdiNOS in BH4-, L-Arg-, and especially in BH4 and L-Arg supplemented animals was found to significantly enhance the antirestenotic effects of AdiNOS-mediated gene therapy. Conclusions Fine-tuning of iNOS function by L-Arg and BH4 supplementation in the transduced vasculature augments the therapeutic potential of gene therapy with iNOS for the prevention of restenosis. PMID:23958248

  8. Direct evidence of iNOS-mediated in vivo free radical production and protein oxidation in acetone-induced ketosis

    PubMed Central

    Stadler, Krisztian; Bonini, Marcelo G.; Dallas, Shannon; Duma, Danielle; Mason, Ronald P.; Kadiiska, Maria B.

    2008-01-01

    Diabetic patients frequently encounter ketosis that is characterized by the breakdown of lipids with the consequent accumulation of ketone bodies. Several studies have demonstrated that reactive species are likely to induce tissue damage in diabetes, but the role of the ketone bodies in the process has not been fully investigated. In this study, electron paramagnetic resonance (EPR) spectroscopy combined with novel spin-trapping and immunological techniques has been used to investigate in vivo free radical formation in a murine model of acetone-induced ketosis. A six-line EPR spectrum consistent with the α-(4-pyridyl-1-oxide)-N-t-butylnitrone radical adduct of a carbon-centered lipid-derived radical was detected in the liver extracts. To investigate the possible enzymatic source of these radicals, inducible nitric oxide synthase (iNOS) and NADPH oxidase knockout mice were used. Free radical production was unchanged in the NADPH oxidase knockout but much decreased in the iNOS knockout mice, suggesting a role for iNOS in free radical production. Longer-term exposure to acetone revealed iNOS overexpression in the liver together with protein radical formation, which was detected by confocal microscopy and a novel immunospin-trapping method. Immunohistochemical analysis revealed enhanced lipid peroxidation and protein oxidation as a consequence of persistent free radical generation after 21 days of acetone treatment in control and NADPH oxidase knockout but not in iNOS knockout mice. Taken together, our data demonstrate that acetone administration, a model of ketosis, can lead to protein oxidation and lipid peroxidation through a free radical-dependent mechanism driven mainly by iNOS overexpression. PMID:18559982

  9. Technical report writing

    NASA Technical Reports Server (NTRS)

    Vidoli, Carol A.

    1992-01-01

    This manual covers the fundamentals of organizing, writing, and reviewing NASA technical reports. It was written to improve the writing skills of LeRC technical authors and the overall quality of their reports.

  10. NOS1AP is associated with increased severity of PTSD and depression in untreated combat veterans.

    PubMed

    Lawford, Bruce R; Morris, Charles P; Swagell, Christopher D; Hughes, Ian P; Young, Ross McD; Voisey, Joanne

    2013-05-01

    Posttraumatic stress disorder (PTSD) and depressive disorder are over represented in combat veterans. Veterans with both disorders have an increased risk of suicide. The nitric oxide synthase 1 adaptor protein (NOS1AP) gene, which modulates stress-evoked N-methyl-d-aspartate (NMDA) activity, was investigated in combat veterans. A comprehensive genetic analysis of NOS1AP and its association with PTSD was investigated in Vietnam combat veterans with PTSD (n=121) and a group of healthy control individuals (n=237). PTSD patients were assessed for symptom severity and level of depression using the Mississippi Scale for Combat-Related PTSD and the Beck Depression Inventory-II (BDI). The G allele of NOS1AP SNP rs386231 was significantly associated with PTSD (p=0.002). Analysis of variance revealed significant differences in BDI-II and Mississippi scores between genotypes for rs386231 with the GG genotype associated with increased severity of depression (p=0.002 F=6.839) and higher Mississippi Scale for Combat-Related PTSD scores (p=0.033). Haplotype analysis revealed that the C/G haplotype (rs451275/rs386231) was significantly associated with PTSD (p=0.001). The sample sizes in our study were not sufficient to detect SNP associations with very small effects. In addition the study was limited by its cross sectional design. This is the first study reporting that a variant of the NOS1AP gene is associated with PTSD. Our data also suggest that a genetic variant in NOS1AP may increase the susceptibility to severe depression in patients with PTSD and increased risk for suicide. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  11. NASA Technical Standards Program

    NASA Technical Reports Server (NTRS)

    Gill, Paul S.; Vaughan, William W.; Parker, Nelson C. (Technical Monitor)

    2002-01-01

    The NASA Technical Standards Program was officially established in 1997 as result of a directive issued by the Administrator. It is responsible for Agency wide technical standards development, adoption (endorsement), and conversion of Center-unique standards for Agency wide use. One major element of the Program is the review of NSA technical standards products and replacement with non-Government Voluntary Consensus Standards in accordance with directions issued by the Office of Management and Budget. As part of the Program's function, it developed a NASA Integrated Technical Standards Initiative that consists of and Agency wide full-text system, standards update notification system, and lessons learned-standards integration system. The Program maintains a 'one stop-shop' Website for technical standards ad related information on aerospace materials, etc. This paper provides information on the development, current status, and plans for the NAS Technical Standards Program along with metrics on the utility of the products provided to both users within the nasa.gov Domain and the Public Domain.

  12. NASA Technical Standards Program

    NASA Technical Reports Server (NTRS)

    Gill, Paul S.; Vaughan, WIlliam W.

    2003-01-01

    The NASA Technical Standards Program was officially established in 1997 as result of a directive issued by the Administrator. It is responsible for Agency wide technical standards development, adoption (endorsement), and conversion of Center-unique standards for Agency wide use. One major element of the Program is the review of NSA technical standards products and replacement with non-Government Voluntary Consensus Standards in accordance with directions issued by the Office of Management and Budget. As part of the Program s function, it developed a NASA Integrated Technical Standards Initiative that consists of and Agency wide full-text system, standards update notification system, and lessons learned - standards integration system. The Program maintains a "one stop-shop" Website for technical standards ad related information on aerospace materials, etc. This paper provides information on the development, current status, and plans for the NAS Technical Standards Program along with metrics on the utility of the products provided to both users within the nasa.gov Domain and the Public Domain.

  13. 1980 Bibliography of Technical Writing.

    ERIC Educational Resources Information Center

    Book, Virginia Alm; And Others

    1981-01-01

    Offers resources on technical writing that were published in 1980. Arranges the citations under 12 categories: bibliographies, books, reviews, and articles on theory and philosophy; pedagogy; writing technical articles and reports; research; technical writing and the computer; graphic/visual aids; correspondence; technical speech; and designing…

  14. 1981 Bibliography of Technical Writing.

    ERIC Educational Resources Information Center

    Book, Virginia Alm; And Others

    1982-01-01

    Offers resources on technical writing published in 1981. Arranges the citations under the following categories: bibliographies, books, reviews, and articles on the profession; theory and philosophy; pedagogy; technical speech; research; designing degree programs; technical writing and the computer; writing technical articles and reports;…

  15. Gastric cancer is associated with NOS2 -954G/C polymorphism and environmental factors in a Brazilian population

    PubMed Central

    2010-01-01

    Background Gastric cancer can progress from a chronic inflammation of the gastric mucosa resulting from Helicobacter pylori infection that activates the inflammatory response of the host. Therefore, polymorphisms in genes involved in the inflammatory response, such as inducible nitric oxide synthase (NOS2), have been implicated in gastric carcinogenesis. The aim of this study was to evaluate the association of NOS2 polymorphisms Ser608Leu (rs2297518) in exon 16, -954G/C and -1173C/T, both in the promoter region, with gastric cancer and chronic gastritis and the association of cancer with risk factors such as smoking, alcohol intake and H. pylori infection. Methods We conducted a population-based case-control study in 474 Southeast Brazilian individuals (150 with gastric cancer, 160 with chronic gastritis, and 164 healthy individuals), in which we performed NOS2 genotyping by PCR-RFLP. Results SNP Ser608Leu was not associated with risk of chronic gastritis or gastric cancer. The polymorphic allele -1173T was not found in the studied population. However, the frequency of -954GC+CC genotypes was significantly higher (p < 0.01) in the cancer group (48.7%) than in both the gastritis (28.1%) and the control (29.9%) groups. Multivariate logistic regression showed that the NOS2 SNP -954G/C was associated with higher risk of gastric cancer (OR = 1.87; 95% CI = 1.12-3.13). We also observed an association with risk factors such as smoking and alcohol intake in both the gastric cancer (OR = 2.68; 95% CI = 1.58-4.53; OR = 3.60; 95% CI = 2.05-6.32, respectively) and the chronic gastritis (OR = 1.93; 95% CI = 1.19-3.13; OR = 2.79; 95% CI = 1.55-5.02, respectively) groups. This is the first report of increased risk of gastric cancer in association with the -954G/C polymorphism. These findings show that several polymorphisms in the promoter region of the NOS2 gene may contribute to the susceptibility to gastric cancer. Conclusions Polymorphism NOS2 -954 G/C, along with alcohol

  16. Training the Technical Editor.

    ERIC Educational Resources Information Center

    Cathcart, Margaret E.

    The demand for skilled technical editors is growing as society places increasing emphasis on receiving accurate, concise, and complete technical data. Since many organizations do not have inhouse programs for training technical editors, a need exists to provide inexperienced people with basic editing skills. One organization has developed two…

  17. Endothelial NOS is required for SDF-1alpha/CXCR4-mediated peripheral endothelial adhesion of c-kit+ bone marrow stem cells.

    PubMed

    Kaminski, Alexander; Ma, Nan; Donndorf, Peter; Lindenblatt, Nicole; Feldmeier, Gregor; Ong, Lee-Lee; Furlani, Dario; Skrabal, Christian A; Liebold, Andreas; Vollmar, Brigitte; Steinhoff, Gustav

    2008-01-01

    In the era of intravascular approaches for regenerative cell therapy, the underlying mechanisms of stem cell migration to non-marrow tissue have not been clarified. We hypothesized that next to a local inflammatory response implying adhesion molecule expression, endothelial nitric oxide synthase (eNOS)-dependent signaling is required for stromal- cell-derived factor-1 alpha (SDF-1alpha)-induced adhesion of c-kit+ cells to the vascular endothelium. SDF-1alpha/tumor necrosis factor-alpha (TNF-alpha)-induced c-kit+-cell shape change and migration capacity was studied in vitro using immunohistochemistry and Boyden chamber assays. In vivo interaction of c-kit+ cells from bone marrow with the endothelium in response to SDF-1alpha/TNF-alpha stimulation was visualized in the cremaster muscle microcirculation of wild-type (WT) and eNOS (-/-) mice using intravital fluorescence microscopy. In addition, NOS activity was inhibited with N-nitro-L-arginine-methylester-hydrochloride in WT mice. To reveal c-kit+-specific adhesion behavior, endogenous leukocytes (EL) and c-kit+ cells from peripheral blood served as control. Moreover, intercellular adhesion molecule-1 (ICAM-1) and CXCR4 were blocked systemically to determine their role in inflammation-related c-kit+-cell adhesion. In vitro, SDF-1alpha enhanced c-kit+-cell migration. In vivo, SDF-1alpha alone triggered endothelial rolling-not firm adherence-of c-kit+ cells in WT mice. While TNF-alpha alone had little effect on adhesion of c-kit+ cells, it induced maximum endothelial EL adherence. However, after combined treatment with SDF-1alpha+TNF-alpha, endothelial adhesion of c-kit+ cells increased independent of their origin, while EL adhesion was not further incremented. Systemic treatment with anti-ICAM-1 and anti-CXCR4-monoclonal antibody completely abolished endothelial c-kit+-cell adhesion. In N-nitro-L-arginine-methylester-hydrochloride-treated WT mice as well as in eNOS (-/-) mice, firm endothelial adhesion of c-kit+ cells

  18. Withaferin A inhibits iNOS expression and nitric oxide production by Akt inactivation and down-regulating LPS-induced activity of NF-kappaB in RAW 264.7 cells.

    PubMed

    Oh, Jung Hwa; Lee, Tae-Jin; Park, Jong-Wook; Kwon, Taeg Kyu

    2008-12-03

    Induction of inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production is thought to have beneficial immunomodulatory effects in acute and chronic inflammatory disorders. In Raw 264.7 cells stimulated with lipopolysaccharide (LPS) to mimic inflammation, withaferin A inhibited LPS-induced expression of both iNOS protein and mRNA in a dose-dependent manner. To investigate the mechanism by which withaferin A inhibits iNOS gene expression, we examined activation of mitogen-activated protein kinases (MAPKs) and Akt in Raw 264.7 cells. We did not observe any significant changes in the phosphorylation of p38 MAPK in cells treated with LPS alone or LPS plus withaferin A. However, LPS-induced Akt phosphorylation was markedly inhibited by withaferin A, while the phosphorylation of p42/p44 extracellular signal-regulated kinases (ERKs) was slightly inhibited by withaferin A treatment. Withaferin A prevented IkappaB phosphorylation, blocking the subsequent nuclear translocation of nuclear factor-kappaB (NF-kappaB) and inhibiting its DNA binding activity. LPS-induced p65 phosphorylation, which is mediated by extracellular signal-regulated kinase (ERK) and Akt pathways, was attenuated by withaferin A treatment. Moreover, LPS-induced NO production and NF-kappaB activation were inhibited by SH-6, a specific inhibitor of Akt. Taken together, these results suggest that withaferin A inhibits inflammation through inhibition of NO production and iNOS expression, at least in part, by blocking Akt and subsequently down-regulating NF-kappaB activity.

  19. [Effect of twirling-reinforcing-reducing needling manipulations on contents of serum acetylcholine and arterial NOS and cGMP in stress-induced hypertension rats].

    PubMed

    Liu, Wei; Zhu, Ling-Qun; Chen, Si-Si; Lu, Shu-Chao; Tang, Jie; Liu, Qing-Guo

    2015-04-01

    To observe the effect of twirling-reinforcing or reducing needling manipulations on plasma acetylcholine (Ach) content and expression of nitric oxide synthetase (NOS) and cyclic guanosine monophosphate (cGMP) in thoracic artery tissue in stress-induced hypertension rats. A total of 60 male rats were randomly divided into blank control, model, acupuncture (no-needle-manipulation) , twirling-reinforcing needling and twirling-reducing needling groups (n = 12 in each group). The stress hypertension model was established by giving the animals with noise and electric shock stimulation (paw), twice a day for 15 days. Acupuncture stimulation was applied to bilateral "Taichong" (LR 3) for 1 min, followed by retaining the needles for 20 min. The treatment was conducted once daily for 7 days. Systolic blood pressure of the rat's tail was detected with non-invasive method and plasma Ach, and NOS and cGMP contents in the thoracic artery tissue were measured using ELISA method. Compared with the control group, the systolic blood pressure was significantly higher in the model group after 15 days' stress stimulation (P < 0.01), while the contents of plasma Ach, arterial NOS and cGMP were markedly down-regulated (P < 0.01). Following 7 days' acupuncture interventions, the increased blood pressure was down-regulated in the no-needle-manipulation, twirling-reinforcing needling and twirling-reducing needling groups (P < 0.05, P < 0.01); and the decreased Ach and NOS in the 3 treatment groups, and cGMP levels in the twirling-reinforcing and twirling-reducing needling groups were remarkably up-regulated (P < 0.01, P < 0.05). No significant change of arterial cGMP content was found in the no-needle-manipulation group (P > 0.05). The effect of the twirling-reducing needling was superior to that of no-needle-manipulation and twirling-reinforcing needling in lowering blood pressure and raising plasma Ach content (P < 0.05, P < 0.01). The twirling-reducing needling of acupuncture has a

  20. Technical Subjects in Secondary Schools

    ERIC Educational Resources Information Center

    Howard, A. E.

    2008-01-01

    Purpose: This paper aims to examine technical education in various types of secondary schools, and suggests three levels of technical courses to be taught in secondary schools. Design/methodology/approach: The paper discusses the differences between technical schools and colleges, and vocational technical courses taught in "academic"…

  1. Dependability of technical items: Problems of standardization

    NASA Astrophysics Data System (ADS)

    Fedotova, G. A.; Voropai, N. I.; Kovalev, G. F.

    2016-12-01

    This paper is concerned with problems blown up in the development of a new version of the Interstate Standard GOST 27.002 "Industrial product dependability. Terms and definitions". This Standard covers a wide range of technical items and is used in numerous regulations, specifications, standard and technical documentation. A currently available State Standard GOST 27.002-89 was introduced in 1990. Its development involved a participation of scientists and experts from different technical areas, its draft was debated in different audiences and constantly refined, so it was a high quality document. However, after 25 years of its application it's become necessary to develop a new version of the Standard that would reflect the current understanding of industrial dependability, accounting for the changes taking place in Russia in the production, management and development of various technical systems and facilities. The development of a new version of the Standard makes it possible to generalize on a terminological level the knowledge and experience in the area of reliability of technical items, accumulated over a quarter of the century in different industries and reliability research schools, to account for domestic and foreign experience of standardization. Working on the new version of the Standard, we have faced a number of issues and problems on harmonization with the International Standard IEC 60500-192, caused first of all by different approaches to the use of terms and differences in the mentalities of experts from different countries. The paper focuses on the problems related to the chapter "Maintenance, restoration and repair", which caused difficulties for the developers to harmonize term definitions both with experts and the International Standard, which is mainly related to differences between the Russian concept and practice of maintenance and repair and foreign ones.

  2. 78 FR 27963 - Reliability Technical Conference; Notice of Technical Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-13

    ... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. AD13-6-000] Reliability Technical Conference; Notice of Technical Conference Take notice that the Federal Energy Regulatory... related to the reliability of the Bulk-Power System. A more formal agenda will be issued at a later date...

  3. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy

    PubMed Central

    Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

    2017-01-01

    Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95–nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95–nNOS interactions in MHE. PMID:28932186

  4. DA Negatively Regulates IGF-I Actions Implicated in Cognitive Function via Interaction of PSD95 and nNOS in Minimal Hepatic Encephalopathy.

    PubMed

    Ding, Saidan; Zhuge, Weishan; Wang, Xuebao; Yang, Jianjing; Lin, Yuanshao; Wang, Chengde; Hu, Jiangnan; Zhuge, Qichuan

    2017-01-01

    Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons. Ribosomal S6 protein kinase (RSK) phosphorylated nNOS in response to IGF-I by recruiting extracellular signal-regulated kinase (ERK1/2). In turn, DA inactivated the ERK1/2/RSK pathway and stimulated the PSD95-nNOS interaction by downregulating IGF-I. Inhibition of the interaction between PSD95 and nNOS ameliorated DA-induced memory impairment. As DA induced deficits in the ERK1/2/RSK pathway and the interaction between PSD95 and nNOS in MHE brains, IGF-I administration exerted a protective effect via interruption of the interaction between PSD95 and nNOS. These results suggest that IGF-I antagonizes DA-induced cognitive loss by disrupting PSD95-nNOS interactions in MHE.

  5. 78 FR 35990 - All Operating Boiling-Water Reactor Licensees With Mark I And Mark II Containments; Docket Nos...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-14

    ... NUCLEAR REGULATORY COMMISSION [NRC-2013-0128] All Operating Boiling-Water Reactor Licensees With Mark I And Mark II Containments; Docket Nos. (As Shown In Attachment 1), License Nos. (As Shown In Attachment 1), EA-13-109; Order Modifying Licenses With Regard to Reliable Hardened Containment Vents Capable of Operation Under Severe Accident...

  6. Bubbles, shocks and elementary technical trading strategies

    NASA Astrophysics Data System (ADS)

    Fry, John

    2014-01-01

    In this paper we provide a unifying framework for a set of seemingly disparate models for bubbles, shocks and elementary technical trading strategies in financial markets. Markets operate by balancing intrinsic levels of risk and return. This seemingly simple observation is commonly over-looked by academics and practitioners alike. Our model shares its origins in statistical physics with others. However, under our approach, changes in market regime can be explicitly shown to represent a phase transition from random to deterministic behaviour in prices. This structure leads to an improved physical and econometric model. We develop models for bubbles, shocks and elementary technical trading strategies. The list of empirical applications is both interesting and topical and includes real-estate bubbles and the on-going Eurozone crisis. We close by comparing the results of our model with purely qualitative findings from the finance literature.

  7. The Skills that Technical Communicators Need: An Investigation of Technical Communication Graduates, Managers, and Curricula

    ERIC Educational Resources Information Center

    Whiteside, Aimee L.

    2003-01-01

    This study examines the skills that recent technical communication graduates and managers believe technical communication students need before entering business and industry as new technical communicators. Through questionnaires and interviews with recent graduates and managers of technical communication departments as well as an analysis of the…

  8. SREM (Software Requirements Engineering Methodology) Evaluation. Volume 2. Specifications and Technical Data.

    DTIC Science & Technology

    1984-02-01

    and is approved for publication. APPROVED: ’"" " Project Engineer APPROVED:k 1 4 RAYMOND P. URTZ, JR. Acting Technical Director Command and Control ...Technical Director Command and Control Division FOR THE COMMANDER: JOHN A. RITZ Acting Chief, Plans Office If your address has changed or if you wish to be...179 55812203 Denver CO 80201 55812203 I. CONTROLLING OFFICE NAME AND ADDRESS 12. REPORT DATE Rome Air Development Center (COEE) February 1984 Griffiss

  9. SUPERFUND TECHNICAL SUPPORT

    EPA Science Inventory

    Under this task, technical support is provided to Regional Remedial Project Managers (RPMs)/On-Scene Coordinators (OSCs) at Superfund, RCRA, and Brownfields sites contaminated with hazardous materials by the Technical Support Center (TSC) for Monitoring and Site Characterization....

  10. Hydrogen sulfide ameliorated L-NAME-induced hypertensive heart disease by the Akt/eNOS/NO pathway.

    PubMed

    Jin, Sheng; Teng, Xu; Xiao, Lin; Xue, Hongmei; Guo, Qi; Duan, Xiaocui; Chen, Yuhong; Wu, Yuming

    2017-12-01

    Reductions in hydrogen sulfide (H 2 S) production have been implicated in the pathogenesis of hypertension; however, no studies have examined the functional role of hydrogen sulfide in hypertensive heart disease. We hypothesized that the endogenous production of hydrogen sulfide would be reduced and exogenous hydrogen sulfide would ameliorate cardiac dysfunction in N ω -nitro- L-arginine methyl ester ( L-NAME)-induced hypertensive rats. Therefore, this study investigated the cardioprotective effects of hydrogen sulfide on L-NAME-induced hypertensive heart disease and explored potential mechanisms. The rats were randomly divided into five groups: Control, Control + sodium hydrosulfide (NaHS), L-NAME, L-NAME + NaHS, and L-NAME + NaHS + glibenclamide (Gli) groups. Systolic blood pressure was monitored each week. In Langendorff-isolated rat heart, cardiac function represented by ±LV dP/dt max and left ventricular developing pressure was recorded after five weeks of treatment. Hematoxylin and Eosin and Masson's trichrome staining and myocardium ultrastructure under transmission electron microscopy were used to evaluate cardiac remodeling. The plasma nitric oxide and hydrogen sulfide concentrations, as well as nitric oxide synthases and cystathionine-γ-lyase activity in left ventricle tissue were determined. The protein expression of p-Akt, Akt, p-eNOS, and eNOS in left ventricle tissue was analyzed using Western blot. After five weeks of L-NAME treatment, there was a time-dependent hypertension, cardiac remodeling, and dysfunction accompanied by a decrease in eNOS phosphorylation, nitric oxide synthase activity, and nitric oxide concentration. Meanwhile, cystathionine-γ-lyase activity and hydrogen sulfide concentration were also decreased. NaHS treatment significantly increased plasma hydrogen sulfide concentration and subsequently promoted the Akt/eNOS/NO pathway which inhibited the development of hypertension and attenuated cardiac remodeling and

  11. Osthole relaxes pulmonary arteries through endothelial phosphatidylinositol 3-kinase/Akt-eNOS-NO signaling pathway in rats.

    PubMed

    Yao, Li; Lu, Ping; Li, Yumei; Yang, Lijing; Feng, Hongxuan; Huang, Yong; Zhang, Dandan; Chen, Jianguo; Zhu, Daling

    2013-01-15

    Pulmonary arterial hypertension is a life-threatening disease lacking effective therapies. Osthole is a natural coumarin compound isolated from Angelica pubescens Maxim., which possesses hypotensive effect. Although its effects on isolated thoracic aorta (systemic circulating system) are clarified, it remains unclear whether Osthole relaxes isolated pulmonary arteries (PAs) (pulmonary circulating system). The aim of this study was to investigate the effects of Osthole on isolated PAs and the underlying mechanisms. We examined PA relaxation induced by Osthole in isolated human and rat PA rings with force-electricity transducers, the expression and activity of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt) with western blot, and nitric oxide (NO) production using DAF-FM DA fluorescent indicator. The results showed that Osthole elicited a dose-dependent vasorelaxation activity with phenylephrine-precontracted human and rat PA rings, which can be diminished by endothelium denudation and inhibition of eNOS, while having no effect on rat mesenteric arteries. Osthole increased NO release as well as activation of Akt and eNOS, indicated with increased phosphorylations of Akt at Ser-473 and eNOS at Ser-1177 in endothelial cells. PI3K inhibitor LY294002 also blocked Osthole induced vasodilation. In summary, dilative effect of Osthole was dependent on endothelial integrity and NO production, and was mediated by endothelial PI3K/Akt-eNOS-NO pathway. These may provide a new pulmonary vasodilator for the therapy of pulmonary arterial hypertension. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Components Needed for the Design of a Sustainable Career and Technical Education Program

    ERIC Educational Resources Information Center

    Lassiter, Vann Mizzelle

    2012-01-01

    As education has changed to meet the needs of society and has been shaped by the enactment of new laws, various aspects included under the massive umbrella of education have also changed to maintain momentum One such educational program is career and technical education (CTE). Changes to CTE have been made to continually meet the needs of all…

  13. Association of NOS1 gene polymorphisms with cerebral palsy in a Han Chinese population: a case-control study.

    PubMed

    Yu, Ting; Xia, Lei; Bi, Dan; Wang, Yangong; Shang, Qing; Zhu, Dengna; Song, Juan; Wang, Yong; Wang, Xiaoyang; Zhu, Changlian; Xing, Qinghe

    2018-06-25

    Cerebral palsy (CP) is the leading cause of motor disability in children; however, its pathogenesis is unknown in most cases. Growing evidence suggests that Nitric oxide synthase 1 (NOS1) is involved in neural development and neurologic diseases. The purpose of this study was to determine whether genetic variants of NOS1 contribute to CP susceptibility in a Han Chinese population. A case-control study involving 652 CP patients and 636 healthy controls was conducted. Six SNPs in the NOS1 gene (rs3782219, rs6490121, rs2293054, rs10774909, rs3741475, and rs2682826) were selected, and the MassARRAY typing technique was applied for genotyping. Data analysis was conducted using SHEsis online software, and multiple test corrections were performed using SNPSpD online software. There were no significant differences in genotype and allele frequencies between patients and controls for the SNPs except rs6490121, which deviated from Hardy-Weinberg equilibrium and was excluded from further analyses. Subgroup analysis revealed differences in genotype frequencies between the CP with neonatal encephalopathy group (CP + NE) and control group for rs10774909, rs3741475, and rs2682826 (after SNPSpD correction, p = 0.004, 0.012, and 0.002, respectively). The T allele of NOS1 SNP rs3782219 was negatively associated with spastic quadriplegia (OR = 0.742, 95% CI = 0.600-0.918, after SNPSpD correction, p = 0.023). There were no differences in allele or genotype frequencies between CP subgroups and controls for the other genetic polymorphisms. NOS1 is associated with CP + NE and spastic quadriplegia, suggesting that NOS1 is likely involved in the pathogenesis of CP and that it is a potential therapeutic target for treatment of cerebral injury.

  14. 75 FR 6223 - PSEG Nuclear LLC; Hope Creek Generating Station and Salem Nuclear Generating Station, Unit Nos. 1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-08

    ... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-272, 50-311 and 50-354; NRC-2010-0043] PSEG Nuclear LLC; Hope Creek Generating Station and Salem Nuclear Generating Station, Unit Nos. 1 and 2; Environmental Assessment and Finding of No Significant Impact The U.S. Nuclear Regulatory Commission (NRC) is considering issuance of an Exemption, pursuant...

  15. 75 FR 77920 - Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 2 and 3; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-14

    ... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-247 and 50-286; NRC-2008-0672] Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating Unit Nos. 2 and 3; Notice of Availability of the Final Supplement 38 to the Generic Environmental Impact Statement for License Renewal of Nuclear Plants Notice is hereby given that the U.S. Nuclear...

  16. 75 FR 3946 - License Nos. DPR-42 and DPR-60; Northern States Power Company; Prairie Island Nuclear Generating...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-25

    ..., Office of Nuclear Reactor Regulation. [FR Doc. 2010-1309 Filed 1-22-10; 8:45 am] BILLING CODE 7590-01-P ... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-282 and 50-306; NRC-2010-0022] License Nos. DPR-42 and DPR-60; Northern States Power Company; Prairie Island Nuclear Generating Plant, Units 1 and 2...

  17. Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein.

    PubMed

    Liu, Songling; Premont, Richard T; Rockey, Don C

    2014-06-27

    Nitric oxide (NO) is a critical regulator of vascular tone and plays an especially prominent role in liver by controlling portal blood flow and pressure within liver sinusoids. Synthesis of NO in sinusoidal endothelial cells by endothelial nitric-oxide synthase (eNOS) is regulated in response to activation of endothelial cells by vasoactive signals such as endothelins. The endothelin B (ETB) receptor is a G-protein-coupled receptor, but the mechanisms by which it regulates eNOS activity in sinusoidal endothelial cells are not well understood. In this study, we built on two previous strands of work, the first showing that G-protein βγ subunits mediated activation of phosphatidylinositol 3-kinase and Akt to regulate eNOS and the second showing that eNOS directly bound to the G-protein-coupled receptor kinase-interacting protein 1 (GIT1) scaffold protein, and this association stimulated NO production. Here we investigated the mechanisms by which the GIT1-eNOS complex is formed and regulated. GIT1 was phosphorylated on tyrosine by Src, and Y293F and Y554F mutations reduced GIT1 phosphorylation as well as the ability of GIT1 to bind to and activate eNOS. Akt phosphorylation activated eNOS (at Ser(1177)), and Akt also regulated the ability of Src to phosphorylate GIT1 as well as GIT1-eNOS association. These pathways were activated by endothelin-1 through the ETB receptor; inhibiting receptor-activated G-protein βγ subunits blocked activation of Akt, GIT1 tyrosine phosphorylation, and ET-1-stimulated GIT1-eNOS association but did not affect Src activation. These data suggest a model in which Src and Akt cooperate to regulate association of eNOS with the GIT1 scaffold to facilitate NO production. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. BASINS Technical Notes

    EPA Pesticide Factsheets

    EPA has developed several technical notes that provide in depth information on a specific function in BASINS. Technical notes can be used to answer questions users may have, or to provide additional information on the application of features in BASINS.

  19. Final Technical Report

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

    Glasser, Alan H.

    Final technical report on DE-SC0016106. This is the final technical report for a portion of the multi-institutional CEMM project. This report is centered around 3 publications and a seminar presentation, which have been submitted to E-Link.

  20. Angiotensin II AT1 receptor alters ACE2 activity, eNOS expression and CD44-hyaluronan interaction in rats with hypertension and myocardial fibrosis.

    PubMed

    Bai, Feng; Pang, Xue-Fen; Zhang, Li-Hui; Wang, Ning-Ping; McKallip, Robert J; Garner, Ronald E; Zhao, Zhi-Qing

    2016-05-15

    This study tested the hypothesis that angiotensin II (Ang II) AT1 receptor is involved in development of hypertension and cardiac fibrosis via modifying ACE2 activity, eNOS expression and CD44-hyaluronan interaction. Male Sprague-Dawley rats were subjected to Ang II infusion (500ng/kg/min) using osmotic minipumps up to 4weeks and the AT1 receptor blocker, telmisartan was administered by gastric gavage (10mg/kg/day) during Ang II infusion. Our results indicated that Ang II enhances AT1 receptor, downregulates AT2 receptor, ACE2 activity and eNOS expression, and increases CD44 expression and hyaluronidase activity, an enzyme for hyaluronan degradation. Further analyses revealed that Ang II increases blood pressure and augments vascular/interstitial fibrosis. Comparison of the Ang II group, treatment with telmisartan significantly increased ACE2 activity and eNOS expression in the intracardiac vessels and intermyocardium. These changes occurred in coincidence with decreased blood pressure. Furthermore, the locally-expressed AT1 receptor was downregulated, as evidenced by an increased ratio of the AT2 over AT1 receptor (1.4±0.4% vs. 0.4±0.1% in Ang II group, P<0.05). Along with these modulations, telmisartan inhibited membrane CD44 expression and hyaluronidase activity, decreased populations of macrophages and myofibroblasts, and reduced expression of TGFβ1 and Smads. Collagen I synthesis and tissue fibrosis were attenuated as demonstrated by the less extensive collagen-rich area. These results suggest that the AT1 receptor is involved in development of hypertension and cardiac fibrosis. Selective activating ACE2/eNOS and inhibiting CD44/HA interaction might be considered as the therapeutic targets for attenuating Ang II induced deleterious cardiovascular effects. Copyright © 2016 Elsevier Inc. All rights reserved.