75 FR 61772 - Certain Coated Paper Suitable for High-Quality Print Graphics Using Sheet-Fed Presses From China...

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76 FR 56797 - Cut-to-Length Carbon-Quality Steel Plate From India, Indonesia, Italy, Japan, and Korea; Revised...

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2011-09-14

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-388-391 and 731-TA-817-821 ;Second Review] Cut-to-Length Carbon-Quality Steel Plate From India, Indonesia, Italy, Japan, and Korea; Revised schedule for the subject reviews. AGENCY: United States International Trade Commission. ACTION: Notice...

Elucidation of the Tubulin-targeted Mechanism of Action of 9-(3-pyridyl) Noscapine.

PubMed

Pradhan, Swagat; Mahaddalkar, Tejashree; Choudhary, Sinjan; Manhcukonda, Naresh; Nagireddy, Praveen Reddy; Kantevari, Srinivas; Lopus, Manu

2017-01-01

We have recently reported the synthesis and antiproliferative potential of a series of biaryl type α-noscapine congeners. Among them, 9-(3-pyridyl) noscapine 3f (9-PyNos, henceforth), which was synthesized by adding pyridine unit to the tetrahydroisoquinoline part of natural α-noscapine core, was found to be the most effective one to inhibit proliferation of a variety of cancer cell lines. However, details of its interactions with its cellular target, tubulin, remain poorly understood. In this report, we examined the nature of interactions of 9-PyNos with tubulin based on the methodologies of spectrofluorimetry, circular dichroism, and turbidimetry techniques. Far-UV circular dichroism spectra indicated perturbation of tubulin secondary structure in the presence of 9-PyNos, not amounting, however, to the perturbation induced by noscapine. The noscapinoid nevertheless altered the surface configuration of the protein considerably, as indicated by an anilinonaphthalene sulphonate binding assay, and promoted colchicine binding to tubulin, the latter indicating its adjacent binding site with colchicine. 9-PyNos however, did not alter microtubule assembly considerably. Investigating the possible reason behind this apparent lack of strong inhibition of microtubule assembly, we found that the binding interactions of tubulin with 9-PyNos do not involve modification of cysteine residues of tubulin. Taken together, our data suggest that the antiproliferative mechanism of action of 9-PyNos involves disruption of structural integrity of tubulin without strong inhibition of tubulin assembly. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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...

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...

75 FR 64751 - Braidwood Station, Units 1 and 2 and Byron Station, Unit Nos. 1 and 2; Notice of Withdrawal of...

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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...

76 FR 54260 - Dominion Nuclear Connecticut, Inc., Millstone Power Station, Unit Nos. 1, 2, and 3; Environmental...

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2011-08-31

... action would provide exemption from the work hour control requirements of 10 CFR 26.205(c) and (d) during... work hour controls on vital personnel could impede the ability to focus on plant safety and security... which the work hour control exemption applies, to exiting the condition, is limited to severe weather...

76 FR 40944 - PSEG Nuclear, LLC, Salem Nuclear Generating Station, Units 1 and 2; Notice of Issuance of Renewed...

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2011-07-12

... no-action alternative. The factors considered in the record of decision can be found in the... serves as the record of decision for the renewal of Facility Operating License Nos. DPR-70 and DPR-75, consistent with Title 10 of the Code of Federal Regulations (10 CFR) 51.103, ``Record of Decision--General...

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

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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...

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...

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.

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

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

75 FR 75706 - Dresden Nuclear Power Station, Units 2 and 3 and Quad Cities Nuclear Power Station, Unit Nos. 1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-06

...- 2010-0373] Dresden Nuclear Power Station, Units 2 and 3 and Quad Cities Nuclear Power Station, Unit Nos... and DPR-25 for Dresden Nuclear Power Station, Units 2 and 3, respectively, located in Grundy County, Illinois, and to Renewed Facility Operating License Nos. DPR-29 and DPR-30 for Quad Cities Nuclear Power...

76 FR 40754 - Duke Energy Carolinas, LLC Catawba Nuclear Station, Units 1 and 2; McGuire Nuclear Station, Units...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0100; Docket Nos. 50-413 and 50-414; Docket Nos. 50-369 and 50-370; Docket Nos. 50-269, 50-270, And 50-287] Duke Energy Carolinas, LLC Catawba Nuclear Station, Units 1 and 2; McGuire Nuclear Station, Units 1 and 2; Oconee Nuclear Station, Units 1, 2, and 3; Notice of Withdrawal of Application for Amendment...

Exploring teachers' beliefs and knowledge about scientific inquiry and the nature of science: A collaborative action research project

NASA Astrophysics Data System (ADS)

Fazio, Xavier Eric

Science curriculum reform goals espouse the need to foster and support the development of scientific literacy in students. Two critical goals of scientific literacy are students' engagement in, and developing more realistic conceptions about scientific inquiry (SI) and the nature of science (NOS). In order to promote the learning of these curriculum emphases, teachers themselves must possess beliefs and knowledge supportive of them. Collaborative action research is a viable form of curriculum and teacher development that can be used to support teachers in developing the requisite beliefs and knowledge that can promote these scientific literacy goals. This research study used a collective case study methodology to describe and interpret the views and actions of four teachers participating in a collaborative action research project. I explored the teachers' SI and NOS views throughout the project as they investigated ideas and theories, critically examined their current curricular practice, and implemented and reflected on these modified curricular practices. By the end of the research study, all participants had uniquely augmented their understanding of SI and NOS. The participants were better able to provide explanatory depth to some SI and NOS ideas; however, specific belief revision with respect to SI and NOS ideas was nominal. Furthermore, their idealized action research plans were not implemented to the extent that they were planned. Explanations for these findings include: impact of significant past educational experiences, prior understanding of SI and NOS, depth of content and pedagogical content knowledge of the discipline, and institutional and instructional constraints. Nonetheless, through participation in the collaborative action research process, the teachers developed professionally, personally, and socially. They identified many positive outcomes from participating in a collaborative action research project; however, they espoused constraints to implementing innovative actions. Indeed, local school cultures were barriers to the participants' development. A model of teacher development embracing all the developmental areas is presented---an integration of social, personal, and professional development. Implications and recommendations for future research on teachers' beliefs and knowledge, as well as the viability of collaborative action research to facilitate teacher and curriculum development are presented.

The Nebivolol action on vascular tone is dependent on actin cytoskeleton polymerization and Rho-A activity into ECs and SMCs.

PubMed

Kadi, A; de Isla, N; Moby, V; Lacolley, P; Labrude, P; Stoltz, J F; Menu, P

2014-01-01

Nitric oxide is implicated in the target action of Nebivolol, a selective β1 adrenoceptor blocker used in hypertension treatment. As the Nitric Oxide (NO) production and the actin cytoskeleton are linked, the aim of this work was to study the involvement of actin cytoskeleton on mechanism of action of Nebivolol in cultured endothelial cells. We studied the effect of Nebivolol (200 μM) on actin filaments remodeling and its impact on NO production and eNOS activation. Results showed that Nebivolol perturbs actin filaments polymerization, increases NO production and eNOS activity between 30 minutes and 1 h. Stabilization of actin filaments with phalloïdine (50 μM) abolishes Nebivolol effects on eNOS activation and NO production. Furthermore, Rho-kinase activity decreased during the first hour of Nebivolol treatment, then increased after 3 h, while actin filaments repolymerized, eNOS activation and NO production decreased. In SMCs, Nebivolol induced a decrease in the Rho-kinase activity from 1 h until 24 h of incubation. In conclusion, we suggest that Nebivolol induced NO production in Endothelial Cells (ECs) via complementary actions between actin cytoskeleton remodeling inducing eNOS activation and Rho-kinase implication. The effect of Nebivolol on ECs occurs during the first hour, this effect on SMCs seems to be maintained until 24 h, explaining persisted action of Nebivolol observed in vivo.

76 FR 24538 - Duke Energy Carolinas, LLC; Catawba Nuclear Station, Units 1 and 2; McGuire Nuclear Station...

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2011-05-02

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-413 and 50-414; NRC-2011-0100; Docket Nos. 50-369 and 50-370; Docket Nos. 50-269, 50-270, and 50-287] Duke Energy Carolinas, LLC; Catawba Nuclear Station, Units 1 and 2; McGuire Nuclear Station, Units 1 and 2; Oconee Nuclear Station, Units 1, 2, and 3; Notice of Withdrawal of Application for Amendmen...

75 FR 66802 - Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

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2010-10-29

... Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2; Notice of Withdrawal of...) has granted the request of Calvert Cliffs Nuclear Power Plant, LLC, the licensee, to withdraw its... for the Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2, located in Calvert County, MD. The...

76 FR 39908 - Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

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2011-07-07

... Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2; Calvert Cliffs.... DPR-53 and DPR-69, for the Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2 (CCNPP), respectively... (ISFSI), currently held by Calvert Cliffs Nuclear Power Plant, LLC as owner and licensed operator...

76 FR 1469 - Calvert Cliffs Nuclear Power Plant, LLC; Calvert Cliffs Nuclear Power Plant, Unit Nos. 1 and 2...

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2011-01-10

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77 FR 12887 - Virgina Electric and Power Company; Receipt of Request for Action

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2012-03-02

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-338 and 50-339; NRC-2012-0051; License Nos. NPF-4 and NPF-7] Virgina Electric and Power Company; Receipt of Request for Action Notice is hereby given that by petition dated September 8, 2011 (Agencywide Documents Access and Management System (ADAMS...

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2012-09-11

... NUCLEAR REGULATORY COMMISSION [Docket Nos.: 50-250, 50-251, 50-335, and 50-389; NRC-2012-0210; License Nos.: DPR-31, DPR-41, DPR-67, and NPF-16] Florida Power & Light Company; Receipt of Request for Action Notice is hereby given that by petition dated April 23, 2012, Mr. Thomas King (petitioner) has...

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...

Leptin action through hypothalamic nitric oxide synthase-1-expressing neurons controls energy balance.

PubMed

Leshan, Rebecca L; Greenwald-Yarnell, Megan; Patterson, Christa M; Gonzalez, Ian E; Myers, Martin G

2012-05-01

Few effective measures exist to combat the worldwide obesity epidemic(1), and the identification of potential therapeutic targets requires a deeper understanding of the mechanisms that control energy balance. Leptin, an adipocyte-derived hormone that signals the long-term status of bodily energy stores, acts through multiple types of leptin receptor long isoform (LepRb)-expressing neurons (called here LepRb neurons) in the brain to control feeding, energy expenditure and endocrine function(2-4). The modest contributions to energy balance that are attributable to leptin action in many LepRb populations(5-9) suggest that other previously unidentified hypothalamic LepRb neurons have key roles in energy balance. Here we examine the role of LepRb in neuronal nitric oxide synthase (NOS1)-expressing LebRb (LepRb(NOS1)) neurons that comprise approximately 20% of the total hypothalamic LepRb neurons. Nos1(cre)-mediated genetic ablation of LepRb (Lepr(Nos1KO)) in mice produces hyperphagic obesity, decreased energy expenditure and hyperglycemia approaching that seen in whole-body LepRb-null mice. In contrast, the endocrine functions in Lepr(Nos1KO) mice are only modestly affected by the genetic ablation of LepRb in these neurons. Thus, hypothalamic LepRb(NOS1) neurons are a key site of action of the leptin-mediated control of systemic energy balance.

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...

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.

Emphasizing the History of Genetics in an Explicit and Reflective Approach to Teaching the Nature of Science

NASA Astrophysics Data System (ADS)

Williams, Cody Tyler; Rudge, David Wÿss

2016-05-01

Science education researchers have long advocated the central role of the nature of science (NOS) for our understanding of scientific literacy. NOS is often interpreted narrowly to refer to a host of epistemological issues associated with the process of science and the limitations of scientific knowledge. Despite its importance, practitioners and researchers alike acknowledge that students have difficulty learning NOS and that this in part reflects how difficult it is to teach. One particularly promising method for teaching NOS involves an explicit and reflective approach using the history of science. The purpose of this study was to determine the influence of a historically based genetics unit on undergraduates' understanding of NOS. The three-class unit developed for this study introduces students to Mendelian genetics using the story of Gregor Mendel's work. NOS learning objectives were emphasized through discussion questions and investigations. The unit was administered to undergraduates in an introductory biology course for pre-service elementary teachers. The influence of the unit was determined by students' responses to the SUSSI instrument, which was administered pre- and post-intervention. In addition, semi-structured interviews were conducted that focused on changes in students' responses from pre- to post-test. Data collected indicated that students showed improved NOS understanding related to observations, inferences, and the influence of culture on science.

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...

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...

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...

Heme oxygenase-1 overexpression fails to attenuate hypertension when the nitric oxide synthase system is not fully operative.

PubMed

Polizio, Ariel H; Santa-Cruz, Diego M; Balestrasse, Karina B; Gironacci, Mariela M; Bertera, Facundo M; Höcht, Christian; Taira, Carlos A; Tomaro, Maria L; Gorzalczany, Susana B

2011-01-01

Heme oxygenase (HO) is an enzyme that is involved in numerous secondary actions. One of its products, CO, seems to have an important but unclear role in blood pressure regulation. CO exhibits a vasodilator action through the activation of soluble guanylate cyclase and the subsequent production of cyclic guanosine monophosphate (cGMP). The aim of the present study was to determine whether pathological and pharmacological HO-1 overexpression has any regulatory role on blood pressure in a renovascular model of hypertension. We examined the effect of zinc protoporyphyrin IX (ZnPP-IX) administration, an inhibitor of HO activity, on mean arterial pressure (MAP) and heart rate in sham-operated and aorta-coarcted (AC) rats and its interaction with the nitric oxide synthase (NOS) pathway. Inhibition of HO increased MAP in normotensive rats with and without hemin pretreatment but not in hypertensive rats. Pretreatment with NG-nitro-L-arginine methyl ester blocked the pressor response to ZnPP-IX, suggesting a key role of NOS in the cardiovascular action of HO inhibition. In the same way, AC rats, an experimental model of hypertension with impaired function and low expression of endothelial NOS (eNOS), did not show any cardiovascular response to inhibition or induction of HO. This finding suggests that eNOS was necessary for modulating the CO response in the hypertensive group. In conclusion, the present study suggests that HO regulates blood pressure through CO only when the NOS pathway is fully operative. In addition, chronic HO induction fails to attenuate the hypertensive stage induced by coarctation as a consequence of the impairment of the NOS pathway. Copyright © 2011 S. Karger AG, Basel.

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

Relationship between students' understandings of nature of science and instructional context

NASA Astrophysics Data System (ADS)

Khishfe, Rola Fouad

The study investigated and compared two different instructional approaches (integrated and nonintegrated), which address the explicit teaching of nature of science (NOS), in relation to improving students' understanding of NOS. Participants were three teachers and their students---a total of 129---which comprised six groups of 89 ninth and 40 10th/11th graders. Each teacher taught two intact sections of the same grade level within a specific science discipline (environmental science, chemistry, or biology). The treatment for all groups spanned five to six weeks and involved teaching a unit, which included both the regular science content and NOS. Participants in each of the two intact classes were taught by the same teacher about their regular science content, with the difference being the context in which NOS was explicitly taught (integrated or nonintegrated). In the integrated group, NOS instruction was related to the science content addressed in the unit. In the nonintegrated group, NOS was taught through a set of generic (non content-embedded) activities that specifically addressed NOS aspects and were "interspersed" across the science content addressed in the unit. An open-ended questionnaire, in conjunction with semi-structured interviews, was used to assess participants' views prior to and following instruction. Data analysis involved a systematic process consistent with analytic induction. Results showed general improvements in participants' views of NOS regardless of whether or not NOS was integrated within the regular science content. The results of this study do not support the appealing assumption held by many science educators that integrating NOS within the context of the science content would better enhance the learning of NOS. However, the results suggest the possibility of an interaction between the type of change (naive to transitional, transitional to informed, naive to informed, no changes, regression) in students' views and the explicit instructional approach (integrated or nonintegrated) to teach NOS. Moreover, the findings suggest the transferability of NOS understandings among various contexts, with the consequence that learning NOS might not be context-dependent. Implications for the teaching and learning of NOS are discussed.

(−)-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

76 FR 29277 - Exelon Generation Company, LLC; Peach Bottom Atomic Power Station Unit Nos. 2 and 3...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

... Company, LLC; Peach Bottom Atomic Power Station Unit Nos. 2 and 3; Environmental Assessment and Finding of..., LLC (Exelon, the licensee) for operation of the Peach Bottom Atomic Power Station, Units 2 and 3...) in the Peach Bottom Atomic Power Station (PBAPS) LLRW Storage Facility. Considering the nature of the...

40 CFR 69.11 - New exemptions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... shall be fired in Cabras Power Plant Units Nos. 1 through 3 and in Piti Power Plant Units Nos. 4 and 5... conditionally exempts Piti Power Plant Units No. 8 and No. 9 from certain CAA requirements. (2) A waiver of the... Administrator of EPA conditionally exempts Guam Power Authority (“GPA”) from certain CAA requirements. (1) A...

A Community College Instructor's Reflective Journey toward Developing Pedagogical Content Knowledge for Nature of Science in a Non-Majors Undergraduate Biology Course

ERIC Educational Resources Information Center

Krajewski, Sarah J.; Schwartz, Renee

2014-01-01

Research supports an explicit-reflective approach to teaching about nature of science (NOS), but little is reported on teachers' journeys as they attempt to integrate NOS into everyday lessons. This participatory action research paper reports the challenges and successes encountered by an in-service teacher, Sarah, implementing NOS for the…

[Effect of vitamin C on the condition of NO-synthase system in experimental stomach ulcer].

PubMed

Zhuroms'kyĭ, V S; Skliarov, O Ia

2011-01-01

We investigated the effect of Vitamin C (Vit C) on the changes of activity of the enzymes of NO-synthase system, nitric oxide content, lipoperoxidation processes, activity of SOD and catalase in gastric mucosa (GM), and concentrations of L-arginine, Vit C and Vit E in the blood of rats under conditions of experimental ulcer of the stomach caused by adrenaline injection. Vit C displayed a pronounced antioxidant action, reduced the degree of destructive affections, diminished the activity of iNOS and lipoperoxidation processes, decreased the NO content and SOD activity. Furthermore, the concentration of L-arginine and Vit C in the blood was increased. Combined action of Vit C with L-arginine reduced the degree of GM lesions, activity of eNOS and the content of NO in GM whereas the concentration of L-arginine in blood was increased. Under conditions of Vit C action and iNOS and COX-2 blockage, the activity of NO-synthases and lipoperoxidation processes were slightly decreased, indicating on dominant action of Vit C.

A Look into Students' Retention of Acquired Nature of Science Understandings

NASA Astrophysics Data System (ADS)

Khishfe, Rola

2015-07-01

Having the learning and retention of science content and skills as a goal of scientific literacy, it is significant to study the issue of retention as it relates to teaching and learning about nature of science (NOS). Then, the purpose of this study was to investigate the development of NOS understandings of students, and the retention of these understandings four months after being acquired through explicit reflective instruction in relation to two contexts. Participants were 24 tenth-grade students at a private high school in a city in the Middle East. Explicit NOS instruction was addressed within a six-week unit about genetic engineering. Three NOS aspects were integrated and dispersed across the unit. A questionnaire, together with semi-structured interviews, was administered as pre-, post-, and delayed post-test to assess the retention of participants' NOS understandings. The questionnaire had two open-ended scenarios addressing controversial socioscientific issues about genetically modified food and water fluoridation. Results showed that most students improved their naïve understandings of NOS in relation to the two contexts following the six-week unit with the explicit NOS instruction. However, these newly acquired NOS understandings were not retained by all students four months after instruction. Many of the students reverted back to their earlier naïve understandings. Conclusions about the factors facilitating the process of retention as the orientation to meaningful learning and the prolonged exposure to the domain were discussed in relation to practical implications in the classroom.

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 translated into classroom practice. The findings also showed that a direct connection can be made between understandings of the NOS and issues of equity and access at the elementary level.

[Expression and antagonist role of endothelin and nitric oxide synthase in atherosclerotic plaque].

PubMed

Song, L; Wang, D; Wang, T

1997-02-01

To study the pathogenetic mechanism of atherosclerotic plaque, the action of mediation and antagonism of endothelin (ET) and nitric oxide synthase (NOS) was investigated. In situ hybridization, RT-PCR on endothelin and NOS, cytochemistry on NOS were measured using the rabbit atherosclerosis model and cultured vascular smooth muscle cells (VSMC) from normal rabbit. Transcription of endothelin mRNA increased and transcription of NOS mRNA decreased in astherosclerotic plaque: compared with normal aorta, expression of ET gene in plaque was increased by 1.2 times and the expression of NOS gene was decreased by 22.2%; cytochemistry combined with image pattern analysis showed that ET could inhibit NOS protien synthesis in VSMC; type A receptor antagonist of ET could inhibit the role of ET which causes a decrease of NOS protein in VSMC. The imbalance between NOS and ET, namely abnormal increase of ET and/or obvious decrease of NOS, is related to atherosclerotic plaque formation.

76 FR 388 - Southern Nuclear Operating Company; Vogtle Electric Generating Plant, Unit Nos. 1 and 2; Notice...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... Design,'' GDC 31, ``Fracture Prevention of Reactor Coolant Pressure Boundary,'' and GDC 32, ``Inspection... Operating Company; Vogtle Electric Generating Plant, Unit Nos. 1 and 2; Notice of Consideration of Issuance of Amendment to Facility Operating License, Proposed No Significant Hazards Consideration...

Transfer of Nature of Science Understandings into Similar Contexts: Promises and Possibilities of an Explicit Reflective Approach

NASA Astrophysics Data System (ADS)

Khishfe, Rola

2013-11-01

The purpose of this study was to (a) investigate the effectiveness of explicit nature of science (NOS) instruction in the context of controversial socioscientific issues and (b) explore whether the transfer of acquired NOS understandings, which were explicitly taught in the context of one socioscientific context, into other similar contexts (familiar and unfamiliar) was possible. Participants were 10th grade students in two intact sections at one high school. The treatment involved teaching a six-week unit about genetic engineering. For one group (non-NOS group), there was no explicit instruction about NOS. For the other group (NOS group), explicit instruction about three NOS aspects (subjective, empirical, and tentative) was dispersed across the genetic engineering unit. A questionnaire including two open-ended scenarios, in conjunction with semi-structured interviews, was used to assess the change in participants' understandings of NOS and their ability to transfer their acquired understandings into similar contexts. The first scenario involved a familiar context about genetically modified food and the second one focused on an unfamiliar context about water fluoridation. Results showed no improvement in NOS understandings of participants in the non-NOS group in relation to the familiar and unfamiliar contexts. On the other hand, there was a general improvement in the NOS understandings of participants in the NOS group in relation to both the familiar and unfamiliar contexts. Implications about the transfer of participants' acquired NOS understandings on the basis of the distance between the context of learning and that of application are highlighted and discussed in link with the classroom learning environment.

13. LONGITUDINAL VIEW OF THE SIX TURBINEGENERATOR UNITS (NO.'S 15 ...

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

13. LONGITUDINAL VIEW OF THE SIX TURBINE-GENERATOR UNITS (NO.'S 1-5 ARE ORIGINAL). TURBINE-GENERATOR NO.1 IS IN THE FOREGROUND, LOOKING WEST. - Washington Water Power Company Post Falls Power Plant, Middle Channel Powerhouse & Dam, West of intersection of Spokane & Fourth Streets, Post Falls, Kootenai County, ID

Towards a Philosophically and a Pedagogically Reasonable Nature of Science Curriculum

NASA Astrophysics Data System (ADS)

Yacoubian, Hagop Azad

This study, primarily theoretical in nature, explores a philosophically and pedagogically reasonable way of addressing nature of science (NOS) in school science. NOS encompasses what science is and how scientific knowledge develops. I critically evaluate consensus frameworks of NOS in school science, which converge contentious philosophical viewpoints into general NOS-related ideas. I argue that they (1) lack clarity in terms of how NOS-related ideas could be applied for various ends, (2) portray a distorted image of the substantive content of NOS and the process of its development, and (3) lack a developmental trajectory for how to address NOS at different grade levels. As a remedy to these problems, I envision a NOS curriculum that (1) explicates and targets both NOS as an educational end and NOS as a means for socioscientific decision making, (2) has critical thinking as its foundational pillar, and (3) provides a developmental pathway for NOS learning using critical thinking as a progression unit. Next, I illustrate a framework for addressing NOS in school science referred to as the critical thinking—nature of science (CT-NOS) framework. This framework brings together the first two of the three elements envisioned in the NOS curriculum. I address the third element by situating the CT-NOS framework in a developmental context, borrowing from the literature on learning progressions in science and using critical thinking as a progression unit. Finally, I present an empirical study of experienced secondary science teachers’ views of a NOS lesson prepared using the CT-NOS framework. The teachers attended a professional development workshop at which the lesson, and the characteristics of the CT-NOS framework, were presented. The analysis of the qualitative data revealed that most teachers found the lesson to be somewhat feasible for a secondary science classroom, useful or somewhat useful to their students, and interesting. The teachers focused on 14 features of the lesson in their judgments and recommendations. The study revealed a number of teacher challenges generally related to critical thinking and its teaching as well as to the distinction between critical thinking about NOS and critical thinking with NOS.

Effects of a water-soluble curcumin protein conjugate vs. pure curcumin in a diabetic model of erectile dysfunction.

PubMed

Abdel Aziz, Mohamed Talaat; Motawi, Tarek; Rezq, Ameen; Mostafa, Taymour; Fouad, Hanan H; Ahmed, Hanan H; Rashed, Laila; Sabry, Dina; Senbel, Amira; Al-Malki, A; El-Shafiey, Raghda

2012-07-01

Curcumin is involved in erectile signaling via elevation of cyclic guanosine monophosphate (cGMP). Assessment of the effects of water-soluble curcumin in erectile dysfunction (ED). One hundred twenty male white albino rats were divided into: 1st and 2nd control groups with or without administration of Zinc protoporphyrin (ZnPP), 3rd and 4th diabetic groups with or without ZnPP, 5th diabetic group on single oral dose of pure curcumin, 6th diabetic group on pure curcumin administered daily for 12 weeks, 7th and 8th diabetic groups on single dose of water-soluble curcumin administered with or without ZnPP, 9th and 10th diabetic groups on water-soluble curcumin administered daily for 12 weeks with or without ZnPP. All curcumin dosage schedules were administered after induction of diabetes. Quantitative gene expression of endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), heme oxygenase-1 (HO-1), nuclear transcription factor-erythroid2 (Nrf2), NF-Кβ, and p38. Cavernous tissue levels of HO and NOS enzyme activities, cGMP and intracavernosal pressure (ICP). Twelve weeks after induction of diabetes, ED was confirmed by the significant decrease in ICP. There was a significant decrease in cGMP, NOS, HO enzymes, a significant decrease in eNOS, nNOS, HO-1 genes and a significant elevation of NF-Кβ, p38, iNOS genes. Administration of pure curcumin or its water-soluble conjugate led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in eNOS, nNOS, HO-1, and Nrf2 genes, and a significant decrease in NF-Кβ, p38, and iNOS genes. Water-soluble curcumin showed significant superiority and more prolonged duration of action. Repeated doses regimens were superior to single dose regimen. Administration of ZnPP significantly reduced HO enzyme, cGMP, ICP/ mean arterial pressure (MAP), HO-1 genes in diabetic groups. Water-soluble curcumin could enhance erectile function with more effectiveness and with more prolonged duration of action. © 2012 International Society for Sexual Medicine.

Requirement of phosphorylatable endothelial nitric oxide synthase at Ser-1177 for vasoinhibin-mediated inhibition of endothelial cell migration and proliferation in vitro.

PubMed

García, Celina; Nuñez-Anita, Rosa Elvira; Thebault, Stéphanie; Arredondo Zamarripa, David; Jeziorsky, Michael C; Martínez de la Escalera, Gonzalo; Clapp, Carmen

2014-03-01

Endothelial nitric oxide synthase (eNOS)-derived nitric oxide is a major vasorelaxing factor and a mediator of vasopermeability and angiogenesis. Vasoinhibins, a family of antiangiogenic prolactin fragments that include 16 K prolactin, block most eNOS-mediated vascular effects. Vasoinhibins activate protein phosphatase 2A, causing eNOS inactivation through dephosphorylation of eNOS at serine residue 1179 in bovine endothelial cells and thereby blocking vascular permeability. In this study, we examined whether human eNOS phosphorylation at S1177 (analogous to bovine S1179) influences other actions of vasoinhibins. Bovine umbilical vein endothelial cells were stably transfected with human wild-type eNOS (WT) or with phospho-mimetic (S1177D) or non-phosphorylatable (S1177A) eNOS mutants. Vasoinhibins inhibited the increases in eNOS activity, migration, and proliferation following the overexpression of WT eNOS but did not affect these responses in cells expressing S1177D and S1177A eNOS mutants. We conclude that eNOS inhibition by dephosphorylation of S1177 is fundamental for the inhibition of endothelial cell migration and proliferation by vasoinhibins.

Induction of calcium-dependent nitric oxide synthases by sex hormones.

PubMed

Weiner, C P; Lizasoain, I; Baylis, S A; Knowles, R G; Charles, I G; Moncada, S

1994-05-24

We have examined the effects of pregnancy and sex hormones on calcium-dependent and calcium-independent nitric oxide synthases (NOSs) in the guinea pig. Pregnancy (near term) caused a > 4-fold increase in the activity of calcium-dependent NOS in the uterine artery and at least a doubling in the heart, kidney, skeletal muscle, esophagus, and cerebellum. The increase in NOS activity in the cerebellum during pregnancy was inhibited by the estrogen-receptor antagonist tamoxifen. Treatment with estradiol (but not progesterone) also increased calcium-dependent NOS activity in the tissues examined from both females and males. Testosterone increased calcium-dependent NOS only in the cerebellum. No significant change in calcium-independent NOS activity was observed either during pregnancy or after the administration of any sex hormone. Both pregnancy and estradiol treatment increased the amount of mRNAs for NOS isozymes eNOS and nNOS in skeletal muscle, suggesting that the increases in NOS activity result from enzyme induction. Thus both eNOS and nNOS are subject to regulation by estrogen, an action that could explain some of the changes that occur during pregnancy and some gender differences in physiology and pathophysiology.

75 FR 6736 - FirstEnergy Nuclear Operating Company, FirstEnergy Nuclear Generation Corp., Ohio Edison Company...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-10

..., Beaver Valley Power 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 to... Operating Company (licensee), for operation of the Beaver Valley Power Station, Unit Nos. 1 and 2 (BVPS-1...

78 FR 16894 - In the Matter of Luminant Generation Company LLC, Comanche Peak Nuclear Power Plant, Units 1 and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-19

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0310; Docket Nos.: 50-445 and 50-446; License Nos.: NPF-87 and NPF-89] In the Matter of Luminant Generation Company LLC, Comanche Peak Nuclear Power Plant, Units 1 and 2; Order Approving the Proposed Internal Restructuring and Indirect Transfer of License...

75 FR 13801 - Exelon Generation Company, LLC; Zion Nuclear Power Station, Units 1 and 2; Order Extending the...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-23

... NUCLEAR REGULATORY COMMISSION [NRC-2008-0285; Docket Nos. 50-295 and 50-304; License Nos. DPR-39 and DPR-48] Exelon Generation Company, LLC; Zion Nuclear Power Station, Units 1 and 2; Order Extending the Effectiveness of the Approval of the Transfer of License and Conforming Amendment I Exelon...

78 FR 11904 - Zion Nuclear Power Station, Units 1 and 2; ZionSolutions, LLC; Consideration of Indirect Transfer

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-20

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-295 and 50-304; NRC-2013-0034] Zion Nuclear Power Station, Units 1 and 2; ZionSolutions, LLC; Consideration of Indirect Transfer AGENCY: Nuclear Regulatory... the indirect transfer of Facility Operating License Nos. DPR-39 and DPR-48 for Zion Nuclear Power...

Students' Environmental NOS Views, Compassion, Intent, and Action: Impact of Place-Based Socioscientific Issues Instruction

ERIC Educational Resources Information Center

Herman, Benjamin C.

2018-01-01

Preparing students to achieve the lofty goal of functional scientific literacy entails addressing the normative and non-normative facets of socioscientific issues (SSI) such as scientific processes, the nature of science (NOS) and diverse sociocultural perspectives. SSI instructional approaches have demonstrated some efficacy for promoting…

78 FR 11987 - Cable Television Act of 1992

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2013-02-21

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 76 [MM Docket Nos. 92-266 and 93-215, FCC 94-286] Cable Television Act of 1992 AGENCY: Federal Communications Commission. ACTION: Final rule; announcement... Reconsideration and Fifth Report and Order in MM Docket Nos. 92-266 and 93-215; FCC 94-286, published in the...

Inhibition of inducible nitric oxide synthesis by azathioprine in a macrophage cell line.

PubMed

Moeslinger, Thomas; Friedl, Roswitha; Spieckermann, Paul Gerhard

2006-06-20

Azathioprine is used as an anti-inflammatory agent. Although there are numerous data demonstrating cytotoxic and immunosuppressive properties of azathioprine and its metabolite 6-mercaptopurine, the mechanism of the anti-inflammatory action of azathioprine has not yet been fully clarified. During our study, we investigated the effects of azathioprine on the inducible nitric oxide synthase (iNOS) in lipopolysaccharide stimulated murine macrophages (RAW 264.7) by measurement of iNOS protein (immunoblotting), iNOS mRNA (semiquantitative competitive RT-PCR), and NO production (nitrite levels). Azathioprine (0-210 muM) induces a concentration dependent inhibition of inducible nitric oxide synthesis (IC50: 33.5 muM). iNOS protein expression showed a concentration dependent reduction as revealed by immunoblotting when cells were incubated with increasing amounts of azathioprine. Azathioprine decreases iNOS mRNA levels as shown by semiquantitative competitive RT-PCR. In contrast, 6-mercaptopurine showed no inhibition of inducible nitric oxide synthesis. Azathioprine did not reduce iNOS mRNA stability after the addition of actinomycin D. Enzymatic activity assays with increasing concentrations of azathioprine (0-210 muM) showed no statistically significant inhibition of iNOS enzyme activity compared to cell lysates without azathioprine. Nuclear translocation of NF-kappaB p65 subunit and binding of NF-kappaB p50 subunit from nuclear extracts to a biotinylated-consensus sequence was unaffected by azathioprine treatment. iNOS inhibition by azathioprine was associated with a decreased expression of IRF-1 (interferon regulatory factor 1) and IFN-beta (beta-interferon) mRNA. Azathioprine induced iNOS inhibition seems to be associated with an action of the methylnitroimidazolyl substituent. This suggests a route to the rational design of nontoxic anti-inflammatory agents by replacing the 6-mercaptopurine component of azathioprine with other substituents. The inhibition of inducible nitric oxide synthesis might contribute to the anti-inflammatory activities of azathioprine.

Changes Observed in Views of Nature of Science During a Historically Based Unit

NASA Astrophysics Data System (ADS)

Rudge, David Wÿss; Cassidy, David Paul; Fulford, Janice Marie; Howe, Eric Michael

2014-09-01

Numerous empirical studies have provided evidence of the effectiveness of an explicit and reflective approach to the learning of issues associated with the nature of science (NOS) (c.f. Abd-El-Khalick and Lederman in J Res Sci Teach 37(10):1057-1095, 2000). This essay reports the results of a mixed-methods association study involving 130 preservice teachers during the course of a three class unit based upon the history of science using such an approach. Within the unit the phenomenon of industrial melanism was presented as a puzzle for students to solve. Students were explicitly asked to reflect upon several NOS issues as they developed and tested their own explanations for the "mystery phenomenon". NOS views of all participants were characterized by means of surveys and follow-up interviews with a subsample of 17 participants, using a modified version of the VNOS protocol (c.f. Lederman et al. in J Res Sci Teach 39(6):497-521, 2002). An analysis of the survey results informed by the interview data suggests NOS views became more sophisticated for some issues, e.g., whether scientific knowledge requires experimentation; but not others, e.g., why scientists experiment. An examination of the interview data informed by our experiences with the unit provides insight into why the unit may have been more effective with regard to some issues than others. This includes evidence that greater sophistication of some NOS issues was fostered by the use of multiple, contextualized examples. The essay concludes with a discussion of limitations, pedagogical implications, and avenues for further research.

78 FR 29783 - Diablo Canyon Power Plant, Units 1 and 2; Application for Amendment to Facility Operating License

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-21

... of all onsite alternating current power supplies and the other offsite electric power circuit, to... NUCLEAR REGULATORY COMMISSION [Docket Nos.: 50-275 and 50-323; NRC-2013-0100] Diablo Canyon Power... License Nos. DPR-80 and DPR-82 for the Diablo Canyon Power Plant, Units 1 and 2, located in San Luis...

Nature of Science and Science Content Learning. The Relation Between Students' Nature of Science Understanding and Their Learning About the Concept of Energy

NASA Astrophysics Data System (ADS)

Michel, Hanno; Neumann, Irene

2016-12-01

Besides viewing knowledge about the nature of science (NOS) as important for its own value with respect to scientific literacy, an adequate understanding of NOS is expected to improve science content learning by fostering the ability to interrelate scientific concepts and, thus, coherently acquire scientific content knowledge. However, there is a lack of systematic investigations, which clarify the relations between NOS and science content learning. In this paper, we present the results of a study, conducted to investigate how NOS understanding relates to students' acquisition of a proper understanding of the concept of energy. A total of 82 sixth and seventh grade students received an instructional unit on energy, with 41 of them receiving generic NOS instruction beforehand. This NOS instruction, however, did not result in students having higher scores on the NOS instrument. Thus, correlational analyses were performed to investigate how students' NOS understanding prior to the energy unit related to their learning about science content. Results show that a more adequate understanding of NOS might relate to students' perspective on the concept of energy and might support them in understanding the nature of energy as a theoretical concept. Students with higher NOS understanding, for example, seemed to be more capable of learning how to relate the different energy forms to each other and to justify why they can be subsumed under the term of energy. Further, we found that NOS understanding may also be related to students' approach toward energy degradation—a concept that can be difficult for students to master—while it does not seem to have a substantive impact on students' learning gain regarding energy forms, transformation, or conservation.

Different Conceptions of the Nature of Science among Preservice Elementary Teachers of Two Countries

ERIC Educational Resources Information Center

Park, Do-Yong; Lee, Yong Bok

2009-01-01

This study examined the differences of the nature of science (NOS) conceptions portrayed by preservice teachers in Korea (N = 42) and the United States (N = 50). We conducted a survey of preservice elementary science teachers' NOS conceptions followed by interviews in both countries to further investigate their viewpoints. The NOS domains of this…

78 FR 29097 - Petition for Reconsideration of Action in Rulemaking Proceeding

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 54 [WC Docket Nos. 10-90 and 05-337; Report No. 2976] Petition for Reconsideration of Action in Rulemaking Proceeding AGENCY: Federal Communications Commission... 11, 2013. [[Page 29098

Evaluation of the preventative effects exerted by Lactobacillus fermentum in an experimental model of septic shock induced in mice.

PubMed

Arribas, Belén; Rodríguez-Cabezas, Maria Elena; Comalada, Mònica; Bailón, Elvira; Camuesco, Desireé; Olivares, Mónica; Xaus, Jordi; Zarzuelo, Antonio; Gálvez, Julio

2009-01-01

The preventative effects of the probiotic Lactobacillus fermentum CECT5716 were evaluated in the lipopolysaccharide (LPS) model of septic shock in mice. The probiotic was administered suspended in drinking water at the final concentration of 108 colony-forming units/ml for 2 weeks before the induction of an endotoxic shock by an intraperitoneal injection of LPS (400 microg/200 microl per mouse). Blood and different organs were collected after 24 h to evaluate the severity of the endotoxic shock and the preventative effects of the probiotic. L. fermentum reduced TNF-alpha levels in blood, which promotes the major alterations observed during septic shock, as well as the infiltration of activated neutrophils into the lungs. Furthermore, free radical overproduction and oxidative stress were associated with a significant decrease in hepatic glutathione levels in septic mice, and with an excessive NO production attributed to the induction of the inducible isoform of NO synthase (iNOS). In fact, hepatic glutathione levels were significantly increased in the group of mice receiving the probiotic, and the increased iNOS expression both in the colon and lungs was down-regulated in those mice treated with L. fermentum. Finally, pre-treatment with L. fermentum may also exert its protective action modulating the expression of different cytokines in splenocyte-derived T cells such us IL-2, IL-5, IL-6 or IL-10. In conclusion, pre-treatment with L. fermentum may exert its protective action against LPS-induced organ damage in mice by a combination of several actions including its antioxidant properties and by reduction of the synthesis of the pro-inflammatory TNF-alpha and IL-6.

78 FR 29158 - In the Matter of Zion Solutions, LLC; Zion Nuclear Power Station, Units 1 and 2; Order Approving...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... NUCLEAR REGULATORY COMMISSION [NRC-2013-0096; Docket Nos. 50-295 and 50-304; License Nos. DPR-39 and DPR-48] In the Matter of Zion Solutions, LLC; Zion Nuclear Power Station, Units 1 and 2; Order Approving Indirect Transfer of Control of Facility Operating Licenses I. ZionSolutions, LLC (ZS) is the...

77 FR 14011 - Rainbow Ranch Wind, LLC, Rainbow West Wind, LLC; Notice of Petition for Enforcement

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-08

... Commission (Commission) initiate an enforcement action against the Idaho Public Utilities Commission (Idaho... Nos. 32256 and 32300, as would allow Petitioners to pursue enforcement action in a U.S. Federal...). Protests will be considered by the Commission in determining the appropriate action to be taken, but will...

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 of different demographics amongst teachers and the 'converging' aspect of their understanding of NOS provide much needed insight for teacher trainers, mentors, and researchers.

In vivo and in vitro effects of lysine clonixinate on nitric oxide synthase in LPS-treated and untreated rat lung preparations.

PubMed

Franchi, A M; Di Girolamo, G; Farina, M; de los Santos, A R; Martí, M L; Gimeno, M A

2001-04-01

Recent studies have shown that some nonsteroidal antiinflammatory drugs (NSAIDS) inhibited the inducible NO synthase (iNOS) without direct effect on the catalytic activity of this enzyme. This study was conducted to investigate the in vitro and in vivo effects of lysine clonixinate (LC) and indomethacin (INDO) on NOS activity in rat lung preparation. LC is a drug with antiinflammatory, antipyretic, and analgesic action. In the in vitro experiments, rats were injected with saline or lipopolysaccharide (LPS) and killed 6 h after treatment. Lung preparations were incubated with LC at 2.3 x 10(-5) M or 3.8 x 10(-5) M. The minimum concentration did not modify NOS activity in control or LPS-treated rats but the maximum dose inhibited increased NO production induced by LPS. Furthermore, INDO at 10(-6) M had no effect on enzymatic activity in control or LPS-treated rats. In the in vivo experiments, 40 mg/kg of LC were injected ip. Such a dose did not affect basal production of NO. When LC and LPS were injected simultaneously 6 h before sacrifice, a significant decrease in LPS-induced NOS activity was observed. INDO 10 mg/kg injected in control animals had no effect on NOS activity and did not block LPS induced stimulation of NO production when injected simultaneously. Finally, when LC (40 mg/kg) was injected 3 h after LPS, the enzymatic activity remained unchanged. Expression of iNOS was detected by Western blotting in rats treated with LPS plus 4, 10, 20, and 40 mg/kg of LC. The lowest dose was the only one showing no effect on LPS-induced increase of iNOS. In short, LC is a NSAID with inhibitory action on the expression of LPS-induced NOS, effect that was not seen with INDO in our experimental conditions. Copyright 2001 Academic Press.

76 FR 40945 - Entergy Nuclear Indian Point 2, LLC, Entergy Nuclear Indian Point 3, LLC, Entergy Nuclear...

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2011-07-12

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0150; Docket Nos. 50-003, 50-247, and 50-286; License Nos. DPR-5, DPR-26, and DPR-64] Entergy Nuclear Indian Point 2, LLC, Entergy Nuclear Indian Point 3, LLC, Entergy Nuclear Operations, Inc.; Receipt of Request for Action Notice is hereby given that by petition...

77 FR 59223 - Notice of Availability of the Proposed Notice of Sale (NOS) for Central Gulf of Mexico Planning...

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2012-09-26

... Proposed Notice of Sale (NOS) for Central Gulf of Mexico Planning Area (CPA) Outer Continental Shelf (OCS) Oil and Gas Lease Sale 227 (CPA Sale 227) AGENCY: Bureau of Ocean Energy Management, Interior. ACTION: Notice of Availability of the Proposed Notice of CPA Sale 227. SUMMARY: BOEM announces the availability...

78 FR 72929 - Notice of Availability of the Proposed Notice of Sale (NOS) for Eastern Gulf of Mexico Planning...

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2013-12-04

... of the Proposed Notice of Sale (NOS) for Eastern Gulf of Mexico Planning Area (EPA) Outer Continental Shelf (OCS) Oil and Gas Lease Sale 225 (EPA Sale 225) AGENCY: Bureau of Ocean Energy Management (BOEM), Interior. ACTION: Notice of Availability of the Proposed Notice of EPA Sale 225. SUMMARY: BOEM announces...

78 FR 64243 - Notice of Availability of the Proposed Notice of Sale (NOS) for Central Gulf of Mexico Planning...

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2013-10-28

... of the Proposed Notice of Sale (NOS) for Central Gulf of Mexico Planning Area (CPA) Outer Continental Shelf (OCS) Oil and Gas Lease Sale 231 (CPA Sale 231) AGENCY: Bureau of Ocean Energy Management, Interior. ACTION: Notice of Availability of the Proposed Notice of CPA Sale 231. SUMMARY: BOEM announces...

78 FR 24435 - Notice of Availability of the Proposed Notice of Sale (NOS) for Western Gulf of Mexico Planning...

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2013-04-25

... of the Proposed Notice of Sale (NOS) for Western Gulf of Mexico Planning Area (WPA) Outer Continental Shelf (OCS) Oil and Gas Lease Sale 233 (WPA Sale 233) AGENCY: Bureau of Ocean Energy Management (BOEM), Interior. ACTION: Notice of Availability of the Proposed Notice of WPA Sale 233 SUMMARY: BOEM announces the...

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...

Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking

PubMed Central

Iwakiri, Yasuko; Satoh, Ayano; Chatterjee, Suvro; Toomre, Derek K.; Chalouni, Cecile M.; Fulton, David; Groszmann, Roberto J.; Shah, Vijay H.; Sessa, William C.

2006-01-01

Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its diffusible nature, NO modifies thiol groups of specific cysteine residues in target proteins and alters protein function via S-nitrosylation. Although intracellular S-nitrosylation is a specific posttranslational modification, the defined localization of an NO source (nitric oxide synthase, NOS) with protein S-nitrosylation has never been directly demonstrated. Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae. Here, we show by using eNOS targeted to either the Golgi or the nucleus that S-nitrosylation is concentrated at the primary site of eNOS localization. Furthermore, localization of eNOS on the Golgi enhances overall Golgi protein S-nitrosylation, the specific S-nitrosylation of N-ethylmaleimide-sensitive factor and reduces the speed of protein transport from the endoplasmic reticulum to the plasma membrane in a reversible manner. These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes. PMID:17170139

Contribution of the frontal eye field to gaze shifts in the head-unrestrained rhesus monkey: neuronal activity.

PubMed

Knight, T A

2012-12-06

The frontal eye field (FEF) has a strong influence on saccadic eye movements with the head restrained. With the head unrestrained, eye saccades combine with head movements to produce large gaze shifts, and microstimulation of the FEF evokes both eye and head movements. To test whether the dorsomedial FEF provides commands for the entire gaze shift or its separate eye and head components, we recorded extracellular single-unit activity in monkeys trained to make large head-unrestrained gaze shifts. We recorded 80 units active during gaze shifts, and closely examined 26 of these that discharged a burst of action potentials that preceded horizontal gaze movements. These units were movement or visuomovement related and most exhibited open movement fields with respect to amplitude. To reveal the relations of burst parameters to gaze, eye, and/or head movement metrics, we used behavioral dissociations of gaze, eye, and head movements and linear regression analyses. The burst number of spikes (NOS) was strongly correlated with movement amplitude and burst temporal parameters were strongly correlated with movement temporal metrics for eight gaze-related burst neurons and five saccade-related burst neurons. For the remaining 13 neurons, the NOS was strongly correlated with the head movement amplitude, but burst temporal parameters were most strongly correlated with eye movement temporal metrics (head-eye-related burst neurons, HEBNs). These results suggest that FEF units do not encode a command for the unified gaze shift only; instead, different units may carry signals related to the overall gaze shift or its eye and/or head components. Moreover, the HEBNs exhibit bursts whose magnitude and timing may encode a head displacement signal and a signal that influences the timing of the eye saccade, thereby serving as a mechanism for coordinating the eye and head movements of a gaze shift. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Corrective Action Investigation Plan for Corrective Action Unit 165: Areas 25 and 26 Dry Well and Washdown Areas, Nevada Test Site, Nevada (including Record of Technical Change Nos. 1, 2, and 3) (January 2002, Rev. 0)

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

U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office

This Corrective Action Investigation Plan contains the U.S. Department of Energy, National Nuclear Security Administration Nevada Operations Office's approach to collect the data necessary to evaluate corrective action alternatives appropriate for the closure of Corrective Action Unit (CAU) 165 under the Federal Facility Agreement and Consent Order. Corrective Action Unit 165 consists of eight Corrective Action Sites (CASs): CAS 25-20-01, Lab Drain Dry Well; CAS 25-51-02, Dry Well; CAS 25-59-01, Septic System; CAS 26-59-01, Septic System; CAS 25-07-06, Train Decontamination Area; CAS 25-07-07, Vehicle Washdown; CAS 26-07-01, Vehicle Washdown Station; and CAS 25-47-01, Reservoir and French Drain. All eight CASsmore » are located in the Nevada Test Site, Nevada. Six of these CASs are located in Area 25 facilities and two CASs are located in Area 26 facilities. The eight CASs at CAU 165 consist of dry wells, septic systems, decontamination pads, and a reservoir. The six CASs in Area 25 are associated with the Nuclear Rocket Development Station that operated from 1958 to 1973. The two CASs in Area 26 are associated with facilities constructed for Project Pluto, a series of nuclear reactor tests conducted between 1961 to 1964 to develop a nuclear-powered ramjet engine. Based on site history, the scope of this plan will be a two-phased approach to investigate the possible presence of hazardous and/or radioactive constituents at concentrations that could potentially pose a threat to human health and the environment. The Phase I analytical program for most CASs will include volatile organic compounds, semivolatile organic compounds, Resource Conservation and Recovery Act metals, total petroleum hydrocarbons, polychlorinated biphenyls, and radionuclides. If laboratory data obtained from the Phase I investigation indicates the presence of contaminants of concern, the process will continue with a Phase II investigation to define the extent of contamination. Based on the results of Phase I sampling, the analytical program for Phase II investigation may be reduced. The results of this field investigation will support a defensible evaluation of corrective action alternatives in the corrective action decision document.« less

Mechanism of Inducible Nitric-oxide Synthase Dimerization Inhibition by Novel Pyrimidine Imidazoles*

PubMed Central

Nagpal, Latika; Haque, Mohammad M.; Saha, Amit; Mukherjee, Nirmalya; Ghosh, Arnab; Ranu, Brindaban C.; Stuehr, Dennis J.; Panda, Koustubh

2013-01-01

Overproduction of nitric oxide (NO) by inducible nitric-oxide synthase (iNOS) has been etiologically linked to several inflammatory, immunological, and neurodegenerative diseases. As dimerization of NOS is required for its activity, several dimerization inhibitors, including pyrimidine imidazoles, are being evaluated for therapeutic inhibition of iNOS. However, the precise mechanism of their action is still unclear. Here, we examined the mechanism of iNOS inhibition by a pyrimidine imidazole core compound and its derivative (PID), having low cellular toxicity and high affinity for iNOS, using rapid stopped-flow kinetic, gel filtration, and spectrophotometric analysis. PID bound to iNOS heme to generate an irreversible PID-iNOS monomer complex that could not be converted to active dimers by tetrahydrobiopterin (H4B) and l-arginine (Arg). We utilized the iNOS oxygenase domain (iNOSoxy) and two monomeric mutants whose dimerization could be induced (K82AiNOSoxy) or not induced (D92AiNOSoxy) with H4B to elucidate the kinetics of PID binding to the iNOS monomer and dimer. We observed that the apparent PID affinity for the monomer was 11 times higher than the dimer. PID binding rate was also sensitive to H4B and Arg site occupancy. PID could also interact with nascent iNOS monomers in iNOS-synthesizing RAW cells, to prevent their post-translational dimerization, and it also caused irreversible monomerization of active iNOS dimers thereby accomplishing complete physiological inhibition of iNOS. Thus, our study establishes PID as a versatile iNOS inhibitor and therefore a potential in vivo tool for examining the causal role of iNOS in diseases associated with its overexpression as well as therapeutic control of such diseases. PMID:23696643

75 FR 66677 - New Postal Products

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-29

... POSTAL REGULATORY COMMISSION 39 CFR Part 3020 [Docket Nos. MC2010-34, et al.] New Postal Products AGENCY: Postal Regulatory Commission. ACTION: Final rule. SUMMARY: The Commission is updating the postal product lists. This action reflects the disposition of recent dockets, as reflected in Commission orders...

75 FR 53216 - New Postal Products

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-31

... POSTAL REGULATORY COMMISSION 39 CFR Part 3020 [Docket Nos. MC2009-19, et al.] New Postal Products AGENCY: Postal Regulatory Commission. ACTION: Final rule. SUMMARY: The Commission is updating the postal product lists. This action reflects the disposition of recent dockets, as reflected in Commission orders...

Superoxide and peroxynitrite generation from inducible nitric oxide synthase in macrophages

PubMed Central

Xia, Yong; Zweier, Jay L.

1997-01-01

Superoxide (O2⨪) and nitric oxide (NO) act to kill invading microbes in phagocytes. In macrophages NO is synthesized by inducible nitric oxide synthase (iNOS, NOS 2) from l-arginine (l-Arg) and oxygen; however, O2⨪ was thought to be produced mainly by NADPH oxidase. Electron paramagnetic resonance (EPR) spin trapping experiments performed in murine macrophages demonstrate a novel pathway of O2⨪ generation. It was observed that depletion of cytosolic l-Arg triggers O2⨪ generation from iNOS. This iNOS-mediated O2⨪ generation was blocked by the NOS inhibitor N-nitro-l-arginine methyl ester or by l-Arg, but not by the noninhibitory enantiomer N-nitro-d-arginine methyl ester. In l-Arg-depleted macrophages iNOS generates both O2⨪ and NO that interact to form the potent oxidant peroxynitrite (ONOO−), which was detected by luminol luminescence and whose formation was blocked by superoxide dismutase, urate, or l-Arg. This iNOS-derived ONOO− resulted in nitrotyrosine formation, and this was inhibited by iNOS blockade. iNOS-mediated O2⨪ and ONOO− increased the antibacterial activity of macrophages. Thus, with reduced l-Arg availability iNOS produces O2⨪ and ONOO− that modulate macrophage function. Due to the existence of l-Arg depletion in inflammation, iNOS-mediated O2⨪ and ONOO− may occur and contribute to cytostatic/cytotoxic actions of macrophages. PMID:9192673

Renal actions of atrial natriuretic peptide in spontaneously hypertensive rats: the role of nitric oxide as a key mediator.

PubMed

Elesgaray, Rosana; Caniffi, Carolina; Savignano, Lucía; Romero, Mariana; Mac Laughlin, Myriam; Arranz, Cristina; Costa, María A

2012-06-01

Atrial natriuretic peptide (ANP) is an important regulator of blood pressure (BP). One of the mechanisms whereby ANP impacts BP is by stimulation of nitric oxide (NO) production in different tissues involved in BP control. We hypothesized that ANP-stimulated NO is impaired in the kidneys of spontaneously hypertensive rats (SHR) and this contributes to the development and/or maintenance of high levels of BP. We investigated the effects of ANP on the NO system in SHR, studying the changes in renal nitric oxide synthase (NOS) activity and expression in response to peptide infusion, the signaling pathways implicated in the signaling cascade that activates NOS, and identifying the natriuretic peptide receptors (NPR), guanylyl cyclase receptors (NPR-A and NPR-B) and/or NPR-C, and NOS isoforms involved. In vivo, SHR and Wistar-Kyoto rats (WKY) were infused with saline (0.05 ml/min) or ANP (0.2 μg·kg(-1)·min(-1)). NOS activity and endothelial (eNOS), neuronal (nNOS), and inducible (iNOS) NOS expression were measured in the renal cortex and medulla. In vitro, ANP-induced renal NOS activity was determined in the presence of iNOS and nNOS inhibitors, NPR-A/B blockers, guanine nucleotide-regulatory (G(i)) protein, and calmodulin inhibitors. Renal NOS activity was higher in SHR than in WKY. ANP increased NOS activity, but activation was lower in SHR than in WKY. ANP had no effect on expression of NOS isoforms. ANP-induced NOS activity was not modified by iNOS and nNOS inhibitors. NPR-A/B blockade blunted NOS stimulation via ANP in kidney. The renal NOS response to ANP was reduced by G(i) protein and calmodulin inhibitors. We conclude that ANP interacts with NPR-C, activating Ca-calmodulin eNOS through G(i) protein. NOS activation also involves NPR-A/B. The NOS response to ANP was diminished in kidneys of SHR. The impaired NO system response to ANP in SHR participates in the maintenance of high blood pressure.

Role of RPL39 in Metaplastic Breast Cancer.

PubMed

Dave, Bhuvanesh; Gonzalez, Daniel D; Liu, Zhi-Bin; Li, Xiaoxian; Wong, Helen; Granados, Sergio; Ezzedine, Nadeer E; Sieglaff, Douglas H; Ensor, Joe E; Miller, Kathy D; Radovich, Milan; KarinaEtrovic, Agda; Gross, Steven S; Elemento, Olivier; Mills, Gordon B; Gilcrease, Michael Z; Chang, Jenny C

2017-06-01

Metaplastic breast cancer is one of the most therapeutically challenging forms of breast cancer because of its highly heterogeneous and chemoresistant nature. We have previously demonstrated that ribosomal protein L39 (RPL39) and its gain-of-function mutation A14V have oncogenic activity in triple-negative breast cancer and this activity may be mediated through inducible nitric oxide synthase (iNOS). The function of RPL39 and A14V in other breast cancer subtypes is currently unknown. The objective of this study was to determine the role and mechanism of action of RPL39 in metaplastic breast cancer. Both competitive allele-specific and droplet digital polymerase chain reaction were used to determine the RPL39 A14V mutation rate in metaplastic breast cancer patient samples. The impact of RPL39 and iNOS expression on patient overall survival was estimated using the Kaplan-Meier method. Co-immunoprecipitation and immunoblot analyses were used for mechanistic evaluation of RPL39. The RPL39 A14V mutation rate was 97.5% (39/40 tumor samples). High RPL39 (hazard ratio = 0.71, 95% confidence interval = 0.55 to 0.91, P = 006) and iNOS expression (P = 003) were associated with reduced patient overall survival. iNOS inhibition with the pan-NOS inhibitor N G -methyl-L-arginine acetate decreased in vitro proliferation and migration, in vivo tumor growth in both BCM-4664 and BCM-3807 patient-derived xenograft models (P = 04 and P = 02, respectively), and in vitro and in vivo chemoresistance. Mechanistically, RPL39 mediated its cancer-promoting actions through iNOS signaling, which was driven by the RNA editing enzyme adenosine deaminase acting on RNA 1. NOS inhibitors and RNA editing modulators may offer novel treatment options for metaplastic breast cancer. © The Author 2016. Published by Oxford University Press.

Differential cholinoceptor modulation of nitric oxide isoforms in experimentally-induced inflammation of dental pulp tissue.

PubMed

De Couto Pita, A; Passafaro, D; Ganzinelli, S; Borda, E; Sterin-Borda, L

2009-06-01

The aim of the study was to investigate the role of muscarinic acetylcholine receptor (mAChR) activity in the regulation of endothelial (e), neuronal (n) and inducible (i) nitric oxide synthase (NOS) activity and expression in experimentally induced inflammation of rat dental pulp tissue. Inflammation was induced by application of bacterial lipopolysaccharide (LPS) to the pulp. Extirpated pulp-tissue samples were incubated in saline solution until the various experiments were performed. Saline-treated pulp and healthy pulp tissues were used as controls. NOS activity was measured by the production of [U-(14)C]-citrulline from [U-(14)C]-arginine. Nitrite/nitrate assay was evaluated by the conversion of nitrate to nitrite in the presence of nicotinamide adenine dinucleotide phosphate. i-nos, e-nos and n-nos mRNA levels were measured using reverse-transcriptase polymerase chain reaction by co-amplification of target cDNA with a single set of primers. Application of LPS to the pulp increased NOS activity and nitrate production (P < 0.001), generated by iNOS over-activity and expression. Pilocarpine acting on mAChRs triggered a biphasic action on NOS activity and NO accumulation. At low concentrations, pilocarpine induced a negative effect associated with a decrease in i-nos mRNA level, whilst at high concentration, it produced a positive effect associated with increased e-nos and n-nos mRNA levels. In control pulp tissue, only the positive effect of pilocarpine was observed. Irreversible pulpitis changes mAChR conformation increasing its efficiency of coupling to transducing molecules that in turn induce activate iNOS. The capacity of pilocarpine to prevent NO accumulation and iNOS activity, by acting on mAChR mutation induced by pulpitis, might be useful therapeutically as a local treatment.

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.

75 FR 44138 - New Postal Products

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-28

... POSTAL REGULATORY COMMISSION 30 CFR Part 3020 [Docket Nos. MC2010-21; CP2010-36 and MC2010-20] New Postal Products AGENCY: Postal Regulatory Commission. ACTION: Final rule. SUMMARY: The Commission is updating postal product lists. This action reflects the disposition of recent dockets, as set out in two...

78 FR 29097 - Petition for Reconsideration of Action in Rulemaking Proceeding

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-17

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 54 [CC Docket Nos. 01-92 and 94-45; GN Docket No. 09... for Reconsideration of Action in Rulemaking Proceeding AGENCY: Federal Communications Commission... Communications Commission, 445 12th Street SW., Washington, DC 20554. FOR FURTHER INFORMATION CONTACT: Alexander...

Gathering Strength: Canada's Aboriginal Action Plan. A Progress Report = Rassembler nos forces: Le plan d'action du Canada pour les questions autochtones. Rapport d'etape.

ERIC Educational Resources Information Center

Department of Indian Affairs and Northern Development, Ottawa (Ontario).

Gathering Strength is an integrated government-wide plan to address the key challenges facing Canada's Aboriginal people. Following an initial section on reconciliation of historic grievances, this report describes initiatives in the four areas addressed by the action plan: (1) partnerships (all schools received public awareness materials;…

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.

Gene Therapy With Inducible Nitric Oxide Synthase Protects Against Myocardial Infarction via a Cyclooxygenase-2—Dependent Mechanism

PubMed Central

Li, Qianhong; Guo, Yiru; Xuan, Yu-Ting; Lowenstein, Charles J.; Stevenson, Susan C.; Prabhu, Sumanth D.; Wu, Wen-Jian; Zhu, Yanqing; Bolli, Roberto

2013-01-01

Although the inducible isoform of NO synthase (iNOS) mediates late preconditioning (PC), it is unknown whether iNOS gene transfer can replicate the cardioprotective effects of late PC, and the role of this protein in myocardial ischemia is controversial. Thus, the cDNA for human iNOS was cloned behind the Rous sarcoma virus (RSV) promoter to create adenovirus (Ad) 5/iNOS lacking E1, E2a, and E3 regions. Intramyocardial injection of Ad5/iNOS in mice increased local iNOS protein expression and activity and markedly reduced infarct size. The infarct-sparing effects of Ad5/iNOS were at least as powerful as those of ischemic PC. The increased iNOS expression was associated with increased cyclooxygenase-2 (COX-2) protein expression and prostanoid levels. Pretreatment with the COX-2–selective inhibitor NS-398 completely abrogated the infarct-sparing actions of Ad5/iNOS, demonstrating that COX-2 is an obligatory downstream effector of iNOS-dependent cardioprotection. We conclude that gene transfer of iNOS (an enzyme commonly thought to be detrimental) affords powerful cardioprotection the magnitude of which is equivalent to that of late PC. This is the first report that upregulation of iNOS, in itself, is sufficient to reduce infarct size. The results provide proof-of-principle for gene therapy against ischemia/reperfusion injury, which increases local myocardial NO synthase levels without the need for continuous intravenous infusion of NO donors and without altering systemic hemodynamics. The data also reveal the existence of a close coupling between iNOS and COX-2, whereby induction of the former enzyme leads to secondary induction of the latter, which in turn mediates the cytoprotective effects of iNOS. We propose that iNOS and COX-2 form a stress-responsive functional module that mitigates ischemia/reperfusion injury. PMID:12702642

Nitric oxide (NO.) stabilizes whereas nitrosonium (NO+) enhances filopodial outgrowth by rat retinal ganglion cells in vitro.

PubMed

Cheung, W S; Bhan, I; Lipton, S A

2000-06-16

Recent observations suggest that nitric oxide (NO(.)) can increase or decrease growth cone motility. Here, these apparently paradoxical results are explained by distinct actions of different NO-related species. Filopodial morphology of 223 rat retinal ganglion cells was monitored under computer-enhanced video microscopy in the presence of NO synthase (NOS) substrates or inhibitors, donors of specific NO-related species, and membrane-permeant cyclic nucleotide analogs. Physiological NOS activity induced filopodial outgrowth, whereas inhibition of NOS stabilized filopodia. Similar to NOS, nitrosonium (NO(+) transfer) and peroxynitrite (ONOO(-)), which can regulate the activity of growth-associated proteins by S-nitrosylation and oxidation, respectively, induced filopodial outgrowth. In contrast, NO(.), which stimulates guanylate cyclase to increase cGMP, stabilized filopodial activity. Thus disparate NO-related species may offer a dynamic process of filopodial growth regulation.

The involvement of neuronal nitric oxide synthase in antiepileptic action of alpha-asarone on pentylenetetrazol molding rats.

PubMed

Su, Jing; Zhu, Wenting; Liu, Jing; Yin, Jian; Qin, Wei; Jiang, Changbin

2014-01-01

The aim of the present study was to research the role of nitric oxide (NO) as a mediator of alpha (α)-asarone effect at the pentylenetetrazol (PTZ)-induced epileptiform discharge in rat. α-Asarone that was injected intraperitoneally twenty minutes before PTZ injection suppressed the clonic discharge effectively and the significant actions lasted for 30 min with no change of clonic amplitude. Administration of α-asarone did not influence interictal discharge. Four kinds of NO regulators were administered, including non-selective NG-nitro-L-arginine methyl ester (L-NAME), selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AG) and NO substrate, L-arginine (ARG) and their influence on the actions of α-asarone were studied, and all of the regulators were administered fifteen minutes before α-asarone injection. L-NAME and 7-NI reversed the anticlonic activity of α-asarone, and a significant increase of clonic activity was induced by L-NAME later in L-NAME +.α-asarone + PTZ group. There were no significant differences between AG + α-asarone + PTZ and α-asarone + PTZ group. L-ARG played a dual role in this study. It aggravated clonic discharge in the early stage but relieved interictal discharge in the late stage compared with PTZ group alone, and the beneficial effect of α-asarone was also reversed. All the above results suggest that nNOS/NO pathway mediates the anticonvulsant effect of α-asarone, and NO played a biphasic role in PTZ modeling process, while iNOS was unrelated to the inhibition effect of α-asarone on PTZ induced epileptiform activity.

An Educational Program to Prevent Adverse Events in Neonates : a Randomised Trial.

ClinicalTrials.gov

2016-10-20

Intensive Care Units, Neonatal; Misadventures to Patients During Surgical and Medical Care; Catheter-related Bloodstream Infection (CRBSI) Nos; Quality of Healthcare; Ventilator Adverse Event; Nosocomial Pneumonia; Immature Newborn; Skin Lesion; Extravasation Injury; Nasal Injury; Intubation Complication; Medication Administered in Error; IV Catheter Nos Deep Venous Thrombosis

75 FR 40012 - Self-Regulatory Organizations; Notice of Filing and Immediate Effectiveness of Proposed Rule...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-13

... most popular products traded on the Exchange. \\8\\ See Securities Exchange Act Release Nos. 49813 (June... Action Because the foregoing proposed rule change does not significantly affect the protection of... Commission may summarily abrogate such rule change if it appears to the Commission that such action is...

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

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.

Post-transcriptional regulation of inducible nitric oxide synthase in chronic lymphocytic leukemia B cells in pro- and antiapoptotic culture conditions.

PubMed

Tiscornia, A C; Cayota, A; Landoni, A I; Brito, C; Oppezzo, P; Vuillier, F; Robello, C; Dighiero, G; Gabús, R; Pritsch, O

2004-01-01

Functional inducible NOS (iNOS) may be involved in the prolonged lifespan of chronic lymphocytic leukemia cells (B-CLL), although the exact mechanisms implicated remain elusive as yet. In this work, we have examined iNOS expression in normal B lymphocytes and B-CLL cells in pro- and antiapoptotic conditions. Our results demonstrate: (1) The existence of a new splice variant characterized by a complete deletion of exon 14 (iNOS 13-16(14del)), which was preferentially detected in normal B lymphocytes and may represent an isoform that could play a role in the regulation of enzyme activity. (2) The existence of another alternatively spliced iNOS mRNA transcript involving a partial deletion of the flavodoxin region (iNOS 13-16(neg)) was correlated to a decreased B-CLL cell viability. The 9-beta-D-arabinofuranosyl-2-fluoradenine or fludarabine (F-ara) treatment induced iNOS 13-16(neg) transcript variants, whereas IL-4 enhanced both the transcription of variants, including these exons (iNOS 13-16(pos)), and the expression of a 122 kDa iNOS protein. These results suggest that in B-CLL, a regulation process involving nitric oxide (.- NO) levels could occur by a post-transcriptional mechanism mediated by soluble factors. Our results also provide an insight into a new complementary proapoptotic action of F-ara in B-CLL by the induction of particular iNOS splice variants, leading to the activation of a caspase-3-dependent apoptotic pathway.

Enforcement actions: Significant actions resolved individual actions. Volume 14, Nos. 3 and 4, Part 1. Semiannual progress report, July--December 1995

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

NONE

1996-02-01

This compilation summarizes significant enforcement actions that have been resolved during the period (July - December 1995) and includes copies of Orders and Notices of Violation sent by the Nuclear Regulatory Commission to individuals with respect to these enforcement actions. It is anticipated that the information in this publication will be widely disseminated to managers and employees engaged in activities licensed by the NRC. The Commission believes this information may be useful to licensees in making employment decisions.

Resveratrol recruits rat muscle microvasculature via a nitric oxide-dependent mechanism that is blocked by TNFα

PubMed Central

Wang, Nasui; Ko, Seung-Hyun; Chai, Weidong; Li, Guolian; Barrett, Eugene J.; Tao, Lijian; Cao, Wenhong

2011-01-01

Resveratrol, a polyphenol found in many plants, has antioxidant and anti-inflammatory actions. It also improves endothelial function and may be cardioprotective. Tumor necrosis factor-α (TNFα) causes oxidative stress and microvascular endothelial dysfunction. Whether resveratrol affects microvascular function in vivo and, if so, whether inflammatory cytokines antagonize its microvascular action are not clear. In cultured bovine aortic endothelial cells (BAECs), reserveratrol (100 nM) increased the phosphorylation of protein kinase B (Akt), endothelial nitric oxide (NO) synthase (eNOS), and ERK1/2 within 15 min by more than twofold, and this effect lasted for at least 2 h. Treatment of BAECs with TNFα (10 ng/ml) significantly increased the NADPH oxidase activity and the production of hydrogen peroxide and superoxide. Pretreatment of cells with resveratrol (100 nM) prevented each of these. Injection (ip) of resveratrol in rats potently increased muscle microvascular blood volume (MBV; P = 0.007) and flow (MBF; P < 0.02) within 30 min, and this was sustained for at least 2 h. The phosphorylation of Akt in liver or muscle was unchanged. Superimposed systemic infusion of l-NAME (NOS inhibitor) completely abolished resveratrol-induced increases in MBV and MBF. Similarly, systemic infusion of TNFα prevented resveratrol-induced muscle microvascular recruitment. In conclusion, resveratrol activates eNOS and increases muscle microvascular recruitment via an NO-dependent mechanism. Despite the potent antioxidant effect of resveratrol, TNFα at concentrations that block insulin-mediated muscle microvascular recruitment completely neutralized resveratrol's microvascular action. Thus, chronic inflammation, as seen in type 2 diabetes, may limit resveratrol's vasodilatory actions on muscle microvasculature. PMID:20978231

Inhibition by sodium nitroprusside of the expression of inducible nitric oxide synthase in rat neutrophils.

PubMed Central

Mariotto, S; Cuzzolin, L; Adami, A; Del Soldato, P; Suzuki, H; Benoni, G

1995-01-01

A well-known nitric oxide (NO)-releasing compound, sodium nitroprusside (SNP), decreases in a dose-dependent manner NO synthase (NOS) activity induced in rat neutrophils by treatment with lipopolysaccharide (LPS). This inhibitory action of SNP seems not to be due to its direct effect on the enzyme activity. The strong nitrosonium ion (NO+) character of SNP could be responsible for its inhibition of NOS induction in neutrophils. PMID:7542530

7-Nitroindazole, a nitric oxide synthase inhibitor, enhances the anticonvulsive action of ethosuximide and clonazepam against pentylenetetrazol-induced convulsions.

PubMed

Borowicz, K K; Luszczki, J; Kleinrok, Z; Czuczwar, S J

2000-01-01

The interaction of 7-nitroindazole (7-NI), a nitric oxide synthase (NOS) inhibitor, with the protective activity of conventional antiepileptics against pentylenetetrazol (PTZ)-induced seizures was tested in mice. Alone, 7-nitroindazole (up to 50mg/kg) was ineffective in this model of experimental epilepsy. However, it potentiated the anticonvulsive activity of ethosuximide and clonazepam, significantly reducing their ED50S against PTZ-induced convulsions (from 144 to 76 mg/kg, and from 0.05 to 0.016 mg/kg, respectively). Conversely, the protective actions of valproate and phenobarbital were not affected by the NOS inhibitor. Since the nitric oxide precursor, L-arginine, did not reverse the action of 7-NI on ethosuximide or clonazepam, an involvement of central NO does not seem probable. Neither ethosuximide nor clonazepam, administered at their ED50S (144 and 0.05 mg/kg, respectively), produced significant adverse effects as regards motor coordination (chimney test) and long-term memory (passive avoidance task). Also 7-NI (50 mg/kg) and its combinations with ethosuximide and clonazepam (providing a 50% protection against PTZ-evoked seizures) did not disturb motor and mnemonic performance in mice. The interaction at the pharmacokinetic level does not seem probable, at least in the case of ethosuximide, because the NOS inhibitor did not interfere with its plasma or brain concentrations.

Cigarette smoking impairs nitric oxide-mediated cerebral blood flow increase: Implications for Alzheimer's disease.

PubMed

Toda, Noboru; Okamura, Tomio

2016-08-01

Cerebral blood flow is mainly regulated by nitrergic (parasympathetic, postganglionic) nerves and nitric oxide (NO) liberated from endothelial cells in response to shear stress and stretch of vasculature, whereas sympathetic vasoconstrictor control is quite weak. On the other hand, peripheral vascular resistance and blood flow are mainly controlled by adrenergic vasoconstrictor nerves; endothelium-derived NO and nitrergic nerves play some roles as vasodilator factors. Cigarette smoking impairs NO synthesis in cerebral vascular endothelial cells and nitrergic nerves leading to interference with cerebral blood flow and glucose metabolism in the brain. Smoking-induced cerebral hypoperfusion is induced by impairment of synthesis and actions of NO via endothelial nitric oxide synthase (eNOS)/neuronal NOS (nNOS) inhibition and by increased production of oxygen radicals, resulting in decreased actions of NO on vascular smooth muscle. Nicotine acutely and chronically impairs the action of endothelial NO and also inhibits nitrergic nerve function in chronic use. Impaired cerebral blood supply promotes the synthesis of amyloid β that accelerates blood flow decrease. This vicious cycle is thought to be one of the important factors involving in Alzheimer's disease (AD). Quitting smoking is undoubtedly one of the important ways to prevent and delay the genesis or slow the progress of impaired cognitive function and AD. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Integrating the Nature of Science

ERIC Educational Resources Information Center

Weiland, Ingrid; Blieden, Katherine; Akerson, Valarie

2014-01-01

The nature of science (NOS) describes what science is and how knowledge in science is developed (NSTA 2013). To develop elementary students' understandings of how scientists explore the world, the authors--an education professor and a third-grade teacher--endeavored to integrate NOS into a third-grade life science unit. Throughout the lesson,…

78 FR 52785 - Sunshine Act Meeting Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-26

... in Inv. Nos. 731-TA-1224 and 1225 (Preliminary) (Ferrosilicon from Russia and Venezuela). The..., 2013. 5. Outstanding action jackets: none. In accordance with Commission policy, subject matter listed...

75 FR 30856 - Ball Bearings From Japan and the United Kingdom

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-02

... Remand)] Ball Bearings From Japan and the United Kingdom AGENCY: United States International Trade... determinations in the five-year reviews of the antidumping orders on ball bearings from Japan and the United... Certain Bearings and Parts Thereof From Japan and the United Kingdom, Inv. Nos. 731-TA- 394-A & 399-A...

Obese Mice Lacking Inducible Nitric Oxide Synthase Are Sensitized to the Metabolic Actions of Peroxisome Proliferator–Activated Receptor-γ Agonism

PubMed Central

Dallaire, Patrice; Bellmann, Kerstin; Laplante, Mathieu; Gélinas, Stéphanie; Centeno-Baez, Carolina; Penfornis, Patrice; Peyot, Marie-Line; Latour, Martin G.; Lamontagne, Julien; Trujillo, Maria E.; Scherer, Philipp E.; Prentki, Marc; Deshaies, Yves; Marette, André

2008-01-01

OBJECTIVE—Synthetic ligands for peroxisome proliferator–activated receptor-γ (PPAR-γ) improve insulin sensitivity in obesity, but it is still unclear whether inflammatory signals modulate their metabolic actions. In this study, we tested whether targeted disruption of inducible nitric oxide (NO) synthase (iNOS), a key inflammatory mediator in obesity, modulates the metabolic effects of rosiglitazone in obese mice. RESEARCH DESIGN AND METHODS—iNOS−/− and iNOS+/+ were subjected to a high-fat diet or standard diet for 18 weeks and were then treated with rosiglitazone for 2 weeks. Whole-body insulin sensitivity and glucose tolerance were determined and metabolic tissues harvested to assess activation of insulin and AMP-activated protein kinase (AMPK) signaling pathways and the levels of inflammatory mediators. RESULTS—Rosiglitazone was found to similarly improve whole-body insulin sensitivity and insulin signaling to Akt/PKB in skeletal muscle of obese iNOS−/− and obese iNOS+/+ mice. However, rosiglitazone further improved glucose tolerance and liver insulin signaling only in obese mice lacking iNOS. This genotype-specific effect of rosiglitazone on glucose tolerance was linked to a markedly increased ability of the drug to raise plasma adiponectin levels. Accordingly, rosiglitazone increased AMPK activation in muscle and liver only in obese iNOS−/− mice. PPAR-γ transcriptional activity was increased in adipose tissue of iNOS−/− mice. Conversely, treatment of 3T3-L1 adipocytes with a NO donor blunted PPAR-γ activity. CONCLUSIONS—Our results identify the iNOS/NO pathway as a critical modulator of PPAR-γ activation and circulating adiponectin levels and show that invalidation of this key inflammatory mediator improves the efficacy of PPAR-γ agonism in an animal model of obesity and insulin resistance. PMID:18458147

Crystal structure of (2E)-3-[4-(di-methyl-amino)-phen-yl]-1-(thio-phen-2-yl)prop-2-en-1-one.

PubMed

de Oliveira, Gabriela Porto; Bresolin, Leandro; Flores, Darlene Correia; de Farias, Renan Lira; de Oliveira, Adriano Bof

2017-04-01

The equimolar reaction between 4-(di-methyl-amino)-benzaldehyde and 2-acetyl-thio-phene in basic ethano-lic solution yields the title compound, C 15 H 15 NOS, whose mol-ecular structure matches the asymmetric unit. The mol-ecule is not planar, the dihedral angle between the aromatic and the thio-phene rings being 11.4 (2)°. In the crystal, mol-ecules are linked by C-H⋯O and weak C-H⋯S inter-actions along [100], forming R 2 2 (8) rings, and by weak C-H⋯O inter-actions along [010], forming chains with a C (6) graph-set motif. In addition, mol-ecules are connected into centrosymmetric dimers by weak C-H⋯π inter-actions, as indicated by the Hirshfeld surface analysis. The most important contributions for the crystal structure are the H⋯H (46.50%) and H⋯C (23.40%) inter-actions. The crystal packing resembles a herringbone arrangement when viewed along [100]. A mol-ecular docking calculation of the title compound with the neuraminidase enzyme was carried out. The enzyme shows ( ASN263 )N-H⋯O, ( PRO245 )C-H⋯ Cg (thio-phene ring) and ( AGR287 )C-H⋯N inter-molecular inter-actions with the title compound. The crystal structure was refined as a two-component twin with a fractional contribution to the minor domain of 0.0181 (8).

Scientific Communication and the Nature of Science

NASA Astrophysics Data System (ADS)

Nielsen, Kristian H.

2013-09-01

Communication is an important part of scientific practice and, arguably, may be seen as constitutive to scientific knowledge. Yet, often scientific communication gets cursory treatment in science studies as well as in science education. In Nature of Science (NOS), for example, communication is rarely mentioned explicitly, even though, as will be argued in this paper, scientific communication could be treated as a central component of NOS. Like other forms of communication, scientific communication is socially and symbolically differentiated. Among other things, it encompasses technical language and grammar, lab communications, and peer reviews, all of which will be treated in this paper in an attempt to engage on an empirical and theoretical level with science as communication. Seeing science as a form of communicative action supplements the epistemological view of science that is standard to both NOS and the philosophy of science. Additions to the seven NOS aspects on Lederman's (Handbook of research on science education. Lawrence Erlbaum, Mahwah, pp. 831-879, 2007) list are put forward as well as preliminary thoughts on the inclusion of scientific communication into NOS instruction.

Countering Anti-Immigrant Discourses in the New Latino South: "Nos Mascan Pero No Nos Tragan"

ERIC Educational Resources Information Center

Fitts, Shanan; McClure, Greg

2015-01-01

The increased visibility of immigrant communities in the southeastern United States coupled with the economic recession has led to a proliferation of anti-immigrant policies and contributed to a climate which positions Latin@ immigrants and the Spanish language as foreign or threatening. In this article, we examine language ideologies related to…

Age-related changes in endothelial function and blood flow regulation.

PubMed

Toda, Noboru

2012-02-01

Vascular endothelial dysfunction is regarded as a primary phenotypic expression of normal human aging. This senescence-induced disorder is the likely culprit underlying the increased cardiovascular and metabolic disease risks associated with aging. The rate of this age-dependent deterioration is largely influenced by the poor-quality lifestyle choice, such as smoking, sedentary daily life, chronic alcohol ingestion, high salt intake, unbalanced diet, and mental stress; and it is accelerated by cardiovascular and metabolic diseases. Although minimizing these detrimental factors is the best course of action, nonetheless chronological age steadily impairs endothelial function through reduced endothelial nitric oxide synthase (eNOS) expression/action, accelerated nitric oxide (NO) degradation, increased phosphodiesterase activity, inhibition of NOS activity by endogenous NOS inhibitors, increased production of reactive oxygen species, inflammatory reactions, decreased endothelial progenitor cell number and function, and impaired telomerase activity or telomere shortening. Endothelial dysfunction in regional vasculatures results in cerebral hypoperfusion triggering cognitive dysfunction and Alzheimer's disease, coronary artery insufficiency, penile erectile dysfunction, and circulatory failures in other organs and tissues. Possible prophylactic measures to minimize age-related endothelial dysfunction are also summarized in this review. Copyright © 2011 Elsevier Inc. All rights reserved.

77 FR 63342 - Virginia Electric and Power Company, Surry Power Station Units 1 and 2 and North Anna Power...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-16

...] Virginia Electric and Power Company, Surry Power Station Units 1 and 2 and North Anna Power Station Units 1... Operating License Nos. DPR-32 and DPR-37, NPF-4 and NPF-7 for Surry Power Station, Units 1 and 2, Surry County, [[Page 63343

76 FR 798 - Ball Bearings From Japan and the United Kingdom

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-06

... Remand)] Ball Bearings From Japan and the United Kingdom AGENCY: United States International Trade... determination in the five-year review of the antidumping duty order on ball bearings from Japan. For further... Certain Bearings and Parts Thereof from Japan and the United Kingdom, Inv. Nos. 731-TA-394-A & 399-A...

Insulin-induced generation of reactive oxygen species and uncoupling of nitric oxide synthase underlie the cerebrovascular insulin resistance in obese rats

PubMed Central

Katakam, Prasad V G; Snipes, James A; Steed, Mesia M; Busija, David W

2012-01-01

Hyperinsulinemia accompanying insulin resistance (IR) is an independent risk factor for stroke. The objective is to examine the cerebrovascular actions of insulin in Zucker obese (ZO) rats with IR and Zucker lean (ZL) control rats. Diameter measurements of cerebral arteries showed diminished insulin-induced vasodilation in ZO compared with ZL. Endothelial denudation revealed vasoconstriction to insulin that was greater in ZO compared with ZL. Nonspecific inhibition of nitric oxide synthase (NOS) paradoxically improved vasodilation in ZO. Scavenging of reactive oxygen species (ROS), supplementation of tetrahydrobiopterin (BH4) precursor, and inhibition of neuronal NOS or NADPH oxidase or cyclooxygenase (COX) improved insulin-induced vasodilation in ZO. Immunoblot experiments revealed that insulin-induced phosphorylation of Akt, endothelial NOS, and expression of GTP cyclohydrolase-I (GTP-CH) were diminished, but phosphorylation of PKC and ERK was enhanced in ZO arteries. Fluorescence studies showed increased ROS in ZO arteries in response to insulin that was sensitive to NOS inhibition and BH4 supplementation. Thus, a vicious cycle of abnormal insulin-induced ROS generation instigating NOS uncoupling leading to further ROS production underlies the cerebrovascular IR in ZO rats. In addition, decreased bioavailability and impaired synthesis of BH4 by GTP-CH induced by insulin promoted NOS uncoupling. PMID:22234336

Journal of the United States Artillery. Volume 56, Number 5, May 1922

DTIC Science & Technology

1922-05-01

ROW, LT. COL. C. C. CARSON. M .... E. W. NILES. M .... L. TURTlE . M .... P. H. WORCESTER. SECOND ROW, M.... A. J. COOPER. LT. COL. R. W. COLLINS. M...when the Coast Artillery Corps as such was still in the dim and nebulous future. Tem- pora nos mutantur et mutamur nos i:l illis-uut Truth is immortal

75 FR 3497 - Entergy Nuclear Operations, Inc., Entergy Nuclear Indian Point 2, LLC, Entergy Nuclear Indian...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-21

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-247 and 50-286; NRC-2010-0006] Entergy Nuclear Operations, Inc., Entergy Nuclear Indian Point 2, LLC, Entergy Nuclear Indian Point 3, LLC,: Indian Point Nuclear Generating Unit Nos. 2 and 3; Notice of Consideration of Issuance of Amendment to Facility Operating License and Opportunity To Request a...

Soluble DPP-4 up-regulates toll-like receptors and augments inflammatory reactions, which are ameliorated by vildagliptin or mannose-6-phosphate.

PubMed

Lee, Dong-Sung; Lee, Eun-Sol; Alam, Md Morshedul; Jang, Jun-Hyeog; Lee, Ho-Sub; Oh, Hyuncheol; Kim, Youn-Chul; Manzoor, Zahid; Koh, Young-Sang; Kang, Dae-Gil; Lee, Dae Ho

2016-02-01

Studies have shown that dipeptidyl peptidase-4 (DPP-4) inhibitors have anti-inflammatory effects. Soluble DPP-4 (sDPP-4) has been considered as an adipokine of which actions need to be further characterized. We investigated the pro-inflammatory actions of sDPP-4 and the anti-inflammatory effects of DPP-4 inhibition, using vildagliptin, as an enzymatic inhibitor, and mannose-6-phosphate (M6P) as a competitive binding inhibitor. In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, vildagliptin suppressed the increased expression of inducible nitric oxide synthase (iNOS) and phosphorylated JNK (pJNK), activation of the NF-κB pathway, and the resultant NO and proinflammatory cytokine production. Although sDPP-4 alone did not affect the protein level of iNOS or pJNK or the production of NO in RAW264.7 cells, it did amplify iNOS expression, NO responses, and proinflammatory cytokine production in LPS-stimulated RAW264 cells. As a probable mechanism, we found that sDPP-4 caused dose-dependent increases in the expression levels of toll-like receptor 4 (TLR4) and TLR2 in RAW264.7 cells, and that these alterations were inhibited by vildagliptin, M6P, or bisindolylmaleimide II, a protein kinase C inhibitor. Either vildagliptin or M6P suppressed iNOS expression and NO and cytokine production in LPS+DPP-4-co-stimulated macrophages, while combined treatment of the co-stimulated cells with both agents had increased anti-inflammatory effects compared with either treatment alone. Intravenous injection of sDPP-4 to C57BL/6J mice increased the expression of both TLRs in kidney and white adipose tissues. Our findings suggest that sDPP-4 enhances inflammatory actions via TLR pathway, while DPP-4 inhibition with either an enzymatic or binding inhibitor has anti-inflammatory effects. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of 5E-SWH learning model on students' view of nature of science

NASA Astrophysics Data System (ADS)

Sinthuwa, Waralee; Sangpradit, Theerapong

2018-01-01

View of Nature of Science (NOS) is one of key factors to support students' scientific literacy. So, it includes in scientific learning goals internationally. As in the literature, the many potential benefits associated with appropriate view of NOS. For instance, it influences students' learning achievement in science and lets students see how science connected to their real world. The aim of this study was to develop the 5E-SWH learning model to enhance 12th grade students' view of NOS. Eighty-eight students participated in this study. They were separated into two groups. Forty-four students had learnt biology by using 5E-SWH learning unit, but another group had learnt by using traditional 5E. View of NOS questionnaire that was adapted from the Views of NOS Questionnaire (VNOS-C) was applied with the both groups as pretest and posttest. The questionnaire consisted of ten open-ended items. The semi-structured interview protocol was also used with thirty students and feedback on the lesson record was provided in order to triangulate students' view of NOS. The analyzed results were approved by peer review. In addition, the during the implementation, data from voice recorder was transcribed and used discourse analysis to show students' NOS views. There were three aspects that relate to genetics technology content. These aspects included the subjective, empirical, and social and culture. Students' responses were categorized into 3 groups including informed, adequate and inadequate view. The results showed that the majority of participants held inadequate views of the subjective and empirical aspect at the beginning of the study. In addition, almost student as well as held adequate view of the social and culture aspect and they had misconception in some target NOS aspects. After that, they had learnt genetics technology content by using 5E-SWH learning model for 15 periods (50 min/ period). Both student groups' view of NOS was compared with each other. The study showed that the group that using 5E-SWH learning model develop their NOS view more than the control group that learnt through on 5E. The experimental group improved to informed view as following 45.46% subjective, 31.82% empirical and 59.09% social and culture. In addition, more than 50% of students shifted their view of NOS to better group in all target aspects. 25.76% of students shifted their view of NOS from inadequate to adequate view and 27.27% of students shifted their view of NOS from inadequate to informed view. 21.21% of students shifted their view of NOS from adequate to informed view. Furthermore, it showed their view of NOS improvement by conversation in class. The feedback on the lesson record was also support that students' view of NOS were improved by engaging in 5E-SWH learning unit. However, some students' comment on the lesson showed that they were still familiar with lecture. Therefore, it was the factor that we should concern in view of NOS development. The implications of this research for teachers were that the learning model could use to be the guideline to teach NOS integrate content in the classroom and they can use this learning model to design lesson plan in science.

78 FR 35646 - Byron Nuclear Station, Units 1 and 2, and Braidwood Nuclear Station, Units 1 and 2

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2013-06-13

... NUCLEAR REGULATORY COMMISSION [Docket Nos.: 50-454, 50-455, 50-456, 50-457; NRC-2013-0126] Byron Nuclear Station, Units 1 and 2, and Braidwood Nuclear Station, Units 1 and 2 AGENCY: Nuclear Regulatory.... Nuclear Regulatory Commission (NRC) has received an application, dated May 29, 2013, from Exelon...

77 FR 11168 - In the Matter of Exelon Corporation; Constellation Energy Group, Inc.; Nine Mile Nuclear Station...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-24

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0193; Docket Nos. 50-220 and 50-410; License Nos. DPR-63 and NPF-69] In the Matter of Exelon Corporation; Constellation Energy Group, Inc.; Nine Mile Nuclear Station, LLC; Nine Mile Point Nuclear Station, Units 1 and 2; Order Approving Application Regarding Proposed Corporate Merger and Indirect Transfer o...

Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure

PubMed Central

Theodorakis, Nicholas G; Wang, Yining N; Korshunov, Vyacheslav A; Maluccio, Mary A; Skill, Nicholas J

2015-01-01

AIM: Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. METHODS: Wild type, inducible nitric oxide synthase (iNOS)-/- and endothelial nitric oxide synthase (eNOS)-/- mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). RESULTS: SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS-/- PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS-/- PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS-/- or iNOS-/- mice. Thalidomide acutely increased plasma NOx in wild type and eNOS-/- mice but not iNOS-/- mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, eNOS-/- and iNOS-/- PVL mice, after which time levels returned to the respective baseline. CONCLUSION: Thalidomide does not reduce portal pressure in the murine PVL model by modulation of NO biosynthesis. Rather, thalidomide reduces PHT by decreasing MAP by an undetermined mechanism. PMID:25892862

Thalidomide ameliorates portal hypertension via nitric oxide synthase independent reduced systolic blood pressure.

PubMed

Theodorakis, Nicholas G; Wang, Yining N; Korshunov, Vyacheslav A; Maluccio, Mary A; Skill, Nicholas J

2015-04-14

Portal hypertension is a common complication of liver cirrhosis and significantly increases mortality and morbidity. Previous reports have suggested that the compound thalidomide attenuates portal hypertension (PHT). However, the mechanism for this action is not fully elucidated. One hypothesis is that thalidomide destabilizes tumor necrosis factor α (TNFα) mRNA and therefore diminishes TNFα induction of nitric oxide synthase (NOS) and the production of nitric oxide (NO). To examine this hypothesis, we utilized the murine partial portal vein ligation (PVL) PHT model in combination with endothelial or inducible NOS isoform gene knockout mice. Wild type, inducible nitric oxide synthase (iNOS)(-/-) and endothelial nitric oxide synthase (eNOS)(-/-) mice received either PVL or sham surgery and were given either thalidomide or vehicle. Serum nitrate (total nitrate, NOx) was measured daily for 7 d as a surrogate of NO synthesis. Serum TNFα level was quantified by enzyme-linked immunosorbent assay. TNFα mRNA was quantified in liver and aorta tissue by reverse transcription-polymerase chain reaction. PHT was determined by recording splenic pulp pressure (SPP) and abdominal aortic flow after 0-7 d. Response to thalidomide was determined by measurement of SPP and mean arterial pressure (MAP). SPP, abdominal aortic flow (Qao) and plasma NOx were increased in wild type and iNOS(-/-) PVL mice when compared to sham operated control mice. In contrast, SPP, Qao and plasma NOx were not increased in eNOS(-/-) PVL mice when compared to sham controls. Serum TNFα level in both sham and PVL mice was below the detection limit of the commercial ELISA used. Therefore, the effect of thalidomide on serum TNFα levels was undetermined in wild type, eNOS(-/-) or iNOS(-/-) mice. Thalidomide acutely increased plasma NOx in wild type and eNOS(-/-) mice but not iNOS(-/-) mice. Moreover, thalidomide temporarily (0-90 min) decreased mean arterial pressure, SPP and Qao in wild type, eNOS(-/-) and iNOS(-/-) PVL mice, after which time levels returned to the respective baseline. Thalidomide does not reduce portal pressure in the murine PVL model by modulation of NO biosynthesis. Rather, thalidomide reduces PHT by decreasing MAP by an undetermined mechanism.

77 FR 41454 - Entergy Nuclear Indian Point Unit 2, LLC, Entergy Nuclear Indian Point Unit 3, LLC, Entergy...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-13

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-247 and 50-286; NRC-2012-0168] Entergy Nuclear Indian Point Unit 2, LLC, Entergy Nuclear Indian Point Unit 3, LLC, Entergy Nuclear Operations, Inc., Indian Point Nuclear Generating Units 2 and 3; Environmental Assessment and Finding of No Significant Impact The U.S. Nuclear Regulatory Commission (NRC...

Explicit Nature of Science and Argumentation Instruction in the Context of Socioscientific Issues: An effect on student learning and transfer

NASA Astrophysics Data System (ADS)

Khishfe, Rola

2014-04-01

The purpose of the study was two-fold: to (a) investigate the influence of explicit nature of science (NOS) and explicit argumentation instruction in the context of a socioscientific issue on the argumentation skills and NOS understandings of students, and (b) explore the transfer of students' NOS understandings and argumentation skills learned in one socioscientific context into other similar contexts (familiar and unfamiliar). Participants were a total of 121 seventh grade students from two schools. The treatment involved an eight-week unit about the water usage and safety, which was taught by two teachers for two intact groups (Treatments I and II). Explicit NOS instruction was integrated for all groups. However, only the Treatment I groups had the additional explicit argumentation instruction. Participants were pre- and post-tested using an open-ended questionnaire and interviews about two socioscientific issues to assess their learning and transfer of argumentation skills and NOS understandings. Results showed improvements in the learning of argumentation practice and NOS understandings for Treatment I group participants. Similarly, there were improvements in the learning and transfer of NOS understandings for Treatment II group participants with only some improvements for the argumentation practice. Further, some of the Treatment I group participants made connections to argumentation when explicating their NOS understandings by the end of the study. Findings were discussed in light of classroom practice that utilizes an explicit approach, contextual approach, as well as an approach that integrates NOS and argumentation simultaneously.

Efficacy of a novel water-soluble curcumin derivative versus sildenafil citrate in mediating erectile function.

PubMed

Zaahkouk, A M S; Abdel Aziz, M T; Rezq, A M; Atta, H M; Fouad, H H; Ahmed, H H; Sabry, D; Yehia, M H

2015-01-01

The present study was conducted to assess the efficacy of a novel curcumin derivative (NCD) versus sildenafil citrate in erectile signaling. The study was conducted on 10 control male rats and 50 diabetic male rats divided into the following groups: diabetic, curcumin, NCD, sildenafil and NCD combined with sildenafil. Cavernous tissue (CC) gene expression levels of heme oxygenase (HO)-1, Nrf2, NF-κβ and p38, enzyme activities of HO and nitric oxide synthase (NOS), cyclic guanosine monophosphate (cGMP) and intracavernosal pressure (ICP) were assessed. Results showed that 12 weeks after induction of diabetes, erectile dysfunction was confirmed by the significant decrease in ICP, a significant decrease in cGMP, NOS, HO enzyme activities, a significant decrease in HO-1 gene and a significant elevation of NF-κβ, p38 genes. Administration of all therapeutic interventions led to a significant elevation in ICP, cGMP levels, a significant increase in HO-1 and NOS enzymes, a significant increase in HO-1 and Nrf2 gene expression, and a significant decrease in NF-κβ, p38 gene expression. NCD or its combination with sildenafil showed significant efficacy and more prolonged duration of action. In conclusion, NCD could enhance erectile function with more efficacy and more prolonged duration of action.

Role of Heat Shock Protein 90 and Endothelial Nitric Oxide Synthase during Early Anesthetic and Ischemic Preconditioning

PubMed Central

Amour, Julien; Brzezinska, Anna K.; Weihrauch, Dorothee; Billstrom, Amie R.; Zielonka, Jacek; Krolikowski, John G.; Bienengraeber, Martin W.; Warltier, David C.; Pratt, Philip F.; Kersten, Judy R.

2009-01-01

Background Nitric oxide is known to be essential for early anesthetic (APC) and ischemic (IPC) preconditioning of myocardium. Heat shock protein 90 (Hsp90) regulates endothelial nitric oxide synthase (eNOS) activity. In this study, we tested the hypothesis that Hsp90-eNOS interactions modulate APC and IPC. Methods Myocardial infarct size was measured in rabbits after coronary occlusion and reperfusion in the absence or presence of preconditioning with 30 min of isoflurane (APC) or 5 min of coronary artery occlusion (IPC), and with or without pre-treatment with geldanamycin or radicicol, two chemically distinct Hsp90 inhibitors, or NG-nitro-L-arginine methylester, a non-specific NOS inhibitor. Isoflurane-dependent nitric oxide production was measured (ozone chemiluminescence) in human coronary artery endothelial cells or mouse cardiomyocytes, in the absence or presence of Hsp90 inhibitors or NG-nitro-L-arginine methylester. Interactions between Hsp90 and eNOS, and eNOS activation were assessed with immunoprecipitation, immunoblotting, and confocal microscopy. Results APC and IPC decreased infarct size (50% and 59%, respectively) and this action was abolished by Hsp90 inhibitors. NG-nitro-L-arginine methylester blocked APC but not IPC. Isoflurane increased nitric oxide production in human coronary artery endothelial cells, concomitantly with an increase in Hsp90-eNOS interaction (immunoprecipitation, immunoblotting, and immunohistochemistry). Pretreatment with Hsp90 inhibitors abolished isoflurane-dependent nitric oxide production and decreased Hsp90-eNOS interactions. Isoflurane did not increase nitric oxide production in mouse cardiomyocytes and eNOS was below the level of detection. Conclusion The results indicate that Hsp90 plays a critical role in mediating APC and IPC through protein-protein interactions, and suggest that endothelial cells are important contributors to nitric oxide-mediated signalling during APC. PMID:19194158

77 FR 62541 - Investor Advisory Committee

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2012-10-15

... SECURITIES AND EXCHANGE COMMISSION [Release Nos. 33-9365; 34-68019; File No. 265-28] Investor Advisory Committee AGENCY: Securities and Exchange Commission. ACTION: Notice of Telephonic Meeting of Securities and Exchange Commission Investor Advisory Committee. SUMMARY: The Securities and Exchange...

Adults' decision-making about the electronic waste issue: The role of the nature of science conceptualizations and moral concerns in socio-scientific decision-making

NASA Astrophysics Data System (ADS)

Yu, Yuqing

Socio-scientific issues have become increasingly important in Science-Technology-Society (STS) education as a means to make science learning more relevant to students' lives. This study used the e-waste issue as a context to investigate two aspects of socio-scientific decision-making: (1) the relationship between the nature of science (NOS) conceptualizations and decision-making; and (2) moral concerns involved in the process of decision-making. This study contributes to the field of socio-scientific issue research and STS education in the following ways. First, it is the first study that performed meta-analysis to seek the relationship between the NOS understanding and decision-making. This study concludes that valuable NOS conceptualizations that are highly related to the socio-scientific issue under investigation, rather than general NOS understanding, exert statistically significant influences on decision-making. Second, this study empirically examined the Multiple Responses Model (MRM), which enables the transfer of qualitative NOS responses into quantitative data, and hence, inferential statistics. The current study justifies the significance of unidimensionality to the application of the MRM. It addresses the limitations associated with the MRM and provides implications for future use of the MRM in other contexts. Finally, the study explores the role of moral concerns in socio-scientific decision-making. Eight participants engaged in interviews that were designed to elicit their reactions and feelings regarding the issue of exporting e-waste to poor countries. Qualitative analyses demonstrated that moral considerations were significant influences on decision-making. In addition, participants' action responses revealed that they were motivated to take action to help the environment. The study has implications for socio-scientific issue studies in other contexts and for teacher education programs that use socio-scientific issues to advance teachers' reasoning and discourse skills.

The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity.

PubMed

Gentile, Daniela; Fornai, Matteo; Colucci, Rocchina; Pellegrini, Carolina; Tirotta, Erika; Benvenuti, Laura; Segnani, Cristina; Ippolito, Chiara; Duranti, Emiliano; Virdis, Agostino; Carpi, Sara; Nieri, Paola; Németh, Zoltán H; Pistelli, Laura; Bernardini, Nunzia; Blandizzi, Corrado; Antonioli, Luca

2018-01-01

Apigenin can exert beneficial actions in the prevention of obesity. However, its putative action on obesity-associated bowel motor dysfunctions is unknown. This study examined the effects of apigenin on colonic inflammatory and motor abnormalities in a mouse model of diet-induced obesity. Male C57BL/6J mice were fed with standard diet (SD) or high-fat diet (HFD). SD or HFD mice were treated with apigenin (10 mg/Kg/day). After 8 weeks, body and epididymal fat weight, as well as cholesterol, triglycerides and glucose levels were evaluated. Malondialdehyde (MDA), IL-1β and IL-6 levels, and let-7f expression were also examined. Colonic infiltration by eosinophils, as well as substance P (SP) and inducible nitric oxide synthase (iNOS) expressions were evaluated. Motor responses elicited under blockade of NOS and tachykininergic contractions were recorded in vitro from colonic longitudinal muscle preparations. When compared to SD mice, HFD animals displayed increased body weight, epididymal fat weight and metabolic indexes. HFD mice showed increments in colonic MDA, IL-1β and IL-6 levels, as well as a decrease in let-7f expression in both colonic and epididymal tissues. HFD mice displayed an increase in colonic eosinophil infiltration. Immunohistochemistry revealed an increase in SP and iNOS expression in myenteric ganglia of HFD mice. In preparations from HFD mice, electrically evoked contractions upon NOS blockade or mediated by tachykininergic stimulation were enhanced. In HFD mice, Apigenin counteracted the increase in body and epididymal fat weight, as well as the alterations of metabolic indexes. Apigenin reduced also MDA, IL-1β and IL-6 colonic levels as well as eosinophil infiltration, SP and iNOS expression, along with a normalization of electrically evoked tachykininergic and nitrergic contractions. In addition, apigenin normalized let-7f expression in epididymal fat tissues, but not in colonic specimens. Apigenin prevents systemic metabolic alterations, counteracts enteric inflammation and normalizes colonic dysmotility associated with obesity.

Contributions of endothelial nitric oxide synthase, noradrenaline, and neuropeptide Y to local warming-induced cutaneous vasodilatation in men.

PubMed

Hodges, Gary J; Sparks, Paul A

2013-11-01

We performed a two-part study to determine the roles of endothelial nitric oxide synthase (eNOS) and the vasoconstrictor nerves neurotransmitters noradrenaline (NA) and neuropeptide Y (NPY) in the cutaneous vasodilator response to local skin warming. Forearm skin sites were instrumented with intradermal microdialysis fibres, local heaters, and laser-Doppler flow (LDF) probes. Sites were locally heated from 34 to 42°C. LDF was expressed as cutaneous vascular conductance (CVC; LDF/mean arterial pressure). In Part I, we tested whether sympathetic noradrenergic nerves acted via eNOS. In 8 male participants, treatments were as follows: 1) untreated; 2) bretylium tosylate (BT), preventing sympathetic neurotransmitter release; 3) l-NAA to inhibit eNOS; and 4) combined BT+l-NAA. At treated sites, the initial peak response was markedly reduced, and the plateau phase response to 35min of local warming was also reduced (P<0.05), which was not different among those sites (P>0.05). In Part II, we tested whether NA and NPY were involved in the vasodilator response to local warming. In Part IIa, treatments were: 1) untreated; 2) propranolol and yohimbine to antagonize α- and β-receptors; 3) l-NAA; and 4) combined propranolol, yohimbine, and l-NAA. In Part IIb, conditions were: 1) untreated; 2) BIBP to antagonize Y1-receptors; 3) l-NAA; and 4) combined BIBP and l-NAA. All treatments caused a reduction in the initial peak and plateau responses to local skin warming (P<0.05). The results of Part II indicate that both NA and NPY play roles in the cutaneous vasodilator response and their actions are achieved via eNOS. These data indicate that NA and NPY are involved in the initial, rapid rise in skin blood flow at the onset of local skin warming. However, their vasodilator actions in response to local skin warming appears to be manifested through eNOS. © 2013.

Crystal structure of the cis and trans polymorphs of bis-[μ-2-(1,3-benzo-thia-zol-2-yl)phenolato]-κ3N,O:O;κ3O:N,O-bis-[fac-tri-carbonyl-rhenium(I)].

PubMed

Priyatharsini, Maruthupandiyan; Shankar, Bhaskaran; Sathiyendiran, Malaichamy; Srinivasan, Navaneethakrishnan; Krishnakumar, Rajaputi Venkatraman

2017-02-01

The title dinuclear complex, [Re 2 (C 13 H 8 NOS) 2 (CO) 6 ], crystallizes in two polymorphs where the 2-(1,3-benzo-thia-zol-2-yl)phenolate ligands and two carbonyl groups are trans - ( I ) or cis -arranged ( II ) with respect to the [Re 2 O 2 (CO) 4 ] core. Polymorphs I and II exhibit a crystallographically imposed centre of symmetry and a twofold rotation axis, respectively. The structures may be described as being formed by two octa-hedrally distorted metal-coordinating units fused through μ-oxido bridges, leading to edge-sharing dimers. The crystal packing is governed by C-H⋯O hydrogen-bonding inter-actions, forming chains parallel to the c axis in I and a three-dimensional network in II .

Cardiac Nitric Oxide Synthases and Na⁺/K⁺-ATPase in the Rat Model of Polycystic Ovary Syndrome Induced by Dihydrotestosterone.

PubMed

Tepavčević, S; Milutinović, D V; Macut, D; Stanišić, J; Nikolić, M; Božić-Antić, I; Rodaljević, S; Bjekić-Macut, J; Matić, G; Korićanac, G

2015-05-01

Nitric oxide synthases (NOSs) and Na(+)/K(+)-ATPase are enzymes essential for regular functioning of the heart. Since both enzymes are under insulin and androgen regulation and since insulin action and androgen level were disturbed in polycystic ovary syndrome (PCOS), we hypothesized that cardiac nitric oxide (NO) production and sodium/potassium transport would be deteriorated in PCOS. To test our hypothesis we introduced animal model of PCOS based on dihydrotestosterone (DHT) treatment of female Wistar rats and analyzed protein expression, phosphorylation or subcellular localization of endothelial NOS (eNOS), inducible NOS (iNOS) and alpha subunits of Na(+)/K(+)-ATPase in the heart. Obtained results indicate that DHT treatment significantly decreased cardiac eNOS protein level and activating phosphorylation at serine 1,177, while inhibitory phosphorylation at threonine 495 was increased. In contrast to expression of eNOS, iNOS protein level in the heart of DHT-treated rats was significantly elevated. Furthermore, cardiac protein level of alpha 1 subunit of the ATPase, as well as its plasma membrane content, were decreased in rats with PCOS. In line with this, alpha 2 subunit protein level in fraction of plasma membranes was also significantly below control level. In conclusion, DHT treatment impaired effectiveness of NOSs and Na(+)/K(+)-ATPase in the female rat heart. Regarding the importance of NO production and sodium/potassium transport in the cardiac contraction and blood flow regulation, it implicates strong consequences of PCOS for heart functioning. © Georg Thieme Verlag KG Stuttgart · New York.

Vascular endothelial growth factor and nitric oxide synthase expression in human tooth germ development.

PubMed

Mastrangelo, F; Sberna, M T; Tettamanti, L; Cantatore, G; Tagliabue, A; Gherlone, E

2016-01-01

Vascular Endothelia Growth Factor (VEGF) and Nitric Oxide Synthase (NOS) expression, were evaluated in human tooth germs at two different stages of embryogenesis, to clarify the role of angiogenesis during tooth tissue differentiation and growth. Seventy-two third molar germ specimens were selected during oral surgery. Thirty-six were in the early stage and 36 in the later stage of tooth development. The samples were evaluated with Semi-quantitative Reverse Transcription-Polymerase chain Reaction analyses (RT-PcR), Western blot analysis (WB) and immunohistochemical analysis. Western blot and immunohistochemical analysis showed a VEGF and NOS 1-2-3 positive reaction in all samples analysed. VEGF high positive decrease reaction was observed in stellate reticulum cells, ameloblast and odontoblast clusters in early stage compared to later stage of tooth germ development. Comparable VEGF expression was observed in endothelial cells of early and advanced stage growth. NOS1 and NOS3 expressions showed a high increased value in stellate reticulum cells, and ameloblast and odontoblast clusters in advanced stage compared to early stage of development. The absence or only moderate positive reaction of NOS2 was detected in all the different tissues. Positive NOS2 expression showed in advanced stage of tissue development compared to early stage. The action of VEGF and NOS molecules are important mediators of angiogenesis during dental tissue development. VEGF high positive expression in stellate reticulum cells in the early stage of tooth development compared to the later stage and the other cell types, suggests a critical role of the stellate reticulum during dental embryo-morphogenesis.

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 mRNA were detected after 48 hours, suggesting that rapamycin can modify iNOS mRNA stability. In this regard, we found that rapamycin significantly reduced the half-life of iNOS mRNA, from 4 h to 50 min when cells were co-incubated with cytokine mixture and 10 nM rapamycin. Similarly, rapamycin induced a significant up-regulation of tristetraprolin (TTP), a protein involved in the regulation of iNOS mRNA stability. Conclusion The present findings show that mTOR controls the rate of iNOS mRNA degradation in astrocytes. Together with the marked anti-inflammatory effects that we previously observed in microglial cells, these data suggest possible beneficial effects of mTOR inhibitors in the treatment of inflammatory-based CNS pathologies. PMID:21208419

75 FR 43579 - Exelon Generation Company, LLC; Victoria County Station, Units 1 and 2; Notice of Withdrawal of...

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2010-07-26

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 52-031 and 52-032; NRC-2008-0542] Exelon Generation... in 10 CFR part 52, ``Licenses, Certifications and Approvals for Nuclear Power Plants.'' Exelon... CFR part 52. The docket numbers established for this application are 52-031 (Unit 1) and 52-032 (Unit...

77 FR 12885 - Millstone Power Station, Units 1, 2 and 3, Dominion Nuclear Connecticut, Inc.; Exemption

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... high wind conditions pass, wind damage to the plant and surrounding area might preclude a sufficient... Power Station, Units 1, 2 and 3, Dominion Nuclear Connecticut, Inc.; Exemption 1.0 Background Dominion..., DPR-65 and NPF-49, which authorize operation of the Millstone Power Station, Unit Nos. 1, 2 and 3...

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 © 2016 Elsevier Inc. All rights reserved.

Nitrite produced by Mycobacterium tuberculosis in human macrophages in physiologic oxygen impacts bacterial ATP consumption and gene expression

PubMed Central

Cunningham-Bussel, Amy; Zhang, Tuo; Nathan, Carl F.

2013-01-01

In high enough concentrations, such as produced by inducible nitric oxide synthase (iNOS), reactive nitrogen species (RNS) can kill Mycobacterium tuberculosis (Mtb). Lesional macrophages in macaques and humans with tuberculosis express iNOS, and mice need iNOS to avoid succumbing rapidly to tuberculosis. However, Mtb’s own ability to produce RNS is rarely considered, perhaps because nitrate reduction to nitrite is only prominent in axenic Mtb cultures at oxygen tensions ≤1%. Here we found that cultures of Mtb-infected human macrophages cultured at physiologic oxygen tensions produced copious nitrite. Surprisingly, the nitrite arose from the Mtb, not the macrophages. Mtb responded to nitrite by ceasing growth; elevating levels of ATP through reduced consumption; and altering the expression of 120 genes associated with adaptation to acid, hypoxia, nitric oxide, oxidative stress, and iron deprivation. The transcriptomic effect of endogenous nitrite was distinct from that of nitric oxide. Thus, whether or not Mtb is hypoxic, the host expresses iNOS, or hypoxia impairs the action of iNOS, Mtb in vivo is likely to encounter RNS by producing nitrite. Endogenous nitrite may slow Mtb’s growth and prepare it to resist host stresses while the pathogen waits for immunopathology to promote its transmission. PMID:24145454

16. LIGHTING PLAN OF GENERATOR ROOM, SHOWING CONFIGURATION OF TURBINEGENERATOR ...

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

16. LIGHTING PLAN OF GENERATOR ROOM, SHOWING CONFIGURATION OF TURBINE-GENERATOR UNITS. UNITS A THROUGH D ARE CURRENTLY DESIGNATED AS NOS. 1 THROUGH 4 (1907) - Nine Mile Hydroelectric Development, Powerhouse, State Highway 291 along Spokane River, Nine Mile Falls, Spokane County, WA

78 FR 66785 - Luminant Generation Company, LLC

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2013-11-06

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 52-034 and 52-035; NRC-2008-0594] Luminant Generation Company, LLC AGENCY: Nuclear Regulatory Commission. ACTION: Notice of receipt; availability. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC) is giving notice once each week for four consecutive weeks...

75 FR 80859 - New Postal Product

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2010-12-23

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2011-11 and CP2011-47; Order No. 612] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a...). The Postal Service contemporaneously filed a contract related to the proposed new product pursuant to...

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... POSTAL REGULATORY COMMISSION [Docket Nos. MC2010-31 and CP2010-76; Order No. 498] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... (Request). The Postal Service contemporaneously filed a contract related to the proposed new product...

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2013-11-27

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L-arginine prevents xanthoma development and inhibits atherosclerosis in LDL receptor knockout mice.

PubMed

Aji, W; Ravalli, S; Szabolcs, M; Jiang, X C; Sciacca, R R; Michler, R E; Cannon, P J

1997-01-21

The potential antiatherosclerotic actions of NO were investigated in four groups of mice (n = 10 per group) lacking functional LDL receptor genes, an animal model of familial hypercholesterolemia. Group 1 was fed a regular chow diet. Groups 2 through 4 were fed a 1.25% high-cholesterol diet. In addition, group 3 received supplemental L-arginine and group 4 received L-arginine and N omega-nitro-L-arginine (L-NA), an inhibitor of NO synthase (NOS). Animals were killed at 6 months; aortas were stained with oil red O for planimetry and with antibodies against constitutive and inducible NOSs. Plasma cholesterol was markedly increased in the animals receiving the high-cholesterol diet. Xanthomas appeared in all mice fed the high-cholesterol diet alone but not in those receiving L-arginine. Aortic atherosclerosis was present in all mice on the high-cholesterol diet. The mean atherosclerotic lesion area was reduced significantly (P < .01) in the cholesterol-fed mice given L-arginine compared with those receiving the high-cholesterol diet alone. The mean atherosclerotic lesion area was significantly larger (P < .01) in cholesterol-fed mice receiving L-arginine + L-NA than in those on the high-cholesterol diet alone. Within the atherosclerotic plaques, endothelial cells immunoreacted for endothelial cell NOS; macrophages, foam cells, and smooth muscle cells immunostained strongly for inducible NOS and nitrotyrosine residues. The data indicate that L-arginine prevents xanthoma formation and reduces atherosclerosis in LDL receptor knockout mice fed a high-cholesterol diet. The abrogation of the beneficial effects of L-arginine by L-NA suggests that the antiatherosclerotic actions of L-arginine are mediated by NOS. The data suggest that L-arginine may be beneficial in familial hypercholesterolemia.

Involvement of PKA-dependent upregulation of nNOS-CGRP in adrenomedullin-initiated mechanistic pathway underlying CFA-induced response in rats.

PubMed

Wang, Dongmei; Ruan, Liqin; Hong, Yanguo; Chabot, Jean-Guy; Quirion, Rémi

2013-01-01

We have previously shown that intrathecal administration of the adrenomedullin (AM) receptor antagonist AM(22-52) produces a long-lasting anti-hyperalgesia effect. This study examined the hypothesis that AM recruits other pronociceptive mediators in complete Freund's adjuvant (CFA)-induced inflammation. Injection of CFA in the hindpaw of rat produced an increase in the expression of nNOS in dorsal root ganglion (DRG) and the spinal dorsal horn. An intrathecal administration of AM(22-52), but not the CGRP antagonist BIBN4096BS, abolished the CFA-induced increase of nNOS. Moreover, AM-induced increase of CGRP was inhibited by the nNOS inhibitors L-NAME and 7-nitroindazole in cultured ganglion explants. Addition of AM to ganglion cultures induced an increase in nNOS protein, which was attenuated by the PKA inhibitor H-89. Treatment with AM also concentration-dependently increased cAMP content and pPKA protein level, but not its non-phosphorylated form, in cultured ganglia. In addition, nNOS was shown to be co-localized with the AM receptor components calcitonin receptor-like receptor and receptor activity-modifying protein 2- and 3 in DRG neurons. The present study suggests that the enhanced activity of nitric oxide (NO) mediates the biological action of AM at the spinal level and that AM recruits NO-CGRP via cAMP/PKA signaling in a mechanistic pathway underlying CFA-induced hyperalgesia. Copyright © 2012 Elsevier Inc. All rights reserved.

Protein Kinase-C Beta Contributes to Impaired Endothelial Insulin Signaling in Humans with Diabetes Mellitus

PubMed Central

Tabit, Corey E; Shenouda, Sherene M; Holbrook, Monica; Fetterman, Jessica L; Kiani, Soroosh; Frame, Alissa A; Kluge, Matthew A; Held, Aaron; Dohadwala, Mustali; Gokce, Noyan; Farb, Melissa; Rosenzweig, James; Ruderman, Neil; Vita, Joseph A; Hamburg, Naomi M

2013-01-01

Background Abnormal endothelial function promotes atherosclerotic vascular disease in diabetes. Experimental studies indicate that disruption of endothelial insulin signaling through the activity of protein kinase C-β (PKCβ) and nuclear factor κB (NFκB) reduces nitric oxide availability. We sought to establish whether similar mechanisms operate in the endothelium in human diabetes mellitus. Methods and Results We measured protein expression and insulin response in freshly isolated endothelial cells from patients with Type 2 diabetes mellitus (n=40) and non-diabetic controls (n=36). Unexpectedly, we observed 1.7-fold higher basal endothelial nitric oxide synthase (eNOS) phosphorylation at serine 1177 in patients with diabetes (P=0.007) without a difference in total eNOS expression. Insulin stimulation increased eNOS phosphorylation in non-diabetic subjects but not in diabetic patients (P=0.003) consistent with endothelial insulin resistance. Nitrotyrosine levels were higher in diabetic patients indicating endothelial oxidative stress. PKCβ expression was higher in diabetic patients and was associated with lower flow-mediated dilation (r=−0.541, P=0.02) Inhibition of PKCβ with LY379196 reduced basal eNOS phosphorylation and improved insulin-mediated eNOS activation in patients with diabetes. Endothelial NFκB activation was higher in diabetes and was reduced with PKCβ inhibition. Conclusions We provide evidence for the presence of altered eNOS activation, reduced insulin action and inflammatory activation in the endothelium of patients with diabetes. Our findings implicate PKCβ activity in endothelial insulin resistance. PMID:23204109

Distinction between critical current effects and intrinsic anomalies in the point-contact Andreev reflection spectra of unconventional superconductors

NASA Astrophysics Data System (ADS)

He, Ge; Wei, Zhong-Xu; Brisbois, Jérémy; Jia, Yan-Li; Huang, Yu-Long; Zhou, Hua-Xue; Ni, Shun-Li; Silhanek, Alejandro V.; Shan, Lei; Zhu, Bei-Yi; Yuan, Jie; Dong, Xiao-Li; Zhou, Fang; Zhao, Zhong-Xian; Jin, Kui

2018-04-01

Not Available Project supported by the National Key Basic Research Program of China (Grant Nos. 2015CB921000, 2016YFA0300301, and 2017YFA0302902), the National Natural Science Foundation of China (Grant Nos. 11674374 and 1474338), the Key Research Program of Frontier Sciences, Chinese Academy of Sciences (Grant No. QYZDB-SSW-SLH008), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant Nos. XDB07020100 and XDB07030200), the Beijing Municipal Science and Technology Project (Grant No. Z161100002116011), the Fonds de la Recherche Scientifique–FNRS and the ARC Grant 13/18-08 for Concerted Research Actions, financed by the French Community of Belgium (Wallonia-Brussels Federation). Jérémy Brisbois acknowledges the support from F.R.S.–FNRS (Research Fellowship), The work of Alejandro V Silhanek is partially supported by PDR T.0106.16 of the F.R.S.–FNRS..

76 FR 25378 - Exelon Generation Company, LLC; PSEG Nuclear, LLC; Peach Bottom Atomic Power Station, Units 2 and...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-04

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-277 and 50-278; NRC-2011-0101] Exelon Generation Company, LLC; PSEG Nuclear, LLC; Peach Bottom Atomic Power Station, Units 2 and 3; Notice of Withdrawal of... for the Peach Bottom Atomic Power Station (PBAPS), Units 2 and 3, located in York and Lancaster...

75 FR 6071 - Exelon Generation Company, LLC; PSEG Nuclear, LLC; Peach Bottom Atomic Power Station Units 2 and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-05

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-277 and 50-278; NRC-2010-0042] Exelon Generation Company, LLC; PSEG Nuclear, LLC; Peach Bottom Atomic Power Station Units 2 and 3; Notice of Withdrawal of... and DPR-56 for the Peach Bottom Atomic Power Station (PBAPS), Units 2 and 3, located in York and...

77 FR 21593 - V. C. Summer Nuclear Station, Units 2 and 3 Combined Licenses and Record of Decision

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-10

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 052-00027 and 052-00028; NRC-2008-0441] V. C. Summer... Licenses for Virgil C. Summer Nuclear Station, Units 2 and 3'' ML11098A044 NUREG-1939, Vol 1, ``Final Environmental Impact Statement for Combined Licenses for Virgil C. Summer Nuclear Station, Units 2 and 3...

PECAM1 regulates flow-mediated Gab1 tyrosine phosphorylation and signaling

PubMed Central

Xu, Suowen; Ha, Chang Hoon; Wang, Weiye; Xu, Xiangbin; Yin, Meimei; Jin, Felix Q.; Mastrangelo, Michael; Koroleva, Marina; Fujiwara, Keigi; Jin, Zheng Gen

2016-01-01

Endothelial dysfunction, characterized by impaired activation of endothelial nitric oxide (NO) synthase (eNOS) and ensued decrease of NO production, is a common mechanism of various cardiovascular pathologies, including hypertension and atherosclerosis. Laminar blood flow-mediated specific signaling cascades modulate vascular endothelial cells (ECs) structure and functions. We have previously shown that flow-stimulated Gab1 (Grb2-associated binder-1) tyrosine phosphorylation mediates eNOS activation in ECs, which in part confers laminar flow atheroprotective action. However, the molecular mechanisms whereby flow regulates Gab1 tyrosine phosphorylation and its downstream signaling events remain unclear. Here we show that platelet endothelial cell adhesion molecule-1 (PECAM1), a key molecule in an endothelial mechanosensing complex, specifically mediates Gab1 tyrosine phosphorylation and its downstream Akt and eNOS activation in ECs upon flow rather than hepatocyte growth factor (HGF) stimulation. Small interfering RNA (siRNA) targeting PECAM1 abolished flow- but not HGF-induced Gab1 tyrosine phosphorylation and Akt, eNOS activation as well as Gab1 membrane translocation. Protein-tyrosine phosphatase SHP2, which has been shown to interact with Gab1, was involved in flow signaling and HGF signaling, as SHP2 siRNA diminished the flow- and HGF-induced Gab1 tyrosine phosphorylation, membrane localization and downstream signaling. Pharmacological inhibition of PI3K decreased flow-, but not HGF-mediated Gab1 phosphorylation and membrane localization as well as eNOS activation. Finally, we observed that flow-mediated Gab1 and eNOS phosphorylation in vivo induced by voluntary wheel running was reduced in PECAM1 knockout mice. These results demonstrate a specific role of PECAM1 in flow-mediated Gab1 tyrosine phosphorylation and eNOS signaling in ECs. PMID:26706435

Protective effect of hexane extracts of Uncaria sinensis against photothrombotic ischemic injury in mice.

PubMed

Park, Sun Haeng; Kim, Ji Hyun; Park, Se Jin; Bae, Sun Sik; Choi, Young Whan; Hong, Jin Woo; Choi, Byung Tae; Shin, Hwa Kyoung

2011-12-08

Uncaria sinensis (US) has been used in traditional Korean medicine to treat vascular disease and to relieve various neurological symptoms. Scientific evidence related to the effectiveness or action mechanism of US on cerebrovascular disease has not been examined experimentally. Here, we investigated the cerebrovascular protective effect of US extracts on photothrombotic ischemic injury in mice. US hexane extracts (HEUS), ethyl acetate extracts (EAEUS) and methanol extracts (MEUS) were administered intraperitoneally 30 min before ischemic insults. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, neurological score and the activation of Akt and eNOS in ischemic brain. HEUS more significantly reduced infarct volume and edema than did EAEUS and MEUS following photothrombotic cortical occlusion. HEUS produced decreased infarct volume and edema size, and improved neurological function in a concentration-dependent manner (10, 50, and 100 mg/kg). However, HEUS did not reduce brain infarction in eNOS KO mice, suggesting that the protective effect of HEUS is primarily endothelium-dependent. Furthermore, HEUS (10-300 μg/ml) produced a concentration-dependent relaxation in mouse aorta and rat basilar artery, which was not seen in eNOS KO mouse aorta, suggesting that HEUS cause vasodilation via an eNOS-dependent mechanism. This correlated with increased phosphorylation of Akt and eNOS in the brains of HEUS-treated mice. HEUS prevent cerebral ischemic damage by regulating Akt/eNOS signaling. US, herbal medicine, may be the basis of a novel strategy for the therapy of stroke. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

CHP1002, a novel andrographolide derivative, inhibits pro-inflammatory inducible nitric oxide synthase and cyclooxygenase-2 expressions in RAW264.7 macrophages via up-regulation of heme oxygenase-1 expression.

PubMed

Zhang, Bo; Yan, Lingdi; Zhou, Peilan; Dong, Zhaoqi; Feng, Siliang; Liu, Keliang; Gong, Zehui

2013-02-01

Andrographolides, a type of diterpene lactone, are widely known to have anti-inflammatory and anti-oxidative properties. CHP1002, a synthetic derivative of andrographolide, has similar anti-inflammatory action in mouse ear swelling test and rat paw edema test. In the present study, the mechanism of anti-inflammatory effects of CHP1002 was investigated in RAW264.7 macrophages. CHP1002 potently suppressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. CHP1002 reduced the production of iNOS-derived nitric oxide (NO) and COX-2-derived prostaglandin E2 (PGE2). CHP1002 induced heme oxygenase-1 (HO-1) expression via activation of extracellular signal-regulated kinase (ERK) and NF-E2 related factor 2 transcription factor (Nrf2). Down-regulation of LPS-induced iNOS and COX-2 expressions was partially reversed by the HO-1 inhibitor zinc protoporphyrin (ZnPP). In addition, CHP1002 significantly attenuated LPS-induced TNF-α, IL-1β and IL-6 production. CHP1002 effectively induced HO-1 and was capable of inhibiting some macrophage-derived pro-inflammatory mediators, which may be closely correlated with its anti-inflammatory action. Copyright © 2012 Elsevier B.V. All rights reserved.

77 FR 76095 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-26

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2013-24 and CP2013-32; Order No. 1586] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal Service request to add First-Class Package Service Contract 34 to the competitive...

75 FR 67146 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2011-13 Through CP2011-18; Order No. 559] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... 4. The Postal Service concludes that its filings demonstrate that each of the new GEPS 3 contracts...

78 FR 63519 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2014-1 and CP2014-1; Order No. 1849] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... contemporaneously filed a redacted contract related to the proposed new product. Id. Attachment B. The instant...

75 FR 57303 - New Postal Product

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2010-09-20

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2010-105 through CP2010-115; Order No. 535] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... concludes that its filings demonstrate that each of the new GEPS 3 contracts complies with the requirements...

77 FR 65023 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-24

... follows: Attachment A--a redacted copy of Governors' Decision No. 11-6, authorizing the new product... POSTAL REGULATORY COMMISSION [Docket Nos. CP2013-4 and MC2013-4; Order No. 1504] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a...

77 FR 65912 - Priority Mail Contract

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2010-1; Order No. 1517] Priority Mail Contract AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing concerning an amendment to Priority Mail Contract 19. This notice informs the public of the filing...

78 FR 55124 - Domestic Mail Contract

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-09

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2013-59 and CP2013-80; Order No. 1826] Domestic Mail Contract AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recent Postal Service filing seeking to add Parcel Select Contract 7 to the competitive product list. This...

Potential role of eNOS in the therapeutic control of myocardial oxygen consumption by ACE inhibitors and amlodipine.

PubMed

Loke, K E; Messina, E J; Shesely, E G; Kaley, G; Hintze, T H

2001-01-01

Our aim was to investigate the potential therapeutic role of endothelial nitric oxide synthase (eNOS) in the modulation of cardiac O(2) consumption induced by the angiotensin converting enzyme (ACE) inhibitor ramiprilat and amlodipine. Three different groups of mice were used; wild type, wild type in the presence of N-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/l) or genetically altered mice lacking the eNOS gene (eNOS -/-). Myocardial O(2) consumption was measured using a Clark-type O(2) electrode in an air-tight stirred bath. Concentration-response curves to ramiprilat (RAM), amlodipine (AMLO), diltiazem (DIL), carbachol (CCL), substance P (SP) and S-nitroso-N-acetyl-penicillamine (SNAP) were performed. The rate of decrease in O(2) concentration was expressed as a percentage of the baseline. Baseline O(2) consumption was not different between the three groups of mice. In tissues from wild type mice, RAM (10(-5) mol/l), AMLO (10(-5) mol/l), DIL (10(-4) mol/l), CCL (10(-4) mol/l), SP (10(-7) mol/l) and SNAP (10(-4) mol/l) reduced myocardial O(2) consumption by -32+/-4, -27+/-10, -20+/-6, -25+/-2, -22+/-4 and -42+/-4%, respectively. The responses to RAM, AMLO, CCL and SP were absent in tissues taken from eNOS -/- mice (-7.1+/-4.3, -5.0+/-6.0, -5.2+/-5.1 and -0.4+/-0.2%, respectively). In addition, L-NAME significantly (P<0.05) inhibited the reduction in O(2) consumption induced by RAM (-9.8+/-4.4%), AMLO (-1.0+/-6.0%), CCL (-8.8+/-3.7%) and SP (-6.6+/-4.9%) in cardiac tissues from wild type mice. In contrast, NO-independent responses to the calcium channel antagonist, DIL, and responses to the NO donor, SNAP, were not affected in cardiac tissues taken from eNOS -/- (DIL: -20+/-4%; SNAP: -46+/-6%) or L-NAME-treated (DIL: -17+/-2%; SNAP: -33+/-5%) mice. These results suggest that endogenous endothelial NO synthase derived NO serves an important role in the regulation of myocardial O(2) consumption. This action may contribute to the therapeutic action of ACE inhibitors and amlodipine.

75 FR 44988 - Wire Decking From China; Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-30

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-466 and 731-TA-1162 (Final)] Wire... establishment of an industry in the United States is not materially retarded, by reason of imports of wire... industry in the United States is materially injured by reason of imports of wire decking from China...

77 FR 40091 - Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating, Units 2 and 3

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-247 and 50-286; NRC-2008-0672] Entergy Nuclear Operations, Inc.; Indian Point Nuclear Generating, Units 2 and 3 AGENCY: Nuclear Regulatory Commission... renewal of nuclear plants; availability. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or the...

78 FR 26662 - Entergy Nuclear Operations, Inc., Indian Point Nuclear Generating Unit No. 3 Extension of Public...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-07

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-286; NRC-2013-0063] Entergy Nuclear Operations, Inc., Indian Point Nuclear Generating Unit No. 3 Extension of Public Comment Period AGENCY: Nuclear Regulatory... FURTHER INFORMATION CONTACT: Douglas V. Pickett, Senior Project Manager, Office of Nuclear Reactor...

Neuronal nitric oxide synthase control mechanisms in the cutaneous vasculature of humans in vivo

PubMed Central

Kellogg, Dean L; Zhao, Joan L; Wu, Yubo

2008-01-01

The physiological roles of constituitively expressed nitric oxide synthase (NOS) isoforms in humans, in vivo, are unknown. Cutaneous vasodilatation during both central nervous system-mediated, thermoregulatory reflex responses to whole-body heat stress and during peripheral axon reflex-mediated, local responses to skin warming in humans depend on nitric oxide (NO) generation by constituitively expressed NOS of uncertain isoform. We hypothesized that neuronal NOS (nNOS, NOS I) effects cutaneous vasodilatation during whole-body heat stress, but not during local skin warming. We examined the effects of the nNOS inhibitor 7-nitroindazole (7-NI) administered by intradermal microdialysis on vasodilatation induced by whole-body heat stress or local skin warming. Skin blood flow (SkBF) was monitored by laser–Doppler flowmetry (LDF). Blood pressure (MAP) was monitored and cutaneous vascular conductance calculated (CVC = LDF/MAP). In protocol 1, whole-body heat stress was induced with water-perfused suits. In protocol 2, local skin warming was induced through local warming units at LDF sites. At the end of each protocol, 56 mm sodium nitroprusside was perfused at microdialysis sites to raise SkBF to maximal levels for data normalization. 7-NI significantly attenuated CVC increases during whole-body heat stress (P < 0.05), but had no effect on CVC increases induced by local skin warming (P > 0.05). These diametrically opposite effects of 7-NI on two NO-dependent processes verify selective nNOS antagonism, thus proving that the nNOS isoform affects NO increases and hence vasodilatation during centrally mediated, reflex responses to whole-body heat stress, but not during locally mediated, axon reflex responses to local skin warming. We conclude that the constituitively expressed nNOS isoform has distinct physiological roles in cardiovascular control mechanisms in humans, in vivo. PMID:18048451

The Muskrat. The Not-So-Common Oyster. The Horseshoe Crab. The Blue Crab. Learning Experiences for Coastal and Oceanic Awareness Studies, Nos. 108, 109, 111, 201. [Project COAST].

ERIC Educational Resources Information Center

Delaware Univ., Newark. Coll. of Education.

Included are four units related to coastal and oceanic awareness. The units are: (1) The Muskrat; (2) The Not-So-Common Oyster; (3) The Horseshoe Crab; and (4) The Blue Crab. All four units are designed for elementary school students. Each unit contains teacher background materials, student activity materials, evaluation materials, transparency…

75 FR 2165 - Puerto Rico Disaster No. PR-00007

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-14

... SMALL BUSINESS ADMINISTRATION [Disaster Declaration Nos. 12004 and 12005; Puerto Rico Disaster No. PR-00007] Puerto Rico Disaster No. PR-00007 AGENCY: U.S. Small Business Administration. ACTION... Puerto Rico dated 01/07/2010. Incident: Severe Storms and Flooding. Incident Period: 12/24/2009 through...

75 FR 65531 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2011-3 and CP2011-4; Order No. 556] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently... Postal Service contemporaneously filed a contract related to the proposed new product pursuant to 39 U.S...

75 FR 65532 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2011-2 and CP2011-3; Order No. 555] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently... Postal Service contemporaneously filed a contract related to the proposed new product pursuant to 39 U.S...

75 FR 80858 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2011-9 and CP2011-44; Order No. 610] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... Service contemporaneously filed a contract related to the proposed new product pursuant to 39 U.S.C. 3632...

75 FR 67148 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2011-5 Through CP2011-12; Order No. 557] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a.... at 4. The Postal Service concludes that its filings demonstrate that each of the new GEPS 3 contracts...

76 FR 592 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-05

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2011-55; Order No. 633] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently-filed Postal... demonstrate that the new GREP contract complies with the requirements of 39 U.S.C. 3633 and is functionally...

78 FR 51073 - Product List Update

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... POSTAL REGULATORY COMMISSION 39 CFR Part 3020 [Docket Nos. MC2012-49, et al.] Product List Update... competitive product list. This action reflects the disposition of recent dockets, as reflected in Commission... updates. The updates are identified in the body of this document. The product lists, which are republished...

77 FR 28410 - Product Change-Parcel Select Negotiated Service Agreement

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-14

... POSTAL SERVICE Product Change--Parcel Select Negotiated Service Agreement AGENCY: Postal Service\\TM\\. ACTION: Notice. SUMMARY: The Postal Service gives notice of filing a request with the Postal... Select Contract 1 to Competitive Product List. Documents are available at www.prc.gov , Docket Nos...

Calycosin and Formononetin Induce Endothelium-Dependent Vasodilation by the Activation of Large-Conductance Ca2+-Activated K+ Channels (BKCa).

PubMed

Tseng, Hisa Hui Ling; Vong, Chi Teng; Leung, George Pak-Heng; Seto, Sai Wang; Kwan, Yiu Wa; Lee, Simon Ming-Yuen; Hoi, Maggie Pui Man

2016-01-01

Calycosin and formononetin are two structurally similar isoflavonoids that have been shown to induce vasodilation in aorta and conduit arteries, but study of their actions on endothelial functions is lacking. Here, we demonstrated that both isoflavonoids relaxed rat mesenteric resistance arteries in a concentration-dependent manner, which was reduced by endothelial disruption and nitric oxide synthase (NOS) inhibition, indicating the involvement of both endothelium and vascular smooth muscle. In addition, the endothelium-dependent vasodilation, but not the endothelium-independent vasodilation, was blocked by BK Ca inhibitor iberiotoxin (IbTX). Using human umbilical vein endothelial cells (HUVECs) as a model, we showed calycosin and formononetin induced dose-dependent outwardly rectifying K + currents using whole cell patch clamp. These currents were blocked by tetraethylammonium chloride (TEACl), charybdotoxin (ChTX), or IbTX, but not apamin. We further demonstrated that both isoflavonoids significantly increased nitric oxide (NO) production and upregulated the activities and expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS). These results suggested that calycosin and formononetin act as endothelial BK Ca activators for mediating endothelium-dependent vasodilation through enhancing endothelium hyperpolarization and NO production. Since activation of BK Ca plays a role in improving behavioral and cognitive disorders, we suggested that these two isoflavonoids could provide beneficial effects to cognitive disorders through vascular regulation.

Calycosin and Formononetin Induce Endothelium-Dependent Vasodilation by the Activation of Large-Conductance Ca2+-Activated K+ Channels (BKCa)

PubMed Central

Tseng, Hisa Hui Ling; Vong, Chi Teng; Leung, George Pak-Heng; Seto, Sai Wang; Lee, Simon Ming-Yuen

2016-01-01

Calycosin and formononetin are two structurally similar isoflavonoids that have been shown to induce vasodilation in aorta and conduit arteries, but study of their actions on endothelial functions is lacking. Here, we demonstrated that both isoflavonoids relaxed rat mesenteric resistance arteries in a concentration-dependent manner, which was reduced by endothelial disruption and nitric oxide synthase (NOS) inhibition, indicating the involvement of both endothelium and vascular smooth muscle. In addition, the endothelium-dependent vasodilation, but not the endothelium-independent vasodilation, was blocked by BKCa inhibitor iberiotoxin (IbTX). Using human umbilical vein endothelial cells (HUVECs) as a model, we showed calycosin and formononetin induced dose-dependent outwardly rectifying K+ currents using whole cell patch clamp. These currents were blocked by tetraethylammonium chloride (TEACl), charybdotoxin (ChTX), or IbTX, but not apamin. We further demonstrated that both isoflavonoids significantly increased nitric oxide (NO) production and upregulated the activities and expressions of endothelial NOS (eNOS) and neuronal NOS (nNOS). These results suggested that calycosin and formononetin act as endothelial BKCa activators for mediating endothelium-dependent vasodilation through enhancing endothelium hyperpolarization and NO production. Since activation of BKCa plays a role in improving behavioral and cognitive disorders, we suggested that these two isoflavonoids could provide beneficial effects to cognitive disorders through vascular regulation. PMID:27994632

PILING PLAN OF SHIPBUILDING WAYS AND WHIRLEY CRANE SUPPORT. United ...

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

PILING PLAN OF SHIPBUILDING WAYS AND WHIRLEY CRANE SUPPORT. United Engineering Company Ltd., Alameda Shipbuilding Plant. General plan and two sections. James J. Walsh, Consulting Engineer. Sheet no. 2. Scales 1 inch to 10 feet, and 1/4 inch to one foot. April 20, 1941, revised 5/7/41. blueprint - United Engineering Company Shipyard, Shipway Nos. 1 & 2, 2900 Main Street, Alameda, Alameda County, CA

Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits.

PubMed

Marrachelli, Vannina G; Miranda, Francisco J; Centeno, José M; Burguete, María C; Castelló-Ruiz, María; Jover-Mengual, Teresa; Pérez, Antonio M; Salom, Juan B; Torregrosa, Germán; Alborch, Enrique

2010-02-01

Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10(-8) to 10(-4)M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10(-5)M), N(G)-nitro-l-arginine (10(-5)M) or tetraethylammonium (10(-5)M) did not modify relaxations to testosterone neither in control nor in diabetic rabbits. In endothelium-denuded arteries indomethacin enhanced the relaxant action of testosterone, both in control and diabetic rabbits. In arteries from diabetic rabbits, eNOS, iNOS and COX-1 expression and testosterone-induced release of thromboxane A(2) and prostacyclin were not significantly different from those observed in control rabbits. However, COX-2 expression was significantly lower in diabetic rabbits that in control rabbits. In nominally Ca(2+)-free medium, cumulative addition of CaCl2 (10(-5) to 3x10(-2)M) contracted previously depolarized arteries. Testosterone (10(-4)M) inhibited CaCl2 contractions of the renal artery both in control and diabetic rabbits. These results show that testosterone relaxes the renal artery both in control and diabetic rabbits. This relaxation is modulated by muscular thromboxane A(2), it is partially mediated by endothelial prostacyclin, and it involves the blocking of extracellular Ca2+ entry. Diabetes does not modify the mechanisms involved in the relaxant action of testosterone in the rabbit renal artery. Copyright 2009 Elsevier Ltd. All rights reserved.

Preservice teachers' use of lesson study in teaching nature of science

NASA Astrophysics Data System (ADS)

McDowell, Amy Virginia

The purpose of this study was to explore preservice teachers' lived experiences in a lesson study focused on teaching and learning nature of science (NOS). The body of knowledge about shifting pre- and in-service novice NOS understandings is substantial. The focus of science education research is now exploring ways to move these informed NOS understandings into classroom practice (Abd-El-Khalick & Lederman, 2000b). The research questions guiding the study were (a) how do preservice teachers' understandings of NOS shift as a result of the lesson study experience?, and (b) how does the reflective practice that occurs in lesson study influence preservice teachers' transition of NOS tenets into classroom practice? The participants in this study represented a sample of graduate preservice teachers, who were part of a middle and secondary science teaching alternative certification program in a southeastern university. In the first summer semester of this certification program, the participants were immersed in reform based science instruction; a section of which included NOS teachings (INTASC, 2002). In the following semester, participants were placed in a practicum setting; where the exploration of the preservice teachers' teaching of NOS was supported through the modified lesson study framework. Data sources included the Views on Nature of Science-Form B (VNOS-b), interviews, and lesson study portfolios. Analysis of NOS understandings was guided by instruments found in literature associated with the VNOS-b (Lederman et al., 2002) and reflection (Ward & McCotter, 2004). Results showed successful transfer of NOS into classroom practice using the modified lesson study framework, with less success in the deepening of participants' NOS understandings. Of particular significance was that results indicated a deepening of NOS pedagogical content knowledge for those participants functioning at higher levels of reflection. The study's results contributes to two knowledge bases. First it provides insight to how lesson study can be used in the United States in alterative teacher preparation programs. Second, it contributes to what is understood about how to support the transition of NOS understandings into classroom practice.

Involvement of AMPK, IKβα-NFκB and eNOS in the sildenafil anti-inflammatory mechanism in a demyelination model.

PubMed

Nunes, Ana Karolina Santana; Rapôso, Catarina; Rocha, Sura Wanessa Santos; Barbosa, Karla Patrícia de Sousa; Luna, Rayana Leal de Almeida; da Cruz-Höfling, Maria Alice; Peixoto, Christina Alves

2015-11-19

Sildenafil (Viagra®) has recently been found to have a neuroprotective effect, which occurs through the inhibition of inflammation and demyelination in the cerebellum. However, the mechanism of action of sildenafil remains unknown. AMPK, the regulatory protein of the lipid and glucose metabolism, plays a protective role by activating the eNOS enzyme. The production of a nanomolar concentration of NO by eNOS has an anti-inflammatory effect through the cGMP signaling pathway and plays an important role in the regulation of the nuclear transcription factor (NFkB), preventing the expression of inflammatory genes. The present study investigated whether AMPK-eNOS-NO-cGMP-IКβα-NFkB is involved in the mechanism of action of sildenafil in a cuprizone-demyelination model. Neuroinflammation and demyelination induced by cuprizone in rodents have been widely used as a model of MS. In the present study, five male C57BL/6 mice (7-10 weeks old) were used. Over a four week period, the groups received: cuprizone (CPZ) 0.2% mixed in feed; CPZ in the diet, combined with the administration of sildenafil (Viagra®, Pfizer, 25mg/kg) orally in drinking water, starting concurrently (sild-T0) or 15 days (sild-T15) after the start of CPZ. Control animals received pure food and water. The cerebella of the mice were dissected and processed for immunohistochemistry, immunofluorescence (frozen), western blotting and dosage of cytokines (Elisa). CPZ induced an increase in the expression of GFAP, IL-1β TNF-α, total NFkB and inactive AMPK, and prompt microglia activation. CPZ also induced a reduction of IKβα. The administration of sildenafil reduced the expression of the pro-inflammatory cytokines IL-1β and TNF-α and increased the expression of the anti-inflammatory cytokine IL-10. In addition, the administration of sildenafil reduced expression of GFAP, NFkB, inactive AMPK and iNOS, and increased IKβα. Interestingly, sildenafil also reduced levels of NGF. In general, the sild-T0 group was more effective than sild-T15 in improving clinical status and promoting the control of neuroinflammation. The present study offers evidence that sildenafil has anti-inflammatory and neuroprotective effects, which are probably achieved through modulation of AMPK-IKβα-NFκB signaling. In addition, eNOS may play a role in the sildenafil neuroprotective mechanism, contributing to the activation of AMPK. However, other pathways such as MAPK-NFkB and the downstream proteins AMPK (AMPK-SIRT1-NFκB) should also be further investigated. An understanding of these mechanisms of action is critical for the clinical use of sildenafil to control neuroinflammation in neurodegenerative diseases such as MS. Copyright © 2015 Elsevier B.V. All rights reserved.

A Multi-Year Program Developing an Explicit Reflective Pedagogy for Teaching Pre-service Teachers the Nature of Science by Ostention

NASA Astrophysics Data System (ADS)

Smith, Mike U.; Scharmann, Lawrence

2008-02-01

This investigation delineates a multi-year action research agenda designed to develop an instructional model for teaching the nature of science (NOS) to preservice science teachers. Our past research strongly supports the use of explicit reflective instructional methods, which includes Thomas Kuhn’s notion of learning by ostention and treating science as a continuum (i.e., comparing fields of study to one another for relative placement as less to more scientific). Instruction based on conceptual change precepts, however, also exhibits promise. Thus, the investigators sought to ascertain the degree to which conceptual change took place among students (n = 15) participating in the NOS instructional model. Three case studies are presented to illustrate successful conceptual changes that took place as a result of the NOS instructional model. All three cases represent students who claim a very conservative Christian heritage and for whom evolution was not considered a legitimate scientific theory prior to participating in the NOS instructional model. All three case study individuals, along with their twelve classmates, placed evolution as most scientific when compared to intelligent design and a fictional field of study called “Umbrellaology.”

Nuclear Interaction between ADR-Induced p65 and p53 Mediates Cardiac Injury in iNOS (−/−) Mice

PubMed Central

Cole, Marsha P.; Tangpong, Jitbanjong; Oberley, Terry D.; Chaiswing, Luksana; Kiningham, Kinsley K.; St. Clair, Daret K.

2014-01-01

Adriamycin (ADR) treatment causes an imbalance in the levels of nitric oxide (•NO) and superoxide (O2 •−) production leading to cardiac injury. Previously we demonstrated that mice lacking inducible nitric oxide synthase (iNOS) have increased oxidative stress and mitochondrial injury. The molecular events leading to increased mitochondrial injury in iNOS deficient mice is unknown. ADR in the absence of iNOS preferentially activates a proapoptotic pathway without a concurrent increase in prosurvival pathways. Treatment with ADR leads to an increase in DNA binding activity of nuclear factor kappa B (NFκB) and p53 in wildtype mice. Following ADR treatment, p53, but not NFκB DNA binding activity, as well as the level of Bax, a p53 target gene, was increased in iNOS (−/−) mice. This apoptotic signaling effect in iNOS (−/−) is alleviated by overexpression of manganese superoxide dismutase (MnSOD). Increases in NFκB and p53 in ADR-treated wildtype mice did not lead to increases in target genes such as MnSOD, bcl-xL, or Bax. Moreover, co-immunoprecipitation analysis revealed that p65, a prominent member of the NFκB family, interacts with p53 in the nucleus. These results suggest that NFκB and p53 may counter act one another's actions in ADR-treated wildtype (WT) mice. Further, these results identify a novel mechanism by which oxidative stress may regulate transcription of proapoptotic genes. PMID:24586632

Neuronal nitric oxide synthase mediates the effect of ethanol on IgA.

PubMed

Budec, Mirela; Markovic, Dragana; Vignjevic, Sanja; Mitrovic, Olivera; Dikic, Dragoslava; Koko, Vesna; Cokic, Vladan P

2013-01-01

We showed previously that the acute effect of ethanol on intestinal immunoglobulin A (IgA) expression might be mediated by endogenous nitric oxide (NO). To extend these findings, this study was designed to investigate a possible role of neuronal NO synthase (nNOS) in the observed phenomenon, using 7-nitroindazole (7-NI), a selective inhibitor of its activity. Adult male Wistar rats were treated with: (a) ethanol (4 g/kg, intraperitoneally, i.p.), (b) 7-NI (25 mg/kg, i.p.) followed by ethanol (4 g/kg, i.p.) 30 min later and (c) 7-NI (25 mg/kg, i.p.) followed by saline 30 min later. Untreated rats were used as controls. The concentrations of serum and intestinal IgA were measured by enzyme-linked immunosorbent assay, while the expression of nNOS was determined using western blot and immunohistochemistry. Acute ethanol treatment significantly increased the concentration of IgA in the ileal extracts, whereas it decreased its serum level. Inhibition of nNOS activity by 7-NI abolished this action of alcohol on IgA. Additionally, western blot analysis revealed that the acute alcohol administration induced an increase in the expression of intestinal nNOS. Furthermore, nNOS-immunoreactive cells, observed within the lamina propria of small intestine, were numerous in ethanol-treated rats. Taken together, these results extended our previous findings suggesting that nNOS mediates the acute effect of ethanol on IgA and supported an immunomodulatory role of this enzyme isoform.

Adult Literacy & Basic Skills Unit Newsletter. Nos. 32-35.

ERIC Educational Resources Information Center

Adult Literacy & Basic Skills Unit Newsletter, 1989

1989-01-01

This packet contains the four issues of a newsletter published in 1989 by the Adult Literacy & Basic Skills Unit in England. The Winter issue contains the following articles: "After the Act"; "An Evening at the Theatre"; "Horticulture: A Practical Project with Autistic Adults"; "Shared Reading"; and "Literacy and Adult Basic Education in…

77 FR 43867 - Notice of Intent To Grant Partially Exclusive License

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-26

...; Phone (281)244-7148; Fax (281) 483-6936. Information about other NASA inventions available for licensing... United States to practice the invention described and claimed in U.S. Patent Nos. 7,295,884 entitled... rights in these inventions have been assigned to the United States of America as represented by the...

77 FR 51780 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-27

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-42] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 62588 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-53] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 30972 - Empowering Consumers to Prevent and Detect Billing for Unauthorized Charges (“Cramming...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 64 [CG Docket Nos. 11-116 and 09-158; CC Docket No... (``Cramming''); Consumer Information and Disclosure; Truth-in-Billing Format AGENCY: Federal Communications Commission. ACTION: Proposed rule. SUMMARY: In this document, the Federal Communications Commission...

78 FR 50110 - Frozen Warmwater Shrimp From China, Ecuador, India, Indonesia, Malaysia, Thailand, and Vietnam...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-16

... INTERNATIONAL TRADE COMMISSION [Inv. Nos. 701-TA-491-497 (Final)] Frozen Warmwater Shrimp From China, Ecuador, India, Indonesia, Malaysia, Thailand, and Vietnam; Commission Determination To Deny a Request To Hold a Portion of a Hearing In Camera AGENCY: U.S. International Trade Commission. ACTION...

77 FR 35429 - Sunshine Act Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-13

...: Room 100, 500 E Street SW., Washington, DC 20436, Telephone: (202) 205-2000. Status: Open to the public... in Inv. Nos. 731-TA-865-867 (Second Review)(Stainless Steel Butt-Weld Fittings from Italy, Malaysia... Commissioners' opinions to the Secretary of Commerce on or before June 29, 2012. 5. Outstanding action jackets...

76 FR 76327 - Installation of Radiation Alarms for Rooms Housing Neutron Sources

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-07

... NUCLEAR REGULATORY COMMISSION 10 CFR Part 73 [Docket Nos. PRM-73-15; NRC-2011-0251] Installation of Radiation Alarms for Rooms Housing Neutron Sources AGENCY: Nuclear Regulatory Commission. ACTION: Petition for rulemaking; request for comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or the...

77 FR 45375 - Certain Liquid Crystal Display Devices, Including Monitors, Televisions, Modules, and Components...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-31

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 337-TA-741/749] Certain Liquid Crystal Display...; Termination of Investigation AGENCY: U.S. International Trade Commission. ACTION: Notice. SUMMARY: Notice is hereby given that the U.S. International Trade Commission has determined not to review initial...

75 FR 44292 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-28

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2010-32 and CP2010-77; Order No. 497] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... contract related to the proposed new product pursuant to 39 U.S.C. 3632(b)(3) and 39 CFR 3015.5. The...

75 FR 65533 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2011-1 and CP2011-2; Order No. 554] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a recently... contemporaneously filed a contract related to the proposed new product pursuant to 39 U.S.C. 3632(b)(3) and 39 CFR...

75 FR 80860 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-23

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2011-12 and CP2011-48; Order No. 613] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... filed a contract related to the proposed new product pursuant to 39 U.S.C. 3632(b)(3) and 39 CFR 3015.5...

75 FR 54401 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-07

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2010-102 and CP2010-103; Order No. 529] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... that each of the new GEPS 3 contracts complies with the requirements of 39 U.S.C. 3633 and is...

76 FR 12141 - New Postal Product and New Price Category

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2011-23 and CP2011-62; Order No. 683] New Postal Product and New Price Category AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The... competitive product list. The Postal Service also states that it has established a new price category under...

75 FR 18244 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2010-21 and CP2010-36; Order No. 437] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... contemporaneously filed a contract related to the proposed new product pursuant to 39 U.S.C. 3632(b)(3) and 39 CFR...

75 FR 65676 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-26

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2010-28 and CP2011-20 through CP2011-25; Order No. 564] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is... demonstrate that each of the new GEPS 3 contracts complies with the requirements of 39 U.S.C. 3633 and is...

75 FR 57995 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-23

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2010-116, CP2010-117, and CP2010-118; Order No. 541] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is... that each of the new GEPS 3 contracts complies with the requirements of 39 U.S.C. 3633 and is...

77 FR 304 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-04

... POSTAL REGULATORY COMMISSION [Docket Nos. MC2012-3 and CP2012-7; Order No. 1072] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing a... proposed new product under 39 U.S.C. 3632(b)(3) and 39 CFR 3015.5. Id. Attachment B. The instant contract...

75 FR 17175 - New Postal Product

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

... POSTAL REGULATORY COMMISSION [Docket Nos. CP2010-33, CP2010-34 and CP2010-35; Order No. 431] New Postal Product AGENCY: Postal Regulatory Commission. ACTION: Notice. SUMMARY: The Commission is noticing... differences. Id. at 6. The Postal Service contends that its filings demonstrate that each of the new GEPS 2...

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...

78 FR 14179 - Adjustments to Civil Monetary Penalty Amounts

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... SECURITIES AND EXCHANGE COMMISSION 17 CFR Part 201 [Release Nos. 33-9387; 34-68994; IA-3557; IC-30408] Adjustments to Civil Monetary Penalty Amounts AGENCY: Securities and Exchange Commission. ACTION... adjusting for inflation the maximum amount of civil monetary penalties under the Securities Act of 1933, the...

76 FR 18726 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-05

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-08] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD ACTION: Notice SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published...

77 FR 66432 - Request for Extension and Revision of a Currently Approved Information Collection for the...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-05

... DEPARTMENT OF AGRICULTURE Agricultural Marketing Service [Doc. Nos. AMS-TM-12-0050; TM-12-02... Market Questionnaire AGENCY: Agricultural Marketing Service, USDA. ACTION: Request for comments. SUMMARY... announces the Agricultural Marketing Service's (AMS) intention to request approval, from the Office of...

75 FR 69922 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-50] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69938 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-44] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 74011 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-24] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69971 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-58] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 48646 - 36(b)(1) Arms Sales Notifications

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-11

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-27, 10-31 and 10-41] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications...

75 FR 60424 - 36(b)(1) Arms Sales Notifications

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-28 and 10-30] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of two section 36(b)(1) arms sales notifications to...

75 FR 74014 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-30

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-49] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 37078 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-68] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 37071 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-03] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69931 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-46] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 29212 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-75] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69957 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-38] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69960 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-43] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 37075 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-77] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69947 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-45] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69953 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-57] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 69926 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-52] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

75 FR 56568 - Application Nos. and Proposed Exemptions; D-11400, Wasatch Advisors, Inc.; D-11585, Retirement...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-16

... DEPARTMENT OF LABOR Employee Benefits Security Administration [D-11400; D-11585; D-11603-07... AG; et al. AGENCY: Employee Benefits Security Administration, Labor. ACTION: Notice of proposed... Employee Benefits Security Administration (EBSA), Office of Exemption Determinations, Room N-5700, U.S...

75 FR 64641 - Facilitating Shareholder Director Nominations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-20

... SECURITIES AND EXCHANGE COMMISSION 17 CFR Parts 200, 232, 240, and 249 [Release Nos. 33-9151; 34...: Securities and Exchange Commission. ACTION: Final rule; notice of stay of effective and compliance dates. SUMMARY: By order dated October 4, 2010 (Release No. 33-9149, 34- 63031), the Securities and Exchange...

75 FR 70235 - Access to Confidential Business Information by Industrial Economics, Incorporated

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2010-11-17

... Industrial Economics, Incorporated AGENCY: Environmental Protection Agency (EPA). ACTION: Notice of Access to Data and Request for Comments. SUMMARY: EPA will authorize its contractor, Industrial Economics... Contracts Nos. GS-10F-0061N (EP10H000898) and EP-W-06- 065/0013, Industrial Economics, Incorporated (IEc...

Irish Educational Studies, Vol. 5, Nos. 1 and 2, 1985.

ERIC Educational Resources Information Center

Coolahan, John, Ed.

1986-01-01

This issue of "Irish Educational Studies" focuses on curriculum and learning issues and includes: (1) "Aesthetic Perspectives in Curriculum Reform" (D. Murphy); (2) "Drama: Less Talk, More Action" (M. Drury); (3)" Out of Tune with Reality: Music and the School in Ireland" (M. O'Suilleabhain); (4)…

76 FR 28888 - Amendment to Procedures for Holding Funds in Dormant Filing Fee Accounts

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-19

... SECURITIES AND EXCHANGE COMMISSION 17 CFR Part 202 [Release Nos. 33-9208; 34-64495; IC-29670] Amendment to Procedures for Holding Funds in Dormant Filing Fee Accounts AGENCY: Securities and Exchange Commission. ACTION: Final rule. SUMMARY: The Securities and Exchange Commission is amending its procedures...

78 FR 41040 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-09

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-27] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 14767 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-13

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-14] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 76823 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-69] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 74832 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-18

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-65] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 36536 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-25] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 60455 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-71] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 68738 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-40] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 62592 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-22

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-51] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 42709 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-24] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 40028 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-18] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 37884 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-25

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-19] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 15004 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-60] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 60467 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-34] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 42711 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-20] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 66338 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-55] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 60471 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-17] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 60457 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-74] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 48426 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-33] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 60461 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-27] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 72184 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-22

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-41] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 72182 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-22

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-40] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 36534 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-34] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 61673 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-05

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-30] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 60469 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-29

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-26] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 40701 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-79] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 72684 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-48] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 42707 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-20

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-35] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 71401 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-30

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-61] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

76 FR 56181 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-12

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-14] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

78 FR 66340 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-05

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-54] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

77 FR 68740 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-16

... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-49] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

Radical-Mediated Enzymatic Carbon Chain Fragmentation-Recombination

PubMed Central

Zhang, Qi; Li, Yuxue; Chen, Dandan; Yu, Yi; Duan, Lian; Shen, Ben; Liu, Wen

2010-01-01

The radical S-adenosylmethionine (S-AdoMet) superfamily contains thousands of proteins that catalyze highly diverse conversions, most of which are poorly understood due to a lack of information regarding chemical products and radical-dependent transformations. We here report that NosL, involved in forming the indole side ring of the thiopeptide nosiheptide (NOS), is a radical S-AdoMet 3-methyl-2-indolic acid (MIA) synthase. NosL catalyzed an unprecedented carbon chain reconstitution of L-Trp to give MIA, showing removal of the Cα-N unit and shift of the carboxylate to the indole ring. Dissection of the enzymatic process upon the identification of products and a putative glycyl intermediate uncovered a radical-mediated, unusual fragmentation-recombination reaction. This finding unveiled a key step in radical S-AdoMet enzyme-catalyzed structural rearrangements during complex biotransformations. Additionally, NosL tolerated fluorinated L-Trps as the substrates, allowing for production of a regiospecifically halogenated thiopeptide that has not been found in over 80 entity-containing, naturally occurring thiopeptide family. PMID:21240261

78 FR 23225 - Endangered Species; File Nos. 14759-01 and 16375-01

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-18

... brevirostrum) and Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus) for purposes of scientific research... Wildlife Research Unit, North Carolina State University, Raleigh, NC 27695 [Joseph Hightower: Responsible...

77 FR 61790 - Pacific Gas and Electric; Diablo Canyon Power Plant, Units 1 and 2; Application for Amendment to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-11

...; Diablo Canyon Power Plant, Units 1 and 2; Application for Amendment to Facility Operating License AGENCY... (PDR) reference staff at 1-800-397-4209, 301-415- 4737, or by email to [email protected] . The ADAMS... License Nos. DPR-80 and DPR-82 for the Diablo Canyon Power Plant, Units 1 and 2, located in San Luis...

Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression.

PubMed

Liebenberg, Nico; Joca, Sâmia; Wegener, Gregers

2015-04-01

We investigated whether the nitric oxide (NO) precursor, L-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-D-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine. Flinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) with L-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluated ex vivo in the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activity and cGMP concentration. L-Arginine pre-treatment prevented the antidepressant-like effect of ketamine in the FST, as well as a ketamine-induced increase in cGMP levels in the frontal cortex and hippocampus of FSL rats. Ketamine reduced cNOS activity only in the hippocampus, and this effect was not reversed by L-arginine. Both the behavioural and molecular results from this study indicate an involvement for the NO signalling pathway in the antidepressant action of ketamine. Although not easily interpretable, these findings broaden our knowledge of effects of ketamine on the NO system.

75 FR 60480 - In the Matter of Certain Bulk Welding Wire Containers and Components Thereof and Welding Wire...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

... Welding Wire Containers and Components Thereof and Welding Wire; Notice of Commission Determination To... within the United States after importation of certain bulk welding wire containers, components thereof, and welding wire by reason of infringement of certain claims of United States Patent Nos. 6,260,781; 6...

75 FR 14206 - FPL Energy Point Beach, LLC; Point Beach Nuclear Plant, Units 1 and 2; Environmental Assessment...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-24

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-266 And 50-301; NRC-2010-0123 FPL Energy Point Beach, LLC; Point Beach Nuclear Plant, Units 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 to...

75 FR 34776 - Florida Power & Light Company; Turkey Point Nuclear Generating Plant, Units 3 and 4...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-18

... changes to the reactor, fuel, plant, structures, support structures, water, or land at the Turkey Point... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-250 and 50-251; NRC-2010-0212] Florida Power & Light Company; Turkey Point Nuclear Generating Plant, Units 3 and 4; Environmental Assessment and Finding of No...

75 FR 13606 - Arizona Public Service Company, Palo Verde Nuclear Generating Station, Units 1, 2, and 3...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... NUCLEAR REGULATORY COMMISSION [Docket Nos. STN 50-528, STN 50-529, and STN 50-530; NRC-2010-0114] Arizona Public Service Company, Palo Verde Nuclear Generating Station, Units 1, 2, and 3; Environmental...-74, issued to Arizona Public Service Company (APS, the licensee), for operation of the Palo Verde...

76 FR 39445 - Northern States Power Company-Minnesota; Prairie Island Nuclear Generating Plant, Units 1 and 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-06

..., combined-cycle plant; a combination of natural gas, wind, and wood-fired generation and conservation; a... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-282 and 50-306; NRC-2009-0507] Northern States Power Company--Minnesota; Prairie Island Nuclear Generating Plant, Units 1 and 2; Notice of Issuance of Renewed...

Viscoelastic properties of levan polysaccharides

NASA Astrophysics Data System (ADS)

Noll, Kenneth; Rende, Deniz; Ozisik, Rahmi; Toksoy-Oner, Ebru

2014-03-01

Levan is a naturally occurring polysaccharide that is composed of β-D-fructofuranose units with β(2-6) linkages between fructose rings. It is synthesized by the action of a secreted levansucrase (EC 2.4.1.10) that converts sucrose into the levan externally (exopolysaccharide). Levan is a homopolysaccharide that is non-toxic, water soluble,, and has anti-tumor activity and low immunological response. Therefore, levan presents great potential to be used as a novel functional biopolymer in foods, feeds, cosmetics, pharmaceutical and chemical industries. Despite these favorable properties, levan has a moderately low mechanical properties and poor film forming capability. In the current study, the agglomeration behavior of levan in water and in saline solutions was investigated at 298 and 310 K by dynamic light scattering and transmission electron microscopy (TEM). The viscoelastic properties of neat and oxidized levan films were studied via nanoindentation experiments in the quasi-static and dynamic modes The material is partially based upon work supported by NSF under Grant Nos. 1200270 and 1003574, and TUBITAK 111M232.

Endothelial Nitric Oxide Synthase (G894T) Gene Polymorphism in a Random Sample of the Egyptian Population: Comparison with Myocardial Infarction Patients

PubMed Central

Abdel Rahman, Mohamed F.; Hashad, Ingy M.; Abdel-Maksoud, Sahar M.; Farag, Nabil M.; Abou-Aisha, Khaled

2012-01-01

Aim: The aim of this study was to detect endothelial nitric oxide synthase (eNOS) Glu298Asp gene variants in a random sample of the Egyptian population, compare it with those from other populations, and attempt to correlate these variants with serum levels of nitric oxide (NO). The association of eNOS genotypes or serum NO levels with the incidence of acute myocardial infarction (AMI) was also examined. Methods: One hundred one unrelated healthy subjects and 104 unrelated AMI patients were recruited randomly from the 57357 Hospital and intensive care units of El Demerdash Hospital and National Heart Institute, Cairo, Egypt. eNOS genotypes were determined by polymerase chain reaction–restriction fragment length polymorphism. Serum NO was determined spectrophotometrically. Results: The genotype distribution of eNOS Glu298Asp polymorphism determined for our sample was 58.42% GG (wild type), 33.66% GT, and 7.92% TT genotypes while allele frequencies were 75.25% and 24.75% for G and T alleles, respectively. No significant association between serum NO and specific eNOS genotype could be detected. No significant correlation between eNOS genotype distribution or allele frequencies and the incidence of AMI was observed. Conclusion: The present study demonstrated the predominance of the homozygous genotype GG over the heterozygous GT and homozygous TT in random samples of Egyptian population. It also showed the lack of association between eNOS genotypes and mean serum levels of NO, as well as the incidence of AMI. PMID:22731641

Nitric oxide alterations following acute ductal constriction in the fetal lamb: a role for superoxide

PubMed Central

Hsu, Jong-Hau; Oishi, Peter; Wiseman, Dean A.; Hou, Yali; Chikovani, Omar; Datar, Sanjeev; Sajti, Eniko; Johengen, Michael J.; Harmon, Cynthia; Black, Stephen M.

2010-01-01

Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2–4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000–1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular response to acute ductal constriction. PMID:20363848

Quantitative Analysis of Representations of Nature of Science in Nordic Upper Secondary School Textbooks Using Framework of Analysis Based on Philosophy of Chemistry

NASA Astrophysics Data System (ADS)

Vesterinen, Veli-Matti; Aksela, Maija; Lavonen, Jari

2013-07-01

The aim of this study was to assess how the different aspects of nature of science (NOS) were represented in Finnish and Swedish upper secondary school chemistry textbooks. The dimensions of NOS were analyzed from five popular chemistry textbook series. The study provides a quantitative method for analysis of representations of NOS in chemistry textbooks informed by domain-specific research on the philosophy of chemistry and chemical education. The selection of sections analyzed was based on the four themes of scientific literacy: knowledge of science, investigate nature of science, science as a way of thinking, and interaction of science, technology and society. For the second round of analysis the theme of science as a way of thinking was chosen for a closer inspection. The units of analysis in this theme were analyzed using seven domain specific dimensions of NOS: tentative, empirical, model-based, inferential, technological products, instrumentation, and social and societal dimensions. Based on the inter-rater agreement, the procedure and frameworks of analysis presented in this study was a reliable way of assessing the emphasis given to the domain specific aspects of NOS. All textbooks have little emphasis on the theme science as a way of thinking on a whole. In line with the differences of curricula, Swedish textbooks emphasize the tentative dimension of NOS more than Finnish textbooks. To provide teachers with a sufficiently wide variety of examples to discuss the different dimensions of NOS changes to the national core curricula are needed. Although changing the emphasis of the curricula would be the most obvious way to affect the emphasis of the textbooks, other efforts such as pre- and in-service courses for developing teachers understanding of NOS and pedagogic approaches for NOS instruction to their classroom practice might also be needed.

Endothelial cellular senescence is inhibited by nitric oxide: Implications in atherosclerosis associated with menopause and diabetes

PubMed Central

Hayashi, Toshio; Matsui-Hirai, Hisako; Miyazaki-Akita, Asaka; Fukatsu, Akiko; Funami, Jun; Ding, Qun-Fang; Kamalanathan, Sumitra; Hattori, Yuichi; Ignarro, Louis J.; Iguchi, Akihisa

2006-01-01

Senescence may contribute to the pathogenesis of atherosclerosis. Although the bioavailability of nitric oxide (NO) is limited in senescence, the effect of NO on senescence and its relationship to cardiovascular risk factors have not been investigated fully. We studied these factors by investigating senescence-associated β-galactosidase (SA-β-gal) and human telomerase activity in human umbilical venous endothelial cells (HUVECs). Treatment with NO donor (Z)-1-[2-(2-aminoethyl)-N-(2-aminoethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO) and transfection with endothelial NO synthase (eNOS) into HUVECs each decreased the number of SA-β-gal positive cells and increased telomerase activity. The NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) abolished the effect of eNOS transfection. The physiological concentration of 17β-estradiol activated hTERT, decreased SA-β-gal-positive cells, and caused cell proliferation. However, ICI 182780, an estrogen receptor-specific antagonist, and l-NAME each inhibited these effects. Finally, we investigated the effect of NO bioavailability on high glucose-promoted cellular senescence of HUVECs. Inhibition by eNOS transfection of this cellular senescence under high glucose conditions was less pronounced. Treatment with l-arginine or l-citrulline of eNOS-transfected cells partially inhibited, and combination of l-arginine and l-citrulline with antioxidants strongly prevented, high glucose-induced cellular senescence. These data demonstrate that NO can prevent endothelial senescence, thereby contributing to the anti-senile action of estrogen. The ingestion of NO-boosting substances, including l-arginine, l-citrulline, and antioxidants, can delay endothelial senescence under high glucose. We suggest that the delay in endothelial senescence through NO and/or eNOS activation may have clinical utility in the treatment of atherosclerosis in the elderly. PMID:17075048

TNF-alpha infusion impairs corpora cavernosa reactivity.

PubMed

Carneiro, Fernando S; Zemse, Saiprazad; Giachini, Fernanda R C; Carneiro, Zidonia N; Lima, Victor V; Webb, R Clinton; Tostes, Rita C

2009-03-01

Erectile dysfunction (ED), as well as cardiovascular diseases (CVDs), is associated with endothelial dysfunction and increased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha). We hypothesized that increased TNF-alpha levels impair cavernosal function. In vitro organ bath studies were used to measure cavernosal reactivity in mice infused with vehicle or TNF-alpha (220 ng/kg/min) for 14 days. Gene expression of nitric oxide synthase isoforms was evaluated by real-time polymerase chain reaction. Corpora cavernosa from TNF-alpha-infused mice exhibited decreased nitric oxide (NO)-dependent relaxation, which was associated with decreased endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) cavernosal expression. Cavernosal strips from the TNF-alpha-infused mice displayed decreased nonadrenergic-noncholinergic (NANC)-induced relaxation (59.4 +/- 6.2 vs. control: 76.2 +/- 4.7; 16 Hz) compared with the control animals. These responses were associated with decreased gene expression of eNOS and nNOS (P < 0.05). Sympathetic-mediated, as well as phenylephrine (PE)-induced, contractile responses (PE-induced contraction; 1.32 +/- 0.06 vs. control: 0.9 +/- 0.09, mN) were increased in cavernosal strips from TNF-alpha-infused mice. Additionally, infusion of TNF-alpha increased cavernosal responses to endothelin-1 and endothelin receptor A subtype (ET(A)) receptor expression (P < 0.05) and slightly decreased tumor necrosis factor-alpha receptor 1 (TNFR1) expression (P = 0.063). Corpora cavernosa from TNF-alpha-infused mice display increased contractile responses and decreased NANC nerve-mediated relaxation associated with decreased eNOS and nNOS gene expression. These changes may trigger ED and indicate that TNF-alpha plays a detrimental role in erectile function. Blockade of TNF-alpha actions may represent an alternative therapeutic approach for ED, especially in pathologic conditions associated with increased levels of this cytokine.

Suppressed G-protein-coupled receptor kinase 2 activity protects female diabetic-mouse aorta against endothelial dysfunction.

PubMed

Taguchi, K; Matsumoto, T; Kamata, K; Kobayashi, T

2013-01-01

Pre-menopausal women have less cardiovascular disease and lower cardiovascular morbidity and mortality than men the same age. Previously, we noted in mice that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the Akt/eNOS pathway in male diabetic aortas and that endothelial function via the Akt/eNOS pathway is less affected in female diabetic aortas. The cellular mechanisms underlying these sex differences remain unclear. We aimed to investigate the ways in which GRK2 might modulate vascular functions in male and female diabetic mice (DM). Vascular functions were examined in aortic rings. GRK2, β-arrestin 2 and Akt/eNOS-signalling-pathway protein levels and activities were assayed by Western blotting. Phenylephrine-induced contraction was greater, while both clonidine-induced and insulin-induced relaxations were weaker (vs. male controls), in aortas from male type 2 DM, suggesting impairments of the Akt/eNOS pathway and α-adrenoceptor function. GRK2-inhibitor reversed only the impairment in Akt/eNOS-pathway-mediated relaxation in male DM. Increases in GRK2 activity, GRK2 expression in the membrane, plasma Ang II and systolic blood pressure were seen in male DM (vs. male controls) but not in female DM; these increases were attenuated by GRK2-inhibitor treatment. Repeatedly obtaining clonidine concentration-response curves led to reduced relaxation in male and in female DM aortas, indicating similar desensitization between female DM and male DM. This effect was reversed by GRK2-inhibitor in both sexes. GRK2 plays a key role in modulating the aortic vasodilator effect of clonidine by selectively affecting the Akt/eNOS pathway. This action of GRK2 is more powerful in male than in female DM. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

Evidence for a pathogenic role of nitric oxide in inflammation-induced osteoporosis.

PubMed

Armour, K E; Van'T Hof, R J; Grabowski, P S; Reid, D M; Ralston, S H

1999-12-01

Inflammatory disease is associated with increased production of nitric oxide (NO) and activation of the inducible nitric oxide synthase (iNOS) pathway. Several studies have addressed the role of NO as a mediator of cytokine effects on bone cell activity in vitro. Stimulatory and inhibitory actions have been found, however, depending on the concentrations produced and model system used. In view of this, it has been difficult to predict whether increased production of NO during inflammation is likely to increase bone loss or prevent it. We have investigated the pathogenic role of NO in an animal model of inflammation-induced osteoporosis (IMO). NO production was increased in IMO when compared with controls (+344%; p < 0.01), and this was accompanied by activation of inducible NOS (iNOS) in the bone marrow space. Bone mineral density (BMD) was reduced in IMO when compared with controls (-64%; p < 0.01), and this was found to be associated with reduced osteoblast numbers (-44%; p < 0.05) and increased osteoclast numbers (+38%; p < 0.01). The NOS inhibitor L-NMMA reversed the deleterious effects of IMO on bone mass and bone turnover, but L-NMMA had no effect on bone mass in control animals. This study has important implications for many inflammatory diseases such as rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel disease which are associated with increased NO production and osteoporosis. Our data not only suggest that iNOS activation and increased NO production contribute to the pathogenesis of osteoporosis in these situations, but also suggest that NOS inhibitors could be of therapeutic value in the prevention and treatment of such bone loss.

78 FR 36711 - Food and Drug Administration Safety and Innovation Act Title VII-Drug Supply Chain; Standards for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-19

...: Food and Drug Administration, HHS. ACTION: Notification of public meeting; request for comments. SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing a public meeting regarding FDA's... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Chapter I [Docket Nos...

78 FR 6673 - National Emission Standards for Hazardous Air Pollutants for Reciprocating Internal Combustion...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

... include alternative testing options for certain large spark ignition (generally natural gas-fueled... action under Docket ID No. EPA-HQ-OAR-2008-0708. The EPA also relies on materials in Docket ID Nos. EPA... Business Information or other information whose disclosure is restricted by statute. Certain other material...

77 FR 71712 - Lifeline and Link Up Reform and Modernization, Advancing Broadband Availability Through Digital...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-04

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 54 [WC Docket Nos. 11-42; 03-109; 12-23 and CC Docket No. 96-45; FCC 12- 11] Lifeline and Link Up Reform and Modernization, Advancing Broadband Availability Through Digital Literacy Training AGENCY: Federal Communications Commission. ACTION: Final rule...

77 FR 25609 - Lifeline and Link Up Reform and Modernization, Advancing Broadband Availability Through Digital...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-01

... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Part 54 [WC Docket Nos. 11-42, 03-109, 12-23 and CC Docket No. 96-45; FCC 12- 11] Lifeline and Link Up Reform and Modernization, Advancing Broadband Availability Through Digital Literacy Training AGENCY: Federal Communications Commission. ACTION: Final rule...

77 FR 38533 - Lifeline and Link Up Reform and Modernization, Advancing Broadband Availability Through Digital...

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21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

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... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

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... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

Code of Federal Regulations, 2014 CFR

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... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

Code of Federal Regulations, 2011 CFR

2011-04-01

... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

21 CFR 520.2610 - Trimethoprim and sulfadiazine tablets.

Code of Federal Regulations, 2012 CFR

2012-04-01

... consecutive days. (5) During long term treatment, periodic platelet counts and white and red blood cell counts.... See Nos. 000061 and 000856 in § 510.600(c) of this chapter. (c) Conditions of use. (1) The drug is used in dogs where systemic antibacterial action against sensitive organisms is required, either alone...

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Regulation of endothelial nitric oxide synthase: involvement of protein kinase G 1 beta, serine 116 phosphorylation and lipid structures.

PubMed

John, Theresa A; Ibe, Basil O; Raj, J Usha

2008-02-01

1. Endothelial nitric oxide synthase (NOS3) is important for vascular homeostasis. The role of protein kinase G (PKG) in regulation of NOS3 activity was studied in primary cultures of newborn lamb lung microvascular endothelial cells (LMVEC). 2. We determined the presence of PKG in fetal and neonatal LMVEC as well as subcellular localization of PKG isoforms in the neonatal cells by fluorescence immunohistochemistry. We used diaminofluorescein (DAF) fluorophore to measure nitric oxide (NO) production from neonatal LMVEC. We confirmed that NO measured was from constitutive NOS3 by inhibiting it with NOS inhibitors. 3. To identify a role for PKG in basal NO production, we measured NO release from LMVEC cells using 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM; 0.5-0.8 micromol/L) with and without prior stimulation with the PKG activator 8-bromo-cGMP (8-Br-cGMP; 0.3 and 3 micromol/L) or prior PKG inhibition with beta-phenyl-1,N2-etheno-8-bromoguanosine-3',5'-cyclic monophosphorothionate (BPC; 0.3 and 3 micromol/L). With the same drugs, we determined the role of PKG on cellular expression of NOS3 and serine 116 phosphorylated NOS (pSer116-NOS) by qualitative and quantitative immunofluorescence assays, as well as western blotting. 4. Because PKG 1 beta was distributed throughout the cytosol in a punctate expression, we used 2 mmol/L cyclodextrin, a cholesterol extractor, to determine a role for lipid vesicles in PKG regulation of NO production. 5. Protein kinase G 1 beta gave a punctate appearance, indicating its presence in intracellular vesicles. Nitric oxide production decreased by approximately 20% with 300 nmol/L and 3 micromol/L 8-Br cGMP (P < 0.05) and increased by 20.8 +/- 3.7% with 3 micromol/L BPC (P < 0.001), indicating that both stimulated and basal PKG activity has inhibitory effects on basal NOS3 function. Nitric oxide synthase immunofluorescence and immunoblot expression were decreased and pSer116-NOS immunofluorescence was increased by 800 nmol/L 8-Br-cGMP and 170 micromol/L (Z)-1-[2-(2-aminoethyl)-N-(2-ammonio-ethyl)amino]diazen-1-ium-1, 2-diolate (DETANONOate). The effect of cyclodextrin indicated that cholesterol extraction interfered with PKG inhibition of NOS. Further examination of pSer116-NOS by immunohistochemistry showed it abundant in the endoplasmic reticulum and colocalized with PKG 1 beta, especially in nuclear vesicles. 6. We conclude that endothelial PKG is involved in endogenous regulation of basal NOS3 activity with the involvement of lipid structures, the endoplasmic reticulum and the nucleus. Protein kinase G 1 beta is colocalized with pSer116-NOS, indicating that PKG action may involve serine 116 phosphorylation on NOS.

Follicular expression of pro-inflammatory cytokines tumour necrosis factor-α (TNFα), interleukin 6 (IL6) and their receptors in cattle: TNFα, IL6 and macrophages suppress thecal androgen production in vitro.

PubMed

Samir, Moafaq; Glister, Claire; Mattar, Dareen; Laird, Mhairi; Knight, Phil G

2017-07-01

Pro-inflammatory cytokines secreted by macrophages and other cell types are implicated as intraovarian factors affecting different aspects of ovarian function including follicle and corpus luteum 'turnover', steroidogenesis and angiogenesis. Here, we compared granulosal (GC) and thecal (TC) expression of TNF, IL6 and their receptors (TNFRSF1A, TNFRSF1B and IL6R) during bovine antral follicle development; all five mRNA transcripts were detected in both GC and TC and statistically significant cell-type and follicle stage-related differences were evident. Since few studies have examined cytokine actions on TC steroidogenesis, we cultured TC under conditions that retain a non-luteinized 'follicular' phenotype and treated them with TNFα and IL6 under basal and LH-stimulated conditions. Both TNFα and IL6 suppressed androgen secretion concomitantly with CYP17A1 and LHCGR mRNA expression. In addition, TNFα reduced INSL3, HSD3B1 and NOS3 expression but increased NOS2 expression. IL6 also reduced LHCGR and STAR expression but did not affect HSD3B1, INSL3, NOS2 or NOS3 expression. As macrophages are a prominent source of these cytokines in vivo , we next co-cultured TC with macrophages and observed an abolition of LH-induced androgen production accompanied by a reduction in CYP17A1, INSL3, LHCGR, STAR, CYP11A1 and HSD3B1 expression. Exposure of TC to bacterial lipopolysaccharide also blocked LH-induced androgen secretion, an effect reduced by a toll-like receptor blocker (TAK242). Collectively, the results support an inhibitory action of macrophages on thecal androgen production, likely mediated by their secretion of pro-inflammatory cytokines that downregulate the expression of LHCGR, CYP17A1 and INSL3. Bovine theca interna cells can also detect and respond directly to lipopolysaccharide. © 2017 Society for Reproduction and Fertility.

Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α.

PubMed

Pang, Yefei; Dong, Jing; Thomas, Peter

2015-05-15

Progesterone exerts beneficial effects on the human cardiovascular system by inducing rapid increases in nitric oxide (NO) production in vascular endothelial cells, but the receptors mediating these nongenomic progesterone actions remain unclear. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that progesterone binds to plasma membranes of HUVECs with the characteristics of membrane progesterone receptors (mPRs). The selective mPR agonist Org OD 02-0 had high binding affinity for the progesterone receptor on HUVEC membranes, whereas nuclear PR (nPR) agonists R5020 and medroxyprogesterone acetate displayed low binding affinities. Immunocytochemical and Western blot analyses confirmed that mPRs are expressed in HUVECs and are localized on their plasma membranes. NO levels increased rapidly after treatment with 20 nM progesterone, Org OD 02-0, and a progesterone-BSA conjugate but not with R5020, suggesting that this progesterone action is at the cell surface and initiated through mPRs. Progesterone and Org OD 02-0 (20 nM) also significantly increased endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation. Knockdown of mPRα expression by treatment with small-interfering RNA (siRNA) blocked the stimulatory effects of 20 nM progesterone on NO production and eNOS phosphorylation, whereas knockdown of nPR was ineffective. Treatment with PI3K/Akt and MAP kinase inhibitors blocked the stimulatory effects of progesterone, Org OD 02-0, and progesterone-BSA on NO production and eNOS phosphorylation and also prevented progesterone- and Org OD 02-0-induced increases in Akt and ERK phosphorylation. The results suggest that progesterone stimulation of NO production in HUVECs is mediated by mPRα and involves signaling through PI3K/Akt and MAP kinase pathways. Copyright © 2015 the American Physiological Society.

Hexane extracts of Polygonum multiflorum improve tissue and functional outcome following focal cerebral ischemia in mice.

PubMed

Lee, Soo Vin; Choi, Kyung Ha; Choi, Young Whan; Hong, Jin Woo; Baek, Jin Ung; Choi, Byung Tae; Shin, Hwa Kyoung

2014-04-01

Polygonum multiflorum is a traditional Korean medicine that has been utilized widely in East Asian countries as a longevity agent. Clinical studies have demonstrated that Polygonum multiflorum improves hypercholesterolemia, coronary heart disease, neurosis and other diseases commonly associated with aging. However, scientific evidence defining the protective effects and mechanisms of Polygonum multiflorum against ischemic stroke is incomplete. In the present study, we investigated the cerebrovascular protective effects of Polygonum multiflorum against ischemic brain injury using an in vivo photothrombotic mouse model. To examine the underlying mechanism of action, we utilized an in vitro human brain microvascular endothelial cell (HBMEC) culture system. Hexane extracts (HEPM), ethyl acetate extracts (EAEPM) and methanol extracts (MEPM) of Polygonum multiflorum (100 mg/kg) were administered intraperitoneally 30 min prior to ischemic insult. Focal cerebral ischemia was induced in C57BL/6J mice and endothelial nitric oxide synthase knockout (eNOS KO) mice by photothrombotic cortical occlusion. We evaluated the infarct volume, as well as neurological and motor function, 24 h after ischemic brain injury. Following ischemic insult, HEPM induced a significant reduction in infarct volume and subsequent neurological deficits, compared with EAEPM and MEPM. HEPM significantly decreased infarct size and improved neurological and motor function, which was not observed in eNOS KO mice, suggesting that this cerebroprotective effect is primarily an eNOS-dependent mechanism. In vitro, HEPM effectively promoted NO production, however these effects were inhibited by the NOS inhibitor, L-NAME and the PI3K/Akt inhibitor, LY-294002. Furthermore, HEPM treatment resulted in increased phosphorylation-dependent activation of Akt and eNOS in HBMEC, suggesting that HEPM increased NO production via phosphorylation-dependent activation of Akt and eNOS. In conclusion, HEPM prevents cerebral ischemic damage through an eNOS-dependent mechanism, and thus may have clinical applications as a protective agent against neurological injury in stroke.

Epigallocatechin-3-Gallate Reduces Neuronal Apoptosis in Rats after Middle Cerebral Artery Occlusion Injury via PI3K/AKT/eNOS Signaling Pathway

PubMed Central

Zhonghang, Xu; Tongtong, Liu; Wanshu, Guo

2018-01-01

Background/Aims Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. Methods Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL. Oxidative stress and brain injury markers were examined using ELISA. Apoptosis-related proteins and PI3K/AKT/eNOS signaling pathway were determined using western blot assay and immunohistochemistry. Results EGCG decreased neurological function score, protected nerve cells, inhibited neuronal apoptosis, and inhibited oxidative stress injury and brain injury markers level after MCAO. EGCG reduced the apoptotic rate of neurons, increased the expression of Bcl-2, and decreased the expression of Caspase-3 and Bax. After LY294002 suppressed the PI3K pathway, the protective effect of EGCG decreased after administration of PI3K inhibitors. Conclusion EGCG has a protective effect on rat brain injury induced by MCAO, possibly by modulating the PI3K/AKT/eNOS signaling pathway. PMID:29770336

Neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole augment the effects of antidepressants acting via serotonergic system in the forced swimming test in rats.

PubMed

Ulak, Güner; Mutlu, Oguz; Akar, Füruzan Yildiz; Komsuoğlu, F Ipek; Tanyeri, Pelin; Erden, B Faruk

2008-10-01

Treatment-resistant depression has necessitated new therapeutic strategies in augmenting the therapeutic actions of currently existing antidepressant drugs. The aim of this study was to investigate the possibility of synergistic interaction between 1-(2-trifluoromethylphenyl)-imidazole (TRIM), a novel neuronal nitric oxide synthase (nNOS) inhibitor and conventional antidepressants of different classes in the forced swimming test (FST) in rats. TRIM decreased the immobility time at 50 mg/kg doses in the FST in rats. Treatment with a behaviourally subeffective dose of TRIM (20 mg/kg) augmented the behavioural effect of tricyclic antidepressant imipramine, selective serotonin re-uptake inhibitor (SSRI) citalopram and fluoxetine or selective serotonin reuptake enhancer tianeptine but failed to augment the antidepressant effect of reboxetine, a noradrenaline re-uptake inhibitor, in this test. Therefore inhibition of NOS augments the effects of antidepressants acting on serotonergic system in the FST. Neither TRIM (10-50 mg/kg) nor other drug treatments affected the locomotor activity of animals. These findings are in agreement with the view that antidepressant effects or augmentation of these effects in the FST may be explained with inhibition of NOS activity and this may be a new approach in offering greater therapeutic efficacy of antidepressants acting via serotonergic system.

Enhancing Nanos expression via the bacterial TomO protein is a conserved strategy used by the symbiont Wolbachia to fuel germ stem cell maintenance in infected Drosophila females.

PubMed

Ote, Manabu; Yamamoto, Daisuke

2018-04-27

The toxic manipulator of oogenesis (TomO) protein has been identified in the wMel strain of Wolbachia that symbioses with the vinegar fly Drosophila melanogaster, as a protein that affects host reproduction. TomO protects germ stem cells (GSCs) from degeneration, which otherwise occurs in ovaries of host females that are mutant for the gene Sex-lethal (Sxl). We isolated the TomO homologs from wPip, a Wolbachia strain from the mosquito Culex quinquefasciatus. One of the homologs, TomO w Pip 1, exerted the GSC rescue activity in fly Sxl mutants when lacking its hydrophobic stretches. The GSC-rescuing action of the TomO w Pip 1 variant was ascribable to its abilities to associate with Nanos (nos) mRNA and to enhance Nos protein expression. The analysis of structure-activity relationships with TomO homologs and TomO deletion variants revealed distinct modules in the protein that are each dedicated to different functions, i.e., subcellular localization, nos mRNA binding or Nos expression enhancement. We propose that modular reshuffling is the basis for structural and functional diversification of TomO protein members. © 2018 Wiley Periodicals, Inc.

78 FR 24761 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting

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Demonstration of nitric oxide synthase activity in crustacean hemocytes and anti-microbial activity of hemocyte-derived nitric oxide.

PubMed

Yeh, Feng-Ching; Wu, Su-Hua; Lai, Chi-Yung; Lee, Chi-Ying

2006-05-01

We determined the biochemical characteristics of nitric oxide synthase (NOS) in hemocytes of the crayfish Procambarus clarkii and investigated the roles of hemocyte-derived NO in host defense. Biochemical analysis indicated the presence of a Ca2+ -independent NOS activity, which was elevated by lipopolysaccharide (LPS) treatment. When bacteria (Staphylococcus aureus) and hemocytes were co-incubated, adhesion of bacteria to hemocytes was observed. NO donor sodium nitroprusside (SNP) significantly increased the numbers of hemocytes to which bacteria adhered. Similarly, LPS elicited bacterial adhesion and the LPS-induced adhesion was prevented by NOS inhibitor NG-monomethyl-L-arginine (L-NMMA). Finally, plate count assay demonstrated that addition of LPS to the hemocytes/bacteria co-incubation resulted in a significant decrease in bacterial colony forming unit (CFU), and that L-NMMA reversed the decreasing effect of LPS on CFU. The combined results demonstrate the presence of a Ca2+ -independent LPS-inducible NOS activity in crayfish hemocytes and suggest that hemocyte-derived NO is involved in promoting bacterial adhesion to hemocytes and enhancing bactericidal activity of hemocytes.

Recapitulating the History of Sickle-Cell Anemia Research: Improving Students' NOS Views Explicitly and Reflectively

NASA Astrophysics Data System (ADS)

Howe, Eric Michael; Wÿss Rudge, David

This paper provides an argument in favor of a specific pedagogical method of using the history of science to help students develop more informed views about nature of science (NOS) issues. The paper describes a series of lesson plans devoted to encouraging students to engage, unbeknownst to them, in similar reasoning that led scientists to understand sickle-cell anemia from the perspective of multiple subdisciplines in biology. Students pursue their understanding of a "mystery disease"; by means of a series of open-ended problems that invite them to discuss it from the perspective of anatomy, physiology, ecology, evolution, and molecular and cell biology. Throughout this unit, instructors incorporate techniques that invite students to explicitly and reflectively discuss various NOS issues with reference to this example and more generally. It is argued on the grounds of constructivist tenets that this pedagogy has substantial advantages over more implicit approaches. The findings of an empirical study using an open-ended survey and follow-up, semi-structured interviews to assess students' pre- and post-instruction NOS conceptions support the efficacy of this approach.

[Quality of life of people with severe dementia in nursing oases: empirical results and methodological implications].

PubMed

Brandenburg, H

2013-07-01

Nursing oases (NOs) are a variant of segregated care for people with severe dementia in nursing homes. They can be understood as a constant living arrangement in one room for 4-7 persons with a special care concept and environmental design. During the daytime nurses are permanently present. Quality of life (QoL) is the focus because the efficacy of medical and nursing interventions should include measurement of QoL. There is a controversy whether NOs are really different from the traditional caring settings in long-term care. Advocates see NOs as a substantial contribution to improve QoL, especially for people with severe dementia but critics fear a rollback to the era of multibed rooms in nursing homes and emphasize the risk of losing autonomy. This article is differentiated into four parts. Firstly, reasons are given why NOs are an option for a professional and adequate fulfillment of needs for people with severe dementia and a definition of NOs is given. Secondly, selected results of NOs studies in Germany are shown which have mainly documented positive effects. Thirdly, on the background of US American research into Special Care Units methodological questions are discussed. The focus is on designs and the utilization of standardized and non-standardized instruments. In the concluding remarks it is discussed whether QoL is an adequate indicator of a good life for people with severe dementia in long-term care.

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 room-air samples. Our preliminary data show that N2O induced a selective increase in nNOS and p53 transcription. These new findings provide evidence of pro-apoptotic action by N2O and may shed new insight on its toxic effects; however, further investigations are necessary.

Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation

PubMed Central

Bonini, Marcelo G.; Stadler, Krisztian; de Oliveira Silva, Sueli; Corbett, Jean; Dore, Michael; Petranka, John; Fernandes, Denise C.; Tanaka, Leonardo Y.; Duma, Danielle; Laurindo, Francisco R. M.; Mason, Ronald P.

2008-01-01

The physiological effects of nitroglycerin as a potent vasodilator have long been documented. However, the molecular mechanisms by which nitroglycerin exerts its biological functions are still a matter of intense debate. Enzymatic pathways converting nitroglycerin to vasoactive compounds have been identified, but none of them seems to fully account for the reported clinical observations. Here, we demonstrate that nitroglycerin triggers constitutive nitric oxide synthase (NOS) activation, which is a major source of NO responsible for low-dose (1–10 nM) nitroglycerin-induced vasorelaxation. Our studies in cell cultures, isolated vessels, and whole animals identified endothelial NOS activation as a fundamental requirement for nitroglycerin action at pharmacologically relevant concentrations in WT animals. PMID:18562300

Induction of nitric oxide synthase in rat intestine by interleukin-1alpha may explain diarrhea associated with zinc deficiency.

PubMed

Cui, L; Takagi, Y; Wasa, M; Iiboshi, Y; Khan, J; Nezu, R; Okada, A

1997-09-01

Synthesis of inducible nitric oxide synthase (iNOS) in the intestine may result in local tissue damage. We investigated whether a challenge with interleukin-1alpha could give rise to intestinal iNOS expression and diarrhea in rats of differing zinc status. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency or a zinc-supplemented diet [50.8 mg zinc/kg; controls, including pair-fed (PF ) and ad libitum (AL) consumption groups], and then subcutaneously injected with interleukin-1alpha (2 x 10(7) units/kg body wt). Without the interleukin-1alpha challenge, ZD rats had significantly lower plasma zinc concentration than the other groups. Intestinal metallothionein-1 mRNA abundance was lower in ZD rats than in AL rats. iNOS was expressed in the intestine of ZD rats but not in the others. None of the rats experienced diarrhea during the feeding period. Interleukin-1alpha led to a reduction in plasma zinc concentration, enhancement in intestinal metallothionein-1 mRNA levels, and expression of the intestinal iNOS gene in all groups. However, the abundance of iNOS mRNA was significantly higher in ZD rats than in the other groups. The presence of iNOS protein was demonstrated by immunohistochemical staining in the intestine of ZD rats that had been treated with interleukin-1alpha 12 h earlier. In addition, diarrhea occurred in most of the ZD rats and some of the PF rats but not in AL rats after interleukin-1alpha treatment. We conclude that ZD rats respond to interleukin-1alpha challenge more severely than controls, reflected by a more marked and prolonged iNOS expression and a greater incidence of diarrhea.

7 CFR 275.18 - Project area/management unit corrective action plan.

Code of Federal Regulations, 2010 CFR

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7 CFR 275.18 - Project area/management unit corrective action plan.

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7 CFR 275.18 - Project area/management unit corrective action plan.

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ARL: A Bimonthly Newsletter of Research Library Issues and Actions, Nos. 190-195. February-December 1997.

ERIC Educational Resources Information Center

Barrett, G. Jaia, Ed.

This document consists of six issues of the ARL (Association of Research Libraries) Newsletter, covering the year 1997. Each issue of the newsletter includes some or all of the following sections: "Current Issues," reports from the Office of Scholarly Communication, Office for Management Services, and Coalition for Networked Information,…

Regulation of Sertoli cell tight junction dynamics in the rat testis via the nitric oxide synthase/soluble guanylate cyclase/3',5'-cyclic guanosine monophosphate/protein kinase G signaling pathway: an in vitro study.

PubMed

Lee, Nikki P Y; Cheng, C Yan

2003-07-01

Nitric oxide (NO) synthase (NOS) catalyzes the oxidation of L-arginine to NO. NO plays a crucial role in regulating various physiological functions, possibly including junction dynamics via its effects on cAMP and cGMP, which are known modulators of tight junction (TJ) dynamics. Although inducible NOS (iNOS) and endothelial NOS (eNOS) are found in the testis and have been implicated in the regulation of spermatogenesis, their role(s) in TJ dynamics, if any, is not known. When Sertoli cells were cultured at 0.5-1.2 x 10(6) cells/cm(2) on Matrigel-coated dishes or bicameral units, functional TJ barrier was formed when the barrier function was assessed by quantifying transepithelial electrical resistance across the cell epithelium. The assembly of the TJ barrier was shown to associate with a significant plummeting in the levels of iNOS and eNOS, seemingly suggesting that their presence by producing NO might perturb TJ assembly. To further confirm the role of NOS on the TJ barrier function in vitro, zinc (II) protoporphyrin-IX (ZnPP), an NOS inhibitor and a soluble guanylate cyclase inhibitor, was added to the Sertoli cell cultures during TJ assembly. Indeed, ZnPP was found to facilitate the assembly and maintenance of the Sertoli cell TJ barrier, possibly by inducing the production of TJ-associated proteins, such as occludin. Subsequent studies by immunoprecipitation and immunoblotting have shown that iNOS and eNOS are structurally linked to TJ-integral membrane proteins, such as occludin, and cytoskeletal proteins, such as actin, vimentin, and alpha-tubulin. When the cAMP and cGMP levels in these ZnPP-treated samples were quantified, a ZnPP-induced reduction of intracellular cGMP, but not cAMP, was indeed detected. Furthermore, 8-bromo-cGMP, a cell membrane-permeable analog of cGMP, could also perturb the TJ barrier dose dependently similar to the effects of 8-bromo-cAMP. KT-5823, a specific inhibitor of protein kinase G, was shown to facilitate the Sertoli cell TJ barrier assembly. Cytokines, such as TGF-beta and TNF-alpha, known to perturb the Sertoli cell TJ barrier, were also shown to stimulate Sertoli cell iNOS and eNOS expression dose dependently in vitro. Collectively, these results illustrate NOS is an important physiological regulator of TJ dynamics in the testis, exerting its effects via the NO/soluble guanylate cyclase/cGMP/protein kinase G signaling pathway.

An image encryption scheme based on three-dimensional Brownian motion and chaotic system

NASA Astrophysics Data System (ADS)

Chai, Xiu-Li; Gan, Zhi-Hua; Yuan, Ke; Lu, Yang; Chen, Yi-Ran

2017-02-01

Not Available Project supported by the National Natural Science Foundation of China (Grant Nos. 41571417 and 61305042), the National Science Foundation of the United States (Grant Nos. CNS-1253424 and ECCS-1202225), the Science and Technology Foundation of Henan Province, China (Grant No. 152102210048), the Foundation and Frontier Project of Henan Province, China (Grant No. 162300410196), China Postdoctoral Science Foundation (Grant No. 2016M602235), the Natural Science Foundation of Educational Committee of Henan Province, China (Grant No. 14A413015), and the Research Foundation of Henan University, China (Grant No. xxjc20140006).

75 FR 30855 - In the Matter of: Certain Lighting Products; Notice of Investigation

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-02

...Notice is hereby given that a complaint was filed with the U.S. International Trade Commission on May 3, 2010, under section 337 of the Tariff Act of 1930, as amended, 19 U.S.C. 1337, on behalf of Blumberg Industries, Inc. d/b/a Fine Art Lamps of Miami Lakes, Florida. A letter supplementing the complaint was filed on May 24, 2010. The complaint alleges violations of section 337 based upon the importation into the United States, the sale for importation, and the sale within the United States after importation of certain lighting products by reason of infringement of U.S. Patent No. D570,038; U.S. Copyright Registration Nos. VA 1-399-618 and VA 1-415-353; and U.S. Trademark Registration Nos. 3,703,710; 3,703,711; 3,700,479, and 3,700,480. The complaint further alleges that an industry in the United States exists as required by subsection (a)(2) of section 337. The complainant requests that the Commission institute an investigation and, after the investigation, issue an exclusion order and a cease and desist order.

Evidence That Intergenic Spacer Repeats of Drosophila Melanogaster Rrna Genes Function as X-Y Pairing Sites in Male Meiosis, and a General Model for Achiasmatic Pairing

PubMed Central

McKee, B. D.; Habera, L.; Vrana, J. A.

1992-01-01

In Drosophila melanogaster males, X-Y meiotic chromosome pairing is mediated by the nucleolus organizers (NOs) which are located in the X heterochromatin (Xh) and near the Y centromere. Deficiencies for Xh disrupt X-Y meiotic pairing and cause high frequencies of X-Y nondisjunction. Insertion of cloned rRNA genes on an Xh(-) chromosome partially restores normal X-Y pairing and disjunction. To map the sequences within an inserted, X-linked rRNA gene responsible for stimulating X-Y pairing, partial deletions were generated by P element-mediated destabilization of the insert. Complete deletions of the rRNA transcription unit did not interfere with the ability to stimulate X-Y pairing as long as most of the intergenic spacer (IGS) remained. Within groups of deletions that lacked the entire transcription unit and differed only in length of residual IGS material, pairing ability was proportional to the dose of 240-bp intergenic spacer repeats. Deletions of the complete rRNA transcription unit or of the 28S sequences alone blocked nucleolus formation, as determined by binding of an antinucleolar antibody, yet did not interfere with pairing ability, suggesting that X-Y pairing may not be mechanistically related to nucleolus formation. A model for achiasmatic pairing in Drosophila males based upon the combined action of topoisomerase I and a strand transferase is proposed. PMID:1330825

Arctigenin promotes apoptosis in ovarian cancer cells via the iNOS/NO/STAT3/survivin signalling.

PubMed

Huang, Ke; Li, Li-an; Meng, Yuan-guang; You, Yan-qin; Fu, Xiao-yu; Song, Lei

2014-12-01

Arctigenin is a biologically active lignan extracted from the seeds of Arctium lappa and shows anticancer activity against a variety of human cancers. The aim of this study was to determine the effects of arctigenin on ovarian cancer cell proliferation and survival and associated molecular mechanisms. Human ovarian cancer OVCAR3 and SKOV3 cells were treated with arctigenin, and cell proliferation and apoptosis were assessed. Western blot analysis was used to examine signal transducer and activator of transcription-3 (STAT3) phosphorylation and survivin and inducible nitric oxide synthase (iNOS) expression. The involvement of STAT3/survivin/iNOS/NO signalling in arctigenin action was checked. Arctigenin treatment resulted in a significant and dose-dependent inhibition of cell proliferation. Arctigenin-treated cells showed a 4-6 times increase in the percentage of apoptosis, compared with control cells. Pre-treatment with Ac-DEVD-CHO, a specific inhibitor of caspase-3, counteracted the induction of apoptosis by arctigenin. Arctigenin treatment significantly inhibited STAT3 phosphorylation and survivin and iNOS expression. Arctigenin-induced apoptosis was impaired by pre-transfection with survivin-expressing plasmid or addition of chemical nitric oxide (NO) donors. Additionally, exogenous NO prevented the suppression of STAT3 phosphorylation and survivin expression by arctigenin. Arctigenin treatment inhibits the proliferation and induces caspase-3-dependent apoptosis of ovarian cancer cells. Suppression of iNOS/NO/STAT3/survivin signalling is causally linked to the anticancer activity of arctigenin. Therefore, arctigenin may be applicable to anticancer therapy for ovarian cancer. © 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

75 FR 41264 - Self-Regulatory Organizations; NYSE Amex LLC; Notice of Filing of Amendment Nos. 2 and 3, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-15

... Exchange proposes to trade Nasdaq Securities within the existing DMM and SLP framework used to trade its... member organization will not be permitted to be registered as both the DMM Unit and an SLP for the same... Nasdaq Securities to a different DMM Unit or to a different SLP or SLPs. \\5\\ A representative of NYSE...

75 FR 3761 - Southern Nuclear Operating Company, Inc., Edwin I. Hatch Nuclear Plant, Units 1 and 2...

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2010-01-22

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-321 and 50-366; NRC-2010-0024] Southern Nuclear Operating Company, Inc., Edwin I. Hatch Nuclear Plant, Units 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 to Title 10 of the Code of...

76 FR 19148 - PSEG Nuclear, LLC, Hope Creek Generating Station and Salem Nuclear Generating Station, Units 1...

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2011-04-06

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-272, 50-311, 50-354; NRC-2009-0390 and NRC-2009-0391] PSEG Nuclear, LLC, Hope Creek Generating Station and Salem Nuclear Generating Station, Units 1 and 2; Notice of Availability of the Final Supplement 45 to the Generic Environmental Impact Statement for License Renewal of Nuclear Plants Notice is...

Vascular effects of the Mangifera indica L. extract (Vimang).

PubMed

Beltrán, Amada E; Alvarez, Yolanda; Xavier, Fabiano E; Hernanz, Raquel; Rodriguez, Janet; Núñez, Alberto J; Alonso, María J; Salaices, Mercedes

2004-09-24

The effects of the Mangiferia indica L. (Vimang) extract, and mangiferin (a C-glucosylxanthone of Vimang) on the inducible isoforms of cyclooxygenase (cyclooxygenase-2) and nitric oxide synthase (iNOS) expression and on vasoconstrictor responses were investigated in vascular smooth muscle cells and mesenteric resistance arteries, respectively, from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Vimang (0.5-0.1 mg/ml) and mangiferin (0.025 mg/ml) inhibited the interleukin-1beta (1 ng/ml)-induced iNOS expression more in SHR than in WKY, and cyclooxygenase-2 expression more in WKY than in SHR. Vimang (0.25-1 mg/ml) reduced noradrenaline (0.1-30 microM)- and U46619 (1 nM-30 microM)- but not KCl (15-70 mM)-induced contractions. Mangiferin (0.05 mg/ml) did not affect noradrenaline-induced contraction. In conclusion, the antiinflammatory action of Vimang would be related with the inhibition of iNOS and cyclooxygenase-2 expression, but not with its effect on vasoconstrictor responses. Alterations in the regulation of both enzymes in hypertension would explain the differences observed in the Vimang effect.

FRONT ELEVATION, HOUSE AT NORTHWEST CORNER OF SEVENTEENTH AND DIAMOND ...

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

FRONT ELEVATION, HOUSE AT NORTHWEST CORNER OF SEVENTEENTH AND DIAMOND STREETS AND THE ATTACHED INTERIOR UNIT (NOS. 1701 AND 1703). - 1700 Block Diamond Street (Houses), North & south sides between Seventeenth & Eighteenth Streets, Philadelphia, Philadelphia County, PA

75 FR 45480 - Approval and Promulgation of Air Quality Implementation Plans; Minnesota

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-03

... consider your comment. Electronic files should avoid the use of special characters, any form of encryption... units at the facility are three fossil fuel- fired boilers (Nos. 1, 2, and 3), and four emergency...

Neuroprotective effects of curcumin alleviate lumbar intervertebral disc degeneration through regulating the expression of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF in a rat model.

PubMed

Hu, Yuan; Tang, Jin-Shu; Hou, Shu-Xun; Shi, Xiu-Xiu; Qin, Jiang; Zhang, Tie-Song; Wang, Xiao-Jing

2017-11-01

Curcumin is a natural product with antimutagenic, antitumor, antioxidant and neuroprotective properties. However, to the best of our knowledge, curcumin has yet to be investigated for the treatment of lumbar intervertebral disc degeneration LIDD). The aim of the present study was to investigate whether curcumin can alleviate LIDD through regulating the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)‑2, transforming growth factor (TGF)‑β1/2, matrix metalloproteinase (MMP)‑9 and brain‑derived neurotrophic factor (BDNF) in a rat model of LIDD. The results of the present study suggest that pretreatment with curcumin can prevent the development of LIDD in rats. It was revealed that treatment with curcumin significantly reduced interleukin (IL)‑1β and IL‑6, iNOS, COX‑2 and MMP‑9 levels in rats with LIDD. In addition, treatment with curcumin reduced the mRNA expression levels of TGF‑β1 and TGF‑β2, whereas it increased the mRNA expression levels of BDNF in rats with LIDD. In conclusion, the present findings indicate that curcumin may exert protective effects on LIDD development, exerting its action through the regulation of iNOS, COX‑2, TGF‑β1/2, MMP‑9 and BDNF.

77 FR 1637 - Connect America Fund; Developing an Unified Intercarrier Compensation Regime; Lifeline and Link Up

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-11

... Communications Commission amends 47 CFR parts 20 and 54 as follows: PART 20--COMMERCIAL MOBILE RADIO SERVICES 0 1... FEDERAL COMMUNICATIONS COMMISSION 47 CFR Parts 20 and 54 [WC Docket Nos. 10-90, 07-135, 05-337, 03... Communications Commission. ACTION: Final rule. SUMMARY: In this document, the Commission amends rules regarding...

77 FR 12274 - Orders Granting Authority To Import and Export Natural Gas and Liquefied Natural Gas During...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-29

... Fossil Energy, Department of Energy (DOE). ACTION: Notice of orders. FE Docket Nos. DOMINION COVE POINT... Fossil Energy (FE) of the Department of Energy gives notice that during January 2012, it issued Orders... in the attached appendix and may be found on the FE Web site at http://www.fossil.energy.gov/programs...

77 FR 31838 - Notice of Orders Granting Authority to Import and Export Natural Gas and Liquefied Natural Gas...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-30

...: Office of Fossil Energy, Department of Energy (DOE). ACTION: Notice of orders. FE Docket Nos. Prometheus... Resources, Inc 12-42-NG Minnesota Energy Resources Corporation... 12-40-NG SUMMARY: The Office of Fossil... attached appendix and may be found on the FE Web site at http://www.fossil.energy.gov/programs...

76 FR 54374 - Disclosure for Asset-Backed Securities Required by Section 943 of the Dodd-Frank Wall Street...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-01

... SECURITIES AND EXCHANGE COMMISSION 17 CFR PART 240 [Release Nos. 33-9175A; 34-63741A; File No. S7-24-10] RIN 3235-AK75 Disclosure for Asset-Backed Securities Required by Section 943 of the Dodd-Frank Wall Street Reform and Consumer Protection Act AGENCY: Securities and Exchange Commission. ACTION...

A Multi-Year Program Developing an Explicit Reflective Pedagogy for Teaching Pre-Service Teachers the Nature of Science by Ostention

ERIC Educational Resources Information Center

Smith, Mike U.; Scharmann, Lawrence

2008-01-01

This investigation delineates a multi-year action research agenda designed to develop an instructional model for teaching the nature of science (NOS) to preservice science teachers. Our past research strongly supports the use of explicit reflective instructional methods, which includes Thomas Kuhn's notion of learning by ostention and treating…

Edaravone attenuates hippocampal damage in an infant mouse model of pneumococcal meningitis by reducing HMGB1 and iNOS expression via the Nrf2/HO-1 pathway.

PubMed

Li, Zheng; Ma, Qian-Qian; Yan, Yan; Xu, Feng-Dan; Zhang, Xiao-Ying; Zhou, Wei-Qin; Feng, Zhi-Chun

2016-09-01

Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger that has shown potent antioxidant, anti-inflammatory and neuroprotective effects in variety of disease models. In this study, we investigated whether edaravone produced neuroprotective actions in an infant mouse model of pneumococcal meningitis. C57BL/6 mice were infected on postnatal d 11 by intracisternal injection of a certain inoculum of Streptococcus pneumoniae. The mice received intracisternal injection of 10 μL of saline containing edaravone (3 mg/kg) once a day for 7 d. The severity of pneumococcal meningitis was assessed with a clinical score. In mice with severe meningitis, the survival rate from the time of infection to d 8 after infection was analyzed using Kaplan-Meier curves. In mice with mild meningitis, the CSF inflammation and cytokine levels in the hippocampus were analyzed d 7 after infection, and the clinical neurological deficit score was evaluated using a neurological scoring system d 14 after infection. The nuclear factor (erythroid-derived 2)-like 2 knockout (Nrf2 KO) mice and heme oxygenase-1 knockout (HO-1 KO) mice were used to confirm the involvement of Nrf2/HO-1 pathway in the neuroprotective actions of edaravone. In mice with severe meningitis, edaravone treatment significantly increased the survival rate (76.4%) compared with the meningitis model group (32.2%). In mice with mild meningitis, edaravone treatment significantly decreased the number of leukocytes and TNF- levels in CSF, as well as the neuronal apoptosis and protein levels of HMGB1 and iNOS in the hippocampus, but did not affect the high levels of IL-10 and IL-6 in the hippocampus. Moreover, edaravone treatment significantly improved the neurological function of mice with mild meningitis. In Nrf2 KO or HO-1 KO mice with the meningitis, edaravone treatment was no longer effective in improving the survival rate of the mice with severe meningitis (20.2% and 53.6%, respectively), nor it affected the protein levels of HMGB1 and iNOS in the hippocampus of the mice with mild meningitis. Edaravone produces neuroprotective actions in a mouse model of pneumococcal meningitis by reducing neuronal apoptosis and HMGB1 and iNOS expression in the hippocampus via the Nrf2/HO-1 pathway. Thus, edaravone may be a promising agent for the treatment of bacterial meningitis.

Edaravone attenuates hippocampal damage in an infant mouse model of pneumococcal meningitis by reducing HMGB1 and iNOS expression via the Nrf2/HO-1 pathway

PubMed Central

Li, Zheng; Ma, Qian-qian; Yan, Yan; Xu, Feng-dan; Zhang, Xiao-ying; Zhou, Wei-qin; Feng, Zhi-chun

2016-01-01

Aim: Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) is a free radical scavenger that has shown potent antioxidant, anti-inflammatory and neuroprotective effects in variety of disease models. In this study, we investigated whether edaravone produced neuroprotective actions in an infant mouse model of pneumococcal meningitis. Methods: C57BL/6 mice were infected on postnatal d 11 by intracisternal injection of a certain inoculum of Streptococcus pneumoniae. The mice received intracisternal injection of 10 μL of saline containing edaravone (3 mg/kg) once a day for 7 d. The severity of pneumococcal meningitis was assessed with a clinical score. In mice with severe meningitis, the survival rate from the time of infection to d 8 after infection was analyzed using Kaplan-Meier curves. In mice with mild meningitis, the CSF inflammation and cytokine levels in the hippocampus were analyzed d 7 after infection, and the clinical neurological deficit score was evaluated using a neurological scoring system d 14 after infection. The nuclear factor (erythroid-derived 2)-like 2 knockout (Nrf2 KO) mice and heme oxygenase-1 knockout (HO-1 KO) mice were used to confirm the involvement of Nrf2/HO-1 pathway in the neuroprotective actions of edaravone. Results: In mice with severe meningitis, edaravone treatment significantly increased the survival rate (76.4%) compared with the meningitis model group (32.2%). In mice with mild meningitis, edaravone treatment significantly decreased the number of leukocytes and TNF- levels in CSF, as well as the neuronal apoptosis and protein levels of HMGB1 and iNOS in the hippocampus, but did not affect the high levels of IL-10 and IL-6 in the hippocampus. Moreover, edaravone treatment significantly improved the neurological function of mice with mild meningitis. In Nrf2 KO or HO-1 KO mice with the meningitis, edaravone treatment was no longer effective in improving the survival rate of the mice with severe meningitis (20.2% and 53.6%, respectively), nor it affected the protein levels of HMGB1 and iNOS in the hippocampus of the mice with mild meningitis. Conclusion: Edaravone produces neuroprotective actions in a mouse model of pneumococcal meningitis by reducing neuronal apoptosis and HMGB1 and iNOS expression in the hippocampus via the Nrf2/HO-1 pathway. Thus, edaravone may be a promising agent for the treatment of bacterial meningitis. PMID:27569388

Muscle contraction induced arterial shear stress increases endothelial nitric oxide synthase phosphorylation in humans.

PubMed

Casey, Darren P; Ueda, Kenichi; Wegman-Points, Lauren; Pierce, Gary L

2017-10-01

We determined if local increases in brachial artery shear during repetitive muscle contractions induce changes in protein expression of endothelial nitric oxide synthase (eNOS) and/or phosphorylated (p-)eNOS at Ser 1177 , the primary activation site on eNOS, in endothelial cells (ECs) of humans. Seven young male subjects (25 ± 1 yr) performed 20 separate bouts (3 min each) of rhythmic forearm exercise at 20% of maximum over a 2-h period. Each bout of exercise was separated by 3 min of rest. An additional six male subjects (24 ± 1 yr) served as time controls (no exercise). ECs were freshly isolated from the brachial artery using sterile J-wires through an arterial catheter at baseline and again after the 2-h exercise or time control period. Expression of eNOS or p-eNOS Ser 1177 in ECs was determined via immunofluorescence. Brachial artery mean shear rate was elevated compared with baseline and the time control group throughout the 2-h exercise protocol ( P < 0.001). p-eNOS Ser 1177 expression was increased 57% in ECs in the exercise group [0.06 ± 0.01 vs. 0.10 ± 0.02 arbitrary units (au), P = 0.02] but not in the time control group (0.08 ± 0.01 vs. 0.07 ± 0.01 au, P = 0.72). In contrast, total eNOS expression did not change in either the exercise (0.13 ± 0.04 vs. 0.12 ± 0.03 au) or time control (0.12 ± 0.03 vs. 0.11 ± 0.03 au) group ( P > 0.05 for both). Our novel results suggest that elevations in brachial artery shear increase eNOS Ser 1177 phosphorylation in the absence of changes in total eNOS in ECs of young healthy male subjects, suggesting that this model is sufficient to alter posttranslational modification of eNOS activity in vivo in humans. NEW & NOTEWORTHY Elevations in brachial artery shear in response to forearm exercise increased endothelial nitric oxide synthase Ser 1177 phosphorylation in brachial artery endothelial cells of healthy humans. Our present study provides the first evidence in humans that muscle contraction-induced increases in conduit arterial shear lead to in vivo posttranslational modification of endothelial nitric oxide synthase activity in endothelial cells. Copyright © 2017 the American Physiological Society.

75 FR 4591 - Virginia Electric and Power Company; North Anna Power Station, Unit Nos. 1 and 2; Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-28

... that effect radiation exposures to plant workers and members of the public. Therefore, no changes or... socioeconomic resources. Therefore, no changes to or different types of non-radiological environmental impacts...

75 FR 9618 - Virginia Electric and Power Company Surry Power Station, Unit Nos. 1 and 2 Environmental...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-03

... change to radioactive effluents that effect radiation exposures to plant workers and members of the.... There would be no impact to socioeconomic resources. Therefore, no changes to or different types of non...

Integrating Scientific Methods and Knowledge into the Teaching of Newton's Theory of Gravitation: An Instructional Sequence for Teachers' and Students' Nature of Science Education

ERIC Educational Resources Information Center

Develaki, Maria

2012-01-01

The availability of teaching units on the nature of science (NOS) can reinforce classroom instruction in the subject, taking into account the related deficiencies in textbook material and teacher training. We give a sequence of teaching units in which the teaching of Newton's gravitational theory is used as a basis for reflecting on the…

Nature of Science and Decision-Making

NASA Astrophysics Data System (ADS)

Khishfe, Rola

2012-01-01

The study investigated the relationship of nature of science (NOS) instruction and students' decision-making (DM) related to a controversial socioscientific issue about genetically modified food. Participants were ninth-grade students in four intact sections (two regulars and two honors) in a public high school in the Midwest. All four groups were taught by their regular science teacher. The treatment comprised a four-week unit about genetic engineering. Two groups (one regular and one honors), referred to as comparison groups, received instruction in genetic engineering and how to formulate arguments and make decisions related to this controversial issue. The other two groups (one regular and one honors), referred to as treatment groups, received instruction in genetic engineering and how to apply NOS aspects as they formulate arguments and make decisions in relation to this controversial issue. Chi-square analyses showed significant differences between the comparison and the treatment groups in relation to the understandings of four NOS aspects. There were no differences in their decisions, but there were differences in their DM factors in the context of the controversial socioscientific issue about genetically modified food. These results are discussed in light of the relationship between students' understandings of NOS and their DM related to controversial socioscientific issues.

Ontogeny of the VIP system in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum: successive appearance of co-existing PACAP and NOS.

PubMed

Badawy, Gamal; Reinecke, Manfred

2003-03-01

Evidence for the presence and potential co-existence of vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP) and nitric oxide synthase (NOS) in gastro-intestinal endocrine cells and/or nerve fibers is conflicting and very few results exist on development. This immunofluorescence study aims to clarify the appearance and localization of VIP, PACAP and NOS in the gastro-intestinal tract of the Axolotl, Ambystoma mexicanum, during ontogeny. VIP-immunoreactivity appeared in nerve fibers as early as on day 3 after hatching likely indicating a particular role, such as a trophic action, of VIP in very early development. PACAP-immunoreactivity was observed 3 days later within the VIP-immunoreactive (-IR) fibers. From this time on, VIP- and PACAP-immunoreactivity exhibited complete co-existence. VIP/PACAP-IR fibers were found throughout the gastro-intestinal tract. They were most prominent in the myenteric plexus and the muscle layers and less frequent in the submucosa. NOS-immunoreactivity appeared as late as at the 1st (64 days) juvenile stage in a subpopulation of the VIP/PACAP-IR fibers that contacted submucosal arteries. We found only very few VIP/PACAP-IR perikarya, indicating that part of the VIP/PACAP-IR fibers is of extrinsic origin. On day 12 and in the 1st and 2nd (104 days) juvenile stage, infrequent PACAP-IR entero-endocrine cells were noted, while neither VIP- nor NOS-immunoreactivity occurred in endocrine cells at any stage of development. The complete coexistence of neuronal PACAP- and VIP-immunoreactivities and their very early appearance in ontogeny may suggest important and coordinated roles of both peptides in the control of Axolotl gastro-intestinal activity, while the VIP/ PACAP/NOS-IR fibers may be involved in the regulation of submucosal blood flow.

Different protective actions of losartan and tempol on the renal inflammatory response to acute sodium overload.

PubMed

Rosón, María I; Della Penna, Silvana L; Cao, Gabriel; Gorzalczany, Susana; Pandolfo, Marcela; Toblli, Jorge E; Fernández, Belisario E

2010-07-01

The aim of this work was to study the role of local intrarenal angiotensin II (Ang II) and the oxidative stress in the up-regulation of pro-inflammatory cytokines expression observed in rats submitted to an acute sodium overload. Sprague-Dawley rats were infused for 2 h with isotonic saline solution (Control group) and with hypertonic saline solution alone (Na group), plus the AT1 receptor antagonist losartan (10 mg kg(-1) in bolus) (Na-Los group), or plus the superoxide dismutase mimetic tempol (0.5 mg min(-1) kg(-1)) (Na-Temp group). Mean arterial pressure, glomerular filtration rate, and fractional sodium excretion (FE(Na)) were measured. Ang II, NF-kappaB, hypoxia inducible factor-1 alpha (HIF-1 alpha), transforming growth factor beta1 (TGF-beta1), smooth muscle actin (alpha-SMA), endothelial nitric oxide synthase (eNOS), and RANTES renal expression was evaluated by immunohistochemistry. Ang II, NF-kappaB, and TGF-beta1 and RANTES early inflammatory markers were overexpressed in Na group, accompanied by enhanced HIF-1 alpha immunostaining, lower eNOS expression, and unmodified alpha-SMA. Losartan and tempol increased FE(Na) in sodium overload group. Although losartan reduced Ang II and NF-kappaB staining and increased eNOS expression, it did not restore HIF-1 alpha expression and did not prevent inflammation. Conversely, tempol increased eNOS and natriuresis, restored HIF-1 alpha expression, and prevented inflammation. Early inflammatory markers observed in rats with acute sodium overload is associated with the imbalance between HIF-1 alpha and eNOS expression. While both losartan and tempol increased natriuresis and eNOS expression, only tempol was effective in restoring HIF-1 alpha expression and down-regulating TGF-beta1 and RANTES expression. The protective role of tempol, but not of losartan, in the inflammatory response may be associated with its greater antioxidant effects. (c) 2010 Wiley-Liss, Inc.

What Faces Reveal: A Novel Method to Identify Patients at Risk of Deterioration Using Facial Expressions.

PubMed

Madrigal-Garcia, Maria Isabel; Rodrigues, Marcos; Shenfield, Alex; Singer, Mervyn; Moreno-Cuesta, Jeronimo

2018-07-01

To identify facial expressions occurring in patients at risk of deterioration in hospital wards. Prospective observational feasibility study. General ward patients in a London Community Hospital, United Kingdom. Thirty-four patients at risk of clinical deterioration. A 5-minute video (25 frames/s; 7,500 images) was recorded, encrypted, and subsequently analyzed for action units by a trained facial action coding system psychologist blinded to outcome. Action units of the upper face, head position, eyes position, lips and jaw position, and lower face were analyzed in conjunction with clinical measures collected within the National Early Warning Score. The most frequently detected action units were action unit 43 (73%) for upper face, action unit 51 (11.7%) for head position, action unit 62 (5.8%) for eyes position, action unit 25 (44.1%) for lips and jaw, and action unit 15 (67.6%) for lower face. The presence of certain combined face displays was increased in patients requiring admission to intensive care, namely, action units 43 + 15 + 25 (face display 1, p < 0.013), action units 43 + 15 + 51/52 (face display 2, p < 0.003), and action units 43 + 15 + 51 + 25 (face display 3, p < 0.002). Having face display 1, face display 2, and face display 3 increased the risk of being admitted to intensive care eight-fold, 18-fold, and as a sure event, respectively. A logistic regression model with face display 1, face display 2, face display 3, and National Early Warning Score as independent covariates described admission to intensive care with an average concordance statistic (C-index) of 0.71 (p = 0.009). Patterned facial expressions can be identified in deteriorating general ward patients. This tool may potentially augment risk prediction of current scoring systems.

Action Recognition Using Nonnegative Action Component Representation and Sparse Basis Selection.

PubMed

Wang, Haoran; Yuan, Chunfeng; Hu, Weiming; Ling, Haibin; Yang, Wankou; Sun, Changyin

2014-02-01

In this paper, we propose using high-level action units to represent human actions in videos and, based on such units, a novel sparse model is developed for human action recognition. There are three interconnected components in our approach. First, we propose a new context-aware spatial-temporal descriptor, named locally weighted word context, to improve the discriminability of the traditionally used local spatial-temporal descriptors. Second, from the statistics of the context-aware descriptors, we learn action units using the graph regularized nonnegative matrix factorization, which leads to a part-based representation and encodes the geometrical information. These units effectively bridge the semantic gap in action recognition. Third, we propose a sparse model based on a joint l2,1-norm to preserve the representative items and suppress noise in the action units. Intuitively, when learning the dictionary for action representation, the sparse model captures the fact that actions from the same class share similar units. The proposed approach is evaluated on several publicly available data sets. The experimental results and analysis clearly demonstrate the effectiveness of the proposed approach.

Polygonum viviparum L. inhibits the lipopolysaccharide-induced inflammatory response in RAW264.7 macrophages through haem oxygenase-1 induction and activation of the Nrf2 pathway.

PubMed

Cheng, Hui-Wen; Lee, Kock-Chee; Cheah, Khoot-Peng; Chang, Ming-Long; Lin, Che-Wei; Li, Joe-Sharg; Yu, Wen-Yu; Liu, E-Tung; Hu, Chien-Ming

2013-02-01

Polygonum viviparum L. (PV) is a member of the family Polygonaceae and is widely distributed in high-elevation areas. It is used as a folk remedy to treat inflammation-related diseases. This study was focused on the anti-inflammatory response of PV against lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. Treatment with PV did not cause cytotoxicity at 0-50 µg mL(-1) in RAW264.7 macrophages, and the IC(50) value was 270 µg mL(-1). PV inhibited LPS-stimulated nitric oxide (NO), prostaglandin (PG)E(2) , interleukin (IL)-1β and tumour necrosis factor (TNF)-α release and inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 protein expression. In addition, PV suppressed the LPS-induced p65 expression of nuclear factor (NF)-κB, which is associated with the inhibition of IκB-α degradation. These results suggest that, among mechanisms of the anti-inflammatory response, PV inhibits the production of NO and these cytokines by down-regulating iNOS and COX-2 gene expression. Furthermore, PV can induce haem oxygenase (HO)-1 protein expression through nuclear factor E2-related factor 2 (Nrf2) activation. A specific inhibitor of HO-1, zinc(II) protoporphyrin IX, inhibited the suppression of iNOS and COX-2 expression by PV. These results suggest that PV possesses anti-inflammatory actions in macrophages and works through a novel mechanism involving Nrf2 actions and HO-1. Thus PV could be considered for application as a potential therapeutic approach for inflammation-associated disorders. Copyright © 2012 Society of Chemical Industry.

Comparative effects of cyclo-oxygenase and nitric oxide synthase inhibition on the development and reversal of spinal opioid tolerance

PubMed Central

Powell, Kelly J; Hosokawa, Akiko; Bell, Andrew; Sutak, Maaja; Milne, Brian; Quirion, Remi; Jhamandas, Khem

1999-01-01

This study examined the effects of the COX inhibitors, ketorolac and ibuprofen, and the NOS inhibitor L-NAME for their potential to both inhibit the development and reverse tolerance to the antinociceptive action of morphine. Repeated administration of intrathecal morphine (15 μg), once daily, resulted in a progressive decline of antinociceptive effect and an increase in the ED50 value in the tailflick and paw pressure tests. Co-administration of ketorolac (30 and 45 μg) or S(+) ibuprofen (10 μg) with morphine (15 μg) prevented the decline of antinociceptive effect and increase in ED50 value. Similar treatment with L-NAME (100 μg) exerted weaker effects. Administration of S(+) but not R(−) ibuprofen (10 mg kg−1) had similar effects on systemic administration of morphine (15 mg kg−1). Intrathecal or systemic administration of the COX or NOS inhibitors did not alter the baseline responses in either tests. Acute keterolac or S(+) ibuprofen also did not potentiate the acute actions of spinal or systemic morphine, but chronic intrathecal administration of these agents increased the potency of acute morphine. In animals already tolerant to intrathecal morphine, subsequent administration of ketorolac (30 μg) with morphine (15 μg) partially restored the antinociceptive effect and ED50 value of acute morphine, reflecting the reversal of tolerance. Intrathecal L-NAME (100 μg) exerted a weaker effect. These data suggest that spinal COX activity, and to a lesser extent NOS activity, contributes to the development and expression of opioid tolerance. Inhibition of COX may represent a useful approach for the prevention as well as reversal of opioid tolerance. PMID:10401553

Anti-inflammatory effects of Zea mays L. husk extracts.

PubMed

Roh, Kyung-Baeg; Kim, Hyoyoung; Shin, Seungwoo; Kim, Young-Soo; Lee, Jung-A; Kim, Mi Ok; Jung, Eunsun; Lee, Jongsung; Park, Deokhoon

2016-08-19

Zea mays L. (Z. mays) has been used for human consumption in the various forms of meal, cooking oil, thickener in sauces and puddings, sweetener in processed food and beverage products, bio-disel. However, especially, in case of husk extract of Z. mays, little is known about its anti-inflammatory effects. Therefore, in this study, the anti-inflammatory effects of Z. mays husk extract (ZMHE) and its mechanisms of action were investigated. The husks of Z. Mays were harvested in kangwondo, Korea. To assess the anti-inflammatory activities of ZMHE, we examined effects of ZMHE on nitric oxide (NO) production, and release of soluble intercellular adhesion molecule-1 (sICAM-1) and eotaxin-1. The expression level of inducible nitric oxide synthase (iNOS) gene was also determined by Western blot and luciferase reporter assays. To determine its mechanisms of action, a luciferase reporter assay for nuclear factor kappa B (NF-kB) and activator protein-1 (AP-1) was introduced. ZMHE inhibited lipopolysaccharide (LPS)-induced production of NO in RAW264.7 cells. In addition, expression of iNOS gene was reduced, as confirmed by Western blot and luciferase reporter assays. Effects of ZMHE on the AP-1 and NF-kB promoters were examined to elucidate the mechanism of its anti-inflammatory activity. Activation of AP-1 and NF-kB promoters induced by LPS was significantly reduced by ZMHE treatment. In addition, LPS-induced production of sICAM-1 and IL-4-induced production of eotaxin-1 were all reduced by ZMHE. Our results indicate that ZMHE has anti-inflammatory effects by downregulating the expression of iNOS gene and its downregulation is mediated by inhibiting NF-kB and AP-1 signaling.

High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ETB receptor expression.

PubMed

Hyndman, Kelly Anne; Dugas, Courtney; Arguello, Alexandra M; Goodchild, Traci T; Buckley, Kathleen M; Burch, Mariah; Yanagisawa, Masashi; Pollock, Jennifer S

2016-08-01

The collecting duct endothelin-1 (ET-1), endothelin B (ETB) receptor, and nitric oxide synthase-1 (NOS1) pathways are critical for regulation of fluid-electrolyte balance and blood pressure control during high-salt feeding. ET-1, ETB receptor, and NOS1 are highly expressed in the inner medullary collecting duct (IMCD) and vasa recta, suggesting that there may be cross talk or paracrine signaling between the vasa recta and IMCD. The purpose of this study was to test the hypothesis that endothelial cell-derived ET-1 (paracrine) and collecting duct-derived ET-1 (autocrine) promote IMCD nitric oxide (NO) production through activation of the ETB receptor during high-salt feeding. We determined that after 7 days of a high-salt diet (HS7), there was a shift to 100% ETB expression in IMCDs, as well as a twofold increase in nitrite production (a metabolite of NO), and this increase could be prevented by acute inhibition of the ETB receptor. ETB receptor blockade or NOS1 inhibition also prevented the ET-1-dependent decrease in ion transport from primary IMCDs, as determined by transepithelial resistance. IMCD were also isolated from vascular endothelial ET-1 knockout mice (VEETKO), collecting duct ET-1 KO (CDET-1KO), and flox controls. Nitrite production by IMCD from VEETKO and flox mice was similarly increased twofold with HS7. However, IMCD NO production from CDET-1KO mice was significantly blunted with HS7 compared with flox control. Taken together, these data indicate that during high-salt feeding, the autocrine actions of ET-1 via upregulation of the ETB receptor are critical for IMCD NO production, facilitating inhibition of ion reabsorption. Copyright © 2016 the American Physiological Society.

Modulation of Lung Function by Increased Nitric Oxide Production

PubMed Central

Yadav, Ram Lochan; Yadav, Prakash Kumar

2017-01-01

Introduction Cigarette smoking reduces endogenous Nitric Oxide (NO) production by reducing Nitric Oxide Synthase (NOS) activity, which is one of the probable reason for increased rate of pulmonary diseases in smokers. Nitric oxide/oxygen blends are used in critical care to promote capillary and pulmonary dilation to treat several pulmonary vascular diseases. Among several supplements, the highest NOS activation has been proved for garlic with its unique mechanism of action. Aim To investigate the effect of dietary supplementation of NO producing garlic on pulmonary function of smokers. Materials and Methods The study was conducted on 40 healthy non-smoker (Group A) and 40 chronic smoker (Group B) males with matched age, height and weight. The pulmonary function tests- Forced Vital Capacity (FVC), Forced Expiratory Volume in one second (FEV1), FEV1/FVC ratio and Peak Expiratory Flow Rate (PEFR) were performed in non-smokers (Group A), smokers (Group B) and smokers after supplementation of approximately 4 gm of raw garlic (2 garlic cloves) per day for three months (Group C). Endogenous NO production was studied in smokers before and after garlic supplementation and in non-smokers without supplementation. The data obtained were compared between the groups using unpaired student’s t-test. The p-value considered significant at <0.05. Results Our results showed that FVC, FEV1, FEV1/FVC ratio and PEFR were reduced significantly along with a significant decreased NOS activity among smokers (Group B) when compared with non-smokers (Group A). Garlic supplementation significantly improved the pulmonary function tests in Group C in comparison to Group B by increasing NOS activity. Conclusion Dietary supplementation of garlic, which might be by increasing NOS activity, has significantly improved pulmonary functions in smokers. PMID:28764150

Heme oxygenase-1 induction by (S)-enantiomer of YS-51 (YS-51S), a synthetic isoquinoline alkaloid, inhibits nitric oxide production and nuclear factor-kappaB translocation in ROS 17/2.8 cells activated with inflammatory stimulants.

PubMed

Chaea, Han-Jung; Kim, Hyung-Ryong; Kang, Young Jin; Hyun, Kwang Chul; Kim, Hye Jung; Seo, Han Geuk; Lee, Jae Heun; Yun-Choi, Hye Sook; Chang, Ki Churl

2007-12-05

Activation of the inducible nitric oxide synthase (iNOS) pathway contributes to inflammation-induced osteoporosis by suppressing bone formation and causing osteoblast apoptosis. We investigated the mechanism of action by which YS-51S, a synthetic isoquinoline alkaloid, inhibits iNOS expression and nitric oxide (NO) production in ROS 17/28 osteoblast cells activated with the mixture of TNF-alpha, IFN-gamma and LPS (MIX). YS-51S, concentration- and time-dependently, increased heme oxygenase (HO-1) expression. Treatment with YS-51S 1 h prior to MIX significantly reduced MIX-induced NO production and iNOS expression with the IC50 to NO production of 47+/-3.3 microM. Electrophoretic mobility shift assay (EMSA) and western blot analysis showed that YS-51S inhibited MIX-mediated activation and translocation of NF-kappaB to nucleus by suppressing the degradation of its inhibitory protein IkappaBalpha in cytoplasm. YS-51S also reduced NF-kappaB-luciferase activity. In addition, an HO-1 inhibitor ZnPPIX, antagonized the inhibitory effect of YS-51S on iNOS expression and DNA strand break induced by MIX, indicating prevention of NO production by YS-51S is associated with HO-1 activity. Moreover, YS-51S inhibited the oxidation of cytochrome c(2+) by peroxynitrite (PN). Our results indicated that YS-51S may be beneficial in NO-mediated inflammatory conditions such as rheumatoid arthritis by alleviating iNOS expression and NO-mediated cell death of osteoblast with 1) inducing HO-1 expression, 2) interfering the activation of NF-kappaB and 3) quenching of PN.

Inflammation triggers constitutive activity and agonist-induced negative responses at M(3) muscarinic receptor in dental pulp.

PubMed

Sterin-Borda, Leonor; Orman, Betina; De Couto Pita, Alejandra; Borda, Enri

2011-02-01

The purpose of this study was to investigate whether the inflammation of rat dental pulp induces the muscarinic acetylcholine receptor (mAChR) constitutive receptor activity. Pulpitis was induced with bacterial lipolysaccharide in rat incisors dental pulp. Saturation assay with [(3)H]-quinuclidinyl benzilate ([(3)H] QNB), competitive binding with different mAChR antagonist subtypes, and nitric oxide synthase (NOS) activity were performed. A drastic change in expression and response to mAChR subtypes was observed in pulpitis. Inflamed pulp expressed high number of M(3) mAChR of high affinity, whereas the M(1) mAChR is the main subtype displayed in normal pulp. Consistent with the identification of the affinity constant (Ki) of M(3) and Ki of M(1) in both pulpitis and in normal pulps are the differences in the subtype functionality of these cells. In pulpitis, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) exerted an inhibitory action on NOS activity that was blocked by J 104129 fumarate (highest selective affinity to M(3) mAChR). In normal pulps, pilocarpine (1 × 10(-11) mol/L to 5 × 10(-9) mol/L) has no effect. NOS basal activity was 5.9 times as high in pulpitis as in the normal pulp as a result of the activation of inducible NOS. The irreversible pulpitis could induce a mAChR alteration, increasing the high-affinity receptor density and transduction-coupling efficiency of inducible NOS activity, leading to a spontaneously active conformation of the receptor. Pilocarpine acting as an inverse agonist might be useful therapeutically to prevent necrosis and subsequent loss of dental pulp. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

76 FR 19476 - Exelon Generation Company, LLC, Peach Bottom Atomic Power Station, Unit Nos. 2 and 3; Exemption

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2011-04-07

... licensee stated that the floor-based combustibles include health physics cleaning supplies, such as mops... undue risk to public health or safety, and are consistent with the common defense and security; and (2...

78 FR 76321 - Monosodium Glutamate From China and Indonesia

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-17

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-503-504 and 731-TA-1229-1230...\\ developed in the subject investigations, the United States International Trade Commission (Commission..., U.S. International Trade Commission, Washington, DC, and by publishing the notice in the Federal...

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 sympathetic vasoconstriction.

76 FR 54259 - Virginia Electric and Power Company, Docket Nos. 50-338 and 50-339, North Anna Power Station...

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2011-08-31

... The proposed action would provide exemption from the work hour control requirements of 10 CFR 26.205(c... conditions similar to entry into the site emergency plan where the imposition of work hour controls on vital.... Additionally, the time from entry into the condition in which the work hour control exemption applies, to...

Business and Organizational Communication: Abstracts of Doctoral Dissertations Published in "Dissertation Abstracts International," July through December 1982 (Vol. 43 Nos. 1 through 6).

ERIC Educational Resources Information Center

ERIC Clearinghouse on Reading and Communication Skills, Urbana, IL.

This collection of abstracts is part of a continuing series providing information on recent doctoral dissertations. The 16 titles deal with a variety of topics, including the following: (1) the delivery of bad news in organizations; (2) the diffusion of judicial innovations; (3) speech action in organizational socialization; (4) differential…

76 FR 82011 - Self-Regulatory Organizations; New York Stock Exchange LLC; NYSE Amex LLC; Notice of Designation...

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2011-12-29

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78 FR 29406 - Self-Regulatory Organizations; New York Stock Exchange LLC; NYSE MKT LLC; Notice of Designation...

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2013-05-20

... SECURITIES AND EXCHANGE COMMISSION [Release No. 34-69575; File Nos. SR-NYSE-2012-57; SR-NYSEMKT-2012-58] Self-Regulatory Organizations; New York Stock Exchange LLC; NYSE MKT LLC; Notice of Designation of Longer Period for Commission Action on Proceedings To Determine Whether To Disapprove Proposed Rule Changes Deleting NYSE Rules 95(c) and (d)...

Using Action Research to Engage K-6 Teachers in Nature of Science Inquiry as Professional Development

NASA Astrophysics Data System (ADS)

Cullen, Theresa A.; Akerson, Valarie L.; Hanson, Deborah L.

2010-12-01

Teachers are required to work with data on a daily basis to assess the effectiveness of their teaching strategies, but may not approach it as research. This paper presents a reflective discussion of how and when a professional development team used an action research project to help 12 K-6 teachers explore the effectiveness of reform based Nature of Science (NOS) teaching strategies in their classrooms. The team encouraged community development and provided “just in time” supports to scaffold the steps of the action research process for teachers. The discussion includes concerns they addressed and issues related to management and support of the professional development model. Evaluation results are shared to suggest how this approach can be improved in the future.

Inducible nitric oxide synthase and apoptosis in murine proximal tubule epithelial cells.

PubMed

Tiwari, Manish M; Messer, Kurt J; Mayeux, Philip R

2006-06-01

Since inducible nitric oxide synthase (iNOS) and proximal tubule injury are known to be critical determinants of lipopolysaccharide (LPS)-induced renal failure, the role of nitric oxide (NO) in proximal tubule cell apoptosis was examined. An 18-h treatment with a combination of LPS (5 microg/ml) and interferon-gamma (IFN-gamma, 100 units/ml) synergistically induced iNOS and produced a 20-fold increase in NO generation in the TKPTS murine proximal tubule cell line. NO generation by LPS + IFN-gamma was blocked by a specific iNOS blocker, L-N6-(1-iminoethyl)-lysine (L-NIL, 1 mM). To assess the role of iNOS-derived NO in proximal tubule cell apoptosis, annexin V- and propidium iodide-labeled cells were analyzed by flow cytometry. Neither the induction of iNOS nor its inhibition produced significant apoptotic cell death in TKPTS cells. Two exogenous NO donors were used to examine the role of NO more directly in proximal tubule apoptosis. Although both sodium nitroprusside (SNP), an iron-containing, nitrosonium cation donor, and S-nitroso-N-acetylpenicillamine (SNAP), a noniron-containing, NO generator, produced a concentration-dependent increase in NO generation, only SNP increased apoptotic cell death in TKPTS cells (5.9 +/- 0.7% in control cells vs. 21.6 +/- 3.8% in SNP [500 microM]-treated cells; n = 4-9; p < 0.01). SNP-mediated tubule cell apoptosis was not dependent on the activation of caspases or p53 but was possibly related to the generation of reactive oxygen species by SNP. Thus, in TKPTS cells induction of iNOS and generation of NO by LPS does not lead to tubular epithelial cell death.

78 FR 10636 - Large Residential Washers From Korea and Mexico

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2013-02-14

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-488 and 731-TA-1199-1200 (Final)] Large... subject investigations, the United States International Trade Commission (Commission) determines, pursuant... notice in the Office of the Secretary, U.S. International Trade Commission, Washington, DC, and by...

78 FR 76857 - Hardwood Plywood From China; Determinations

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2013-12-19

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-490 and 731-TA-1204 (Final)] Hardwood..., the United States International Trade Commission (Commission) determines, pursuant to sections 705(b.... International Trade Commission, Washington, DC, and by publishing the notice in the Federal Register on June 19...

78 FR 66382 - Certain Steel Threaded Rod From India and Thailand

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2013-11-05

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-498 and 731-TA-1213-1214 (Preliminary... in the subject investigations, the United States International Trade Commission (Commission.... International Trade Commission, Washington, DC, and by publishing the notice in the Federal Register of July 3...

Particle-in-cell simulations with charge-conserving current deposition on graphic processing units

NASA Astrophysics Data System (ADS)

Ren, Chuang; Kong, Xianglong; Huang, Michael; Decyk, Viktor; Mori, Warren

2011-10-01

Recently using CUDA, we have developed an electromagnetic Particle-in-Cell (PIC) code with charge-conserving current deposition for Nvidia graphic processing units (GPU's) (Kong et al., Journal of Computational Physics 230, 1676 (2011). On a Tesla M2050 (Fermi) card, the GPU PIC code can achieve a one-particle-step process time of 1.2 - 3.2 ns in 2D and 2.3 - 7.2 ns in 3D, depending on plasma temperatures. In this talk we will discuss novel algorithms for GPU-PIC including charge-conserving current deposition scheme with few branching and parallel particle sorting. These algorithms have made efficient use of the GPU shared memory. We will also discuss how to replace the computation kernels of existing parallel CPU codes while keeping their parallel structures. This work was supported by U.S. Department of Energy under Grant Nos. DE-FG02-06ER54879 and DE-FC02-04ER54789 and by NSF under Grant Nos. PHY-0903797 and CCF-0747324.

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

PubMed Central

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

2012-01-01

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

Anti-inflammatory effects of shea butter through inhibition of iNOS, COX-2, and cytokines via the Nf-κB pathway in LPS-activated J774 macrophage cells.

PubMed

Verma, Nandini; Chakrabarti, Rina; Das, Rakha H; Gautam, Hemant K

2012-01-12

Shea butter is traditionally used in Africa for its anti-inflammatory and analgesic effects. In this study we explored the anti-inflammatory activities of the methanolic extract of shea butter (SBE) using lipopolysaccharide (LPS)-induced murine macrophage cell line J774. It was observed that SBE significantly reduced the levels of LPS-induced nitric oxide, Tumor necrosis factor-α (TNF-α), interleukins, 1β (IL-1β), and -12 (IL-12) in the culture supernatants in a dose dependent manner. Expression of pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were also inhibited by SBE. These anti-inflammatory effects were due to an inhibitory action of SBE on LPS-induced iNOS, COX-2, TNF-α, IL-1β, and IL-12 mRNA expressions. Moreover, SBE efficiently suppressed IκB phosphorylation and NF-κB nuclear translocation induced by LPS. These findings explain the molecular bases of shea butter's bioactivity against various inflammatory conditions and substantiate it as a latent source of novel therapeutic agents.

Effects of nitric oxide on red blood cell deformability.

PubMed

Bor-Kucukatay, Melek; Wenby, Rosalinda B; Meiselman, Herbert J; Baskurt, Oguz K

2003-05-01

In addition to its known action on vascular smooth muscle, nitric oxide (NO) has been suggested to have cardiovascular effects via regulation of red blood cell (RBC) deformability. The present study was designed to further explore this possibility. Human RBCs in autologous plasma were incubated for 1 h with NO synthase (NOS) inhibitors [N(omega)-nitro-l-arginine methyl ester (l-NAME) and S-methylisothiourea], NO donors [sodium nitroprusside (SNP) and diethylenetriamine (DETA)-NONOate], an NO precursor (l-arginine), soluble guanylate cyclase inhibitors (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one and methylene blue), and a potassium channel blocker [triethylammonium (TEA)]. After incubation, RBC deformability at various shear stresses was determined by ektacytometry. Both NOS inhibitors significantly reduced RBC deformability above a threshold concentration, whereas the NO donors increased deformability at optimal concentrations. NO donors, as well as the NO precursor l-arginine and the potassium blocker TEA, were able to reverse the effects of NOS inhibitors. Guanylate cyclase inhibition reduced RBC deformation, with both SNP and DETA-NONOate able to reverse this effect. These results thus indicate the importance of NO as a determinant of RBC mechanical behavior and suggest its regulatory role for normal RBC deformability.

Arctigenin inhibits lipopolysaccharide-induced iNOS expression in RAW264.7 cells through suppressing JAK-STAT signal pathway.

PubMed

Kou, Xianjuan; Qi, Shimei; Dai, Wuxing; Luo, Lan; Yin, Zhimin

2011-08-01

Arctigenin has been demonstrated to have an anti-inflammatory function, but the precise mechanisms of its action remain to be fully defined. In the present study, we determined the effects of arctigenin on lipopolysaccharide (LPS)-induced production of proinflammatory mediators and the underlying mechanisms involved in RAW264.7 cells. Our results indicated that arctigenin exerted its anti-inflammatory effect by inhibiting ROS-dependent STAT signaling through its antioxidant activity. Arctigenin also significantly reduced the phosphorylation of STAT1 and STAT 3 as well as JAK2 in LPS-stimulated RAW264.7 cells. The inhibitions of STAT1 and STAT 3 by arctigenin prevented their translocation to the nucleus and consequently inhibited expression of iNOS, thereby suppressing the expression of inflammation-associated genes, such as IL-1β, IL-6 and MCP-1, whose promoters contain STAT-binding elements. However, COX-2 expression was slightly inhibited at higher drug concentrations (50 μM). Our data demonstrate that arctigenin inhibits iNOS expression via suppressing JAK-STAT signaling pathway in macrophages. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Identification of copper/zinc superoxide dismutase as a novel nitric oxide-regulated gene in rat glomerular mesangial cells and kidneys of endotoxemic rats.

PubMed

Frank, S; Zacharowski, K; Wray, G M; Thiemermann, C; Pfeilschifter, J

1999-05-01

To define the mechanism of nitric oxide (NO) action in the glomerulus, we attempted to identify genes that are regulated by NO in rat glomerular mesangial cells. We identified a Cu/Zn superoxide dismutase (SOD) that was strongly induced in these cells by treatment with S-nitroso-glutathione as a NO-donating agent. Bacterial lipopolysaccharide (LPS) acutely decreased Cu/Zn SOD mRNA levels. The LPS-mediated decrease in Cu/Zn SOD is reversed by endogenously produced NO, as LPS also induced a delayed strong iNOS expression in these cells in vitro, which is accompanied by increased Cu/Zn SOD expression. NO dependency of Cu/Zn SOD mRNA recovery could be demonstrated by inhibition of this process by L-NG-monomethylarginine, an inhibitor of NOS enzymatic activity. To demonstrate the in vivo relevance of our observations, we have chosen LPS-treated rats as a model for induction of a systemic inflammatory response. In these animals, we demonstrate a direct coupling of Cu/Zn SOD expression levels to the presence of NO, as Cu/Zn SOD mRNA levels declined during acute inflammation in the presence of a selective inhibitor of iNOS. We propose that the up-regulation of Cu/Zn SOD by endogenous NO may serve as an adaptive, protective mechanism to prevent the formation of toxic quantities of peroxynitrite in conditions associated with iNOS induction during endotoxic shock.

Isn't Citizen Science a Hoot? A Case-study Exploring the Effectiveness of Citizen Science As an Instrument to Teach the Nature of Science through a Local Nocturnal Owl-monitoring Project

NASA Astrophysics Data System (ADS)

Kreofsky, Tess Marie

Citizen science projects present a distinctive opportunity for professional and volunteer scientists to coordinate their efforts to gather unique sets of data that can benefit the scientific and local communities. These projects are assumed to be an effective educational tool to teach nature of science (NOS) to participants (Brossard, Lewenstein, Bonney, 2005). This case study evaluates the effectiveness of participation in a citizen science project as a way to learn about NOS. Through enhancement of the Tryon Creek Owl Monitoring Project the researcher reviewed the characteristics of a citizen science project that were thought to be necessary to impact the volunteers' knowledge of NOS. The study also explored the benefits and limitations to organizing the citizen science protect using the principles of action research. Analysis of participants' knowledge and the effectiveness of active research theory, was evaluated through pre- and post- questionnaires and interviews. Although volunteers were able to explore the core themes of NOS through actively engaging in the scientific process, they did not experience a statistically significant change in their demonstration of understanding. For a multitude of reasons, participants had a positive experience with the presence of an embedded researcher within the project. This case study supports the use of active research as a guide to ensure that within each project the needs of both the scientific community and the volunteer scientists are met.

FRONT ELEVATION, PAIR OF HOUSES ON THE NORTH SIDE OF ...

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

FRONT ELEVATION, PAIR OF HOUSES ON THE NORTH SIDE OF DIAMOND STREET FURTHER WEST THAN THE UNITS DEPICTED IN HABS NOS. PA-6701-1 AND PA-6701-2. - 1700 Block Diamond Street (Houses), North & south sides between Seventeenth & Eighteenth Streets, Philadelphia, Philadelphia County, PA

76 FR 63657 - Certain Flat Panel Display Devices, and Products Containing the Same; Notice of Commission...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-13

... the same by reason of infringement of various claims of United States Patent Nos. 6,281,955; 7,697,093... Mobility LLC of Atlanta, Georgia; Best Buy Stores, L.P. of Richfield, Minnesota; BestBuy.com , LLC of Eden...

78 FR 70069 - Circular Welded Carbon-Quality Steel Pipe From China

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2013-11-22

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-447 and 731-TA-1116 (Review)] Circular Welded Carbon-Quality Steel Pipe From China Determination On the basis of the record \\1\\ developed in the subject five-year reviews, the United States International Trade Commission (Commission) determines...

78 FR 76857 - 1,1,1,2-Tetrafluoroethane From China; Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-509 and 731-TA-1244 (Preliminary)] 1,1,1... subject investigations, the United States International Trade Commission (Commission) determines, pursuant... Secretary, U.S. International Trade Commission, Washington, DC, and by publishing the notice in the Federal...

7 CFR 868.308 - Percentages.

Code of Federal Regulations, 2011 CFR

2011-01-01

... FOR CERTAIN AGRICULTURAL COMMODITIES United States Standards for Milled Rice Principles Governing... in U.S. Nos. 1 and 2 Milled Rice and the percentage of objectionable seeds in U.S. No. 1 Brewers Milled Rice is reported to the nearest hundredth percent. The percentages of all other factors are...

7 CFR 868.308 - Percentages.

Code of Federal Regulations, 2010 CFR

2010-01-01

... FOR CERTAIN AGRICULTURAL COMMODITIES United States Standards for Milled Rice Principles Governing... in U.S. Nos. 1 and 2 Milled Rice and the percentage of objectionable seeds in U.S. No. 1 Brewers Milled Rice is reported to the nearest hundredth percent. The percentages of all other factors are...

75 FR 7519 - In the Matter of Certain Digital Cameras; Notice of Commission Determination Not To Review an...

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2010-02-19

... United States Patent Nos. 5,731,852 and 6,229,695. The complaint named Eastman Kodak Company of Rochester, New York (``Kodak'') as respondent. On January 8, 2010, Samsung and Kodak filed a joint motion to...

76 FR 57075 - Helical Spring Lock Washers From China and Taiwan

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... Functionally Equivalent Agreement, August 12, 2011 (Notice). See also Docket Nos. MC2010-35, R2010-5 and R2010... Operators 1 product and two functionally equivalent agreements, Strategic Bilateral Agreement Between United...[egrave]s Service Agreement is functionally equivalent to the delivery confirmation service provided with...

University of California, Irvine, Student Affirmative Action Five-Year Plan and Planning Process, 1984-1988. Volume II.

ERIC Educational Resources Information Center

Galligani, Dennis J.

This second volume of the University of California, Irvine (UCI), Student Affirmative Action (SAA) Five-Year Plan contains the complete student affirmative action plans as submitted by 33 academic and administrative units at UCI. The volume is organized by type of unit: academic units, academic retention units, outreach units, and student life…

Bench Test of the Vibration Compensation Interferometer for EAST Tokamak

NASA Astrophysics Data System (ADS)

Li, Gongshun; Yang, Yao; Liu, Haiqing; Jie, Yinxian; Zou, Zhiyong; Wang, Zhengxing; Zeng, Long; Wei, Xuechao; Li, Weiming; Lan, Ting; Zhu, Xiang; Liu, Yukai; Gao, Xiang

2016-02-01

A visible laser-based vibration compensation interferometer has recently been designed for the EAST tokamak and the bench test has been finished. The system was optimized for its installation on EAST. The value of the final optical power before the detectors without plasma has been calculated from the component bench test result, which is quite close to the measured value. A nanometer level displacement (of the order of the laser's wavelength) has been clearly measured by a modulation of piezoelectric ceramic unit, proving the system's capability. supported by the National Magnetic Confinement Fusion Program of China (Nos. 2014GB106002, 2014GB106003, 2014GB106004) and National Natural Science Foundation of China (Nos. 11105184, 11375237, 11505238)

The "RA" Expeditions: The Archaeological and Anthropological Background. The "RA" Expeditions: The Coriolis Effect. The "RA" Expeditions: The Papyrus Reed. Learning Experiences for Coastal and Oceanic Awareness Studies, Nos. 211, 212, 213. [Project COAST].

ERIC Educational Resources Information Center

Delaware Univ., Newark. Coll. of Education.

Included are three units related to coastal and oceanic awareness. These are: (1) The "RA" Expeditions: The Archaeological and Anthropological Background; (2) The "RA" Expeditions: The Coriolis Effect; and (3) The "RA" Expeditions: The Papyrus Reed. Each of the three units are designed for students in grades 6-12.…

Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

PubMed

Fazio, Francesco; Carrizzo, Albino; Lionetto, Luana; Damato, Antonio; Capocci, Luca; Ambrosio, Mariateresa; Battaglia, Giuseppe; Bruno, Valeria; Madonna, Michele; Simmaco, Maurizio; Nicoletti, Ferdinando; Vecchione, Carmine

2017-01-01

The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS), and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS). LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO) inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension.

Vasorelaxing Action of the Kynurenine Metabolite, Xanthurenic Acid: The Missing Link in Endotoxin-Induced Hypotension?

PubMed Central

Fazio, Francesco; Carrizzo, Albino; Lionetto, Luana; Damato, Antonio; Capocci, Luca; Ambrosio, Mariateresa; Battaglia, Giuseppe; Bruno, Valeria; Madonna, Michele; Simmaco, Maurizio; Nicoletti, Ferdinando; Vecchione, Carmine

2017-01-01

The kynurenine pathway of tryptophan metabolism is activated by pro-inflammatory cytokines. L-kynurenine, an upstream metabolite of the pathway, acts as a putative endothelium-derived relaxing factor, and has been hypothesized to play a causative role in the pathophysiology of inflammation-induced hypotension. Here, we show that xanthurenic acid (XA), the transamination product of 3-hydroxykynurenine, is more efficacious than L-kynurenine in causing relaxation of a resistance artery, but fails to relax pre-contracted aortic rings. In the mesenteric artery, XA enhanced activating phosphorylation of endothelial nitric oxide synthase (NOS), and the relaxing action of XA was abrogated by pharmacological inhibition of NOS and endothelial-derived hyperpolarizing factor. Systemic injection of XA reduced blood pressure in mice, and serum levels of XA increased by several fold in response to a pulse with the endotoxin, lipopolysaccharide (LPS). LPS-induced hypotension in mice was prevented by pre-treatment with the kynurenine monooxygenase (KMO) inhibitor, Ro-618048, which lowered serum levels of XA but enhanced serum levels of L-kynurenine. UPF 648, another KMO inhibitor, could also abrogate LPS-induced hypotension. Our data identify XA as a novel vasoactive compound and suggest that formation of XA is a key event in the pathophysiology of inflammation-induced hypotension. PMID:28507519

A Neural Basis of Facial Action Recognition in Humans

PubMed Central

Srinivasan, Ramprakash; Golomb, Julie D.

2016-01-01

By combining different facial muscle actions, called action units, humans can produce an extraordinarily large number of facial expressions. Computational models and studies in cognitive science and social psychology have long hypothesized that the brain needs to visually interpret these action units to understand other people's actions and intentions. Surprisingly, no studies have identified the neural basis of the visual recognition of these action units. Here, using functional magnetic resonance imaging and an innovative machine learning analysis approach, we identify a consistent and differential coding of action units in the brain. Crucially, in a brain region thought to be responsible for the processing of changeable aspects of the face, multivoxel pattern analysis could decode the presence of specific action units in an image. This coding was found to be consistent across people, facilitating the estimation of the perceived action units on participants not used to train the multivoxel decoder. Furthermore, this coding of action units was identified when participants attended to the emotion category of the facial expression, suggesting an interaction between the visual analysis of action units and emotion categorization as predicted by the computational models mentioned above. These results provide the first evidence for a representation of action units in the brain and suggest a mechanism for the analysis of large numbers of facial actions and a loss of this capacity in psychopathologies. SIGNIFICANCE STATEMENT Computational models and studies in cognitive and social psychology propound that visual recognition of facial expressions requires an intermediate step to identify visible facial changes caused by the movement of specific facial muscles. Because facial expressions are indeed created by moving one's facial muscles, it is logical to assume that our visual system solves this inverse problem. Here, using an innovative machine learning method and neuroimaging data, we identify for the first time a brain region responsible for the recognition of actions associated with specific facial muscles. Furthermore, this representation is preserved across subjects. Our machine learning analysis does not require mapping the data to a standard brain and may serve as an alternative to hyperalignment. PMID:27098688

77 FR 45653 - Stainless Steel Bar From Brazil, India, Japan, and Spain; Determination

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-01

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 731-TA-678, 679, 681, and 682 (Third Review)] Stainless Steel Bar From Brazil, India, Japan, and Spain; Determination Determination On the basis of the record \\1\\ developed in the subject five-year reviews, the United States International Trade Commission...

78 FR 64243 - 1,1,1,2-Tetrafluoroethane From China; Institution of Antidumping and Countervailing Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-28

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-509 and 731-TA-1244 (Preliminary)] 1,1,1... and Scheduling of Preliminary Phase Investigations AGENCY: United States International Trade... CONTACT: Chris Cassise (202-708-5408), Office of Investigations, U.S. International Trade Commission, 500...

78 FR 7452 - Steel Wire Garment Hangers From Vietnam; Determinations

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2013-02-01

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-487 and 731-TA-1198 (Final)] Steel Wire...), that an industry in the United States is materially injured by reason of imports of steel wire garment... duty orders on steel wire garment hangers from Vietnam. Background The Commission instituted these...

21 CFR 522.1680 - Oxytocin.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Oxytocin. 522.1680 Section 522.1680 Food and Drugs..., AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1680 Oxytocin. (a) Specifications. Each milliliter (mL) of solution contains 20 USP units oxytocin. (b) Sponsors. See Nos. , 000859...

76 FR 29791 - Bottom Mount Combination Refrigerator-Freezers From Korea and Mexico

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-23

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-477 and 731-TA-1180-1181 (Preliminary)] Bottom Mount Combination Refrigerator-Freezers From Korea and Mexico Determinations On the basis of the record \\1\\ developed in the subject investigations, the United States International Trade Commission (Commission) determines, pursuant to section...

76 FR 28807 - High Pressure Steel Cylinders From China; Institution of Antidumping and Countervailing Duty...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-18

... the United States is materially retarded, by reason of imports from China of High Pressure Steel... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-480 and 731-TA-1188 (Preliminary)] High Pressure Steel Cylinders From China; Institution of Antidumping and Countervailing Duty Investigations and...

76 FR 5609 - Government in the Sunshine Act Meeting Notice

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2011-02-01

... INTERNATIONAL TRADE COMMISSION [USITC SE-11-002] Government in the Sunshine Act Meeting Notice AGENCY HOLDING THE MEETING: United States International Trade Commission. TIME AND DATE: February 9, 2011.... Ratification List. 4. Vote in Inv. Nos. 731-TA-1071 and 1072 (Review)(Magnesium from China and Russia). The...

75 FR 63222 - Claymore Exchange-Traded Fund Trust, et al.;

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2010-10-14

... Exchange-Traded Fund Trust, et al.; Notice of Application October 7, 2010. AGENCY: Securities and Exchange... Fund Trust, et al., Investment Company Act Release Nos. 27469 (Aug. 28, 2006) (notice) and 27483 (Sept... investment companies and unit investment trusts outside of the same group of investment companies as the...

78 FR 65389 - United States Enrichment Corporation, Paducah Gaseous Diffusion Plant

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2013-10-31

..., USEC notified the NRC of its decision to permanently cease uranium enrichment activities at the PGDP... Accession Nos. ML13105A010 and ML13176A151, respectively. NRC's PDR: You may examine and purchase copies of... in Paducah, Kentucky, using the gaseous [[Page 65390

The estrogen-dependent baroreflex dysfunction caused by nicotine in female rats is mediated via NOS/HO inhibition: Role of sGC/PI3K/MAPK{sub ERK}

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

Fouda, Mohamed A.; El-Gowelli, Hanan M.; El-Gowilly, Sahar M.

We have previously reported that estrogen (E2) exacerbates the depressant effect of chronic nicotine on arterial baroreceptor activity in female rats. Here, we tested the hypothesis that this nicotine effect is modulated by nitric oxide synthase (NOS) and/or heme oxygenase (HO) and their downstream soluble guanylate cyclase (sGC)/phosphatidylinositol 3-kinase (PI3K)/mitogen-activated protein kinases (MAPKs) signaling. We investigated the effects of (i) inhibition or facilitation of NOS or HO on the interaction of nicotine (2 mg/kg/day i.p., 2 weeks) with reflex bradycardic responses to phenylephrine in ovariectomized (OVX) rats treated with E2 or vehicle, and (ii) central pharmacologic inhibition of sGC, PI3K,more » or MAPKs on the interaction. The data showed that the attenuation by nicotine of reflex bradycardia in OVXE2 rats was abolished after treatment with hemin (HO inducer) or L-arginine (NOS substrate). The hemin or L-arginine effect disappeared after inhibition of NOS (Nω-Nitro-L-arginine methyl ester hydrochloride, L-NAME) and HO (zinc protoporphyrin IX, ZnPP), respectively, denoting the interaction between the two enzymatic pathways. E2-receptor blockade (ICI 182,780) reduced baroreflexes in OVXE2 rats but had no effect on baroreflex improvement induced by hemin or L-arginine. Moreover, baroreflex enhancement by hemin was eliminated following intracisternal (i.c.) administration of wortmannin, ODQ, or PD98059 (inhibitors of PI3K, sGC, and extracellular signal-regulated kinases, MAPK{sub ERK}, respectively). In contrast, the hemin effect was preserved after inhibition of MAPK{sub p38} (SB203580) or MAPK{sub JNK} (SP600125). Overall, NOS/HO interruption underlies baroreflex dysfunction caused by nicotine in female rats and the facilitation of NOS/HO-coupled sGC/PI3K/MAPK{sub ERK} signaling might rectify the nicotine effect. - Highlights: • Hemin or L-arginine blunts baroreflex dysfunction caused by nicotine in OVXE2 rats. • NO/CO crosstalk mediates favorable baroreflex effect of hemin or L-arginine. • Central sGC/PI3K/MAPK{sub ERK} is required for hemin facilitation of baroreflexes. • The favorable baroreflex action of hemin is independent of estrogen receptors.« less

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity

PubMed Central

2012-01-01

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure–activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, Ki = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain. PMID:24900459

NOpiates: Novel Dual Action Neuronal Nitric Oxide Synthase Inhibitors with μ-Opioid Agonist Activity.

PubMed

Renton, Paul; Green, Brenda; Maddaford, Shawn; Rakhit, Suman; Andrews, John S

2012-03-08

A novel series of benzimidazole designed multiple ligands (DMLs) with activity at the neuronal nitric oxide synthase (nNOS) enzyme and the μ-opioid receptor was developed. Targeting of the structurally dissimilar heme-containing enzyme and the μ-opioid GPCR was predicated on the modulatory role of nitric oxide on μ-opioid receptor function. Structure-activity relationship studies yielded lead compound 24 with excellent nNOS inhibitory activity (IC50 = 0.44 μM), selectivity over both endothelial nitric oxide synthase (10-fold) and inducible nitric oxide synthase (125-fold), and potent μ-opioid binding affinity, K i = 5.4 nM. The functional activity as measured in the cyclic adenosine monosphospate secondary messenger assay resulted in full agonist activity (EC50 = 0.34 μM). This work represents a novel approach in the development of new analgesics for the treatment of pain.

Primary health care assessment from the users' perspectives: a systematic review.

PubMed

Paula, Weslla Karla Albuquerque Silva de; Samico, Isabella Chagas; Caminha, Maria de Fátima Costa; Filho, Malaquias Batista; Silva, Suzana Lins da

2016-04-01

Analyze the evaluation of the attributes of primary care made by users of basic units of Brazilian health by using PCATool instrument adapted to Brazil. A systematic literature review conducted in the PubMed database, IBECS, LILACS, SciELO and BDTD. 4,405 documents were found, selected 23 full texts. After Full reading and application of eligibility criteria, 14 articles were evaluated. The studies showed that primary care performs well in longitudinality attributes, completeness and coordination and worse performance on attributes access first contact, family counseling and community orientation, even in the basic units with the Family Health. The users of basic health units assessed as unsatisfactory attributes considered essential for a health care more equitable and competing for user autonomy and social control. It is inferred that there are still obstacles hindering user access to basic health services and care actions are still being developed without favoring user participation and the community context in which they live. Analisar a avaliação dos atributos da Atenção Básica feita por usuários de unidades básicas de saúde brasileiras, mediante utilização de adaptações do instrumento PCATool para o Brasil. Revisão sistemática da literatura realizada nas bases de dados Medline/PubMed, LILACS, IBECS, SciELO e BDTD. Foram encontrados 4.405 documentos, sendo selecionados 23 textos completos. Após leitura integral e aplicação dos critérios de elegibilidade, 14 artigos foram avaliados. Os estudos apontaram que a Atenção Básica tem bom desempenho nos atributos longitudinalidade, integralidade e coordenação e pior desempenho nos atributos acesso de primeiro contato, orientação familiar e a orientação comunitária, mesmo nas unidades básicas com Saúde da Família. Os usuários das unidades básicas de saúde avaliaram como insatisfatórios atributos considerados fundamentais para uma atenção à saúde mais equânime e concorrente para autonomia do usuário e controle social. Infere-se que ainda existem obstáculos que dificultam o acesso dos usuários aos serviços básicos de saúde e que ações do cuidado ainda estejam sendo desenvolvidas sem privilegiar a participação do usuário e o contexto comunitário onde vivem.

Substance P Activates Ca2+-Permeable Nonselective Cation Channels through a Phosphatidylcholine-Specific Phospholipase C Signaling Pathway in nNOS-Expressing GABAergic Neurons in Visual Cortex.

PubMed

Endo, Toshiaki; Yanagawa, Yuchio; Komatsu, Yukio

2016-02-01

To understand the functions of the neocortex, it is essential to characterize the properties of neurons constituting cortical circuits. Here, we focused on a distinct group of GABAergic neurons that are defined by a specific colocalization of intense labeling for both neuronal nitric oxide synthase (nNOS) and substance P (SP) receptor [neurokinin 1 (NK1) receptors]. We investigated the mechanisms of the SP actions on these neurons in visual cortical slices obtained from young glutamate decarboxylase 67-green fluorescent protein knock-in mice. Bath application of SP induced a nonselective cation current leading to depolarization that was inhibited by the NK1 antagonists in nNOS-immunopositive neurons. Ruthenium red and La(3+), transient receptor potential (TRP) channel blockers, suppressed the SP-induced current. The SP-induced current was mediated by G proteins and suppressed by D609, an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), but not by inhibitors of phosphatidylinositol-specific PLC, adenylate cyclase or Src tyrosine kinases. Ca(2+) imaging experiments under voltage clamp showed that SP induced a rise in intracellular Ca(2+) that was abolished by removal of extracellular Ca(2+) but not by depletion of intracellular Ca(2+) stores. These results suggest that SP regulates nNOS neurons by activating TRP-like Ca(2+)-permeable nonselective cation channels through a PC-PLC-dependent signaling pathway. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Galantamine and carbon monoxide protect brain microvascular endothelial cells by heme oxygenase-1 induction

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

Nakao, Atsunori; Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; Kaczorowski, David J.

2008-03-14

Galantamine, a reversible inhibitor of acetylcholine esterase (AChE), is a novel drug treatment for mild to moderate Alzheimer's disease and vascular dementia. Interestingly, it has been suggested that galantamine treatment is associated with more clinical benefit in patients with mild-to-moderate Alzheimer disease compared to other AChE inhibitors. We hypothesized that the protective effects of galantamine would involve induction of the protective gene, heme oxygenase-1 (HO-1), in addition to enhancement of the cholinergic system. Brain microvascular endothelial cells (mvECs) were isolated from spontaneous hypertensive rats. Galantamine significantly reduced H{sub 2}O{sub 2}-induced cell death of mvECs in association with HO-1 induction. Thesemore » protective effects were completely reversed by nuclear factor-{kappa}B (NF-{kappa}B) inhibition or HO inhibition. Furthermore, galantamine failed to induce HO-1 in mvECs which lack inducible nitric oxide synthase (iNOS), supplementation of a nitric oxide (NO) donor or iNOS gene transfection on iNOS-deficient mvECs resulted in HO-1 induction with galantamine. These data suggest that the protective effects of galantamine require NF-{kappa}B activation and iNOS expression, in addition to HO-1. Likewise, carbon monoxide (CO), one of the byproducts of HO, up-regulated HO-1 and protected mvECs from oxidative stress in a similar manner. Our data demonstrate that galantamine mediates cytoprotective effects on mvECs through induction HO-1. This pharmacological action of galantamine may, at least in part, account for the superior clinical efficacy of galantamine in vascular dementia and Alzheimer disease.« less

7 CFR 275.16 - Corrective action planning.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 4 2010-01-01 2010-01-01 false Corrective action planning. 275.16 Section 275.16... Corrective action planning. (a) Corrective action planning is the process by which State agencies shall...)/management unit(s) in the planning, development, and implementation of corrective action are those which: (1...

Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway

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

Ou, Hsiu-Chung; Lee, Wen-Jane; Tunghai University, Taichung, Taiwan

Endothelial apoptosis is a driving force in atherosclerosis development. Oxidized low-density lipoprotein (oxLDL) promotes inflammatory and thrombotic processes and is highly atherogenic, as it stimulates macrophage cholesterol accumulation and foam cell formation. Previous studies have shown that the phosphatidylinositol 3-kinase/Akt/endothelial nitric oxide synthase/nitric oxide (PI3K/Akt/eNOS/NO) pathway is involved in oxLDL-induced endothelial apoptosis. Ellagic acid, a natural polyphenol found in berries and nuts, has in recent years been the subject of intense research within the fields of cancer and inflammation. However, its protective effects against oxLDL-induced injury in vascular endothelial cells have not been clarified. In the present study, we investigatedmore » the anti-apoptotic effect of ellagic acid in human umbilical vein endothelial cells (HUVECs) exposed to oxLDL and explored the possible mechanisms. Our results showed that pretreatment with ellagic acid (5-20 {mu}M) significantly attenuated oxLDL-induced cytotoxicity, apoptotic features, and generation of reactive oxygen species (ROS). In addition, the anti-apoptotic effect of ellagic acid was partially inhibited by a PI3K inhibitor (wortmannin) and a specific eNOS inhibitor (cavtratin) but not by an ERK inhibitor (PD98059). In exploring the underlying mechanisms of ellagic acid action, we found that oxLDL decreased Akt and eNOS phosphorylation, which in turn activated NF-{kappa}B and downstream pro-apoptotic signaling events including calcium accumulation, destabilization of mitochondrial permeability, and disruption of the balance between pro- and anti-apoptotic Bcl-2 proteins. Those alterations induced by oxLDL, however, were attenuated by pretreatment with ellagic acid. The inhibition of oxLDL-induced endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway.« less

Hydrogen sulfide triggers late-phase preconditioning in postischemic small intestine by an NO- and p38 MAPK-dependent mechanism

PubMed Central

Yusof, Mozow; Kamada, Kazuhiro; Kalogeris, Theodore; Gaskin, F. Spencer; Korthuis, Ronald J.

2009-01-01

Hydrogen sulfide (H2S) is one of three endogenous gases, along with carbon monoxide (CO) and nitric oxide (NO), that exert a variety of important vascular actions in vivo. Although it has been demonstrated that CO or NO can trigger the development of a preconditioned phenotype in postischemic tissues, it is unclear whether H2S may also induce protection in organs subsequently exposed to ischemia-reperfusion (I/R). In light of these observations, we postulated that preconditioning with the exogenous H2S donor sodium hydrosulfide (NaHS-PC) would inhibit leukocyte rolling (LR) and adhesion (LA) induced by I/R. We used intravital microscopic techniques to demonstrate that NaHS-PC 24 h, but not 1 h, before I/R causes postcapillary venules to shift to an anti-inflammatory phenotype in wild-type (WT) mice such that these vessels fail to support LR and LA during reperfusion. The protective effect of NaHS-PC on LR was largely abolished by coincident pharmacological inhibition of NO synthase (NOS) in WT animals and was absent in endothelial NOS-deficient (eNOS−/−) mice. A similar pattern of response was noted in WT mice treated concomitantly with NaHS plus p38 mitogen-activated protein kinase (MAPK) inhibitors (SB 203580 or SK-86002). Whereas the reduction in LA induced by antecedent NaHS was attenuated by pharmacological inhibition of NOS or p38 MAPK in WT mice, the antiadhesive effect of NaHS was still evident in eNOS−/− mice. Thus NaHS-PC prevents LR and LA by triggering the activation of an eNOS- and p38 MAPK-dependent mechanism. However, the role of eNOS in the antiadhesive effect of NaHS-PC was less prominent than its effect to reduce LR. PMID:19168723

Single-dose rosuvastatin ameliorates lung ischemia-reperfusion injury via upregulation of endothelial nitric oxide synthase and inhibition of macrophage infiltration in rats with pulmonary hypertension.

PubMed

Matsuo, Satoshi; Saiki, Yuriko; Adachi, Osamu; Kawamoto, Shunsuke; Fukushige, Shinichi; Horii, Akira; Saiki, Yoshikatsu

2015-03-01

Lung ischemia-reperfusion (IR) injury during cardiopulmonary surgery is associated with postoperative morbidity and mortality, particularly in patients with pulmonary hypertension (PH). Using a rat model for monocrotaline-induced PH, we investigated the protective effect of rosuvastatin against IR injury in lungs affected by PH and attempted to elucidate its mechanism of action. Male Sprague-Dawley monocrotaline-treated rats were divided into 4 groups (n = 8-9): sham, control + IR, statin + IR, and statin + mevalonolactone + IR. Lung ischemia was induced by left pulmonary artery occlusion (1 hour), followed by reperfusion (4 hours). Rosuvastatin (2 mg/kg) was injected 18 hours before reperfusion and mevalonolactone (1 mg/kg) was injected immediately before reperfusion. The arterial oxygen tension/inspired oxygen fraction ratio was used as a measure of lung oxygenation. Left lung tissue was analyzed for the wet-to-dry lung weight ratio and protein expression of endothelial nitric oxide synthase (eNOS) and phospho-eNOS. Macrophage recruitment was assessed by CD68 immunostaining. Our results showed that rosuvastatin decreased IR lung injury (control + IR vs statin + IR) in terms of the arterial oxygen tension/inspired oxygen fraction ratio (272 ± 43 vs 442 ± 13), wet-to-dry ratio (5.7 ± 0.7 vs 4.8 ± 0.6), and macrophage infiltration (8.0 ± 0.6/field vs 4.0 ± 0.5/field) (P < .05 for all). eNOS and phospho-eNOS were downregulated by IR, which was blocked by rosuvastatin. Effects of rosuvastatin were blunted by mevalonolactone. Single-dose rosuvastatin decreased IR injury in lungs affected by PH via 2 anti-inflammatory mechanisms: preserving eNOS function and inhibiting macrophage infiltration. Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Leptin-dependent neuronal NO signaling in the preoptic hypothalamus facilitates reproduction.

PubMed

Bellefontaine, Nicole; Chachlaki, Konstantina; Parkash, Jyoti; Vanacker, Charlotte; Colledge, William; d'Anglemont de Tassigny, Xavier; Garthwaite, John; Bouret, Sebastien G; Prevot, Vincent

2014-06-01

The transition to puberty and adult fertility both require a minimum level of energy availability. The adipocyte-derived hormone leptin signals the long-term status of peripheral energy stores and serves as a key metabolic messenger to the neuroendocrine reproductive axis. Humans and mice lacking leptin or its receptor fail to complete puberty and are infertile. Restoration of leptin levels in these individuals promotes sexual maturation, which requires the pulsatile, coordinated delivery of gonadotropin-releasing hormone to the pituitary and the resulting surge of luteinizing hormone (LH); however, the neural circuits that control the leptin-mediated induction of the reproductive axis are not fully understood. Here, we found that leptin coordinated fertility by acting on neurons in the preoptic region of the hypothalamus and inducing the synthesis of the freely diffusible volume-based transmitter NO, through the activation of neuronal NO synthase (nNOS) in these neurons. The deletion of the gene encoding nNOS or its pharmacological inhibition in the preoptic region blunted the stimulatory action of exogenous leptin on LH secretion and prevented the restoration of fertility in leptin-deficient female mice by leptin treatment. Together, these data indicate that leptin plays a central role in regulating the hypothalamo-pituitary-gonadal axis in vivo through the activation of nNOS in neurons of the preoptic region.

Maslinic acid, a natural triterpenoid compound from Olea europaea, protects cortical neurons against oxygen-glucose deprivation-induced injury.

PubMed

Qian, Yisong; Guan, Teng; Tang, Xuzhen; Huang, Longfei; Huang, Menghao; Li, Yunman; Sun, Hongbin

2011-11-16

Maslinic acid is a triterpenoid compound present in plants of Olea europaea. This compound has been reported to have potent antioxidant, anti-cancer, anti-HIV and anti-inflammatory activities. In this study, we investigated the neuroprotective effect of maslinic acid and its mechanism of action. With presence or absence of maslinic acid, cortical neurons were subjected to 1h of oxygen-glucose deprivation and 24h of reoxygenation. Cell injury was determined by lactate dehydrogenase (LDH) measurement and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Neuronal apoptosis was evaluated by flow cytometry assay, caspase-3 expression/activity, caspase-9 activity and Bcl-2/Bax ratio. Nitric Oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were also detected. Results showed that maslinic acid dose-dependently ameliorated neuron injury and apoptosis. Maslinic acid treatment normalized the caspase expression/activation and increased the Bcl-2/Bax ratio. In addition, maslinic acid inhibited oxygen-glucose deprivation-induced NO production and iNOS expression. These results indicated that maslinic acid has beneficial effects on hypoxic neurons by suppressing iNOS activation, which may, in turn, provide neuroprotection. Copyright © 2011 Elsevier B.V. All rights reserved.

75 FR 82070 - Light-Walled Rectangular Pipe and Tube From China, Korea, and Mexico

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... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-449 and 731-TA-1118-1120 (Remand)] Light... panel proceeding in Light-Walled Rectangular Pipe and Tube from Mexico, USA-MEX-1904-04, to file... that an industry in the United States was materially injured by reason of subsidized imports of light...

76 FR 37830 - Polyester Staple Fiber From Korea and Taiwan; Scheduling of Expedited Five-Year Reviews...

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Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-07

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75 FR 16517 - Dominion Nuclear Connecticut, Inc.; Millstone Power Station, Unit Nos 1, 2, and 3; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

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Federal Register 2010, 2011, 2012, 2013, 2014

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Federal Register 2010, 2011, 2012, 2013, 2014

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Explicit Reflective Nature of Science Instruction: Evolution, Intelligent Design, and Umbrellaology

ERIC Educational Resources Information Center

Scharmann, Lawrence C.; Smith, Mike U.; James, Mark C.; Jensen, Murray

2005-01-01

The investigators sought to design an instructional unit to enhance an understanding of the nature of science (NOS) by taking into account both instructional best practices and suggestions made by noted science philosopher Thomas Kuhn. Preservice secondary science teachers enrolled in a course, "Laboratory Techniques in the Teaching of Science,"…

Joint Facial Action Unit Detection and Feature Fusion: A Multi-conditional Learning Approach.

PubMed

Eleftheriadis, Stefanos; Rudovic, Ognjen; Pantic, Maja

2016-10-05

Automated analysis of facial expressions can benefit many domains, from marketing to clinical diagnosis of neurodevelopmental disorders. Facial expressions are typically encoded as a combination of facial muscle activations, i.e., action units. Depending on context, these action units co-occur in specific patterns, and rarely in isolation. Yet, most existing methods for automatic action unit detection fail to exploit dependencies among them, and the corresponding facial features. To address this, we propose a novel multi-conditional latent variable model for simultaneous fusion of facial features and joint action unit detection. Specifically, the proposed model performs feature fusion in a generative fashion via a low-dimensional shared subspace, while simultaneously performing action unit detection using a discriminative classification approach. We show that by combining the merits of both approaches, the proposed methodology outperforms existing purely discriminative/generative methods for the target task. To reduce the number of parameters, and avoid overfitting, a novel Bayesian learning approach based on Monte Carlo sampling is proposed, to integrate out the shared subspace. We validate the proposed method on posed and spontaneous data from three publicly available datasets (CK+, DISFA and Shoulder-pain), and show that both feature fusion and joint learning of action units leads to improved performance compared to the state-of-the-art methods for the task.

26 CFR 301.7403-1 - Action to enforce lien or to subject property to payment of tax.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Action to enforce lien or to subject property... Proceedings Civil Actions by the United States § 301.7403-1 Action to enforce lien or to subject property to... to be filed in a district court of the United States to enforce the lien of the United States under...

Corrective Action Decision Document for Corrective Action Unit 340: Pesticide Release sites, Nevada Test Site, Nevada

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

DOE /NV

This Corrective Action Decision Document has been prepared for Corrective Action Unit 340, the NTS Pesticide Release Sites, in accordance with the Federal Facility Agreement and Consent Order of 1996 (FFACO, 1996). Corrective Action Unit 340 is located at the Nevada Test Site, Nevada, and is comprised of the following Corrective Action Sites: 23-21-01, Area 23 Quonset Hut 800 Pesticide Release Ditch; 23-18-03, Area 23 Skid Huts Pesticide Storage; and 15-18-02, Area 15 Quonset Hut 15-11 Pesticide Storage. The purpose of this Corrective Action Decision Document is to identify and provide a rationale for the selection of a recommended correctivemore » action alternative for each Corrective Action Site. The scope of this Corrective Action Decision Document consists of the following tasks: Develop corrective action objectives; Identify corrective action alternative screening criteria; Develop corrective action alternatives; Perform detailed and comparative evaluations of the corrective action alternatives in relation to the corrective action objectives and screening criteria; and Recommend and justify a preferred corrective action alternative for each Corrective Action Site.« less

Transition from an open-plan to a two-cot neonatal intensive care unit: a participatory action research approach.

PubMed

Broom, Margaret; Gardner, Anne; Kecskes, Zsuzsoka; Kildea, Sue

2017-07-01

To facilitate staff transition from an open-plan to a two-cot neonatal intensive care unit design. In 2012, an Australian regional neonatal intensive care unit transitioned from an open-plan to a two-cot neonatal intensive care unit design. Research has reported single- and small-room neonatal intensive care unit design may negatively impact on the distances nurses walk, reducing the time they spend providing direct neonatal care. Studies have also reported nurses feel isolated and need additional support and education in such neonatal intensive care units. Staff highlighted their concerns regarding the impact of the new design on workflow and clinical practice. A participatory action research approach. A participatory action group titled the Change and Networking Group collaborated with staff over a four-year period (2009-2013) to facilitate the transition. The Change and Networking Group used a collaborative, cyclical process of planning, gathering data, taking action and reviewing the results to plan the next action. Data sources included meeting and workshop minutes, newsletters, feedback boards, subgroup reports and a staff satisfaction survey. The study findings include a description of (1) how the participatory action research cycles were used by the Change and Networking Group: providing examples of projects and strategies undertaken; and (2) evaluations of participatory action research methodology and Group by neonatal intensive care unit staff and Change and Networking members. This study has described the benefits of using participatory action research to facilitate staff transition from an open-plan to a two-cot neonatal intensive care unit design. Participatory action research methodology enabled the inclusion of staff to find solutions to design and clinical practice questions. Future research is required to assess the long-term effect of neonatal intensive care unit design on staff workload, maintaining and supporting a skilled workforce as well as the impact of a new neonatal intensive care unit design on the neonatal intensive care unit culture. A supportive work environment for staff is critical in providing high-quality health care. © 2016 John Wiley & Sons Ltd.

Epidemiology of otologic diagnoses in United States emergency departments.

PubMed

Kozin, Elliott D; Sethi, Rosh K V; Remenschneider, Aaron K; Kaplan, Alyson B; Del Portal, Daniel A; Gray, Stacey T; Shrime, Mark G; Lee, Daniel J

2015-08-01

Otologic complaints may place a significant burden on emergency departments (EDs) in the United States; however, few studies have comprehensively examined this discrete patient population. We aimed to identify utilization of EDs by patients with primary otologic complaints. Retrospective analysis of the Nationwide Emergency Department Sample (NEDS) from 2009 through 2011. The NEDS database was queried for patient encounters with a primary otologic diagnosis based on International Classification of Diseases, Ninth Revision codes (380-389). Weighted estimates for demographics, diagnostic characteristics, socioeconomic status, and trends over time were extracted. Predictors of mortality and admission were determined by multivariable logistic regression. A weighted total of 8,611,282 visits between 2009 and 2011 were attributed to otologic diagnoses, representing 2.21% of all ED visits. Stratified by patient age, otologic diagnoses encompassed 1.01% and 6.79% of all adult and pediatric ED visits, respectively. The majority of patients were treated and released (98.17%). The average age of patients presenting with an otologic complaint was 17.9 years (standard error = 0.23). Overall, 62.7% of patients who presented with an otologic complaint were 0 to 17 years old. The most common diagnoses among all age groups included otitis media not otherwise specified (NOS) (60.6%), infected otitis externa NOS (11.8%), and otalgia NOS (6.8%). We provide a comprehensive overview of otologic complaints that are an overlooked diagnostic category in public health research. NEDS data demonstrate a significant number of visits related to otologic complaints, especially in the pediatric population, that are nonemergent. 4 © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

Treatment with Sulforaphane Produces Antinociception and Improves Morphine Effects during Inflammatory Pain in Mice.

PubMed

Redondo, Alejandro; Chamorro, Pablo Aníbal Ferreira; Riego, Gabriela; Leánez, Sergi; Pol, Olga

2017-12-01

The activation of nuclear factor erythroid 2-related factor 2 (Nrf2) exerts potent antioxidative and anti-inflammatory effects; however, its participation in the modulation of chronic inflammatory pain and on the antinociceptive effects of μ -opioid receptor (MOR) agonists has not been evaluated. We investigated whether the induction of Nrf2 could alleviate chronic inflammatory pain and augment the analgesic effects of morphine and mechanisms implicated. In male C57BL/6 mice with inflammatory pain induced by complete Freund's adjuvant (CFA) subplantarly administered, we assessed: 1) antinociceptive actions of the administration of 5 and 10 mg/kg of a Nrf2 activator, sulforaphane (SFN); and 2) effects of SFN on the antinociceptive actions of morphine and on protein levels of Nrf2, heme oxygenase 1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) enzymes, microglial activation and inducible nitric oxide synthase (NOS2) overexpression, as well as on mitogen-activated protein kinase (MAPK) and MOR expression in the spinal cord and paw of animals with inflammatory pain. Results showed that treatment with SFN inhibited allodynia and hyperalgesia induced by CFA and increased the local antinociceptive actions of morphine. This treatment also augmented the expression of Nrf2, HO-1, NQO1, and MOR, and inhibited NOS2 and CD11b/c overexpression and MAPK phosphorylation induced by inflammation. Thus, this study shows that the induction of Nrf2 might inhibit inflammatory pain and enhance the analgesic effects of morphine by inhibiting oxidative stress and inflammatory responses induced by peripheral inflammation. This study suggests the administration of SFN alone and in combination with morphine are potential new ways of treating chronic inflammatory pain. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Comparison of anti-inflammatory activities of an anthocyanin-rich fraction from Portuguese blueberries (Vaccinium corymbosum L.) and 5-aminosalicylic acid in a TNBS-induced colitis rat model

PubMed Central

Pereira, Sónia R.; Pereira, Rita; Figueiredo, Isabel; Freitas, Victor; Dinis, Teresa C. P.; Almeida, Leonor M.

2017-01-01

Despite the actual therapeutic approaches for inflammatory bowel disease (IBD), efficient and secure alternative options remain a research focus. In this context, anthocyanins seem promising natural anti-inflammatory agents, but their action mechanisms and efficacy as compared with established drugs still require more clarification. The main aim of this study was to compare the anti-inflammatory action of a chemically characterized anthocyanin-rich fraction (ARF), obtained from Portuguese blueberries (Vaccinium corymbosum L.), with that of 5-aminosalicylic acid (5-ASA), a first-line drug in IBD, in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model. Such fraction showed a high content and great molecular diversity of anthocyanins, with malvidin-3-galactoside and petunidin-3-arabinoside in the highest concentrations. After daily administration by intragastric infusion for 8 days, ARF, at a molar anthocyanin concentration about 30 times lower than 5-ASA, showed a higher effectiveness in counteracting the intestinal inflammation, as assessed by i) body weight variation and colon damage score, ii) reduction in leukocyte infiltration, iii) increase in antioxidant defenses and iv) by downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in colon tissue homogenates. The strong inhibition of COX-2 expression seems to be a crucial anti-inflammatory mechanism common to both ARF and 5-ASA, but the additional higher abilities of anthocyanins to downregulate iNOS and to decrease leukocytes infiltration and to increase antioxidant defenses in colon may account for the much higher anti-inflammatory action of anthocyanins. These data may contribute to the development of a promising natural approach in IBD management. PMID:28329021

Comparison of anti-inflammatory activities of an anthocyanin-rich fraction from Portuguese blueberries (Vaccinium corymbosum L.) and 5-aminosalicylic acid in a TNBS-induced colitis rat model.

PubMed

Pereira, Sónia R; Pereira, Rita; Figueiredo, Isabel; Freitas, Victor; Dinis, Teresa C P; Almeida, Leonor M

2017-01-01

Despite the actual therapeutic approaches for inflammatory bowel disease (IBD), efficient and secure alternative options remain a research focus. In this context, anthocyanins seem promising natural anti-inflammatory agents, but their action mechanisms and efficacy as compared with established drugs still require more clarification. The main aim of this study was to compare the anti-inflammatory action of a chemically characterized anthocyanin-rich fraction (ARF), obtained from Portuguese blueberries (Vaccinium corymbosum L.), with that of 5-aminosalicylic acid (5-ASA), a first-line drug in IBD, in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis rat model. Such fraction showed a high content and great molecular diversity of anthocyanins, with malvidin-3-galactoside and petunidin-3-arabinoside in the highest concentrations. After daily administration by intragastric infusion for 8 days, ARF, at a molar anthocyanin concentration about 30 times lower than 5-ASA, showed a higher effectiveness in counteracting the intestinal inflammation, as assessed by i) body weight variation and colon damage score, ii) reduction in leukocyte infiltration, iii) increase in antioxidant defenses and iv) by downregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in colon tissue homogenates. The strong inhibition of COX-2 expression seems to be a crucial anti-inflammatory mechanism common to both ARF and 5-ASA, but the additional higher abilities of anthocyanins to downregulate iNOS and to decrease leukocytes infiltration and to increase antioxidant defenses in colon may account for the much higher anti-inflammatory action of anthocyanins. These data may contribute to the development of a promising natural approach in IBD management.

Nitric oxide donors attenuate clongenic potential in rat C6 glioma cells treated with alkylating chemotherapeutic agents.

PubMed

Yang, Jir-Jei; Yin, Jiu-Haw; Yang, Ding-I

2007-05-11

1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) kills tumor cells via multiple actions including alkylation and carbamoylation. Previously, we have reported that formation of S-nitrosoglutathione (GSNO) in glioma cells overexpressing inducible nitric oxide synthase (iNOS) contributed to nitric oxide (NO)-dependent carbamoylating chemoresistance against BCNU. To further characterize the effects of NO on alkylating cytotoxicity, colony formation assay was applied to evaluate the effects of various NO donors on rat C6 glioma cells challenged with alkylating agents. We demonstrate that NO donors including GSNO, diethylamine NONOate (DEA/NO), and sodium nitroprusside (SNP) substantially reduced the extent of colony formation in glioma cells treated with alkylating agents, namely methyl methanesulfonate (MMS), N-methyl-N-nitrosourea (MNU), and N-ethyl-N-nitrosourea (ENU). Without alkylating agents these NO-releasing agents alone had no effects on clongenic potential of rat C6 glioma cells. Among these three NO donors used, the effectiveness in potentiating alkylating cytotoxicity is in the order of "GSNO>DEA/NO>SNP" when applied at the same dosages. GSNO also exerted similar synergistic actions reducing the extents of colony formation when co-administrated with 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-hydrazine (compound #1), another alkylating agent that mimics the chloroethylating action of BCNU. Together with our previous findings, we propose that NO donors may be used as adjunct chemotherapy with alkylating agents for such malignant brain tumors as glioblastoma multiforme (GBM). In contrast, production of NO as a result of iNOS induction, such as that occurring after surgical resection of brain tumors, may compromise the efficacy of carbamoylating chemotherapy.

Closure report for Corrective Action Unit 211, Area 15 EPA Farm waste sites, Nevada Test Site, Nevada

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

NONE

1998-04-01

This Closure Report summarizes the corrective actions which were completed at the Corrective Action Sites within Corrective Action Unit 211 Area 15 Farm Waste Sties at the Nevada Test Site. Current site descriptions, observations and identification of wastes removed are included on FFACO Corrective Action Site housekeeping closure verification forms.

Effects of IFN-β1a and IFN-β1b treatment on the expression of cytokines, inducible NOS (NOS type II), and myelin proteins in animal model of multiple sclerosis.

PubMed

Lubina-Dąbrowska, Natalia; Stepień, Adam; Sulkowski, Grzegorz; Dąbrowska-Bouta, Beata; Langfort, Józef; Chalimoniuk, Małgorzata

2017-08-01

The aim of this study was to investigate the effects of interferon (IFN)-β1a and IFN-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund's complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra). The rats were treated three times per week with subcutaneous applications of 300,000 units IFN-β1a or IFN-β1b. The treatments were started 8 days prior to immunization and continued until day 14 after immunization. The rats were killed on the 14th day of the experiment. EAE induced dramatic increase in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-concentrations and inducible nitric oxide synthase (iNOS) expression in the brain, which closely corresponded to the course of neurological symptoms and the loss of weight. Both IFN-β1b and IFN-β1a treatments inhibited the pro-inflammatory cytokines (IL-6, IL-1β, TNF-α and IFN-γ), decreased the activation of astrocytes, increased the myelin protein level in the brain cortex, and improved the neurological status of EAE rats by different mechanisms; IFN-β1a reduced iNOS expression, at least in part, by the enhancement of IL-10, while IFN-β1b diminished IL-10 concentration and did not decrease EAE-induced iNOS expression.

Cuminum cyminum, a dietary spice, attenuates hypertension via endothelial nitric oxide synthase and NO pathway in renovascular hypertensive rats.

PubMed

Kalaivani, Periyathambi; Saranya, Ramesh Babu; Ramakrishnan, Ganapathy; Ranju, Vijayan; Sathiya, Sekar; Gayathri, Veeraraghavan; Thiyagarajan, Lakshmi Kantham; Venkhatesh, Jayakothanda Ramaswamy; Babu, Chidambaram Saravana; Thanikachalam, Sadagopan

2013-01-01

Cuminum cyminum (CC) is a commonly used spice in South Indian foods. It has been traditionally used for the treatment and management of sleep disorders, indigestion, and hypertension. The present study was carried out to scientifically evaluate the anti-hypertensive potential of standardized aqueous extract of CC seeds and its role in arterial endothelial nitric oxide synthase expression, inflammation, and oxidative stress in renal hypertensive rats. Renal hypertension was induced by the two-kidney one-clip (2K/1C) method in rats. Systolic blood pressure (SBP), plasma nitrate/nitrite, carotid-eNOS, renal-TNF-α, IL-6, Bax, Bcl-2, thioredoxin 1 (TRX1), and thioredoxin reductase 1 (TRXR1) mRNA expressions were studied to demonstrate the anti-hypertensive action of CC. Cuminum cyminum was administered orally (200 mg/kg b.wt) for a period of 9 weeks; it improved plasma nitric oxide and decreased the systolic blood pressure in hypertensive rats. It also up-regulated the gene expression of eNOS, Bcl-2, TRX1, and TRXR1; and down-regulated Bax, TNF-α, and IL-6. These data reveal that CC seeds augment endothelial functions and ameliorate inflammatory and oxidative stress in hypertensive rats. The present report is the first of its kind to demonstrate the mechanism of anti-hypertensive action of CC seeds in an animal model of renovascular hypertension.

Reflections on Race: Affirmative Action Policies Influencing Higher Education in France and the United States

ERIC Educational Resources Information Center

Donahoo, Saran

2008-01-01

Background/Context: Although frequently associated with the United States, affirmative action is not a uniquely American social policy. Indeed, 2003 witnessed review and revision of affirmative action policies affecting higher education institutions in both France and the United States. Using critical race theory (CRT) as a theoretical lens, this…

77 FR 48586 - Notice of Final Federal Agency Actions on United States Highway 77

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-14

.... Sec. 139(l)(1). The actions relate to a proposed highway project, United States (US) 77, extending from Interstate Highway 37 (IH 37) in Corpus Christi, Texas to US 83 in Harlingen, Texas. Those actions..., permits, and approvals for the following highway project in the State of Texas: United States highway (US...

Interim Action Proposed Plan for the Chemicals, Metals, and Pesticides (CMP) Pits Operable Unit

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

Bradley, J.

2002-06-18

The purpose of this Interim Action Proposed Plan (IAPP) is to describe the preferred interim remedial action for addressing the Chemicals, Metals, and Pesticides (CMP) Pits Operable Unit and to provide an opportunity for public input into the remedial action selection process.

Corrective Action Decision Document/Closure Report for Corrective Action Unit 477: Area 12 N-Tunnel Muckpile, Nevada Test Site

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

NSTec Environmental Restoration

This Corrective Action Decision Document (CADD)/Closure Report (CR) was prepared by the Defense Threat Reduction Agency (DTRA) for Corrective Action Unit (CAU) 477, N-Tunnel Muckpile. This CADD/CR is consistent with the requirements of the Federal Facility Agreement and Consent Order (FFACO) agreed to by the State of Nevada, the U.S. Department of Energy, and the U.S. Department of Defense. Corrective Action Unit 477 is comprised of one Corrective Action Site (CAS): • 12-06-03, Muckpile The purpose of this CADD/CR is to provide justification and documentation supporting the recommendation for closure with no further action, by placing use restrictions on CAUmore » 477.« less

76 FR 60871 - Ball Bearings and Parts Thereof From France, Germany, and Italy; Termination of Five-Year Reviews

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-30

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 731-TA-391A-393A (Third Review)] Ball Bearings and Parts Thereof From France, Germany, and Italy; Termination of Five-Year Reviews AGENCY: United... parts thereof from France, Germany, and Italy would be likely to lead to continuation or recurrence of...

77 FR 40092 - License Amendment To Increase the Maximum Reactor Power Level, Florida Power & Light Company, St...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-06

... Increase the Maximum Reactor Power Level, Florida Power & Light Company, St. Lucie, Units 1 and 2 AGENCY... amendment for Renewed Facility Operating License Nos. DPR-67 and NPF-16, issued to Florida Power & Light... St. Lucie County, Florida. The proposed license amendment would increase the maximum thermal power...

The Story behind the Science: Bringing Science and Scientists to Life in Post-Secondary Science Education

ERIC Educational Resources Information Center

Clough, Michael P.

2011-01-01

With funding from the United States National Science Foundation, 30 historical short stories designed to teach science content and draw students' attention to the nature of science (NOS) have been created for post-secondary introductory astronomy, biology, chemistry, geology, and physics courses. The project rationale, story development and…

Case Studies of Actual and Alleged Overflights, 1930-1953. Supplement

DTIC Science & Technology

1955-08-15

the SECRET volume than would have been possible if all the case studies had been presented in the same volume, regardless of classification. The character of the intelligence mission of United States reconnaissance aircraft referred to in case studies Nos. 115-118, 120-123, and 129-131 is not precisely identified in the discussion of those

75 FR 80546 - Virginia Electric and Power Company; Surry Power Station Unit Nos. 1 and 2; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-22

... used to predict the rates of energy release, hydrogen concentration, and cladding oxidation from the... associated hydrogen pickup) for Optimized ZIRLO TM at any given burnup would be less than both zircaloy-4 and... between cladding hydrogen content (due to in-service corrosion) and post-quench ductility. \\2\\ ADAMS...

78 FR 15046 - Certain Pasta From Italy and Turkey; Revised Schedule for the Subject Reviews

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-08

... INTERNATIONAL TRADE COMMISSION [Investigation Nos. 701-TA-365-366 and 731-TA-734-735 (Third Review)] Certain Pasta From Italy and Turkey; Revised Schedule for the Subject Reviews AGENCY: United States... pasta from Italy and Turkey (78 FR 9937, February 12, 2013). The Commission is revising its schedule as...

76 FR 16012 - STP Nuclear Operating Company, et al. South Texas Project, Units 1 and 2 Notice of Consideration...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-22

... NUCLEAR REGULATORY COMMISSION [NRC-2011-0063; Docket Nos. 50-498 And 50-499] STP Nuclear Operating... Facility Operating License, Proposed No Significant Hazards Consideration Determination, and Opportunity... on the NRC Web site and on the Federal rulemaking Web site http://www.regulations.gov . Because your...

76 FR 24064 - Arizona Public Service Company, Palo Verde Nuclear Generating Station, Units 1, 2, and 3, Notice...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-29

... Decision Notice is hereby given that the U.S. Nuclear Regulatory Commission (NRC, the Commission) has... notice also serves as the record of decision for Renewed Facility Operating License Nos. NPF-41, NPF-51... Decision--General.'' NUREG-1437, ``Generic Environmental Impact Statement for License Renewal of Nuclear...

78 FR 36574 - Certain Dimmable Compact Fluorescent Lamps and Products Containing Same; Termination as to Three...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

... domestic industry requirement. The Commission has also determined to review the ALJ's claim construction of.... 1337, by reason of the infringement of certain claims of United States Patent Nos. 5,434,480 (``the... (``ULA''); and Golden U Lighting Manufacturing (Shenzhen) of Shenzhen, China (``Golden U''). Claim 9 of...

75 FR 9956 - PSEG Nuclear LLC, Hope Creek Generating Station and Salem Nuclear Generating Station, Unit Nos. 1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-04

... letter number LR-N09- 0248 and the second enclosure is an environmental impact statement. Based on a... November 3, and November 20, 2009, submittals, with the exception of the environmental impact statement... M. S. Fertel, Nuclear Energy Institute, ADAMS Accession No. ML091410309). The licensee's request for...

75 FR 16872 - Indian Point Nuclear Generating Unit Nos. 1, 2, and 3; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-02

... rule's compliance date for all operating nuclear power plants, but noted that the Commission's... compliance date (Reference: June 4, 2009, letter from R. W. Borchardt, NRC, to M. S. Fertel, Nuclear Energy... significant effect on the quality of the human environment (75 FR 14639; dated March 26, 2010). This exemption...

75 FR 16521 - Virginia Electric and Power Company Surry Power Station, Unit Nos. 1 and 2; Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

... generic industry request to extend the rule's compliance date for all operating nuclear power plants, but... M.S. Fertel, Nuclear Energy Institute). The licensee's request for an exemption is therefore... granting of this exemption will not have a significant effect on the quality of the human environment (75...

Fast Facts: Recent Statistics from the Library Research Service, Nos. 131-137. September-November 1997.

ERIC Educational Resources Information Center

Fast Facts: Recent Statistics from the Library Research Service, 1997

1997-01-01

Seven issues of a newsletter on recent library statistics in Colorado provide information Internet service in Colorado public libraries, technology in public libraries, school library media centers, and the number of public library outlets in Colorado and the United States. Almost all of Colorado's public libraries provide electronic access to…

Minimal Pharmacophoric Elements and Fragment Hopping, an Approach Directed at Molecular Diversity and Isozyme Selectivity. Design of Selective Neuronal Nitric Oxide Synthase Inhibitors

PubMed Central

Ji, Haitao; Stanton, Benjamin Z.; Igarashi, Jotaro; Li, Huiying; Martásek, Pavel; Roman, Linda J.; Poulos, Thomas L.; Silverman, Richard B.

2010-01-01

Fragment hopping, a new fragment-based approach for de novo inhibitor design focusing on ligand diversity and isozyme selectivity, is described. The core of this approach is the derivation of the minimal pharmacophoric element for each pharmacophore. Sites for both ligand binding and isozyme selectivity are considered in deriving the minimal pharmacophoric elements. Five general-purpose libraries are established: the basic fragment library, the bioisostere library, the rules for metabolic stability, the toxicophore library, and the side chain library. These libraries are employed to generate focused fragment libraries to match the minimal pharmacophoric elements for each pharmacophore and then to link the fragment to the desired molecule. This method was successfully applied to neuronal nitric oxide synthase (nNOS), which is implicated in stroke and neurodegenerative diseases. Starting with the nitroarginine-containing dipeptide inhibitors we developed previously, a small organic molecule with a totally different chemical structure was designed, which showed nanomolar nNOS inhibitory potency and more than 1000-fold nNOS selectivity. The crystallographic analysis confirms that the small organic molecule with a constrained conformation can exactly mimic the mode of action of the dipeptide nNOS inhibitors. Therefore, a new peptidomimetic strategy, referred to as fragment hopping, which creates small organic molecules that mimic the biological function of peptides by a pharmacophore-driven strategy for fragment-based de novo design, has been established as a new type of fragment-based inhibitor design. As an open system, the newly established approach efficiently incorporates the concept of early “ADME/Tox” considerations and provides a basic platform for medicinal chemistry-driven efforts. PMID:18321097

Curcumin, a Curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis.

PubMed

Camacho-Barquero, Laura; Villegas, Isabel; Sánchez-Calvo, Juan Manuel; Talero, Elena; Sánchez-Fidalgo, Susana; Motilva, Virginia; Alarcón de la Lastra, Catalina

2007-03-01

Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and up-regulation of pro-inflammatory cytokines. Mitogen-activated protein kinases (MAPKs), such as the p38 and the c-Jun N-terminal kinase (JNK) modulate the transcription of many genes involved in the inflammatory process. Curcumin is a polyphenol derived from Curcuma longa, which is known to have anti-inflammatory activity. The aim of this study was to study the effects and mechanisms of action of curcumin, on chronic colitis in rats. Inflammation response was assessed by histology and myeloperoxidase activity (MPO). We determined the production of Th1 and Th2 cytokines and nitrites in colon mucosa, as well as the expression of inducible nitric oxide synthase (iNOS), cyclo-oxygenase(COX)-1 and-2 by western blotting and inmmunohistochemistry. Finally, we studied the involvement of MAPKs signaling in the protective effect of curcumin in chronic colonic inflammation. Curcumin (50-100 mg/kg/day) were administered by oral gavage 24 h after trinitrobenzensulfonic acid (TNBS) instillation, and daily during 2 weeks before sacrifice. Curcumin significantly attenuated the damage and caused substantial reductions of the rise in MPO activity and tumour necrosis factor alpha (TNF)-alpha. Also curcumine was able to reduce nitrites colonic levels and induced down-regulation of COX-2 and iNOS expression, and a reduction in the activation of p38 MAPK; however, no changes in the activation of JNK could be observed. In conclusion, we suggest that inhibition of p38 MAPK signaling by curcumin could explain the reduced COX-2 and iNOS immunosignals and the nitrite production in colonic mucosa reducing the development of chronic experimental colitis.

Analysis of NO-suppressing activity of Strawberry Wine supplemented with ball-milled achenes.

PubMed

Lee, Pao-Ju; Tsai, Tsung-Yu; Chen, Shaun

2018-04-01

Inflammation is generally thought to be involved in the development of several chronical diseases, therefore, phytochemicals to modulate immune responses has attracted great interests. The objective of the present study was to evaluate the potential anti-inflammatory effects of wine supplemented using ball-milled achene on modulating NO production and inducible nitric oxide synthase (iNOS) expression. Ball-milled achenes were added in strawberry must prior to fermentation, and the wine samples were then concentrated and extracted with water and/or ethanol prior to analysis. Bioactivities of wine extracts were evaluated using the cell viability assay, cell cycle measurements, NO production and iNOS expression in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Treatments of achenes supplemented strawberry wine extract up to 100 μg/mL inhibited the proliferation of LPS-stimulated RAW264.7 cell via affecting the progression of cell cycle. Moreover, no detectable cytotoxicity in RAW264.7 cells was observed. The supplemented wine extract suppressed the action of LPS and led to a decreased NO production in stimulated cells. The inhibitory effect of the wine extract on NO production was determined to be a 25-40% decrease in the level of 25-100 μg/mL, in contrast to a 10% decrease for conventional wine samples. Additionally, an alcoholic wine extract (100 μg/mL) led to a 40.31% decrease in iNOS expression in LPS-stimulated cells, which was more effective than the same dose of tocopherol. The results show that strawberry wine supplemented with ball-milled achenes causes a substantial inhibition of NO production, and this biofunction is exerted via the down-regulation of iNOS expression.

Cyclooxygenase 2 inhibition suppresses tubuloglomerular feedback: roles of thromboxane receptors and nitric oxide

PubMed Central

Araujo, Magali; Welch, William J.

2009-01-01

Thromboxane (TxA2) and nitric oxide (NO) are potent vasoactive autocoids that modulate tubuloglomerular feedback (TGF). Each is produced in the macula densa (MD) by cyclooxygenase-2 (COX-2) and neuronal nitric oxide synthase (nNOS), respectively. Both enzymes are similarly regulated in the MD and their interaction may be an important factor in the regulation of TGF and glomerular filtration rate. We tested the hypothesis that TGF is modified by the balance between MD nNOS-dependent NO and MD COX-2-dependent TxA2. We measured maximal TGF during perfusion of the loop of Henle (LH) by continuous recording of the proximal tubule stopped flow pressure response to LH perfusion of artificial tubular fluid (ATF) at 0 and 40 nl/min. The response to inhibitors of COX-1 (SC-560), COX-2 [parecoxib (Pxb)], and nNOS (l-NPA) added to the ATF solution was measured in separate nephrons. COX-2 inhibition with Pxb reduced TGF by 46% (ATF + vehicle vs. ATF + Pxb), whereas COX-1 inhibition with SC-560 reduced TGF by only 23%. Pretreatment with intravenous infusion of SQ-29,548, a selective thromboxone/PGH2 receptor (TPR) antagonist, blocked all of the SC-560 effect on TGF, suggesting that this effect was due to activation of TPR. However, SQ-29,548 only partially diminished the effect of Pxb (−66%). Specific inhibition of nNOS with l-NPA increased TGF, as expected. However, the ability of Pxb to reduce TGF was significantly impaired with comicroperfusion of l-NPA. These data suggest that COX-2 modulates TGF by two proconstrictive actions: generation of TxA2 acting on TPR and by simultaneous reduction of NO. PMID:19144694

The Role of cGMP on Adenosine A1 Receptor-mediated Inhibition of Synaptic Transmission at the Hippocampus

PubMed Central

Pinto, Isa; Serpa, André; Sebastião, Ana M.; Cascalheira, José F.

2016-01-01

Both adenosine A1 receptor and cGMP inhibit synaptic transmission at the hippocampus and recently it was found that A1 receptor increased cGMP levels in hippocampus, but the role of cGMP on A1 receptor-mediated inhibition of synaptic transmission remains to be established. In the present work we investigated if blocking the NOS/sGC/cGMP/PKG pathway using nitric oxide synthase (NOS), protein kinase G (PKG), and soluble guanylyl cyclase (sGC) inhibitors modify the A1 receptor effect on synaptic transmission. Neurotransmission was evaluated by measuring the slope of field excitatory postsynaptic potentials (fEPSPs) evoked by electrical stimulation at hippocampal slices. N6-cyclopentyladenosine (CPA, 15 nM), a selective A1 receptor agonist, reversibly decreased the fEPSPs by 54 ± 5%. Incubation of the slices with an inhibitor of NOS (L-NAME, 200 μM) decreased the CPA effect on fEPSPs by 57 ± 9% in female rats. In males, ODQ (10 μM), an sGC inhibitor, decreased the CPA inhibitory effect on fEPSPs by 23 ± 6%, but only when adenosine deaminase (ADA,1 U/ml) was present; similar results were found in females, where ODQ decreased CPA-induced inhibition of fEPSP slope by 23 ± 7%. In male rats, the presence of the PKG inhibitor (KT5823, 1 nM) decreased the CPA effect by 45.0 ± 9%; similar results were obtained in females, where KT5823 caused a 32 ± 9% decrease on the CPA effect. In conclusion, the results suggest that the inhibitory action of adenosine A1 receptors on synaptic transmission at hippocampus is, in part, mediated by the NOS/sGC/cGMP/PKG pathway. PMID:27148059

Participation of non-neuronal muscarinic receptors in the effect of carbachol with paclitaxel on human breast adenocarcinoma cells. Roles of nitric oxide synthase and arginase.

PubMed

Español, Alejandro Javier; Salem, Agustina; Rojo, Daniela; Sales, María Elena

2015-11-01

Breast cancer is the most common type of cancer in women and represents a major issue in public health. The most frequent methods to treat these tumors are surgery and/or chemotherapy. The latter can exert not only beneficial effects by reducing tumor growth and metastasis, but also toxic actions on normal tissues. Metronomic therapy involves the use of low doses of cytotoxic drugs alone or in combination to improve efficacy and to reduce adverse effects. We have previously reported that breast tumors highly express functional muscarinic acetylcholine receptors (mAChRs) that regulate tumor progression. For this reason, mAChRs could be considered as therapeutic targets in breast cancer. In this paper, we investigated the ability of a combination of the cytotoxic drug paclitaxel plus carbachol, a cholinergic agonist, at low doses, to induce death in breast tumor MCF-7 cells, via mAChR activation, and the role of nitric oxide synthase (NOS) and arginase in this effect. We observed that the combination of carbachol plus paclitaxel at subthreshold doses significantly increased cytotoxicity in tumor cells without affecting MCF-10A cells, derived from human normal mammary gland. This effect was reduced in the presence of the muscarinic antagonist atropine. The combination also increased nitric oxide production by NOS1 and NOS3 via mAChR activation, concomitantly with an up-regulation of NOS3 expression. The latter effects were accompanied by a reduction in arginase II activity. In conclusion, our work demonstrates that mAChRs expressed in breast tumor cells could be considered as candidates to become targets for metronomic therapy in cancer treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

Designing an educative curriculum unit for teaching molecular geometry in high school chemistry

NASA Astrophysics Data System (ADS)

Makarious, Nader N.

Chemistry is a highly abstract discipline that is taught and learned with the aid of various models. Among the most challenging, yet a fundamental topic in general chemistry at the high school level, is molecular geometry. This study focused on developing exemplary educative curriculum materials pertaining to the topic of molecular geometry. The methodology used in this study consisted of several steps. First, a diverse set of models were analyzed to determine to what extent each model serves its purpose in teaching molecular geometry. Second, a number of high school teachers and college chemistry professors were asked to share their experiences on using models in teaching molecular geometry through an online questionnaire. Third, findings from the comparative analysis of models, teachers’ experiences, literature review on models and students’ misconceptions, the curriculum expectations of the Next Generation Science Standards and their emphasis on three-dimensional learning and nature of science (NOS) contributed to the development of the molecular geometry unit. Fourth, the developed unit was reviewed by fellow teachers and doctoral-level science education experts and was revised to further improve its coherence and clarity in support of teaching and learning of the molecular geometry concepts. The produced educative curriculum materials focus on the scientific practice of developing and using models as promoted in the Next Generations Science Standards (NGSS) while also addressing nature of science (NOS) goals. The educative features of the newly developed unit support teachers’ pedagogical knowledge (PK) and pedagogical content knowledge (PCK). The unit includes an overview, teacher’s guide, and eight detailed lesson plans with inquiry oriented modeling activities replete with models and suggestions for teachers, as well as formative and summative assessment tasks. The unit design process serves as a model for redesigning other instructional units in science disciplines in general and chemistry courses in particular.

Annual Summary Report Calendar Year 2000 for the 100-HR-3, 100-KR-4, and 100-NR-2 Operable Units and Pump-and-Treat Operations

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

G. B. Mitchem

2001-08-22

This annual progress and performance evaluation report discusses the groundwater remedial actions in the 100 Area, including the interim actions at the 100-HR-3 and 100-KR-4 Operable Units, and also discusses the expedited response action in the 100-NR-2 operable unit.

77 FR 60613 - National Energy Action Month, 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... National Energy Action Month, 2012 By the President of the United States of America A Proclamation A secure... sustainable, vibrant economy. We took bold action to double our use of renewable energy sources like solar... the laws of the United States, do hereby proclaim October 2012 as National Energy Action Month. I call...

NASA Operational Simulator for Small Satellites: Tools for Software Based Validation and Verification of Small Satellites

NASA Technical Reports Server (NTRS)

Grubb, Matt

2016-01-01

The NASA Operational Simulator for Small Satellites (NOS3) is a suite of tools to aid in areas such as software development, integration test (IT), mission operations training, verification and validation (VV), and software systems check-out. NOS3 provides a software development environment, a multi-target build system, an operator interface-ground station, dynamics and environment simulations, and software-based hardware models. NOS3 enables the development of flight software (FSW) early in the project life cycle, when access to hardware is typically not available. For small satellites there are extensive lead times on many of the commercial-off-the-shelf (COTS) components as well as limited funding for engineering test units (ETU). Considering the difficulty of providing a hardware test-bed to each developer tester, hardware models are modeled based upon characteristic data or manufacturers data sheets for each individual component. The fidelity of each hardware models is such that FSW executes unaware that physical hardware is not present. This allows binaries to be compiled for both the simulation environment, and the flight computer, without changing the FSW source code. For hardware models that provide data dependent on the environment, such as a GPS receiver or magnetometer, an open-source tool from NASA GSFC (42 Spacecraft Simulation) is used to provide the necessary data. The underlying infrastructure used to transfer messages between FSW and the hardware models can also be used to monitor, intercept, and inject messages, which has proven to be beneficial for VV of larger missions such as James Webb Space Telescope (JWST). As hardware is procured, drivers can be added to the environment to enable hardware-in-the-loop (HWIL) testing. When strict time synchronization is not vital, any number of combinations of hardware components and software-based models can be tested. The open-source operator interface used in NOS3 is COSMOS from Ball Aerospace. For testing, plug-ins are implemented in COSMOS to control the NOS3 simulations, while the command and telemetry tools available in COSMOS are used to communicate with FSW. NOS3 is actively being used for FSW development and component testing of the Simulation-to-Flight 1 (STF-1) CubeSat. As NOS3 matures, hardware models have been added for common CubeSat components such as Novatel GPS receivers, ClydeSpace electrical power systems and batteries, ISISpace antenna systems, etc. In the future, NASA IVV plans to distribute NOS3 to other CubeSat developers and release the suite to the open-source community.

Literacy in Industrialized Countries: A Focus on Practice = L'Alphabetisation en pays industrialises: Point de Mire sur la Pratique. Proceedings of the International Seminar on Literacy in Industrialized Countries (Toronto, Ontario, October 13-15, 1987). Convergence, Volume 20, Nos. 3-4, 1987.

ERIC Educational Resources Information Center

Gayfer, Margaret, Ed.

1987-01-01

The following papers are included: "Seminar's Focus on Practice Puts Action on the Human Level" (Margaret Gayfer); "Literacy: What Do Definitions Tell Us?" (Carman Hunter); "The Practice of Literacy in the Netherlands" (Ella Bohnenn); "The Approach of Popular Literacy Groups in Quebec" (Louise Miller); "Perspectives and Lessons from the Adult…

Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway

PubMed Central

Mao, Mao; Sudhahar, Varadarajan; Ansenberger-Fricano, Kristine; Fernandes, Denise C.; Tanaka, Leonardo Y.; Fukai, Tohru; Laurindo, Francisco R.M.; Mason, Ronald P.; Vasquez-Vivar, Jeannette; Minshall, Richard D.; Stadler, Krisztian; Bonini, Marcelo G.

2012-01-01

Nitroglycerin (GTN) has been clinically used to treat angina pectoris and acute heart episodes for over 100 years. The effects of GTN have long been recognized and active research has contributed to the unraveling of numerous metabolic routes capable of converting GTN to the potent vasoactive messenger nitric oxide. Recently, the mechanism by which minute doses of GTN elicit robust pharmacological responses was revisited and eNOS activation was implicated as an important route mediating vasodilation induced by low GTN doses (1–50 nM). Here, we demonstrate that at such concentrations the pharmacologic effects of nitroglycerin are largely dependent on the phosphatidylinositol 3-kinase, Akt/PKB, and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signal transduction axis. Furthermore, we demonstrate that nitroglycerin-dependent accumulation of 3,4,5-InsP3, probably because of inhibition of PTEN, is important for eNOS activation, conferring a mechanistic basis for GTN pharmacological action at pharmacologically relevant doses. PMID:22037515

Corrective Action Investigation Plan for Corrective Action Unit 563: Septic Systems, Nevada Test Site, Nevada, with Errata Sheet, Revision 0 (in English; Afrikaans)

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

Alfred Wickline

Corrective Action Unit 563, Septic Systems, is located in Areas 3 and 12 of the Nevada Test Site, which is 65 miles northwest of Las Vegas, Nevada. Corrective Action Unit 563 is comprised of the four corrective action sites (CASs) below: • 03-04-02, Area 3 Subdock Septic Tank • 03-59-05, Area 3 Subdock Cesspool • 12-59-01, Drilling/Welding Shop Septic Tanks • 12-60-01, Drilling/Welding Shop Outfalls These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives. Additional information will be obtained by conducting a corrective actionmore » investigation (CAI) before evaluating corrective action alternatives and selecting the appropriate corrective action for each CAS. The results of the field investigation will support a defensible evaluation of viable corrective action alternatives that will be presented in the Corrective Action Decision Document.« less

Anti-inflammatory effect of tricin 4′-O-(threo-β-guaiacylglyceryl) ether, a novel flavonolignan compound isolated from Njavara on in RAW264.7 cells and in ear mice edema

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

Jung, Young-Suk; Kim, Dae Hwan; Hwang, Jae Yeon

Although recent study has shown tricin 4′-O-(threo-β-guaiacylglyceryl) ether (TTGE), an isolated compound from Njavara rice, to have the most potent anti-inflammatory effects, the action mechanism has not been fully understood. Here, we examined the effect of TTGE on the inflammation and elucidated the potential mechanism. We demonstrated that TTGE significantly inhibited LPS-induced NO and ROS generation in RAW264.7 cells, which was correlated with the down-regulating effect of TTGE on the iNOS and COX-2 expression via NF-κB and STAT3. TPA-induced ear edema was also efficiently inhibited by the TTGE treatment. TTGE blocked the induction of iNOS and COX-2 through the regulationmore » of NF-κB and STAT3, which could explain the reduced TPA-induced edema symptoms. Moreover, the introduction of ERK inhibitor abrogated the anti-inflammatory effect of TTGE via the recovery of NF-κB and STAT3 signalings. Taken together, these results suggest that TTGE has anti-inflammatory properties through down-regulation of NF-κB and STAT3 pathways. - Highlights: • TTGE inhibited expression of iNOS and COX-2, NF-kB activity and ear edema through inhibition of ERK pathway.« less

A benzoxazine derivative induces vascular endothelial cell apoptosis in the presence of fibroblast growth factor-2 by elevating NADPH oxidase activity and reactive oxygen species levels.

PubMed

Zhao, Jing; He, Qiuxia; Cheng, Yizhe; Zhao, Baoxiang; Zhang, Yun; Zhang, Shangli; Miao, Junying

2009-09-01

Previously, we found that 6,8-dichloro-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine (DBO) promoted apoptosis of human umbilical vascular endothelial cells (HUVECs) deprived of growth factors. In this study, we aimed to investigate the effect of DBO and its mechanism of action on angiogenesis and apoptosis of HUVECs in the presence of fibroblast growth factor-2 (FGF-2), which promotes angiogenesis and inhibits apoptosis in vivo and in vitro. DBO significantly inhibited capillary-like tube formation by promoting apoptosis of HUVECs in the presence of FGF-2 in vitro. Furthermore, DBO elevated the levels of reactive oxygen species (ROS) and nitric oxide (NO) and increased the activity of NADPH oxidase and inducible nitric oxide synthase (iNOS) in promoting apoptosis under this condition. Moreover, when NADPH oxidase was inhibited by its specific inhibitor, dibenziodolium chloride (DPI), DBO could not elevate ROS and NO levels in HUVECs. The data suggest that DBO is a new modulator of apoptosis in vitro, and it might function by increasing the activity of NADPH oxidase and iNOS, subsequently elevating the levels of ROS and NO in HUVECs. The findings of this study provide a new small molecule for investigating the FGF-2/NADPH oxidase/iNOS signaling pathway in apoptosis.

[Effects of combined use of total alkaloids of Uncaria rhynchophylla and Coryadlis ambailis migo on cerebral ischemia-reperfusion injury in rats].

PubMed

Hu, Xue-yong; Sun, An-sheng; Sui, Yu-xia

2007-11-01

To study the effects of combined use of total alkaloids (TA) of Uncaria rhynchophylla (UR) and Coryadlis ambailis migo (CAM) on cerebral ischemia/reperfusion injury in rats. Rat model of middle cerebral artery ischemia/reperfusion was established, the changes of neurological state was scored before and after treatment with the two kinds of TA, single or combined, and the changes of cerebral infarcted volume, cerebral water content, activities of NOS and SOD and content of MDA in rats' brain were estimated as well. After being treated with the combination of both TA, the average neurological score, cerebral infracted volume, cerebral water content, activity of NOS and content of MDA in the model rats significantly decreased, and the activity of SOD was significantly increased (all P < 0.05). The effect of combined use of the two TA was higher than that of use TA of UR or CAM alone (P <0.05). Moreover, the central nervous system inhibitory effect induced by combined TA was significantly weaker than that of UR. Combined use of TA of UR and CAM may facilitate the protection against cerebral ischemia/reperfusion damage, the action mechanism might be relevant to reducing the lipid peroxidation injury of brain cells through inhibiting the NOS activity and increasing the SOD activity.

Potential effect and mechanism of action of topical chamomile (Matricaria chammomila L.) oil on migraine headache: A medical hypothesis.

PubMed

Zargaran, Arman; Borhani-Haghighi, Afshin; Faridi, Pouya; Daneshamouz, Saeid; Kordafshari, Gholamreza; Mohagheghzadeh, Abdolali

2014-11-01

Migraine is a chronic recurring headache for which no complete treatment has been found yet. Therefore, finding new treatment approaches and medicines is important. In this review, we consider the probable mechanism of action of a traditional and ethnic formulary of chamomile extract in sesame oil as a new topical medication for migraine pain relief. Chamomile oil is prepared in Traditional Persian Medicine by boiling aqueous extract of chamomile in sesame oil. To optimize the procedure, we can use a Clevenger-type apparatus to extract the essential oil and add it to the end product. The preparation includes both essential oils (chamazulene and bisabolol oxide) and polyphenols (a flavonoid such as apigenin and its derivatives). It probably possesses pain relief effects for migraines because of the following properties: (1) chamazulene and apigenin, which inhibit iNOS expression in activated macrophages and can lead to the prohibition of NO release and synthesis; (2) chamomile flavonoids, which have a strong inhibitory effect on endogenous prostaglandin E2 (PGE2) levels in RAW 264.7 macrophages and can play the role of selective COX-2 inhibitor; (3) chamomile polyphenols, which possess anti-inflammatory effects due to the inhibition of pro-inflammatory biomarkers in THP1 macrophages and which can reduce inflammation in neurovascular units (NVU) at the site of migraine pain; (4) chamomile, which has neuroprotective effects because of reduced NO levels; (5) sesamine in sesame oil, which possesses an anti-inflammatory effect. These effects are supported by main pathophysiological theories of migraine such as neural and sensitization theories. Chamomile oil is a traditional formulation still used in Iran as an ethno-medicine. Because of the mentioned mechanisms of action, it can be hypothesized that chamomile oil is a novel medicine for the relief of migraine pain. Copyright © 2014 Elsevier Ltd. All rights reserved.

76 FR 11522 - In the Matter of Progress Energy Florida, Inc. (Combined License Application, Levy County Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 52-029-COL, 52-030-COL] In the Matter of Progress Energy Florida, Inc. (Combined License Application, Levy County Nuclear Power Plant, Units 1 and 2... of 10 CFR 2.347 and 2.348 in their communications with Mr. Dehmel. It is so ordered. Dated at...

76 FR 28457 - In the Matter of Certain Toner Cartridges and Components Thereof; Determination Not To Review an...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-17

...'s electronic docket (EDIS) at http://edis.usitc.gov . Hearing-impaired persons are advised that... United States Patent Nos. 5,903,803 and 6,128,454. The complaint named as respondents Ninestar Image Int...., Ltd. of Zhuhai, China; Zhuhai Seine Technology Co. of Zhuhai, China; Seine Image Int'l Co. of Shatin...

Cooperative Learning about Nature of Science with a Case from the History of Science

ERIC Educational Resources Information Center

Wolfensberger, Balz; Canella, Claudia

2015-01-01

This paper reports a predominantly qualitative classroom study on cooperative learning about nature of science (NOS) using a case from the history of science. The purpose of the research was to gain insight into how students worked with the historical case study during cooperative group work, how students and teachers assessed the teaching unit,…

Changes Observed in Views of Nature of Science during a Historically Based Unit

ERIC Educational Resources Information Center

Rudge, David Wÿss; Cassidy, David Paul; Fulford, Janice Marie; Howe, Eric Michael

2014-01-01

Numerous empirical studies have provided evidence of the effectiveness of an explicit and reflective approach to the learning of issues associated with the nature of science (NOS) (c.f. Abd-El-Khalick and Lederman in "J Res Sci Teach" 37(10):1057-1095, 2000). This essay reports the results of a mixed-methods association study involving…

78 FR 49305 - Luminant Generation Company LLC, Comanche Peak Nuclear Power Plant, Unit Nos. 1 and 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-13

... http://www.regulations.gov and search for Docket ID NRC-2013-0182. Address questions about NRC dockets... NRC Library at http://www.nrc.gov/reading-rm/adams.html . To begin the search, select ``ADAMS Public Documents'' and then select ``Begin Web- based ADAMS Search.'' For problems with ADAMS, please contact the...

75 FR 57061 - Public Land Order No. 7749; Extension of Public Land Order Nos. 6801 and 6812; Arizona

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2010-09-17

... National Forest System lands from location or entry under the United States mining laws (30 U.S.C. chapter... Service Coronado National Forest Office, Federal Building, 300 West Congress Street, Tucson, Arizona 85701.... Public Land Order No. 6801 (55 FR 38550, (1990)) that withdrew 61.356 acres of National Forest System...

75 FR 23820 - Notice of Docketing of Amendment Request for Materials License No. SNM-2506; Northern States...

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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...

76 FR 78702 - Progress Energy Florida, Inc. (Combined License Application for Levy County Nuclear Power Plant...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-19

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 52-029-COL, 52-030-COL; ASLBP No. 09-879-04-COL-BD01] Progress Energy Florida, Inc. (Combined License Application for Levy County Nuclear Power Plant, Units 1 and 2) Notice of Atomic Safety and Licensing Board Reconstitution Pursuant to 10 CFR 2.313(c) and 2...

76 FR 39910 - Nine Mile Point Nuclear Station, LLC; Nine Mile Point Nuclear Station, Unit Nos. 1 and 2; Notice...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-07

... hearing and intervention via electronic submission through the NRC E-filing system. Requests for a hearing... accordance with the NRC E-Filing rule (72 FR 49139, August 28, 2007). The E-Filing process requires... requirements of E-Filing, at least ten (10) days prior to the filing deadline, the [[Page 39912

77 FR 36015 - Atomic Safety and Licensing Board; Entergy Nuclear Operations, Inc. (Indian Point Nuclear...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-15

... NUCLEAR REGULATORY COMMISSION [Docket Nos. 50-247-LR and 50-286-LR; ASLBP No. 07-858-03-LR-BD01] Atomic Safety and Licensing Board; Entergy Nuclear Operations, Inc. (Indian Point Nuclear Generating Units 2 and 3); Notice of Hearing (Application for License Renewal) June 8, 2012. Before Administrative Judges: Lawrence G. McDade, Chairman, Dr....