Science.gov

Sample records for system eno oyo

  1. Oyo-first field Deepwater Nigeria?

    SciTech Connect

    Lilletveit, R.; Nelson, L.; Osahon, G.

    1996-08-01

    The Oyo-1 well was drilled in 3Q95 in OPL 210. The partners in the block are Allied Energy (Operator) and the Statoil and BP Alliance. This well was the first well drilled in Deepwater Nigeria and is a reported hydrocarbon discovery. Although the well was within the Niger Delta depositional system, the deepwater play types drilled were quite different than anything previously tested on the Nigerian shelf or onshore. One year on, some of the questions to be asked are: (1) What did Oyo-1 discover? (2) What has been done to establish the commerciality, or otherwise, of the hydrocarbon pools encountered? (3) What impact does this discovery have on other prospects identified in the deepwater area? The answer to these questions will help to identify whether a new hydrocarbon province in the deepwater Nigeria area can be developed, or not.

  2. Suitability assessment and mapping of Oyo State, Nigeria, for rice cultivation using GIS

    NASA Astrophysics Data System (ADS)

    Ayoade, Modupe Alake

    2016-07-01

    Rice is one of the most preferred food crops in Nigeria. However, local rice production has declined with the oil boom of the 1970s causing demand to outstrip supply. Rice production can be increased through the integration of Geographic Information Systems (GIS) and crop-land suitability analysis and mapping. Based on the key predictor variables that determine rice yield mentioned in relevant literature, data on rainfall, temperature, relative humidity, slope, and soil of Oyo state were obtained. To develop rice suitability maps for the state, two MCE-GIS techniques, namely the Overlay approach and weighted linear combination (WLC), using fuzzy AHP were used and compared. A Boolean land use map derived from a landsat imagery was used in masking out areas currently unavailable for rice production. Both suitability maps were classified into four categories of very suitable, suitable, moderate, and fairly moderate. Although the maps differ slightly, the overlay and WLC (AHP) approach found most parts of Oyo state (51.79 and 82.9 % respectively) to be moderately suitable for rice production. However, in areas like Eruwa, Oyo, and Shaki, rainfall amount received needs to be supplemented by irrigation for increased rice yield.

  3. Living Water. Eno River State Park: An Environmental Education Learning Experience Designed for the Middle Grades.

    ERIC Educational Resources Information Center

    Hartley, Scott; Woods, Martha

    This learning packet, one in a series of eight, was developed by the Eno River State Park in North Carolina for Grades 5-6 to teach about various aspects of water life on the Eno River. Loose-leaf pages are presented in nine sections that contain: (1) introductions to the North Carolina State Park System, the Eno River State Park, and to the…

  4. Multi-dimensional ENO schemes for general geometries

    NASA Technical Reports Server (NTRS)

    Harten, Ami; Chakravarthy, Sukumar R.

    1991-01-01

    A class of ENO schemes is presented for the numerical solution of multidimensional hyperbolic systems of conservation laws in structured and unstructured grids. This is a class of shock-capturing schemes which are designed to compute cell-averages to high order accuracy. The ENO scheme is composed of a piecewise-polynomial reconstruction of the solution form its given cell-averages, approximate evolution of the resulting initial value problem, and averaging of this approximate solution over each cell. The reconstruction algorithm is based on an adaptive selection of stencil for each cell so as to avoid spurious oscillations near discontinuities while achieving high order of accuracy away from them.

  5. Assessment of Users Information Needs and Satisfaction in Selected Seminary Libraries in Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Adekunjo, Olalekan Abraham; Adepoju, Samuel Olusegun; Adeola, Anuoluwapo Odebunmi

    2015-01-01

    The study assessed users' information needs and satisfaction in selected seminary libraries in Oyo State, Nigeria. This paper employed the descriptive survey research design, whereby the expost-facto was employed with a sample size of three hundred (300) participants, selected from six seminaries located in Ibadan, Oyo and Ogbomoso, all in Oyo…

  6. Perceived Indices of Truancy among Selected Adolescents in Oyo Town: Implications for Behavioural Change

    ERIC Educational Resources Information Center

    Adika, Lawrence Olagoke

    2016-01-01

    The study investigated perceived indices of truancy behaviour among selected adolescents in Oyo town. The descriptive survey study had 200 randomly selected adolescents from five secondary schools in Oyo town. A self-designed instrument tagged Adolescent Truancy Scale (ATS) was employed in collecting data for the study and the data was subjected…

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

    PubMed Central

    Förstermann, Ulrich; Li, Huige

    2011-01-01

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

  8. Efficient implementation of weighted ENO schemes

    NASA Technical Reports Server (NTRS)

    Jiang, Guang-Shan; Shu, Chi-Wang

    1995-01-01

    In this paper, we further analyze, test, modify and improve the high order WENO (weighted essentially non-oscillatory) finite difference schemes of Liu, Osher and Chan. It was shown by Liu et al. that WENO schemes constructed from the r-th order (in L1 norm) ENO schemes are (r+1)-th order accurate. We propose a new way of measuring the smoothness of a numerical solution, emulating the idea of minimizing the total variation of the approximation, which results in a 5-th order WENO scheme for the case r = 3, instead of the 4-th order with the original smoothness measurement by Liu et al. This 5-th order WENO scheme is as fast as the 4-th order WENO scheme of Liu et al., and both schemes are about twice as fast as the 4-th order ENO schemes on vector supercomputers and as fast on serial and parallel computers. For Euler systems of gas dynamics, we suggest computing the weights from pressure and entropy instead of the characteristic values to simplify the costly characteristic procedure. The resulting WENO schemes are about twice as fast as the WENO schemes using the characteristic decompositions to compute weights, and work well for problems which do not contain strong shocks or strong reflected waves. We also prove that, for conservation laws with smooth solutions, all WENO schemes are convergent. Many numerical tests, including the 1D steady state nozzle flow problem and 2D shock entropy wave interaction problem, are presented to demonstrate the remarkable capability of the WENO schemes, especially the WENO scheme using the new smoothness measurement, in resolving complicated shock and flow structures. We have also applied Yang's artificial compression method to the WENO schemes to sharpen contact discontinuities.

  9. Essentially nonoscillatory (ENO) reconstructions via extrapolation

    NASA Technical Reports Server (NTRS)

    Suresh, Ambady; Jorgenson, Philip C. E.

    1995-01-01

    In this paper, the algorithm for determining the stencil of a one-dimensional Essentially Nonoscillatory (ENO) reconstruction scheme on a uniform grid is reinterpreted as being based on extrapolation. This view leads to another extension of ENO reconstruction schemes to two-dimensional unstructured triangular meshes. The key idea here is to select several cells of the stencil in one step based on extrapolation rather than one cell at a time. Numerical experiments confirm that the new scheme yields sharp nonoscillatory reconstructions and that it is about five times faster than previous schemes.

  10. Space chimp Enos returns to Patrick Air Force Base

    NASA Technical Reports Server (NTRS)

    1961-01-01

    Enos the chimpanzee that orbited the earth twice in a Mercury spacecraft arrives back at Patrick Air Force Base. Enos landed some 220 nautical miles south of Bermuda and was picked up up by the U.S.S. Stormes.

  11. Correlates of Examination Malpractice among Secondary School Students in Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Animasahun, R. A.; Ogunniran, J. O.

    2014-01-01

    The purpose of this study is to investigate the correlates of examination malpractice among secondary school students in Oyo State, Nigeria. The instrument used for the study was tagged Predisposing Factors towards Examination Malpractice Questionnaire (PFTEMQ). The instrument was administered to 300 students randomly selected from 20 multi staged…

  12. Policymakers Dependence on Evidence in Education Decision Making in Oyo State Ministry of Education

    ERIC Educational Resources Information Center

    Babalola, Joel B.; Gbolahan, Sowunmi

    2016-01-01

    This study investigated policymaker dependence on evidence in education decision making in Oyo State Ministry of Education. The study was conducted under a descriptive survey design, 44 out of the 290 policymakers of the Ministry and Board of Education across the State were purposively selected for the study. Descriptive statistics of frequency…

  13. Participation of Elderly Women in Community Welfare Activities in Akinyele Local Government, Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Odebode, Stella O.

    2009-01-01

    This paper assessed the participation of elderly women in community welfare activities in Oyo State, Nigeria. Simple random sampling technique was used to select 120 elderly women from six out of the twelve political wards in the study area. Both qualitative and quantitative methods of data collection were used to elicit information from the…

  14. Multi-resolution analysis for ENO schemes

    NASA Technical Reports Server (NTRS)

    Harten, Ami

    1991-01-01

    Given an function, u(x), which is represented by its cell-averages in cells which are formed by some unstructured grid, we show how to decompose the function into various scales of variation. This is done by considering a set of nested grids in which the given grid is the finest, and identifying in each locality the coarsest grid in the set from which u(x) can be recovered to a prescribed accuracy. This multi-resolution analysis was applied to essentially non-oscillatory (ENO) schemes in order to advance the solution by one time-step. This is accomplished by decomposing the numerical solution at the beginning of each time-step into levels of resolution, and performing the computation in each locality at the appropriate coarser grid. An efficient algorithm for implementing this program in the 1-D case is presented; this algorithm can be extended to the multi-dimensional case with Cartesian grids.

  15. Vascular nitric oxide: Beyond eNOS.

    PubMed

    Zhao, Yingzi; Vanhoutte, Paul M; Leung, Susan W S

    2015-10-01

    As the first discovered gaseous signaling molecule, nitric oxide (NO) affects a number of cellular processes, including those involving vascular cells. This brief review summarizes the contribution of NO to the regulation of vascular tone and its sources in the blood vessel wall. NO regulates the degree of contraction of vascular smooth muscle cells mainly by stimulating soluble guanylyl cyclase (sGC) to produce cyclic guanosine monophosphate (cGMP), although cGMP-independent signaling [S-nitrosylation of target proteins, activation of sarco/endoplasmic reticulum calcium ATPase (SERCA) or production of cyclic inosine monophosphate (cIMP)] also can be involved. In the blood vessel wall, NO is produced mainly from l-arginine by the enzyme endothelial nitric oxide synthase (eNOS) but it can also be released non-enzymatically from S-nitrosothiols or from nitrate/nitrite. Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis. PMID:26499181

  16. Multi-resolution analysis for ENO schemes

    NASA Technical Reports Server (NTRS)

    Harten, Ami

    1993-01-01

    Given a function u(x) which is represented by its cell-averages in cells which are formed by some unstructured grid, we show how to decompose the function into various scales of variation. This is done by considering a set of nested grids in which the given grid is the finest, and identifying in each locality the coarsest grid in the set from which u(x) can be recovered to a prescribed accuracy. We apply this multi-resolution analysis to Essentially Non-oscillatory Schemes (ENO) schemes in order to reduce the number of numerical flux computations which is needed in order to advance the solution by one time-step. This is accomplished by decomposing the numerical solution at the beginning of each time-step into levels of resolution, and performing the computation in each locality at the appropriate coarser grid. We present an efficient algorithm for implementing this program in the one-dimensional case; this algorithm can be extended to the multi-dimensional case with cartesian grids.

  17. Some Aspects of Essentially Nonoscillatory (ENO) Formulations for the Euler Equations, Part 3

    NASA Technical Reports Server (NTRS)

    Chakravarthy, Sukumar R.

    1990-01-01

    An essentially nonoscillatory (ENO) formulation is described for hyperbolic systems of conservation laws. ENO approaches are based on smart interpolation to avoid spurious numerical oscillations. ENO schemes are a superset of Total Variation Diminishing (TVD) schemes. In the recent past, TVD formulations were used to construct shock capturing finite difference methods. At extremum points of the solution, TVD schemes automatically reduce to being first-order accurate discretizations locally, while away from extrema they can be constructed to be of higher order accuracy. The new framework helps construct essentially non-oscillatory finite difference methods without recourse to local reductions of accuracy to first order. Thus arbitrarily high orders of accuracy can be obtained. The basic general ideas of the new approach can be specialized in several ways and one specific implementation is described based on: (1) the integral form of the conservation laws; (2) reconstruction based on the primitive functions; (3) extension to multiple dimensions in a tensor product fashion; and (4) Runge-Kutta time integration. The resulting method is fourth-order accurate in time and space and is applicable to uniform Cartesian grids. The construction of such schemes for scalar equations and systems in one and two space dimensions is described along with several examples which illustrate interesting aspects of the new approach.

  18. Tested, Trusted, Yet Frustrating: An Investigation into the Effectiveness of Environmental Radio Jingles in Oyo State Nigeria

    ERIC Educational Resources Information Center

    Ojebode, Ayo

    2005-01-01

    Radio stations have used jingles for environmental education and communication in Nigeria for decades though not much has been done to study the impact of such use--which is the purpose of this article. Through 12 focus group discussions (FGDs) in six local government areas of Oyo state, Nigeria, interviews with the program directors of two radio…

  19. Effects of Training Programme on HIV/AIDS Prevention among Primary Health Care Workers in Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Ajuwon, Ademola; Funmilayo, Fawole; Oladepo, Oladimeji; Osungbade, Kayode; Asuzu, Michael

    2008-01-01

    Purpose: The purpose of this paper is to train primary health care workers to be trainers and implementers of community-based AIDS prevention activities in Oyo State, Nigeria, by describing an evaluation of the project. Design/methodology/approach: A total of 148 primary health care workers recruited from the 33 local government areas (LGA) of the…

  20. Buckling Reduces eNOS Production and Stimulates Extracellular Matrix Remodeling in Arteries in Organ Culture.

    PubMed

    Xiao, Yangming; Liu, Qin; Han, Hai-Chao

    2016-09-01

    Artery buckling alters the fluid shear stress and wall stress in the artery but its temporal effect on vascular wall remodeling is poorly understood. The purpose of this study was to investigate the early effect of artery buckling on endothelial nitric oxide synthase (eNOS) expression and extracellular matrix remodeling. Bilateral porcine carotid arteries were maintained in an ex vivo organ culture system with and without buckling while under the same physiological pressure and flow rate for 3-7 days. Matrix metalloproteinase-2 (MMP-2), MMP-9, fibronectin, elastin, collagen I, III and IV, tissue inhibitor of metalloproteinase-2 (TIMP-2), and eNOS were determined using Western blotting and immunohistochemistry. Our results showed that MMP-2 expression level was significantly higher in buckled arteries than in the controls and higher at the inner curve than at the outer curve of buckled arteries, while collagen IV content showed an opposite trend, suggesting that artery buckling increased MMP-2 expression and collagen IV degradation in a site-specific fashion. However, no differences for MMP-9, fibronectin, elastin, collagen I, III, and TIMP-2 were observed among the outer and inner curve sides of buckled arteries and straight controls. Additionally, eNOS expression was significantly decreased in buckled arteries. These results suggest that artery buckling triggers uneven wall remodeling that could lead to development of tortuous arteries. PMID:26913855

  1. Librarian-initiated HIV/AIDS prevention intervention program outcome in rural communities in Oyo State, Nigeria.

    PubMed

    Ajuwon, G A; Komolafe-Opadeji, H O; Ikhizama, B

    2013-01-01

    The objective of this study was to meet the HIV/AIDS information and service needs of citizens living in selected rural, underserved communities in Oyo State, Nigeria. This was a librarian-initiated intervention program (pre-post) study of heads of rural households in Oyo State. A questionnaire was used for pre- and post-intervention assessment. The education covered knowledge about HIV/AIDS, routes of transmission, prevention strategies, and attitude toward persons living with HIV. It increased participants' knowledge about AIDS and improved attitude toward those living with HIV. Provision and dissemination of information on HIV/AIDS through librarians to rural settlers is an important prevention strategy and librarians can make major contributions. PMID:25228485

  2. Effect of Exercise Training on Enos Expression, NO Production and Oxygen Metabolism in Human Placenta

    PubMed Central

    Ramírez-Vélez, Robinson; Bustamante, Juanita; Czerniczyniec, Analia; Aguilar de Plata, Ana C.; Lores-Arnaiz, Silvia

    2013-01-01

    Objective To determine the effects of combined aerobic and resistance exercise training during the second half of pregnancy on endothelial NOS expression (eNOS), nitric oxide (NO) production and oxygen metabolism in human placenta. Methods The study included 20 nulliparous in gestational week 16–20, attending prenatal care at three tertiary hospitals in Colombia who were randomly assigned into one of two groups: The exercise group (n = 10) took part in an exercise session three times a week for 12 weeks which consisted of: aerobic exercise at an intensity of 55–75% of their maximum heart rate for 60 min and 25 mins. Resistance exercise included 5 exercise groups circuit training (50 repetitions of each) using barbells (1–3 kg/exercise) and low-to-medium resistance bands. The control group (n = 10) undertook their usual physical activity. Mitochondrial and cytosol fractions were isolated from human placental tissue by differential centrifugation. A spectrophotometric assay was used to measure NO production in cytosolic samples from placental tissue and Western Blot technique to determine eNOS expression. Mitochondrial superoxide levels and hydrogen peroxide were measured to determine oxygen metabolism. Results Combined aerobic and resistance exercise training during pregnancy leads to a 2-fold increase in eNOS expression and 4-fold increase in NO production in placental cytosol (p = 0.05). Mitochondrial superoxide levels and hydrogen peroxide production rate were decreased by 8% and 37% respectively in the placental mitochondria of exercising women (p = 0.05). Conclusion Regular exercise training during the second half of pregnancy increases eNOS expression and NO production and decreases reactive oxygen species generation in human placenta. Collectively, these data demonstrate that chronic exercise increases eNOS/NO production, presumably by increasing endothelial shear stress. This adaptation may contribute to the beneficial effects of

  3. PECAM-1 Isoforms, eNOS, and Endoglin Axis in Regulation of Angiogenesis

    PubMed Central

    Park, SunYoung; Sorenson, Christine M.; Sheibani, Nader

    2016-01-01

    Vascular development and maintenance of proper vascular function through various regulatory mechanisms are critical to our wellbeing. Delineating the regulatory processes involved in development of vascular system and function is one of the most important topics in human physiology and pathophysiology. Platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31), a cell adhesion molecule with proangiogenic and proinflammatory activity, has been subject of numerous studies. Here we will review the important roles PECAM-1 and its isoforms play during angiogenesis, and its molecular mechanisms of action in the endothelium. In the endothelium, PECAM-1 not only plays a role as an adhesion molecule but also participates in intracellular signaling pathways which impact various cell adhesive mechanisms and endothelial nitric oxide (eNOS) expression and activity. In addition, recent studies from our laboratory have revealed an important relationship between PECAM-1 and endoglin expression. Endoglin is an essential molecule during angiogenesis, vascular development and integrity whose expression and activity are compromised in the absence of PECAM-1. Here we will discuss the roles PECAM-1 isoforms may play in modulation of endothelial cell adhesive mechanisms, eNOS and endoglin expression and activity, and angiogenesis. PMID:25976664

  4. eNOS activation and NO function: pregnancy adaptive programming of capacitative entry responses alters nitric oxide (NO) output in vascular endothelium--new insights into eNOS regulation through adaptive cell signaling.

    PubMed

    Boeldt, D S; Yi, F X; Bird, I M

    2011-09-01

    In pregnancy, vascular nitric oxide (NO) production is increased in the systemic and more so in the uterine vasculature, thereby supporting maximal perfusion of the uterus. This high level of functionality is matched in the umbilical vein, and in corresponding disease states such as pre-eclampsia, reduced vascular responses are seen in both uterine artery and umbilical vein. In any endothelial cell, NO actually produced by endothelial NO synthase (eNOS) is determined by the maximum capacity of the cell (eNOS expression levels), eNOS phosphorylation state, and the intracellular [Ca(2+)](i) concentration in response to circulating hormones or physical forces. Herein, we discuss how pregnancy-specific reprogramming of NO output is determined as much by pregnancy adaptation of [Ca(2+)](i) signaling responses as it is by eNOS expression and phosphorylation. By examining the changes in [Ca(2+)](i) signaling responses from human hand vein endothelial cells, uterine artery endothelial cells, and human umbilical vein endothelial cells in (where appropriate) nonpregnant, normal pregnant, and pathological pregnant (pre-eclamptic) state, it is clear that pregnancy adaptation of NO output occurs at the level of sustained phase 'capacitative entry' [Ca(2+)](i) response, and the adapted response is lacking in pre-eclamptic pregnancies. Moreover, gap junction function is an essential permissive regulator of the capacitative response and impairment of NO output results from any inhibitor of gap junction function, or capacitative entry using TRPC channels. Identifying these [Ca(2+)](i) signaling mechanisms underlying normal pregnancy adaptation of NO output not only provides novel targets for future treatment of diseases of pregnancy but may also apply to other common forms of hypertension. PMID:21555345

  5. Reversal of SIN-1-induced eNOS dysfunction by the spin trap, DMPO, in bovine aortic endothelial cells via eNOS phosphorylation

    PubMed Central

    Das, Amlan; Gopalakrishnan, Bhavani; Druhan, Lawrence J; Wang, Tse-Yao; De Pascali, Francesco; Rockenbauer, Antal; Racoma, Ira; Varadharaj, Saradhadevi; Zweier, Jay L; Cardounel, Arturo J; Villamena, Frederick A

    2014-01-01

    Background and Purpose Nitric oxide (NO) derived from eNOS is mostly responsible for the maintenance of vascular homeostasis and its decreased bioavailability is characteristic of reactive oxygen species (ROS)-induced endothelial dysfunction (ED). Because 5,5-dimethyl-1-pyrroline-N-oxide (DMPO), a commonly used spin trap, can control intracellular nitroso-redox balance by scavenging ROS and donating NO, it was employed as a cardioprotective agent against ED but the mechanism of its protection is still not clear. This study elucidated the mechanism of protection by DMPO against SIN-1-induced oxidative injury to bovine aortic endothelial cells (BAEC). Experimental Approach BAEC were treated with SIN-1, as a source of peroxynitrite anion (ONOO−), and then incubated with DMPO. Cytotoxicity following SIN-1 alone and cytoprotection by adding DMPO was assessed by MTT assay. Levels of ROS and NO generation from HEK293 cells transfected with wild-type and mutant eNOS cDNAs, tetrahydrobiopterin bioavailability, eNOS activity, eNOS and Akt kinase phosphorylation were measured. Key Results Post-treatment of cells with DMPO attenuated SIN-1-mediated cytotoxicity and ROS generation, restoration of NO levels via increased in eNOS activity and phospho-eNOS levels. Treatment with DMPO alone significantly increased NO levels and induced phosphorylation of eNOS Ser1179 via Akt kinase. Transfection studies with wild-type and mutant human eNOS confirmed the dual role of eNOS as a producer of superoxide anion (O2−) with SIN-1 treatment, and a producer of NO in the presence of DMPO. Conclusion and Implications Post-treatment with DMPO of oxidatively challenged cells reversed eNOS dysfunction and could have pharmacological implications in the treatment of cardiovascular diseases. PMID:24405159

  6. Gender and ethnic differences in onchocercal skin disease in Oyo State, Nigeria.

    PubMed

    Brieger, W R; Ososanya, O O; Kale, O O; Oshiname, F O; Oke, G A

    1997-06-01

    During preparation for a study on the effects of ivermectin treatment on onchocercal skin disease in the Ifeloju Local Government Area of Oyo State, Nigeria, 1032 adults aged 20 years and older were examined for skin lesions and palpable nodules. It was found that for 4 types of skin lesions, acute papular onchodermatitis (APOD), chronic papular onchodermatitis (CPOD), lichenified onchodermatitis (LOD) and depigmentation (leopard skin), as well as for subcutaneous nodules, females had a significantly higher prevalence than males. Although the area is inhabited primarily by the Yoruba people, the study also included some of the cattle-herding Fulani ethnic group. The reactive skin lesions, APOD, CPOD and LOD, were found to be more common among the Fulani, although there were no significant differences in leopard skin and nodules between both groups. While there is need for further research on both immunological and behavioural factors that may lead to these differences in disease. The need to achieve equity in health programming by ensuring that women and ethnic minorities receive full disease control services is of more immediate concern. PMID:9236819

  7. Convex ENO High Order Multi-dimensional Schemes without Field by Field Decomposition or Staggered Grids

    NASA Astrophysics Data System (ADS)

    Liu, Xu-Dong; Osher, Stanley

    1998-05-01

    Second order accurate (first order at extrema) cell averaged based approximations extending the Lax-Friedrichs central scheme, using component-wise rather than field-by-field limiting, have been found to give surprisingly good results for a wide class of problems involving shocks (see H. Nessyahu and E. Tadmor, J. Comput. Phys.87, 408, 1990). The advantages of component-wise limiting compared to its counterpart, field-by-field limiting, are apparent: (1) No complete set of eigenvectors is needed and hence weakly hyperbolic systems can be solved. (2) Component-wise limiting is faster than field-by-field limiting. (3) The programming is much simpler, especially for complicated coupled systems of many equations. However, these methods are based on cell-averages in a staggered grid and are thus a bit complicated to extend to multiple dimensions. Moreover the staggering causes slight difficulties at the boundaries. In this work we modify and extend this component-wise central differencing based procedure in two directions: (1) Point values, rather than cell averages are used, thus removing the need for staggered grids, and also making the extension to multi-dimensions quite simple. We use TVD Runge-Kutta time discretizations to update the solution. (2) A new type of decision process, which follows the general ENO philosophy is introduced and used. This procedure enables us to extend our method to a third order component-wise central ENO scheme, which apparently works well and is quite simple to implement in multi-dimensions. Additionally, our numerical viscosity is governed by the local magnitude of the maximum eigenvalue of the Jacobian, thus reducing the smearing in the numerical results. We found a speed up of a factor of 2 in each space dimension, on a SGI O2workstation, over methods based on field-by-field decomposition limiting. The new decision process leads to new, "convex" ENO schemes which, we believe, are of interest in a more general setting. Our numerical

  8. Teacher Self-Efficacy Enhancement and School Location: Implication for Students' Achievement in Economics in Senior Secondary School in Ibadan, Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Durowoju, Esther O.; Onuka, Adams O. U.

    2015-01-01

    The paper investigated the effect of teacher self-efficacy enhancement and school location on students' achievement in Economics in Senior Secondary School in Ibadan Metropolis of Oyo State, Nigeria. Three hypotheses were tested at 0.05 level of significance. Multi-stage sampling technique was adopted in the study. Four Local Government Areas (two…

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

    PubMed Central

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

    2016-01-01

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

  10. Heat shock protein 90 and tyrosine kinase regulate eNOS NO* generation but not NO* bioactivity.

    PubMed

    Ou, Jingsong; Fontana, Jason T; Ou, Zhijun; Jones, Deron W; Ackerman, Allan W; Oldham, Keith T; Yu, Jun; Sessa, William C; Pritchard, Kirkwood A

    2004-02-01

    An increase in the association of heat shock protein 90 (HSP90) with endothelial nitric oxide (NO) synthase (eNOS) is well recognized for increasing NO (NO*) production. Despite the progress in this field, the mechanisms by which HSP90 modulates eNOS remain unclear due, in part, to the fact that geldanamycin (GA) redox cycles to generate superoxide anion (O(2)(-*) and the fact that inhibiting HSP90 with GA or radicicol (RAD) destabilizes tyrosine kinases that rely on the chaperone for maturation. In this report, we determine the extent to which these side effects alter vascular and endothelial cell function in physiologically relevant systems and in cultured endothelial cells. Vascular endothelial growth factor (VEGF)-stimulated vascular permeability, as measured by Evans blue leakage in the ears of male Swiss mice in vivo, and acetylcholine-induced vasodilation of isolated, pressurized mandibular arterioles from male C57BL6 mice ex vivo were attenuated by N(omega)-nitro-L-arginine methyl ester (L-NAME), GA, and RAD. Z-1[N-(2-aminoethyl)-N-(2-ammonoethyl)amino]diazen-1-ium-1,2-dioate (DETA-NONOate), a slow releasing NO. donor, increased vasodilation of arterioles pretreated with GA, RAD, and L-NAME equally well except at 10(-5) M, the highest concentration used, where vasodilation was greater in pressurized arterioles treated with L-NAME than in arterioles pretreated with GA or RAD alone. Both GA and RAD reduced NO* release from stimulated endothelial cell cultures and increased O(2)(-*) production in the endothelium of isolated aortas by an L-NAME-inhibitable mechanism. Pretreatment with RAD increased stimulated O(2)(-*) production from eNOS, whereas pretreatment with genistein (GE), a broad-spectrum tyrosine kinase inhibitor, did not; however, pretreatment with GE + RAD resulted in a super-induced state of uncoupled eNOS activity upon stimulation. These data suggest that the tyrosine kinases, either directly or indirectly, and HSP90-dependent signaling pathways

  11. High-order ENO methods for the unsteady compressible Navier-Stokes equations

    NASA Technical Reports Server (NTRS)

    Atkins, H. L.

    1991-01-01

    The adaptive stencil concepts of ENO (Essentially Non-Oscillatory) methods are applied to the laminar Navier-Stokes equations to yield a high-order, time-accurate algorithm with a shock-capturing capability. The method targets problems in the areas of nonlinear acoustics, compressible transition, and turbulence which, due to the presence of shocks or complex geometries, are not easily solved by spectral methods. The present approach has been implemented and tested for the full three-dimensional Navier-Stokes equations in a transformed curvilinear coordinate system. Validation results are presented for a variety of problems which verify the method's accuracy properties and shock capturing capabilities, as well as demonstrate its use as a direct simulation tool.

  12. Ethnobotanical study of fuelwood and timber wood consumption and replenishment in Ogbomoso, Oyo State, Nigeria.

    PubMed

    Ogunkunle, A T J; Oladele, F A

    2004-02-01

    A survey of both urban and rural communities in five Local Government Areas (LGA) of Oyo State in Nigeria showed that 76% of households depend on fuelwood for cooking. The total annual wood consumption for fuelling by bread bakers, food sellers and in domestic cooking was 5984 metric tons for the region. The sawmills in the study area also convert 79 889 metric tons of wood yearly into boards of different grades. Total wood consumption outstrips the quantity of wood extracted from the forests. The balance of over 60 000 metric tons of wood is sourced from neighbouring forest locations. The quantity of wood harvested for various purposes did not show a significant difference (p < 0.05) among the five LGAs. However, a significant difference at p > 0.05 existed in the quantity of wood actually consumed in the various LGAs. Moreover. the number of trees cut down outstrips the number of trees planted with a significant difference (p > 0.05) between the mean quantity of wood removed from the forests and the mean quantity replaced by reforestation. The practice in the study area was that of 'cut-eight-plant-one' which is at variance to the much publicized operation 'cut-one-plant-one'. The study concludes that residents of Ogbomoso in Nigeria have not shown positive disposition to tree planting. It therefore suggests scientific tree conservation strategies aimed at improved burning of fuel wood and maximized use of timber products as complementary efforts to enforced tree planting for conservation of our forests. PMID:14969446

  13. Effect of long-term piceatannol treatment on eNOS levels in cultured endothelial cells.

    PubMed

    Kinoshita, Yosuke; Kawakami, Shinpei; Yanae, Koji; Sano, Shoko; Uchida, Hiroko; Inagaki, Hiroyuki; Ito, Tatsuhiko

    2013-01-18

    Piceatannol (3, 3', 4, 5'-tetrahydroxy-trans-stilbene) is a naturally occurring phytochemical found in passion fruit (Passiflora edulis) seeds. Previously, we demonstrated that piceatannol has acute vasorelaxant effects in rat thoracic aorta. It was suggested that endothelial NO synthase (eNOS) might be involved in piceatannol-induced acute vasorelaxation. Here, we investigated the expression of eNOS in EA.hy926 human umbilical vein cells after long-term treatment with piceatannol, and compared this effect with that of resveratrol, an analog of piceatannol. Long-term treatment with piceatannol up-regulated eNOS mRNA expression and increased eNOS protein expression in a dose-dependent manner. Moreover, piceatannol increased the levels of phosphorylated eNOS. Treatment with resveratrol also increased eNOS expression, but to a lesser degree than piceatannol. These findings indicate that piceatannol may improve vascular function by up-regulating eNOS expression. PMID:23246837

  14. On the application of ENO scheme with subcell resolution to conservation laws with stiff source terms

    NASA Technical Reports Server (NTRS)

    Chang, Shih-Hung

    1991-01-01

    Two approaches are used to extend the essentially non-oscillatory (ENO) schemes to treat conservation laws with stiff source terms. One approach is the application of the Strang time-splitting method. Here the basic ENO scheme and the Harten modification using subcell resolution (SR), ENO/SR scheme, are extended this way. The other approach is a direct method and a modification of the ENO/SR. Here the technique of ENO reconstruction with subcell resolution is used to locate the discontinuity within a cell and the time evolution is then accomplished by solving the differential equation along characteristics locally and advancing in the characteristic direction. This scheme is denoted ENO/SRCD (subcell resolution - characteristic direction). All the schemes are tested on the equation of LeVeque and Yee (NASA-TM-100075, 1988) modeling reacting flow problems. Numerical results show that these schemes handle this intriguing model problem very well, especially with ENO/SRCD which produces perfect resolution at the discontinuity.

  15. Social support seeking and self-efficacy-building strategies in enhancing the emotional well-being of informal HIV/AIDS caregivers in Ibadan, Oyo state, Nigeria.

    PubMed

    Okeke, Bernedette Okwuchukwu

    2016-01-01

    This study examined the relative efficacy of social support seeking (SSS) and self-efficacy building (SEB) in the management of emotional well-being of caregivers of people suffering from HIV/AIDS. It was based at the United States President's Emergency Plan for AIDS Relief (PEPFAR) center in the University College Hospital, Ibadan, Oyo state, being the first and the largest teaching hospital in Nigeria. A 3 × 2 factorial design consisting of treatment and a control group was used. The columns have two levels of gender being male and female caregivers. One-hundred and sixty-five (165) caregivers who were taking care of people that are suffering from HIV/AIDS were purposively selected and randomly assigned to the treatment groups and control. The treatment was carried out for a period of eight weeks. Two null hypotheses were tested, both at .05 levels of significance. Data were collected with the use of standardized intruments rating scale; social support scale, general self-efficacy scale and emotional well-being scale. ANCOVA was used to establish significant treatment effects with the pretest as covariate. Even though SSS and SEB were both found to be effective in enhancing the emotional well-being of informal caregivers in this study when compared to the controls, SSS was significantly more effective than SEB in achieving this goal. Since the HIV/AIDS patients cannot be adequately cared for in the hospital settings due to severe shortages of material, personnel and time, serious efforts should be made by the three levels of the health care system viz: the primary, secondary and tertiary health care systems, to encourage the employment of the psychological management of caregivers of people suffering from HIV/AIDS. Also, the psychologists, clinical psychologists and the significant others should be encouraged to employ this psychological management in the care of HIV/AIDS informal caregivers. PMID:26831832

  16. The Contribution of Enos Nuttall to the Development of Education in Jamaica.

    ERIC Educational Resources Information Center

    Allen, Beryl M.

    1984-01-01

    Describes Enos Nuttall's contribution to educational thought and practice in Jamaica. His beliefs on education for all (but differentiated according to individual needs and capabilities) are discussed, as well as his influence on educational reform and curriculum development. (SK)

  17. Assessment of Mobile Health Nursing Intervention Knowledge among Community Health Nurses in Oyo State, Nigeria

    PubMed Central

    Titilayo, Odetola D; Okanlawon, FA

    2014-01-01

    Maternal mortality is high in Nigeria especially in rural areas due to knowledge deficit about expected care and labour process, socio-cultural belief, health care workers’ attitude, physical and financial barriers to quality health care access. Mobile health (m-health) technology which is the use of mobile telecommunication devices in health care delivery reduces costs, improves care access, removes time and distance barriers and facilitates patient-provider communications needed to make appropriate health decisions. Previous studies empowering nurses with m-health knowledge resulted in improved uptake of health care services. There exists a literature dearth about knowledge and perception of nurses in Nigeria. This study became expedient to empower nurses working at the grassroots with the knowledge of m-health and assess the impact of educational training on their perception of its effectiveness. This quasi-experimental study carried out in four randomly selected LGAs across Oyo South Senatorial district involved participants at experimental (20 nurses) and control levels (27 nurses). A validated 25-item questionnaire explored nurses’ perception, knowledge and perceived effectiveness of m-health in improving uptake of maternal health services in Nigeria among both groups before intervention. Intervention group nurses had a training equipping them with knowledge of m-health nursing intervention (MNHI) for a period of one week. Their perception, knowledge and perceived effectiveness were re-assessed at three-months and six-months after MHNI. Data were analyzed using Chi-square and repeated measures ANOVA at 5% significance level. In the EG, knowledge score significantly increased from 21.9±4.5 at baseline to 23.6±4.6 and 23.2±5.6 at three-month and six-month respectively while there was no significant difference in knowledge score among CG over the study period. A very significant difference was shown in the knowledge and perception of mobile health and its

  18. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells

    PubMed Central

    Tran, Jason; Magenau, Astrid; Rodriguez, Macarena; Rentero, Carles; Royo, Teresa; Enrich, Carlos; Thomas, Shane R.; Grewal, Thomas; Gaus, Katharina

    2016-01-01

    Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells. PMID:26977592

  19. Fenofibrate activates AMPK and increases eNOS phosphorylation in HUVEC

    SciTech Connect

    Murakami, Hisashi; Murakami, Ryuichiro . E-mail: ryuichi@med.nagoya-u.ac.jp; Kambe, Fukushi; Cao, Xia; Takahashi, Ryotaro; Asai, Toru; Hirai, Toshihisa; Numaguchi, Yasushi; Okumura, Kenji; Seo, Hisao; Murohara, Toyoaki

    2006-03-24

    Fenofibrate improves endothelial function by lipid-lowering and anti-inflammatory effects. Additionally, fenofibrate has been demonstrated to upregulate endothelial nitric oxide synthase (eNOS). AMP-activated protein kinase (AMPK) has been reported to phosphorylate eNOS at Ser-1177 and stimulate vascular endothelium-derived nitric oxide (NO) production. We report here that fenofibrate activates AMPK and increases eNOS phosphorylation and NO production in human umbilical vein endothelial cells (HUVEC). Incubation of HUVEC with fenofibrate increased the phosphorylation of AMPK and acetyl-CoA carboxylase. Fenofibrate simultaneously increased eNOS phosphorylation and NO production. Inhibitors of protein kinase A and phosphatidylinositol 3-kinase failed to suppress the fenofibrate-induced eNOS phosphorylation. Neither bezafibrate nor WY-14643 activated AMPK in HUVEC. Furthermore, fenofibrate activated AMPK without requiring any transcriptional activities. These results indicate that fenofibrate stimulates eNOS phosphorylation and NO production through AMPK activation, which is suggested to be a novel characteristic of this agonist and unrelated to its effects on peroxisome proliferator-activated receptor {alpha}.

  20. Vanadyl sulfate inhibits NO production via threonine phosphorylation of eNOS.

    PubMed Central

    Li, Zhuowei; Carter, Jacqueline D; Dailey, Lisa A; Huang, Yuh-Chin T

    2004-01-01

    Exposure to excessive vanadium occurs in some occupations and with consumption of some dietary regimens for weight reduction and body building. Because vanadium is vasoactive, individuals exposed to excessive vanadium may develop adverse vascular effects. We have previously shown that vanadyl sulfate causes acute pulmonary vasoconstriction, which could be attributed in part to inhibition of nitric oxide production. In the present study we investigated whether NO inhibition was related to phosphorylation of endothelial nitric oxide synthase (eNOS). VOSO4 produced dose-dependent constriction of pulmonary arteries in isolated perfused lungs and pulmonary arterial rings and a right shift of the acetylcholine-dependent vasorelaxation curve. VOSO4 inhibited constitutive as well as A23187-stimulated NO production. Constitutive NO inhibition was accompanied by increased Thr495 (threonine at codon 495) phosphorylation of eNOS, which would inhibit eNOS activity. Thr495 phosphorylation of eNOS and inhibition of NO were partially reversed by pretreatment with calphostin C, a protein kinase C (PKC) inhibitor. There were no changes in Ser1177 (serine at codon 1177) or tyrosine phosphorylation of eNOS. These results indicate that VOSO4 induced acute pulmonary vasoconstriction that was mediated in part by the inhibition of endothelial NO production via PKC-dependent phosphorylation of Thr495 of eNOS. Exposure to excessive vanadium may contribute to pulmonary vascular diseases. PMID:14754574

  1. Antimicrobials in animal production: usage and practices among livestock farmers in Oyo and Kaduna States of Nigeria.

    PubMed

    Ojo, Olufemi Ernest; Fabusoro, Eniola; Majasan, Ademola Adetokunbo; Dipeolu, Morenike Atinuke

    2016-01-01

    Antimicrobials have proven to be important for sustainable livestock production by their use as growth promoters and in the control of animal infections. However, injudicious use of antimicrobials could accelerate the emergence and spread of resistant bacterial strains with attendant socioeconomic and public health issues. This work assessed antimicrobial usage in animal production with emphasis on usage and practices by livestock producers in Oyo and Kaduna States of Nigeria. Data on antimicrobial usage were collected through interviews, questionnaire and focus group discussions. Four hundred and fifty-four farmers in 11 communities within 11 Local Government Areas of Oyo and Kaduna States of Nigeria were sampled in a multi-stage sampling procedure. The study showed that antimicrobial agents were widely distributed, readily accessible and commonly used in animal production. Fluoroquinolones and other critically important antimicrobials for human medicine were widely used in animals as prophylactics. Potentially harmful antimicrobials including furazolidones and chloramphenicol already banned for use in humans and animals were freely marketed and used in livestock production. Most of the respondents believed that veterinarians should be responsible for the administration of antimicrobials to animals, but in practice, they buy and administer antimicrobials without consulting veterinary professionals. It was observed that the ready availability of antimicrobial agents promoted the use of antimicrobials in livestock production and may encourage non-adherence to hygienic principles and management laxity in farm operations. The non-involvement of veterinary professionals and laboratory investigations in disease diagnosis prior to antimicrobial use could lead to improper usage that contribute to the development of antimicrobial resistance in bacterial strains. Responsible antimicrobial stewardship and strict regulations are vital to prolonging the benefits derivable from

  2. TNFα reduces eNOS activity in endothelial cells through serine 116 phosphorylation and Pin1 binding: Confirmation of a direct, inhibitory interaction of Pin1 with eNOS.

    PubMed

    Kennard, Simone; Ruan, Ling; Buffett, Ryan J; Fulton, David; Venema, Richard C

    2016-06-01

    Production of NO by the endothelial nitric oxide synthase (eNOS) has a major role in blood pressure control and suppression of atherosclerosis. In a previous study, we presented evidence implicating the Pin1 prolyl isomerase in negative modulation of eNOS activity in bovine aortic endothelial cells (BAECs). Pin1 recognizes phosphoserine/phosphothreonine-proline motifs in target proteins and catalyzes prolyl isomerization at the peptide bond. In the present study, we show, first, with purified proteins, that Pin1 binds to eNOS directly via the Pin1 WW domain. Binding is enhanced by mimicking phosphorylation of eNOS at S116. Interaction of Pin1 with eNOS markedly reduces eNOS enzymatic activity. Second, in BAECs, we show that TNFα induces ERK 1/2-mediated S116 phosphorylation of eNOS, accompanied by Pin1 binding. TNFα treatment of BAECs results in a reduction in NO release from the cells in a manner that depends on the activities of both Pin1 and ERK 1/2. Evidence is also presented that this mechanism of eNOS regulation cannot occur in rat and mouse cells because there is no proline residue in the mouse and rat amino acid sequences adjacent to the putative phosphorylation site. Moreover, we find that phosphorylation of this site is not detectable in mouse eNOS. PMID:27073025

  3. Influence of coronary artery diameter on eNOS protein content

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  5. ENO1 promotes tumor proliferation and cell adhesion mediated drug resistance (CAM-DR) in Non-Hodgkin's Lymphomas

    SciTech Connect

    Zhu, Xinghua; Miao, Xiaobing; Wu, Yaxun; Li, Chunsun; Guo, Yan; Liu, Yushan; Chen, Yali; Lu, Xiaoyun; Wang, Yuchan; He, Song

    2015-07-15

    Enolases are glycolytic enzymes responsible for the ATP-generated conversion of 2-phosphoglycerate to phosphoenolpyruvate. In addition to the glycolytic function, Enolase 1 (ENO1) has been reported up-regulation in several tumor tissues. In this study, we investigated the expression and biologic function of ENO1 in Non-Hodgkin's Lymphomas (NHLs). Clinically, by western blot analysis we observed that ENO1 expression was apparently higher in diffuse large B-cell lymphoma than in the reactive lymphoid tissues. Subsequently, immunohistochemical staining of 144 NHLs suggested that the expression of ENO1 was significantly lower in the indolent lymphomas compared with the progressive lymphomas. Further, we identified ENO1 as an independent prognostic factor, and it was significantly correlated with overall survival of NHL patients. In addition, we found that ENO1 could promote cell proliferation, regulate cell cycle associated gene and PI3K/AKT signaling pathway in NHLs. Finally, we verified that ENO1 participated in the process of lymphoma cell adhesion mediated drug resistance (CAM-DR). Adhesion to FN or HS5 cells significantly protected OCI-Ly8 and Daudi cells from cytotoxicity compared with those cultured in suspension, and these effects were attenuated when transfected with ENO1-siRNA. Based on the study, we propose that inhibition of ENO1 expression may be a novel strategy for therapy for NHLs patients, and it may be a target for drug resistance. - Highlights: • ENO1 expression is reversely correlated with clinical outcomes of patients with NHLs. • ENO1 promotes the proliferation of NHL cells. • ENO1 regulates cell adhesion mediated drug resistance.

  6. Ubiad1 Is an Antioxidant Enzyme that Regulates eNOS Activity by CoQ10 Synthesis

    PubMed Central

    Mugoni, Vera; Postel, Ruben; Catanzaro, Valeria; De Luca, Elisa; Turco, Emilia; Digilio, Giuseppe; Silengo, Lorenzo; Murphy, Michael P.; Medana, Claudio; Stainier, Didier Y.R.; Bakkers, Jeroen; Santoro, Massimo M.

    2013-01-01

    Summary Protection against oxidative damage caused by excessive reactive oxygen species (ROS) by an antioxidant network is essential for the health of tissues, especially in the cardiovascular system. Here, we identified a gene with important antioxidant features by analyzing a null allele of zebrafish ubiad1, called barolo (bar). bar mutants show specific cardiovascular failure due to oxidative stress and ROS-mediated cellular damage. Human UBIAD1 is a nonmitochondrial prenyltransferase that synthesizes CoQ10 in the Golgi membrane compartment. Loss of UBIAD1 reduces the cytosolic pool of the antioxidant CoQ10 and leads to ROS-mediated lipid peroxidation in vascular cells. Surprisingly, inhibition of eNOS prevents Ubiad1-dependent cardiovascular oxidative damage, suggesting a crucial role for this enzyme and nonmitochondrial CoQ10 in NO signaling. These findings identify UBIAD1 as a nonmitochondrial CoQ10-forming enzyme with specific cardiovascular protective function via the modulation of eNOS activity. PMID:23374346

  7. Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis

    PubMed Central

    2010-01-01

    Background In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model. Methods Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation. Results The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR and ELISA. Human eNOS ELISA levels were significantly raised 24 hours after transfection compared to controls (125 pg eNOS compared to <50 pg for all controls including naked DNA). Local eNOS production suppressed smooth muscle cell proliferation and promoted re-endothelialization of the artery showing a significant reduction in restenosis of 1.75 neointima/media ratio for stents with lipoplexes encoding eNOS compared with 2.3 neointima/media ratio for stents with lipoplexes encosing an empty vector. Conclusions These results support the hypothesis that a potent non-viral gene vector encoding for eNOS coated onto a stent can inhibit restenosis through inhibition of smooth muscle cell growth and promotion of a healthy endothelium. PMID:20875110

  8. S-glutathionylation uncouples eNOS and regulates its cellular and vascular function

    PubMed Central

    Chen, Chun-An; Wang, Tse-Yao; Varadharaj, Saradhadevi; Reyes, Levy A.; Hemann, Craig; Hassan Talukder, M. A.; Chen, Yeong-Renn; Druhan, Lawrence J.; Zweier, Jay L.

    2012-01-01

    Endothelial nitric oxide synthase (eNOS) is critical in the regulation of vascular function, and can generate both nitric oxide (NO) and superoxide (O2•−), which are key mediators of cellular signalling. In the presence of Ca2+/calmodulin, eNOS produces NO, endothelial-derived relaxing factor, from L-arginine (L-Arg) by means of electron transfer from NADPH through a flavin containing reductase domain to oxygen bound at the haem of an oxygenase domain, which also contains binding sites for tetrahydrobiopterin (BH4) and L-Arg1–3. In the absence of BH4, NO synthesis is abrogated and instead O2•− is generated4–7. While NOS dysfunction occurs in diseases with redox stress, BH4 repletion only partly restores NOS activity and NOS-dependent vasodilation7. This suggests that there is an as yet unidentified redox-regulated mechanism controlling NOS function. Protein thiols can undergo S-glutathionylation, a reversible protein modification involved in cellular signalling and adaptation8,9. Under oxidative stress, S-glutathionylation occurs through thiol–disulphide exchange with oxidized glutathione or reaction of oxidant-induced protein thiyl radicals with reduced glutathione10,11. Cysteine residues are critical for the maintenance of eNOS function12,13; we therefore speculated that oxidative stress could alter eNOS activity through S-glutathionylation. Here we show that S-glutathionylation of eNOS reversibly decreases NOS activity with an increase in O2•− generation primarily from the reductase, in which two highly conserved cysteine residues are identified as sites of S-glutathionylation and found to be critical for redox-regulation of eNOS function. We show that eNOS S-glutathionylation in endothelial cells, with loss of NO and gain of O2•− generation, is associated with impaired endothelium-dependent vasodilation. In hypertensive vessels, eNOS S-glutathionylation is increased with impaired endothelium-dependent vasodilation that is restored by thiol

  9. Extensive Ethnogenomic Diversity of Endothelial Nitric Oxide Synthase (eNOS) Polymorphisms

    PubMed Central

    Thomas, Bolaji N.; Thakur, Tanya J.; Yi, Li; Guindo, Aldiouma; Diallo, Dapa A.; Ott, Jurg

    2013-01-01

    Nitric oxide (NO) is highly reactive, produced in endothelial cells by endothelial NO synthase (eNOS) and has been implicated in sickle cell pathophysiology. We evaluated the distribution of functionally significant eNOS variants (the T786C variant in the promoter region, the Glu298Asp variant in exon 7, and the variable number of tandem repeats (VNTR) in intron 4) in Africans, African Americans and Caucasians. The C-786 variant was more common in Caucasians than in Africans and African Americans. Consistent with other findings, the Asp-298 variant had the highest frequency in Caucasians followed by African Americans, but was completely absent in Africans. The very rare intron 4 allele, eNOS 4c, was found in some Africans and African Americans, but not in Caucasians. eNOS 4d allele was present in 2 Africans. These findings suggest a consistent and widespread genomic diversity in the distribution of eNOS variants in Africans, comparative to African Americans and Caucasians. PMID:23400313

  10. Extensive ethnogenomic diversity of endothelial nitric oxide synthase (eNOS) polymorphisms.

    PubMed

    Thomas, Bolaji N; Thakur, Tanya J; Yi, Li; Guindo, Aldiouma; Diallo, Dapa A; Ott, Jurg

    2013-01-01

    Nitric oxide (NO) is highly reactive, produced in endothelial cells by endothelial NO synthase (eNOS) and has been implicated in sickle cell pathophysiology. We evaluated the distribution of functionally significant eNOS variants (the T786C variant in the promoter region, the Glu298Asp variant in exon 7, and the variable number of tandem repeats (VNTR) in intron 4) in Africans, African Americans and Caucasians. The C-786 variant was more common in Caucasians than in Africans and African Americans. Consistent with other findings, the Asp-298 variant had the highest frequency in Caucasians followed by African Americans, but was completely absent in Africans. The very rare intron 4 allele, eNOS 4c, was found in some Africans and African Americans, but not in Caucasians. eNOS 4d allele was present in 2 Africans. These findings suggest a consistent and widespread genomic diversity in the distribution of eNOS variants in Africans, comparative to African Americans and Caucasians. PMID:23400313

  11. Cardioprotective effects of luteolin on ischemia/reperfusion injury in diabetic rats are modulated by eNOS and the mitochondrial permeability transition pathway.

    PubMed

    Yang, Jin-Ting; Qian, Ling-Bo; Zhang, Feng-Jiang; Wang, Jue; Ai, Heng; Tang, Li-Hui; Wang, Hui-Ping

    2015-04-01

    Myocardial ischemia/reperfusion (I/R) injury in diabetes is associated with oxidative stress, endothelial nitric oxide synthase (eNOS) dysfunction, and mitochondrial collapse, whereas luteolin is known to protect the cardiovascular system against diabetes and I/R injury. Here, we investigated whether luteolin pretreatment diminishes myocardial I/R injury in diabetic rats by affecting eNOS and the mitochondrial permeability transition pore (mPTP). After diabetic rats were produced by streptozotocin treatment (65 mg/kg) for 3 weeks, luteolin (100 mg·kg·d) or L-NAME (25 mg·kg·d) was administered intragastrically for 2 weeks. Hearts were then isolated and subjected to 30 minutes of global ischemia followed by 120 minutes of reperfusion. Pretreatment with luteolin significantly improved left ventricular function and coronary flow throughout reperfusion, increased cardiac tissue viability and manganese superoxide dismutase (MnSOD) activity, and reduced coronary lactate dehydrogenase release, and the myocardial malonaldehyde level in diabetic I/R rat hearts. All these improving effects of luteolin were significantly attenuated by L-NAME. Luteolin also significantly upregulated eNOS expression in diabetic rat hearts after I/R. Ca-induced mPTP opening and mitochondrial inner membrane potential reduction were significantly inhibited in ventricular myocytes isolated from luteolin-treated diabetic rats, and this effect was attenuated by L-NAME. These findings indicate that luteolin protects the diabetic heart against I/R injury by upregulating the myocardial eNOS pathway, and downstream effects include the enhancement of MnSOD and inhibition of mPTP. PMID:25502309

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

    PubMed Central

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

    2012-01-01

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

  13. High-order ENO schemes applied to two- and three-dimensional compressible flow

    NASA Technical Reports Server (NTRS)

    Shu, Chi-Wang; Erlebacher, Gordon; Zang, Thomas A.; Whitaker, David; Osher, Stanley

    1991-01-01

    High order essentially non-oscillatory (ENO) finite difference schemes are applied to the 2-D and 3-D compressible Euler and Navier-Stokes equations. Practical issues, such as vectorization, efficiency of coding, cost comparison with other numerical methods, and accuracy degeneracy effects, are discussed. Numerical examples are provided which are representative of computational problems of current interest in transition and turbulence physics. These require both nonoscillatory shock capturing and high resolution for detailed structures in the smooth regions and demonstrate the advantage of ENO schemes.

  14. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation

    PubMed Central

    Wen, Jiaming; Grenz, Almut; Zhang, Yujin; Dai, Yingbo; Kellems, Rodney E.; Blackburn, Michael R.; Eltzschig, Holger K.; Xia, Yang

    2011-01-01

    Normal penile erection is under the control of multiple factors and signaling pathways. Although adenosine signaling is implicated in normal and abnormal penile erection, the exact role and the underlying mechanism for adenosine signaling in penile physiology remain elusive. Here we report that shear stress leads to increased adenosine release from endothelial cells. Subsequently, we determined that ecto-5′-nucleotidase (CD73) is a key enzyme required for the production of elevated adenosine from ATP released by shear-stressed endothelial cells. Mechanistically, we demonstrate that shear stress-mediated elevated adenosine functions through the adenosine A2B receptor (A2BR) to activate the PI3K/AKT signaling cascade and subsequent increased endothelial nitric oxide synthase (eNOS) phosphorylation. These in vitro studies led us to discover further that adenosine was induced during sustained penile erection and contributes to PI3K/AKT activation and subsequent eNOS phosphorylation via A2BR signaling in intact animal. Finally, we demonstrate that lowering adenosine in wild-type mice or genetic deletion of A2BR in mutant mice significantly attenuated PI3K/AKT activation, eNOS phosphorylation, and subsequent impaired penile erection featured with the reduction of ratio of maximal intracavernosal pressure to systemic arterial pressure from 0.49 ± 0.03 to 0.41 ± 0.05 and 0.38 ± 0.04, respectively (both P<0.05). Overall, using biochemical, cellular, genetic, and physiological approaches, our findings reveal that adenosine is a novel molecule signaling via A2BR activation, contributing to penile erection via PI3K/AKT-dependent eNOS activation. These studies suggest that this signaling pathway may be a novel therapeutic target for erectile disorders.—Wen, J., Grenz, A., Zhang, Y., Dai, Y., Kellems, R. E., Blackburn, M. R., Eltzschig, H. K., Xia, Y. A2B adenosine receptor contributes to penile erection via PI3K/AKT signaling cascade-mediated eNOS activation. PMID

  15. L-theanine promotes nitric oxide production in endothelial cells through eNOS phosphorylation.

    PubMed

    Siamwala, Jamila H; Dias, Paul M; Majumder, Syamantak; Joshi, Manoj K; Sinkar, Vilas P; Banerjee, Gautam; Chatterjee, Suvro

    2013-03-01

    Consumption of tea (Camellia sinensis) improves vascular function and is linked to lowering the risk of cardiovascular disease. Endothelial nitric oxide is the key regulator of vascular functions in endothelium. In this study, we establish that l-theanine, a non-protein amino-acid found in tea, promotes nitric oxide (NO) production in endothelial cells. l-theanine potentiated NO production in endothelial cells was evaluated using Griess reaction, NO sensitive electrode and a NO specific fluorescent probe (4-amino-5-methylamino-2',7'-difluororescein diacetate). l-Theanine induced NO production was partially attenuated in presence of l-NAME or l-NIO and completely abolished using eNOS siRNA. eNOS activation was Ca(2+) and Akt independent, as assessed by fluo-4AM and immunoblotting experiments, respectively and was associated with phosphorylation of eNOS Ser 1177. eNOS phosphorylation was inhibited in the presence of ERK1/2 inhibitor, PD-98059 and partially inhibited by PI3K inhibitor, LY-294002 and Wortmanin suggesting PI3K-ERK1/2 dependent pathway. Increased NO production was associated with vasodilation in ex ovo (chorioallantoic membrane) model. These results demonstrated that l-theanine administration in vitro activated ERK/eNOS resulting in enhanced NO production and thereby vasodilation in the artery. The results of our experiments are suggestive of l-theanine mediated vascular health benefits of tea. PMID:22819553

  16. VANADL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF ENOS

    EPA Science Inventory

    VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF eNOS. Zhuowei Li, Jacqueline D. Carter, Lisa A. Dailey, Joleen Soukup, Yuh-Chin T. Huang. CEMALB, University of North Carolina and ORD, US EPA, Chapel Hill, North Carolina
    V...

  17. VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF ENOS

    EPA Science Inventory

    VANADYL SULFATE INHIBITS NO PRODUCTION BY DIFFERENTIALLY REGULATING SERINE/THREONINE PHOSPHORYLATION OF eNOS.

    Zhuowei Li, Jacqueline D. Carter, Lisa A. Dailey, Joleen Soukup, Yuh-Chin T. Huang. CEMALB, University of North Carolina and NHEERL, US EPA, Chapel Hill, North Ca...

  18. International note: awareness and context of cyber-harassment among secondary school students in Oyo state, Nigeria.

    PubMed

    Olumide, Adesola O; Adams, Patricia; Amodu, Olukemi K

    2015-02-01

    We determined the awareness and context of cyber-harassment among secondary school students (653 survey respondents and 18 in-depth interviewees) in Oyo state, Nigeria. Respondents' mean age was 14.2 ± 2.2 years and 53.9% were aware of cyber-harassment occurring in their school or among their friends. Cyber-harassment was often perpetrated via phone calls (62.5%), text messaging (36.9%), chat rooms (28.7%), through pictures or video clips sent via mobile phones (11.9%), emails (6.8%) or websites (5.9%). Cyber-harassment behaviours mentioned were the use of abusive words (25.4%), saying mean things or making fun of the victim (13.9%), solicitations for relationships (7.9%) or sex (6.8%) and spreading rumours about the victim (6.8%). In-depth interviewees recounted experiences of cyber-harassment suffered by their friends. Many were relationship-related, sexual solicitations and threats and corroborated quantitative findings. Respondents are aware of cyber-harassment occurring among students in the study area. Comprehensive interventions to address the problem need to be instituted. PMID:25544425

  19. Knowledge, Attitude, and Preventive Practices among Prison Inmates in Ogbomoso Prison at Oyo State, South West Nigeria.

    PubMed

    Saliu, Abdulsalam; Akintunde, Babatunde

    2014-01-01

    Prisoners are at special risk for infection with human immunodeficiency virus (HIV) because of overcrowded prisons, unprotected sex and sexual assault, occurrence of sexual practices that are risky to health, unsafe injecting practices, and inadequate HIV prevention, care, and support services. This study aimed to describe the knowledge, attitude, and preventive practices towards HIV/AIDS by male inmates in Ogbomoso Prison at Oyo State, South West Nigeria. This was a cross-sectional study. A simple random sampling method was employed to select 167 male participants and data were collected using pretested structured interviewer-administered questionnaire. The data were collated and analyzed using the Statistical Package for Social Sciences version 17. Fifty (29.9%) were in the age group 20-24 years with mean age of 30.99 ± 11.41. About half (50.3%) had been married before incarceration. Family and friends (30%), health care workers (25%), prison staff (20%), and mass media (25%) were the commonest sources of information on HIV/AIDS. Knowledge about HIV was found to be high (94.6%). About 68.9% believed that people with the disease should be avoided. The knowledge about HIV/AIDS among inmates was high, but misconceptions about HIV/AIDS are still rife among the prisoners and educational programs would be required to correct this. PMID:25763397

  20. Acceptance and Utilisation of Sulphadoxine-Pyrimethamine and Insecticide-Treated Nets among Pregnant Women in Oyo State, Nigeria

    PubMed Central

    Adeola, Aderonke A.; Okwilagwe, Eugenia A.

    2015-01-01

    The study is an investigation of the acceptance and utilisation of Sulphadoxine-Pyrimethamine (Fansidar), the drug of choice for Intermittent Preventive Treatment in pregnancy, and Insecticide-Treated Nets among pregnant women who access different health facilities in Oyo State, Nigeria. Pregnant women (582) attending government primary healthcare antenatal clinics and 50 attending faith clinics purposively selected responded to structured instruments that were analysed using percentages, t-test correlation, and multiple regression. Acceptance and utilisation of RBM tools were higher in government clinics than faith clinics and in rural areas. Pregnant women in government clinics, 60.8% and 66.8%, and faith clinics, 18% and 38.0%, utilised Roll Back Malaria tools, significant at t(630) = 5.81, p ≤ 0.05, and t(630) = 3.99, p ≤ 0.05, respectively. Pregnant women in rural locations who accessed government clinics utilised Roll Back Malaria tools more than those in urban areas, t(580) = −641, p ≤ 0.05. Number of pregnancies, educational qualification of the pregnant women, and marital status significantly and consistently influenced acceptance and utilisation of these tools. To ensure that set targets are met, the utilization of RBM tools among the two categories of pregnant women can be improved by increasing the supply of the tools and ensuring that treatment is free. PMID:26839732

  1. Ablation of eNOS does not promote adipose tissue inflammation.

    PubMed

    Jurrissen, Thomas J; Sheldon, Ryan D; Gastecki, Michelle L; Woodford, Makenzie L; Zidon, Terese M; Rector, R Scott; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-04-15

    Adipose tissue (AT) inflammation is a hallmark characteristic of obesity and an important determinant of insulin resistance and cardiovascular disease; therefore, a better understanding of factors regulating AT inflammation is critical. It is well established that reduced vascular endothelial nitric oxide (NO) bioavailability promotes arterial inflammation; however, the role of NO in modulating inflammation in AT remains disputed. In the present study, 10-wk-old C57BL6 wild-type and endothelial nitric oxide synthase (eNOS) knockout male mice were randomized to either a control diet (10% kcal from fat) or a Western diet (44.9% kcal from fat, 17% sucrose, and 1% cholesterol) for 18 wk (n= 7 or 8/group). In wild-type mice, Western diet-induced obesity led to increased visceral white AT expression of inflammatory genes (e.g., MCP1, TNF-α, and CCL5 mRNAs) and markers of macrophage infiltration (e.g., CD68, ITGAM, EMR1, CD11C mRNAs, and Mac-2 protein), as well as reduced markers of mitochondrial content (e.g., OXPHOS complex I and IV protein). Unexpectedly, these effects of Western diet on visceral white AT were not accompanied by decreases in eNOS phosphorylation at Ser-1177 or increases in eNOS phosphorylation at Thr-495. Also counter to expectations, eNOS knockout mice, independent of the diet, were leaner and did not exhibit greater white or brown AT inflammation compared with wild-type mice. Collectively, these findings do not support the hypothesis that reduced NO production from eNOS contributes to obesity-related AT inflammation. PMID:26864812

  2. Malaria knowledge and agricultural practices that promote mosquito breeding in two rural farming communities in Oyo State, Nigeria

    PubMed Central

    2010-01-01

    Background Agricultural practices such as the use of irrigation during rice cultivation, the use of ponds for fish farming and the storage of water in tanks for livestock provide suitable breeding grounds for anthropophylic mosquitoes. The most common anthropophylic mosquito in Nigeria which causes much of the morbidity and mortality associated with malaria is the anopheles mosquito. Farmers are therefore at high risk of malaria - a disease which seriously impacts on agricultural productivity. Unfortunately information relating to agricultural practices and farmers' behavioural antecedent factors that could assist malaria programmers plan and implement interventions to reduce risk of infections among farmers is scanty. Farmers' knowledge about malaria and agricultural practices which favour the breeding of mosquitoes in Fashola and Soku, two rural farming communities in Oyo State were therefore assessed in two rural farming communities in Oyo State. Methods This descriptive cross-sectional study involved the collection of data through the use of eight Focus Group Discussions (FGDs) and the interview of 403 randomly selected farmers using semi-structured questionnaires. These sets of information were supplemented with observations of agricultural practices made in 40 randomly selected farms. The FGD data were recorded on audio-tapes, transcribed and subjected to content analysis while the quantitative data were analyzed using descriptive and inferential statistics. Results Most respondents in the two communities had low level of knowledge of malaria causation as only 12.4% stated that mosquito bite could transmit the disease. Less than half (46.7%) correctly mentioned the signs and symptoms of malaria as high body temperature, body pains, headache, body weakness and cold/fever. The reported main methods for preventing mosquito bites in the farming communities included removal of heaps of cassava tuber peelings (62.3%), bush burning/clearing (54.6%) and clearing of

  3. Diesel exhaust exposure enhances venoconstriction via uncoupling of eNOS

    SciTech Connect

    Knuckles, Travis L.; Lund, Amie K.; Lucas, Selita N.; Campen, Matthew J.

    2008-08-01

    Environmental air pollution is associated with adverse cardiovascular events, including increased hospital admissions due to heart failure and myocardial infarction. The exact mechanism(s) by which air pollution affects the heart and vasculature is currently unknown. Recent studies have found that exposure to air pollution enhances arterial vasoconstriction in humans and animal models. Work in our laboratory has shown that diesel emissions (DE) enhance vasoconstriction of mouse coronary arteries. Thus, we hypothesized that DE could enhance vasoconstriction in arteries and veins through uncoupling of endothelial nitric oxide synthase (eNOS). To test this hypothesis, we first bubbled DE through a physiological saline solution and exposed isolated mesenteric veins. Second, we exposed animals, whole body, to DE at 350 {mu}g/m{sup 3} for 4 h, after which mesenteric arteries and veins were isolated. Results from these experiments show that saline bubbled with DE as well as inhaled DE enhances vasoconstriction in veins but not arteries. Exposure to several representative volatile organic compounds found in the DE-exposed saline did not enhance arterial constriction. L-nitro-arginine-methyl-ester (L-NAME), an eNOS inhibitor, normalized the control vessels to the DE-exposed vessels implicating an uncoupling of eNOS as a mechanism for enhanced vasoconstriction. The principal conclusions of this research are 1) veins exhibit endothelial dysfunction following in vivo and ex vivo exposures to DE, 2) veins appear to be more sensitive to DE effects than arteries, and 3) DE components most likely induce endothelial dysfunction through the uncoupling of eNOS.

  4. An artificial compression method for ENO schemes: The slope modification method

    NASA Technical Reports Server (NTRS)

    Yang, Huanan

    1988-01-01

    A simple and effective method of artificial compression is introduced. This method is based on a modification of the slopes of the ENO (essentially nonoscillatory) reconstruction and, with the help of suitable chosen parameters, greatly improves the resolution of the contact discontinuities. Numerical examples are provided to test the performance of the method and to give some suggestions as to the choice of the parameters.

  5. Ezetimibe potently reduces vascular inflammation and arteriosclerosis in eNOS deficient ApoE ko mice

    PubMed Central

    Kuhlencordt, Peter J.; Padmapriya, P.; Rützel, S.; Schödel, J.; Hu, K.; Schäfer, A.; Huang, P.L.; Ertl, G.; Bauersachs, J.

    2013-01-01

    Objective Hypercholesterolemia is associated with decreased vascular nitric oxide bioavailability and deletion of endothelial nitric oxide synthase (eNOS) markedly accelerates atherosclerosis development in apolipoprotein E knockout (apoE ko) mice. The current study tests whether atheroprotection provided by a lipid lowering therapy with Ezetimibe depends on eNOS. Methods/Results ApoE ko and apoE/eNOS double ko (dko) mice received a high fat diet with or without 0.05% Ezetimibe. Ezetimibe significantly reduced plasma cholesterol concentrations and atherogenic lipoproteins in both genotypes to a similar extent. Moreover, the drug reduced vascular inflammation, as it significantly reduced Vascular Cell Adhesion Molecule-1 (VCAM-1) expression and vascular CD14 expression, a marker for mononuclear cell infiltration, in both genotypes. Neither NOS protein expression nor vascular reactivity of aortic rings were changed in apoE ko mice following Ezetimibe treatment. Significant lesion reduction was seen in Ezetimibe treated male and female apoE ko and apoE/eNOS dko animals (p≤0.05). Interestingly, the drug mediated additional atheroprotection in male apoE ko, compared to male eNOS dko mice, suggesting that lipid lowering does provide additional eNOS dependent atheroprotection in this experimental group. Conclusion Lipid lowering with Ezetimibe potently reduces atherosclerosis and vascular inflammation independent of eNOS. Moreover, Ezetimibe did not exert any effects on eNOS protein expression or enzyme activity. However, additional atheroprotection by Ezetimibe was observed in eNOS competent apoE ko mice, suggesting that some of the drug's antiatherosclerotic effects are mediated by the eNOS pathway. PMID:18479686

  6. PGC-1α ameliorates AngiotensinII-induced eNOS dysfunction in human aortic endothelial cells.

    PubMed

    Li, Jie; Geng, Xiao-Yong; Cong, Xiao-Liang

    2016-08-01

    Increasing evidences support that PGC-1α participates in regulating endothelial homeostasis, in part by mediating endothelial nitric oxide (NO) synthase (eNOS) activity and NO production. However, the molecular mechanisms by which PGC-1α regulates eNOS activity are not completely understood. In the present study, we investigated the effects of PGC-1α on eNOS dysfunction and further explore the underlying mechanisms. The results showed that PGC-1α expression was downregulated after AngiotensinII (AngII) treatment and paralleled with the decreased NO generation in human aortic endothelial cells. Overexpression of PGC-1α with adenovirus or pharmacological agonist ameliorated AngII-induced the decrease of NO generation, evidenced by the restoration of cGMP and nitrite concentration. Rather than affecting eNOS expression and uncoupling, PGC-1α inhibited AngII-induced decrease of eNOS serine 1177 phosphorylation through activation of PI3K/Akt signaling. In addition, PGC-1α overexpression suppressed AngII-induced the increase of PP2A-A/eNOS interaction and PP2A phosphatase activity, with a concomitant decrease in PP2A phosphorylation, leading to eNOS serine 1177 phosphorylation. However, pharmacological inhibition of PI3K/Akt signaling blunted the observed effect of PGC-1α on PP2A activity. Taken together, our findings suggest that PGC-1α overexpression improves AngII-induced eNOS dysfunction and that improved eNOS dysfunction is associated with activated PI3K/Akt pathway, impaired PP2A activity and reduced PP2A-A/eNOS association. These date indicate that forced PGC-1α expression may be a novel therapeutic approach for endothelial dysfunction. PMID:27235860

  7. Ambient ultrafine particles reduce endothelial nitric oxide production via S-glutathionylation of eNOS

    PubMed Central

    Du, Yunfeng; Navab, Mohamad; Shen, Melody; Hill, James; Pakbin, Payam; Sioutas, Constantinos; Hsiai, Tzung; Li, Rongsong

    2013-01-01

    Exposure to airborne particulate pollutants is intimately linked to vascular oxidative stress and inflammatory responses with clinical relevance to atherosclerosis. Particulate matter (PM) has been reported to induce endothelial dysfunction and atherosclerosis. Here, we tested whether ambient ultrafine particles (UFP, diameter < 200 nm) modulate eNOS activity in terms of nitric oxide (NO) production via protein S-glutathionylation. Treatment of human aortic endothelial cells (HAEC) with UFP significantly reduced NO production. UFP-mediated reduction in NO production was restored in the presence of JNK inhibitor (SP600125), NADPH oxidase inhibitor (Apocynin), anti-oxidant (N-acetyl cysteine), and superoxide dismutase mimetics (Tempol and MnTMPyP). UFP exposure increased the GSSG/GSH ratio and eNOS S-glutathionylation, whereas over-expression of Glutaredoxin-1 (to inhibit S-glutathionylation) restored UFP-mediated reduction in NO production by nearly 80%. Thus, our findings suggest that eNOS S-glutathionylation is a potential mechanism underlying ambient UFP-induced reduction of NO production. PMID:23751346

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

    SciTech Connect

    Nagane, Masaki; Yasui, Hironobu; Sakai, Yuri; Yamamori, Tohru; Niwa, Koichi; Hattori, Yuichi; Kondo, Takashi; Inanami, Osamu

    2015-01-02

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

  9. A novel multiplex PCR-RFLP method for simultaneous detection of the MTHFR 677 C > T, eNOS +894 G > T and - eNOS -786 T > C variants among Malaysian Malays

    PubMed Central

    2012-01-01

    Background Hyperhomocysteinemia as a consequence of the MTHFR 677 C > T variant is associated with cardiovascular disease and stroke. Another factor that can potentially contribute to these disorders is a depleted nitric oxide level, which can be due to the presence of eNOS +894 G > T and eNOS −786 T > C variants that make an individual more susceptible to endothelial dysfunction. A number of genotyping methods have been developed to investigate these variants. However, simultaneous detection methods using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis are still lacking. In this study, a novel multiplex PCR-RFLP method for the simultaneous detection of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants was developed. A total of 114 healthy Malay subjects were recruited. The MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C variants were genotyped using the novel multiplex PCR-RFLP and confirmed by DNA sequencing as well as snpBLAST. Allele frequencies of MTHFR 677 C > T and eNOS +894 G > T and eNOS −786 T > C were calculated using the Hardy Weinberg equation. Methods The 114 healthy volunteers were recruited for this study, and their DNA was extracted. Primer pair was designed using Primer 3 Software version 0.4.0 and validated against the BLAST database. The primer specificity, functionality and annealing temperature were tested using uniplex PCR methods that were later combined into a single multiplex PCR. Restriction Fragment Length Polymorphism (RFLP) was performed in three separate tubes followed by agarose gel electrophoresis. PCR product residual was purified and sent for DNA sequencing. Results The allele frequencies for MTHFR 677 C > T were 0.89 (C allele) and 0.11 (T allele); for eNOS +894 G > T, the allele frequencies were 0.58 (G allele) and 0.43 (T allele); and for eNOS −786 T > C, the allele frequencies were 0.87 (T allele

  10. Altered VEGF-stimulated Ca2+ signaling in part underlies pregnancy-adapted eNOS activity in UAEC.

    PubMed

    Boeldt, Derek S; Grummer, Mary A; Magness, Ronald R; Bird, Ian M

    2014-10-01

    In pregnancy, the uterine vasculature undergoes dramatic vasodilatory adaptations. Previously, vascular endothelial growth factor (VEGF) has been shown to stimulate endothelial nitric oxide synthase (eNOS) in uterine artery endothelial cells (UAECs) derived from pregnant ewes to a greater extent than those from non-pregnant ewes in a manner not fully explained by changes in the phosphorylation of eNOS. In this study, we used Fura-2 Ca(2+) imaging and arginine-to-citrulline conversion eNOS activity assays to assess the importance of VEGF-stimulated Ca(2+) responses in pregnancy-related changes in NO production in UAEC. In this study, we show that pregnancy-induced changes in VEGF-stimulated Ca(2+) responses could account in part for the greater capacity of VEGF to stimulate eNOS in UAECs from pregnant versus non-pregnant animals. VEGF-stimulated Ca(2+) responses in UAECs from pregnant and non-pregnant animals were mediated through VEGF receptor 2 and were detected in roughly 15% of all cells. There were no pregnancy-specific differences in area under the curve or peak height. UAECs from pregnant animals were more consistent in the time to response initiation, had a larger component of extracellular Ca(2+) entry, and were more sensitive to a submaximal dose of VEGF. In UAECs from pregnant and non-pregnant animals Ca(2+) responses and eNOS activation were sensitive to the phospholipase C/inositol 1,4,5-trisphosphate pathway inhibitors 2-aminoethoxydiphenylborane and U73122. Thus, changes in VEGF-stimulated [Ca(2+)]i are necessary for eNOS activation in UAECs, and pregnancy-induced changes in Ca(2+) responses could also in part explain the pregnancy-specific adaptive increase in eNOS activity in UAECs. PMID:25063757

  11. Evaluation of methylation status of the eNOS promoter at birth in relation to childhood bone mineral content

    PubMed Central

    Harvey, Nicholas C.; Lillycrop, Karen A.; Garratt, Emma; Sheppard, Allan; McLean, Cameron; Burdge, Graham; Slater-Jefferies, Jo; Rodford, Joanne; Crozier, Sarah; Inskip, Hazel; Emerald, Bright Starling; Gale, Catharine R; Hanson, Mark; Gluckman, Peter; Godfrey, Keith; Cooper, Cyrus

    2013-01-01

    Aim Our previous work has shown associations between childhood adiposity and perinatal methylation status of several genes in umbilical cord tissue, including endothelial nitric oxide synthase (eNOS). There is increasing evidence that eNOS is important in bone metabolism; we therefore related the methylation status of the eNOS gene promoter in stored umbilical cord to childhood bone size and density in a group of 9-year old children. Methods We used Sequenom MassARRAY to assess the methylation status of 2 CpGs in the eNOS promoter, identified from our previous study, in stored umbilical cords of 66 children who formed part of a Southampton birth cohort and who had measurements of bone size and density at age 9 years (Lunar DPXL DXA instrument). Results Percentage methylation varied greatly between subjects. For one of the two CpGs, eNOS chr7:150315553+, after taking account of age and sex there was a strong positive association between methylation status and the child’s whole body bone area (r=0.28,p=0.02), bone mineral content (r=0.34,p=0.005) and areal bone mineral density (r=0.34,p=0.005) at age 9 years. These associations were independent of previously documented maternal determinants of offspring bone mass. Conclusions Our findings suggest an association between methylation status at birth of a specific CpG within the eNOS promoter and bone mineral content in childhood. This supports a role for eNOS in bone growth and metabolism and implies that its contribution may at least in part occur during early skeletal development. PMID:22159788

  12. Hemoglobin α / eNOS Coupling at Myoendothelial Junctions is Required for Nitric Oxide Scavenging During Vasoconstriction

    PubMed Central

    Straub, Adam C.; Butcher, Joshua T.; Billaud, Marie; Mutchler, Stephanie M.; Artamonov, Mykhaylo V.; Nguyen, Anh T.; Johnson, Tyler; Best, Angela K.; Miller, Megan P.; Palmer, Lisa A.; Columbus, Linda; Somlyo, Avril V.; Le, Thu H.; Isakson, Brant E.

    2014-01-01

    Objective Hb α and eNOS form a macromolecular complex at myoendothelial junctions; the functional role of this interaction remains undefined. To test if coupling of eNOS and Hb α regulates NO signaling, vascular reactivity and blood pressure using a mimetic peptide of Hb α to disrupt this interaction. Approach and Results In silico modeling of Hb α and eNOS identified a conserved sequence of interaction. By mutating portions of Hb α, we identified a specific sequence that binds eNOS. A mimetic peptide of the Hb α sequence (Hb α X) was generated to disrupt this complex. Utilizing in vitro binding assays with purified Hb α and eNOS and ex vivo proximity ligation assays on resistance arteries, we have demonstrated that Hb α X significantly decreased interaction between eNOS and Hb α. FITC-labeling of Hb α X revealed localization to holes in the internal elastic lamina (i.e., myoendothelial junctions). To test the functional effects of Hb α X, we measured cGMP and vascular reactivity. Our results reveal augmented cGMP production and altered vasoconstriction with Hb α X. To test the in vivo effects of these peptides on blood pressure, normotensive and hypertensive mice were injected with Hb α X which caused a significant decrease in blood pressure; injection of Hb α X into eNOS−/− mice had no effect. Conclusion These results identify a novel sequence on Hb α that is important for Hb α / eNOS complex formation and is critical for nitric oxide signaling at myoendothelial junctions. PMID:25278292

  13. Salmonella and Escherichia coli contamination of poultry meat from a processing plant and retail markets in Ibadan, Oyo State, Nigeria.

    PubMed

    Adeyanju, Gladys Taiwo; Ishola, Olayinka

    2014-01-01

    Salmonella spp and Escherichia coli are the two most important food-borne pathogens of public health interest incriminated in poultry meat worldwide. This study is to access their levels in frozen poultry meat obtained in Ibadan, Oyo State and compare those obtained from a commercial Nigerian-registered poultry company having a broiler-processing plant, Sayed Farms Ltd(R), with that obtained from retail stores. These retail stores source their products as illegal imports from neighboring Benin Republic or Togo because of a ban imposed by Government policy in Nigeria since July 2002 (USDA, GAIN report #NI2025:1-6, 2002). Microbiological Standards and Guidelines by USDA (National Agricultural library) (USDA 2011) and NCCLS guidelines (from Global Salm-Surv, 2003) were used during the research work. The study was approved by the Ethical Research Review Board (ERRB, Research Management Office 2011), University of Ibadan, Nigeria. A total of one hundred and fifty-two (152) frozen poultry meat samples comprising ninety-nine retail poultry (53 chicken and 46 turkey) and 53 chicken from the processing plant were accessed. ISO Standards catalogue 07.100.30 (2011) was used in accessing the levels of Salmonella, Escherichia coli, Enterobacteriaceae counts and Aerobic plate count. ISO 6579: 2002 was used for Salmonella isolation and ISO-16654:2001 for Escherichia coli isolation. There was a higher level of Aerobic plate counts and Enterobacteriaceae counts in frozen retail poultry meat than from the processing plant. Salmonella contamination from the ninety-nine poultry samples (53 chicken and 46 turkey) obtained from retail markets was at 33% [chicken 32.1% (17/53) and turkey 34.8% (16/46)] while Escherichia coli at 43.4% [chicken 47.2% (25/53) and turkey 39.1% (18/46)]. From the processing plant, twelve (12) Salmonella isolates were obtained and prevalence rate calculated as 22.6% while three (3) Escherichia coli isolates at 5.7% was obtained. Antibiotic sensitivity for

  14. Fenofibrate Improves Vascular Endothelial Function by Reducing Oxidative Stress While Increasing eNOS in Healthy Normolipidemic Older Adults

    PubMed Central

    Walker, Ashley E; Kaplon, Rachelle E; Lucking, Sara Marian S; Russell-Nowlan, Molly J; Eckel, Robert H; Seals, Douglas R

    2013-01-01

    Vascular endothelial dysfunction develops with aging, as indicated by impaired endothelium-dependent dilation(EDD), and is related to increased cardiovascular disease risk. We hypothesized that short-term treatment with fenofibrate, a lipid-lowering agent with potential pleiotropic effects, would improve EDD in middle-aged and older normolipidemic adults by reducing oxidative stress. Brachial artery flow-mediated dilation (FMD), a measure of EDD, was assessed in 22healthy adults aged 50-77 years before and after 7days of fenofibrate (145 mg/d; n=12/7M) or placebo (n=10/5M). Brachial FMD was unchanged with placebo, but improved after 2 and 7 days of fenofibrate (5.1±0.7 vs. 2d: 6.0±0.7 and 7d: 6.4±0.6 %Δ; both P<0.005). The improvements in FMD after 7 days remained significant (P<0.05) after accounting for modest changes in plasma total and LDL-cholesterol. Endothelium-independent dilation was not affected by fenofibrate or placebo (P>0.05). Infusion (i.v.) of the antioxidant vitamin C improved brachial FMD at baseline in both groups and during placebo treatment (P<0.05), but not after 2 and 7 days of fenofibrate (P>0.05). Fenofibrate treatment also reduced plasma oxidized LDL, a systemic marker of oxidative stress, compared with placebo (P<0.05). In vascular endothelial cells sampled from peripheral veins of the subjects, endothelial nitric oxide synthase (eNOS) protein expression was unchanged with placebo and after 2 days of fenofibrate, but was increased after 7 days of fenofibrate (0.54±0.03 vs. 2d: 0.52±0.04 and 7d: 0.76±0.11 intensity/HUVEC control; P<0.05 7d). Short-term treatment with fenofibrate improves vascular endothelial function in healthy normolipidemic middle-aged/older adults by reducing oxidative stress and induces increases in eNOS. PMID:23108655

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

    PubMed

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

    2016-07-01

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

  16. Endothelial Nitric Oxide Synthase (eNOS) 4a/b and G894T Polymorphisms and Susceptibility to Preeclampsia

    PubMed Central

    Rahimi, Zohreh; Aghaei, Amir; Rahimi, Ziba; Vaisi-Raygani, Asad

    2013-01-01

    Background Preeclampsia is a pregnancy complication with unknown etiology and its incidence is associated with genetic and environmental factors. There are inconsistent reports related to the role of endothelial nitric oxide synthase (eNOS) 4a/b polymorphism on the risk of preeclampsia development. The aim of the present study was to investigate the possible influence of eNOS 4a/b and its synergism with eNOS G894T polymorphism on the risk of preeclampsia. Methods The present case-control study consisted of 179 unrelated women with preeclampsia including 118 with mild and 61 with severe preeclampsia and 96 unrelated women with normal pregnancy as controls. All studied women were from Kermanshah Province of Iran. eNOS 4a/b and G894T genotypes were detected using polymerase chain reaction (PCR), and PCR-restriction fragment length polymorphism (RFLP) methods, respectively. The categorical variables between groups were compared using χ2 test and the Odds ratios (OR) were obtained by SPSS logistic regression. Statistical significance was assumed at p<0.05 level. Results The frequency of eNOS a allele was slightly higher in both mild (16.5%) and severe (17.2%) preeclamptic women than controls (15.1%). Also, no significant difference was found between early- and late-onset preeclamptic women regarding the distribution of eNOS 4a/b genotypes. The presence of each allele of eNOS a or T was not associated with the risk of preeclampsia. However, the concomitant presence of both eNOS a and T alleles was associated with a non significant increased risk of severe preeclampsia by 1.77-fold (p=0.35). Conclusion The present study indicates the lack of association between eNOS a and T alleles with the risk of mild preeclampsia and a non significant increased risk of severe preeclampsia in the presence of both alleles which needs to be investigated in a study with larger samples. PMID:24551572

  17. WLS-ENO: Weighted-least-squares based essentially non-oscillatory schemes for finite volume methods on unstructured meshes

    NASA Astrophysics Data System (ADS)

    Liu, Hongxu; Jiao, Xiangmin

    2016-06-01

    ENO (Essentially Non-Oscillatory) and WENO (Weighted Essentially Non-Oscillatory) schemes are widely used high-order schemes for solving partial differential equations (PDEs), especially hyperbolic conservation laws with piecewise smooth solutions. For structured meshes, these techniques can achieve high order accuracy for smooth functions while being non-oscillatory near discontinuities. For unstructured meshes, which are needed for complex geometries, similar schemes are required but they are much more challenging. We propose a new family of non-oscillatory schemes, called WLS-ENO, in the context of solving hyperbolic conservation laws using finite-volume methods over unstructured meshes. WLS-ENO is derived based on Taylor series expansion and solved using a weighted least squares formulation. Unlike other non-oscillatory schemes, the WLS-ENO does not require constructing sub-stencils, and hence it provides a more flexible framework and is less sensitive to mesh quality. We present rigorous analysis of the accuracy and stability of WLS-ENO, and present numerical results in 1-D, 2-D, and 3-D for a number of benchmark problems, and also report some comparisons against WENO.

  18. Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism

    NASA Technical Reports Server (NTRS)

    Boo, Yong Chool; Hwang, Jinah; Sykes, Michelle; Michell, Belinda J.; Kemp, Bruce E.; Lum, Hazel; Jo, Hanjoong

    2002-01-01

    Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli.

  19. Association of eNOS Gene Polymorphisms G894T and T-786C with Risk of Hepatorenal Syndrome

    PubMed Central

    Yigit, Ali; Yesilada, Elif; Gulbay, Gonca; Bılgıc, Yılmaz; Yildirim, Oguzhan; Turkoz, Yusuf; Aksungur, Zeynep

    2016-01-01

    Background. There are no studies investigating the relationship between endothelial nitric oxide synthase (eNOS) gene polymorphisms and hepatorenal syndrome (HRS). Aim. The purpose of this study is to elucidate whether eNOS gene polymorphisms (G894T and T-786C) play a role in the development of type-2 HRS. Methods. This study was carried out in a group of 92 patients with cirrhosis (44 patients with type-2 HRS and 48 without HRS) and 50 healthy controls. Polymorphisms were determined by polymerase chain reaction (PCR) and melting curve analysis. Results. We did not find any significant difference in allele and genotype distributions of the eNOS -T-786C polymorphism among the groups (p = 0.440). However, the frequency of GT (40.9%) and TT (13.6%) genotypes and mutant allele T (34.1%) for the eNOS G894T polymorphism were significantly higher (p < 0.001 and p < 0.001, resp.) in the HRS group than in both the stable cirrhosis (14.6%, 4.2%, and 11.5%, resp.) and the control (22.0%, 2.0%, and 13.0%, resp.) groups. Conclusion. The occurrence of mutant genotypes (GT/TT) and mutant allele T in eNOS -G894T polymorphisms should be considered as a potential risk factor in cirrhotic patients with HRS. PMID:27594880

  20. Maintenance of normal blood pressure is dependent on IP3R1-mediated regulation of eNOS.

    PubMed

    Yuan, Qi; Yang, Jingyi; Santulli, Gaetano; Reiken, Steven R; Wronska, Anetta; Kim, Mindy M; Osborne, Brent W; Lacampagne, Alain; Yin, Yuxin; Marks, Andrew R

    2016-07-26

    Endothelial cells (ECs) are critical mediators of blood pressure (BP) regulation, primarily via the generation and release of vasorelaxants, including nitric oxide (NO). NO is produced in ECs by endothelial NO synthase (eNOS), which is activated by both calcium (Ca(2+))-dependent and independent pathways. Here, we report that intracellular Ca(2+) release from the endoplasmic reticulum (ER) via inositol 1,4,5-trisphosphate receptor (IP3R) is required for Ca(2+)-dependent eNOS activation. EC-specific type 1 1,4,5-trisphosphate receptor knockout (IP3R1(-/-)) mice are hypertensive and display blunted vasodilation in response to acetylcholine (ACh). Moreover, eNOS activity is reduced in both isolated IP3R1-deficient murine ECs and human ECs following IP3R1 knockdown. IP3R1 is upstream of calcineurin, a Ca(2+)/calmodulin-activated serine/threonine protein phosphatase. We show here that the calcineurin/nuclear factor of activated T cells (NFAT) pathway is less active and eNOS levels are decreased in IP3R1-deficient ECs. Furthermore, the calcineurin inhibitor cyclosporin A, whose use has been associated with the development of hypertension, reduces eNOS activity and vasodilation following ACh stimulation. Our results demonstrate that IP3R1 plays a crucial role in the EC-mediated vasorelaxation and the maintenance of normal BP. PMID:27402766

  1. eNOS polymorphisms and clinical outcome in advanced HCC patients receiving sorafenib: final results of the ePHAS study.

    PubMed

    Casadei Gardini, Andrea; Marisi, Giorgia; Faloppi, Luca; Scarpi, Emanuela; Foschi, Francesco Giuseppe; Iavarone, Massimo; Lauletta, Gianfranco; Corbelli, Jody; Valgiusti, Martina; Facchetti, Floriana; Della Corte, Cristina; Neri, Luca Maria; Tamberi, Stefano; Cascinu, Stefano; Scartozzi, Mario; Amadori, Dino; Nanni, Oriana; Tenti, Elena; Ulivi, Paola; Frassineti, Giovanni Luca

    2016-05-10

    Sorafenib may reduce endothelial nitric oxide synthase (eNOS) activity by inhibiting vascular endothelial growth factor receptors (VEGF-R), leading to a decrease in nitric oxide production. In the Italian multicenter ePHAS (eNOS polymorphisms in HCC and sorafenib) study, we analyzed the role of eNOS polymorphisms in relation to clinical outcome in patients with hepatocellular carcinoma (HCC) receiving sorafenib. Our retrospective study included a training cohort of 41 HCC patients and a validation cohort of 87 HCC patients, all undergoing sorafenib treatment. Three eNOS polymorphisms (eNOS -786T>C, eNOS VNTR 27bp 4a/b and eNOS+894G>T) were analyzed by direct sequencing or Real Time PCR in relation to progression-free survival (PFS) and overall survival (OS) (log-rank test). In univariate analysis, training cohort patients homozygous for eNOS haplotype (HT1:T-4b at eNOS-786/eNOS VNTR) had a lower median PFS (2.6 vs. 5.8 months, P < 0.0001) and OS (3.2 vs.14.6 months, P = 0.024) than those with other haplotypes. In the validation set, patients homozygous for HT1 had a lower median PFS (2.0 vs. 6.7 months, P < 0.0001) and OS (6.4 vs.18.0 months, P < 0.0001) than those with other haplotypes. Multivariate analysis confirmed this haplotype as the only independent prognostic factor. Our results suggest that haplotype HT1 in the eNOS gene may be capable of identifying a subset of HCC patients who are resistant to sorafenib. PMID:27058899

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

    PubMed

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

    2015-10-01

    The balance of nitric oxide (NO) versus superoxide generation has a major role in the initiation and progression of endothelial dysfunction. Under conditions of high glucose, endothelial nitric oxide synthase (eNOS) functions as a chief source of superoxide rather than NO. In order to improve NO bioavailability within the vessel wall in type-1 diabetes, we investigated treatment strategies that improve eNOS phosphorylation and NO-dependent vasorelaxation. We evaluated methods to increase the eNOS activity by (1) feeding Ins2(Akita) spontaneously diabetic (type-1) mice with l-arginine in the presence of sepiapterin, a precursor of tetrahydrobiopterin; (2) preventing eNOS/NO deregulation by the inclusion of inhibitor kappa B kinase beta (IKKβ) inhibitor, salsalate, in the diet regimen in combination with l-arginine and sepiapterin; and (3) independently increasing eNOS expression to improve eNOS activity and associated NO production through generating Ins2(Akita) diabetic mice that overexpress human eNOS predominantly in vascular endothelial cells. Our results clearly demonstrated that diet supplementation with l-arginine, sepiapterin along with salsalate improved phosphorylation of eNOS and enhanced vasorelaxation of thoracic/abdominal aorta in type-1 diabetic mice. More interestingly, despite the overexpression of eNOS, the in-house generated transgenic eNOS-GFP (TgeNOS-GFP)-Ins2(Akita) cross mice showed an unanticipated effect of reduced eNOS phosphorylation and enhanced superoxide production. Our results demonstrate that enhancement of endogenous eNOS activity by nutritional modulation is more beneficial than increasing the endogenous expression of eNOS by gene therapy modalities. PMID:26214584

  3. Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice

    PubMed Central

    Champion, Hunter C.; Bivalacqua, Trinity J.; Greenberg, Stanley S.; Giles, Thomas D.; Hyman, Albert L.; Kadowitz, Philip J.

    2002-01-01

    It has been shown that mice deficient in the gene coding for endothelial nitric-oxide synthase (eNOS) have increased pulmonary arterial pressure and pulmonary vascular resistance. In the present study, the effect of transfer to the lung of an adenoviral vector encoding the eNOS gene (AdCMVeNOS) on pulmonary arterial pressure and pulmonary vascular resistance was investigated in eNOS-deficient mice. One day after intratracheal administration of AdCMVeNOS to eNOS−/− mice, there was an increase in eNOS protein, cGMP levels, and calcium-dependent conversion of l-arginine to l-citrulline in the lung. The increase in eNOS protein and activity in eNOS−/− mice was associated with a reduction in mean pulmonary arterial pressure and pulmonary vascular resistance when compared with values in eNOS-deficient mice treated with vehicle or a control adenoviral vector coding for β-galactosidase, AdCMVβgal. These data suggest that in vivo gene transfer of eNOS to the lung in eNOS−/− mice can increase eNOS staining, eNOS protein, calcium-dependent NOS activity, and cGMP levels and partially restore pulmonary arterial pressure and pulmonary vascular resistance to near levels measured in eNOS+/+ mice. Thus, the major finding in this study is that in vivo gene transfer of eNOS to the lung in large part corrects a genetic deficiency resulting from eNOS deletion and may be a useful therapeutic intervention for the treatment of pulmonary hypertensive disorders in which eNOS activity is reduced. PMID:12237402

  4. ICAM-1-activated Src and eNOS signaling increase endothelial cell surface PECAM-1 adhesivity and neutrophil transmigration.

    PubMed

    Liu, Guoquan; Place, Aaron T; Chen, Zhenlong; Brovkovych, Viktor M; Vogel, Stephen M; Muller, William A; Skidgel, Randal A; Malik, Asrar B; Minshall, Richard D

    2012-08-30

    Polymorphonuclear neutrophil (PMN) extravasation requires selectin-mediated tethering, intercellular adhesion molecule-1 (ICAM-1)-dependent firm adhesion, and platelet/endothelial cell adhesion molecule 1 (PECAM-1)-mediated transendothelial migration. An important unanswered question is whether ICAM-1-activated signaling contributes to PMN transmigration mediated by PECAM-1. We tested this concept and the roles of endothelial nitric oxide synthase (eNOS) and Src activated by PMN ligation of ICAM-1 in mediating PECAM-1-dependent PMN transmigration. We observed that lung PMN infiltration in vivo induced in carrageenan-injected WT mice was significantly reduced in ICAM-1(-/-) and eNOS(-/-) mice. Crosslinking WT mouse ICAM-1 expressed in human endothelial cells (ECs), but not the phospho-defective Tyr(518)Phe ICAM-1 mutant, induced SHP-2-dependent Src Tyr530 dephosphorylation that resulted in Src activation. ICAM-1 activation also stimulated phosphorylation of Akt (p-Ser473) and eNOS (p-Ser1177), thereby increasing NO production. PMN migration across EC monolayers was abolished in cells expressing the Tyr(518)Phe ICAM-1 mutant or by pretreatment with either the Src inhibitor PP2 or eNOS inhibitor L-NAME. Importantly, phospho-ICAM-1 induction of Src signaling induced PECAM-1 Tyr686 phosphorylation and increased EC surface anti-PECAM-1 mAb-binding activity. These results collectively show that ICAM-1-activated Src and eNOS signaling sequentially induce PECAM-1-mediated PMN transendothelial migration. Both Src and eNOS inhibition may be important therapeutic targets to prevent or limit vascular inflammation. PMID:22806890

  5. A numerical study of ENO and TVD schemes for shock capturing

    NASA Technical Reports Server (NTRS)

    Chang, Shih-Hung; Liou, Meng-Sing

    1988-01-01

    The numerical performance of a second-order upwind-based total variation diminishing (TVD) scheme and that of a uniform second-order essentially non-oscillatory (ENO) scheme for shock capturing are compared. The TVD scheme used is a modified version of Liou, using the flux-difference splitting (FDS) of Roe and his superbee function as the limiter. The construction of the basic ENO scheme is based on Harten, Engquist, Osher, and Chakravarthy, and the 2-D extensions are obtained by using a Strang-type of fractional-step time-splitting method. Numerical results presented include both steady and unsteady, 1-D and 2-D calculations. All the chosen test problems have exact solutions so that numerical performance can be measured by comparing the computer results to them. For 1-D calculations, the standard shock-tube problems of Sod and Lax are chosen. A very strong shock-tube problem, with the initial density ratio of 400 to 1 and pressure ratio of 500 to 1, is also used to study the behavior of the two schemes. For 2-D calculations, the shock wave reflection problems are adopted for testing. The cases presented in this report include flows with Mach numbers of 2.9, 5.0, and 10.0.

  6. A family of high-order targeted ENO schemes for compressible-fluid simulations

    NASA Astrophysics Data System (ADS)

    Fu, Lin; Hu, Xiangyu Y.; Adams, Nikolaus A.

    2016-01-01

    Although classical WENO schemes have achieved great success and are widely accepted, they exhibit several shortcomings. They are too dissipative for direct simulations of turbulence and lack robustness when very-high-order versions are applied to complex flows. In this paper, we propose a family of high-order targeted ENO schemes which are applicable for compressible-fluid simulations involving a wide range of flow scales. In order to increase the numerical robustness as compared to very-high-order classical WENO schemes, the reconstruction dynamically assembles a set of low-order candidate stencils with incrementally increasing width. While discontinuities and small-scale fluctuations are efficiently separated, the numerical dissipation is significantly diminished by an ENO-like stencil selection, which either applies a candidate stencil with its original linear weight, or removes its contribution when it is crossed by a discontinuity. The background linear scheme is optimized under the constraint of preserving an approximate dispersion-dissipation relation. By means of quasi-linear analyses and practical numerical experiments, a set of case-independent parameters is determined. The general formulation of arbitrarily high-order schemes is presented in a straightforward way. A variety of benchmark-test problems, including broadband waves, strong shock and contact discontinuities are studied. Compared to well-established classical WENO schemes, the present schemes exhibit significantly improved robustness, low numerical dissipation and sharp discontinuity capturing. They are particularly suitable for DNS and LES of shock-turbulence interactions.

  7. High-order ENO schemes for unstructured meshes based on least-squares reconstruction

    SciTech Connect

    Ollivier-Gooch, C.F.

    1997-03-01

    High-order accurate schemes for conservation laws for unstructured meshes are not nearly so well advanced as such schemes for structured meshes. Consequently, little or nothing is known about the possible practical advantages of high-order discretization on unstructured meshes. This article is part of an ongoing effort to develop high-order schemes for unstructured meshes to the point where meaningful information can be obtained about the trade-offs involved in using spatial discretizations of higher than second-order accuracy on unstructured meshes. This article describes a high-order accurate ENO reconstruction scheme, called DD-L{sub 2}-ENO, for use with vertex-centered upwind flow solution algorithms on unstructured meshes. The solution of conservation equations in this context can be broken naturally into three phases: (1) solution reconstruction, in which a polynomial approximation of the solution is obtained in each control volume. (2) Flux integration around each control volume, using an appropriate flux function and a quadrature rule with accuracy commensurate with that of the reconstruction. (3) Time evolution, which may be implicit, explicit, multigrid, or some hybrid.

  8. Uric acid enhances PKC-dependent eNOS phosphorylation and mediates cellular ER stress: A mechanism for uric acid-induced endothelial dysfunction

    PubMed Central

    LI, PENG; ZHANG, LINA; ZHANG, MEI; ZHOU, CHANGYONG; LIN, NAN

    2016-01-01

    The mechanism by which hyperuricemia induced-endothelial dysfunction contributes to cardiovascular diseases (CVDs) is not yet fully understood. In the present study, we used uric acid (UA) to trigger endothelial dysfunction in cultured endothelial cells, and investigated the effects of induced reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress induction, and the protein kinase C (PKC)-dependent endothelial nitric oxide synthase (eNOS) signaling pathway. Human umbilical vein endothelial cells (HUVECs) were incubated with 6, 9 or 12 mg/dl UA, ROS scavenger polyethylene glycol-superoxide dismutase (PEG-SOD), ER stress inhibitor 4-phenylbutyric acid (4-PBA), and PKC inhibitor polymyxin B for 6–48 h. Nitric oxide (NO) production, eNOS activity, intracellular ROS, ER stress levels, and the interaction between eNOS and calmodulin (CaM) and cytosolic calcium levels were assessed using fluorescence microscopy and western blot analysis. Apoptosis was assessed by annexin V staining. UA increased HUVEC apoptosis and reduced eNOS activity and NO production in a dose- and time-dependent manner. Intracellular ROS was elevated after 3 h, while ER stress level increased after 6 h. UA did not alter intracellular Ca2+, CaM, or eNOS concentration, or eNOS Ser1177 phosphorylation. However, PKC-dependent eNOS phosphorylation at Thr495 was greatly enhanced, and consequently interaction between eNOS and CaM was reduced. Cellular ROS depletion, ER stress inhibition and PKC activity reduction inhibited the effect of UA on eNOS activity, NO release and apoptosis in HUVECs. Thus, we concluded that UA induced HUVEC apoptosis and endothelial dysfunction by triggering oxidative and ER stress through PKC/eNOS-mediated eNOS activity and NO production. PMID:26935704

  9. Modulation of cardiac contraction, relaxation and rate by the endothelial nitric oxide synthase (eNOS): lessons from genetically modified mice

    PubMed Central

    Massion, P B; Balligand, J-L

    2003-01-01

    The modulatory role of endothelial nitric oxide synthase (eNOS) on heart contraction, relaxation and rate is examined in light of recent studies using genetic deletion or overexpression in mice under specific conditions. Unstressed eNOS-/- hearts in basal conditions exhibit a normal inotropic and lusitropic function, with either decreased or unchanged heart rate. Under stimulation with catecholamines, eNOS-/- mice predominantly show a potentiation in their β-adrenergic inotropic and lusitropic responsiveness. A similar phenotype is observed in β3-adrenoceptor deficient mice, pointing to a key role of this receptor subtype for eNOS coupling. The effect of eNOS on the muscarinic cholinergic modulation of cardiac function probably operates in conjunction with other NO-independent mechanisms, the persistence of which may explain the apparent dispensability of this isoform for the effect of acetylcholine in some eNOS-/- mouse strains. eNOS-/- hearts submitted to short term ischaemia-reperfusion exhibit variable alterations in systolic and diastolic function and infarct size, while those submitted to myocardial infarction present a worsened ventricular remodelling, increased 1 month mortality and loss of benefit from ACE inhibitor or angiotensin II type I receptor antagonist therapy. Although non-conditional eNOS gene deletion may engender phenotypic adaptations (e.g. ventricular hypertrophy resulting from chronic hypertension, or upregulation of the other NOS isoforms) potentially confounding the interpretation of comparative studies, the use of eNOS-/- mice has undoubtedly advanced (and will probably continue to improve) our understanding of the complex role of eNOS (in conjunction with the other NOSs) in the regulation of cardiac function. The challenge is now to confirm the emerging paradigms in human cardiac physiology and hopefully translate them into therapy. PMID:12509479

  10. Pretreatment with β-Boswellic Acid Improves Blood Stasis Induced Endothelial Dysfunction: Role of eNOS Activation.

    PubMed

    Wang, Mingming; Chen, Minchun; Ding, Yi; Zhu, Zhihui; Zhang, Yikai; Wei, Peifeng; Wang, Jingwen; Qiao, Yi; Li, Liang; Li, Yuwen; Wen, Aidong

    2015-01-01

    Vascular endothelial cells play an important role in modulating anti-thrombus and maintaining the natural function of vascular by secreting many active substances. β-boswellic acid (β-BA) is an active triterpenoid compound from the extract of boswellia serrate. In this study, it is demonstrated that β-BA ameliorates plasma coagulation parameters, protects endothelium from blood stasis induced injury and prevents blood stasis induced impairment of endothelium-dependent vasodilatation. Moreover, it is found that β-BA significantly increases nitric oxide (NO) and cyclic guanosine 3', 5'-monophosphate (cGMP) levels in carotid aortas of blood stasis rats. To stimulate blood stasis-like conditions in vitro, human umbilical vein endothelial cells (HUVECs) were exposed to transient oxygen and glucose deprivation (OGD). Treatment of β-BA significantly increased intracellular NO level. Western blot and immunofluorescence as well as immunohistochemistry reveal that β-BA increases phosphorylation of enzyme nitric oxide synthase (eNOS) at Ser1177. In addition, β-BA mediated endothelium-dependent vasodilatation can be markedly blocked by eNOS inhibitor L-NAME in blood stasis rats. In OGD treated HUEVCs, the protective effect of β-BA is attenuated by knockdown of eNOS. In conclusion, the above findings provide convincing evidence for the protective effects of β-BA on blood stasis induced endothelial dysfunction by eNOS signaling pathway. PMID:26482008

  11. Pretreatment with β-Boswellic Acid Improves Blood Stasis Induced Endothelial Dysfunction: Role of eNOS Activation

    PubMed Central

    Wang, Mingming; Chen, Minchun; Ding, Yi; Zhu, Zhihui; Zhang, Yikai; Wei, Peifeng; Wang, Jingwen; Qiao, Yi; Li, Liang; Li, Yuwen; Wen, Aidong

    2015-01-01

    Vascular endothelial cells play an important role in modulating anti-thrombus and maintaining the natural function of vascular by secreting many active substances. β-boswellic acid (β-BA) is an active triterpenoid compound from the extract of boswellia serrate. In this study, it is demonstrated that β-BA ameliorates plasma coagulation parameters, protects endothelium from blood stasis induced injury and prevents blood stasis induced impairment of endothelium-dependent vasodilatation. Moreover, it is found that β-BA significantly increases nitric oxide (NO) and cyclic guanosine 3’, 5’-monophosphate (cGMP) levels in carotid aortas of blood stasis rats. To stimulate blood stasis-like conditions in vitro, human umbilical vein endothelial cells (HUVECs) were exposed to transient oxygen and glucose deprivation (OGD). Treatment of β-BA significantly increased intracellular NO level. Western blot and immunofluorescence as well as immunohistochemistry reveal that β-BA increases phosphorylation of enzyme nitric oxide synthase (eNOS) at Ser1177. In addition, β-BA mediated endothelium-dependent vasodilatation can be markedly blocked by eNOS inhibitor L-NAME in blood stasis rats. In OGD treated HUEVCs, the protective effect of β-BA is attenuated by knockdown of eNOS. In conclusion, the above findings provide convincing evidence for the protective effects of β-BA on blood stasis induced endothelial dysfunction by eNOS signaling pathway. PMID:26482008

  12. Triterpenoic Acids from Apple Pomace Enhance the Activity of the Endothelial Nitric Oxide Synthase (eNOS).

    PubMed

    Waldbauer, Katharina; Seiringer, Günter; Nguyen, Dieu Linh; Winkler, Johannes; Blaschke, Michael; McKinnon, Ruxandra; Urban, Ernst; Ladurner, Angela; Dirsch, Verena M; Zehl, Martin; Kopp, Brigitte

    2016-01-13

    Pomace is an easy-accessible raw material for the isolation of fruit-derived compounds. Fruit consumption is associated with health-promoting effects, such as the prevention of cardiovascular disease. Increased vascular nitric oxide (NO) bioavailability, for example, due to an enhanced endothelial nitric oxide synthase (eNOS) activity, could be one molecular mechanism mediating this effect. To identify compounds from apple (Malus domestica Borkh.) pomace that have the potential to amplify NO bioavailability via eNOS activation, a bioassay-guided fractionation of the methanol/water (70:30) extract has been performed using the (14)C-L-arginine to (14)C-L-citrulline conversion assay (ACCA) in the human endothelium-derived cell line EA.hy926. Phytochemical characterization of the active fractions was performed using the spectrophotometric assessment of the total phenolic content, as well as TLC, HPLC-DAD-ELSD, and HPLC-MS analyses. Eleven triterpenoic acids, of which one is a newly discovered compound, were identified as the main constituents in the most active fraction, accompanied by only minor contents of phenolic compounds. When tested individually, none of the tested compounds exhibited significant eNOS activation. Nevertheless, cell stimulation with the reconstituted compound mixture restored eNOS activation, validating the potential of apple pomace as a source of bioactive components. PMID:26682617

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

    PubMed

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

    2016-07-01

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

  14. Development of confocal immunofluorescence FRET microscopy to Investigate eNOS and GSNOR localization and interaction in pulmonary endothelial cells

    NASA Astrophysics Data System (ADS)

    Rehman, Shagufta; Brown-Steinke, Kathleen; Palmer, Lisa; Periasamy, Ammasi

    2015-03-01

    Confocal FRET microscopy is a widely used technique for studying protein-protein interactions in live or fixed cells. Endothelial nitric oxide synthase (eNOS) and S-nitrosoglutathione reductase (GSNOR) are enzymes involved in regulating the bioavailability of S-nitrosothiols (SNOs) in the pulmonary endothelium and have roles in the development of pulmonary arterial hypertension. Labeling of endogenous proteins to better understand a disease process can be challenging. We have used immunofluorescence to detect endogenous eNOS and GSNOR in primary pulmonary endothelial cells to co-localize these proteins as well as to study their interaction by FRET. The challenge has been in selecting the right immunofluorescence labeling condition, right antibody, the right blocking reagent, the right FRET pair and eliminating cross-reactivity of secondary antibodies. We have used Alexa488 and Alexa568 as a FRET pair. After a series of optimizations, the data from Confocal Laser Scanning Microscopy (CLSM) demonstrate co-localization of eNOS and GSNOR in the perinuclear region of the pulmonary endothelial cell primarily within the cis-Golgi with lower levels of co-localization seen within the trans-Golgi. FRET studies demonstrate, for the first time, interaction between eNOS and GSNOR in both murine and bovine pulmonary endothelial cells. Further characterization of eNOSGSNOR interaction and the subcellular location of this interaction will provide mechanistic insight into the importance of S-nitrosothiol signaling in pulmonary biology, physiology and pathology.

  15. Regulation of Endothelial Glutathione by ICAM-1 governs VEGF-A mediated eNOS Activity and Angiogenesis

    PubMed Central

    Langston, Will; Chidlow, John H.; Booth, Blake A.; Barlow, Shayne C.; Lefer, David J.; Patel, Rakesh P.; Kevil, Christopher G.

    2007-01-01

    Previous studies suggest that inflammatory cell adhesion molecules may modulate endothelial cell migration and angiogenesis through unknown mechanisms. Using a combination of in vitro and in vivo approaches, herein we reveal a novel redox sensitive mechanism by which ICAM-1 modulates endothelial GSH that controls VEGF-A induced eNOS activity, endothelial chemotaxis, and angiogenesis. In vivo disk angiogenesis assays showed attenuated VEGF-A mediated angiogenesis in ICAM-1−/− mice. Moreover, VEGF-A dependent chemotaxis, eNOS phosphorylation, and nitric oxide (NO) production were impaired in ICAM-1−/− MAEC compared to WT MAEC. Decreasing intracellular GSH in ICAM-1−/− MAEC to levels observed in WT MAEC with 150 μM buthionine sulfoximine (BSO) restored VEGF-A responses. Conversely, GSH supplementation of WT MAEC with 5 mM glutathione ethyl ester (GEE) mimicked defects observed in ICAM-1−/− cells. Deficient angiogenic responses in ICAM-1−/− cells were associated with increased expression of the lipid phosphatase, PTEN, consistent with antagonism of signaling pathways leading to eNOS activation. PTEN expression was also sensitive to GSH status, decreasing or increasing in proportion to intracellular GSH concentrations. These data suggest a novel role for ICAM-1 in modulating VEGF-A induced angiogenesis and eNOS activity through regulation of PTEN expression via modulation of intracellular GSH status. PMID:17291995

  16. A high-order symmetrical weighted hybrid ENO-flux limiter scheme for hyperbolic conservation laws

    NASA Astrophysics Data System (ADS)

    Abedian, Rooholah; Adibi, Hojatollah; Dehghan, Mehdi

    2014-01-01

    In this paper, we propose a new weighted essentially non-oscillatory (WENO) procedure for solving hyperbolic conservation laws, on uniform meshes. The new scheme combines essentially non-oscillatory (ENO) reconstructions together with monotone upwind schemes for scalar conservation laws' interpolants. In a one-dimensional context, first, we obtain an optimum polynomial on a five-cells stencil. This optimum polynomial is fifth-order accurate in regions of smoothness. Next, we modify a third-order ENO polynomial by choosing an additional point inside the stencil in order to obtain the highest accuracy when combined with the Harten-Osher reconstruction-evolution method limiter. Then, we consider the optimum polynomial as a symmetric and convex combination of four polynomials with ideal weights. After that, following the methodology of the classic WENO procedure, we calculate non-oscillatory weights with the ideal weights. Also, the numerical solution is advanced in time by means of the linear multi-step total variation bounded (TV B) technique. Numerical examples on both scalar and gas dynamics problems confirm that the new scheme is non-oscillatory and yields sharp results when solving profiles with discontinuities. Comparing the new scheme with high-order WENO schemes shows that our method reduces smearing near shocks and corners, and in some cases it is more accurate near discontinuities. Finally, the new method is extended to multi-dimensional problems by a dimension-by-dimension approach. Several multi-dimensional examples are performed to show that our method remains non-oscillatory while giving good resolution of discontinuities.

  17. Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy.

    PubMed

    Luizon, Marcelo R; Sandrim, Valeria C; Palei, Ana Ct; Lacchini, Riccardo; Cavalli, Ricardo C; Duarte, Geraldo; Tanus-Santos, Jose E

    2012-09-01

    Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and -90(CA)₁₃-₂₅, rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P>0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P<0.05). Moreover, the combination of MMP-9-1562CC with VEGF-634CC or MMP-9-1562CT with VEGF-634CC or-634GG was more frequent in women with PE than in NP women (P<0.05). These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of MMP-9 and VEGF contribute to PE susceptibility. PMID:22573202

  18. eNOS3 Genetic Polymorphism Is Related to Post-Ablation Early Recurrence of Atrial Fibrillation

    PubMed Central

    Shim, Jaemin; Park, Jae Hyung; Lee, Ji-Young; Uhm, Jae-Sun; Joung, Boyoung; Lee, Moon-Hyoung; Ellinor, Patrick T.

    2015-01-01

    Purpose Previous studies have demonstrated an association between eNOS polymorphisms and atrial fibrillation (AF). We sought to determine whether eNOS polymorphisms are associated with AF recurrence after a radiofrequency catheter ablation (RFCA). Materials and Methods A total of 500 consecutive patients (56±11 years, 77% male) with paroxysmal (68%) or persistent (32%) AF who underwent RFCA and 500 age, gender-matched controls were genotyped for the eNOS3 single nucleotide polymorphism (rs1799983). AF recurrence was monitored according to 2012 ACC/AHA/ESC guidelines. Results The frequencies of the rs1799983 variant alleles (T) in the case and control group were not significantly different (OR 1.05, 95% CI 0.75-1.46, p=0.798). AF patients with rs1799983 variants were more likely to have coronary artery disease or stroke than those without genetic variant at this gene (31.0% vs. 17.3%, p=0.004). During mean 17 months follow-up, early recurrence of AF (ERAF; within 3 months) and clinical recurrence (CR) of AF were 31.8% and 24.8%, respectively. The rs1799983 variant was associated with higher risk of ERAF (OR 1.71, 95% CI 1.06-2.79, p=0.028), but not with CR. ERAF occurred earlier (11±16 days) in variant group than those without variant allele (20±25 days, p=0.016). A multiple logistic regression analysis showed that presence of the rs1799983 variant (OR 1.75, 95% CI 1.07-2.86, p=0.026) and persistent AF were independent predictors for ERAF after AF ablation. Conclusion The rs1799983 variant of the eNOS3 gene was associated with ERAF, but not with CR, after RFCA. eNOS3 gene variants may have a potential role for stratification of post-ablation management. PMID:26256966

  19. Ursolic acid from the Chinese herb danshen (Salvia miltiorrhiza L.) upregulates eNOS and downregulates Nox4 expression in human endothelial cells.

    PubMed

    Steinkamp-Fenske, Katja; Bollinger, Larissa; Völler, Natalie; Xu, Hui; Yao, Ying; Bauer, Rudolf; Förstermann, Ulrich; Li, Huige

    2007-11-01

    Danshen, the dried root of Salvia miltiorrhiza Bunge (Lamiaceae), is one of the most commonly used traditional Chinese medicines for cardiovascular indications. In EA.hy 926 cells, a cell line derived from human umbilical vein endothelial cells (HUVEC), an aqueous extract of danshen, and also a methanol extract of the plant, increased eNOS promoter activity, eNOS mRNA and protein expression, as well as endothelial NO production. A dichloromethane extract, in contrast, did not change eNOS gene expression. Thus, the active danshen constituent(s) responsible for eNOS upregulation is (are) hydrophilic and/or alcohol-soluble. One such compound is ursolic acid that significantly increased eNOS expression in EA.hy 926 cells and native HUVEC, and enhanced bioactive NO production measured in terms of its cGMP increasing activity. Other tested hydrophilic and alcohol-soluble compounds isolated from danshen had no effect on eNOS expression. Interestingly, ursolic acid also reduced the expression of the NADPH oxidase subunit Nox4 and suppressed the production of reactive oxygen species in human endothelial cells. Upregulation of eNOS and a parallel downregulation of Nox4 lead to an increase in bioactive NO. This in turn could mediate some of the beneficial effects of danshen. Ursolic acid is a prototypical compound responsible for this effect of the plant. PMID:17481637

  20. The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production

    PubMed Central

    Choi, Jiyea; Kim, Hyemin; Kim, Yejin; Jang, Mirim; Jeon, Jane; Hwang, Young-il; Shon, Won Jun; Song, Yeong Wook; Lee, Wang Jae

    2015-01-01

    GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-κB activation following ENO1 stimulation. PMID:26770183

  1. The Anti-inflammatory Effect of GV1001 Mediated by the Downregulation of ENO1-induced Pro-inflammatory Cytokine Production.

    PubMed

    Choi, Jiyea; Kim, Hyemin; Kim, Yejin; Jang, Mirim; Jeon, Jane; Hwang, Young-Il; Shon, Won Jun; Song, Yeong Wook; Kang, Jae Seung; Lee, Wang Jae

    2015-12-01

    GV1001 is a peptide derived from the human telomerase reverse transcriptase (hTERT) sequence that is reported to have anti-cancer and anti-inflammatory effects. Enolase1 (ENO1) is a glycolytic enzyme, and stimulation of this enzyme induces high levels of pro-inflammatory cytokines from concanavalin A (Con A)-activated peripheral blood mononuclear cells (PBMCs) and ENO1-expressing monocytes in healthy subjects, as well as from macrophages in rheumatoid arthritis (RA) patients. Therefore, this study investigated whether GV1001 downregulates ENO1-induced pro-inflammatory cytokines as an anti-inflammatory peptide. The results showed that GV1001 does not affect the expression of ENO1 in either Con A-activated PBMCs or RA PBMCs. However, ENO1 stimulation increased the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6, and these cytokines were downregulated by pretreatment with GV1001. Moreover, p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB were activated when ENO1, on the surface of Con A-activated PBMCs and RA PBMCs, was stimulated, and they were successfully suppressed by pre-treatment with GV1001. These results suggest that GV1001 may be an effective anti-inflammatory peptide that downregulates the production of pro-inflammatory cytokines through the suppression of p38 MAPK and NF-κB activation following ENO1 stimulation. PMID:26770183

  2. AB037. Icariside II improves human cavernous endothelial cells function by regulating miR-155/eNOS signal pathway

    PubMed Central

    Guan, Ruili; Lei, Hongen; Yang, Bicheng; Li, Huixi; Wang, Lin; Guo, Yinglu; Xin, Zhongcheng

    2016-01-01

    Background To investigate the changes of miR-155/endothelial nitric oxide synthase (eNOS) signal pathway under the stimulation of age-BSA and glucose with or without icariside II (ICAII) intervention inhuman cavernous endothelial cells (HCECs). Methods Purified HCECs were first divided into three groups randomly: normal group + BSA (NC group), age-BSA + glucose group (DM group), ICAII treatment group (DM + ICAII group with different concentrations at 0.1, 1, 10 µM). Western Blot to detect the protein expression of eNOS and RAGE; real time PCR to detect the expression of miR-155 and eNOS; DAF-FM DA fluorescent probes assay and NaNO3/NaNO2 assay to detect the NO concentration. Lentivirus mediated miR-155 over-expression was constructed to observe the changes of eNOS and NO. Results The eNOS and RAGE expression in DM group is significantly reduced and increased respectively compared with that of NC group (P<0.05), while ICAII intervention could reverse this change effectively. The 10 µM of ICAII has the most powerful effect. MiR-155 has the highest fold changes among candidate miRNAs in diabetic like HCECs (P<0.05). MiR-155 increased and eNOS decreased remarkably in DM group, while ICAII intervention could inhibit the miR-155 expression, which led to the significantly higher eNOS expression and NO concentration (P<0.05). In lentivirus mediated miR-155 overexpression with or without ICAII intervention model, we found the similar trend with the above diabetic model. Conclusions MiR-155/eNOS signal pathway may be involved in the process of diabetic HCECs dysfunction. ICAII could promote the recovery of the endothelial dysfunction by regulating the miR-155/eNOS signal pathway.

  3. Work-related stress perception and hypertension amongst health workers of a mission hospital in Oyo State, south-western Nigeria

    PubMed Central

    Owolabi, Mojisola O.; OlaOlorun, Akintayo D.; Olofin, Ayo

    2012-01-01

    Abstract Background Globalisation and changes in the nature of work have resulted in increasing work-related stress in people in developing countries. Work stress is at present already acknowledged as one of the epidemics of modern working life. It is associated with a number of disease conditions, such as hypertension, cardiovascular diseases, affective disorders, depression, disturbed metabolism (risk of Type II diabetes) and musculoskeletal disorders. Objective This study was a work site cross-sectional descriptive study carried out amongst the health workers at the Baptist Medical Centre Ogbomoso, Oyo State, south-western Nigeria. The aim of the study was to discern the prevalence of perceived work stress and to explore the relationship between perceived work stress and the presence of hypertension. Methods A total of 324 consenting health workers of the institution were administered the job demand-control questionnaire to assess work stress. A standardised questionnaire was used to collect socio-demographic data and other personal data. Measurements of blood pressure, weight and height were carried out and body mass indices were calculated. Results More than a quarter (26.2%) of the subjects perceived themself as stressed at work. The single largest group of hypertensive subjects was seen amongst subjects with work stress. Conclusion A significant number of health workers in this study is afflicted by work-related stress and perceived work stress was found to be significantly associated with higher hypertension prevalence.

  4. Sympathetic activation increases NO release from eNOS but neither eNOS nor nNOS play an essential role in exercise hyperemia in the human forearm

    PubMed Central

    Shabeeh, Husain; Seddon, Michael; Brett, Sally; Melikian, Narbeh; Casadei, Barbara; Shah, Ajay M.

    2013-01-01

    Nitric oxide (NO) release from endothelial NO synthase (eNOS) and/or neuronal NO synthase (nNOS) could be modulated by sympathetic nerve activity and contribute to increased blood flow after exercise. We examined the effects of brachial-arterial infusion of the nNOS selective inhibitor S-methyl-l-thiocitrulline (SMTC) and the nonselective NOS inhibitor NG-monomethyl-l-arginine (l-NMMA) on forearm arm blood flow at rest, during sympathetic activation by lower body negative pressure, and during lower body negative pressure immediately after handgrip exercise. Reduction in forearm blood flow by lower body negative pressure during infusion of SMTC was not significantly different from that during vehicle (−28.5 ± 4.02 vs. −34.1 ± 2.96%, respectively; P = 0.32; n = 8). However, l-NMMA augmented the reduction in forearm blood flow by lower body negative pressure (−44.2 ± 3.53 vs. −23.4 ± 5.71%; n = 8; P < 0.01). When lower body negative pressure was continued after handgrip exercise, there was no significant effect of either l-NMMA or SMTC on forearm blood flow immediately after low-intensity exercise (P = 0.91 and P = 0.44 for l-NMMA vs. saline and SMTC vs. saline, respectively; each n = 10) or high-intensity exercise (P = 0.46 and P = 0.68 for l-NMMA vs. saline and SMTC vs. saline, respectively; each n = 10). These results suggest that sympathetic activation increases NO release from eNOS, attenuating vasoconstriction. Dysfunction of eNOS could augment vasoconstrictor and blood pressure responses to sympathetic activation. However, neither eNOS nor nNOS plays an essential role in postexercise hyperaemia, even in the presence of increased sympathetic activation. PMID:23436331

  5. Two functionally distinct pools of eNOS in endothelium are facilitated by myoendothelial junction lipid composition.

    PubMed

    Biwer, Lauren A; Taddeo, Evan P; Kenwood, Brandon M; Hoehn, Kyle L; Straub, Adam C; Isakson, Brant E

    2016-07-01

    In resistance arteries, endothelial cells (EC) make contact with smooth muscle cells (SMC), forming myoendothelial junctions (MEJ). Endothelial nitric oxide synthase (eNOS) is present in the luminal side of the EC (apical EC) and the basal side of the EC (MEJ). To test if these eNOS pools acted in sync or separately, we co-cultured ECs and SMCs, then stimulated SMCs with phenylephrine (PE). Adrenergic activation causes inositol [1,4,5] triphosphate (IP3) to move from SMC to EC through gap junctions at the MEJ. PE increases MEJ eNOS phosphorylation (eNOS-P) at S1177, but not in EC. Conversely, we used bradykinin (BK) to increase EC calcium; this increased EC eNOS-P but did not affect MEJ eNOS-P. Inhibiting gap junctions abrogated the MEJ eNOS-P after PE, but had no effect on BK eNOS-P. Differential lipid composition between apical EC and MEJ may account for the compartmentalized eNOS-P response. Indeed, DAG and phosphatidylserine are both enriched in MEJ. These lipids are cofactors for PKC activity, which was significantly increased at the MEJ after PE. Because PKC activity also relies on endoplasmic reticulum (ER) calcium release, we used thapsigargin and xestospongin C, BAPTA, and PKC inhibitors, which caused significant decreases in MEJ eNOS-P after PE. Functionally, BK inhibited leukocyte adhesion and PE caused an increase in SMC cGMP. We hypothesize that local lipid composition of the MEJ primes PKC and eNOS-P for stimulation by PE, allowing for compartmentalized function of eNOS in the blood vessel wall. PMID:27106139

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

    PubMed

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

    2016-08-01

    Long-term effects of high protein diets (HPDs) on kidneys are still not sufficiently studied. Irisin which increases oxygen consumption and thermogenesis in white fat cells was shown in skeletal muscles and many tissues. Nitric oxide synthases (NOS) are a family of enzymes catalyzing the production of nitric oxide (NO) from L-arginine. We aimed to investigate the effects of HPD, irisin and NO expression in kidney and relation of them with exercise and among themselves. Animals were grouped as control, exercise, HPD and exercise combined with HPD (exercise-HPD). Rats were kept on a HPD for 5 weeks and an exercise program was given them as 5 exercise and 2 rest days per week exercising on a treadmill with increasing speed and angle. In our study, while HPD group had similar total antioxidant capacity (TAC) levels with control group, exercise and exercise-HPD groups had lower levels (p < 0.05). Kidneys of exercising rats had no change in irisin or eNOS expression but their iNOS expression had increased (p < 0.001). HPD-E group has not been observed to cause kidney damage and not have a significant effect on rat kidney irisin, eNOS, or iNOS expression. Localization of irisin, eNOS, and iNOS staining in kidney is highly selective and quite clear in this study. Effects of exercise and HPD on kidney should be evaluated with different exercise protocols and contents of the diet. İrisin, eNOS, and iNOS staining localizations should be supported with various research studies. PMID:27277302

  7. Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling.

    PubMed

    Battault, Sylvain; Singh, François; Gayrard, Sandrine; Zoll, Joffrey; Reboul, Cyril; Meyer, Grégory

    2016-02-01

    Exercise training is a well-recognized way to improve vascular endothelial function by increasing nitric oxide (NO) bioavailability. However, in hypertensive subjects, unlike low- and moderate-intensity exercise training, the beneficial effects of continuous high-intensity exercise on endothelial function are not clear, and the underlying mechanisms remain unknown. The aim of this study was to investigate the impact of high-intensity exercise on vascular function, especially on the NO pathway, in spontaneous hypertensive rats (SHR). These effects were studied on WKY, sedentary SHR and SHR that exercised at moderate (SHR-MOD) and high intensity (SHR-HI) on a treadmill (1 h per day; 5 days per week for 6 weeks at 55% and 80% of their maximal aerobic velocity, respectively). Endothelial function and specific NO contributions to acetylcholine-mediated relaxation were evaluated by measuring the aortic ring isometric forces. Endothelial nitric oxide synthase (eNOS) expression and phosphorylation (ser1177) were evaluated by western blotting. The total aortic and eNOS-dependent reactive oxygen species (ROS) production was assessed using electron paramagnetic resonance in aortic tissue. Although the aortas of SHR-HI had increased eNOS levels without alteration of eNOS phosphorylation, high-intensity exercise had no beneficial effect on endothelium-dependent vasorelaxation, unlike moderate exercise. This result was associated with increased eNOS-dependent ROS production in the aortas of SHR-HI. Notably, the use of the recoupling agent BH4 or a thiol-reducing agent blunted eNOS-dependent ROS production in the aortas of SHR-HI. In conclusion, the lack of a positive effect of high-intensity exercise on endothelial function in SHR was mainly explained by redox-dependent eNOS uncoupling, resulting in a switch from NO to O2(-) generation. PMID:26537830

  8. eNOS Glu298Asp Polymorphism and Endothelial Dysfunction in Patients with and without End-stage Renal Disease

    PubMed Central

    İlhan, Nevin; Ateş, Kadir; İlhan, Necip; Kaman, Dilara; Çeliker, Hüseyin

    2016-01-01

    Background: Chronic kidney diseases are known to influence nitric oxide metabolites (NOx) and asymmetric dimethylarginine (ADMA), though the exact mechanism is still poorly understood. Aims: The purpose of the present study was to examine eNOS Glu298Asp gene polymorphism, plasma NOx and ADMA concentration in subjects with and without End-stage Renal Disease. Study Design: Case-control study. Methods: In this study, genotype distributions of Glu-298Asp in exon 7 of the eNOS gene polymorphisms in 130 hemodialysis and 64 peritoneal dialysis patients were compared with 92 controls. NOx was measured by using the Griess reaction while arginine, ADMA and SDMA measurements were performed by HPLC. Genotyping for eNOS Glu298Asp polymorphism was detected with the polymerase chain reaction and/or polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Results: When the genotype frequencies of TT and GT genes were compared between both groups, there was no detected statistically important difference, even-though a TT genotype frequency was 27 (20.8%) versus 17 (26.6%), GT heterozygote genotype frequency was 52 (40%) versus 22 (34.4%), and GG homozygote genotype frequency was 51 (39.2%) versus 25 (39.1%), respectively (p>0.05). NOx, SDMA and ADMA concentrations were significantly elevated in subjects with hemodialysis patients as compared to their corresponding controls. Whereas nitrite was found to be significantly decreased in the patient with peritoneal dialysis. Conclusion: Not observed any connection between the Glu298Asp polymorphism in the eNOS gene and end-stage Renal Diseases in our study population under different dialysis treatments. However, higher ADMA and SDMA concentrations in subjects with ESRD support the existing hypothesis that NOx overproduction affects endothelial dysfunction. Thus, the reduction of ADMA and SDMA concentrations might play a protective role in ESRD patients. PMID:27403380

  9. Simvastatin induces a central hypotensive effect via Ras-mediated signalling to cause eNOS up-regulation

    PubMed Central

    Cheng, Wen-Han; Ho, Wen-Yu; Chang, Chien-Feng; Lu, Pei-Jung; Cheng, Pei-Wen; Yeh, Tung-Chen; Hong, Ling-Zong; Sun, Gwo-Ching; Hsiao, Michael; Tseng, Ching-Jiunn

    2013-01-01

    BACKGROUND AND PURPOSE Clinical studies indicate that statins have a BP-lowering effect in hypercholesterolemic individuals with hypertension. Specifically, statins modulate BP through the up-regulation of endothelial NOS (eNOS) activation in the brain. However, the signalling mechanisms through which statins enhance eNOS activation remain unclear. Therefore, we examined the possible signalling pathways involved in statin-mediated BP regulation in the nucleus tractus solitarii (NTS). EXPERIMENTAL APPROACH To investigate the involvement of Ras and other signalling pathways in simvastatin-induced effects on BP, BP and renal sympathetic nerve activity (RSNA) were determined in spontaneously hypertensive rats (SHRs) before and after i.c.v. administration of simvastatin in the absence and presence of a Ras-specific inhibitor (farnesyl thiosalicylic acid, FTS), a geranylgeranyltransferase inhibitor (GGTI-2133), a PI3K inhibitor (LY294002) or a MAPK-ERK kinase (MEK) inhibitor (PD98059). KEY RESULTS FTS significantly attenuated the decrease in BP and increased NO evoked by simvastatin and reversed the decrease in basal RSNA induced by simvastatin. Immunoblotting and pharmacological studies showed that inhibition of Ras activity by FTS significantly abolished simvastatin-induced phosphorylation of ERK1/2, ribosomal protein S6 kinase (RSK), Akt and decreased eNOS phosphorylation. Likewise, administration of Akt and ERK1/2 signalling inhibitors, LY294002 and PD98059, attenuated the reduction in BP evoked by simvastatin. Furthermore, i.c.v. simvastatin decreased Rac1 activation and the number of ROS-positive cells in the NTS. CONCLUSIONS AND IMPLICATIONS Simvastatin modulates central BP control in the NTS of SHRs by increasing Ras-mediated activation of the PI3K-Akt and ERK1/2-RSK signalling pathways, which then up-regulates eNOS activation. PMID:23889671

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

    PubMed Central

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

    2016-01-01

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

  11. Resveratrol Prevented Lipopolysaccharide-Induced Endothelial Dysfunction in Rat Thoracic Aorta Through Increased eNOS Expression

    PubMed Central

    Uğurel, Seda Sultan; Kuşçu, Nilay; Özenci, Çiler Çelik; Dalaklıoğlu, Selvinaz; Taşatargil, Arda

    2016-01-01

    Background: The cardiovascular benefits of Resveratrol (RVT) have been well established by previous experimental and clinical studies. Aims: The goal of this study was to test the effectiveness of RVT administration on the impaired endothelial function induced by lipopolysaccharide (LPS), and to elucidate the role of endothelial nitric oxide synthase (eNOS)/Sirtuin 1 (SIRT1) pathway. Study Design: Animal experiment. Methods: Endotoxemia was induced by intraperitoneal injection of 10 mg/kg LPS, and the thoracic aorta was isolated six hours later. RVT was injected intraperitoneally 15 minutes before LPS administration. Six hours after LPS injection, potassium chloride (KCl), phenylephrine (Phe), acetylcholine (ACh), and sodium nitroprusside (SNP) were used to examine to vascular reactivity and endothelial function. eNOS, phospho-eNOS (p-eNOS) (Ser 1177), and SIRT1 expressions in thoracic aorta were evaluated by Western blot. Results: LPS administration significantly inhibited the relaxation response induced by ACh, while the relaxation to SNP was not significantly altered. Phe- and KCl-induced contractile responses in the thoracic aorta significantly decreased in LPS-injected group. eNOS and p-eNOS expression decreased significantly in arteries obtained from LPS group rats. The impaired vasoreactivity as well as decreased expressions of eNOS, p-eNOS, and SIRT1 in vessels from LPS-injected rats were improved by RVT treatment. Conclusion: The endothelium-dependent vasodilatation of the thoracic aorta was significantly inhibited by LPS administration, and RVT treatment may improve vascular endothelial function. The protective effect of RVT might be associated with increased eNOS expression and activity.

  12. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells.

    PubMed

    Fleming, Ingrid; Fisslthaler, Beate; Dixit, Madhulika; Busse, Rudi

    2005-09-15

    The application of fluid shear stress to endothelial cells elicits the formation of nitric oxide (NO) and phosphorylation of the endothelial NO synthase (eNOS). Shear stress also elicits the enhanced tyrosine phosphorylation of endothelial proteins, especially of those situated in the vicinity of cell-cell contacts. Since a major constituent of these endothelial cell-cell contacts is the platelet endothelial cell adhesion molecule-1 (PECAM-1) we assessed the role of PECAM-1 in the activation of eNOS. In human endothelial cells, shear stress induced the tyrosine phosphorylation of PECAM-1 and enhanced the association of PECAM-1 with eNOS. Endothelial cell stimulation with shear stress elicited the phosphorylation of Akt and eNOS as well as of the AMP-activated protein kinase (AMPK). While the shear-stress-induced tyrosine phosphorylation of PECAM-1 as well as the serine phosphorylation of Akt and eNOS were abolished by the pre-treatment of cells with the tyrosine kinase inhibitor PP1 the phosphorylation of AMPK was unaffected. Down-regulation of PECAM-1 using a siRNA approach attenuated the shear-stress-induced phosphorylation of Akt and eNOS, as well as the shear-stress-induced accumulation of cyclic GMP levels while the shear-stress-induced phosphorylation of AMPK remained intact. A comparable attenuation of Akt and eNOS (but not AMPK) phosphorylation and NO production was also observed in endothelial cells generated from PECAM-1-deficient mice. These data indicate that the shear-stress-induced activation of Akt and eNOS in endothelial cells is modulated by the tyrosine phosphorylation of PECAM-1 whereas the shear-stress-induced phosphorylation of AMPK is controlled by an alternative signaling pathway. PMID:16118242

  13. Roles of ROS and PKC-βII in ionizing radiation-induced eNOS activation in human vascular endothelial cells.

    PubMed

    Sakata, Kimimasa; Kondo, Takashi; Mizuno, Natsumi; Shoji, Miki; Yasui, Hironobu; Yamamori, Tohru; Inanami, Osamu; Yokoo, Hiroki; Yoshimura, Naoki; Hattori, Yuichi

    2015-07-01

    Vascular endothelial cells can absorb higher radiation doses than any other tissue in the body, and post-radiation impaired endothelial nitric oxide synthase (eNOS) function may be developed as a potential contributor to the pathogenesis of vascular injury. In this study, we investigated early alterations of eNOS signaling in human umbilical venous endothelial cells (HUVECs) exposed to X-ray radiation. We found that ionizing radiation increased eNOS phosphorylation at Ser-1177 and dephosphorylation at Thr-495 in HUVECs in a dose-dependent (≤ 20 Gy) and time-dependent (6-72 h) manner. The total expression levels of eNOS were unchanged by radiation. Although a transient but significant increase in extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation and a biphasic decline in Akt phosphorylation were observed after irradiation, these inhibitors were without effect on the radiation-induced changes in eNOS phosphorylation. There was an increase in protein kinase C-βII (PKC-βII) expression and the ablation of PKC-βII by small interfering RNA (siRNA) negated the radiation effect on the two eNOS phosphorylation events. Furthermore, when the radiation-induced increase in reactive oxygen species (ROS) generation was prevented by the anti-oxidant N-acetyl-L-cysteine, eNOS Ser-1177 phosphorylation and Thr-495 dephosphorylation in irradiated HUVECs were significantly reduced. However, transfection of PKC-β siRNA did not alter ROS production after irradiation, and NAC failed to block the radiation-induced increase in PKC-βII expression. Taken together, our results suggest that ionizing radiation-induced eNOS activation in human vascular endothelial cells is attributed to both the up-regulation of PKC-βII and the increase in ROS generation which were independent of each other. PMID:25869503

  14. Antiphospholipid antibodies promote leukocyte-endothelial cell adhesion and thrombosis in mice by antagonizing eNOS via β2GPI and apoER2.

    PubMed

    Ramesh, Sangeetha; Morrell, Craig N; Tarango, Cristina; Thomas, Gail D; Yuhanna, Ivan S; Girardi, Guillermina; Herz, Joachim; Urbanus, Rolf T; de Groot, Philip G; Thorpe, Philip E; Salmon, Jane E; Shaul, Philip W; Mineo, Chieko

    2011-01-01

    In antiphospholipid syndrome (APS), antiphospholipid antibodies (aPL) binding to β2 glycoprotein I (β2GPI) induce endothelial cell-leukocyte adhesion and thrombus formation via unknown mechanisms. Here we show that in mice both of these processes are caused by the inhibition of eNOS. In studies of cultured human, bovine, and mouse endothelial cells, the promotion of monocyte adhesion by aPL entailed decreased bioavailable NO, and aPL fully antagonized eNOS activation by diverse agonists. Similarly, NO-dependent, acetylcholine-induced increases in carotid vascular conductance were impaired in aPL-treated mice. The inhibition of eNOS was caused by antibody recognition of domain I of β2GPI and β2GPI dimerization, and it was due to attenuated eNOS S1179 phosphorylation mediated by protein phosphatase 2A (PP2A). Furthermore, LDL receptor family member antagonism with receptor-associated protein (RAP) prevented aPL inhibition of eNOS in cell culture, and ApoER2-/- mice were protected from aPL inhibition of eNOS in vivo. Moreover, both aPL-induced increases in leukocyte-endothelial cell adhesion and thrombus formation were absent in eNOS-/- and in ApoER2-/- mice. Thus, aPL-induced leukocyte-endothelial cell adhesion and thrombosis are caused by eNOS antagonism, which is due to impaired S1179 phosphorylation mediated by β2GPI, apoER2, and PP2A. Our results suggest that novel therapies for APS can now be developed targeting these mechanisms. PMID:21123944

  15. RNase G-dependent degradation of the eno mRNA encoding a glycolysis enzyme enolase in Escherichia coli.

    PubMed

    Kaga, Naoko; Umitsuki, Genryou; Nagai, Kazuo; Wachi, Masaaki

    2002-10-01

    Escherichia coli RNase G, encoded by the rng gene, is involved in the processing of 16S rRNA and degradation of the adhE mRNA encoding a fermentative alcohol dehydrogenase. In a search for the intracellular target RNAs of RNase G other than the 16S rRNA precursor and adhE mRNA, total cellular proteins from rng+ and rng::cat cells were compared by two-dimensional gel electrophoresis. The amount of enolase encoded by the eno gene reproducibly increased two- to three-fold in the rng::cat mutant strain compared with the rng+ parent strain. Rifampicin chase experiments showed that the half-life of the eno mRNA was some 3 times longer in the rng::cat mutant than in the wild type. These results indicate that the eno mRNA was a substrate of RNase G in vivo, in addition to 16S rRNA precursor and adhE mRNA. PMID:12450135

  16. Obligatory Role for Endothelial Heparan Sulphate Proteoglycans and Caveolae Internalization in Catestatin-Dependent eNOS Activation

    PubMed Central

    Fornero, Sara; Bassino, Eleonora; Ramella, Roberta; Mahata, Sushil K.; Tota, Bruno; Alloatti, Giuseppe

    2014-01-01

    The chromogranin-A peptide catestatin modulates a wide range of processes, such as cardiovascular functions, innate immunity, inflammation, and metabolism. We recently found that the cardiac antiadrenergic action of catestatin requires a PI3K-dependent NO release from endothelial cells, although the receptor involved is yet to be identified. In the present work, based on the cationic properties of catestatin, we tested the hypothesis of its interaction with membrane heparan sulphate proteoglycans, resulting in the activation of a caveolae-dependent endocytosis. Experiments were performed on bovine aortic endothelial cells. Endocytotic vesicles trafficking was quantified by confocal microscopy using a water-soluble membrane dye; catestatin colocalization with heparan sulphate proteoglycans and caveolin 1 internalization were studied by fluorimetric measurements in live cells. Modulation of the catestatin-dependent eNOS activation was assessed by immunofluorescence and immunoblot analysis. Our results demonstrate that catestatin (5 nM) colocalizes with heparan sulphate proteoglycans and induces a remarkable increase in the caveolae-dependent endocytosis and caveolin 1 internalization, which were significantly reduced by both heparinase and wortmannin. Moreover, catestatin was unable to induce Ser1179 eNOS phosphorylation after pretreatments with heparinase and methyl-β-cyclodextrin. Taken together, these results highlight the obligatory role for proteoglycans and caveolae internalization in the catestatin-dependent eNOS activation in endothelial cells. PMID:25136621

  17. Recoupling of eNOS with Folic Acid Prevents Abdominal Aortic Aneurysm Formation in Angiotensin II-Infused Apolipoprotein E Null Mice

    PubMed Central

    Siu, Kin Lung; Miao, Xiao Niu; Cai, Hua

    2014-01-01

    We have previously shown that eNOS uncoupling mediates abdominal aortic aneurysm (AAA) formation in hph-1 mice. In the present study we examined whether recoupling of eNOS prevents AAA formation in a well-established model of Angiotensin II-infused apolipoprotein E (apoE) null mice by targeting some common pathologies of AAA. Infusion of Ang II resulted in a 92% incidence rate of AAA in the apoE null animals. In a separate group, animals were treated orally with folic acid (FA), which is known to recouple eNOS through augmentation of dihydrofolate reductase (DHFR) function. This resulted in a reduction of AAA rate to 19.5%. Imaging with ultrasound showed that FA markedly inhibited expansion of abdominal aorta. FA also abolished elastin breakdown and macrophage infiltration in the AAA animals. The eNOS uncoupling activity, assessed by L-NAME-sensitive superoxide production, was minimal at baseline but greatly exaggerated with Ang II infusion, which was completely attenuated by FA. This was accompanied by markedly improved tetrahydrobiopterin and nitric oxide bioavailability. Furthermore, the expression and activity of DHFR was decreased in Ang II-infused apoE null mice specifically in the endothelial cells, while FA administration resulted in its recovery. Taken together, these data further establish a significant role of uncoupled eNOS in mediating AAA formation, and a universal efficacy of FA in preventing AAA formation via restoration of DHFR to restore eNOS function. PMID:24558445

  18. Purinergic glio-endothelial coupling during neuronal activity: role of P2Y1 receptors and eNOS in functional hyperemia in the mouse somatosensory cortex.

    PubMed

    Toth, Peter; Tarantini, Stefano; Davila, Antonio; Valcarcel-Ares, M Noa; Tucsek, Zsuzsanna; Varamini, Behzad; Ballabh, Praveen; Sonntag, William E; Baur, Joseph A; Csiszar, Anna; Ungvari, Zoltan

    2015-12-01

    Impairment of moment-to-moment adjustment of cerebral blood flow (CBF) via neurovascular coupling is thought to play a critical role in the genesis of cognitive impairment associated with aging and pathological conditions associated with accelerated cerebromicrovascular aging (e.g., hypertension, obesity). Although previous studies demonstrate that endothelial dysfunction plays a critical role in neurovascular uncoupling in these conditions, the role of endothelial NO mediation in neurovascular coupling responses is not well understood. To establish the link between endothelial function and functional hyperemia, neurovascular coupling responses were studied in mutant mice overexpressing or deficient in endothelial NO synthase (eNOS), and the role of P2Y1 receptors in purinergic glioendothelial coupling was assessed. We found that genetic depletion of eNOS (eNOS(-/-)) and pharmacological inhibition of NO synthesis significantly decreased the CBF responses in the somatosensory cortex evoked by whisker stimulation and by administration of ATP. Overexpression of eNOS enhanced NO mediation of functional hyperemia. In control mice, the selective and potent P2Y1 receptor antagonist MRS2179 attenuated both whisker stimulation-induced and ATP-mediated CBF responses, whereas, in eNOS(-/-) mice, the inhibitory effects of MRS2179 were blunted. Collectively, our findings provide additional evidence for purinergic glio-endothelial coupling during neuronal activity, highlighting the role of ATP-mediated activation of eNOS via P2Y1 receptors in functional hyperemia. PMID:26453330

  19. Assessment of caprine corpora lutea growth, progesterone concentration, and eNOS expression: effect of a compensatory gain model.

    PubMed

    Thammasiri, J; Navanukraw, C; Uriyapongson, S; Khanthusaeng, V; Lertchunhakiat, K; Boonkong, S

    2016-07-01

    The experiment was conducted to evaluate corpus luteum (CL) growth, progesterone (P4) concentration, and endothelial nitric oxide synthase (eNOS) expression in nutrient stair-step fed goats. Female goats (n = 32) that exhibited at least 2, normal, consecutive estrous cycles were randomly assigned to either the control or stair-step fed group. In the control group, goats were fed ad libitum (100% of nutrient requirement for goats). The goats in the stair-step group were fed 70% of the control consumption for the first 42 d and 130% for the later 42 d during 4 consecutive estrous cycles (84 d). Blood and luteal samples were collected on days 3, 8, 13, and 18 of the estrous cycle to determine concentration of glucose, insulin, P4, luteal growth, and eNOS expression. Luteal growth was determined using fresh CL weight, DNA content, DNA and protein concentrations, and cell proliferation (labeling index of Ki-67). During realimentation phase at 4 h, glucose and insulin concentrations were greater (P < 0.05) in stair-step fed goat than those in control goats. Fresh CL weight, DNA content, protein concentrations, and labeling index of Ki67 on day 8 of the estrous cycle in the stair-step group were greater (P < 0.05) than that in the control group. Protein for eNOS was located in the capillaries of CL throughout of the estrous cycle in both groups. Greater serum P4 concentrations and eNOS protein (P < 0.05) were observed in the stair-step fed goats on day 3 (1.83 ng/mL and 6.79%) compared with the control goats (0.98 ng/mL and 6.02%) and on day 8 (5.15 ng/mL and 7.88%) compared with the control goats (4.54 ng/mL and 7.07%). These data demonstrate that luteal growth, progesterone concentration, and eNOS protein were partially affected by nutrient compensatory gain in goats. PMID:27088602

  20. Prevention of Mother-to-Child Transmission of HIV/AIDS: Perception of Health Care Workers in Rural Areas of Oyo State

    PubMed Central

    Aishat, Usman; Olubunmi, Ayinde

    2016-01-01

    Introduction. Proper implementation of prevention of mother-to-child transmission (PMTCT) services requires adequate knowledge and appropriate attitudes and practices on the part of the health care providers especially in rural areas where access to health care delivery is very limited in Oyo State. Materials and Methods. This is a descriptive cross-sectional survey of 350 health care workers in a two-stage sampling technique. Data was obtained using interviewer-administered, pretested, semistructured questionnaires. The data was analyzed using Epi Info software version 7. Results. The knowledge of PMTCT of HIV was poor among the health care workers (69.1%). However, more than half (58.3%) had good attitudes towards PMTCT of HIV/AIDS. Predictors of good knowledge of PMTCT were religion [AOR = 1.6, 95% CI (1.1–2.6)], cadre of occupation [AOR = 10.2, 95% CI (2.9–35.1)], and length of service [AOR = 4.3, 95% CI (2.3–19.4)]. Predictors of good attitude towards PMTCT were length of service in the current hospital [AOR = 2.8, 95% CI (1.5–5.2)] and cadre of occupation [AOR = 3.9, 95% CI (1.28–11.9)]. Conclusion. Despite poor knowledge of PMTCT of HIV/AIDS among the health care workers, the attitude towards PMTCT of HIV/AIDS was good. There is need for the involvement of the stakeholders in bridging the gap between knowledge of and attitude towards prevention of MTCT of HIV/AIDS among health care workers in the rural areas. PMID:26904361

  1. Up-Regulation of ENO1 by HIF-1α in Retinal Pigment Epithelial Cells after Hypoxic Challenge Is Not Involved in the Regulation of VEGF Secretion

    PubMed Central

    Zheng, Feihui; Jang, Wai-Chi; Fung, Frederic K. C.; Lo, Amy C. Y.; Wong, Ian Y. H.

    2016-01-01

    Purpose Alpha-enolase (ENO1), a major glycolytic enzyme, is reported to be over-expressed in various cancer tissues. It has been demonstrated to be regulated by the Hypoxia-inducible factor 1-α (HIF-1α), a crucial transcriptional factor implicated in tumor progression and cancer angiogenesis. Choroidal neovascularization (CNV), which is a leading cause of severe vision loss caused by newly formed blood vessels in the choroid, is also engendered by hypoxic stress. In this report, we investigated the expression of ENO1 and the effects of its down-regulation upon cobalt (II) chloride-induced hypoxia in retinal pigment epithelial cells, identified as the primary source of ocular angiogenic factors. Methods HIF-1α-diminished retinal pigment epithelial cells were generated by small interfering RNA (siRNA) technology in ARPE-19 cells, a human retinal pigment epithelial cell line. Both normal and HIF-1α-diminished ARPE-19 cells were then subjected to hypoxic challenge using cobalt (II) chloride (CoCl2) or anaerobic chamber. The relation between ENO1 expression and vascular endothelial growth factor (VEGF) secretion by retinal pigment epithelial cells were examined. Protein levels of HIF-1α and ENO1 were analyzed using Western Blot, while VEGF secretion was essayed by enzyme-linked immunosorbent assay (ELISA). Cytotoxicity after hypoxia was detected by Lactate Dehydrogenase (LDH) Assay. Results Upon 24 hr of CoCl2-induced hypoxia, the expression levels of ENO1 and VEGF were increased along with HIF-1α in ARPE-19 cells, both of which can in turn be down-regulated by HIF-1α siRNA application. However, knockdown of ENO1 alone or together with HIF-1α did not help suppress VEGF secretion in hypoxic ARPE-19 cells. Conclusion ENO1 was demonstrated to be up-regulated by HIF-1α in retinal pigment epithelial cells in response to hypoxia, without influencing VEGF secretion. PMID:26882120

  2. Sodium nitrite exerts an antihypertensive effect and improves endothelial function through activation of eNOS in the SHR.

    PubMed

    Ling, Wei Chih; Murugan, Dharmani Devi; Lau, Yeh Siang; Vanhoutte, Paul M; Mustafa, Mohd Rais

    2016-01-01

    Sodium nitrite (NaNO2) induces relaxation in isolated arteries partly through an endothelium-dependent mechanism involving NO-eNOS-sGC-cGMP pathway. The present study was designed to investigate the effect of chronic NaNO2 administration on arterial systolic blood pressure (SBP) and vascular function in hypertensive rats. NaNO2 (150 mg L-1) was given in drinking water for four weeks to spontaneously (SHR) and Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) treated hypertensive SD rats. Arterial SBP and vascular function in isolated aortae were studied. Total plasma nitrate/nitrite and vascular cyclic guanosine monophosphate (cGMP) levels were measured using commercially available assay kits. Vascular nitric oxide (NO) levels were evaluated by DAF-FM fluorescence while the proteins involved in endothelial nitric oxide synthase (eNOS) activation was determined by Western blotting. NaNO2 treatment reduced SBP, improved the impaired endothelium-dependent relaxation, increased plasma total nitrate/nitrite level and vascular tissue NO and cGMP levels in SHR. Furthermore, increased presence of phosphorylated eNOS and Hsp-90 was observed in NaNO2-treated SHR. The beneficial effect of nitrite treatment was not observed in L-NAME treated hypertensive SD rats. The present study provides evidence that chronic treatment of genetically hypertensive rats with NaNO2 improves endothelium-dependent relaxation in addition to its antihypertensive effect, partly through mechanisms involving activation of eNOS. PMID:27616322

  3. Heme changes HIF-α, eNOS and nitrite production in HUVECs after simvastatin, HU, and ascorbic acid therapies.

    PubMed

    da Guarda, Caroline C; Santiago, Rayra P; Pitanga, Thassila N; Santana, Sanzio S; Zanette, Dalila L; Borges, Valéria M; Goncalves, Marilda S

    2016-07-01

    The sickle cell disease (SCD) is a hemolytic genetic anemia characterized by free heme and hemoglobin release into intravascular spaces, with endothelial activation. Heme is a proinflammatory molecule able to directly activate vascular endothelium, thus, endothelial dysfunction and vascular disease are major chronic events described in SCD. The aim of this study was to evaluate the production of endothelial nitric oxide synthase (eNOS), nitrite and hypoxia inducible factor alpha (HIF-α) in HUVECs (human umbilical vein endothelial cells) activated by heme in response to simvastatin, hydroxyurea (HU), and ascorbic acid therapies. eNOS and HIF-α production were evaluated by ELISA and nitrite was measured by the Griess technique. The production of HIF-α increased when the cells were stimulated by heme (p<0.01), while treatment with HU and simvastatin reduced the production (p<0.01), and treatment with ascorbic acid increased HIF-1a production by the cells (p<0.01). Heme increased eNOS production, (p<0.01) but showed a heterogeneous pattern, and the lowest concentrations of all the treatments reduced the enzyme production (p<0.01). The nitrite production by HUVECs was enhanced by stimulation with heme (p<0.001) and was reduced by treatment with HU (p<0.001), ascorbic acid (p<0.001) and simvastatin (p<0.01). In summary, our results suggest that the hemolytic vascular microenvironment in SCD requires different therapeutic approaches to promote clinical improvement, and that a combination of therapies may be a viable strategy for treating patients. PMID:27089822

  4. Resveratrol Ameliorates High Glucose and High-Fat/Sucrose Diet-Induced Vascular Hyperpermeability Involving Cav-1/eNOS Regulation

    PubMed Central

    Peng, Xiao lin; Qu, Wei; Wang, Lin zhi; Huang, Bin qing; Ying, Chen jiang; Sun, Xiu fa; Hao, Li ping

    2014-01-01

    Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation. PMID:25419974

  5. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in L-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT₁R Expression.

    PubMed

    Maneesai, Putcharawipa; Prasarttong, Patoomporn; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Tangsucharit, Panot; Prachaney, Parichat; Pakdeechote, Poungrat

    2016-03-01

    This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in N(ω)-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS. PMID:26938552

  6. Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of eNOS and AT1R Expression

    PubMed Central

    Maneesai, Putcharawipa; Prasarttong, Patoomporn; Bunbupha, Sarawoot; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Tangsucharit, Panot; Prachaney, Parichat; Pakdeechote, Poungrat

    2016-01-01

    This study examined the effect of Carthamus tinctorius (CT) extract plus captopril treatment on blood pressure, vascular function, nitric oxide (NO) bioavailability, oxidative stress and renin-angiotensin system (RAS) in Nω-Nitro-l-arginine methyl ester (l-NAME)-induced hypertension. Rats were treated with l-NAME (40 mg/kg/day) for five weeks and given CT extract (75 or 150 or 300 or 500 mg/kg/day): captopril (5 mg/kg/day) or CT extract (300 mg/kg/day) plus captopril (5 mg/kg/day) for two consecutive weeks. CT extract reduced blood pressure dose-dependently, and the most effective dose was 300 mg/kg/day. l-NAME-induced hypertensive rats showed abnormalities including high blood pressure, high vascular resistance, impairment of acetylcholine-induced vasorelaxation in isolated aortic rings and mesenteric vascular beds, increased vascular superoxide production and plasma malondialdehyde levels, downregulation of eNOS, low level of plasma nitric oxide metabolites, upregulation of angiotensin II type 1 receptor and increased plasma angiotensin II. These abnormalities were alleviated by treatment with either CT extract or captopril. Combination treatment of CT extract and captopril normalized all the abnormalities found in hypertensive rats except endothelial dysfunction. These data indicate that there are synergistic antihypertensive effects of CT extract and captopril. These effects are likely mediated by their anti-oxidative properties and their inhibition of RAS. PMID:26938552

  7. Cicletanine stimulates eNOS phosphorylation and NO production via Akt and MAP kinase/Erk signaling in sinusoidal endothelial cells.

    PubMed

    Liu, Songling; Rockey, Don C

    2013-07-15

    The function of the endothelial isoform of nitric oxide synthase (eNOS) and production of nitric oxide (NO) is altered in a number of disease states. Pharmacological approaches to enhancing NO synthesis and thus perhaps endothelial function could have substantial benefits in patients. We analyzed the effect of cicletanine, a synthetic pyridine with potent vasodilatory characteristics, on eNOS function and NO production in normal (liver) and injured rat sinusoidal endothelial cells, and we studied the effect of cicletanine-induced NO on stellate cell contraction and portal pressure in an in vivo model of liver injury. Sinusoidal endothelial cells were isolated from normal and injured rat livers. After exposure to cicletanine, eNOS phosphorylation, NO synthesis, and the signaling pathway regulating eNOS activation were measured. Cicletanine led to an increase in eNOS (Ser¹¹⁷⁷) phosphorylation, cytochrome c reductase activity, L-arginine conversion to L-citrulline, as well as NO production. The mechanism of the effect of cicletanine appeared to be via the protein kinase B (Akt) and MAP kinase/Erk signaling pathways. Additionally, cicletanine improved NO synthesis in injured sinusoidal endothelial cells. NO production induced by cicletanine in sinusoidal endothelial cells increased protein kinase G (PKG) activity as well as relaxation of stellate cells. Finally, administration of cicletanine to mice with portal hypertension induced by bile duct ligation led to reduction of portal pressure. The data indicate that cicletanine might improve eNOS activity in injured sinusoidal endothelial cells and likely activates hepatic stellate cell NO/PKG signaling. It raises the possibility that cicletanine could improve intrahepatic vascular function in portal hypertensive patients. PMID:23639812

  8. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation

    PubMed Central

    Du, Xueliang; Edelstein, Diane; Obici, Silvana; Higham, Ninon; Zou, Ming-Hui; Brownlee, Michael

    2006-01-01

    Insulin resistance markedly increases cardiovascular disease risk in people with normal glucose tolerance, even after adjustment for known risk factors such as LDL, triglycerides, HDL, and systolic blood pressure. In this report, we show that increased oxidation of FFAs in aortic endothelial cells without added insulin causes increased production of superoxide by the mitochondrial electron transport chain. FFA-induced overproduction of superoxide activated a variety of proinflammatory signals previously implicated in hyperglycemia-induced vascular damage and inactivated 2 important antiatherogenic enzymes, prostacyclin synthase and eNOS. In 2 nondiabetic rodent models — insulin-resistant, obese Zucker (fa/fa) rats and high-fat diet–induced insulin-resistant mice — inactivation of prostacyclin synthase and eNOS was prevented by inhibition of FFA release from adipose tissue; by inhibition of the rate-limiting enzyme for fatty acid oxidation in mitochondria, carnitine palmitoyltransferase I; and by reduction of superoxide levels. These studies identify what we believe to be a novel mechanism contributing to the accelerated atherogenesis and increased cardiovascular disease risk occurring in people with insulin resistance. PMID:16528409

  9. Finite-volume application of high order ENO schemes to multi-dimensional boundary-value problems

    NASA Technical Reports Server (NTRS)

    Casper, Jay; Dorrepaal, J. Mark

    1990-01-01

    The finite volume approach in developing multi-dimensional, high-order accurate essentially non-oscillatory (ENO) schemes is considered. In particular, a two dimensional extension is proposed for the Euler equation of gas dynamics. This requires a spatial reconstruction operator that attains formal high order of accuracy in two dimensions by taking account of cross gradients. Given a set of cell averages in two spatial variables, polynomial interpolation of a two dimensional primitive function is employed in order to extract high-order pointwise values on cell interfaces. These points are appropriately chosen so that correspondingly high-order flux integrals are obtained through each interface by quadrature, at each point having calculated a flux contribution in an upwind fashion. The solution-in-the-small of Riemann's initial value problem (IVP) that is required for this pointwise flux computation is achieved using Roe's approximate Riemann solver. Issues to be considered in this two dimensional extension include the implementation of boundary conditions and application to general curvilinear coordinates. Results of numerical experiments are presented for qualitative and quantitative examination. These results contain the first successful application of ENO schemes to boundary value problems with solid walls.

  10. Association of Common Variants in eNOS Gene with Primary Open Angle Glaucoma: A Meta-Analysis

    PubMed Central

    Xiang, Yang; Dong, Yi; Li, Xuan; Tang, Xin

    2016-01-01

    Purpose. To clarify the association of endothelial nitric oxide synthase (eNOS) polymorphisms and primary open angle glaucoma (POAG). Methods. After a systematic literature search in the MEDLINE, EMBASE, and ISI Web of Science databases, all relevant studies evaluating the association between the polymorphisms (rs2070744 and rs1799983) of eNOS gene and POAG were screened and included. The pooled odds ratios (ORs) and the 95% confidence interval (CI) of each single-nucleotide polymorphism (SNP) in five genetic models were estimated using fixed-effect model if I2 < 50% in the test for heterogeneity; otherwise the random-effects model was used. Results. Thirty-one records were obtained, with five being suitable for meta-analysis. The overall results showed that both TT genotype in rs2070744 and GG genotype in rs1799983 are associated with decreased risk of POAG susceptibility. Stratified analysis based on ethnicity showed that the association of rs2070744 with POAG remained only in Caucasians. Results of subgroup analysis by sex indicated association between both polymorphisms and POAG in female group, but not in male group. Conclusions. TT genotype and/or T-allele in rs2070744, as well as GG genotype and/or G-allele in rs1799983, was associated with decreased risk for POAG overall and in female group. PMID:27242919

  11. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

    PubMed Central

    Morsy, Mohamed A.; Ibrahim, Salwa A.; Amin, Entesar F.; Kamel, Maha Y.; Rifaai, Rehab A.; Hassan, Magdy K.

    2014-01-01

    Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p.) for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS) expression, while expression of endothelial nitric oxide synthase (eNOS) was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production. PMID:25120567

  12. Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice

    PubMed Central

    Veron, Delma; Aggarwal, Pardeep K.; Velazquez, Heino; Kashgarian, Michael; Moeckel, Gilbert

    2014-01-01

    VEGF-A and nitric oxide are essential for glomerular filtration barrier homeostasis and are dysregulated in diabetic nephropathy. Here, we examined the effect of excess podocyte VEGF-A on the renal phenotype of endothelial nitric oxide synthase (eNOS) knockout mice. Podocyte-specific VEGF164 gain of function in eNOS−/− mice resulted in nodular glomerulosclerosis, mesangiolysis, microaneurysms, and arteriolar hyalinosis associated with massive proteinuria and renal failure in the absence of diabetic milieu or hypertension. In contrast, podocyte-specific VEGF164 gain of function in wild-type mice resulted in less pronounced albuminuria and increased creatinine clearance. Transmission electron microscopy revealed glomerular basement membrane thickening and podocyte effacement in eNOS−/− mice with podocyte-specific VEGF164 gain of function. Furthermore, glomerular nodules overexpressed collagen IV and laminin extensively. Biotin-switch and proximity ligation assays demonstrated that podocyte-specific VEGF164 gain of function decreased glomerular S-nitrosylation of laminin in eNOS−/− mice. In addition, treatment with VEGF-A decreased S-nitrosylated laminin in cultured podocytes. Collectively, these data indicate that excess glomerular VEGF-A and eNOS deficiency is necessary and sufficient to induce Kimmelstiel-Wilson–like nodular glomerulosclerosis in mice through a process that involves deposition of laminin and collagen IV and de-nitrosylation of laminin. PMID:24578128

  13. Xuezhikang, Extract of Red Yeast Rice, Improved Abnormal Hemorheology, Suppressed Caveolin-1 and Increased eNOS Expression in Atherosclerotic Rats

    PubMed Central

    Yang, Ya-Bing; Liu, Mei-Lin

    2013-01-01

    Background Xuezhikang is the extract of red yeast rice, which has been widely used for the management of atherosclerotic disease, but the molecular basis of its antiatherosclerotic effects has not yet been fully identified. Here we investigated the changes of eNOS in vascular endothelia and RBCs, eNOS regulatory factor Caveolin-1 in endothelia, and hemorheological parameters in atherosclerotic rats to explore the protective effects of Xuezhikang. Methodology/Principal Findings Wistar rats were divided into 4 groups (n = 12/group) group C, controls; group M, high-cholesterol diet (HCD) induced atherosclerotic models; group X, HCD+Xuezhikang; and group L, HCD +Lovastatin. In group X, Xuezhikang inhibited oxidative stress, down-regulated caveolin-1 in aorta wall (P<0.05), up-regulated eNOS expression in vascular endothelia and erythrocytes (P<0.05), increased NOx (nitrite and nitrate) in plasma and cGMP in erythrocyte plasma and aorta wall (P<0.05), increased erythrocyte deformation index (EDI), and decreased whole blood viscosity and plasma viscosity (P<0.05), with the improvement of arterial pathology. Conclusions/Significance Xuezhikang up-regulated eNOS expression in vascular endothelia and RBCs, increased plasma NOx and improved abnormal hemorheology in high cholesterol diet induced atherosclerotic rats. The elevated eNOS/NO and improved hemorheology may be beneficial to atherosclerotic disease. PMID:23675421

  14. Grape seed extract enhances eNOS expression and NO production through regulating calcium-mediated AKT phosphorylation in H2O2-treated endothelium.

    PubMed

    Feng, Zhe; Wei, Ri-Bao; Hong, Quan; Cui, Shao-Yuan; Chen, Xiang-Mei

    2010-10-01

    GSE (grape seed extract) has been shown to exhibit protective effects against cardiovascular events and atherosclerosis, although the underlying molecular mechanisms of action are unknown. Herein, we assessed the ability of GSE to enhance eNOS (endothelial nitric oxide synthase) expression and NO (nitric oxide) production in H2O2 (hydrogen peroxide)-treated HUVECs (human umbilical vein endothelial cells). GSE enhanced eNOS expression and NO release in H2O2-treated cells in a dose-dependent manner. GSE inhibited intracellular ROS (reactive oxygen species) and reduced intracellular calcium in a dose-dependent manner in H2O2-treated cells, as shown by confocal microscopy. ROS was inhibited in cells pretreated with 5.0 microM GSE, 2.0 microM TG (thapsigargin) and 20.0 microM 2-APB (2-aminoethoxydiphenyl borate) instead of 0.25 microM extracellular calcium. In addition, GSE enhanced eNOS expression and reduced ROS production via increasing p-AKT (AKT phosphorylation) with high extracellular calcium (13 mM). In conclusion, GSE protected against endothelial injury by up-regulation of eNOS and NO expression via inhibiting InsP3Rs (inositol 1,4,5-trisphosphate receptors)-mediated intracellular excessive calcium release and by activating p-AKT in endothelial cells. PMID:20513234

  15. Urocortin 2 stimulates nitric oxide production in ventricular myocytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177

    PubMed Central

    Walther, Stefanie; Pluteanu, Florentina; Renz, Susanne; Nikonova, Yulia; Maxwell, Joshua T.; Yang, Li-Zhen; Schmidt, Kurt; Edwards, Joshua N.; Wakula, Paulina; Groschner, Klaus; Maier, Lars S.; Spiess, Joachim; Blatter, Lothar A.; Pieske, Burkert

    2014-01-01

    Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca2+-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling. PMID:25015964

  16. Urocortin 2 stimulates nitric oxide production in ventricular myocytes via Akt- and PKA-mediated phosphorylation of eNOS at serine 1177.

    PubMed

    Walther, Stefanie; Pluteanu, Florentina; Renz, Susanne; Nikonova, Yulia; Maxwell, Joshua T; Yang, Li-Zhen; Schmidt, Kurt; Edwards, Joshua N; Wakula, Paulina; Groschner, Klaus; Maier, Lars S; Spiess, Joachim; Blatter, Lothar A; Pieske, Burkert; Kockskämper, Jens

    2014-09-01

    Urocortin 2 (Ucn2) is a cardioactive peptide exhibiting beneficial effects in normal and failing heart. In cardiomyocytes, it elicits cAMP- and Ca(2+)-dependent positive inotropic and lusitropic effects. We tested the hypothesis that, in addition, Ucn2 activates cardiac nitric oxide (NO) signaling and elucidated the underlying signaling pathways and mechanisms. In isolated rabbit ventricular myocytes, Ucn2 caused concentration- and time-dependent increases in phosphorylation of Akt (Ser473, Thr308), endothelial NO synthase (eNOS) (Ser1177), and ERK1/2 (Thr202/Tyr204). ERK1/2 phosphorylation, but not Akt and eNOS phosphorylation, was suppressed by inhibition of MEK1/2. Increased Akt phosphorylation resulted in increased Akt kinase activity and was mediated by corticotropin-releasing factor 2 (CRF2) receptors (astressin-2B sensitive). Inhibition of phosphatidylinositol 3-kinase (PI3K) diminished both Akt as well as eNOS phosphorylation mediated by Ucn2. Inhibition of protein kinase A (PKA) reduced Ucn2-induced phosphorylation of eNOS but did not affect the increase in phosphorylation of Akt. Conversely, direct receptor-independent elevation of cAMP via forskolin increased phosphorylation of eNOS but not of Akt. Ucn2 increased intracellular NO concentration ([NO]i), [cGMP], [cAMP], and cell shortening. Inhibition of eNOS suppressed the increases in [NO]i and cell shortening. When both PI3K-Akt and cAMP-PKA signaling were inhibited, the Ucn2-induced increases in [NO]i and cell shortening were attenuated. Thus, in rabbit ventricular myocytes, Ucn2 causes activation of cAMP-PKA, PI3K-Akt, and MEK1/2-ERK1/2 signaling. The MEK1/2-ERK1/2 pathway is not required for stimulation of NO signaling in these cells. The other two pathways, cAMP-PKA and PI3K-Akt, converge on eNOS phosphorylation at Ser1177 and result in pronounced and sustained cellular NO production with subsequent stimulation of cGMP signaling. PMID:25015964

  17. Finite-volume application of high-order ENO schemes to two-dimensional boundary-value problems

    NASA Technical Reports Server (NTRS)

    Casper, Jay

    1991-01-01

    Finite-volume applications of high-order accurate ENO schemes to two-dimensional boundary-value problems are studied. These schemes achieve high-order spatial accuracy, in smooth regions, by a piecewise polynomial approximation of the solution from cell averages. In addition, this spatial operation involves an adaptive stencil algorithm in order to avoid the oscillatory behavior that is associated with interpolation across steep gradients. High-order TVD Runge-Kutta methods are employed for time integration, thus making these schemes best suited for unsteady problems. Fifth- and sixth-order accurate applications are validated through a grid refinement study involving the solutions of scalar hyperbolic equations. A previously proposed extension for the Euler equations of gas dynamics is tested, including its application to solutions of boundary-value problems involving solid walls and curvilinear coordinates.

  18. Chronic aerobic exercise associated to dietary modification improve endothelial function and eNOS expression in high fat fed hamsters.

    PubMed

    Boa, Beatriz C S; Souza, Maria das Graças C; Leite, Richard D; da Silva, Simone V; Barja-Fidalgo, Thereza Christina; Kraemer-Aguiar, Luiz Guilherme; Bouskela, Eliete

    2014-01-01

    Obesity is epidemic in the western world and central adipose tissue deposition points to increased cardiovascular morbidity and mortality, independently of any association between obesity and other cardiovascular risk factors. Physical exercise has been used as non-pharmacological treatment to significantly reverse/attenuate obesity comorbidities. In this study we have investigated effects of exercise and/or dietary modification on microcirculatory function, body composition, serum glucose, iNOS and eNOS expression on 120 male hamsters treated for 12 weeks with high fat chow (HF, n = 30) starting on the 21st day of birth. From week 12 to 20, animals were randomly separated in HF (no treatment change), return to standard chow (HFSC, n = 30), high fat chow associated to an aerobic exercise training program (AET) (HFEX, n = 30) and return to standard chow+AET (HFSCEX, n = 30). Microvascular reactivity in response to acetylcholine and sodium nitroprusside and macromolecular permeability increase induced by 30 minutes ischemia followed by reperfusion were assessed on the cheek pouch preparation. Total body fat and aorta eNOS and iNOS expression by immunoblotting assay were evaluated on the experimental day. Compared to HFSC and HFSCEX groups, HF and HFEX ones presented increased visceral fat [(mean±SEM) (HF)4.9±1.5 g and (HFEX)4.7±0.9 g vs. (HFSC)*3.0±0.7 g and (HFSCEX)*1.9±0.4 g/100 g BW]; impaired endothelial-dependent vasodilatation [Ach 10(-8) M (HF)87.9±2.7%; (HFSC)*116.7±5.9%; (HFEX)*109.1±4.6%; (HFSCEX)*105±2.8%; Ach10(-6) M (HF)95.3±3.1%; (HFSC)*126±6.2%; (HFEX)*122.5±2.8%; (HFSCEX)*118.1±4.3% and Ach10(-4) M (HF)109.5±4.8%; (HFSC)*149.6±6.6%; (HFEX)*143.5±5.4% and (HFSCEX)*139.4±5.2%], macromolecular permeability increase after ischemia/reperfusion [(HF)40.5±4.2; (HFSC)*19.0±1.6; (HFEX)*18.6±2.1 and (HFSCEX)* 21.5±3.7 leaks/cm2), decreased eNOS expression, increased leptin and glycaemic levels. Endothelial

  19. High order filtering methods for approximating hyperbolic systems of conservation laws

    NASA Technical Reports Server (NTRS)

    Lafon, F.; Osher, S.

    1991-01-01

    The essentially nonoscillatory (ENO) schemes, while potentially useful in the computation of discontinuous solutions of hyperbolic conservation-law systems, are computationally costly relative to simple central-difference methods. A filtering technique is presented which employs central differencing of arbitrarily high-order accuracy except where a local test detects the presence of spurious oscillations and calls upon the full ENO apparatus to remove them. A factor-of-three speedup is thus obtained over the full-ENO method for a wide range of problems, with high-order accuracy in regions of smooth flow.

  20. New Findings in eNOS gene and Thalidomide Embryopathy Suggest pre-transcriptional effect variants as susceptibility factors.

    PubMed

    Kowalski, Thayne Woycinck; Fraga, Lucas Rosa; Tovo-Rodrigues, Luciana; Sanseverino, Maria Teresa Vieira; Hutz, Mara Helena; Schuler-Faccini, Lavínia; Vianna, Fernanda Sales Luiz

    2016-01-01

    Antiangiogenic properties of thalidomide have created an interest in the use of the drug in treatment of cancer. However, thalidomide is responsible for thalidomide embryopathy (TE). A lack of knowledge regarding the mechanisms of thalidomide teratogenesis acts as a barrier in the aim to synthesize a safer analogue of thalidomide. Recently, our group detected a higher frequency of alleles that impair the pro-angiogenic mechanisms of endothelial nitric oxide synthase (eNOS), coded by the NOS3 gene. In this study we evaluated variable number tandem repeats (VNTR) functional polymorphism in intron 4 of NOS3 in individuals with TE (38) and Brazilians without congenital anomalies (136). Haplotypes were estimated for this VNTR with previously analyzed polymorphisms, rs2070744 (-786C > T) and rs1799983 (894T > G), in promoter region and exon 7, respectively. Haplotypic distribution was different between the groups (p = 0.007). Alleles -786C (rs2070744) and 4b (VNTR), associated with decreased NOS3 expression, presented in higher frequency in TE individuals (p = 0.018; OR = 2.57; IC = 1.2-5.8). This association was not identified with polymorphism 894T > G (p = 0.079), which influences eNOS enzymatic activity. These results suggest variants in NOS3, with pre-transcriptional effects as susceptibility factors, influencing the risk TE development. This finding generates insight for a new approach to research that pursues a safer analogue. PMID:27004986

  1. New Findings in eNOS gene and Thalidomide Embryopathy Suggest pre-transcriptional effect variants as susceptibility factors

    PubMed Central

    Kowalski, Thayne Woycinck; Fraga, Lucas Rosa; Tovo-Rodrigues, Luciana; Sanseverino, Maria Teresa Vieira; Hutz, Mara Helena; Schuler-Faccini, Lavínia; Vianna, Fernanda Sales Luiz

    2016-01-01

    Antiangiogenic properties of thalidomide have created an interest in the use of the drug in treatment of cancer. However, thalidomide is responsible for thalidomide embryopathy (TE). A lack of knowledge regarding the mechanisms of thalidomide teratogenesis acts as a barrier in the aim to synthesize a safer analogue of thalidomide. Recently, our group detected a higher frequency of alleles that impair the pro-angiogenic mechanisms of endothelial nitric oxide synthase (eNOS), coded by the NOS3 gene. In this study we evaluated variable number tandem repeats (VNTR) functional polymorphism in intron 4 of NOS3 in individuals with TE (38) and Brazilians without congenital anomalies (136). Haplotypes were estimated for this VNTR with previously analyzed polymorphisms, rs2070744 (−786C > T) and rs1799983 (894T > G), in promoter region and exon 7, respectively. Haplotypic distribution was different between the groups (p = 0.007). Alleles −786C (rs2070744) and 4b (VNTR), associated with decreased NOS3 expression, presented in higher frequency in TE individuals (p = 0.018; OR = 2.57; IC = 1.2–5.8). This association was not identified with polymorphism 894T > G (p = 0.079), which influences eNOS enzymatic activity. These results suggest variants in NOS3, with pre-transcriptional effects as susceptibility factors, influencing the risk TE development. This finding generates insight for a new approach to research that pursues a safer analogue. PMID:27004986

  2. Enolase 1 (ENO1) and protein disulfide-isomerase associated 3 (PDIA3) regulate Wnt/β-catenin-driven trans-differentiation of murine alveolar epithelial cells

    PubMed Central

    Mutze, Kathrin; Vierkotten, Sarah; Milosevic, Jadranka; Eickelberg, Oliver; Königshoff, Melanie

    2015-01-01

    ABSTRACT The alveolar epithelium represents a major site of tissue destruction during lung injury. It consists of alveolar epithelial type I (ATI) and type II (ATII) cells. ATII cells are capable of self-renewal and exert progenitor function for ATI cells upon alveolar epithelial injury. Cell differentiation pathways enabling this plasticity and allowing for proper repair, however, are poorly understood. Here, we applied proteomics, expression analysis and functional studies in primary murine ATII cells to identify proteins and molecular mechanisms involved in alveolar epithelial plasticity. Mass spectrometry of cultured ATII cells revealed a reduction of carbonyl reductase 2 (CBR2) and an increase in enolase 1 (ENO1) and protein disulfide-isomerase associated 3 (PDIA3) protein expression during ATII-to-ATI cell trans-differentiation. This was accompanied by increased Wnt/β-catenin signaling, as analyzed by qRT-PCR and immunoblotting. Notably, ENO1 and PDIA3, along with T1α (podoplanin; an ATI cell marker), exhibited decreased protein expression upon pharmacological and molecular Wnt/β-catenin inhibition in cultured ATII cells, whereas CBR2 levels were stabilized. Moreover, we analyzed primary ATII cells from mice with bleomycin-induced lung injury, a model exhibiting activated Wnt/β-catenin signaling in vivo. We observed reduced CBR2 significantly correlating with surfactant protein C (SFTPC), whereas ENO1 and PDIA3 along with T1α were increased in injured ATII cells. Finally, siRNA-mediated knockdown of ENO1, as well as PDIA3, in primary ATII cells led to reduced T1α expression, indicating diminished cell trans-differentiation. Our data thus identified proteins involved in ATII-to-ATI cell trans-differentiation and suggest a Wnt/β-catenin-driven functional role of ENO1 and PDIA3 in alveolar epithelial cell plasticity in lung injury and repair. PMID:26035385

  3. Antenatal Maternally-Administered Phosphodiesterase Type 5 Inhibitors Normalize eNOS Expression in the Fetal Lamb Model of Congenital Diaphragmatic Hernia

    PubMed Central

    Shue, Eveline H; Schecter, Samuel C.; Gong, Wenhui; Etemadi, Mozziyar; Johengen, Michael; Iqbal, Corey; Derderian, S. Christopher; Oishi, Peter; Fineman, Jeffrey R.; Miniati, Doug

    2013-01-01

    Purpose Pulmonary hypertension (pHTN), a main determinant of survival in congenital diaphragmatic hernia (CDH), results from in utero vascular remodeling. Phosphodiesterase type 5 (PDE5) inhibitors have never been used antenatally to treat pHTN. The purpose of this study is to determine if antenatal PDE5 inhibitors can prevent pHTN in the fetal lamb model of CDH. Methods CDH were created in pregnant ewes. Postoperatively, pregnant ewes received oral placebo or tadalafil, a PDE5 inhibitor, until delivery. Near term gestation, lambs underwent resuscitations, and lung tissue was snap frozen for protein analysis. Results Mean cGMP levels were 0.53±0.11 in placebo-treated fetal lambs and 1.73±0.21 in tadalafil-treated fetal lambs (p=0.002). Normalized expression of eNOS was 82±12% in Normal-Placebo, 61±5% in CDH-Placebo, 116±6% in Normal-Tadalafil, and 86±8% in CDH-Tadalafil lambs. Normalized expression of β-sGC was 105±15% in Normal-Placebo, 82±3% in CDH-Placebo, 158±16% in Normal-Tadalafil, and 86±8% in CDH-Tadalafil lambs. Endothelial NOS and β-sGC were significantly decreased in CDH (p = 0.0007 and 0.01 for eNOS and β-sGC, respectively), and tadalafil significantly increased eNOS expression (p = 0.0002). Conclusions PDE5 inhibitors can cross the placental barrier. β-sGC and eNOS are downregulated in fetal lambs with CDH. Antenatal PDE5 inhibitors normalize eNOS and may prevent in utero vascular remodeling in CDH. PMID:24439578

  4. Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency

    PubMed Central

    Fallahi, Ali Asghar; Shekarfroush, Shahnaz; Rahimi, Mostafa; Jalali, Amirhossain; Khoshbaten, Ali

    2016-01-01

    Objective(s): High-intensity interval training (HIIT) increases energy expenditure and mechanical energy efficiency. Although both uncoupling proteins (UCPs) and endothelial nitric oxide synthase (eNOS) affect the mechanical efficiency and antioxidant capacity, their effects are inverse. The aim of this study was to determine whether the alterations of cardiac UCP2, UCP3, and eNOS mRNA expression following HIIT are in favor of increased mechanical efficiency or decreased oxidative stress. Materials and Methods: Wistar rats were divided into five groups: control group (n=12), HIIT for an acute bout (AT1), short term HIIT for 3 and 5 sessions (ST3 and ST5), long-term training for 8 weeks (LT) (6 in each group). The rats of the training groups were made to run on a treadmill for 60 min in three stages: 6 min running for warm-up, 7 intervals of 7 min running on treadmill with a slope of 5° to 20° (4 min with an intensity of 80-110% VO2max and 3 min at 50-60% VO2max), and 5-min running for cool-down. The control group did not participate in any exercise program. Rats were sacrificed and the hearts were extracted to analyze the levels of UCP2, UCP3 and eNOS mRNA by RT-PCR. Results: UCP3 expression was increased significantly following an acute training bout. Repeated HIIT for 8 weeks resulted in a significant decrease in UCPs mRNA and a significant increase in eNOS expression in cardiac muscle. Conclusion: This study indicates that Long term HIIT through decreasing UCPs mRNA and increasing eNOS mRNA expression may enhance energy efficiency and physical performance. PMID:27114795

  5. Upregulation of ERK1/2-eNOS via AT2 Receptors Decreases the Contractile Response to Angiotensin II in Resistance Mesenteric Arteries from Obese Rats

    PubMed Central

    Hagihara, Graziela N.; Lobato, Nubia S.; Filgueira, Fernando P.; Akamine, Eliana H.; Aragão, Danielle S.; Casarini, Dulce E.; Carvalho, Maria Helena C.; Fortes, Zuleica B.

    2014-01-01

    It has been clearly established that mitogen-activated protein kinases (MAPKS) are important mediators of angiotensin II (Ang II) signaling via AT1 receptors in the vasculature. However, evidence for a role of these kinases in changes of Ang II-induced vasoconstriction in obesity is still lacking. Here we sought to determine whether vascular MAPKs are differentially activated by Ang II in obese animals. The role of AT2 receptors was also evaluated. Male monosodium glutamate-induced obese (obese) and non-obese Wistar rats (control) were used. The circulating concentrations of Ang I and Ang II, determined by HPLC, were increased in obese rats. Ang II-induced isometric contraction was decreased in endothelium-intact resistance mesenteric arteries from obese compared with control rats and exhibited a retarded AT1 receptor antagonist response. Blocking of AT2 receptors and inhibition of either endothelial nitric oxide synthase (eNOS) or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) restored Ang II-induced contraction in obese rats. Western blot analysis revealed increased protein expression of AT2 receptors in arteries from obese rats. Basal and Ang II-induced ERK1/2 phosphorylation was also increased in obese rats. Blockade of either AT1 or AT2 receptors corrected the increased ERK1/2 phosphorylation in arteries from obese rats to levels observed in control preparations. Phosphorylation of eNOS was increased in obese rats. Incubation with the ERK1/2 inhibitor before Ang II stimulation did not affect eNOS phosphorylation in control rats; however, it corrected the increased phosphorylation of eNOS in obese rats. These results clearly demonstrate that enhanced AT2 receptor and ERK1/2-induced, NO-mediated vasodilation reduces Ang II-induced contraction in an endothelium-dependent manner in obese rats. PMID:25170617

  6. Upregulation of ERK1/2-eNOS via AT2 receptors decreases the contractile response to angiotensin II in resistance mesenteric arteries from obese rats.

    PubMed

    Hagihara, Graziela N; Lobato, Nubia S; Filgueira, Fernando P; Akamine, Eliana H; Aragão, Danielle S; Casarini, Dulce E; Carvalho, Maria Helena C; Fortes, Zuleica B

    2014-01-01

    It has been clearly established that mitogen-activated protein kinases (MAPKS) are important mediators of angiotensin II (Ang II) signaling via AT1 receptors in the vasculature. However, evidence for a role of these kinases in changes of Ang II-induced vasoconstriction in obesity is still lacking. Here we sought to determine whether vascular MAPKs are differentially activated by Ang II in obese animals. The role of AT2 receptors was also evaluated. Male monosodium glutamate-induced obese (obese) and non-obese Wistar rats (control) were used. The circulating concentrations of Ang I and Ang II, determined by HPLC, were increased in obese rats. Ang II-induced isometric contraction was decreased in endothelium-intact resistance mesenteric arteries from obese compared with control rats and exhibited a retarded AT1 receptor antagonist response. Blocking of AT2 receptors and inhibition of either endothelial nitric oxide synthase (eNOS) or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) restored Ang II-induced contraction in obese rats. Western blot analysis revealed increased protein expression of AT2 receptors in arteries from obese rats. Basal and Ang II-induced ERK1/2 phosphorylation was also increased in obese rats. Blockade of either AT1 or AT2 receptors corrected the increased ERK1/2 phosphorylation in arteries from obese rats to levels observed in control preparations. Phosphorylation of eNOS was increased in obese rats. Incubation with the ERK1/2 inhibitor before Ang II stimulation did not affect eNOS phosphorylation in control rats; however, it corrected the increased phosphorylation of eNOS in obese rats. These results clearly demonstrate that enhanced AT2 receptor and ERK1/2-induced, NO-mediated vasodilation reduces Ang II-induced contraction in an endothelium-dependent manner in obese rats. PMID:25170617

  7. Cerebral vasoconstriction reactions and plasma levels of ETBR, ET-1, and eNOS in patients with chronic high altitude disease

    PubMed Central

    Wu, Shizheng; Hao, Guisheng; Zhang, Shukun; Jiang, Dongmei; Wuren, Tana; Luo, Junming

    2016-01-01

    The aim of the present study was to examine cerebral vasoconstriction in patients with chronic high altitude disease [cerebrovascular reactivity (CVR)], and to evaluate differences in alterations of brain vascular contractile reactivity of chronic mountain sickness (CMS) patients and healthy controls. Alterations of endothelin (ET) and its receptor, as well as endothelial nitric oxide synthase (eNOS) levels in the plasma were examined to determine the cerebral reservation capacities in CMS patients. Transcranial Doppler ultrasound and carbon dioxide analysis methods were used to detect the CVR variances. At the same time, enzyme-linked immunosorbent assay approaches were utilized to detect the ET and ET B receptor and the eNOS levels in serum of the CMS patients and healthy controls. CVR and CVRI levels in CMS patients were lower than those of the healthy control subjects and the difference was statistically significant (P<0.05). By contrast, eNOS and ET-1 levels were not statistically significant for CMS and healthy controls (P>0.05). However, the ET receptor concentration level was higher in CMS than the healthy controls. Thus, ET-1 may not be a direct etiological variation but may play compensatory roles in CMS patients. The results of the study may provide scientific clues for the prevention and treatment of CMS with higher blood coagulation states of cerebral infarction in patients with chronic high altitude disease. PMID:27485004

  8. Cerebral vasoconstriction reactions and plasma levels of ETBR, ET-1, and eNOS in patients with chronic high altitude disease.

    PubMed

    Wu, Shizheng; Hao, Guisheng; Zhang, Shukun; Jiang, Dongmei; Wuren, Tana; Luo, Junming

    2016-09-01

    The aim of the present study was to examine cerebral vasoconstriction in patients with chronic high altitude disease [cerebrovascular reactivity (CVR)], and to evaluate differences in alterations of brain vascular contractile reactivity of chronic mountain sickness (CMS) patients and healthy controls. Alterations of endothelin (ET) and its receptor, as well as endothelial nitric oxide synthase (eNOS) levels in the plasma were examined to determine the cerebral reservation capacities in CMS patients. Transcranial Doppler ultrasound and carbon dioxide analysis methods were used to detect the CVR variances. At the same time, enzyme‑linked immunosorbent assay approaches were utilized to detect the ET and ET B receptor and the eNOS levels in serum of the CMS patients and healthy controls. CVR and CVRI levels in CMS patients were lower than those of the healthy control subjects and the difference was statistically significant (P<0.05). By contrast, eNOS and ET‑1 levels were not statistically significant for CMS and healthy controls (P>0.05). However, the ET receptor concentration level was higher in CMS than the healthy controls. Thus, ET‑1 may not be a direct etiological variation but may play compensatory roles in CMS patients. The results of the study may provide scientific clues for the prevention and treatment of CMS with higher blood coagulation states of cerebral infarction in patients with chronic high altitude disease. PMID:27485004

  9. Exercise Training Could Improve Age-Related Changes in Cerebral Blood Flow and Capillary Vascularity through the Upregulation of VEGF and eNOS

    PubMed Central

    Viboolvorakul, Sheepsumon; Patumraj, Suthiluk

    2014-01-01

    This study aimed to investigate the effect of exercise training on age-induced microvascular alterations in the brain. Additionally, the association with the protein levels of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) was also assessed. Male Wistar rats were divided into four groups: sedentary-young (SE-Young, n = 5), sedentary aged (SE-Aged, n = 8), immersed-aged (IM-Aged, n = 5), and exercise trained-aged (ET-Aged, 60 minutes/day and 5 days/week for 8 weeks, n = 8) rats. The MAPs of all aged groups, SE-Aged, IM-Aged, and ET-Aged, were significantly higher than that of the SE-Young group. The regional cerebral blood flow (rCBF) in the SE-Aged and IM-Aged was significantly decreased as compared to SE-Young groups. However, rCBF of ET-Aged group was significantly higher than that in the IM-Aged group (P < 0.05). Moreover, the percentage of capillary vascularity (%CV) and the levels of VEGF and eNOS in the ET-Aged group were significantly increased compared to the IM-Aged group (P < 0.05). These results imply that exercise training could improve age-induced microvascular changes and hypoperfusion closely associated with the upregulation of VEGF and eNOS. PMID:24822184

  10. Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure.

    PubMed

    Winzer, Ephraim B; Gaida, Pauline; Höllriegel, Robert; Fischer, Tina; Linke, Axel; Schuler, Gerhard; Adams, Volker; Erbs, Sandra

    2016-01-01

    Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser(1177), dephosphorylation at Thr(495), and diminished phosphorylation of PKC-βII at Ser(660). The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function. PMID:27563480

  11. Impact of Rosuvastatin Treatment on HDL-Induced PKC-βII and eNOS Phosphorylation in Endothelial Cells and Its Relation to Flow-Mediated Dilatation in Patients with Chronic Heart Failure

    PubMed Central

    Gaida, Pauline; Höllriegel, Robert; Fischer, Tina; Linke, Axel; Schuler, Gerhard; Adams, Volker; Erbs, Sandra

    2016-01-01

    Background. Endothelial function is impaired in chronic heart failure (CHF). Statins upregulate endothelial NO synthase (eNOS) and improve endothelial function. Recent studies demonstrated that HDL stimulates NO production due to eNOS phosphorylation at Ser1177, dephosphorylation at Thr495, and diminished phosphorylation of PKC-βII at Ser660. The aim of this study was to elucidate the impact of rosuvastatin on HDL mediated eNOS and PKC-βII phosphorylation and its relation to endothelial function. Methods. 18 CHF patients were randomized to 12 weeks of rosuvastatin or placebo. At baseline, 12 weeks, and 4 weeks after treatment cessation we determined lipid levels and isolated HDL. Human aortic endothelial cells (HAEC) were incubated with isolated HDL and phosphorylation of eNOS and PKC-βII was evaluated. Flow-mediated dilatation (FMD) was measured at the radial artery. Results. Rosuvastatin improved FMD significantly. This effect was blunted after treatment cessation. LDL plasma levels were reduced after rosuvastatin treatment whereas drug withdrawal resulted in significant increase. HDL levels remained unaffected. Incubation of HAEC with HDL had no impact on phosphorylation of eNOS or PKC-βII. Conclusion. HDL mediated eNOS and PKC-βII phosphorylation levels in endothelial cells do not change with rosuvastatin in CHF patients and do not mediate the marked improvement in endothelial function. PMID:27563480

  12. MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity

    SciTech Connect

    Weber, Martina; Baker, Meredith B.; Moore, Jeffrey P.; Searles, Charles D.

    2010-03-19

    Mechanical forces associated with blood flow play an important role in regulating vascular signaling and gene expression in endothelial cells (ECs). MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. miRNAs are known to have an important role in modulating EC biology, but their expression and functions in cells subjected to shear stress conditions are unknown. We sought to determine the miRNA expression profile in human ECs subjected to unidirectional shear stress and define the role of miR-21 in shear stress-induced changes in EC function. TLDA array and qRT-PCR analysis performed on HUVECs exposed to prolonged unidirectional shear stress (USS, 24 h, 15 dynes/cm{sup 2}) identified 13 miRNAs whose expression was significantly upregulated (p < 0.05). The miRNA with the greatest change was miR-21; it was increased 5.2-fold (p = 0.002) in USS-treated versus control cells. Western analysis demonstrated that PTEN, a known target of miR-21, was downregulated in HUVECs exposed to USS or transfected with pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and increased eNOS phosphorylation and nitric oxide (NO{sup {center_dot}}) production. These data demonstrate that shear stress forces regulate the expression of miRNAs in ECs, and that miR-21 influences endothelial biology by decreasing apoptosis and activating the NO{sup {center_dot}} pathway. These studies advance our understanding of the mechanisms by which shear stress forces modulate vascular homeostasis.

  13. Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis.

    PubMed

    Song, Pingping; Zou, Shasha; Chen, Tingting; Chen, Jianhua; Wang, Yanan; Yang, Juanjuan; Song, Zhijian; Jiang, Huayu; Shi, Huijuan; Huang, Yiran; Li, Zheng; Shi, Yongyong; Hu, Hongliang

    2015-02-01

    Recent studies on the eNOS gene and male infertility show that expression of eNOS regulates normal spermatogenesis in the testis, and the eNOS gene variants (T-786C, 4a4b, and G894T) are potentially involved in impairment of spermatogenesis and sperm function. Thus, we conducted this association and meta-analysis study to further validate whether variants of those three loci affected the risk of idiopathic asthenozoospermia (AZS) and male infertility. Approximately 340 Chinese idiopathic AZS patients and 342 healthy men were included for this case-control study, genotyped by gel electrophoresis analysis or direct sequencing of PCR products. The eNOS mRNA isolated from the semen of patients was further examined by quantitative real-time PCR. Also, a meta-analysis of association between eNOS gene polymorphisms and male infertility was performed. A significant association was identified on allelic level between 4a4b variant and AZS in our study (chi-squared = 7.53, corrected P = 0.018, odds ratio (OR) = 1.808), while there were no significant difference of T-786C and G894T for asthenozoospermia in both genotype and allele distributions. In addition, expression of eNOS was up-regulated in patients compared with controls (about 2.4-fold, P < 0.001). Furthermore, the results of the meta-analysis support the conclusion that the T-786C and 4a4b loci were associated with male infertility in both Asian and Caucasian populations. Our study provides genetic evidence for the eNOS gene being a risk factor for idiopathic AZS and male infertility. Considering genetic differences among populations and complex pathogenesis of male infertility, more validating studies using independent samples are suggested in the future. PMID:25505202

  14. 17-beta-oestradiol-induced vasorelaxation in vitro is mediated by eNOS through hsp90 and akt/pkb dependent mechanism.

    PubMed

    Bucci, Mariarosaria; Roviezzo, Fiorentina; Cicala, Carla; Pinto, Aldo; Cirino, Giuseppe

    2002-04-01

    1. The L-arginine-NO pathway has been implicated in the vasorelaxant effect of 17-beta-oestradiol. Here we have addressed the involvement of two distinct activation steps of endothelial nitric oxide synthase (eNOS) in the 17-beta-oestradiol-induced vasorelaxant effect on rat aortic rings. 2. Rat aortic rings contracted with phenylephrine (PE) 1 microM relaxed in a concentration related fashion to 17-beta-oestradiol water soluble cyclodextrin-encapsulated (E2) only when endothelium was present. The pure anti-oestrogen of E2 receptor ICI 182,780 (20 microM) significantly inhibited E2-induced vasorelaxation. 3. Geldanamycin (10 microM), a specific inhibitor of heat shock protein 90 (hsp90) and N(omega)-nitro-L-arginine-methyl ester (L-NAME, 100 microM), a nitric oxide synthase inhibitor, significantly inhibited E2-induced vasorelaxation. 4. Incubation of rat aortic rings up to 6 h with LY 294002 (25 microM), a specific inhibitor of PI(3)K akt/pkb pathway reduced E2-induced vasorelaxation. 5. Incubation of rat isolated aorta with E2, induced prostacyclin (PGI(2)) release. PGI(2) levels, measured as 6-keto PGF(1alpha), were abolished by ibuprofen (10 microM), both L-NAME and GA did not influence basal or E2-stimulated PGI(2) confirming the specificity of these two compounds on eNOS pathway. 6. In conclusion, we demonstrate that E2 interaction with its receptor is followed by a vasorelaxant effect in rat aortic rings mediated by eNOS activation through both hsp90 and akt/pkb dependent mechanisms. PMID:11934809

  15. Association of G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms with susceptibility to myocardial infarction in Morocco

    PubMed Central

    Hassani Idrissi, Hind; Hmimech, Wiam; Diakite, Brehima; Korchi, Farah; Baghdadi, Dalila; Habbal, Rachida; Nadifi, Sellama

    2016-01-01

    Background Myocardial infarction (MI) is a common multifactorial disease. Numerous studies have found that genetic plays an essential role in MI occurrence. The main objective of our case–control study is to explore the association of G894T eNOS (rs1799983), 4G/5G PAI (rs1799889) and T1131C APOA5 (rs662799) polymorphisms with MI susceptibility in the Moroccan population. Methods and results 118 MI patients were recruited vs 184 healthy controls. DNA samples were genotyped by PCR-RFLP method using MboI, BslI and MseI restriction enzymes respectively for the G894T eNOS, 4G/5G PAI and T1131C APOA5 polymorphisms. Our results show that the G894T eNOS was significantly associated with increased risk of MI under the three genetic transmission models (dominant: OR = 1.64, 95% CI = 1.05–2.58, P = 0.003; recessive: OR = 2.15, 95% CI = 0.74–6.16, P = 0.03; additive: OR = 1.54, 95% CI = 1.06–2.23, P = 0.001). The T1131C APOA5 polymorphism was associated to MI risk in recessive and additive models (OR = 1.53, 95% CI = 0.72–3.2, P = 0.04 and OR = 1.78, 95% CI = 1.26–2.51, P = 0.03 respectively). For the 4G/5G PAI variant, even the cases and controls groups were not in Hardy–Weinberg Equilibrium (HWE), the dominant and additive models show a statistically significant association with MI risk (OR = 7.96, 95%CI = 3.83–16.36, P = 0.01 and OR = 1.96, 95% CI = 1.4–2.72, P = 0.03 respectively). Conclusion Our results suggest that G894T eNOS and T1131C APOA5 polymorphisms may be considered as genetic markers of MI among the Moroccan population. Further studies including larger sample sizes and exploring more genetic associations are needed to confirm our results and to better understand the susceptibility to MI. PMID:27222817

  16. Performance characteristics of methods for quantifying spontaneous intracerebral haemorrhage: data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial

    PubMed Central

    Krishnan, Kailash; Mukhtar, Siti F; Lingard, James; Houlton, Aimee; Walker, Elizabeth; Jones, Tanya; Sprigg, Nikola; Cala, Lesley A; Becker, Jennifer L; Dineen, Robert A; Koumellis, Panos; Adami, Alessandro; Casado, Ana M; Bath, Philip M W; Wardlaw, Joanna M

    2015-01-01

    Background Poor prognosis after intracerebral haemorrhage (ICH) is related to haemorrhage characteristics. Along with developing therapeutic interventions, we sought to understand the performance of haemorrhage descriptors in large clinical trials. Methods Clinical and neuroimaging data were obtained for 548 participants with ICH from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Independent observers performed visual categorisation of the largest diameter, measured volume using ABC/2, modified ABC/2, semiautomated segmentation (SAS), fully automatic measurement methods; shape, density and intraventricular haemorrhage were also assessed. Intraobserver and interobserver reliability were determined for these measures. Results ICH volume was significantly different among standard ABC/2, modified ABC/2 and SAS: (mean) 12.8 (SD 16.3), 8.9 (9.2), 12.8 (13.1) cm3, respectively (p<0.0001). There was excellent agreement for haemorrhage volume (n=193): ABC/2 intraobserver intraclass correlation coefficient (ICC) 0.96–0.97, interobserver ICC 0.88; modified ABC/2 intraobserver ICC 0.95–0.97, interobserver ICC 0.91; SAS intraobserver ICC 0.95–0.99, interobserver ICC 0.93; largest diameter: (visual) interadjudicator ICC 0.82, (visual vs measured) adjudicator vs observer ICC 0.71; shape intraobserver ICC 0.88 interobserver ICC 0.75; density intraobserver ICC 0.86, interobserver ICC 0.73. Graeb score (mean 3.53) and modified Graeb (5.22) scores were highly correlated. Using modified ABC/2, ICH volume was underestimated in regular (by 2.2-2.5 cm3, p<0.0001) and irregular-shaped haemorrhages (by 4.8-4.9 cm3, p<0.0001). Fully automated measurement of haemorrhage volume was possible in only 5% of cases. Conclusions Formal measurement of haemorrhage characteristics and visual estimates are reproducible. The standard ABC/2 method is superior to the modified ABC/2 method for quantifying ICH volume. Clinical trial registration ISRCTN9941422. PMID:25575847

  17. Computational and anti-tumor studies of 7a-Aza-B-homostigmast-5-eno [7a, 7-d] tetrazole-3β-yl chloride

    NASA Astrophysics Data System (ADS)

    Alam, Mahboob; Alam, Mohammad Jane; Nami, Shahab A. A.; Lee, Dong-Ung; Azam, Mohammad; Ahmad, Shabbir

    2016-03-01

    The present paper reports the detailed computational study including molecular docking of a biologically active steroidal tetrazole, 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole-3β-yl chloride. The molecular structure, IR and NMR (13C and 1H) spectra of the tetrazole were interpreted by comparing the experimental results with the theoretical, B3LYP/6-311G(d,p) calculations. The vibrational bands appearing in the FTIR are assigned with great accuracy using animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and natural atomic charges have been presented at the same level of theory. The theoretical results are found in good correlation with the experimental data. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The in vitro anti-tumor activity of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole-3β-yl chloride has also been carried out against five human tumor cell lines. Doxorubicin is used as a standard drug for the in vitro anti-tumor screening.

  18. DFT, Hirshfeld surfaces, spectral and in vivo cytotoxic studies of 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole

    NASA Astrophysics Data System (ADS)

    Alam, Mahboob; Alam, Mohammad Jane; Nami, Shahab A. A.; Khan, Mohd Shoeb; Ahmad, Shabbir; Lee, Dong-Ung

    2015-11-01

    The DFT (B3LYP) calculations on a synthetic steroidal molecule 7a-Aza-B-homostigmast-5-eno [7a,7-d] tetrazole, C29H48N4, have been performed. The molecular structure, IR and NMR (13C and 1H) spectra of the present compound were interpreted using experiments (XRD, FTIR, NMR) as well as theoretical, B3LYP/6-311 + G(2d,p), calculations. The vibrational bands appearing in FTIR are assigned with great accuracy using animated modes. Molecular properties like HOMO-LUMO analysis, chemical reactivity descriptors, MEP mapping, dipole moment and Mullikan's atomic charges have been presented at the same level of theory. The theoretical results are found in good correlation with experimental data. Moreover, the Hirshfeld analysis was carried out to ascertain the secondary interactions and associated 2D fingerprint plots. The in vivo cytotoxicity of 7a-Aza-B-homostigmast-5-eno [7a,7-d] has also been carried out against brine shrimp nauplii by lethality bioassay.

  19. eNOS and iNOS trigger apoptosis in the brains of sheep and goats naturally infected with the border disease virus.

    PubMed

    Dincel, Gungor Cagdas; Kul, Oguz

    2015-10-01

    In this study, apoptotic and anti-apoptotic mechanisms and if present, which pathway to trigger the apoptosis in the brains of Border Disease Virus (BDV) infected lambs (n=10) and goat kids (n=5) were investigated. Briefly, apoptotic (caspase 3, caspase 9) and anti-apoptotic markers (Bcl-2), cytokine response (TNF-α, INF-γ), reactive gliosis and myelin loss were examined. eNOS, iNOS, caspase 9, caspase 3 and GFAP expressions were higher in BDV infected tissues compared to control animals (6 kids and 6 lambs) (p<0.05). Double immunoperoxidase test revealed that TUNEL positive apoptotic cells showed significant association with increased eNOS-iNOS and iNOS-BDV expressions. However, no significant differences were found for TNFR1, TNF-α and INF-γ expressions in BD (p>0.05). There was a positive correlation between the intensity of myelin loss, GFAP activity and severity of infection. Inconclusion, as a novel finding, it is established that eNOS and iNOS overexpressions are co-associated with apoptosis in BDV infected neurons and neuroglia. The results also strongly suggested that BDV infected apoptotic cells mainly prefer the intrinsic pathway that might be most likely related to increased nitric oxide levels. PMID:25882134

  20. Differential effect of beetroot bread on postprandial DBP according to Glu298Asp polymorphism in the eNOS gene: a pilot study.

    PubMed

    Hobbs, D A; George, T W; Lovegrove, J A

    2014-12-01

    Our objective was to investigate whether the presence of Glu298Asp polymorphism in the endothelial NO synthase (eNOS) gene differentially affects the postprandial blood pressure response to dietary nitrate-rich beetroot bread. A randomised, single-blind, controlled, crossover acute pilot study was performed in 14 healthy men (mean age: 34±9 years) who were retrospectively genotyped for Glu298Asp polymorphism (7GG; T carriers 7). Volunteers were randomised to receive 200 g beetroot-enriched bread (1.1 mmol nitrate) or control bread (no beetroot; 0.01 mmol nitrate) on two separate occasions 10 days apart. Baseline and incremental area under the curve of blood pressure and NOx (nitrate/nitrite) were measured for a 6-h postprandial period. A treatment × genotype interaction was observed for diastolic blood pressure (P<0.02), which was significantly lower in T carriers (P<0.01) after consumption of beetroot bread compared with control bread. No significant differences were observed in the GG group. The beneficial diastolic blood pressure reduction was observed only in the T carriers of the Glu298Asp polymorphism in the eNOS gene after consumption of nitrate-rich beetroot bread. These data require confirmation in a larger population group. PMID:24670328

  1. Redox-sensitive up-regulation of eNOS by purple grape juice in endothelial cells: role of PI3-kinase/Akt, p38 MAPK, JNK, FoxO1 and FoxO3a.

    PubMed

    Alhosin, Mahmoud; Anselm, Eric; Rashid, Sherzad; Kim, Jong Hun; Madeira, Socorro Vanesca Frota; Bronner, Christian; Schini-Kerth, Valérie B

    2013-01-01

    The vascular protective effect of grape-derived polyphenols has been attributable, in part, to their direct action on blood vessels by stimulating the endothelial formation of nitric oxide (NO). The aim of the present study was to determine whether Concord grape juice (CGJ), which contains high levels of polyphenols, stimulates the expression of endothelial NO synthase (eNOS) in porcine coronary artery endothelial cells and, if so, to determine the signaling pathway involved. CGJ dose- and time-dependently increased eNOS mRNA and protein levels and this effect is associated with an increased formation of NO in endothelial cells. The stimulatory effect of CGJ on eNOS mRNA is not associated with an increased eNOS mRNA stability and inhibited by antioxidants such as MnTMPyP, PEG-catalase, and catalase, and by wortmannin (an inhibitor of PI3-kinase), SB 203580 (an inhibitor of p38 MAPK), and SP 600125 (an inhibitor of JNK). Moreover, CGJ induced the formation of reactive oxygen species (ROS) in endothelial cells and this effect is inhibited by MnTMPyP, PEG-catalase, and catalase. The CGJ-induced the phosphorylation of p38 MAPK and JNK kinases is abolished by MnTMPyP. CGJ induced phosphorylation of transcription factors FoxO1 and FoxO3a, which regulate negatively eNOS expression, and this effect is prevented by MnTMPyP, PEG-catalase, wortmannin, SB203580 and SP600125. Moreover, chromatin immunoprecipitation assay indicated that the FoxO3a protein is associated with the eNOS promoter in control cells and that CGJ induced its dissociation. Thus, the present study indicates that CGJ up-regulates the expression of eNOS mRNA and protein leading to an increased formation of NO in endothelial cells. The stimulatory effect of CGJ is a redox-sensitive event involving PI3-kinase/Akt, p38 MAPK and JNK pathways, and the inactivation of the FoxO transcription factors, FoxO1 and FoxO3a, thereby preventing their repression of the eNOS gene. PMID:23533577

  2. Redox-Sensitive Up-Regulation of eNOS by Purple Grape Juice in Endothelial Cells: Role of PI3-Kinase/Akt, p38 MAPK, JNK, FoxO1 and FoxO3a

    PubMed Central

    Rashid, Sherzad; Kim, Jong Hun; Frota Madeira, Socorro Vanesca; Bronner, Christian; Schini-Kerth, Valérie B.

    2013-01-01

    The vascular protective effect of grape-derived polyphenols has been attributable, in part, to their direct action on blood vessels by stimulating the endothelial formation of nitric oxide (NO). The aim of the present study was to determine whether Concord grape juice (CGJ), which contains high levels of polyphenols, stimulates the expression of endothelial NO synthase (eNOS) in porcine coronary artery endothelial cells and, if so, to determine the signaling pathway involved. CGJ dose- and time-dependently increased eNOS mRNA and protein levels and this effect is associated with an increased formation of NO in endothelial cells. The stimulatory effect of CGJ on eNOS mRNA is not associated with an increased eNOS mRNA stability and inhibited by antioxidants such as MnTMPyP, PEG-catalase, and catalase, and by wortmannin (an inhibitor of PI3-kinase), SB 203580 (an inhibitor of p38 MAPK), and SP 600125 (an inhibitor of JNK). Moreover, CGJ induced the formation of reactive oxygen species (ROS) in endothelial cells and this effect is inhibited by MnTMPyP, PEG-catalase, and catalase. The CGJ-induced the phosphorylation of p38 MAPK and JNK kinases is abolished by MnTMPyP. CGJ induced phosphorylation of transcription factors FoxO1 and FoxO3a, which regulate negatively eNOS expression, and this effect is prevented by MnTMPyP, PEG-catalase, wortmannin, SB203580 and SP600125. Moreover, chromatin immunoprecipitation assay indicated that the FoxO3a protein is associated with the eNOS promoter in control cells and that CGJ induced its dissociation. Thus, the present study indicates that CGJ up-regulates the expression of eNOS mRNA and protein leading to an increased formation of NO in endothelial cells. The stimulatory effect of CGJ is a redox-sensitive event involving PI3-kinase/Akt, p38 MAPK and JNK pathways, and the inactivation of the FoxO transcription factors, FoxO1 and FoxO3a, thereby preventing their repression of the eNOS gene. PMID:23533577

  3. Wall stretch and thromboxane A2 activate NO synthase (eNOS) in pulmonary arterial smooth muscle cells via H2O2 and Akt-dependent phosphorylation.

    PubMed

    Kim, Hae Jin; Yoo, Hae Young; Jang, Ji Hyun; Lin, Hai Yue; Seo, Eun Yeong; Zhang, Yin Hua; Kim, Sung Joon

    2016-04-01

    Pulmonary arteries (PAs) have high compliance, buffering the wide ranges of blood flow. Here, we addressed a hypothesis that PA smooth muscle cells (PASMCs) express nitric oxide synthases (NOS) that might be activated by mechanical stress and vasoactive agonists. In the myograph study of endothelium-denuded rat PAs, NOS inhibition (L-NAME) induced strong contraction (96 % of 80 mM KCl-induced contraction (80K)) in the presence of 5 nM U46619 (thromboxane A2 (TXA2) analogue) with relatively high basal stretch (2.94 mN, S(+)). With lower basal stretch (0.98 mN, S(-)), however, L-NAME application following U46619 (TXA2/L-NAME) induced weak contraction (27 % of 80K). Inhibitors of nNOS and iNOS had no such effect in S(+) PAs. In endothelium-denuded S(+) mesenteric and renal arteries, TXA2/L-NAME-induced contraction was only 18 and 21 % of 80K, respectively. Expression of endothelial-type NOS (eNOS) in rat PASMCs was confirmed by RT-PCR and immunohistochemistry. Even in S(-) PAs, pretreatment with H2O2 (0.1-10 μM) effectively increased the sensitivity to TXA2/L-NAME (105 % of 80K). Vice versa, NADPH oxidase inhibitors, reactive oxygen species scavengers, or an Akt inhibitor (SC-66) suppressed TXA2/L-NAME-induced contraction in S(+) PAs. In a human PASMC line, immunoblot analysis showed the following: (1) eNOS expression, (2) Ser(1177) phosphorylation by U46619 and H2O2, and (3) Akt activation (Ser(473) phosphorylation) by U46619. In the cell-attached patch clamp study, H2O2 facilitated membrane stretch-activated cation channels in rat PASMCs. Taken together, the muscular eNOS in PAs can be activated by TXA2 and mechanical stress via H2O2 and Akt-mediated signaling, which may counterbalance the contractile signals from TXA2 and mechanical stimuli. PMID:26729266

  4. L-Arginine ameliorates cardiac left ventricular oxidative stress by upregulating eNOS and Nrf2 target genes in alloxan-induced hyperglycemic rats

    SciTech Connect

    Ramprasath, Tharmarajan; Hamenth Kumar, Palani; Syed Mohamed Puhari, Shanavas; Senthil Murugan, Ponniah; Vasudevan, Varadaraj; Selvam, Govindan Sadasivam

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer L-Arginine treatment reduced the metabolic disturbances in diabetic animals. Black-Right-Pointing-Pointer Antioxidant marker proteins were found high in myocardium by L-arginine treatment. Black-Right-Pointing-Pointer Elevated antioxidant status, mediates the reduced TBA-reactivity in left ventricle. Black-Right-Pointing-Pointer L-Arginine treatment enhanced the Nrf2 and eNOS signaling in left ventricle. Black-Right-Pointing-Pointer Improved cell survival signaling by arginine, offers a novel tactic for targeting. -- Abstract: Hyperglycemia is independently related with excessive morbidity and mortality in cardiovascular disorders. L-Arginine-nitric oxide (NO) pathway and the involvement of NO in modulating nuclear factor-E2-related factor-2 (Nrf2) signaling were well established. In the present study we investigated, whether L-arginine supplementation would improve the myocardial antioxidant defense under hyperglycemia through activation of Nrf2 signaling. Diabetes was induced by alloxan monohydrate (90 mg kg{sup -1} body weight) in rats. Both non-diabetic and diabetic group of rats were divided into three subgroups and they were administered either with L-arginine (2.25%) or L-NAME (0.01%) in drinking water for 12 days. Results showed that L-arginine treatment reduced the metabolic disturbances in diabetic rats. Antioxidant enzymes and glutathione levels were found to be increased in heart left ventricles, thereby reduction of lipid peroxidation by L-arginine treatment. Heart histopathological analysis further validates the reversal of typical diabetic characteristics consisting of alterations in myofibers and myofibrillary degeneration. qRT-PCR studies revealed that L-arginine treatment upregulated the transcription of Akt and downregulated NF-{kappa}B. Notably, transcription of eNOS and Nrf2 target genes was also upregulated, which were accompanied by enhanced expression of Nrf2 in left ventricular tissue from diabetic

  5. Bezafibrate enhances proliferation and differentiation of osteoblastic MC3T3-E1 cells via AMPK and eNOS activation

    PubMed Central

    Zhong, Xing; Xiu, Ling-ling; Wei, Guo-hong; Liu, Yuan-yuan; Su, Lei; Cao, Xiao-pei; Li, Yan-bing; Xiao, Hai-peng

    2011-01-01

    Aim: To investigate the effects of bezafibrate on the proliferation and differentiation of osteoblastic MC3T3-E1 cells, and to determine the signaling pathway underlying the effects. Methods: MC3T3-E1 cells, a mouse osteoblastic cell line, were used. Cell viability and proliferation were examined using MTT assay and colorimetric BrdU incorporation assay, respectively. NO production was evaluated using the Griess reagent. The mRNA expression of ALP, collagen I, osteocalcin, BMP-2, and Runx-2 was measured using real-time PCR. Western blot analysis was used to detect the expression of AMPK and eNOS proteins. Results: Bezafibrate increased the viability and proliferation of MC3T3-E1 cells in a dose- and time-dependent manner. Bezafibrate (100 μmol/L) significantly enhanced osteoblastic mineralization and expression of the differentiation markers ALP, collagen I and osteocalcin. Bezafibrate (100 μmol/L) increased phosphorylation of AMPK and eNOS, which led to an increase of NO production by 4.08-fold, and upregulating BMP-2 and Runx-2 mRNA expression. These effects could be blocked by AMPK inhibitor compound C (5 μmol/L), or the PPARβ inhibitor GSK0660 (0.5 μmol/L), but not by the PPARα inhibitor MK886 (10 μmol/L). Furthermore, GSK0660, compound C, or NG-nitro-L-arginine methyl ester hydrochloride (L-NAME, 1 mmol/L) could reverse the stimulatory effects of bezafibrate (100 μmol/L) on osteoblast proliferation and differentiation, whereas MK886 only inhibited bezafibrate-induced osteoblast proliferation. Conclusion: Bezafibrate stimulates proliferation and differentiation of MC3T3-E1 cells, mainly via a PPARβ-dependent mechanism. The drug might be beneficial for osteoporosis by promoting bone formation. PMID:21499286

  6. Glioblastomas with copy number gains in EGFR and RNF139 show increased expressions of carbonic anhydrase genes transformed by ENO1

    PubMed Central

    Beckner, Marie E.; Pollack, Ian F.; Nordberg, Mary L.; Hamilton, Ronald L.

    2015-01-01

    Background Prominence of glycolysis in glioblastomas may be non-specific or a feature of oncogene-related subgroups (i.e. amplified EGFR, etc.). Relationships between amplified oncogenes and expressions of metabolic genes associated with glycolysis, directly or indirectly via pH, were therefore investigated. Methods Using multiplex ligation-dependent probe amplification, copy numbers (CN) of 78 oncogenes were quantified in 24 glioblastomas. Related expressions of metabolic genes encoding lactate dehydrogenases (LDHA, LDHC), carbonic anhydrases (CA3, CA12), monocarboxylate transporters (SLC16A3 or MCT4, SLC16A4 or MCT5), ATP citrate lyase (ACLY), glycogen synthase1 (GYS1), hypoxia inducible factor-1A (HIF1A), and enolase1 (ENO1) were determined in 22 by RT-qPCR. To obtain supra-glycolytic levels and adjust for heterogeneity, concurrent ENO1 expression was used to mathematically transform the expression levels of metabolic genes already normalized with delta-delta crossing threshold methodology. Results Positive correlations with EGFR occurred for all metabolic genes. Significant differences (Wilcoxon Rank Sum) for oncogene CN gains in tumors of at least 2.00-fold versus less than 2.00-fold occurred for EGFR with CA3's expression (p < 0.03) and for RNF139 with CA12 (p < 0.004). Increased CN of XIAP associated negatively. Tumors with less than 2.00-fold CN gains differed from those with gains for XIAP with CA12 (p < 0.05). Male gender associated with CA12 (p < 0.05). Conclusions Glioblastomas with CN increases in EGFR had elevated CA3 expression. Similarly, tumors with RNF149 CN gains had elevated CA12 expression. General significance In larger studies, subgroups of glioblastomas may emerge according to oncogene-related effects on glycolysis, such as control of pH via effects on carbonic anhydrases, with prognostic and treatment implications. PMID:27051584

  7. Extract from Ribes nigrum leaves in vitro activates nitric oxide synthase (eNOS) and increases CD39 expression in human endothelial cells.

    PubMed

    Luzak, Boguslawa; Boncler, Magdalena; Rywaniak, Joanna; Dudzinska, Dominika; Rozalski, Marek; Krajewska, Urszula; Balcerczak, Ewa; Podsedek, Anna; Redzynia, Malgorzata; Watala, Cezary

    2014-12-01

    The aim of the present study was to evaluate whether blackcurrant leaf extract (BLE) modulates endothelium antithrombotic function, namely increases the expression/activity of ADPase (CD39) and augments the production of nitric oxide in human umbilical vein endothelial cells (HUVEC). It was found that BLE with proanthocyanidins (60 % of the total polyphenol content) increased the CD39-positive endothelial cell fraction (up to 10 % for 2.5 μg/ml, and up to 33 % for 15 μg/ml, p < 0.05 or less) in a concentration-dependent manner, and enhanced endothelial nitric oxide synthase (eNOS) activation (T495 phosphorylation decreased by 31 ± 6 % for 2.5 μg/ml and 48 ± 6 % for 15 μg/ml; S1177 phosphorylation increased by 13 ± 3 % for 2.5 μg/ml and 18 ± 7 % for 15 μg/ml, compared to untreated cells, p < 0.05 or less). Additionally, incubation for 24 or 48 h with BLE at a lower range of polyphenol concentrations, significantly increased cell viability with a maximal effect at 2.5 μg/ml (viability increased by 24.8 ± 1.0 % for 24 h and by 32.5 ± 2.7 % for 48-h time incubation, p < 0.0001). The increased CD39 expression and the increased eNOS activation in HUVEC can be regarded as the beneficial markers of the improvement of antiplatelet action of endothelial cells. Unexpectedly, these assumptions were not confirmed in the experimental model of platelet-endothelial cell interactions. These observations lead to the conclusion that BLE may improve endothelial cell viability at low physiological concentrations without affecting the antiplatelet action of endothelium. PMID:25407137

  8. Allele, Genotype and Haplotype Structures of Functional Polymorphic Variants in Endothelial Nitric Oxide Synthase (eNOS), Angiotensinogen (ACE) and Aldosterone Synthase (CYP11B2) Genes in Healthy Pregnant Women of Indian Ethnicity

    PubMed Central

    Devendran, Anichavezhi; Nampoothiri, Sreekala; Shewade, Deepak Gopal; Chatterjee, Suvro; Jayaraman, Balachandar; Chandrasekharan, Adithan

    2015-01-01

    Background: Variants in the candidate genes eNOS, CYP11B2 and ACE have been implicated as liable biomarkers that can predict complications like hypertension and preeclampsia. Studies on the impact and distribution of these variants on healthy pregnancy have not been done so far in south Indian or in any of the native Indian population. Examining these variants could lay a strong basis in understanding the genetic aspects of preeclampsia and further offer effective means in early risk assessment in a preeclampsia. Methods: Genotyping for 303 unrelated healthy women of Tamilian origin who underwent uncomplicated term pregnancies was executed by PCR-RFLP for eNOS, CYP11B2 and ACE variants. Haplotype assessment and pairwise linkage disequilibrium (LD) investigation were performed by Haploview software. Results: The prevalence of eNOS variants (−786T>C, Glu298Asp and intron 4 VNTR) was 12%, 21.6% and 21.1%, respectively. The incidence of CYP11B2 (−344 C>T) and ACE (287 bp Alu I/D) variants was found to be 43.8% and 42.7%. The observed frequencies of the studied polymorphisms did not diverge from the HWE (p>0.05). Significant LD was observed between 3 eNOS gene polymorphisms. Six different haplotype structures with a frequency of >1% were generated from three eNOS variants. Among the haplotypes generated, the haplotype T-4b-G was the most common with the frequency of 64.4%. There was a statistically significant inconsistency in the study population in comparison to other global races. Conclusion: The outcome of this study could be used for investigating future therapeutic value of the variants in a preeclamptic set-up which could pose a credible diagnostic potential for primary risk assessment of women susceptible to preeclampsia/other pregnancy related complications. PMID:27110515

  9. High order filtering methods for approximating hyberbolic systems of conservation laws

    NASA Technical Reports Server (NTRS)

    Lafon, F.; Osher, S.

    1990-01-01

    In the computation of discontinuous solutions of hyperbolic systems of conservation laws, the recently developed essentially non-oscillatory (ENO) schemes appear to be very useful. However, they are computationally costly compared to simple central difference methods. A filtering method which is developed uses simple central differencing of arbitrarily high order accuracy, except when a novel local test indicates the development of spurious oscillations. At these points, the full ENO apparatus is used, maintaining the high order of accuracy, but removing spurious oscillations. Numerical results indicate the success of the method. High order of accuracy was obtained in regions of smooth flow without spurious oscillations for a wide range of problems and a significant speed up of generally a factor of almost three over the full ENO method.

  10. Ratio of 5,6,7,8-tetrahydrobiopterin to 7,8-dihydrobiopterin in endothelial cells determines glucose-elicited changes in NO vs. superoxide production by eNOS

    PubMed Central

    Crabtree, Mark J.; Smith, Caroline L.; Lam, George; Goligorsky, Michael S.; Gross, Steven S.

    2009-01-01

    5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthases (NOSs). Oxidation of BH4, in the setting of diabetes and other chronic vasoinflammatory conditions, can cause cofactor insufficiency and uncoupling of endothelial NOS (eNOS), manifest by a switch from nitric oxide (NO) to superoxide production. Here we tested the hypothesis that eNOS uncoupling is not simply a consequence of BH4 insufficiency, but rather results from a diminished ratio of BH4 vs. its catalytically incompetent oxidation product, 7,8-dihydrobiopterin (BH2). In support of this hypothesis, [3H]BH4 binding studies revealed that BH4 and BH2 bind eNOS with equal affinity (Kd ≈ 80 nM) and BH2 can rapidly and efficiently replace BH4 in preformed eNOS-BH4 complexes. Whereas the total biopterin pool of murine endothelial cells (ECs) was unaffected by 48-h exposure to diabetic glucose levels (30 mM), BH2 levels increased from undetectable to 40% of total biopterin. This BH2 accumulation was associated with diminished calcium ionophore-evoked NO activity and accelerated superoxide production. Since superoxide production was suppressed by NOS inhibitor treatment, eNOS was implicated as a principal superoxide source. Importantly, BH4 supplementation of ECs (in low and high glucose-containing media) revealed that calcium ionophore-evoked NO bioactivity correlates with intracellular BH4: BH2 and not absolute intracellular levels of BH4. Reciprocally, superoxide production was found to negatively correlate with intracellular BH4:BH2. Hyperglycemia-associated BH4 oxidation and NO insufficiency was recapitulated in vivo, in the Zucker diabetic fatty rat model of type 2 diabetes. Together, these findings implicate diminished intracellular BH4:BH2, rather than BH4 depletion per se, as the molecular trigger for NO insufficiency in diabetes. PMID:18192221

  11. Numerical methods for systems of conservation laws of mixed type using flux splitting

    NASA Technical Reports Server (NTRS)

    Shu, Chi-Wang

    1990-01-01

    The essentially non-oscillatory (ENO) finite difference scheme is applied to systems of conservation laws of mixed hyperbolic-elliptic type. A flux splitting, with the corresponding Jacobi matrices having real and positive/negative eigenvalues, is used. The hyperbolic ENO operator is applied separately. The scheme is numerically tested on the van der Waals equation in fluid dynamics. Convergence was observed with good resolution to weak solutions for various Riemann problems, which are then numerically checked to be admissible as the viscosity-capillarity limits. The interesting phenomena of the shrinking of elliptic regions if they are present in the initial conditions were also observed.

  12. One-sided Post-processing for the Discontinuous Galerkin Method Using ENO Type Stencil Choosing and the Local Edge Detection Method

    SciTech Connect

    Archibald, Richard K; Gelb, Anne; Gottlieb, Sigal; Ryan, Jennifer

    2006-01-01

    In a previous paper by Ryan and Shu [Ryan, J. K., and Shu, C.-W. (2003). Methods Appl. Anal. 10(2), 295-307], a one-sided post-processing technique for the discontinuous Galerkin method was introduced for reconstructing solutions near computational boundaries and discontinuities in the boundaries, as well as for changes in mesh size. This technique requires prior knowledge of the discontinuity location in order to determine whether to use centered, partially one-sided, or one-sided post-processing. We now present two alternative stencil choosing schemes to automate the choice of post-processing stencil. The first is an ENO type stencil choosing procedure, which is designed to choose centered post-processing in smooth regions and one-sided or partially one-sided post-processing near a discontinuity, and the second method is based on the edge detection method designed by Archibald, Gelb, and Yoon [Archibald, R., Gelb, A., and Yoon, J. (2005). SIAM J. Numeric. Anal. 43, 259-279; Archibald, R., Gelb, A., and Yoon, J. (2006). Appl. Numeric. Math. (submitted)]. We compare these stencil choosing techniques and analyze their respective strengths and weaknesses. Finally, the automated stencil choices are applied in conjunction with the appropriate post-processing procedures and it is determine that the resulting numerical solutions are of the correct order.

  13. Ellagic Acid Prevents L-NAME-Induced Hypertension via Restoration of eNOS and p47phox Expression in Rats

    PubMed Central

    Berkban, Thewarid; Boonprom, Pattanapong; Bunbupha, Sarawoot; Umka Welbat, Jariya; Kukongviriyapan, Upa; Kukongviriyapan, Veerapol; Pakdeechote, Poungrat; Prachaney, Parichat

    2015-01-01

    The effect of ellagic acid on oxidative stress and hypertension induced by Nω-Nitro-l-arginine methyl ester hydrochloride (L-NAME) was investigated. Male Sprague-Dawley rats were administrated with L-NAME (40 mg/kg/day) for five weeks. L-NAME induced high systolic blood pressure (SBP) and increased heart rate (HR), hindlimb vascular resistance (HVR) and oxidative stress. Concurrent treatment with ellagic acid (7.5 or 15 mg/kg) prevented these alterations. Co-treatment with ellagic acid was associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein production and alleviation of oxidative stress as indicated by decreased superoxide production in the vascular tissue, reduced plasma malondialdehyde levels, reduced NADPH oxidase subunit p47phox expression and increased plasma nitrate/nitrite levels. Our results indicate that ellagic acid attenuates hypertension by reducing NADPH oxidase subunit p47phox expression, which prevents oxidative stress and restores NO bioavailability. PMID:26133972

  14. BET Bromodomain Suppression Inhibits VEGF-induced Angiogenesis and Vascular Permeability by Blocking VEGFR2-mediated Activation of PAK1 and eNOS

    PubMed Central

    Huang, Mingcheng; Qiu, Qian; Xiao, Youjun; Zeng, Shan; Zhan, Mingying; Shi, Maohua; Zou, Yaoyao; Ye, Yujin; Liang, Liuqin; Yang, Xiuyan; Xu, Hanshi

    2016-01-01

    The tyrosine kinase receptor vascular endothelial growth factor receptor 2 (VEGFR2) is a critical modulator of angiogenesis. Increasing evidence indicate the important role of bromodomain and extra-terminal domain (BET) of chromatin adaptors in regulating tumor growth and inflammatory response. However, whether BET proteins have a role in angiogenesis and endothelial permeability is unclear. In this study, we observed that treatment with JQ1, a specific BET inhibitor, suppressed in vitro tube formation of human umbilical vein endothelial cells (HUVECs) and in vivo angiogenesis in a Matrigel plug and oxygen-induced retinopathy neovascularization. JQ1 attenuated the VEGF-induced decrease in TEER in HUVECs and prevented Evans blue dye leakage in the VEGF-induced Miles assay in athymic Balb/c nude mice. BET inhibition with JQ1 or shRNA for Brd2 or Brd4 suppressed VEGF-induced migration, proliferation, and stress fiber formation of HUVECs. Furthermore, BET inhibition suppressed phosphorylation of VEGFR2 and PAK1, as well as eNOS activation in VEGF-stimulated HUVECs. Inhibition with VEGFR2 and PAK1 also reduced migration and proliferation, and attenuated the VEGF-induced decrease in TEER. Thus, our observations suggest the important role of BET bromodomain in regulating VEGF-induced angiogenesis. Strategies that target the BET bromodomain may provide a new therapeutic approach for angiogenesis-related diseases. PMID:27044328

  15. Disturbance effects of PM₁₀ on iNOS and eNOS mRNA expression levels and antioxidant activity induced by ischemia-reperfusion injury in isolated rat heart: protective role of vanillic acid.

    PubMed

    Dianat, Mahin; Radmanesh, Esmat; Badavi, Mohammad; Mard, Seyed Ali; Goudarzi, Gholamraza

    2016-03-01

    Myocardial infarction is the acute condition of myocardial necrosis that occurs as a result of imbalance between coronary blood supply and myocardial demand. Air pollution increases the risk of death from cardiovascular diseases (CVDs). The aim of this study was to investigate the effects of particulate matter (PM) on oxidative stress, the expression of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) messenger RNA (mRNA) level induced by ischemia-reperfusion injury, and the protective effects of vanillic acid (VA) in the isolated rat heart. Male Wistar rats were randomly divided into eight groups (n = 10), namely control, VAc, sham, VA, PMa (0.5 mg/kg), PMb (2.5 mg/kg), PMc (5 mg/kg), and PMc + VA groups. Particles with an aerodynamic diameter <10 μm (PM10) was instilled into the trachea through a fine intubation tube. Two days following the PM10 instillation, the animal's hearts were isolated and transferred to a Langendorff apparatus. The hearts were subjected to 30 min of global ischemia followed by 60 min of reperfusion. The activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), xanthine oxidase (XOX), and lactate dehydrogenase (LDH) were measured using special kits. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine levels of iNOS and eNOS mRNA. An increase in left ventricular end-diastolic pressure (LVEDP), S-T elevation, and oxidative stress in PM10 groups was observed. Ischemia-reperfusion (I/R) induction showed a significant augment in the expression of iNOS mRNA level and a significant decrease in the expression eNOS mRNA level. This effect was more pronounced in the PM groups than in the control and sham groups. Vanillic acid caused a significant decrease in LVEDP, S-T elevation, and also a significant difference in eNOS mRNA expression level, antioxidant enzymes, iNOS mRNA expression level, and oxidative stress occurred on myocardial dysfunction

  16. The relationship between inflammation and the anticoagulant pathway: the emerging role of endothelial nitric oxide synthase (eNOS).

    PubMed

    Hooper, W Craig

    2004-01-01

    Inflammation represents the interaction of the immune and coagulation systems in an attempt to restore normal hemostasis following injury. The underlying basis of the interrelationship between these two physiological systems revolves around the following: a) the activation of coagulation by inflammation, b) the augmentation of the inflammatory response by coagulation, c) the significant attenuation of inflammation by the anticoagulant response and d) the separate influence of the vascular endothelium on coagulation and inflammation as well as its mediation or control of the cross-talk between these two physiological systems. In hemostasis, the protein C anticoagulant pathway is a major mechanism that functions to prevent the development of a pathological thrombus through the regulation of the procoagulant pathway. The endothelium is essential in maintaining a physiological balance between the anticoagulant and procoagulant pathways with proinflammatory cytokines functioning, in part, to regulate endothelial-cell- surface associated coagulation and anticoagulation proteins. In addition to its anticoagulant properties, activated protein C can also function as a regulator of proinflammatory cytokine production. Current evidence suggests that activated protein C may act to control inflammation through NF-kappaB and/or nitric oxide synthase. A better understanding of the relationship between APC and inflammation may provide new targets for drug design. PMID:15032695

  17. Roles of endothelial nitric oxide synthase (eNOS) and mitochondrial permeability transition pore (MPTP) in epoxyeicosatrienoic acid (EET)-induced cardioprotection against infarction in intact rat hearts.

    PubMed

    Gross, Garrett J; Hsu, Anna; Pfeiffer, Adam W; Nithipatikom, Kasem

    2013-06-01

    We previously demonstrated that 11,12 and 14,15-epoxeicosatrienoic acids (EETs) produce cardioprotection against ischemia-reperfusion injury in dogs and rats. Several signaling mechanisms have been implicated in the cardioprotective actions of the EETs; however, their mechanisms remain largely elusive. Since nitric oxide (NO) plays a significant role in cardioprotection and EETs have been demonstrated to induce NO production in various tissues, we hypothesized that NO is involved in mediating the EET actions in cardioprotection. To test this hypothesis, we used an in vivo rat model of infarction in which intact rat hearts were subjected to 30-min occlusion of the left coronary artery and 2-hr reperfusion. 11,12-EET or 14,15-EET (2.5mg/kg) administered 10min prior to the occlusion reduced infarct size, expressed as a percentage of the AAR (IS/AAR), from 63.9±0.8% (control) to 45.3±1.2% and 45.5±1.7%, respectively. A nonselective nitric oxide synthase (NOS) inhibitor, L-NAME (1.0mg/kg) or a selective endothelial NOS inhibitor, L-NIO (0.30mg/kg) alone did not affect IS/AAR but they completely abolished the cardioprotective effects of the EETs. On the other hand, a selective neuronal NOS inhibitor, nNOS I (0.03mg/kg) and a selective inducible NOS inhibitor, 1400W (0.10mg/kg) did not affect IS/AAR or block the cardioprotective effects of the EETs. Administration of 11,12-EET (2.5mg/kg) to the rats also transiently increased the plasma NO concentration. 14,15-EET (10μM) induced the phosphorylation of eNOS (Ser(1177)) as well as a transient increase of NO production in rat cardiomyoblast cell line (H9c2 cells). When 11,12-EET or 14,15-EET was administered at 5min prior to reperfusion, infarct size was also reduced to 42.8±2.2% and 42.6±1.9%, respectively. Interestingly, L-NAME (1.0mg/kg) and a mitochondrial KATP channel blocker, 5-HD (10mg/kg) did not abolish while a sarcolemmal KATP channel blocker, HMR 1098 (6.0mg/kg) and a mitochondrial permeability transition

  18. MicroRNA-27b plays a role in pulmonary arterial hypertension by modulating peroxisome proliferator-activated receptor γ dependent Hsp90-eNOS signaling and nitric oxide production

    SciTech Connect

    Bi, Rui; Bao, Chunrong; Jiang, Lianyong; Liu, Hao; Yang, Yang; Mei, Ju; Ding, Fangbao

    2015-05-01

    Pulmonary artery endothelial dysfunction is associated with pulmonary arterial hypertension (PAH). Based on recent studies showing that microRNA (miR)-27b is aberrantly expressed in PAH, we hypothesized that miR-27b may contribute to pulmonary endothelial dysfunction and vascular remodeling in PAH. The effect of miR-27b on pulmonary endothelial dysfunction and the underlying mechanism were investigated in human pulmonary artery endothelial cells (HPAECs) in vitro and in a monocrotaline (MCT)-induced model of PAH in vivo. miR-27b expression was upregulated in MCT-induced PAH and inversely correlated with the levels of peroxisome proliferator-activated receptor (PPAR)-γ, and miR-27b inhibition attenuated MCT-induced endothelial dysfunction and remodeling and prevented PAH associated right ventricular hypertrophy and systolic pressure in rats. PPARγ was confirmed as a direct target of miR-27b in HPAECs and shown to mediate the effect of miR-27b on the disruption of endothelial nitric oxide synthase (eNOS) coupling to Hsp90 and the suppression of NO production associated with the PAH phenotype. We showed that miR-27b plays a role endothelial function and NO release and elucidated a potential mechanism by which miR-27b regulates Hsp90-eNOS and NO signaling by modulating PPARγ expression, providing potential therapeutic targets for the treatment of PAH. - Highlights: • miR-27b plays a role in endothelial function and NO release. • miR-27b inhibition ameliorates MCT-induced endothelial dysfunction and PAH. • miR-27b targets PPARγ in HPAECs. • miR-27b regulates PPARγ dependent Hsp90-eNOS and NO signaling.

  19. Genome-wide association study using a high-density SNP-array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of eNOS

    PubMed Central

    Salvi, Erika; Kutalik, Zoltán; Glorioso, Nicola; Benaglio, Paola; Frau, Francesca; Kuznetsova, Tatiana; Arima, Hisatomi; Hoggart, Clive; Tichet, Jean; Nikitin, Yury P.; Conti, Costanza; Seidlerova, Jitka; Tikhonoff, Valérie; Stolarz-Skrzypek, Katarzyna; Johnson, Toby; Devos, Nabila; Zagato, Laura; Guarrera, Simonetta; Zaninello, Roberta; Calabria, Andrea; Stancanelli, Benedetta; Troffa, Chiara; Thijs, Lutgarde; Rizzi, Federica; Simonova, Galina; Lupoli, Sara; Argiolas, Giuseppe; Braga, Daniele; D’Alessio, Maria C.; Ortu, Maria F.; Ricceri, Fulvio; Mercurio, Maurizio; Descombes, Patrick; Marconi, Maurizio; Chalmers, John; Harrap, Stephen; Filipovsky, Jan; Bochud, Murielle; Iacoviello, Licia; Ellis, Justine; Stanton, Alice V.; Laan, Maris; Padmanabhan, Sandosh; Dominiczak, Anna F.; Samani, Nilesh J.; Melander, Olle; Jeunemaitre, Xavier; Manunta, Paolo; Shabo, Amnon; Vineis, Paolo; Cappuccio, Francesco P.; Caulfield, Mark J.; Matullo, Giuseppe; Rivolta, Carlo; Munroe, Patricia B.; Barlassina, Cristina; Staessen, Jan A; Beckmann, Jacques S.; Cusi, Daniele

    2012-01-01

    Essential hypertension is a multi-factorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a two-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1,865 cases and 1,750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1,385 cases and 1,246 controls that were genotyped with a custom array of 14,055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial nitric oxide synthase (eNOS) gene (odds ratio 1.54; 95% CI 1.37-1.73; combined p=2.58·10−13). A meta-analysis, using other in-silico/de novo genotyping data for a total of 21714 subjects, resulted in an overall odds ratio of 1.34 (95% CI 1.25-1.44, p=1.032·10−14). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI 0.16-3.66) for systolic and 1.40 (95% CI 0.25-2.55) for diastolic blood pressure. We identified in-silico a potential binding site for ETS transcription-factors directly next to rs3918226, suggesting a potential modulation of eNOS expression. Biological evidence links eNOS with hypertension, as it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus. PMID:22184326

  20. High-order central ENO finite-volume scheme for hyperbolic conservation laws on three-dimensional cubed-sphere grids

    NASA Astrophysics Data System (ADS)

    Ivan, L.; De Sterck, H.; Susanto, A.; Groth, C. P. T.

    2015-02-01

    A fourth-order accurate finite-volume scheme for hyperbolic conservation laws on three-dimensional (3D) cubed-sphere grids is described. The approach is based on a central essentially non-oscillatory (CENO) finite-volume method that was recently introduced for two-dimensional compressible flows and is extended to 3D geometries with structured hexahedral grids. Cubed-sphere grids feature hexahedral cells with nonplanar cell surfaces, which are handled with high-order accuracy using trilinear geometry representations in the proposed approach. Varying stencil sizes and slope discontinuities in grid lines occur at the boundaries and corners of the six sectors of the cubed-sphere grid where the grid topology is unstructured, and these difficulties are handled naturally with high-order accuracy by the multidimensional least-squares based 3D CENO reconstruction with overdetermined stencils. A rotation-based mechanism is introduced to automatically select appropriate smaller stencils at degenerate block boundaries, where fewer ghost cells are available and the grid topology changes, requiring stencils to be modified. Combining these building blocks results in a finite-volume discretization for conservation laws on 3D cubed-sphere grids that is uniformly high-order accurate in all three grid directions. While solution-adaptivity is natural in the multi-block setting of our code, high-order accurate adaptive refinement on cubed-sphere grids is not pursued in this paper. The 3D CENO scheme is an accurate and robust solution method for hyperbolic conservation laws on general hexahedral grids that is attractive because it is inherently multidimensional by employing a K-exact overdetermined reconstruction scheme, and it avoids the complexity of considering multiple non-central stencil configurations that characterizes traditional ENO schemes. Extensive numerical tests demonstrate fourth-order convergence for stationary and time-dependent Euler and magnetohydrodynamic flows on

  1. Assessing Library Automation and Virtual Library Development in Four Academic Libraries in Oyo, Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Gbadamosi, Belau Olatunde

    2011-01-01

    The paper examines the level of library automation and virtual library development in four academic libraries. A validated questionnaire was used to capture the responses from academic librarians of the libraries under study. The paper discovers that none of the four academic libraries is fully automated. The libraries make use of librarians with…

  2. Altered Nitric Oxide System in Cardiovascular and Renal Diseases

    PubMed Central

    Bae, Eun Hui; Ma, Seong Kwon; Kim, Soo Wan

    2016-01-01

    Nitric oxide (NO) is synthesized by a family of NO synthases (NOS), including neuronal, inducible, and endothelial NOS (n/i/eNOS). NO-mediated effects can be beneficial or harmful depending on the specific risk factors affecting the disease. In hypertension, the vascular relaxation response to acetylcholine is blunted, and that to direct NO donors is maintained. A reduction in the activity of eNOS is mainly responsible for the elevation of blood pressure, and an abnormal expression of iNOS is likely to be related to the progression of vascular dysfunction. While eNOS/nNOS-derived NO is protective against the development of atherosclerosis, iNOS-derived NO may be proatherogenic. eNOS-derived NO may prevent the progression of myocardial infarction. Myocardial ischemia/reperfusion injury is significantly enhanced in eNOS-deficient animals. An important component of heart failure is the loss of coronary vascular eNOS activity. A pressure-overload may cause severer left ventricular hypertrophy and dysfunction in eNOS null mice than in wild-type mice. iNOS-derived NO has detrimental effects on the myocardium. NO plays an important role in regulating the angiogenesis and slowing the interstitial fibrosis of the obstructed kidney. In unilateral ureteral obstruction, the expression of eNOS was decreased in the affected kidney. In triply n/i/eNOS null mice, nephrogenic diabetes insipidus developed along with reduced aquaporin-2 abundance. In chronic kidney disease model of subtotal-nephrectomized rats, treatment with NOS inhibitors decreased systemic NO production and induced left ventricular systolic dysfunction (renocardiac syndrome). PMID:27231671

  3. Mechanistic link between erectile dysfunction and systemic endothelial dysfunction in type 2 diabetic rats.

    PubMed

    Musicki, B; Hannan, J L; Lagoda, G; Bivalacqua, T J; Burnett, A L

    2016-09-01

    Men with type 2 diabetes mellitus (T2DM) and erectile dysfunction (ED) have greater risk of cardiovascular events than T2DM men without ED, suggesting ED as a predictor of cardiovascular events in diabetic men. However, molecular mechanisms underlying endothelial dysfunction in the diabetic penis explaining these clinical observations are not known. We evaluated whether the temporal relationship between ED and endothelial dysfunction in the systemic vasculature in T2DM involves earlier redox imbalance and endothelial nitric oxidase synthase (eNOS) dysfunction in the penis than in the systemic vasculature, such as the carotid artery. Rats were rendered T2DM by high-fat diet for 2 weeks, followed by an injection with low-dose streptozotocin. After 3 weeks, erectile function (intracavernosal pressure) was measured and penes and carotid arteries were collected for molecular analyses of eNOS uncoupling, protein S-glutathionylation, oxidative stress (4-hydroxy-2-nonenal, 4-HNE), protein expression of NADPH oxidase subunit gp91(phox) , endothelium-dependent vasodilation in the carotid artery, and non-adrenergic, non-cholinergic (NANC)-mediated cavernosal relaxation. Erectile response to electrical stimulation of the cavernous nerve and NANC-mediated cavernosal relaxation was decreased (p < 0.05), while relaxation of the carotid artery to acetylcholine was not impaired in T2DM rats. eNOS monomerization, protein expressions of 4-HNE and gp91(phox) , and protein S-glutathionylation, were increased (p < 0.05) in the penis, but not in the carotid artery, of T2DM compared to non-diabetic rats. In conclusion, redox imbalance, increased oxidative stress by NADPH oxidase, and eNOS uncoupling, occur early in T2DM in the penis, but not in the carotid artery. These molecular changes contribute to T2DM ED, while vascular function in the systemic vasculature remains preserved. PMID:27153512

  4. NF-κB activation was involved in reactive oxygen species-mediated apoptosis and autophagy in 1-oxoeudesm-11(13)-eno-12,8α-lactone-treated human lung cancer cells.

    PubMed

    Liu, Shanshan; Wu, Di; Li, Lin; Sun, Xiao; Xie, Weidong; Li, Xia

    2014-08-01

    1-oxoeudesm-11(13)-eno-12,8α-lactone (OEL), a novel eudesmane-type sesquiterpene compound, has been shown to inhibit the growth of some cancer cell lines and induce significant apoptosis. Here, we investigated the anti-cancer activities of OEL in human lung cancer cells. Our studies demonstrated that OEL induced both apoptosis and autophagy in A549 and H460 cells. OEL-induced autophagy was assessed by appearance of autophagic vacuoles, formation of acidic vesicular organelles, conversion of LC3-I to LC3-II, recruitment of LC3-II to the autophagosomes, and activation of autophagy genes. Furthermore, administration of autophagic inhibitor 3-methyladenine augments OEL-induced apoptotic cell death. The induction of autophagy and apoptosis by OEL links to NF-κB activation and the generation of reactive oxygen species (ROS). Interruption of NF-κB activation by specific inhibitor promotes apoptosis, but decreases autophagy. ROS antioxidants (N-acetylcysteine) attenuated both OEL-induced autophagy and apoptosis. Further experiments confirmed that OEL-induced activation of ROS was increased by NF-κB inhibitor whereas NF-κB activation was not affected by ROS inhibition. These findings suggest that OEL-elicited autophagic response plays a protective role that impedes cell death, and inhibition of autophagy could be an adjunctive strategy for enhancing the chemotherapeutic effect of OEL as an antitumor agent. PMID:24194260

  5. A multilevel prediction of physiological response to challenge: Interactions among child maltreatment, neighborhood crime, endothelial nitric oxide synthase gene (eNOS), and GABA(A) receptor subunit alpha-6 gene (GABRA6).

    PubMed

    Lynch, Michael; Manly, Jody Todd; Cicchetti, Dante

    2015-11-01

    Physiological response to stress has been linked to a variety of healthy and pathological conditions. The current study conducted a multilevel examination of interactions among environmental toxins (i.e., neighborhood crime and child maltreatment) and specific genetic polymorphisms of the endothelial nitric oxide synthase gene (eNOS) and GABA(A) receptor subunit alpha-6 gene (GABRA6). One hundred eighty-six children were recruited at age 4. The presence or absence of child maltreatment as well as the amount of crime that occurred in their neighborhood during the previous year were determined at that time. At age 9, the children were brought to the lab, where their physiological response to a cognitive challenge (i.e., change in the amplitude of the respiratory sinus arrhythmia) was assessed and DNA samples were collected for subsequent genotyping. The results confirmed that complex Gene × Gene, Environment × Environment, and Gene × Environment interactions were associated with different patterns of respiratory sinus arrhythmia reactivity. The implications for future research and evidence-based intervention are discussed. PMID:26535938

  6. Meiji shoki no kyoiku seisaku to chiho eno teichaku (Educational Policies and Their Localization in the Earlier Years of the Meiji).

    ERIC Educational Resources Information Center

    Naka, Arita

    This document is an English-language abstract (approximately 1,500 words) of a history of education during the Meiji period in Japan. Gakusei was the first school code, passed in 1872; it created Japan's first system of modern education. The study deals with the relations between the educational policies of the central government and the actual…

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

    PubMed

    Wheatley, Carmen

    2007-09-01

    The up-regulation of transcobalamins [hitherto posited as indicating a central need for cobalamin (Cbl) in inflammation], whose expression, like inducible nitric oxide synthase (iNOS), is Sp1- and interferondependent, together with increased intracellular formation of glutathionylcobalamin (GSCbl), adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), may be essential for the timely promotion and later selective inhibition of iNOS and concordant regulation of endothelial and neuronal NOS (eNOS/nNOS.) Cbl may ensure controlled high output of nitric oxide (NO) and its safe deployment, because: (1) Cbl is ultimately responsible for the synthesis or availability of the NOS substrates and cofactors heme, arginine, BH(4) flavin adenine dinucleotide/flavin mononucleotide (FAD/FMN) and NADPH, via the far-reaching effects of the two Cbl coenzymes, methionine synthase (MS) and methylmalonyl CoA mutase (MCoAM) in, or on, the folate, glutathione, tricarboxylic acid (TCA) and urea cycles, oxidative phosphorylation, glycolysis and the pentose phosphate pathway. Deficiency of any of theNOS substrates and cofactors results in 'uncoupled' NOS reactions, decreasedNO production and increased or excessive O(2) (-), H(2)O(2), ONOO(-) and other reactive oxygen species (ROS), reactive nitric oxide species (RNIS) leading to pathology. (2) Cbl is also the overlooked ultimate determinant of positive glutathione status, which favours the formation of more benign NO species, s-nitrosothiols, the predominant form in which NO is safely deployed. Cbl status may consequently act as a 'back-up disc' that ensures the active status of antioxidant systems, as well as reversing and modulating the effects of nitrosylation in cell signal transduction.New evidence shows that GSCbl can significantly promote iNOS/ eNOS NO synthesis in the early stages of inflammation, thus lowering high levels of tumour necrosis factor-a that normally result in pathology, while existing evidence shows that in extreme

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

    PubMed Central

    Wheatley, Carmen

    2007-01-01

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

  9. Effect of dietary arginine and N-carbamoylglutamate supplementation on reproduction and gene expression of eNOS, VEGFA and PlGF1 in placenta in late pregnancy of sows.

    PubMed

    Wu, X; Yin, Y L; Liu, Y Q; Liu, X D; Liu, Z Q; Li, T J; Huang, R L; Ruan, Z; Deng, Z Y

    2012-06-01

    The objectives of this study were to investigate the potential mechanisms of dietary arginine (Arg) and N-carbamoylglutamate (NCG) supplementation on reproductive performance of sows. Twenty-seven crossbred (Landrace×Large White) sows with similar body weight and parity at day (90±1) of gestation were assigned randomly into 3 groups (n=9) control group, Arg group, NCG group, and fed with the following diets: a control diet, and the control diet supplemented with 1.0% Arg or 0.1% NCG. Litter size was recorded. Blood samples were obtained for biochemical analyses. Placenta chorioallantoic membrane tissue collected immediately after birth to preserve in RNA stabilizer for mRNA analysis of endothelial nitric oxide synthase (eNOS), endothelial growth factor a (VEGFA) and placenta growth factor 1 (PlGF1) by real time-PCR. The results showed that compared with the control group, the average birth weight of all piglets born alive were 16.2% and 14.3% higher in the Arg and NCG groups (P<0.05), respectively; plasma VEGFA was higher in the Arg group (P<0.05). The expression of VEGFA in the allantochorion tissue of the NCG-supplemented group was higher (P<0.01), and tended to be higher in the Arg-supplemented group (0.05

  10. In Vitro Activation of eNOS by Mangifera indica (Careless™) and Determination of an Effective Dosage in a Randomized, Double-Blind, Human Pilot Study on Microcirculation.

    PubMed

    Gerstgrasser, Alexandra; Röchter, Sigrid; Dressler, Dirk; Schön, Christiane; Reule, Claudia; Buchwald-Werner, Sybille

    2016-03-01

    Mangifera indica fruit preparation (Careless™) activates the evolutionary conserved metabolic sensors sirtuin 1 and adenosine monophosphate-activated protein kinase, which have been identified as playing a key role in microcirculation and endothelial function. Here, an acute effect of a single dose of 100 mg or 300 mg Careless™ on microcirculation was investigated in a randomized, double-blind, crossover pilot study in ten healthy women to determine the effective dosage. Microcirculation and endothelial function were assessed by the Oxygen-to-see system and pulse amplitude tonometry (EndoPAT™), respectively. Cutaneous blood flow was increased over time by 100 mg (54% over pre-values, p = 0.0157) and 300 mg (35% over pre-value, p = 0.209) Careless™. The EndoPAT™ reactive hyperemia response was slightly improved 3 h after intake compared to pretesting with 300 mg Careless™. Furthermore, activation of endothelial nitric oxide synthase, as an important regulator for endothelial function, was tested in vitro in primary human umbilical vein endothelial cells. Careless™, after simulation of digestion, increased the activated form of endothelial nitric oxide synthase dose-dependently by 23% (300 µg/mL), 42% (1500 µg/mL), and 60% (3000 µg/mL) compared to the untreated control. In conclusion, the study suggests moderate beneficial effects of Careless™ on microcirculation, which is at least partly mediated by endothelial nitric oxide synthase activation. PMID:26584454

  11. Effects of tyrosine kinase inhibitor E7080 and eNOS inhibitor L-NIO on colorectal cancer alone and in combination

    PubMed Central

    Temiz, Tijen Kaya; Balcı, Ezgi; Polat, Zübeyde Akın; Turan, Mustafa

    2013-01-01

    Objective To investigate the effects of E7080 and N5-(1-iminoethyl)-L-ornithine dihydrochloride (L-NIO) on colorectal cancer alone and in combination. Methods HT29 colorectal cancer cell line from Sap Institute was used. Real-time cell analysis (xCELLigence system) was performed to determine the effects of E7080 and L-NIO on colorectal cell proliferation. While apoptosis was determined with Annexin V staining, and the effect of agents on angiogenesis was determined with chorioallantoic membrane (CAM) model. Results We found that E7080 has a strong antiproliferative effect with an half maximum inhibition of concentration (IC50) value of 5.60×10–8 mol/L. Also it has been observed that E7080 showed antiangiogenic and apoptotic effects on HT29 colorectal cancer cells. Antiangiogenic scores of E7080 were 1.2, 1.0 and 0.6 for 100, 10 and 1 nmol/L E7080 concentrations, respectively. Furthermore, apoptosis has been detected in 71% of HT29 colorectal cancer cells after administration of 100 nmol/L E7080 which may indicate strong apoptotic effect. Meanwhile administration of L-NIO alone did not show any effect, but the combination of E7080 with L-NIO increased the antiproliferative, antiangiogenic and apoptotic effects of E7080. Conclusions Results of this study indicate that E7080 may be a good choice in treatment of colorectal tumors. Furthermore the increased effects of E7080 when combined with L-NIO raise the possibility to use a lower dose of E7080 and therefore avoid/minimize the side effects observed with E7080. PMID:24255582

  12. Highly efficient biodiesel production by a whole-cell biocatalyst employing a system with high lipase expression in Aspergillus oryzae.

    PubMed

    Takaya, Tomohiro; Koda, Risa; Adachi, Daisuke; Nakashima, Kazunori; Wada, Junpei; Bogaki, Takayuki; Ogino, Chiaki; Kondo, Akihiko

    2011-05-01

    In the present study, a system with high lipase expression in Aspergillus oryzae was developed using an improved enolase promoter (P-enoA124) and the 5' untranslated region of a heat-shock protein (Hsp-UTR). P-enoA142 enhanced the transcriptional level of a heterologous lipase gene and Hsp-UTR improved its translational efficiency. Fusarium heterosporum lipase (FHL) was inserted into a pSENSU-FHL expression vector harboring P-enoA142 and Hsp-UTR and was transformed into an A. oryzae NS4 strain. Transformants possessing pSENSU-FHL in single (pSENSU-FHL#1) and double copies (pSENSU-FHL#2) were selected to evaluate the lipase activity of the whole-cell biocatalyst. The two strains, pSENSU-FHL#1 and #2, showed excellent lipase activity in hydrolysis compared with the strain transformed with conventional expression vector pNAN8142-FHL. Furthermore, by using pSENSU-FHL#2, methanolysis could proceed much more effectively without deactivation, which allowed a swift addition of methanol to the reaction mixture, thereby reducing reaction time. PMID:21380514

  13. AAR in concrete of Asejire spillway (OYO state - Nigeria)

    SciTech Connect

    Lamaudiere, J.P.; Spaeti, F.

    1995-12-31

    The Asejire dam at Ibadan, Nigeria was constructed in the late sixties for the purpose of providing water for the city of Ibadan (presently about 4,5 million inhabitants). It is located on the Oshun river approximately fifteen miles from the city. In 1982 cracks were observed on the wing walls and although these continued to develop, no attempt was made at that time to investigate their causes and no repair was carried out. In 1989 the SGI ENGINEERING Group of Geneva, Switzerland was appointed as the consultant for the complete refurbishment of the Asejire water scheme. The consortium Degremont-Poat-Clemessy was awarded the contract for the project. The African Development Bank and the Nigerian Government have provided the loan to finance the project.

  14. Entrepreneurship Education and Graduates Unemployment in Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Emunemu, B. O.; Kasali, O. J.

    2014-01-01

    This study investigated entrepreneurship and graduates' unemployment in Nigeria.The problem of unemployment in Nigeria has become endemic. There have been reported cases of under-employment, seasonal, casual and full blown unemployment. Previous studies on unemployment and factors influencing it in Nigeria identify poor educational standards,…

  15. Optimal design and control strategies for novel combined heat and power (CHP) fuel cell systems. Part I of II, datum design conditions and approach.

    SciTech Connect

    Colella, Whitney G.

    2010-06-01

    Energy network optimization (ENO) models identify new strategies for designing, installing, and controlling stationary combined heat and power (CHP) fuel cell systems (FCSs) with the goals of (1) minimizing electricity and heating costs for building owners and (2) reducing emissions of the primary greenhouse gas (GHG) - carbon dioxide (CO{sub 2}). A goal of this work is to employ relatively inexpensive simulation studies to discover more financially and environmentally effective approaches for installing CHP FCSs. ENO models quantify the impact of different choices made by power generation operators, FCS manufacturers, building owners, and governments with respect to two primary goals - energy cost savings for building owners and CO{sub 2} emission reductions. These types of models are crucial for identifying cost and CO{sub 2} optima for particular installations. Optimal strategies change with varying economic and environmental conditions, FCS performance, the characteristics of building demand for electricity and heat, and many other factors. ENO models evaluate both 'business-as-usual' and novel FCS operating strategies. For the scenarios examined here, relative to a base case of no FCSs installed, model results indicate that novel strategies could reduce building energy costs by 25% and CO{sub 2} emissions by 80%. Part I of II articles discusses model assumptions and methodology. Part II of II articles illustrates model results for a university campus town and generalizes these results for diverse communities.

  16. Antidepressant action via the nitric oxide system: A pilot study in an acute depressive model induced by arginin.

    PubMed

    Yoshino, Yuta; Ochi, Shinichiro; Yamazaki, Kiyohiro; Nakata, Shunsuke; Abe, Masao; Mori, Yoko; Ueno, Shu-ichi

    2015-07-10

    Nitric oxide (NO) may be a neurotransmitter related to major depressive disorder (MDD) because the selective neuronal NO synthase (NOS) inhibitor, 7-nitroindazole, induces dose-dependent antidepressant-like effects. However, its role in MDD is not yet known. The purpose of our study was to determine if antidepressants improve depression via the NO pathway using an acute depressive rat model induced by L-arginine (AR). Three types of antidepressants were examined, fluoxetine (FLX, 10 mg/kg), milnacipran (MIL, 30 mg/kg), and mirtazapine (MIR, 10 mg/kg), in a depressive model that used AR (750 mg/kg) pretreatment. mRNA expression levels of three NOS subtypes were analyzed by real-time PCR, as well as serum NO levels. Significant increases in iNOS mRNA expression levels were found in brain regions after AR treatment, although the eNOS gene tended to decrease with AR injection. After antidepressant treatment, there were no mRNA expression changes in either nNOS or iNOS. However, eNOS mRNA expression significantly increased with FLX (cerebellum, P=0.011; hippocampus, P=0.011; midbrain, P=0.011; pons, P=0.013; striatum, P=0.011; and thalamus, P<0.001). There was a statistically significant increase in serum NO levels with MIL treatment (P=0.011). We conclude that changes in eNOS mRNA levels in the brain with FLX treatment, and amount of serum NO with MIL treatment may be related to antidepressant effects of both agents, but further experiments are needed to confirm involvement of the NO system in MDD. PMID:26007704

  17. The endothelial nitric oxide synthase/nitric oxide system is involved in the defective quality of bovine oocytes from low mid-antral follicle count ovaries.

    PubMed

    Tessaro, I; Luciano, A M; Franciosi, F; Lodde, V; Corbani, D; Modina, S C

    2011-08-01

    In a previous survey concerning cows of reproductive age, we demonstrated that oocytes isolated from ovaries with <10 medium antral follicles of 2 to 6 mm in diameter (low ovaries; Lo) show less developmental competence than oocytes collected from ovaries with >10 medium antral follicles (high ovaries; Hi). The aim of the present study was to evaluate whether a defective endothelial nitric oxide synthase/nitric oxide (eNOS/NO) system and vasculature in healthy medium antral follicles is likely to reduce oocyte competence from Lo ovaries. Thus, experiments were conducted to 1) immunolocalize eNOS protein during folliculogenesis; 2) quantify eNOS protein/vasculature in the follicle wall; and 3) verify if NO donor, S-nitroso acetyl penicillamine (SNAP) administration during in vitro maturation affects developmental competence of oocytes isolated from Lo ovaries. Endothelial nitric oxide synthase protein was detected in granulosa and theca cells, as well as in blood vessels from primordial to antral follicles. Quantitative analysis indicated that in medium antral follicles from Lo ovaries, eNOS protein expression and vasculature were reduced (P < 0.05). The addition of SNAP improved blastocyst and hatching rates of oocytes from Lo ovaries, promoting a percentage similar to oocytes from Hi ovaries, and reduced the percentage of apoptotic nuclei in in vitro-produced blastocysts (P < 0.05). Results from our study suggest that in bovine ovaries with small mid antral follicle number, a defective eNOS/NO system is related to a reduced follicle vasculature and may affect oocyte quality, thus inducing a premature decline of fertility. PMID:21421835

  18. Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation.

    PubMed

    Davel, Ana Paula; Lemos, Miriam; Pastro, Luciana Manfré; Pedro, Sibelli Cosme; de André, Paulo Afonso; Hebeda, Cristina; Farsky, Sandra Helena; Saldiva, Paulo Hilário; Rossoni, Luciana Venturini

    2012-05-16

    Clinical evidence has identified the pulmonary circulation as an important target of air pollution. It was previously demonstrated that in vitro exposure to fine particulate matter (aerodynamic diameter≤2.5 μm, PM2.5) induces endothelial dysfunction in isolated pulmonary arteries. We aimed to investigate the effects of in vivo exposure to urban concentrated PM2.5 on rat pulmonary artery reactivity and the mechanisms involved. For this, adult Wistar rats were exposed to 2 weeks of concentrated São Paulo city air PM2.5 at an accumulated daily dose of approximately 600 μg/m3. Pulmonary arteries isolated from PM2.5-exposed animals exhibited impaired endothelium-dependent relaxation to acetylcholine without significant changes in nitric oxide donor response compared to control rats. PM2.5 caused vascular oxidative stress and enhanced protein expression of Cu/Zn- and Mn-superoxide dismutase in the pulmonary artery. Protein expression of endothelial nitric oxide synthase (eNOS) was reduced, while tumor necrosis factor (TNF)-α was enhanced by PM2.5 inhalation in pulmonary artery. There was a significant positive correlation between eNOS expression and maximal relaxation response (Emax) to acetylcholine. A negative correlation was found between vascular TNF-α expression and Emax to acetylcholine. Plasma cytokine levels, blood cells count and coagulation parameters were similar between control and PM2.5-exposed rats. The present findings showed that in vivo daily exposure to concentrated urban PM2.5 could decrease endothelium-dependent relaxation and eNOS expression on pulmonary arteries associated with local high TNF-α level but not systemic pro-inflammatory factors. Taken together, the present results elucidate the mechanisms underlying the trigger of cardiopulmonary diseases induced by urban ambient levels of PM2.5. PMID:22361244

  19. VANADYL SULFATE INHIBITS NO PRODUCTION VIA THREONINE PHOSPHORYLATION OF ENOS

    EPA Science Inventory

    Exposure to excessive vanadium (V) occurs in some occupations and with consumption of some dietary regimens for weight reduction and body-building. Because vanadium is vasoactive, individuals exposed to excessive V may develop adverse vascular effects. We showed previously that v...

  20. The placental cholinergic system: localization to the cytotrophoblast and modulation of nitric oxide

    PubMed Central

    Bhuiyan, Md Badiul; Murad, Ferid; Fant, Michael E

    2006-01-01

    Background The human placenta, a non-neuronal tissue, contains an active cholinergic system comprised of acetylcholine (ACh), choline acetyltransferase (ChAT), acetylcholinesterase (AChE), and high affinity muscarinic receptors. The cell(s) of origin of placental ACh and its role in trophoblast function has not been defined. These studies were performed to define the cellular location of ACh synthesis (ChAT) in the human placenta and to begin studying its functional role. Results Using immunohistochemical techniques, ChAT was observed primarily within the cytotrophoblasts of preterm placentae as well as some mesenchymal elements. Similar intense immunostaining of the cytotrophoblast was observed for endothelium-derived nitric oxide synthase (eNOS) suggesting that ACh may interact with nitric oxide (NO)-dependent signaling pathways. The ability of carbamylcholine (CCh), an ACh analogue, to stimulate a rise in intracellular Ca++ and NO production in trophoblasts was therefore tested using the BeWob30 choriocarcinoma cell as a model system. First, CCh significantly increased intracellular calcium as assessed by fluorescence microscopy. We then examined the ability of CCh to stimulate NO production by measuring total nitrite/nitrate production in conditioned media using chemiluminescence-based analysis. CCh, alone, had no effect on NO production. However, CCh increased measurable NO approximately 100% in the presence of 10 nM estradiol. This stimulatory effect was inhibited by 1 (micro)M scopolamine suggesting mediation via muscarinic receptors. Estradiol, alone, had no effect on total NO or eNOS protein or mRNA. Conclusion These data demonstrate that placental ChAT localizes to the cytotrophoblast and some mesenchymal cells in human placenta. It further suggests that ACh acts via muscarinic receptors on the trophoblast cell membrane to modulate NO in an estrogen-dependent manner. PMID:16686954

  1. Parents and Teachers' Knowledge of Violent Disciplinary Practices against Secondary School Students in Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Omoyemiju, M. A.; Ojo, O. O.; Olatomide, O. O.

    2015-01-01

    The study investigated the Violent Disciplinary Practices (VDP) perpetrated by parents and by teachers against secondary schools students. The study adopted a descriptive survey research design. Six hundred and sixteen participants comprising 336 and 280 parents and teachers, respectively, were selected to participate in the study. Two instruments…

  2. Microbiological Safety Assessment of Fermented Cassava Flour "Lafun" Available in Ogun and Oyo States of Nigeria.

    PubMed

    Adebayo-Oyetoro, A O; Oyewole, O B; Obadina, A O; Omemu, M A

    2013-01-01

    The microorganisms involved in the fermentation and spoilage of fermented cassava flour were investigated. The water samples used at the different processing sites were also investigated to determine their safety status. There was predominance of Staphylococcus aureus, Aspergillus spp., and Escherichia coli in all samples. Coliforms were observed to be present in all of the processing water. In the fermented cassava flour, the total bacterial count ranged between 4.9 × 10(6) cfu/mL from Eleso, Bakatari, and Oja Odan processing sites and 8.10 × 10(6) cfu/mL in Eruku processing site. The majority of the microorganisms involved in the spoilage of "lafun" were found to be Aspergillus niger which ranged between 4.6 × 10(5) cfu/mL in Eleso and 8.1 × 10(5) cfu/mL in Kila. The control sample prepared in the laboratory had a low microbial load compared to samples collected from various sites and markets. PMID:26904609

  3. Functional role of connexins and pannexins in the interaction between vascular and nervous system.

    PubMed

    Gaete, Pablo S; Lillo, Mauricio A; Figueroa, Xavier F

    2014-10-01

    The microvascular network of the microcirculation works in tight communication with surrounding tissues to control blood supply and exchange of solutes. In cerebral circulation, microvascular endothelial cells constitute a selective permeability barrier that controls the environment of parenchymal brain tissue, which is known as the blood-brain barrier (BBB). Connexin- and pannexin-formed channels (gap junctions and hemichannels) play a central role in the coordination of endothelial and smooth muscle cell function and connexin-mediated signaling in endothelial cells is essential in the regulation of BBB permeability. Likewise, gap junction communication between astrocyte end-feet also contributes to maintain the BBB integrity, but the participation of hemichannels in this process cannot be discarded. Sympathetic and sensory perivascular nerves are also involved in the control and coordination of vascular function through the release of vasoconstrictor or vasodilator signals and by the regulation of gap junction communication in the vessel wall. Conversely, ATP release through pannexin-1-formed channels mediates the α1-adrenergic signaling. Furthermore, here we show that capsaicin-induced CGRP release from mesenteric perivascular sensory nerves induces pannexin-1-formed channel opening, which in turn leads to reduction of pannexin-1 and endothelial nitric oxide synthase (eNOS) expression along the time. Interestingly, blockade of CGRP receptors with CGRP8-37 increased eNOS expression by ∼5-fold, suggesting that capsaicin-sensitive sensory nerves are involved in the control of key signaling proteins for vascular function. In this review, we discuss the importance of connexin-based channels in the control of BBB integrity and the functional interaction of vascular connexins and pannexins with the peripheral nervous system. PMID:24446239

  4. Age-Associated Changes in the Vascular Renin-Angiotensin System in Mice

    PubMed Central

    Yoon, Hye Eun; Kim, Eun Nim; Kim, Min Young; Lim, Ji Hee; Jang, In-Ae; Ban, Tae Hyun; Shin, Seok Joon; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-01-01

    Background. This study evaluated whether the change in the renin-angiotensin system (RAS) is associated with arterial aging in mice. Methods. Histologic changes and expressions of transforming growth factor-β (TGF-β), collagen IV, fibronectin, angiotensin II (Ang II), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme 2 (ACE2), angiotensin II type 1 receptor (AT1R), angiotensin II type 2 receptor (AT2R), prorenin receptor (PRR), Mas receptor (MasR), endothelial nitric oxide synthase (eNOS), NADPH oxidase 2 and oxidase 4 (Nox2 and Nox4), 8-hydroxy-2′-deoxyguanosine (8-OHdG), 3-nitrotyrosine, and superoxide dismutase 1 and dismutase 2 (SOD1 and SOD2) were measured in the thoracic aortas from 2-month-old, 12-month-old, and 24-month-old C57/BL6 mice. Results. Twenty-four-month-old mice showed significantly increased aortic media thickness and expressions of TGF-β, collagen IV, and fibronectin, compared to 2-month-old and 12-month-old mice. The expressions of PRR, ACE, and Ang II, and AT1R-positive area significantly increased, whereas expressions of ACE2 and MasR and AT2R-positive area decreased with age. The expressions of phosphorylated serine1177-eNOS, SOD1, and SOD2 decreased, and the 8-OHdG-positive area and the 3-nitrotyrosine-positive area increased with age. The expression of Nox2 significantly increased with age, but that of Nox4 did not change. Conclusions. The enhanced PRR-ACE-Ang II-AT1R axis and reduced ACE2-MasR axis were associated with arterial aging in mice. PMID:27200147

  5. Diverse Functions of Endothelial NO Synthases System: NO and EDH

    PubMed Central

    Godo, Shigeo

    2016-01-01

    Abstract: Endothelium-dependent relaxations are predominantly regulated by nitric oxide (NO) in large conduit arteries and by endothelium-dependent hyperpolarization (EDH) in small resistance vessels. Although the nature of EDH factors varies depending on species and vascular beds, we have previously demonstrated that endothelial NO synthases (eNOS)-derived hydrogen peroxide (H2O2) is an EDH factor in animals and humans. This vessel size-dependent contribution of NO and EDH is, at least in part, attributable to the diverse roles of endothelial NOSs system; in large conduit arteries, eNOS mainly serves as a NO-generating system to elicit soluble guanylate cyclase–cyclic guanosine monophosphate-mediated relaxations, whereas in small resistance vessels, it serves as a superoxide-generating system to cause EDH/H2O2-mediated relaxations. Endothelial caveolin-1 may play an important role for the diverse roles of NOSs. Although reactive oxygen species are generally regarded harmful, the physiological roles of H2O2 have attracted much attention as accumulating evidence has shown that endothelium-derived H2O2 contributes to cardiovascular homeostasis. The diverse functions of endothelial NOSs system with NO and EDH/H2O2 could account for a compensatory mechanism in the setting of endothelial dysfunction. In this review, we will briefly summarize the current knowledge on the diverse functions of endothelial NOSs system: NO and EDH/H2O2. PMID:26647119

  6. Diverse Functions of Endothelial NO Synthases System: NO and EDH.

    PubMed

    Shimokawa, Hiroaki; Godo, Shigeo

    2016-05-01

    Endothelium-dependent relaxations are predominantly regulated by nitric oxide (NO) in large conduit arteries and by endothelium-dependent hyperpolarization (EDH) in small resistance vessels. Although the nature of EDH factors varies depending on species and vascular beds, we have previously demonstrated that endothelial NO synthases (eNOS)-derived hydrogen peroxide (H2O2) is an EDH factor in animals and humans. This vessel size-dependent contribution of NO and EDH is, at least in part, attributable to the diverse roles of endothelial NOSs system; in large conduit arteries, eNOS mainly serves as a NO-generating system to elicit soluble guanylate cyclase-cyclic guanosine monophosphate-mediated relaxations, whereas in small resistance vessels, it serves as a superoxide-generating system to cause EDH/H2O2-mediated relaxations. Endothelial caveolin-1 may play an important role for the diverse roles of NOSs. Although reactive oxygen species are generally regarded harmful, the physiological roles of H2O2 have attracted much attention as accumulating evidence has shown that endothelium-derived H2O2 contributes to cardiovascular homeostasis. The diverse functions of endothelial NOSs system with NO and EDH/H2O2 could account for a compensatory mechanism in the setting of endothelial dysfunction. In this review, we will briefly summarize the current knowledge on the diverse functions of endothelial NOSs system: NO and EDH/H2O2. PMID:26647119

  7. Computational modeling of shear forces and experimental validation of endothelial cell responses in an orbital well shaker system.

    PubMed

    Filipovic, Nenad; Ghimire, Kedar; Saveljic, Igor; Milosevic, Zarko; Ruegg, Curzio

    2016-01-01

    Vascular endothelial cells are continuously exposed to hemodynamic shear stress. Intensity and type of shear stress are highly relevant to vascular physiology and pathology. Here, we modeled shear stress distribution in a tissue culture well (R = 17.5 mm, fill volume 2 ml) under orbital translation using computational fluid dynamics with the finite element method. Free surface distribution, wall shear stress, inclination angle, drag force, and oscillatory index on the bottom surface were modeled. Obtained results predict nonuniform shear stress distribution during cycle, with higher oscillatory shear index, higher drag force values, higher circular component, and larger inclination angle of the shear stress at the periphery of the well compared with the center of the well. The oscillatory index, inclination angle, and drag force are new quantitative parameters modeled in this system, which provide a better understanding of the hydrodynamic conditions experienced and reflect the pulsatile character of blood flow in vivo. Validation experiments revealed that endothelial cells at the well periphery aligned under flow and increased Kruppel-like Factor 4 (KLF-4), cyclooxygenase-2 (COX-2) expression and endothelial nitric oxide synthase (eNOS) phosphorylation. In contrast, endothelial cells at the center of the well did not show clear directional alignment, did not induce the expression of KLF-4 and COX-2 nor increased eNOS phosphorylation. In conclusion, this improved computational modeling predicts that the orbital shaker model generates different hydrodynamic conditions at the periphery versus the center of the well eliciting divergent endothelial cell responses. The possibility of generating different hydrodynamic conditions in the same well makes this model highly attractive to study responses of distinct regions of the same endothelial monolayer to different types of shear stresses thereby better reflecting in vivo conditions. PMID:26096592

  8. Toward a Reduced-Wire Readout System for Ultrasound Imaging

    PubMed Central

    Lim, Jaemyung; Arkan, Evren F.; Degertekin, F. Levent; Ghovanloo, Maysam

    2015-01-01

    We present a system-on-a-chip (SoC) for use in high-frequency capacitive micromachined ultrasonic transducer (CMUT) imaging systems. This SoC consists of trans-impedance amplifiers (TIA), delay locked loop (DLL) based clock multiplier, quadrature sampler, and pulse width modulator (PWM). The SoC down converts RF echo signal to baseband by quadrature sampling which facilitates modulation. To send data through a 1.6 m wire in the catheter which has limited bandwidth and is vulnerable to noise, the SoC creates a pseudo-digital PWM signal which can be used for back telemetry or wireless readout of the RF data. In this implementation, using a 0.35-μm std. CMOS process, the TIA and single-to-differential (STD) converter had 45 MHz bandwidth, the quadrature sampler had 10.1 dB conversion gain, and the PWM had 5-bit ENoB. Preliminary results verified front-end functionality, and the power consumption of a TIA, STD, quadrature sampler, PWM, and clock multiplier was 26 mW from a 3 V supply. PMID:25571135

  9. Toward a reduced-wire readout system for ultrasound imaging.

    PubMed

    Lim, Jaemyung; Arkan, Evren F; Degertekin, F Levent; Ghovanloo, Maysam

    2014-01-01

    We present a system-on-a-chip (SoC) for use in high-frequency capacitive micromachined ultrasonic transducer (CMUT) imaging systems. This SoC consists of trans-impedance amplifiers (TIA), delay locked loop (DLL) based clock multiplier, quadrature sampler, and pulse width modulator (PWM). The SoC down converts RF echo signal to baseband by quadrature sampling which facilitates modulation. To send data through a 1.6 m wire in the catheter which has limited bandwidth and is vulnerable to noise, the SoC creates a pseudo-digital PWM signal which can be used for back telemetry or wireless readout of the RF data. In this implementation, using a 0.35-μm std. CMOS process, the TIA and single-to-differential (STD) converter had 45 MHz bandwidth, the quadrature sampler had 10.1 dB conversion gain, and the PWM had 5-bit ENoB. Preliminary results verified front-end functionality, and the power consumption of a TIA, STD, quadrature sampler, PWM, and clock multiplier was 26 mW from a 3 V supply. PMID:25571135

  10. Aspirin and lipid mediators in the cardiovascular system.

    PubMed

    Schrör, Karsten; Rauch, Bernhard H

    2015-09-01

    Aspirin is an unique compound because it bears two active moieties within one and the same molecule: a reactive acetyl group and the salicylate metabolite. Salicylate has some effects similar to aspirin, however only at higher concentrations, usually in the millimolar range, which are not obtained at conventional antiplatelet aspirin doses of 100-300 mg/day. Pharmacological actions of aspirin in the cardiovascular system at these doses are largely if not entirely due to target structure acetylation. Several classes of lipid mediators become affected: Best known is the cyclooxygenase-1 (COX-1) in platelets with subsequent inhibition of thromboxane and, possibly, thrombin formation. By this action, aspirin also inhibits paracrine thromboxane functions on other lipid mediators, such as the platelet storage product sphingosine-1-phosphate (S1P), an inflammatory mediator. Acetylation of COX-2 allows for generation of 15-(R)HETE and subsequent formation of "aspirin-triggered lipoxin" (ATL) by interaction with white cell lipoxygenases. In the cardiovascular system, aspirin also acetylates eNOS with subsequent upregulation of NO formation and enhanced expression of the antioxidans heme-oxygenase-1. This action is possibly also COX-2/ATL mediated. Many more acetylation targets have been identified in live cells by quantitative acid-cleavable activity-based protein profiling and might result in discovery of even more aspirin targets in the near future. PMID:26201059

  11. Exercise and NO production: relevance and implications in the cardiopulmonary system

    PubMed Central

    Nosarev, Alexei V.; Smagliy, Lyudmila V.; Anfinogenova, Yana; Popov, Sergey V.; Kapilevich, Leonid V.

    2015-01-01

    This article reviews the existing knowledge about the effects of physical exercise on nitric oxide (NO) production in the cardiopulmonary system. The authors review the sources of NO in the cardiopulmonary system; involvement of three forms of NO synthases (eNOS, nNOS, and iNOS) in exercise physiology; exercise-induced modulation of NO and/or NOS in physiological and pathophysiological conditions in human subjects and animal models in the absence and presence of pharmacological modulators; and significance of exercise-induced NO production in health and disease. The authors suggest that physical activity significantly improves functioning of the cardiovascular system through an increase in NO bioavailability, potentiation of antioxidant defense, and decrease in the expression of reactive oxygen species-forming enzymes. Regular physical exercises are considered a useful approach to treat cardiovascular diseases. Future studies should focus on detailed identification of (i) the exercise-mediated mechanisms of NO exchange; (ii) optimal exercise approaches to improve cardiovascular function in health and disease; and (iii) physical effort thresholds. PMID:25610830

  12. Recent progress on essentially non-oscillatory shock capturing schemes

    NASA Technical Reports Server (NTRS)

    Osher, Stanley; Shu, Chi-Wang

    1989-01-01

    An account is given of the construction of efficient implementations of 'essentially nonoscillatory' (ENO) schemes that approximate systems of hyperbolic conservation laws. ENO schemes use a local adaptive stencil to automatically obtain information from regions of smoothness when the solution develops discontinuities. Approximations employing ENOs can thereby obtain uniformly high accuracy to the very onset of discontinuities, while retaining a sharp and essentially nonoscillatory shock transition. For ease of implementation, ENO schemes applying the adaptive stencil concept to the numerical fluxes and employing a TVD Runge-Kutta-type time discretization are constructed.

  13. Assessment of numerical methods for the solution of fluid dynamics equations for nonlinear resonance systems

    NASA Technical Reports Server (NTRS)

    Przekwas, A. J.; Yang, H. Q.

    1989-01-01

    The capability of accurate nonlinear flow analysis of resonance systems is essential in many problems, including combustion instability. Classical numerical schemes are either too diffusive or too dispersive especially for transient problems. In the last few years, significant progress has been made in the numerical methods for flows with shocks. The objective was to assess advanced shock capturing schemes on transient flows. Several numerical schemes were tested including TVD, MUSCL, ENO, FCT, and Riemann Solver Godunov type schemes. A systematic assessment was performed on scalar transport, Burgers' and gas dynamic problems. Several shock capturing schemes are compared on fast transient resonant pipe flow problems. A system of 1-D nonlinear hyperbolic gas dynamics equations is solved to predict propagation of finite amplitude waves, the wave steepening, formation, propagation, and reflection of shocks for several hundred wave cycles. It is shown that high accuracy schemes can be used for direct, exact nonlinear analysis of combustion instability problems, preserving high harmonic energy content for long periods of time.

  14. Stable gastric pentadecapeptide BPC 157-NO-system relation.

    PubMed

    Sikiric, Predrag; Seiwerth, Sven; Rucman, Rudolf; Turkovic, Branko; Rokotov, Dinko Stancic; Brcic, Luka; Sever, Marko; Klicek, Robert; Radic, Bozo; Drmic, Domagoj; Ilic, Spomenko; Kolenc, Danijela; Aralica, Gorana; Stupnisek, Mirjana; Suran, Jelena; Barisic, Ivan; Dzidic, Senka; Vrcic, Hrvoje; Sebecic, Bozidar

    2014-01-01

    We reviewed stable gastric pentadecapeptide BPC 157-NO-system-relation, its close participation in Moncada's (maintained vascular integrity, platelets control) homeostatic healing response of NO-system to injury. Namely, BPC 157's particular healing effect also affects all events after vascular integrity loss (dependent on circumstances, it reduces either thrombosis (abdominal aorta anastomosis) or bleeding/thrombocytopenia (amputation, heparin, warfarin, aspirin)) and in a series of different injurious models, acute and chronic, BPC 157 consistently advances healing after severe injuries in various tissues spontaneously unable to heal; stimulates egr-1 and naB2 genes; exhibits high safety (LD1 not achieved)). Hypothesis, that BPC 157 (since formed constitutively in the gastric mucosa, stable in human gastric juice, along with significance of NO-synthase and the basal formation of NO in stomach mucosa, greater than that seen in other tissues) exhibits a general, effective competing both with L-arginine analogues (i. e., L-NAME) and L-arginine, and that this has some physiologic importance (NO-generation), later, practically supports its beneficial effects illustrating BPC 157 and NOsystem mutual (with L-NAME/L-arginine; alone and together) relations in (i) gastric mucosa and mucosal protection, following alcohol lesions, in cytoprotection course, NO-generation, and blood pressure regulation; (ii) alcohol acute/chronic intoxication, and withdrawal; (iii) cardiovascular disturbances, chronic heart failure, pulmonary hypertension, and arrhythmias; (iv) disturbances after hypokalemia and hyperkalemia, and potassium-cell membrane dysfunction; and finally, in (v) complex healing failure, proved by the fistulas healing, colocutaneous and esophagocutaneous. However, how this advantage of modulating NO-system (i. e., particular effect on eNOS gene), may be practically translated into an enhanced clinical performance remains to be determined. PMID:23755725

  15. Arsenite induces endothelial cytotoxicity by down-regulation of vascular endothelial nitric oxide synthase

    SciTech Connect

    Tsou, T.-C. . E-mail: tctsou@nhri.org.tw; Tsai, F.-Y.; Hsieh, Y.-W.; Li, L.-A.; Yeh, S.C; Chang, L.W.

    2005-11-01

    Epidemiological studies have demonstrated a high association of inorganic arsenic exposure with vascular diseases. Recent research has also linked this vascular damage to impairment of endothelial nitric oxide synthase (eNOS) function by arsenic exposure. However, the role of eNOS in regulating the arsenite-induced vascular dysfunction still remains to be clarified. In our present study, we investigated the effect of arsenite on Akt1 and eNOS and its involvement in cytotoxicity of vascular endothelial cells. Our study demonstrated that arsenite decreased the protein levels of both Akt1 and eNOS accompanied with increased levels of ubiquitination of total cell lysates. We found that inhibition of the ubiquitin-proteasome pathway by MG-132 could partially protect Akt1 and eNOS from degradation by arsenite together with a proportional protection from the arsenite-induced cytoxicity. Moreover, up-regulation of eNOS protein expression significantly attenuated the arsenite-induced cytotoxicity and eNOS activity could be significantly inhibited after incubation with arsenite for 24 h in a cell-free system. Our study indicated that endothelial eNOS activity could be attenuated by arsenite via the ubiquitin-proteasome-mediated degradation of Akt1/eNOS as well as via direct inhibition of eNOS activity. Our study also demonstrated that eNOS actually played a protective role in arsenite-induced cytoxicity. These observations supported the hypothesis that the impairment of eNOS function by arsenite is one of the mechanisms leading to vascular changes and diseases.

  16. Comparison of Knowledge on Diarrheal Disease Management between Two Types of Community-Based Distributors in Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Ande, Oluyinka; Oladepo, Oladimeji; Brieger, William R.

    2004-01-01

    Community-based distributors (CBDs) have been trained and utilized to promote a variety of health commodities. In addition, a variety of different types of community residents have been trained ranging from traditional birth attendants (TBAs) to patent medicine vendors. A training programme for CBD agents in the Akinyele Local Government Area of…

  17. Instructional Resources as Determinants of English Language Performance of Secondary School High-Achieving Students in Ibadan, Oyo State

    ERIC Educational Resources Information Center

    Adelodun, Gboyega Adelowo; Asiru, Abdulahi Babatunde

    2015-01-01

    This study examined the role played by instructional resources in enhancing performance of students, especially that of high-achievers, in English Language. The study is descriptive in nature and it adopted a survey design. Simple random sampling technique was used for the selection of fifty (50) SSI-SSIII students from five schools in Ibadan…

  18. Sociodemographic Correlates of Modifiable Risk Factors for Hypertension in a Rural Local Government Area of Oyo State South West Nigeria

    PubMed Central

    Abdulsalam, Saliu; Olugbenga-Bello, Adenike; Olarewaju, Olakunle; Abdus-salam, Ismail

    2014-01-01

    Modifiable risk factors of hypertension contribute significantly to all-cause morbidity and mortality worldwide. The study aimed to determine the prevalence of and the association of modifiable risk factors with hypertension in rural community. A cross-sectional study was conducted among 166 male and 201 female adults of 18 years and above using cluster sampling technique. Data were collected using modified WHO STEPS instrument and hypertensive subjects were defined as those with systolic greater than or equal to 140 and diastolic of 90 mmHg. Data were analyzed with SPSS version 17 with level of significance at P < 0.05. The mean age of the subjects was 36.36 (±16.88) years and mean systolic and diastolic pressures were 124 (±16.93) and 76.32 (±11.85) mmHg, respectively. The prevalence of hypertension was high (22.9%) in this rural communities but awareness was low, 10.71%. The prevalence of alcohol consumption, sedentary lifestyle, abnormal weight, inadequate sleep, smoking, significant stress, and female use of hormonal contraceptives was 149 (40.6%), 91 (24.8%), 88 (24.0%), 122 (33.2%), 14 (3.8%), 65 (17.7%), and 53 (26.5%), respectively. Overweight, sex, inadequate sleep, and stress were established as positive predictors of hypertension. The rising prevalence of hypertension and its modifiable risk factors in rural communities require prompt interventions directed at reversing these trends. PMID:25580284

  19. Microbiological Safety Assessment of Fermented Cassava Flour “Lafun” Available in Ogun and Oyo States of Nigeria

    PubMed Central

    Adebayo-Oyetoro, A. O.; Oyewole, O. B.; Obadina, A. O.; Omemu, M. A.

    2013-01-01

    The microorganisms involved in the fermentation and spoilage of fermented cassava flour were investigated. The water samples used at the different processing sites were also investigated to determine their safety status. There was predominance of Staphylococcus aureus, Aspergillus spp., and Escherichia coli in all samples. Coliforms were observed to be present in all of the processing water. In the fermented cassava flour, the total bacterial count ranged between 4.9 × 106 cfu/mL from Eleso, Bakatari, and Oja Odan processing sites and 8.10 × 106 cfu/mL in Eruku processing site. The majority of the microorganisms involved in the spoilage of “lafun” were found to be Aspergillus niger which ranged between 4.6 × 105 cfu/mL in Eleso and 8.1 × 105 cfu/mL in Kila. The control sample prepared in the laboratory had a low microbial load compared to samples collected from various sites and markets. PMID:26904609

  20. Paracoccidioides brasiliensis Enolase Is a Surface Protein That Binds Plasminogen and Mediates Interaction of Yeast Forms with Host Cells ▿

    PubMed Central

    Nogueira, Sarah Veloso; Fonseca, Fernanda L.; Rodrigues, Marcio L.; Mundodi, Vasanth; Abi-Chacra, Erika A.; Winters, Michael S.; Alderete, John F.; Soares, Célia Maria de Almeida

    2010-01-01

    Paracoccidioidomycosis (PCM), caused by the dimorphic fungus Paracoccidioides brasiliensis, is a disseminated, systemic disorder that involves the lungs and other organs. The ability of the pathogen to interact with host components, including extracellular matrix (ECM) proteins, is essential to further colonization, invasion, and growth. Previously, enolase (EC 4.2.1.11) was characterized as a fibronectin binding protein in P. brasiliensis. Interaction of surface-bound enolase with plasminogen has been incriminated in tissue invasion for pathogenesis in several pathogens. In this paper, enolase was expressed in Escherichia coli as a recombinant glutathione S-transferase (GST) fusion protein (recombinant P. brasiliensis enolase [rPbEno]). The P. brasiliensis native enolase (PbEno) was detected at the fungus surface and cytoplasm by immunofluorescence with an anti-rPbEno antibody. Immobilized purified rPbEno bound plasminogen in a specific, concentration-dependent fashion. Both native enolase and rPbEno activated conversion of plasminogen to plasmin through tissue plasminogen activator. The association between PbEno and plasminogen was lysine dependent. In competition experiments, purified rPbEno, in its soluble form, inhibited plasminogen binding to fixed P. brasiliensis, suggesting that this interaction required surface-localized PbEno. Plasminogen-coated P. brasiliensis yeast cells were capable of degrading purified fibronectin, providing in vitro evidence for the generation of active plasmin on the fungus surface. Exposure of epithelial cells and phagocytes to enolase was associated with an increased expression of surface sites of adhesion. In fact, the association of P. brasiliensis with epithelial cells and phagocytes was increased in the presence of rPbEno. The expression of PbEno was upregulated in yeast cells derived from mouse-infected tissues. These data indicate that surface-associated PbEno may contribute to the pathogenesis of P. brasiliensis. PMID

  1. Serine 1179 Phosphorylation of Endothelial Nitric Oxide Synthase Increases Superoxide Generation and Alters Cofactor Regulation

    PubMed Central

    Harbeck, Mark C.; He, Donghong; Xie, Lishi; Chen, Weiguo

    2015-01-01

    Endothelial nitric oxide synthase (eNOS) is responsible for maintaining systemic blood pressure, vascular remodeling and angiogenesis. In addition to producing NO, eNOS can also generate superoxide (O2-.) in the absence of the cofactor tetrahydrobiopterin (BH4). Previous studies have shown that bovine eNOS serine 1179 (Serine 1177/human) phosphorylation critically modulates NO synthesis. However, the effect of serine 1179 phosphorylation on eNOS superoxide generation is unknown. Here, we used the phosphomimetic form of eNOS (S1179D) to determine the effect of S1179 phosphorylation on superoxide generating activity, and its sensitivity to regulation by BH4, Ca2+, and calmodulin (CAM). S1179D eNOS exhibited significantly increased superoxide generating activity and NADPH consumption compared to wild-type eNOS (WT eNOS). The superoxide generating activities of S1179D eNOS and WT eNOS did not differ significantly in their sensitivity to regulation by either Ca2+ or CaM. The sensitivity of the superoxide generating activity of S1179D eNOS to inhibition by BH4 was significantly reduced compared to WT eNOS. In eNOS-overexpressing 293 cells, BH4 depletion with 10mM DAHP for 48 hours followed by 50ng/ml VEGF for 30 min to phosphorylate eNOS S1179 increased ROS accumulation compared to DAHP-only treated cells. Meanwhile, MTT assay indicated that overexpression of eNOS in HEK293 cells decreased cellular viability compared to control cells at BH4 depletion condition (P<0.01). VEGF-mediated Serine 1179 phosphorylation further decreased the cellular viability in eNOS-overexpressing 293 cells (P<0.01). Our data demonstrate that eNOS serine 1179 phosphorylation, in addition to enhancing NO production, also profoundly affects superoxide generation: S1179 phosphorylation increases superoxide production while decreasing sensitivity to the inhibitory effect of BH4 on this activity. PMID:26560496

  2. Vitamin D improves endothelial dysfunction and restores myeloid angiogenic cell function via reduced CXCL-10 expression in systemic lupus erythematosus.

    PubMed

    Reynolds, John A; Haque, Sahena; Williamson, Kate; Ray, David W; Alexander, M Yvonne; Bruce, Ian N

    2016-01-01

    Patients with systemic lupus erythematosus (SLE) have accelerated cardiovascular disease and dysfunctional endothelial repair mechanisms. Myeloid angiogenic cells (MACs), derived from circulating monocytes, augment vascular repair by paracrine secretion of pro-angiogenic factors. We observed that SLE MACs are dysfunctional and secrete pro-inflammatory cytokines. We also found that the vitamin D receptor was transiently expressed during MAC differentiation and that in vitro, calcitriol increased differentiation of monocytes into MACs in both SLE and in a model using the prototypic SLE cytokine, interferon-alpha. The active form of vitamin D (calcitriol) restored the SLE MAC phenotype towards that of healthy subjects with reduced IL-6 secretion, and normalised surface marker expression. Calcitriol also augmented the angiogenic capacity of MACs via the down-regulation of CXCL-10. In SLE patients treated with cholecalciferol for 12 weeks, the improvement in endothelial function correlated with increase in serum 25(OH)D concentrations independently of disease activity. We also show that MACs were able to positively modulate eNOS expression in human endothelial cells in vitro, an effect further enhanced by calcitriol treatment of SLE MACs. The results demonstrate that vitamin D can positively modify endothelial repair mechanisms and thus endothelial function in a population with significant cardiovascular risk. PMID:26930567

  3. Vitamin D improves endothelial dysfunction and restores myeloid angiogenic cell function via reduced CXCL-10 expression in systemic lupus erythematosus

    PubMed Central

    Reynolds, John A.; Haque, Sahena; Williamson, Kate; Ray, David W.; Alexander, M. Yvonne; Bruce, Ian N.

    2016-01-01

    Patients with systemic lupus erythematosus (SLE) have accelerated cardiovascular disease and dysfunctional endothelial repair mechanisms. Myeloid angiogenic cells (MACs), derived from circulating monocytes, augment vascular repair by paracrine secretion of pro-angiogenic factors. We observed that SLE MACs are dysfunctional and secrete pro-inflammatory cytokines. We also found that the vitamin D receptor was transiently expressed during MAC differentiation and that in vitro, calcitriol increased differentiation of monocytes into MACs in both SLE and in a model using the prototypic SLE cytokine, interferon-alpha. The active form of vitamin D (calcitriol) restored the SLE MAC phenotype towards that of healthy subjects with reduced IL-6 secretion, and normalised surface marker expression. Calcitriol also augmented the angiogenic capacity of MACs via the down-regulation of CXCL-10. In SLE patients treated with cholecalciferol for 12 weeks, the improvement in endothelial function correlated with increase in serum 25(OH)D concentrations independently of disease activity. We also show that MACs were able to positively modulate eNOS expression in human endothelial cells in vitro, an effect further enhanced by calcitriol treatment of SLE MACs. The results demonstrate that vitamin D can positively modify endothelial repair mechanisms and thus endothelial function in a population with significant cardiovascular risk. PMID:26930567

  4. [Adrenomedullin-Receptor Activity-modifying Protein 2 (RAMP2) System in Retinal Angiogenesis].

    PubMed

    Iesato, Yasuhiro

    2015-11-01

    Adrenomedullin (ADM) was originally identified as an endogenous peptide having vasodilating functions. Following that, ADM has been shown to possess pleiotropic functions including angiogenic potency. The vascular function of ADM is mainly regulated by a receptor activity-modifying protein 2 (RAMP2). However, pathophysiological roles of ADM-RAMP2 system in retinal angiogenesis remain to be clarified. We analyzed (1) a oxygen-induced retinopathy (OIR) model using heterozygous ADM and RAMP2 knockout mice (ADMJ+/- and RAMP2+/-, respectively), (2) proliferation and migration of retinal endothelial cells in vitro, (3) retinal angiogenesis during developmental stage using drug-inducible endothelial cell-specific RAMP2 knockout mice (DI-E-RAMP2-/-), and (4) an OIR model treated with intravitreal injection of anti-ADM antibody. We found that ADM mRNA expression was upregulated under hypoxic conditions in OIR model. In ADM+/-, pathological neovascularization as well as VEGF and eNOS mRNA expression was suppressed. In addition, proliferation and migration effects of ADM on retinal endothelial cells were confirmed in vitro. We found that ADM-RAMP2 system also plays important roles in retinal vascular development, and Notch signaling is possibly involved. Finally, we revealed that intravitreal injection of anti-ADM antibody reduced pathological retinal angiogenesis in OIR model. From these results, we clarified that ADM-RAMP2 system plays important roles in both the pathological and physiological retinal angiogenesis. ADM-RAMP2 system is a hopeful new therapeutic method for controlling pathological retinal angiogenesis in ocular diseases. PMID:26685480

  5. NOSTRIN: A protein modulating nitric oxide release and subcellular distribution of endothelial nitric oxide synthase

    PubMed Central

    Zimmermann, Kirstin; Opitz, Nils; Dedio, Jürgen; Renné, Christoph; Müller-Esterl, Werner; Oess, Stefanie

    2002-01-01

    Activity and localization of endothelial nitric oxide synthase (eNOS) is regulated in a remarkably complex fashion, yet the complex molecular machinery mastering stimulus-induced eNOS translocation and trafficking is poorly understood. In a search by the yeast two-hybrid system using the eNOS oxygenase domain as bait, we have identified a previously uncharacterized eNOS-interacting protein, dubbed NOSTRIN (for eNOS traffic inducer). NOSTRIN contains a single polypeptide chain of 506-aa residues of 58 kDa with an N-terminal cdc15 domain and a C-terminal SH3 domain. NOSTRIN mRNA is abundant in highly vascularized tissues such as placenta, kidney, lung, and heart, and NOSTRIN protein is expressed in vascular endothelial cells. Coimmunoprecipitation experiments demonstrated the eNOS–NOSTRIN interaction in vitro and in vivo, and NOSTRIN's SH3 domain was essential and sufficient for eNOS binding. NOSTRIN colocalized extensively with eNOS at the plasma membrane of confluent human umbilical venous endothelial cells and in punctate cytosolic structures of CHO-eNOS cells. NOSTRIN overexpression induced a profound redistribution of eNOS from the plasma membrane to vesicle-like structures matching the NOSTRIN pattern and at the same time led to a significant inhibition of NO release. We conclude that NOSTRIN contributes to the intricate protein network controlling activity, trafficking, and targeting of eNOS. PMID:12446846

  6. PArthENoPE: Public Algorithm Evaluating the Nucleosynthesis of Primordial Elements

    SciTech Connect

    Pisanti, O.; Cirillo, A.; Esposito, S.; Iocco, F.; Mangano, G.; Miele, G.; Serpico, P.D.

    2007-05-04

    We describe a program for computing the abundances of light elements produced during Big Bang Nucleosynthesis which is publicly available at http://parthenope.na.infn.it/. Starting from nuclear statistical equilibrium conditions the program solves the set of coupled ordinary differential equations, follows the departure from chemical equilibrium of nuclear species, and determines their asymptotic abundances as function of several input cosmological parameters as the baryon density, the number of effective neutrino, the value of cosmological constant and the neutrino chemical potential.

  7. High-order central ENO finite-volume scheme for ideal MHD

    NASA Astrophysics Data System (ADS)

    Susanto, A.; Ivan, L.; De Sterck, H.; Groth, C. P. T.

    2013-10-01

    A high-order accurate finite-volume scheme for the compressible ideal magnetohydrodynamics (MHD) equations is proposed. The high-order MHD scheme is based on a central essentially non-oscillatory (CENO) method combined with the generalized Lagrange multiplier divergence cleaning method for MHD. The CENO method uses k-exact multidimensional reconstruction together with a monotonicity procedure that switches from a high-order reconstruction to a limited low-order reconstruction in regions of discontinuous or under-resolved solution content. Both reconstructions are performed on central stencils, and the switching procedure is based on a smoothness indicator. The proposed high-order accurate MHD scheme can be used on general polygonal grids. A highly sophisticated parallel implementation of the scheme is described that is fourth-order accurate on two-dimensional dynamically-adaptive body-fitted structured grids. The hierarchical multi-block body-fitted grid permits grid lines to conform to curved boundaries. High-order accuracy is maintained at curved domain boundaries by employing high-order spline representations and constraints at the Gauss quadrature points for flux integration. Detailed numerical results demonstrate high-order convergence for smooth flows and robustness against oscillations for problems with shocks. A new MHD extension of the well-known Shu-Osher test problem is proposed to test the ability of the high-order MHD scheme to resolve small-scale flow features in the presence of shocks. The dynamic mesh adaptation capabilities of the approach are demonstrated using adaptive time-dependent simulations of the Orszag-Tang vortex problem with high-order accuracy and unprecedented effective resolution.

  8. The Last Days of the Avant Garde; or How to Tell Your Glass from Your Eno.

    ERIC Educational Resources Information Center

    Jaffe, Lee David

    1983-01-01

    Discussion of the nature of Experimental and avant garde music highlights the Western musical tradition, technological innovations having an impact on music (telephone, phonograph, tape recording), Third World influence, avant garde composer/musicians, and library collections. A 24-item discography, addresses of five record distributors, and a…

  9. Statistical analysis plan for the 'Efficacy of Nitric Oxide in Stroke' (ENOS) trial.

    PubMed

    Bath, Philip M W; Houlton, Aimee; Woodhouse, Lisa; Sprigg, Nikola; Wardlaw, Joanna; Pocock, Stuart

    2014-04-01

    High blood pressure is common during the acute phase of stroke and is associated with a poor outcome. However, the management of high blood pressure remains unclear. The 'Efficacy of Nitric Oxide in Stroke' trial tested whether transdermal glyceryl trinitrate, a nitric oxide donor that lowers blood pressure, is safe and effective in improving outcome after acute stroke. Efficacy of Nitric Oxide in Stroke is an international multicenter, prospective, randomized, single-blind, blinded endpoint trial, with funding from the U.K. Medical Research Council. Patients with acute ischemic stroke or intracerebral hemorrhage and systolic blood pressure 140-220 mmHg were randomized to glyceryl trinitrate or no glyceryl trinitrate and, where relevant, to continue or stop prestroke antihypertensive therapy. The primary outcome is shift in modified Rankin Scale at three-months. Patients or relatives gave written informed (proxy) consent, and all sites had research ethics approval. Analyses will be done by intention to treat. This paper and attachment describe the trial's statistical analysis plan, developed prior to unblinding of date. The statistical analysis plan contains design and methods for analyses, and unpopulated tables and figures for the two primary publications and some secondary publications. The database will be locked in late February 2014 in preparation for presentation of the results in May 2014. The data from the trial will improve the precision of the estimates of the overall treatment effects (efficacy and safety) of results from completed trials of blood pressure management in acute stroke, and provide the first large-scale randomized evidence on transdermal glyceryl trinitrate, and of continuing (vs. stopping) prestroke antihypertensive medications, in acute stroke. PMID:24588789

  10. System requirements. [Space systems

    SciTech Connect

    Austin, R.E.

    1982-06-01

    Requirements of future space systems, including large space systems, that operate beyond the space shuttle are discussed. Typical functions required of propulsion systems in this operational regime include payload placement, retrieval, observation, servicing, space debris control and support to large space systems. These functional requirements are discussed in conjunction with two classes of propulsion systems: (1) primary or orbit transfer vehicle (OTV) and (2) secondary or systems that generally operate within or relatively near an operational base orbit. Three propulsion system types are described in relation to these requirements: cryogenic OTV, teleoperator maneuvering system and a solar electric OTV.

  11. The impact of theaflavins on systemic-and microcirculation alterations: The murine and randomized feasibility trials.

    PubMed

    Saito, Akiko; Nakazato, Risa; Suhara, Yoshitomo; Shibata, Masahiro; Fukui, Toshiki; Ishii, Takeshi; Asanuma, Toshimichi; Mochizuki, Kazuo; Nakayama, Tsutomu; Osakabe, Naomi

    2016-06-01

    Theaflavins are polyphenols found in black tea; their physiological activities were not well investigated. The present study in rats evaluated the influence of theaflavins on circulation. In addition, an intervention pilot study examined the influence of a theaflavin drink on postprandial hemodynamic change. In an animal study, a single oral dose of theaflavin rich fraction (TF, 10mg/kg) caused transient increase in mean blood pressure (MBP) and heart rate (HR). TF also elevated cremastric blood flow significantly, and the magnitude of this effect was in this order: theaflavin 3'-O-gallate (TF2B) >theaflavin-3-O-gallate (TF2A) >theaflavin (TF1)=theaflavin-3, 3'-di-O-gallate (TF3). In addition, these hemodynamic alterations in mammals totally disappeared when pretreated with carvedilol as an adrenaline blocker. We also treated 10-mg/kg/day TF to the rats for 2 weeks. At the end of the ingestion period, MBP was reduced significantly, and aortic eNOS level was elevated by the repeated ingestion of TF compared with distilled water. In the intervention trial, blood pressure of the volunteers was increased significantly 2 and 4h after ingestion of the TF drink (45mg/drink) compared with before treatment. A significant difference was observed in FMD between the placebo and theaflavin groups 4h after ingestion. These results suggested that theaflavin has potent activity to alter hemodynamics in both murine and healthy subjects. Further studies is needed to elucidate the details; however, the results of animal study suggested that the possible involvement of sympathetic nervous system in the hemodynamic changes caused by TF. PMID:27142743

  12. Systems biological analyses reveal the HCV-specific regulation of hematopoietic development

    PubMed Central

    Velazquez, Victoria M.; Uebelhoer, Luke S.; Thapa, Manoj; Ibegbu, Chris; Courtney, Cynthia; Bosinger, Steven E.; Magliocca, Joseph F.; Adams, Andrew B.; Kirk, Allan D.; Knechtle, Stuart J.; Kalman, Daniel; Suthar, Mehul; Grakoui, Arash

    2014-01-01

    Chronic liver disease is characterized by the liver enrichment of myeloid DCs. To assess the role of disease on myelopoiesis, we utilized a systems biology approach to study development in liver-resident cells expressing stem cell marker CD34. In patients with end-stage liver disease, liver CD34+ cells were comprised by two subsets, designated CD34+CD146+ and CD34+CD146−, and hematopoietic function was restricted to CD34+CD146− cells. Liver CD34 frequencies were reduced during nonalcoholic steatohepatitis (NASH) and chronic hepatitis C virus (HCV) compared to alcohol liver disease (ALD), and this reduction correlated with viral load in the HCV cohort. To better understand the relationship between liver CD34+CD146+ and CD34+CD146− subsets and any effects of disease on CD34 development, we used gene expression profiling and computational modeling to compare each subset during ALD and HCV. For CD34+CD146+ cells, increased expression of endothelial cell genes including von Willebrand factor, VE-cadherin and eNOS were observed when compared to CD34+CD146− cells, and minimal effects of ALD and HCV diseases on gene expression were observed. Importantly for CD34+CD146− cells, chronic HCV was associated with a distinct ‘imprint’ of programs related to cell cycle, DNA repair, chemotaxis, development, and activation, with an emphasis on myeloid and B lymphocyte lineages. This HCV signature was further translated in side-by-side analyses, where HCV CD34+CD146− cells demonstrated superior hematopoietic growth, colony formation, and diversification compared to ALD and NASH when cultured identically. Disease-associated effects on hematopoiesis were also evident by phenotypic alterations in the expression of CD14, HLA-DR and CD16 by myeloid progeny cells. Conclusion Etiology drives progenitor fate within diseased tissues. The liver may be a useful source of hematopoietic cells for therapy, or as therapeutic targets. PMID:25331524

  13. Soluble alpha-enolase activates monocytes by CD14-dependent TLR4 signalling pathway and exhibits a dual function

    PubMed Central

    Guillou, Clément; Fréret, Manuel; Fondard, Emeline; Derambure, Céline; Avenel, Gilles; Golinski, Marie-Laure; Verdet, Mathieu; Boyer, Olivier; Caillot, Frédérique; Musette, Philippe; Lequerré, Thierry; Vittecoq, Olivier

    2016-01-01

    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory rheumatism. Identifying auto-antigens targeted by RA auto-antibodies is of major interest. Alpha-enolase (ENO1) is considered to be a pivotal auto-antigen in early RA but its pathophysiologic role remains unknown. The main objective of this study was to investigate the in vitro effects of soluble ENO1 on peripheral blood mononuclear cells (PBMC) from healthy donors and RA patients in order to determine the potential pathogenic role of ENO1. ELISA, transcriptomic analysis, experiments of receptor inhibition and flow cytometry analysis were performed to determine the effect, the target cell population and the receptor of ENO1. We showed that ENO1 has the ability to induce early production of pro-inflammatory cytokines and chemokines with delayed production of IL-10 and to activate the innate immune system. We demonstrated that ENO1 binds mainly to monocytes and activates the CD14-dependent TLR4 pathway both in healthy subjects and in RA patients. Our results establish for the first time that ENO1 is able to activate in vitro the CD14-dependent TLR4 pathway on monocytes involving a dual mechanism firstly pro-inflammatory and secondly anti-inflammatory. These results contribute to elucidating the role of this auto-antigen in the pathophysiologic mechanisms of RA. PMID:27025255

  14. A constitutive expression system for glycosyl hydrolase family 7 cellobiohydrolases in Hypocrea jecorina

    DOE PAGESBeta

    Linger, Jeffrey G.; Taylor, II, Larry E.; Baker, John O.; Vander Wall, Todd; Hobdey, Sarah E.; Podkaminer, Kara; Himmel, Michael E.; Decker, Stephen R.

    2015-03-18

    One of the primary industrial-scale cellulase producers is the ascomycete fungus, Hypocrea jecorina, which produces and secretes large quantities of diverse cellulolytic enzymes. Perhaps the single most important biomass degrading enzyme is cellobiohydrolase I (cbh1or Cel7A) due to its enzymatic proficiency in cellulose depolymerization. However, production of Cel7A with native-like properties from heterologous expression systems has proven difficult. In this study, we develop a protein expression system in H. jecorina (Trichoderma reesei) useful for production and secretion of heterologous cellobiohydrolases from glycosyl hydrolase family 7. Building upon previous work in heterologous protein expression in filamentous fungi, we have integrated amore » native constitutive enolase promoter with the native cbh1 signal sequence. The results are the following: The constitutive eno promoter driving the expression of Cel7A allows growth on glucose and results in repression of the native cellulase system, severely reducing background endo- and other cellulase activity and greatly simplifying purification of the recombinant protein. Coupling this system to a Δcbh1 strain of H. jecorina ensures that only the recombinant Cel7A protein is produced. Two distinct transformant colony morphologies were observed and correlated with high and null protein production. Production levels in ‘fast’ transformants are roughly equivalent to those in the native QM6a strain of H. jecorina, typically in the range of 10 to 30 mg/L when grown in continuous stirred-tank fermenters. ‘Slow’ transformants showed no evidence of Cel7A production. Specific activity of the purified recombinant Cel7A protein is equivalent to that of native protein when assayed on pretreated corn stover, as is the thermal stability and glycosylation level. Purified Cel7A produced from growth on glucose demonstrated remarkably consistent specific activity. Purified Cel7A from the same strain grown on lactose

  15. Solar system positioning system

    NASA Technical Reports Server (NTRS)

    Penanen, Konstantin I.; Chui, Talso

    2006-01-01

    Power-rich spacecraft envisioned in Prometheus initiative open up possibilities for long-range high-rate communication. A constellation of spacecraft on orbits several A.U. from the Sun, equipped with laser transponders and precise clocks can be configured to measure their mutual distances to within few cm. High on-board power can create substantial non-inertial contribution to the spacecraft trajectory. We propose to alleviate this contribution by employing secondary ranging to a passive daughter spacecraft. Such constellation can form the basis of it navigation system capable of providing position information anywhere in the soIar system with similar accuracy. Apart from obvious Solar System exploration implications, this system can provide robust reference for GPS and its successors.

  16. Systems autonomy

    NASA Technical Reports Server (NTRS)

    Lum, Henry, Jr.

    1988-01-01

    Information on systems autonomy is given in viewgraph form. Information is given on space systems integration, intelligent autonomous systems, automated systems for in-flight mission operations, the Systems Autonomy Demonstration Project on the Space Station Thermal Control System, the architecture of an autonomous intelligent system, artificial intelligence research issues, machine learning, and real-time image processing.

  17. Cell Walls of Saccharomyces cerevisiae Differentially Modulated Innate Immunity and Glucose Metabolism during Late Systemic Inflammation

    PubMed Central

    Baurhoo, Bushansingh; Ferket, Peter; Ashwell, Chris M.; de Oliviera, Jean; Zhao, Xin

    2012-01-01

    Background Salmonella causes acute systemic inflammation by using its virulence factors to invade the intestinal epithelium. But, prolonged inflammation may provoke severe body catabolism and immunological diseases. Salmonella has become more life-threatening due to emergence of multiple-antibiotic resistant strains. Mannose-rich oligosaccharides (MOS) from cells walls of Saccharomyces cerevisiae have shown to bind mannose-specific lectin of Gram-negative bacteria including Salmonella, and prevent their adherence to intestinal epithelial cells. However, whether MOS may potentially mitigate systemic inflammation is not investigated yet. Moreover, molecular events underlying innate immune responses and metabolic activities during late inflammation, in presence or absence of MOS, are unknown. Methods and Principal Findings Using a Salmonella LPS-induced systemic inflammation chicken model and microarray analysis, we investigated the effects of MOS and virginiamycin (VIRG, a sub-therapeutic antibiotic) on innate immunity and glucose metabolism during late inflammation. Here, we demonstrate that MOS and VIRG modulated innate immunity and metabolic genes differently. Innate immune responses were principally mediated by intestinal IL-3, but not TNF-α, IL-1 or IL-6, whereas glucose mobilization occurred through intestinal gluconeogenesis only. MOS inherently induced IL-3 expression in control hosts. Consequent to LPS challenge, IL-3 induction in VIRG hosts but not differentially expressed in MOS hosts revealed that MOS counteracted LPS's detrimental inflammatory effects. Metabolic pathways are built to elucidate the mechanisms by which VIRG host's higher energy requirements were met: including gene up-regulations for intestinal gluconeogenesis (PEPCK) and liver glycolysis (ENO2), and intriguingly liver fatty acid synthesis through ATP citrate synthase (CS) down-regulation and ATP citrate lyase (ACLY) and malic enzyme (ME) up-regulations. However, MOS host's lower energy

  18. Parental Involvement, Interest in Schooling and School Environment as Predictors of Academic Self-Efficacy among Fresh Secondary School Students in Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Adeyemo, David Akinlolu

    2005-01-01

    The purpose of this study was to investigate the impact of parental involvement, interest in schooling and school environment on academic self-efficacy of fresh secondary school students. Two hundred and fifty students constituted the study's sample. Both the independent and the dependent variables were measured with relevant standardized…

  19. An Assessment of Farmers' Willingness to Pay for Extension Services Using the Contingent Valuation Method (CVM): The Case of Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Ajayi, A. O.

    2006-01-01

    This study assessed farmers' willingness to pay (WTP) for extension services. The Contingent Valuation Method (CVM) was used to assess the amount which farmers are willing to pay. Primary data on the demographic, socio-economic variables of farmers and their WTP were collected from 228 farmers selected randomly in a stage-wise sampling procedure…

  20. Disciplining of Student's vis-a-vis the Duties/Responsibilities of Vice Principals in Secondary Institutions in Oyo State: Yesterday and Today

    ERIC Educational Resources Information Center

    Adewusi, Aderogba Oladiran

    2012-01-01

    This paper focused on how Nigeria' teeming youth requires a high level of seriousness from all stakeholders: the student, school administrators, teaching staff, parents, educational agencies and the government. There had been much emphasis on the need for everyone to understand and play specifically assigned roles, and to ensure that the posterity…

  1. Media Choice in Environmental Information Dissemination for Solid Waste Management among Policy Formulators and Implementors: A Case Study of Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Akintola, B. A.; Temowo, O. O.; Ajiboye, J. O.

    2009-01-01

    Environmental information has been described as central to the issues of solid waste management and disposal. This study investigated the availability and accessibility of environmental information to the solid waste policy formulators and implementors with regard to the media/channels used for disseminating environmental information to the…

  2. Adult Learners' Demographic Variable as Predictor of Access and Participation in Literacy Programmes in Oyo and Ondo States, Nigeria

    ERIC Educational Resources Information Center

    Olojede, Adeshina Abideen; Oladitan, Idowu Oladiran

    2013-01-01

    Literacy is an indispensable foundation that enables young people and adults to engage in learning opportunities at all stages of the learning continuum. Literacy is a prerequisite for the development of personal, social, economic and political empowerment. In Nigeria, attempt to increase access to literacy education for the enhancement of…

  3. Immune System

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  4. Determination of exhaled nitric oxide distributions in a diverse sample population using tunable diode laser absorption spectroscopy

    NASA Astrophysics Data System (ADS)

    Namjou, K.; Roller, C. B.; Reich, T. E.; Jeffers, J. D.; McMillen, G. L.; McCann, P. J.; Camp, M. A.

    2006-11-01

    A liquid-nitrogen free mid-infrared tunable diode laser absorption spectroscopy (TDLAS) system equipped with a folded-optical-path astigmatic Herriott cell was used to measure levels of exhaled nitric oxide (eNO) and exhaled carbon dioxide (eCO2) in breath. Quantification of absolute eNO concentrations was performed using NO/CO2 absorption ratios measured by the TDLAS system coupled with absolute eCO2 concentrations measured with a non-dispersive infrared sensor. This technique eliminated the need for routine calibrations using standard cylinder gases. The TDLAS system was used to measure eNO in children and adults (n=799, ages 5 to 64) over a period of more than one year as part of a field study. Volunteers for the study self-reported data including age, height, weight, and health status. The resulting data were used to assess system performance and to generate eNO and eCO2 distributions, which were found to be log-normal and Gaussian, respectively. There were statistically significant differences in mean eNO levels for males and females as well as for healthy and steroid naïve asthmatic volunteers not taking corticosteroid therapies. Ambient NO levels affected measured eNO concentrations only slightly, but this effect was not statistically significant.

  5. Nitric oxide breath testing by tunable-diode laser absorption spectroscopy: application in monitoring respiratory inflammation

    NASA Astrophysics Data System (ADS)

    Roller, Chad; Namjou, Khosrow; Jeffers, James D.; Camp, Mark; Mock, Adam; McCann, Patrick J.; Grego, Joe

    2002-10-01

    We used a high-resolution mid-IR tunable-laser absorption spectroscopy (TLAS) system with a single IV-VI laser operating near 5.2 mum to measure the level of exhaled nitric oxide (eNO) in human breath. A method of internal calibration using simultaneous eNO and exhaled CO2 measurements eliminated the need for system calibration with gas standards. The results observed from internally calibrating the instrument for eNO measurements were compared with measurements of eNO calibrated to gas standards and were found to be similar. Various parameters of the TLAS system for eNO breath testing were examined and include gas cell pressure, exhalation time, and ambient NO concentrations. A reduction in eNO from elevated concentrations (approx44 parts in 109) to near-normal levels (<20 parts in 109) from an asthmatic patient was observed after the patient had received treatment with an inhaled glucocorticoid anti-inflammatory medication. Such measurements can help in evaluating airway inflammation and in monitoring the effectiveness of anti-inflammatory therapies.

  6. A constitutive expression system for glycosyl hydrolase family 7 cellobiohydrolases in Hypocrea jecorina

    SciTech Connect

    Linger, Jeffrey G.; Taylor, II, Larry E.; Baker, John O.; Vander Wall, Todd; Hobdey, Sarah E.; Podkaminer, Kara; Himmel, Michael E.; Decker, Stephen R.

    2015-03-18

    One of the primary industrial-scale cellulase producers is the ascomycete fungus, Hypocrea jecorina, which produces and secretes large quantities of diverse cellulolytic enzymes. Perhaps the single most important biomass degrading enzyme is cellobiohydrolase I (cbh1or Cel7A) due to its enzymatic proficiency in cellulose depolymerization. However, production of Cel7A with native-like properties from heterologous expression systems has proven difficult. In this study, we develop a protein expression system in H. jecorina (Trichoderma reesei) useful for production and secretion of heterologous cellobiohydrolases from glycosyl hydrolase family 7. Building upon previous work in heterologous protein expression in filamentous fungi, we have integrated a native constitutive enolase promoter with the native cbh1 signal sequence. The results are the following: The constitutive eno promoter driving the expression of Cel7A allows growth on glucose and results in repression of the native cellulase system, severely reducing background endo- and other cellulase activity and greatly simplifying purification of the recombinant protein. Coupling this system to a Δcbh1 strain of H. jecorina ensures that only the recombinant Cel7A protein is produced. Two distinct transformant colony morphologies were observed and correlated with high and null protein production. Production levels in ‘fast’ transformants are roughly equivalent to those in the native QM6a strain of H. jecorina, typically in the range of 10 to 30 mg/L when grown in continuous stirred-tank fermenters. ‘Slow’ transformants showed no evidence of Cel7A production. Specific activity of the purified recombinant Cel7A protein is equivalent to that of native protein when assayed on pretreated corn stover, as is the thermal stability and glycosylation level. Purified Cel7A produced from growth on glucose demonstrated remarkably consistent specific activity. Purified Cel7A from the same strain grown on lactose

  7. Stable and accurate hybrid finite volume methods based on pure convexity arguments for hyperbolic systems of conservation law

    NASA Astrophysics Data System (ADS)

    De Vuyst, Florian

    2004-01-01

    This exploratory work tries to present first results of a novel approach for the numerical approximation of solutions of hyperbolic systems of conservation laws. The objective is to define stable and "reasonably" accurate numerical schemes while being free from any upwind process and from any computation of derivatives or mean Jacobian matrices. That means that we only want to perform flux evaluations. This would be useful for "complicated" systems like those of two-phase models where solutions of Riemann problems are hard, see impossible to compute. For Riemann or Roe-like solvers, each fluid model needs the particular computation of the Jacobian matrix of the flux and the hyperbolicity property which can be conditional for some of these models makes the matrices be not R-diagonalizable everywhere in the admissible state space. In this paper, we rather propose some numerical schemes where the stability is obtained using convexity considerations. A certain rate of accuracy is also expected. For that, we propose to build numerical hybrid fluxes that are convex combinations of the second-order Lax-Wendroff scheme flux and the first-order modified Lax-Friedrichs scheme flux with an "optimal" combination rate that ensures both minimal numerical dissipation and good accuracy. The resulting scheme is a central scheme-like method. We will also need and propose a definition of local dissipation by convexity for hyperbolic or elliptic-hyperbolic systems. This convexity argument allows us to overcome the difficulty of nonexistence of classical entropy-flux pairs for certain systems. We emphasize the systematic feature of the method which can be fastly implemented or adapted to any kind of systems, with general analytical or data-tabulated equations of state. The numerical results presented in the paper are not superior to many existing state-of-the-art numerical methods for conservation laws such as ENO, MUSCL or central scheme of Tadmor and coworkers. The interest is rather

  8. Systems Thinking (and Systems Doing).

    ERIC Educational Resources Information Center

    Brethower, Dale M.; Dams, Peter-Cornelius

    1999-01-01

    Introduces human performance technology (HPT) by answering the following questions related to: what systems does; practical issues and questions to which systems thinking is relevant; research questions and answers with respect to systems thinking; how HPT practitioners can do systems thinking; systems thinking tools; what is and is not known…

  9. A high-order vertex-based central ENO finite-volume scheme for three-dimensional compressible flows

    SciTech Connect

    Charest, Marc R.J.; Canfield, Thomas R.; Morgan, Nathaniel R.; Waltz, Jacob; Wohlbier, John G.

    2015-03-11

    High-order discretization methods offer the potential to reduce the computational cost associated with modeling compressible flows. However, it is difficult to obtain accurate high-order discretizations of conservation laws that do not produce spurious oscillations near discontinuities, especially on multi-dimensional unstructured meshes. A novel, high-order, central essentially non-oscillatory (CENO) finite-volume method that does not have these difficulties is proposed for tetrahedral meshes. The proposed unstructured method is vertex-based, which differs from existing cell-based CENO formulations, and uses a hybrid reconstruction procedure that switches between two different solution representations. It applies a high-order k-exact reconstruction in smooth regions and a limited linear reconstruction when discontinuities are encountered. Both reconstructions use a single, central stencil for all variables, making the application of CENO to arbitrary unstructured meshes relatively straightforward. The new approach was applied to the conservation equations governing compressible flows and assessed in terms of accuracy and computational cost. For all problems considered, which included various function reconstructions and idealized flows, CENO demonstrated excellent reliability and robustness. Up to fifth-order accuracy was achieved in smooth regions and essentially non-oscillatory solutions were obtained near discontinuities. The high-order schemes were also more computationally efficient for high-accuracy solutions, i.e., they took less wall time than the lower-order schemes to achieve a desired level of error. In one particular case, it took a factor of 24 less wall-time to obtain a given level of error with the fourth-order CENO scheme than to obtain the same error with the second-order scheme.

  10. A high-order vertex-based central ENO finite-volume scheme for three-dimensional compressible flows

    DOE PAGESBeta

    Charest, Marc R.J.; Canfield, Thomas R.; Morgan, Nathaniel R.; Waltz, Jacob; Wohlbier, John G.

    2015-03-11

    High-order discretization methods offer the potential to reduce the computational cost associated with modeling compressible flows. However, it is difficult to obtain accurate high-order discretizations of conservation laws that do not produce spurious oscillations near discontinuities, especially on multi-dimensional unstructured meshes. A novel, high-order, central essentially non-oscillatory (CENO) finite-volume method that does not have these difficulties is proposed for tetrahedral meshes. The proposed unstructured method is vertex-based, which differs from existing cell-based CENO formulations, and uses a hybrid reconstruction procedure that switches between two different solution representations. It applies a high-order k-exact reconstruction in smooth regions and a limited linearmore » reconstruction when discontinuities are encountered. Both reconstructions use a single, central stencil for all variables, making the application of CENO to arbitrary unstructured meshes relatively straightforward. The new approach was applied to the conservation equations governing compressible flows and assessed in terms of accuracy and computational cost. For all problems considered, which included various function reconstructions and idealized flows, CENO demonstrated excellent reliability and robustness. Up to fifth-order accuracy was achieved in smooth regions and essentially non-oscillatory solutions were obtained near discontinuities. The high-order schemes were also more computationally efficient for high-accuracy solutions, i.e., they took less wall time than the lower-order schemes to achieve a desired level of error. In one particular case, it took a factor of 24 less wall-time to obtain a given level of error with the fourth-order CENO scheme than to obtain the same error with the second-order scheme.« less

  11. Report to the Nuclear Regulatory Commission from the staff panel on the Commission's determination of an Extraordinary Nuclear Occurrence (ENO)

    SciTech Connect

    1980-01-01

    The Panel finds that the first criterion, pertaining to whether the accident caused a discharge of radioactive material or levels of radiation offsite as defined in 10 CFR 140.84, has not been met. It further finds that there is presently insufficient information to support any definitive finding as to whether or not the second criterion, relating to damage to persons or property offsite as defined in 10 CFR 140.85, has been met. Since the Panel has not found that both criteria have been met, it recommends that the Commission determine that the accident at Three Mile Island did not constitute an extraordinary nuclear occurrence.

  12. Crystal Systems.

    ERIC Educational Resources Information Center

    Schomaker, Verner; Lingafelter, E. C.

    1985-01-01

    Discusses characteristics of crystal systems, comparing (in table format) crystal systems with lattice types, number of restrictions, nature of the restrictions, and other lattices that can accidently show the same metrical symmetry. (JN)

  13. Concentrator Systems

    NASA Astrophysics Data System (ADS)

    Luque-Heredia, Ignacio; Luque, Antonio

    2015-10-01

    The following sections are included: * Introduction * The early development of CPV * Concentrator solar cells * Optics for photovoltaic concentrators * Photovoltaic concentration modules * Tracking systems for photovoltaic concentration * High-concentration systems * Rating and performance * Cost considerations * Conclusions * References

  14. Discovery Systems

    NASA Technical Reports Server (NTRS)

    Pell, Barney

    2003-01-01

    A viewgraph presentation on NASA's Discovery Systems Project is given. The topics of discussion include: 1) NASA's Computing Information and Communications Technology Program; 2) Discovery Systems Program; and 3) Ideas for Information Integration Using the Web.

  15. Fluid Management System (FMS) fluid systems overview

    NASA Technical Reports Server (NTRS)

    Baird, R. S.

    1990-01-01

    Viewgraphs on fluid management system (FMS) fluid systems overview are presented. Topics addressed include: fluid management system description including system requirements (integrated nitrogen system, integrated water system, and integrated waste gas system) and physical description; and fluid management system evolution.

  16. Linked Systems.

    ERIC Educational Resources Information Center

    Association of Research Libraries, Washington, DC.

    Three papers are compiled here for research library directors: (1) "Background: Open Systems Interconnection," in which David F. Bishop provides fundamental background information to explain the concept of the emerging technology of linked systems and open systems interconnection--i.e., an agreed upon standard set of conventions or rules that,…

  17. Systems Engineering

    NASA Technical Reports Server (NTRS)

    Pellerano, Fernando

    2015-01-01

    This short course provides information on what systems engineering is and how the systems engineer guides requirements, interfaces with the discipline leads, and resolves technical issues. There are many system-wide issues that either impact or are impacted by the thermal subsystem. This course will introduce these issues and illustrate them with real life examples.

  18. Expert systems and fuzzy systems

    SciTech Connect

    Negoita, C.

    1985-01-01

    This book examines the design of the expert computer system and how fuzzy systems can be used to deal with imprecise information. As the author explores the effects of semantic systems on decision support systems, he asserts that the utilization of fuzzy set theory can help an expert system draw from its knowledge base more efficiently and therefore make more accurate and reliable decisions. The book includes realistic status reports in approximate reasoning and knowledge representation that are supported by a ''theory of categories'' mathematical approach. The differences between symbolic and semantic manipulation are outline, and detailed information is given on the actual theory of knowledge-based systems.

  19. System Effectiveness

    SciTech Connect

    Powell, Danny H; Elwood Jr, Robert H

    2011-01-01

    An effective risk assessment system is needed to address the threat posed by an active or passive insider who, acting alone or in collusion, could attempt diversion or theft of nuclear material. It is critical that a nuclear facility conduct a thorough self-assessment of the material protection, control, and accountability (MPC&A) system to evaluate system effectiveness. Self-assessment involves vulnerability analysis and performance testing of the MPC&A system. The process should lead to confirmation that mitigating features of the system effectively minimize the threat, or it could lead to the conclusion that system improvements or upgrades are necessary to achieve acceptable protection against the threat. Analysis of the MPC&A system is necessary to understand the limits and vulnerabilities of the system to internal threats. Self-assessment helps the facility be prepared to respond to internal threats and reduce the risk of theft or diversion of nuclear material. MSET is a self-assessment or inspection tool utilizing probabilistic risk assessment (PRA) methodology to calculate the system effectiveness of a nuclear facility's MPC&A system. MSET analyzes the effectiveness of an MPC&A system based on defined performance metrics for MPC&A functions based on U.S. and international best practices and regulations. A facility's MC&A system can be evaluated at a point in time and reevaluated after upgrades are implemented or after other system changes occur. The total system or specific subareas within the system can be evaluated. Areas of potential performance improvement or system upgrade can be assessed to determine where the most beneficial and cost-effective improvements should be made. Analyses of risk importance factors show that sustainability is essential for optimal performance. The analyses reveal where performance degradation has the greatest detrimental impact on total system risk and where performance improvements have the greatest reduction in system risk

  20. Cryogenic Systems

    NASA Astrophysics Data System (ADS)

    Hosoyama, Kenji

    2002-02-01

    In this lecture we discuss the principle of method of cooling to a very low temperature, i.e. cryogenic. The "gas molecular model" will be introduced to explain the mechanism cooling by the expansion engine and the Joule-Thomson expansion valve. These two expansion processes are normally used in helium refrigeration systems to cool the process gas to cryogenic temperature. The reverse Carnot cycle will be discussed in detail as an ideal refrigeration cycle. First the fundamental process of liquefaction and refrigeration cycles will be discussed, and then the practical helium refrigeration system. The process flow of the system and the key components; -compressor, expander, and heat exchanger- will be discussed. As an example of an actual refrigeration system, we will use the cryogenic system for the KEKB superconducting RF cavity. We will also discuss the liquid helium distribution system, which is very important, especially for the cryogenic systems used in accelerator applications. 1 Principles of Cooling and Fundamental Cooling Cycle 2 Expansion engine, Joule-Thomson expansion, kinetic molecular theory, and enthalpy 3 Liquefaction Systems 4 Refrigeration Systems 5 Practical helium liquefier/refrigeration system 6 Cryogenic System for TRISTAN Superconducting RF Cavity

  1. Geothermal systems

    NASA Technical Reports Server (NTRS)

    Mohl, C.

    1978-01-01

    Several tasks of JPL related to geothermal energy are discussed. The major task is the procurement and test and evaluation of a helical screw drive (wellhead unit). A general review of geothermal energy systems is given. The presentation focuses attention on geothermal reservoirs in California, with graphs and charts to support the discussion. Included are discussions on cost analysis, systems maintenance, and a comparison of geothermal and conventional heating and cooling systems.

  2. [Information systems].

    PubMed

    Rodríguez Maniega, José Antonio; Trío Maseda, Reyes

    2005-03-01

    The arrival of victims of the terrorist attacks of 11 March at the hospital put the efficiency of its information systems to the test. To be most efficient, these systems should be simple and directed, above all, to the follow-up of victims and to providing the necessary information to patients and families. A specific and easy to use system is advisable. PMID:15771852

  3. Systemic darwinism.

    PubMed

    Winther, Rasmus Grønfeldt

    2008-08-19

    Darwin's 19th century evolutionary theory of descent with modification through natural selection opened up a multidimensional and integrative conceptual space for biology. We explore three dimensions of this space: explanatory pattern, levels of selection, and degree of difference among units of the same type. Each dimension is defined by a respective pair of poles: law and narrative explanation, organismic and hierarchical selection, and variational and essentialist thinking. As a consequence of conceptual debates in the 20th century biological sciences, the poles of each pair came to be seen as mutually exclusive opposites. A significant amount of 21st century research focuses on systems (e.g., genomic, cellular, organismic, and ecological/global). Systemic Darwinism is emerging in this context. It follows a "compositional paradigm" according to which complex systems and their hierarchical networks of parts are the focus of biological investigation. Through the investigation of systems, Systemic Darwinism promises to reintegrate each dimension of Darwin's original logical space. Moreover, this ideally and potentially unified theory of biological ontology coordinates and integrates a plurality of mathematical biological theories (e.g., self-organization/structure, cladistics/history, and evolutionary genetics/function). Integrative Systemic Darwinism requires communal articulation from a plurality of perspectives. Although it is more general than these, it draws on previous advances in Systems Theory, Systems Biology, and Hierarchy Theory. Systemic Darwinism would greatly further bioengineering research and would provide a significantly deeper and more critical understanding of biological reality. PMID:18697926

  4. Anticipatory systems as linguistic systems

    NASA Astrophysics Data System (ADS)

    Ekdahl, Bertil

    2000-05-01

    The idea of system is well established although not well defined. What makes up a system depends on the observer. Thinking in terms of systems is only a convenient way to conceptualize organizations, natural or artificial, that show coherent properties. Among all properties, which can be ascribed to systems, one property seems to be more outstanding than others, namely that of being anticipatory. In nature, anticipatory properties are found only in living organizations. In this way it can be said to separate non-living systems from living because there is no indication that any natural phenomenon occurring in systems where there is no indication of life is anticipatory. The characteristic of living systems is that they are exposed to the evolution contrary to causal systems that do not undergo changes due to the influence of the environment. Causal systems are related to the past in such a way that subsequent situations can be calculated from knowledge of past situations. In causal systems the past is the cause of the present and there is no reference to the future as a determining agent, contrary to anticipatory systems where expectations are the cause of the present action. Since anticipatory properties are characteristic of living systems, this property, as all other properties in living systems, is a result of the evolution and can be found in plants as well as in animals. Thus, it is not only tied to consciousness but is found at a more basic level, i.e., in the interplay between genotype and phenotype. Anticipation is part of the genetic language in such a way that appropriate actions, for events in the anticipatory systems environment, are inscribed in the genes. Anticipatory behavior, as a result of the interpretation of the genetic language, has been selected by the evolution. In this paper anticipatory systems are regarded as linguistic systems and I argue that as such anticipation cannot be fragmented but must be holistically studied. This has the

  5. Educational Systems.

    ERIC Educational Resources Information Center

    Archer, Margaret

    1981-01-01

    Presents a general review of research on educational systems, with emphasis on variations in the definition of an educational system, neglected questions, areas of major concern, research needs, traditional and modern stands in the sociology of education, educational politics, and researcher bias. (DB)

  6. Systemic Change.

    ERIC Educational Resources Information Center

    Tosti, Donald T.

    2000-01-01

    Examines three factors contributing to organizational success: use of a systemic model to design and guide the change effort; analysis of interdependencies within the system and of the change potential; and use of communication methods to help ensure that the change will be supported. Presents characteristics of successful change efforts with…

  7. Power system

    DOEpatents

    Hickam, Christopher Dale

    2008-03-18

    A power system includes a prime mover, a transmission, and a fluid coupler having a selectively engageable lockup clutch. The fluid coupler may be drivingly connected between the prime mover and the transmission. Additionally, the power system may include a motor/generator drivingly connected to at least one of the prime mover and the transmission. The power-system may also include power-system controls configured to execute a control method. The control method may include selecting one of a plurality of modes of operation of the power system. Additionally, the control method may include controlling the operating state of the lockup clutch dependent upon the mode of operation selected. The control method may also include controlling the operating state of the motor/generator dependent upon the mode of operation selected.

  8. Electronic system

    DOEpatents

    Robison, G H; Dickson, J F

    1960-11-15

    An electronic system is designed for indicating the occurrence of a plurality of electrically detectable events within predetermined time intervals. The system comprises separate input means electrically associated with the events under observation an electronic channel associated with each input means, including control means and indicating means; timing means adapted to apply a signal from the input means after a predetermined time to the control means to deactivate each of the channels; and means for resetting the system to its initial condition after the observation of each group of events. (D.L.C.)

  9. System identification

    NASA Astrophysics Data System (ADS)

    Juang, Jer-Nan

    Major issues in system identification are summarized and recent advances are reviewed. Modal testing and system identification used in control theory are examined, and the mathematical relationships and conversions of the models appropriate to modal testing and those appropriate to modern control design methods are discussed. The importance of obtaining input and output matrices in modal testing is emphasized, and the changes that may be needed in modal testing procedures to meet the needs of the control system designer are addressed. Directions for future research are considered.

  10. Saturn Systems.

    PubMed

    U Rehman, Habib; McKee, Nida A; McKee, Michael L

    2016-01-15

    Several ring systems (Saturn systems) have been studied using DFT methods that include dispersion effects. Comparison with X-ray structures are made with three systems, and the agreement is quite good. Binding enthalpies and binding free energies in dichloromethane and toluene have been computed. The effect of an encapsulated lithium cation is accessed by comparing C60 @(C6 H4 )10 and [Li@C60 @(C6 H4 )10 ](+). The [Li@C60 ](+) cation is a much better acceptor than C60 which leads to greater donor-acceptor interactions and larger charge transfer from the ring to [Li@C60 ](+). PMID:26096724

  11. Processing system

    NASA Technical Reports Server (NTRS)

    Hilland, J. E.

    1983-01-01

    To implement the analysis techniques and to provide end-to-end processing, a system was designed with the following capabilities: receive and catalog data from many sources; organize the data on mass storage for rapid access; edit for reasonableness; create new data sets by sorting on parameter, averaging and merging; provide statistical analysis and display tools; and distribute data on demand. Consideration was given to developing a flexible system that could meet immediate workshop needs and respond to future requirements. System architecture and data set details implemented are discussed.

  12. Respiratory system

    NASA Technical Reports Server (NTRS)

    Bartlett, R. G., Jr.

    1973-01-01

    The general anatomy and function of the human respiratory system is summarized. Breathing movements, control of breathing, lung volumes and capacities, mechanical relations, and factors relevant to respiratory support and equipment design are discussed.

  13. Microelectromechanical Systems

    NASA Technical Reports Server (NTRS)

    Gabriel, Kaigham J.

    1995-01-01

    Micro-electromechanical systems (MEMS) is an enabling technology that merges computation and communication with sensing and actuation to change the way people and machines interact with the physical world. MEMS is a manufacturing technology that will impact widespread applications including: miniature inertial measurement measurement units for competent munitions and personal navigation; distributed unattended sensors; mass data storage devices; miniature analytical instruments; embedded pressure sensors; non-invasive biomedical sensors; fiber-optics components and networks; distributed aerodynamic control; and on-demand structural strength. The long term goal of ARPA's MEMS program is to merge information processing with sensing and actuation to realize new systems and strategies for both perceiving and controlling systems, processes, and the environment. The MEMS program has three major thrusts: advanced devices and processes, system design, and infrastructure.

  14. Lymph system

    MedlinePlus

    ... the lymph nodes make more infection-fighting white blood cells, which cause the nodes to swell. The swollen nodes are sometimes felt in the neck, under the arms, and groin. The lymph system includes the: Tonsils Adenoids Spleen Thymus

  15. [Systemic urticarias].

    PubMed

    Hachulla, E

    2003-05-01

    Systemic urticaria remains a challenge in terms of etiology, investigation and management. Most of cases are urticarial vasculitis consequence of inflammatory injury of capillaries and postcapillary venules in the skin. If hypocomplementemic urticarial vasculitis syndrome is a classical cause, the majority of patients have an underlying systemic disease like systemic lupus erythematosus, Sjögren's syndrome, mixed cryoglobulinemia, Still disease or cancer. Others systemic urticaria have been reported without clearly evidence of vasculitis like in primary or acquired angioedema, hereditary periodic fever syndromes and in some thyroiditis. Diagnosis needs a step to step procedure. Treatment depends the underlying disease. Some patients respond to nonsteroidal antiinflammatory drugs, some other need corticosteroids or immunosuppression. If urticarial vasculitis seems isolated in the absence of chronic obstructive pulmonary disease, antihistamines, nonsteroidal antiinflammatory drugs, colchicine, dapsone or hydroxychloroquine must be first used. PMID:12843810

  16. SAMPLING SYSTEM

    DOEpatents

    Hannaford, B.A.; Rosenberg, R.; Segaser, C.L.; Terry, C.L.

    1961-01-17

    An apparatus is given for the batch sampling of radioactive liquids such as slurries from a system by remote control, while providing shielding for protection of operating personnel from the harmful effects of radiation.

  17. Recommender systems

    NASA Astrophysics Data System (ADS)

    Lü, Linyuan; Medo, Matúš; Yeung, Chi Ho; Zhang, Yi-Cheng; Zhang, Zi-Ke; Zhou, Tao

    2012-10-01

    The ongoing rapid expansion of the Internet greatly increases the necessity of effective recommender systems for filtering the abundant information. Extensive research for recommender systems is conducted by a broad range of communities including social and computer scientists, physicists, and interdisciplinary researchers. Despite substantial theoretical and practical achievements, unification and comparison of different approaches are lacking, which impedes further advances. In this article, we review recent developments in recommender systems and discuss the major challenges. We compare and evaluate available algorithms and examine their roles in the future developments. In addition to algorithms, physical aspects are described to illustrate macroscopic behavior of recommender systems. Potential impacts and future directions are discussed. We emphasize that recommendation has great scientific depth and combines diverse research fields which makes it interesting for physicists as well as interdisciplinary researchers.

  18. Systems and Components Fuel Delivery System, Water Delivery System, ...

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

    Systems and Components - Fuel Delivery System, Water Delivery System, Derrick Crane System, and Crane System Details - Marshall Space Flight Center, F-1 Engine Static Test Stand, On Route 565 between Huntsville and Decatur, Huntsville, Madison County, AL

  19. Systems Studies

    SciTech Connect

    Graham, R.L.

    1998-03-17

    The Systems Studies Activity had two objectives: (1) to investigate nontechnical barriers to the deployment of biomass production and supply systems and (2) to enhance and extend existing systems models of bioenergy supply and use. For the first objective, the Activity focused on existing bioenergy markets. Four projects were undertaken: a comparative analysis of bioenergy in Sweden and Austria; a one-day workshop on nontechnical barriers jointly supported by the Production Systems Activity; the development and testing of a framework for analyzing barriers and drivers to bioenergy markets; and surveys of wood pellet users in Sweden, Austria and the US. For the second objective, two projects were undertaken. First, the Activity worked with the Integrated BioEnergy Systems (TBS) Activity of TEA Bioenergy Task XIII to enhance the BioEnergy Assessment Model (BEAM). This model is documented in the final report of the IBS Activity. The Systems Studies Activity contributed to enhancing the feedstock portion of the model by developing a coherent set of willow, poplar, and switchgrass production modules relevant to both the US and the UK. The Activity also developed a pretreatment module for switchgrass. Second, the Activity sponsored a three-day workshop on modeling bioenergy systems with the objectives of providing an overview of the types of models used to evaluate bioenergy and promoting communication among bioenergy modelers. There were nine guest speakers addressing different types of models used to evaluate different aspects of bioenergy, ranging from technoeconomic models based on the ASPEN software to linear programming models to develop feedstock supply curves for the US. The papers from this workshop have been submitted to Biomass and Bioenergy and are under editorial review.

  20. Systemic trauma.

    PubMed

    Goldsmith, Rachel E; Martin, Christina Gamache; Smith, Carly Parnitzke

    2014-01-01

    Substantial theoretical, empirical, and clinical work examines trauma as it relates to individual victims and perpetrators. As trauma professionals, it is necessary to acknowledge facets of institutions, cultures, and communities that contribute to trauma and subsequent outcomes. Systemic trauma-contextual features of environments and institutions that give rise to trauma, maintain it, and impact posttraumatic responses-provides a framework for considering the full range of traumatic phenomena. The current issue of the Journal of Trauma & Dissociation is composed of articles that incorporate systemic approaches to trauma. This perspective extends conceptualizations of trauma to consider the influence of environments such as schools and universities, churches and other religious institutions, the military, workplace settings, hospitals, jails, and prisons; agencies and systems such as police, foster care, immigration, federal assistance, disaster management, and the media; conflicts involving war, torture, terrorism, and refugees; dynamics of racism, sexism, discrimination, bullying, and homophobia; and issues pertaining to conceptualizations, measurement, methodology, teaching, and intervention. Although it may be challenging to expand psychological and psychiatric paradigms of trauma, a systemic trauma perspective is necessary on both scientific and ethical grounds. Furthermore, a systemic trauma perspective reflects current approaches in the fields of global health, nursing, social work, and human rights. Empirical investigations and intervention science informed by this paradigm have the potential to advance scientific inquiry, lower the incidence of a broader range of traumatic experiences, and help to alleviate personal and societal suffering. PMID:24617751

  1. Systemic fluoride.

    PubMed

    Sampaio, Fábio Correia; Levy, Steven Marc

    2011-01-01

    There is substantial evidence that fluoride, through different applications and formulas, works to control caries development. The first observations of fluoride's effects on dental caries were linked to fluoride naturally present in the drinking water, and then from controlled water fluoridation programs. Other systemic methods to deliver fluoride were later suggested, including dietary fluoride supplements such as salt and milk. These systemic methods are now being questioned due to the fact that many studies have indicated that fluoride's action relies mainly on its post-eruptive effect from topical contact with the tooth structure. It is known that even the methods of delivering fluoride known as 'systemic' act mainly through a topical effect when they are in contact with the teeth. The effectiveness of water fluoridation in many geographic areas is lower than in previous eras due to the widespread use of other fluoride modalities. Nevertheless, this evidence should not be interpreted as an indication that systemic methods are no longer relevant ways to deliver fluoride on an individual basis or for collective health programs. Caution must be taken to avoid excess ingestion of fluoride when prescribing dietary fluoride supplements for children in order to minimize the risk of dental fluorosis, particularly if there are other relevant sources of fluoride intake - such as drinking water, salt or milk and/or dentifrice. Safe and effective doses of fluoride can be achieved when combining topical and systemic methods. PMID:21701196

  2. Turbine system

    DOEpatents

    McMahan, Kevin Weston; Dillard, Daniel Jackson

    2016-05-03

    A turbine system is disclosed. The turbine system includes a transition duct having an inlet, an outlet, and a passage extending between the inlet and the outlet and defining a longitudinal axis, a radial axis, and a tangential axis. The outlet of the transition duct is offset from the inlet along the longitudinal axis and the tangential axis. The turbine system further includes a turbine section connected to the transition duct. The turbine section includes a plurality of shroud blocks at least partially defining a hot gas path, a plurality of buckets at least partially disposed in the hot gas path, and a plurality of nozzles at least partially disposed in the hot gas path. At least one of a shroud block, a bucket, or a nozzle includes means for withstanding high temperatures.

  3. Memory systems.

    PubMed

    Wolk, David A; Budson, Andrew E

    2010-08-01

    Converging evidence from patient and neuroimaging studies suggests that memory is a collection of abilities that use different neuroanatomic systems. Neurologic injury may impair one or more of these memory systems. Episodic memory allows us to mentally travel back in time and relive an episode of our life. Episodic memory depends on the hippocampus, other medial temporal lobe structures, the limbic system, and the frontal lobes, as well as several other brain regions. Semantic memory provides our general knowledge about the world and is unconnected to any specific episode of our life. Although semantic memory likely involves much of the neocortex, the inferolateral temporal lobes (particularly the left) are most important. Procedural memory enables us to learn cognitive and behavioral skills and algorithms that operate at an automatic, unconscious level. Damage to the basal ganglia, cerebellum, and supplementary motor area often impair procedural memory. PMID:22810510

  4. Lindenmayer Systems

    NASA Astrophysics Data System (ADS)

    Honkala, Juha

    The theory of Lindenmayer systems studies free monoid morphisms, free monoid substitutions and their iterations. In this chapter, we discuss similar ideas in a more general framework. Instead of a free monoid, we consider the free semi-algebra S<Σ*> consisting of polynomials with non-commuting variables in Σ and coefficients in a semiring S and we study the iteration of endomorphisms of S<Σ*>. We allow various modes of iteration and we consider various classes of morphisms. Classical L systems are obtained as special cases by taking S to be the Boolean semiring. Our approach also generalizes the theory of algebraic series in noncommuting variables.

  5. ELECTRONIC SYSTEM

    DOEpatents

    Robison, G.H. et al.

    1960-11-15

    An electronic system is described for indicating the occurrence of a plurality of electrically detectable events within predetermined time intervals. It is comprised of separate input means electrically associated with the events under observation: an electronic channel associated with each input means including control means and indicating means; timing means associated with each of the input means and the control means and adapted to derive a signal from the input means and apply it after a predetermined time to the control means to effect deactivation of each of the channels; and means for resetting the system to its initial condition after observation of each group of events.

  6. Complex Systems

    PubMed Central

    Goldberger, Ary L.

    2006-01-01

    Physiologic systems in health and disease display an extraordinary range of temporal behaviors and structural patterns that defy understanding based on linear constructs, reductionist strategies, and classical homeostasis. Application of concepts and computational tools derived from the contemporary study of complex systems, including nonlinear dynamics, fractals and “chaos theory,” is having an increasing impact on biology and medicine. This presentation provides a brief overview of an emerging area of biomedical research, including recent applications to cardiopulmonary medicine and chronic obstructive lung disease. PMID:16921107

  7. Computer systems

    NASA Technical Reports Server (NTRS)

    Olsen, Lola

    1992-01-01

    In addition to the discussions, Ocean Climate Data Workshop hosts gave participants an opportunity to hear about, see, and test for themselves some of the latest computer tools now available for those studying climate change and the oceans. Six speakers described computer systems and their functions. The introductory talks were followed by demonstrations to small groups of participants and some opportunities for participants to get hands-on experience. After this familiarization period, attendees were invited to return during the course of the Workshop and have one-on-one discussions and further hands-on experience with these systems. Brief summaries or abstracts of introductory presentations are addressed.

  8. Microbiology System

    NASA Technical Reports Server (NTRS)

    1992-01-01

    Technology originating in a NASA-sponsored study of the measurement of microbial growth in zero gravity led to the development of Biomerieux Vitek, Inc.'s VITEK system. VITEK provides a physician with accurate diagnostic information and identifies the most effective medication. Test cards are employed to identify organisms and determine susceptibility to antibiotics. A photo-optical scanner scans the card and monitors changes in the growth of cells contained within the card. There are two configurations - VITEK and VITEK JR as well as VIDAS, a companion system that detects bacteria, viruses, etc. from patient specimens. The company was originally created by McDonnell Douglas, the NASA contractor.

  9. Auditory system

    NASA Technical Reports Server (NTRS)

    Ades, H. W.

    1973-01-01

    The physical correlations of hearing, i.e. the acoustic stimuli, are reported. The auditory system, consisting of external ear, middle ear, inner ear, organ of Corti, basilar membrane, hair cells, inner hair cells, outer hair cells, innervation of hair cells, and transducer mechanisms, is discussed. Both conductive and sensorineural hearing losses are also examined.

  10. Immune System

    EPA Science Inventory

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  11. Metric System.

    ERIC Educational Resources Information Center

    Del Mod System, Dover, DE.

    This autoinstructional unit deals with the identification of units of measure in the metric system and the construction of relevant conversion tables. Students in middle school or in grade ten, taking a General Science course, can handle this learning activity. It is recommended that high, middle or low level achievers can use the program.…

  12. Irrigation System

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Under contract with Marshall Space Flight Center, Midwest Research Institute compiled a Lubrication Handbook intended as a reference source for designers and manufacturers of aerospace hardware and crews responsible for maintenance of such equipment. Engineers of Lindsay Manufacturing Company learned of this handbook through NASA Tech Briefs and used it for supplemental information in redesigning gear boxes for their center pivot agricultural irrigation system.

  13. Cardiovascular system

    MedlinePlus Videos and Cool Tools

    The cardiovascular system is composed of the heart and the network of arteries, veins, and capillaries that transport blood throughout the body. The ... which they are eliminated. Most of the blood is made up of a watery, protein-laden fluid ...

  14. Systems Science

    ERIC Educational Resources Information Center

    Christakis, Alexander; Hammond, Debora; Jackson, Michael; Laszlo, Alexander; Mitroff, Ian; Snowden, Dave; Troncale, Len; Carr-Chellman, Alison; Spector, J. Michael; Wilson, Brent

    2013-01-01

    Scholars representing the field of systems science were asked to identify what they considered to be the most exciting and imaginative work currently being done in their field, as well as how that work might change our understanding. The scholars included Alexander Christakis, Debora Hammond, Michael Jackson, Alexander Laszlo, Ian Mitroff, Dave…

  15. STAR System.

    ERIC Educational Resources Information Center

    Doverspike, James E.

    The STAR System is a developmental guidance approach to be used with elementary school children in the 5th or 6th grades. Two basic purposes underlie STAR: to increase learning potential and to enhance personal growth and development. STAR refers to 4 basic skills: sensory, thinking, adapting, and revising. Major components of the 4 skills are:…

  16. System Dynamics

    NASA Astrophysics Data System (ADS)

    Morecroft, John

    System dynamics is an approach for thinking about and simulating situations and organisations of all kinds and sizes by visualising how the elements fit together, interact and change over time. This chapter, written by John Morecroft, describes modern system dynamics which retains the fundamentals developed in the 1950s by Jay W. Forrester of the MIT Sloan School of Management. It looks at feedback loops and time delays that affect system behaviour in a non-linear way, and illustrates how dynamic behaviour depends upon feedback loop structures. It also recognises improvements as part of the ongoing process of managing a situation in order to achieve goals. Significantly it recognises the importance of context, and practitioner skills. Feedback systems thinking views problems and solutions as being intertwined. The main concepts and tools: feedback structure and behaviour, causal loop diagrams, dynamics, are practically illustrated in a wide variety of contexts from a hot water shower through to a symphony orchestra and the practical application of the approach is described through several real examples of its use for strategic planning and evaluation.

  17. Systems Biology

    SciTech Connect

    Wiley, H S.

    2006-06-01

    The biology revolution over the last 50 years has been driven by the ascendancy of molecular biology. This was enthusiastically embraced by most biologists because it took us into increasingly familiar territory. It took mysterious processes, such as the replication of genetic material and assigned them parts that could be readily understood by the human mind. When we think of ''molecular machines'' as being the underlying basis of life, we are using a paradigm derived from everyday experience. However, the price that we paid was a relentless drive towards reductionism and the attendant balkanization of biology. Now along comes ''systems biology'' that promises us a solution to the problem of ''knowing more and more about less and less''. Unlike molecular biology, systems biology appears to be taking us into unfamiliar intellectual territory, such as statistics, mathematics and computer modeling. Not surprisingly, systems biology has met with widespread skepticism and resistance. Why do we need systems biology anyway and how does this new area of research promise to change the face of biology in the next couple of decades?

  18. Surveying System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Sunrise Geodetic Surveys are setting up their equipment for a town survey. Their equipment differs from conventional surveying systems that employ transit rod and chain to measure angles and distances. They are using ISTAC Inc.'s Model 2002 positioning system, which offers fast accurate surveying with exceptional signals from orbiting satellites. The special utility of the ISTAC Model 2002 is that it can provide positioning of the highest accuracy from Navstar PPS signals because it requires no knowledge of secret codes. It operates by comparing the frequency and time phase of a Navstar signal arriving at one ISTAC receiver with the reception of the same set of signals by another receiver. Data is computer processed and translated into three dimensional position data - latitude, longitude and elevation.

  19. Burner systems

    DOEpatents

    Doherty, Brian J.

    1984-07-10

    A burner system particularly useful for downhole deployment includes a tubular combustion chamber unit housed within a tubular coolant jacket assembly. The combustion chamber unit includes a monolithic tube of refractory material whose inner surface defines the combustion zone. A metal reinforcing sleeve surrounds and extends the length of the refractory tube. The inner surface of the coolant jacket assembly and outer surface of the combustion chamber unit are dimensioned so that those surfaces are close to one another in standby condition so that the combustion chamber unit has limited freedom to expand with that expansion being stabilized by the coolant jacket assembly so that compression forces in the refractory tube do not exceed about one-half the safe compressive stress of the material; and the materials of the combustion chamber unit are selected to establish thermal gradient parameters across the combustion chamber unit to maintain the refractory tube in compression during combustion system start up and cool down sequences.

  20. Copernican System

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    The heliocentric (i.e. `Sun-centered') theory proposed by the Polish astronomer Nicolaus Copernicus (1473-1543), and published by him in 1543 in his book, De Revolutionibus Orbium Coelestium. In this system Copernicus placed the Sun at the center of the universe and regarded the Earth and the planets as moving around it in circular orbits. Because of his retention of the notion of circular motion...

  1. Gasification system

    DOEpatents

    Haldipur, Gaurang B.; Anderson, Richard G.; Cherish, Peter

    1985-01-01

    A method and system for injecting coal and process fluids into a fluidized bed gasification reactor. Three concentric tubes extend vertically upward into the fluidized bed. Coal particulates in a transport gas are injected through an inner tube, and an oxygen rich mixture of oxygen and steam are injected through an inner annulus about the inner tube. A gaseous medium relatively lean in oxygen content, such as steam, is injected through an annulus surrounding the inner annulus.

  2. Gasification system

    DOEpatents

    Haldipur, Gaurang B.; Anderson, Richard G.; Cherish, Peter

    1983-01-01

    A method and system for injecting coal and process fluids into a fluidized bed gasification reactor. Three concentric tubes extend vertically upward into the fluidized bed. Coal particulates in a transport gas are injected through an inner tube, and an oxygen rich mixture of oxygen and steam are injected through an inner annulus about the inner tube. A gaseous medium relatively lean in oxygen content, such as steam, is injected through an annulus surrounding the inner annulus.

  3. Tychonic System

    NASA Astrophysics Data System (ADS)

    Murdin, P.

    2000-11-01

    The world system proposed in 1583 by the Danish astronomer Tycho Brahe (1546-1601). Unable to accept the Copernican doctrine that the Earth moves around the Sun, he put forward the view, later disproved by Kepler (1571-1630), that the planets move around the Sun, but the Sun and Moon move around the Earth. The theory explained the observed variations of the phases of Venus, for which the Ptolemai...

  4. Imaging System

    NASA Technical Reports Server (NTRS)

    1995-01-01

    The 1100C Virtual Window is based on technology developed under NASA Small Business Innovation (SBIR) contracts to Ames Research Center. For example, under one contract Dimension Technologies, Inc. developed a large autostereoscopic display for scientific visualization applications. The Virtual Window employs an innovative illumination system to deliver the depth and color of true 3D imaging. Its applications include surgery and Magnetic Resonance Imaging scans, viewing for teleoperated robots, training, and in aviation cockpit displays.

  5. Security system

    DOEpatents

    Baumann, Mark J.; Kuca, Michal; Aragon, Mona L.

    2016-02-02

    A security system includes a structure having a structural surface. The structure is sized to contain an asset therein and configured to provide a forceful breaching delay. The structure has an opening formed therein to permit predetermined access to the asset contained within the structure. The structure includes intrusion detection features within or associated with the structure that are activated in response to at least a partial breach of the structure.

  6. Mine system

    SciTech Connect

    Stoppani, B.R.

    1983-10-04

    A mine system comprises at least one mining machine adapted to haul itself, in a reciprocating manner, along a mineral face, and a control box housing means to control the various electrical elements of the machine(s), the box being located in a mine roadway at one end of the mineral face along which the machine(s) is reciprocating, and the box being electrically connected to a terminal box housed in a body of the machine(s).

  7. Systemic amyloidosis.

    PubMed

    Wechalekar, Ashutosh D; Gillmore, Julian D; Hawkins, Philip N

    2016-06-25

    Tissue deposition of protein fibrils causes a group of rare diseases called systemic amyloidoses. This Seminar focuses on changes in their epidemiology, the current approach to diagnosis, and advances in treatment. Systemic light chain (AL) amyloidosis is the most common of these conditions, but wild-type transthyretin cardiac amyloidosis (ATTRwt) is increasingly being diagnosed. Typing of amyloid fibrils, a critical determinant of therapy, has improved with the wide availability of laser capture and mass spectrometry from fixed histological tissue sections. Specific and accurate evaluation of cardiac amyloidosis is now possible using cardiac magnetic resonance imaging and cardiac repurposing of bone scintigraphy tracers. Survival in AL amyloidosis has improved markedly as novel chemotherapy agents have become available, but challenges remain in advanced disease. Early diagnosis, a key to better outcomes, still remains elusive. Broadening the amyloid-specific therapeutic landscape to include RNA inhibitors, fibril formation stabilisers and inhibitors, and immunotherapeutic targeting of amyloid deposits holds promise to transform outcomes in systemic amyloidoses. PMID:26719234

  8. Braking system

    DOEpatents

    Norgren, D.U.

    1982-09-23

    A balanced braking system comprising a plurality of braking assemblies located about a member to be braked. Each of the braking assemblies consists of a spring biased piston of a first material fitted into a body of a different material which has a greater contraction upon cooling than the piston material. The piston is provided with a recessed head portion over which is positioned a diaphragm and forming a space therebetween to which is connected a pressurized fluid supply. The diaphragm is controlled by the fluid in the space to contact or withdraw from the member to be braked. A cooling means causes the body within which the piston is fitted to contract more than the piston, producing a tight shrink fit therebetween. The braking system is particularly applicable for selectively braking an arbor of an electron microscope which immobilizes, for example, a vertically adjustable low temperature specimen holder during observation. The system provides balanced braking forces which can be easily removed and re-established with minimal disturbance to arbor location.

  9. Anti-obesogenic role of endothelial nitric oxide synthase

    PubMed Central

    Sansbury, Brian E.; Hill, Bradford G.

    2015-01-01

    The prevalence of obesity has increased remarkably in the past four decades. Because obesity can promote the development of type 2 diabetes and cardiovascular disease, understanding the mechanisms that engender weight gain and discovering safe anti-obesity therapies are of critical importance. In particular, the gaseous signaling molecule, nitric oxide (NO), appears to be a central factor regulating adiposity and systemic metabolism. Obese and diabetic states are characterized by a deficit in bioavailable NO, with such decreases commonly attributed to downregulation of endothelial NO synthase (eNOS), loss of eNOS activity, or quenching of NO by its reaction with oxygen radicals. Gain-of-function studies, in which vascular-derived NO has been increased pharmacologically or genetically, reveal remarkable actions of NO on body composition and systemic metabolism. This review addresses the metabolic actions of eNOS and the potential therapeutic utility of harnessing its anti-obesogenic effects. PMID:25189393

  10. Calorie Restriction Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

    PubMed Central

    Ding, Mingge; Lei, Jingyi; Qu, Yinxian; Zhang, Huan; Xin, Weichuan; Ma, Feng; Liu, Shuwen; Li, Zhichao; Jin, Faguang

    2015-01-01

    Abstract: Calorie restriction (CR) is one of the most effective nonpharmacological interventions protecting against cardiovascular disease, such as hypertension in the systemic circulation. However, whether CR could attenuate pulmonary arterial hypertension (PAH) is largely unknown. The PAH model was developed by subjecting the rats to a single subcutaneous injection of monocrotaline. CR lowered mean pulmonary arterial pressure (mPAP) and reduced vascular remodeling and right ventricular hypertrophy in PAH rats. Meanwhile, CR attenuated endothelial dysfunction as evidenced by increased relaxation in response to acetylcholine. The beneficial effects of CR were associated with restored sirtuin-1 (SIRT1) expression and endothelial nitric oxide synthase (eNOS) phosphorylation and reduced eNOS acetylation in pulmonary arteries of PAH rats. To further clarify the role of SIRT1 in the protective effects of CR, adenoviral vectors for overexpression of SIRT1 were administered intratracheally at 1 day before monocrotaline injection. Overexpression of SIRT1 exhibited similar beneficial effects on mPAP and endothelial function, and increased eNOS phosphorylation and reduced eNOS acetylation in the absence of CR. Moreover, SIRT1 overexpression attenuated the increase in mPAP in hypoxia-induced PAH animals. Overall, the present data demonstrate that CR may serve as an effective treatment of PAH, and targeting the SIRT1/eNOS pathway may improve treatment of PAH. PMID:25636073

  11. Asymmetric dimethylarginine inhibits HSP90 activity in Pulmonary Arterial Endothelial Cells: Role of Mitochondrial Dysfunction

    PubMed Central

    Sud, Neetu; Wells, Sandra M.; Wiseman, Dean A.; Wilham, Jason; Black, Stephen M.

    2013-01-01

    Increased ADMA levels have been implicated in the pathogenesis of a number of conditions affecting the cardiovascular system. However, the mechanism(s) by which ADMA exerts its effect has not been adequately elucidated. Thus, the purpose of this study was to determine the effect of increased ADMA on nitric oxide (NO) signaling and to begin to elucidate the mechanism by which ADMA acts. Our initial data demonstrated that that ADMA increased NOS uncoupling both in recombinant human endothelial NO synthase (eNOS) and pulmonary arterial endothelial cells (PAEC). Further, we found that this eNOS uncoupling increased 3-nitrotyrosine levels preferentially in the mitochondria of PAEC due to a redistribution of eNOS from the plasma membrane to the mitochondria. This increase in nitration in the mitochondria was found to induce mitochondrial dysfunction as determined by increased mitochondrial derived reactive oxygen species and decreased generation of ATP. Finally, we found that the decrease in ATP resulted in a reduction in the chaperone activity of HSP90 resulting in a decrease in its interaction with eNOS. In conclusion increased levels of ADMA causes mitochondrial dysfunction and a loss of HSP90 chaperone activity secondary to an uncoupling of eNOS. Mitochondrial dysfunction may be an understudied component of the endothelial dysfunction associated with various cardiovascular disease states. PMID:18385287

  12. Bearing system

    DOEpatents

    Kapich, Davorin D.

    1987-01-01

    A bearing system includes backup bearings for supporting a rotating shaft upon failure of primary bearings. In the preferred embodiment, the backup bearings are rolling element bearings having their rolling elements disposed out of contact with their associated respective inner races during normal functioning of the primary bearings. Displacement detection sensors are provided for detecting displacement of the shaft upon failure of the primary bearings. Upon detection of the failure of the primary bearings, the rolling elements and inner races of the backup bearings are brought into mutual contact by axial displacement of the shaft.

  13. Sterilization System

    NASA Technical Reports Server (NTRS)

    1990-01-01

    Cox Sterile Products, Inc.'s Rapid Heat Transfer Sterilizer employs a heat exchange process that induces rapid air movement; the air becomes the heat transfer medium, maintaining a uniform temperature of 375 degrees Fahrenheit. It features pushbutton controls for three timing cycles for different instrument loads, a six-minute cycle for standard unpackaged instruments, eight minutes for certain specialized dental/medical instruments and 12 minutes for packaged instruments which can then be stored in a drawer in sterile condition. System will stay at 375 degrees all day. Continuous operation is not expensive because of the sterilizer's very low power requirements.

  14. Relaxation System

    NASA Technical Reports Server (NTRS)

    1987-01-01

    Environ Corporation's relaxation system is built around a body lounge, a kind of super easy chair that incorporates sensory devices. Computer controlled enclosure provides filtered ionized air to create a feeling of invigoration, enhanced by mood changing aromas. Occupant is also surrounded by multidimensional audio and the lighting is programmed to change colors, patterns, and intensity periodically. These and other sensory stimulators are designed to provide an environment in which the learning process is stimulated, because research has proven that while an individual is in a deep state of relaxation, the mind is more receptive to new information.

  15. Purification system

    NASA Technical Reports Server (NTRS)

    Flanagan, David T. (Inventor); Gibbons, Randall E. (Inventor)

    1992-01-01

    A system for prolonging the life of a granulated activated charcoal (GAC) water treatment device is disclosed in which an ultraviolet light transparent material is used to constrain water to flow over carbon surfaces. It is configured to receive maximum flux from a UV radiation source for the purpose of preventing microbial proliferation on the carbon surfaces; oxidizing organic contaminants adsorbed from the water onto the carbon surfaces and from biodegradation of adsorbed microbial forms; disinfecting water; and oxidizing organic contaminants in the water.

  16. Videobasierte Systeme

    NASA Astrophysics Data System (ADS)

    Knoll, Peter

    Videosensoren spielen für Fahrerassistenz systeme eine zentrale Rolle, da sie die Interpretation visueller Informationen (Objektklassifikation) gezielt unterstützen. Im Heckbereich kann die Video sensorik in der einfachsten Variante die ultraschallbasierte Einparkhilfe bei Einpark- und Rangiervorgängen unterstützen. Beim Nachtsichtsystem NightVision wird das mit Infrarotlicht angestrahlte Umfeld vor dem Fahrzeug mit einer Frontkamera aufgenommen und im Fahrzeugcockpit auf einem Display dem Fahrer angezeigt (s. Nachtsichtsysteme). Andere Fahrerassistenzsysteme verarbeiten die Videosignale und generieren daraus gezielt Informationen, die für eigenständige Funktionen (z. B. Spurverlassenswarner) oder aber als Zusatzinformation für andere Funktionen ausgewertet werden (Sensordatenfusion).

  17. Balance System

    NASA Technical Reports Server (NTRS)

    1988-01-01

    TherEx Inc.'s AT-1 Computerized Ataxiameter precisely evaluates posture and balance disturbances that commonly accompany neurological and musculoskeletal disorders. Complete system includes two-strain gauged footplates, signal conditioning circuitry, a computer monitor, printer and a stand-alone tiltable balance platform. AT-1 serves as assessment tool, treatment monitor, and rehabilitation training device. It allows clinician to document quantitatively the outcome of treatment and analyze data over time to develop outcome standards for several classifications of patients. It can evaluate specifically the effects of surgery, drug treatment, physical therapy or prosthetic devices.

  18. Transfer system

    DOEpatents

    Kurosawa, Kanji; Koga, Bunichiro; Ito, Hideki; Kiriyama, Shigeru; Higuchi, Shizuo

    2003-05-20

    A transport system includes a traveling rail (1) which constitutes a transport route and a transport body (3) which is capable of traveling on the traveling rail in the longitudinal direction of the traveling rail. Flexible drive tubes (5) are arranged on the traveling rail in the longitudinal direction of the traveling rail. The transport body includes a traveling wheel (4) which is capable of rolling on the traveling rail and drive wheels (2) which are capable of rolling on the drive tubes upon receiving the rotational drive power generated by pressure of a pressure medium supplied to the drive tubes while depressing the drive tubes. The traveling rail includes a plurality of transport sections and the transport body is capable of receiving a rotational drive force from the drive tubes at every transport sections. If necessary, a transport route changeover switch which changes over the transport route can be provided between the transport sections.

  19. Dataflow systems

    SciTech Connect

    Cohen, A.T.

    1982-01-01

    Dataflow languages are stream-oriented and functional, and assume a different operating environment. Programs in these languages are functions which define output as a function of input, with each program being a composition of subfunctions. There is no notion of a global store and, hence, there are no assignment statements. Control flow is determined by the availability of data (function arguments) and need not be explicitly specified by the programmer. The use and development of dataflow languages are motivated by three considerations. They represent parallelism naturally, particularly as it occurs in networks and distributed systems. They readily support very high level programming and their modularity and lack of side-effects makes their programs amenable to analysis. The paper briefly discusses their advantages in each of these three areas. 32 references.

  20. Systems toxicology.

    PubMed

    Hartung, Thomas; van Vliet, Erwin; Jaworska, Joanna; Bonilla, Leo; Skinner, Nigel; Thomas, Russell

    2012-01-01

    The need for a more mechanistic understanding of the ways in which chemicals modulate biological pathways is urgent if we are to identify and better assess safety issues relating to a wide range of substances developed by the pharmaceutical, chemical, agri-bio, and cosmetic industries. Omics technologies provide a valuable opportunity to refine existing methods and provide information for so-called integrated testing strategies via the creation of signatures of toxicity. By mapping these signatures to underlying pathways of toxicity, some of which have been identified by toxicologists over the last few decades, and bringing them together with pathway information determined from biochemistry and molecular biology, a "systems toxicology" approach will enable virtual experiments to be conducted that can improve the prediction of hazard and the assessment of compound toxicity. PMID:22562485

  1. Intelligent Engine Systems: Bearing System

    NASA Technical Reports Server (NTRS)

    Singh, Arnant P.

    2008-01-01

    The overall requirements necessary for sensing bearing distress and the related criteria to select a particular rotating sensor were established during the phase I. The current phase II efforts performed studies to evaluate the Robustness and Durability Enhancement of the rotating sensors, and to design, and develop the Built-in Telemetry System concepts for an aircraft engine differential sump. A generic test vehicle that can test the proposed bearing diagnostic system was designed, developed, and built. The Timken Company, who also assisted with testing the GE concept of using rotating sensors for the differential bearing diagnostics during previous phase, was selected as a subcontractor to assist General Electric (GE) for the design, and procurement of the test vehicle. A purchase order was prepared to define the different sub-tasks, and deliverables for this task. The University of Akron was selected to provide the necessary support for installing, and integrating the test vehicle with their newly designed test facility capable of simulating the operating environment for the planned testing. The planned testing with good and damaged bearings will be on hold pending further continuation of this effort during next phase.

  2. Separation system

    DOEpatents

    Rubin, Leslie S.

    1986-01-01

    A separation system for dewatering radioactive waste materials includes a disposal container, drive structure for receiving the container, and means for releasably attaching the container to the drive structure. Separation structure disposed in the container adjacent the inner surface of the side wall structure retains solids while allowing passage of liquids. Inlet port structure in the container top wall is normally closed by first valve structure that is centrifugally actuated to open the inlet port and discharge port structure at the container periphery receives liquid that passes through the separation structure and is normally closed by second valve structure that is centrifugally actuated to open the discharge ports. The container also includes coupling structure for releasable engagement with the centrifugal drive structure. Centrifugal force produced when the container is driven in rotation by the drive structure opens the valve structures, and radioactive waste material introduced into the container through the open inlet port is dewatered, and the waste is compacted. The ports are automatically closed by the valves when the container drum is not subjected to centrifugal force such that containment effectiveness is enhanced and exposure of personnel to radioactive materials is minimized.

  3. [Systemic sclerosis].

    PubMed

    Tamborrini, Giorgio; Distler, Meike; Distler, Oliver

    2008-05-01

    Systemic sclerosis (SSc) is a severe fibrotic multiorgan connective tissue disease. Vascular abnormalities such as fingertip ulcers and Raynaud's syndrome as well as involvement of organs including the lungs, heart, kidney and the gastrointestinal tract are prominent features of the disease. There are currently no disease modifying drugs available that can modify the course of the disease. In this review we will discuss medications that have been found to be effective in improving specific organ involvement due to SSc. For the treatment of gastroesophageal reflux disease (GERD), proton pump inhibitors are effective agents. In the setting of clinically significant gastrointestinal dysmotility, metoclopramide, erythromycin and octreotide may be beneficial. Small bowel bacterial overgrowth should be treated with oral antibiotics. Angiotensin converting enzyme inhibitors are the first-line agents for acute renal crisis. A variety of treatment options are available for Raynaud's phenomenon and include calcium channel blockers, iloprost (i. v.), losartan, fluoxetine and sildenafil. Fingertip ulcers can be prevented by using the endothelin receptor antagonist bosentan. The therapeutic options for treatment of pulmonary hypertension associated with SSc include bosentan, sildenafil and various prostacyclin analogs (eg, epoprostenol, treprostinil, iloprost). Sitaxentan, ambrisentan and new phosphodiesterase-5 inhibitors could be new options for therapy as well. Therapeutic options for interstitial lung fibrosis include cyclophosphamide, however, clinical effects are mild to moderate. Methotrexate has been used to treat skin fibrosis and can be beneficial when arthritis is present. PMID:18552072

  4. Incinerator system

    SciTech Connect

    Rathmell, R.K.

    1986-10-07

    An incineration system is described which consists of: combustion chamber structure having an inlet, an outlet, and burner structure in the combustion chamber, heat exchanger structure defining a chamber, divider structure between the heat exchanger chamber and the combustion chamber, an array of tubes extending through the heat exchanger chamber to the inlet of the combustion chamber at the divider structure. The heat exchanger chamber has an inlet coupled to the outlet of the combustion chamber for flow of the combustion products discharged from the combustion chamber through the heat exchanger chamber over the tubes in heat exchange relation, and an outlet for discharge of products from the heat exchanger chamber, aspirator sleeve structure secured to the divider structure between the heat exchanger chamber and the combustion chamber. Each aspirator sleeve receives the outlet end of a heat exchanger tube in slip fit relation so that the heat exchanger tubes are free to thermally expand longitudinally within the aspirator sleeves, and means for flowing vapor through the heat exchanger tubes into the combustion chamber at sufficiently high velocity to produce a reduced pressure effect in the aspirator sleeves in the heat exchanger chamber to draw a minor fraction of combustion products through the aspirator sleeves into the combustion chamber for reincineration.

  5. A Systems View of the Differences between APOE ε4 Carriers and Non-carriers in Alzheimer’s Disease

    PubMed Central

    Jiang, Shan; Tang, Ling; Zhao, Na; Yang, Wanling; Qiu, Yu; Chen, Hong-Zhuan

    2016-01-01

    APOE ε4 is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD) and accounts for 50–65% of late-onset AD. Late-onset AD patients carrying or not carrying APOE ε4 manifest many clinico-pathological distinctions. Thus, we applied a weighted gene co-expression network analysis to identify specific co-expression modules in AD based on APOE ε4 stratification. Two specific modules were identified in AD APOE ε4 carriers and one module was identified in non-carriers. The hub genes of one module of AD APOE ε4 carriers were ISOC1, ENO3, GDF10, GNB3, XPO4, ACLY and MATN2. The other module of AD APOE ε4 carriers consisted of 10 hub genes including ANO3, ARPP21, HPCA, RASD2, PCP4 and ADORA2A. The module of AD APOE ε4 non-carriers consisted of 16 hub genes including DUSP5, TNFRSF18, ZNF331, DNAJB5 and RIN1. The module of AD APOE ε4 carriers including ISOC1 and ENO3 and the module of non-carriers contained the most highly connected hub gene clusters. mRNA expression of the genes in the cluster of the ISOC1 and ENO3 module of carriers was shown to be correlated in a time-dependent manner under APOE ε4 treatment but not under APOE ε3 treatment. In contrast, mRNA expression of the genes in the cluster of non-carriers’ module was correlated under APOE ε3 treatment but not under APOE ε4 treatment. The modules of carriers demonstrated genetic bases and were mainly enriched in hereditary disorders and neurological diseases, energy metabolism-associated signaling and G protein-coupled receptor-associated pathways. The module including ISOC1 and ENO3 harbored two conserved promoter motifs in its hub gene cluster that could be regulated by common transcription factors and miRNAs. The module of non-carriers was mainly enriched in neurological, immunological and cardiovascular diseases and was correlated with Parkinson’s disease. These data demonstrate that AD in APOE ε4 carriers involves more genetic factors and particular biological processes

  6. A Systems View of the Differences between APOE ε4 Carriers and Non-carriers in Alzheimer's Disease.

    PubMed

    Jiang, Shan; Tang, Ling; Zhao, Na; Yang, Wanling; Qiu, Yu; Chen, Hong-Zhuan

    2016-01-01

    APOE ε4 is the strongest genetic risk factor for late-onset Alzheimer's disease (AD) and accounts for 50-65% of late-onset AD. Late-onset AD patients carrying or not carrying APOE ε4 manifest many clinico-pathological distinctions. Thus, we applied a weighted gene co-expression network analysis to identify specific co-expression modules in AD based on APOE ε4 stratification. Two specific modules were identified in AD APOE ε4 carriers and one module was identified in non-carriers. The hub genes of one module of AD APOE ε4 carriers were ISOC1, ENO3, GDF10, GNB3, XPO4, ACLY and MATN2. The other module of AD APOE ε4 carriers consisted of 10 hub genes including ANO3, ARPP21, HPCA, RASD2, PCP4 and ADORA2A. The module of AD APOE ε4 non-carriers consisted of 16 hub genes including DUSP5, TNFRSF18, ZNF331, DNAJB5 and RIN1. The module of AD APOE ε4 carriers including ISOC1 and ENO3 and the module of non-carriers contained the most highly connected hub gene clusters. mRNA expression of the genes in the cluster of the ISOC1 and ENO3 module of carriers was shown to be correlated in a time-dependent manner under APOE ε4 treatment but not under APOE ε3 treatment. In contrast, mRNA expression of the genes in the cluster of non-carriers' module was correlated under APOE ε3 treatment but not under APOE ε4 treatment. The modules of carriers demonstrated genetic bases and were mainly enriched in hereditary disorders and neurological diseases, energy metabolism-associated signaling and G protein-coupled receptor-associated pathways. The module including ISOC1 and ENO3 harbored two conserved promoter motifs in its hub gene cluster that could be regulated by common transcription factors and miRNAs. The module of non-carriers was mainly enriched in neurological, immunological and cardiovascular diseases and was correlated with Parkinson's disease. These data demonstrate that AD in APOE ε4 carriers involves more genetic factors and particular biological processes, whereas AD

  7. New Systems Produced by Systemic Change

    ERIC Educational Resources Information Center

    Battino, Wendy; Clem, Jo; Caine, Renate N.; Reigeluth, Charles M.; Chapman, Carrie; Flinders, David J.; Malopinsky, Larissa V.

    2006-01-01

    This article presents new systems produced by systemic change. First is Systemic Changes in the Chugach School District by Wendy Battino and Jo Clem. Second is Systemic Changes in Public Schools through Brain-Based Learning by Renate N. Caine. Third is A Vision of an Information-Age Educational System by Charles M. Reigeluth. Fourth is Systemic…

  8. System safety education focused on system management

    NASA Technical Reports Server (NTRS)

    Grose, V. L.

    1971-01-01

    System safety is defined and characteristics of the system are outlined. Some of the principle characteristics include role of humans in hazard analysis, clear language for input and output, system interdependence, self containment, and parallel analysis of elements.

  9. Distinguishing Systemic from Systematic.

    ERIC Educational Resources Information Center

    Carr, Alison A.

    1996-01-01

    Describes the difference between systemic and systematic as they relate to school reform and instructional design. Highlights include a history of systems theory; systems engineering; instructional systems design; systemic versus reductionist thinking; social systems; and systemic change in education, including power relationships. (LRW)

  10. Distribution of nitric oxide synthase in normal and cirrhotic human liver

    PubMed Central

    McNaughton, Lance; Puttagunta, Lakshmi; Martinez-Cuesta, Maria Angeles; Kneteman, Norm; Mayers, Irvin; Moqbel, Redwan; Hamid, Qutayba; Radomski, Marek W.

    2002-01-01

    Chronic liver disorders represent a serious health problem, considering that 300 million people worldwide are hepatitis B virus carriers, and 8,000–10,000 patients per year, in the U.S. alone, die as a result of liver failure caused by hepatitis C infection. Nitric oxide synthase (NOS) regulates hepatic vasculature; however, the patterns of expression and activity of NOS proteins in healthy and diseased human livers are unknown. Sections of diseased (n = 42) and control livers (n = 14) were collected during orthotopic liver transplants and partial hepatectomy. The diseased sections included alcoholic cirrhosis, viral hepatitis, cholestasis, acute necrosis, and uncommon pathologies including α1-anti-trypsin disorder. The endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were studied by using the citrulline assay, Western immunoblot, immunohistochemistry, and in situ hybridization. The systemic generation of plasma NO metabolites was measured by HPLC. In control livers, Ca2+-dependent and –independent NOS activities were identified by Western analysis as eNOS and iNOS, respectively. The eNOS was uniformly distributed in the hepatocytes and also detected in the endothelium of hepatic arteries, terminal hepatic venules, sinusoids, and in biliary epithelium. The iNOS was detected in hepatocytes and localized mainly in the periportal zone of the liver acinus. This pattern of distribution of eNOS and iNOS in normal liver was confirmed by in situ hybridization. In diseased livers, there was a significant increase in Ca2+-independent NOS with the corresponding strong appearance of iNOS in the cirrhotic areas. The eNOS was translocated to hepatocyte nuclei. Thus, eNOS and iNOS proteins are differentially expressed in healthy human liver, and this expression is significantly altered in cirrhotic liver disorders. PMID:12482944

  11. System design description cone penetrometer system

    SciTech Connect

    Seda, R.Y., Westinghouse Hanford

    1996-08-12

    The system design description documents in detail the design of the cone penetrometer system. The systems includes the cone penetrometer physical package, raman spectroscopy package and moisture sensor package. Information pertinent to the system design, development, fabrication and testing is provided.

  12. Systems view of power systems autonomy

    SciTech Connect

    Anderson, J.L.

    1984-08-01

    A space station will involve the formation and sustained operation of an assembly of humans and machines in space for a period of 10-20 years. Technology and mission studies of a permanently manned, evolutionary space station have identified the need for automated and eventually some degree of autonomous systems operation. A space station power system will have a high degree of interaction with other onboard systems which will act as power loads. By examining the evolution of an operational power system from a systems viewpoint through increasing degrees of automation the system and technology requirements are identified for an evolutionary system.

  13. Networked control of microgrid system of systems

    NASA Astrophysics Data System (ADS)

    Mahmoud, Magdi S.; Rahman, Mohamed Saif Ur; AL-Sunni, Fouad M.

    2016-08-01

    The microgrid has made its mark in distributed generation and has attracted widespread research. However, microgrid is a complex system which needs to be viewed from an intelligent system of systems perspective. In this paper, a network control system of systems is designed for the islanded microgrid system consisting of three distributed generation units as three subsystems supplying a load. The controller stabilises the microgrid system in the presence of communication infractions such as packet dropouts and delays. Simulation results are included to elucidate the effectiveness of the proposed control strategy.

  14. Systems design of long-life systems

    NASA Technical Reports Server (NTRS)

    Miles, R. F., Jr.

    1974-01-01

    A long-life system is defined as a system which cannot be life-tested in its operational environment. Another restriction is that preventive maintenance and repair shall be either impossible or economically disadvantageous. Examples of such systems include planetary spacecraft, communication satellites, undersea telephone cables, and nuclear power plants. The questions discussed are related to the implementation of system functions, approaches to determine the required level of system reliability, and aspects of tradeoffs between requirements and reliability.

  15. Female Reproductive System

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Female Reproductive System KidsHealth > For Teens > Female Reproductive System Print A ... and female reproductive systems. continue What Is the Female Reproductive System? Most species have two sexes: male and female. ...

  16. Multiple System Atrophy

    MedlinePlus

    ... Enhancing Diversity Find People About NINDS NINDS Multiple System Atrophy Information Page Condensed from Multiple System Atrophy ... Trials Organizations Publicaciones en Español What is Multiple System Atrophy? Multiple system atrophy (MSA) is a progressive ...

  17. Gender Disparities and Socio-Economic Factors on Learning Achievements in Agricultural Science in Rural and Urban Secondary Schools of Ogbomoso North Local Government Area of Oyo State, Nigeria

    ERIC Educational Resources Information Center

    Amao, S. R.; Gbadamosi, J.

    2015-01-01

    To contribute to the realization of the Millennium Development Goal (MDG) by the United Nations on the promotion of gender equity, the researchers sought to empirically verify the existence or otherwise of gender inequality in the agricultural and science achievement of urban and rural, male and female students in Ogbomoso North Local Government…

  18. System of systems modeling and analysis.

    SciTech Connect

    Campbell, James E.; Anderson, Dennis James; Longsine, Dennis E.; Shirah, Donald N.

    2005-01-01

    This report documents the results of an LDRD program entitled 'System of Systems Modeling and Analysis' that was conducted during FY 2003 and FY 2004. Systems that themselves consist of multiple systems (referred to here as System of Systems or SoS) introduce a level of complexity to systems performance analysis and optimization that is not readily addressable by existing capabilities. The objective of the 'System of Systems Modeling and Analysis' project was to develop an integrated modeling and simulation environment that addresses the complex SoS modeling and analysis needs. The approach to meeting this objective involved two key efforts. First, a static analysis approach, called state modeling, has been developed that is useful for analyzing the average performance of systems over defined use conditions. The state modeling capability supports analysis and optimization of multiple systems and multiple performance measures or measures of effectiveness. The second effort involves time simulation which represents every system in the simulation using an encapsulated state model (State Model Object or SMO). The time simulation can analyze any number of systems including cross-platform dependencies and a detailed treatment of the logistics required to support the systems in a defined mission.

  19. System Software Framework for System of Systems Avionics

    NASA Technical Reports Server (NTRS)

    Ferguson, Roscoe C.; Peterson, Benjamin L; Thompson, Hiram C.

    2005-01-01

    Project Constellation implements NASA's vision for space exploration to expand human presence in our solar system. The engineering focus of this project is developing a system of systems architecture. This architecture allows for the incremental development of the overall program. Systems can be built and connected in a "Lego style" manner to generate configurations supporting various mission objectives. The development of the avionics or control systems of such a massive project will result in concurrent engineering. Also, each system will have software and the need to communicate with other (possibly heterogeneous) systems. Fortunately, this design problem has already been solved during the creation and evolution of systems such as the Internet and the Department of Defense's successful effort to standardize distributed simulation (now IEEE 1516). The solution relies on the use of a standard layered software framework and a communication protocol. A standard framework and communication protocol is suggested for the development and maintenance of Project Constellation systems. The ARINC 653 standard is a great start for such a common software framework. This paper proposes a common system software framework that uses the Real Time Publish/Subscribe protocol for framework-to-framework communication to extend ARINC 653. It is highly recommended that such a framework be established before development. This is important for the success of concurrent engineering. The framework provides an infrastructure for general system services and is designed for flexibility to support a spiral development effort.

  20. Possible involvement of PPARγ-associated eNOS signaling activation in rosuvastatin-mediated prevention of nicotine-induced experimental vascular endothelial abnormalities.

    PubMed

    Kathuria, Sonam; Mahadevan, Nanjaian; Balakumar, Pitchai

    2013-02-01

    Nicotine exposure via cigarette smoking and tobacco chewing is associated with vascular complications. The present study investigated the effect of rosuvastatin in nicotine (2 mg/kg/day, i.p., 4 weeks)-induced vascular endothelial dysfunction (VED) in rats. The development of VED was assessed by employing isolated aortic ring preparation and estimating aortic and serum nitrite/nitrate concentration. Further, scanning electron microscopy and hematoxylin-eosin staining of thoracic aorta were performed to assess the vascular endothelial integrity. Moreover, oxidative stress was assessed by estimating aortic superoxide anion generation and serum thiobarbituric acid-reactive substances. The nicotine administration produced VED by markedly reducing acetylcholine-induced endothelium-dependent relaxation, impairing the integrity of vascular endothelium, decreasing aortic and serum nitrite/nitrate concentration, increasing oxidative stress, and inducing lipid alteration. However, treatment with rosuvastatin (10 mg/kg/day, i.p., 4 weeks) markedly attenuated nicotine-induced vascular endothelial abnormalities, oxidative stress, and lipid alteration. Interestingly, the co-administration of peroxisome proliferator-activated receptor γ (PPARγ) antagonist, GW9662 (1 mg/kg/day, i.p., 2 weeks) submaximally, significantly prevented rosuvastatin-induced improvement in vascular endothelial integrity, endothelium-dependent relaxation, and nitrite/nitrate concentration in rats administered nicotine. However, GW9662 co-administration did not affect rosuvastatin-associated vascular anti-oxidant and lipid-lowering effects. The incubation of aortic ring, isolated from rosuvastatin-treated nicotine-administered rats, with L-NAME (100 μM), an inhibitor of nitric oxide synthase (NOS), significantly attenuated rosuvastatin-induced improvement in acetylcholine-induced endothelium-dependent relaxation. Rosuvastatin prevents nicotine-induced vascular endothelial abnormalities by activating PPARγ and endothelial NOS signaling pathways. Moreover, the PPARγ-independent anti-oxidant and lipid-lowering effects of rosuvastatin might additionally play a role in the improvement of vascular endothelial function. PMID:23149826

  1. Mechanisms of the vasorelaxing effects of CORM-3, a water-soluble carbon monoxide-releasing molecule: interactions with eNOS.

    PubMed

    Alshehri, Ali; Bourguignon, Marie-Pierre; Clavreul, Nicolas; Badier-Commander, Cécile; Gosgnach, Willy; Simonet, Serge; Vayssettes-Courchay, Christine; Cordi, Alex; Fabiani, Jean-Noël; Verbeuren, Tony J; Félétou, Michel

    2013-03-01

    The purpose of the present work was to elucidate the mechanisms underlying the endothelium-dependent and endothelium-independent components of the vascular relaxation induced by a water-soluble and ruthenium-based carbon monoxide (CO)-releasing agent, tricarbonylchloro(glycinato)ruthenium(II) (CORM-3). Changes in isometric tension and cyclic guanosine monophosphate (cGMP) production were measured in isolated aortic rings from normotensive Wistar-Kyoto rats. Nitric oxide (NO) generation was assessed in cultured human umbilical vein endothelial cells (HUVEC) by electron spin resonance. In rat aortic rings, CORM-3, but not the inactivated compound, iCORM, induced relaxations. In rings with but not in those without endothelium relaxations were partially inhibited by L-nitro-arginine (L-NA), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ), or hydroxocobalamin, inhibitors of NO-synthase, soluble guanylyl cyclase, and scavenger of NO, respectively. In rings with and without endothelium, deoxyhemoglobin abolished the relaxations. A combination of potassium channel blockers (barium, glibenclamide, and iberiotoxin) blunted the relaxation in rings without endothelium. CORM-3 produced an endothelium-dependent generation of cGMP that was inhibited by L-NA. CORM-3, but not iCORM, inhibited the endothelium-dependent relaxation to acetylcholine without affecting the response to sodium nitroprusside. In HUVEC, CORM-3 produced a concentration-dependent release of NO. Therefore, CORM-3-induced relaxations involve the soluble guanylyl cyclase-independent activation of smooth muscle potassium channels. Additionally, CO can produce concomitantly activation and inhibition of NO synthase, the former being responsible for the endothelium- and cGMP-dependent effect of CORM-3, the latter for the inhibition of acetylcholine-induced endothelium-dependent relaxations. PMID:23296254

  2. eNOS signaling is essential in GLP-2-mediated stimulation of blood flow, but not cell proliferation in the mouse gut

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Through a G protein-coupled receptor, glucagon-like peptide-2 (GLP-2) stimulates intestinal crypt cell proliferation and mucosal blood flow. GLP-2 receptor is localized to enteric neurons, endocrine cells, and myofibroblasts, but not enterocytes. However, it is largely unknown how GLP-2 receptor-act...

  3. Glucagon-like peptide-2 intracellularly stimulates eNOS phosphorylation and specifically induces submucosal arteriole vasodilation via a sheer stress-independent, local neural mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive neuropeptide that exerts diverse actions in the gastrointestinal tract, including enhancing mucosal cell survival and proliferation, mucosal blood flow, luminal nutrient uptake, and suppressing gastric motility and secretion. We have shown th...

  4. Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress

    PubMed Central

    Hsu, Lewis L.; Berkowitz, Dan E.; Champion, Hunter C.; Burnett, Arthur L.

    2013-01-01

    Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders. PMID:23844149

  5. Ca2+-activated K+ channels of small and intermediate conductance control eNOS activation through NAD(P)H oxidase.

    PubMed

    Gaete, Pablo S; Lillo, Mauricio A; Ardiles, Nicolás M; Pérez, Francisco R; Figueroa, Xavier F

    2012-03-01

    Ca(2+)-activated K(+) channels (K(Ca)) and NO play a central role in the endothelium-dependent control of vasomotor tone. We evaluated the interaction of K(Ca) with NO production in isolated arterial mesenteric beds of the rat. In phenylephrine-contracted mesenteries, acetylcholine (ACh)-induced vasodilation was reduced by NO synthase (NOS) inhibition with N(ω)-nitro-L-arginine (L-NA), but in the presence of tetraethylammonium, L-NA did not further affect the response. In KCl-contracted mesenteries, the relaxation elicited by 100 nM ACh or 1 μM ionomycin was abolished by L-NA, tetraethylammonium, or simultaneous blockade of small-conductance K(Ca) (SK(Ca)) channels with apamin and intermediate-conductance K(Ca) (IK(Ca)) channels with triarylmethane-34 (TRAM-34). Apamin-TRAM-34 treatment also abolished 100 nM ACh-activated NO production, which was associated with an increase in superoxide formation. Endothelial cell Ca(2+) buffering with BAPTA elicited a similar increment in superoxide. Apamin-TRAM-34 treatment increased endothelial NOS phosphorylation at threonine 495 (P-eNOS(Thr495)). Blockade of NAD(P)H oxidase with apocynin or superoxide dismutation with PEG-SOD prevented the increment in superoxide and changes in P-eNOS(Thr495) observed during apamin and TRAM-34 application. Our results indicate that blockade of SK(Ca) and IK(Ca) activates NAD(P)H oxidase-dependent superoxide formation, which leads to inhibition of NO release through P-eNOS(Thr495). These findings disclose a novel mechanism involved in the control of NO production. PMID:22210378

  6. Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial

    PubMed Central

    2015-01-01

    Summary Background High blood pressure is associated with poor outcome after stroke. Whether blood pressure should be lowered early after stroke, and whether to continue or temporarily withdraw existing antihypertensive drugs, is not known. We assessed outcomes after stroke in patients given drugs to lower their blood pressure. Methods In our multicentre, partial-factorial trial, we randomly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure (systolic 140–220 mm Hg) to 7 days of transdermal glyceryl trinitrate (5 mg per day), started within 48 h of stroke onset, or to no glyceryl trinitrate (control group). A subset of patients who were taking antihypertensive drugs before their stroke were also randomly assigned to continue or stop taking these drugs. The primary outcome was function, assessed with the modified Rankin Scale at 90 days by observers masked to treatment assignment. This study is registered, number ISRCTN99414122. Findings Between July 20, 2001, and Oct 14, 2013, we enrolled 4011 patients. Mean blood pressure was 167 (SD 19) mm Hg/90 (13) mm Hg at baseline (median 26 h [16–37] after stroke onset), and was significantly reduced on day 1 in 2000 patients allocated to glyceryl trinitrate compared with 2011 controls (difference −7·0 [95% CI −8·5 to −5·6] mm Hg/–3·5 [–4·4 to −2·6] mm Hg; both p<0·0001), and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients randomised to stop them (difference −9·5 [95% CI −11·8 to −7·2] mm Hg/–5·0 [–6·4 to −3·7] mm Hg; both p<0·0001). Functional outcome at day 90 did not differ in either treatment comparison—the adjusted common odds ratio (OR) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1·01 (95% CI 0·91–1·13; p=0·83), and with continue versus stop antihypertensive drugs OR was 1·05 (0·90–1·22; p=0·55). Interpretation In patients with acute stroke and high blood pressure, transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome. We show no evidence to support continuing prestroke antihypertensive drugs in patients in the first few days after acute stroke. Funding UK Medical Research Council. PMID:25465108

  7. Growth Hormone Effects in Immune Stress: AKT/eNOS Signaling Module in the Cellular Response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The activation of the constitutive endothelial nitric-oxide synthase (eNOS) and expression of inducible NOS (iNOS) with subsequent nitric oxide production are among the early cellular responses that follow in a systemic exposure of animals to lipopolysaccharide (LPS). Growth hormone (GH) has been sh...

  8. Intelligent systems technology infrastructure for integrated systems

    NASA Technical Reports Server (NTRS)

    Lum, Henry, Jr.

    1991-01-01

    Significant advances have occurred during the last decade in intelligent systems technologies (a.k.a. knowledge-based systems, KBS) including research, feasibility demonstrations, and technology implementations in operational environments. Evaluation and simulation data obtained to date in real-time operational environments suggest that cost-effective utilization of intelligent systems technologies can be realized for Automated Rendezvous and Capture applications. The successful implementation of these technologies involve a complex system infrastructure integrating the requirements of transportation, vehicle checkout and health management, and communication systems without compromise to systems reliability and performance. The resources that must be invoked to accomplish these tasks include remote ground operations and control, built-in system fault management and control, and intelligent robotics. To ensure long-term evolution and integration of new validated technologies over the lifetime of the vehicle, system interfaces must also be addressed and integrated into the overall system interface requirements. An approach for defining and evaluating the system infrastructures including the testbed currently being used to support the on-going evaluations for the evolutionary Space Station Freedom Data Management System is presented and discussed. Intelligent system technologies discussed include artificial intelligence (real-time replanning and scheduling), high performance computational elements (parallel processors, photonic processors, and neural networks), real-time fault management and control, and system software development tools for rapid prototyping capabilities.

  9. Systems engineering and analysis

    SciTech Connect

    Blanchard, B.S.; Fabrycky, W.J.

    1981-01-01

    An introduction to systems is provided and tools for systems analysis are considered, taking into account system definitions and concepts, approaches for bringing systems into being, models in systems analysis, economic analysis techniques, mathematical modeling and optimization, probability and statistics, queuing theory and analysis, and control concepts and techniques. The system design process is discussed along with the design for operational feasibility, systems engineering management, and system design case studies. Attention is given to conceptual design, preliminary system design, detail design and development, system test and evaluation, design for reliability, design for maintainability, design for supportability, design for economic feasibility, communication system design, finite population system design, energy storage system design, and procurement-inventory system design.

  10. [X-33 Systems

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Lockheed Martin Skunk Works has compiled an Annual Performance Report of the X-33/RLV Program. This report consists of individual reports from all industry team members, as well as NASA team centers. This portion of the report is comprised of a status report of Allied-Signal Aerospace's contribution to the program. The following is a summary of the work reviewed under their portion of the agreement: (1) Communication Systems; (2) Environmental Control Systems- Active Thermal Control System (ATCS), Purge and Vent System, Hydrogen Detection System (HDS), Avionics Bay Inerting System (ABIS), and Flush Air Data System (FADS); (2) Landing Systems; (3) Power Management and Generation Systems; (4) Flight Control Actuation System (FCAS)- Electric Power Control & Distribution System (EPCDS), and Battery Power System (BPS); and (5) Vehicle Management Systems (VMS)- VMS Hardware, VMS Software Development Activities, and System Integration Laboratory (SIL).

  11. Freedom System Text and Graphics System (TAGS)

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The Text and Graphics System (TAGS) is a high-resolution facsimile system that scans text or graphics material and converts the analog SCAN data into serial digital data. This video shows the TAGS in operation.

  12. Language as a System of Systems

    ERIC Educational Resources Information Center

    Mulder, J. W. F.; Hervey, S. G. J.

    1975-01-01

    Based on Mulder's previous classification of all semiotic systems designed to describe the system of discrete features in human languages, this article explores a further subclassification of the genus language into species. (CLK)

  13. Intelligent tutoring systems for systems engineering methodologies

    NASA Technical Reports Server (NTRS)

    Meyer, Richard J.; Toland, Joel; Decker, Louis

    1991-01-01

    The general goal is to provide the technology required to build systems that can provide intelligent tutoring in IDEF (Integrated Computer Aided Manufacturing Definition Method) modeling. The following subject areas are covered: intelligent tutoring systems for systems analysis methodologies; IDEF tutor architecture and components; developing cognitive skills for IDEF modeling; experimental software; and PC based prototype.

  14. System Design of the SWRL Financial System.

    ERIC Educational Resources Information Center

    Ikeda, Masumi

    To produce various management and accounting reports in order to maintain control of SWRL (Southwest Regional Laboratory) operational and financial activities, a computer-based SWRL financial system was developed. The system design is outlined, and various types of system inputs described. The kinds of management and accounting reports generated…

  15. Optical system defect propagation in ABCD systems.

    PubMed

    McKinley, W G; Yura, H T; Hanson, S G

    1988-05-01

    We describe how optical system defects (tilt/jitter, decenter, and despace) propagate through an arbitrary paraxial optical system that can be described by an ABCD ray transfer matrix. A pedagogical example is given that demonstrates the effect of alignment errors on a typical optical system. PMID:19745889

  16. General Systems Theory and Instructional Systems Design.

    ERIC Educational Resources Information Center

    Salisbury, David F.

    1990-01-01

    Describes basic concepts in the field of general systems theory (GST) and identifies commonalities that exist between GST and instructional systems design (ISD). Models and diagrams that depict system elements in ISD are presented, and two matrices that show how GST has been used in ISD literature are included. (11 references) (LRW)

  17. PECAM-1 is involved in neutrophil transmigration across Histophilus somni treated bovine brain endothelial cells.

    PubMed

    Tiwari, Raksha; Sullivan, J; Czuprynski, C J

    2009-09-01

    Histophilus somni (H. somni) is a gram-negative bacterial pathogen that causes respiratory, reproductive, and central nervous system disease in cattle. The hallmark of systemic H. somni infection is diffused vasculitis that can lead to an acute central nervous system disease known as thrombotic meningoencephalitis (TME). Because platelet endothelial cell adhesion molecule-1 (PECAM-1) and endothelial nitric oxide synthase (eNOS) play fundamental roles in maintaining homeostasis in blood vessels, we sought to determine if PECAM-1 and eNOS expression play a role in events related to the pathogenesis of TME. Our findings demonstrate that neutrophil transmigration across H. somni-treated TBBEC (SV-40 transformed bovine brain endothelial cell line) was reduced by treatment with anti-PECAM-1 antibodies. Confocal microscopy indicated that H. somni treatment leads to redistribution of PECAM-1 and eNOS on the surface of TBBEC. These findings suggest that PECAM-1 and eNOS may play a role in the early pathogenesis of TME. PMID:19524660

  18. Biodegradable and biocompatible epoxidized vegetable oil modified thermostable poly(vinyl chloride): thermal and performance characteristics post biodegradation with Pseudomonas aeruginosa and Achromobacter sp.

    PubMed

    Das, Gautam; Bordoloi, Naba K; Rai, Sudhir K; Mukherjee, Ashis K; Karak, Niranjan

    2012-03-30

    The increased production of municipal solid waste by the disposal of plastic materials heightens the urgency to develop biodegradable materials for daily use. In vitro-biodegradation study on poly(vinyl chloride) (PVC) plasticized by epoxidized Mesua ferrea L. seed oil at three different weight percentages (PVC/ENO ratio of 75/25, 50/50 and 25/75) was conducted by using Pseudomonas aeruginosa and Achromobacter sp. bacteria. The test bacterial species were able to grow on the polymer matrix by using it as a source of energy; however the pristine PVC did not support the microbial growth. The PVC/ENO material of 25/75 ratio showed the highest percent (%) of biodegradation compared to other tested systems. The bacterial count and the dry biomass post 180 days of inoculation in 25/75 plasticized PVC suggested bacterial growth at the expense of degradation of the system. The tensile strength of 25/75 PVC/ENO system, post 180 days of inoculation by Pseudomonas aeruginosa and Achromobacter sp. decreased by about 53% and 43% respectively. Further, surface erosion phenomenon and structural change of the matrix after bacterial growth, as studied by FTIR and SEM analysis of PVC/ENO of 25/75 ratio exhibited noticeable deterioration post 180 days of inoculation. PMID:22316688

  19. Osthole relaxes pulmonary arteries through endothelial phosphatidylinositol 3-kinase/Akt-eNOS-NO signaling pathway in rats.

    PubMed

    Yao, Li; Lu, Ping; Li, Yumei; Yang, Lijing; Feng, Hongxuan; Huang, Yong; Zhang, Dandan; Chen, Jianguo; Zhu, Daling

    2013-01-15

    Pulmonary arterial hypertension is a life-threatening disease lacking effective therapies. Osthole is a natural coumarin compound isolated from Angelica pubescens Maxim., which possesses hypotensive effect. Although its effects on isolated thoracic aorta (systemic circulating system) are clarified, it remains unclear whether Osthole relaxes isolated pulmonary arteries (PAs) (pulmonary circulating system). The aim of this study was to investigate the effects of Osthole on isolated PAs and the underlying mechanisms. We examined PA relaxation induced by Osthole in isolated human and rat PA rings with force-electricity transducers, the expression and activity of endothelial nitric oxide synthase (eNOS) and protein kinase B (Akt) with western blot, and nitric oxide (NO) production using DAF-FM DA fluorescent indicator. The results showed that Osthole elicited a dose-dependent vasorelaxation activity with phenylephrine-precontracted human and rat PA rings, which can be diminished by endothelium denudation and inhibition of eNOS, while having no effect on rat mesenteric arteries. Osthole increased NO release as well as activation of Akt and eNOS, indicated with increased phosphorylations of Akt at Ser-473 and eNOS at Ser-1177 in endothelial cells. PI3K inhibitor LY294002 also blocked Osthole induced vasodilation. In summary, dilative effect of Osthole was dependent on endothelial integrity and NO production, and was mediated by endothelial PI3K/Akt-eNOS-NO pathway. These may provide a new pulmonary vasodilator for the therapy of pulmonary arterial hypertension. PMID:23220709

  20. DDL system: Design systhesis of digital systems

    NASA Technical Reports Server (NTRS)

    Shiva, S. G.

    1983-01-01

    Digital Systems Design Language was integrated into the CADAT system environment of NASA-MSFC. The major technical aspects of this integration are summarized. Automatic hardware synthesis is now possible starting with a high level description of the system to be synthesized. The DDL system provides a high level design verification capability, thereby minimizing design changes in the later stages of the design cycle. An overview of the DDL system covering the translation, simulation and synthesis capabilities is provided. Two companion documents (the user's and programmer's manuals) are to be consulted for detailed discussions.

  1. Lighting system with thermal management system

    SciTech Connect

    Arik, Mehmet; Weaver, Stanton Earl; Stecher, Thomas Elliot; Seeley, Charles Erklin; Kuenzler, Glenn Howard; Wolfe, Jr., Charles Franklin; Utturkar, Yogen Vishwas; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2015-08-25

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  2. Lighting system with thermal management system

    DOEpatents

    Arik, Mehmet; Weaver, Stanton; Stecher, Thomas; Seeley, Charles; Kuenzler, Glenn; Wolfe, Jr., Charles; Utturkar, Yogen; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2013-05-07

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  3. Lighting system with thermal management system

    DOEpatents

    Arik, Mehmet; Weaver, Stanton Earl; Stecher, Thomas Elliot; Seeley, Charles Erklin; Kuenzler, Glenn Howard; Wolfe, Jr., Charles Franklin; Utturkar, Yogen Vishwas; Sharma, Rajdeep; Prabhakaran, Satish; Icoz, Tunc

    2015-02-24

    Lighting systems having unique configurations are provided. For instance, the lighting system may include a light source, a thermal management system and driver electronics, each contained within a housing structure. The light source is configured to provide illumination visible through an opening in the housing structure. The thermal management system is configured to provide an air flow, such as a unidirectional air flow, through the housing structure in order to cool the light source. The driver electronics are configured to provide power to each of the light source and the thermal management system.

  4. Microwave landing system autoland system analysis

    NASA Technical Reports Server (NTRS)

    Feather, J. B.; Craven, B. K.

    1991-01-01

    The objective was to investigate the ability of present day aircraft equipped with automatic flight control systems to fly advanced Microwave Landing Systems (MLS) approaches. The tactical approach used to achieve this objective included reviewing the design and autoland operation of the MD-80 aircraft, simulating the MLS approaches using a batch computer program, and assessing the performance of the autoland system from computer generated data. The results showed changes were required to present Instrument Landing System (ILS) procedures to accommodate the new MLS curved paths. It was also shown that in some cases, changes to the digital flight guidance systems would be required so that an autoland could be performed.

  5. Intelligent test integration system

    NASA Technical Reports Server (NTRS)

    Sztipanovits, J.; Padalkar, S.; Rodriguez-Moscoso, J.; Kawamura, K.; Purves, B.; Williams, R.; Biglari, H.

    1988-01-01

    A new test technology is described which was developed for space system integration. The ultimate purpose of the system is to support the automatic generation of test systems in real time, distributed computing environments. The Intelligent Test Integration System (ITIS) is a knowledge based layer above the traditional test system components which can generate complex test configurations from the specification of test scenarios.

  6. Collaborative Systems Testing

    ERIC Educational Resources Information Center

    Pocatilu, Paul; Ciurea, Cristian

    2009-01-01

    Collaborative systems are widely used today in various activity fields. Their complexity is high and the development involves numerous resources and costs. Testing collaborative systems has a very important role for the systems' success. In this paper we present taxonomy of collaborative systems. The collaborative systems are classified in many…

  7. Energy Systems Design

    NASA Technical Reports Server (NTRS)

    1986-01-01

    PRESTO, a COSMIC program, handles energy system specifications and predicts design efficiency of cogeneration systems. These systems allow a company to use excess energy produced to generate electricity. PRESTO is utilized by the Energy Systems Division of Thermo Electron Corporation in the custom design of cogeneration systems.

  8. Systems Intelligence Inventory

    ERIC Educational Resources Information Center

    Törmänen, Juha; Hämäläinen, Raimo P.; Saarinen, Esa

    2016-01-01

    Purpose: Systems intelligence (SI) (Saarinen and Hämäläinen, 2004) is a construct defined as a person's ability to act intelligently within complex systems involving interaction and feedback. SI relates to our ability to act in systems and reason about systems to adaptively carry out productive actions within and with respect to systems such as…

  9. The LSST: A System of Systems

    NASA Astrophysics Data System (ADS)

    Claver, Chuck F.; Debois-Felsmann, G. P.; Delgado, F.; Hascall, P.; Marshall, S.; Nordby, M.; Schumacher, G.; Sebag, J.; LSST Collaboration

    2011-01-01

    The Large Synoptic Survey Telescope (LSST) is a complete observing system that acquires and archives images, processes and analyzes them, and publishes reduced images and catalogs of sources and objects. The LSST will operate over a ten year period producing a survey of 20,000 square degrees over the entire [Southern] sky in 6 filters (ugrizy) with each field having been visited several hundred times enabling a wide spectrum of science from fast transients to exploration of dark matter and dark energy. The LSST itself is a complex system of systems consisting of the 8.4m 3-mirror telescope, a 3.2 billion pixel camera, and a peta-scale data management system. The LSST project uses a Model Based Systems Engineering (MBSE) methodology to ensure an integrated approach to system design and rigorous definition of system interfaces and specifications. The MBSE methodology is applied through modeling of the LSST's systems with the System Modeling Language (SysML). The SysML modeling recursively establishes the threefold relationship between requirements, logical & physical functional decomposition and definition, and system and component behavior at successively deeper level of abstraction and detail. The LSST modeling includes the analysis and documenting the flow of command and control information and data between the suite of systems in the LSST observatory that are needed to carry out the activities of the survey. The MBSE approach is applied throughout all stages of the project from design, to validation and verification, though to commissioning.

  10. Levonorgestrel Intrauterine System

    MedlinePlus

    ... new system inserted at any time during your menstrual cycle. If you have chosen to use a different ... of your intrauterine system and you have regular menstrual cycles, you should have the system removed during the ...

  11. Manned systems technology discipline

    NASA Technical Reports Server (NTRS)

    Bretoi, Remus

    1990-01-01

    Viewgraphs on manned systems technology discipline for Space Station Freedom are presented. Topics covered include: crew-systems interfaces and interactions; crew training; on-board systems maintenance and support; habitability and environment; and computational human factors.

  12. Autonomic Nervous System Disorders

    MedlinePlus

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating of your heart ... breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as the result ...

  13. Autonomic Nervous System Disorders

    MedlinePlus

    Your autonomic nervous system is the part of your nervous system that controls involuntary actions, such as the beating ... with breathing and swallowing Erectile dysfunction in men Autonomic nervous system disorders can occur alone or as ...

  14. Immune System Involvement

    MedlinePlus

    ... Tips" to find out more! Email * Zipcode The Immune System and Psoriatic Disease What is an autoimmune disease? ... swollen and painful joints and tendons. Treating the immune system The immune system is not only the key ...

  15. Female Reproductive System

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Female Reproductive System KidsHealth > For Parents > Female Reproductive System Print A ... the egg or sperm. continue Components of the Female Reproductive System Unlike the male, the human female has a ...

  16. Wind energy systems

    NASA Technical Reports Server (NTRS)

    Stewart, H. J.

    1978-01-01

    A discussion on wind energy systems involved with the DOE wind energy program is presented. Some of the problems associated with wind energy systems are discussed. The cost, efficiency, and structural design of wind energy systems are analyzed.

  17. Photovoltaic systems test facility

    NASA Technical Reports Server (NTRS)

    1979-01-01

    Facility provides broad and flexible capability for evaluating photovoltaic systems and design concepts. As 'breadboard' system, it can be used to check out complete systems, subsystems, and components before installation in actual service.

  18. Alternative Videodisc Systems.

    ERIC Educational Resources Information Center

    Heath, Ted

    1981-01-01

    Discusses consumer and industrial videodisc systems for information storage including cost, technology utilized, formats, and features. Reflective and transmissive laser optical systems are described, as well as the grooved and grooveless mechanical systems. Tables containing product data are included. (JJD)

  19. Emerging Systems of Systems for Environmental Data

    NASA Astrophysics Data System (ADS)

    Middleton, D. E.; Fox, P.; Cinquini, L.; Burek, M.

    2007-05-01

    The scientific research community increasingly has complex, difficult questions to ask of its observations and model results - questions that will increasingly span disparate datasets, multiple disciplines, and international boundaries. Our future information systems are going to need to satisfy these growing demands. GEOSS, the Global Earth Observing System of Systems, puts forth a compelling vision in this area. Solid steps in the direction of this vision are already well underway, moving us towards the next generation of global, federated environmental data systems. For example, last year the World Meteorological Organization demonstrated its first prototype for WIS, the WMO Information System. WIS is a step in the direction of GEOSS, providing a federated system that provides aggregation of environmental data and services at national and regional levels, combined with a small number of redundant peer systems that can service large-scale geographical regions. Forming a foundational layer for efforts like WIS, the global community is in the process of building other systems of systems that essentially aggregate and integrate the output of data and modeling efforts, in areas such as weather, climate, space physics, and many others. This encouraging trend towards federation of new and existing systems is driven by scientific needs and underpinned by shared technology, interfaces, protocols, metadata standards, and the world of Grid computing. NCAR, working with many partners, is contributing to a number of projects that are focused upon some of these challenges. In this presentation we will describe a suite of complimentary and interconnected efforts, including the Earth System Grid (climate), the Community Data Portal (and WIS connections), TIGGE (weather), the Virtual Solar Terrestrial Observatory, and related metadata thrusts. The main emphasis here is the pursuit of systems of systems as well as progress towards semantic integration, which will be very

  20. Propulsion Systems Panel deliberations

    NASA Technical Reports Server (NTRS)

    Bianca, Carmelo J.; Miner, Robert; Johnston, Lawrence M.; Bruce, R.; Dennies, Daniel P.; Dickenson, W.; Dreshfield, Robert; Karakulko, Walt; Mcgaw, Mike; Munafo, Paul M.

    1993-01-01

    The Propulsion Systems Panel was established because of the specialized nature of many of the materials and structures technology issues related to propulsion systems. This panel was co-chaired by Carmelo Bianca, MSFC, and Bob Miner, LeRC. Because of the diverse range of missions anticipated for the Space Transportation program, three distinct propulsion system types were identified in the workshop planning process: liquid propulsion systems, solid propulsion systems and nuclear electric/nuclear thermal propulsion systems.

  1. Performance Measurement Analysis System

    Energy Science and Technology Software Center (ESTSC)

    1989-06-01

    The PMAS4.0 (Performance Measurement Analysis System) is a user-oriented system designed to track the cost and schedule performance of Department of Energy (DOE) major projects (MPs) and major system acquisitions (MSAs) reporting under DOE Order 5700.4A, Project Management System. PMAS4.0 provides for the analysis of performance measurement data produced from management control systems complying with the Federal Government''s Cost and Schedule Control Systems Criteria.

  2. System status display information

    NASA Technical Reports Server (NTRS)

    Summers, L. G.; Erickson, J. B.

    1984-01-01

    The system Status Display is an electronic display system which provides the flight crew with enhanced capabilities for monitoring and managing aircraft systems. Guidelines for the design of the electronic system displays were established. The technical approach involved the application of a system engineering approach to the design of candidate displays and the evaluation of a Hernative concepts by part-task simulation. The system engineering and selection of candidate displays are covered.

  3. Lightside Atmospheric Revitalization System

    NASA Technical Reports Server (NTRS)

    Colling, A. K.; Cushman, R. J.; Hultman, M. M.; Nason, J. R.

    1980-01-01

    The system was studied as a replacement to the present baseline LiOH system for extended duration shuttle missions. The system consists of three subsystems: a solid amine water desorbed regenerable carbon dioxide removal system, a water vapor electrolysis oxygen generating system, and a Sabatier reactor carbon dioxide reduction system. The system is designed for use on a solar powered shuttle vehicle. The majority of the system's power requirements are utilized on the Sun side of each orbit, when solar power is available.

  4. Control system design method

    DOEpatents

    Wilson, David G.; Robinett, III, Rush D.

    2012-02-21

    A control system design method and concomitant control system comprising representing a physical apparatus to be controlled as a Hamiltonian system, determining elements of the Hamiltonian system representation which are power generators, power dissipators, and power storage devices, analyzing stability and performance of the Hamiltonian system based on the results of the determining step and determining necessary and sufficient conditions for stability of the Hamiltonian system, creating a stable control system based on the results of the analyzing step, and employing the resulting control system to control the physical apparatus.

  5. Umbra's system representation.

    SciTech Connect

    McDonald, Michael James

    2005-07-01

    This document describes the Umbra System representation. Umbra System representation, initially developed in the spring of 2003, is implemented in Incr/Tcl using concepts borrowed from Carnegie Mellon University's Architecture Description Language (ADL) called Acme. In the spring of 2004 through January 2005, System was converted to Umbra 4, extended slightly, and adopted as the underlying software system for a variety of Umbra applications that support Complex Systems Engineering (CSE) and Complex Adaptive Systems Engineering (CASE). System is now a standard part Of Umbra 4. While Umbra 4 also includes an XML parser for System, the XML parser and Schema are not described in this document.

  6. Integrated Systems Health Management for Intelligent Systems

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. It is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this paper, concepts, procedures, and approaches are presented as a foundation for implementing an intelligent systems ]relevant ISHM capability. The capability stresses integration of DIaK from all elements of a system. Both ground-based (remote) and on-board ISHM capabilities are compared and contrasted. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  7. Systems engineering for very large systems

    NASA Technical Reports Server (NTRS)

    Lewkowicz, Paul E.

    1993-01-01

    Very large integrated systems have always posed special problems for engineers. Whether they are power generation systems, computer networks or space vehicles, whenever there are multiple interfaces, complex technologies or just demanding customers, the challenges are unique. 'Systems engineering' has evolved as a discipline in order to meet these challenges by providing a structured, top-down design and development methodology for the engineer. This paper attempts to define the general class of problems requiring the complete systems engineering treatment and to show how systems engineering can be utilized to improve customer satisfaction and profit ability. Specifically, this work will focus on a design methodology for the largest of systems, not necessarily in terms of physical size, but in terms of complexity and interconnectivity.

  8. Epilogue: Systems Approaches and Systems Practice

    NASA Astrophysics Data System (ADS)

    Reynolds, Martin; Holwell, Sue

    Each of the five systems approaches discussed in this volume: system dynamics (SD), the viable systems model (VSM), strategic options development and analysis (SODA), soft systems methodology (SSM) and critical systems heuristics (CSH) has a pedigree. Not in the sense of the sometimes absurd spectacle of animals paraded at dog shows. Rather, their pedigree derives from their systems foundations, their capacity to evolve and their flexibility in use. None of the five approaches has developed out of use in restricted and controlled contexts of either low or high levels of complicatedness. Neither has any one of them evolved as a consequence of being applied only to situations with either presumed stakeholder agreement on purpose, or courteous disagreement amongst stakeholders, or stakeholder coercion. The compilation is not a celebration of abstract ‘methodologies', but of theoretically robust approaches that have a genuine pedigree in practice.

  9. Expert system modeling of a vision system

    NASA Astrophysics Data System (ADS)

    Reihani, Kamran; Thompson, Wiley E.

    1992-05-01

    The proposed artificial intelligence-based vision model incorporates natural recognition processes depicted as a visual pyramid and hierarchical representation of objects in the database. The visual pyramid, with based and apex representing pixels and image, respectively, is used as an analogy for a vision system. This paper provides an overview of recognition activities and states in the framework of an inductive model. Also, it presents a natural vision system and a counterpart expert system model that incorporates the described operations.

  10. INSENS sensor system

    SciTech Connect

    Myers, D.W.; Baker, J.; Benzel, D.M.; Fuess, D.A.

    1993-09-29

    This paper describes an unattended ground sensor system that has been developed for the immigration and Naturalization Service (INS). The system, known as INSENS, was developed at the Lawrence Livermore National Laboratory for use by the United States Border Patrol. This system assists in the detection of illegal entry of aliens and contraband (illegal drugs, etc.) into the United States along its land borders. Key to the system is its flexible modular design which allows future software and hardware enhancements to the system without altering the fundamental architecture of the system. Elements of the system include a sensor system capable of processing signals from multiple directional probes, a repeater system, and a handheld monitor system. Seismic, passive infrared (PIR), and magnetic probes are currently supported. The design of the INSENS system elements and their performance are described.

  11. Precision digital control systems

    NASA Astrophysics Data System (ADS)

    Vyskub, V. G.; Rozov, B. S.; Savelev, V. I.

    This book is concerned with the characteristics of digital control systems of great accuracy. A classification of such systems is considered along with aspects of stabilization, programmable control applications, digital tracking systems and servomechanisms, and precision systems for the control of a scanning laser beam. Other topics explored are related to systems of proportional control, linear devices and methods for increasing precision, approaches for further decreasing the response time in the case of high-speed operation, possibilities for the implementation of a logical control law, and methods for the study of precision digital control systems. A description is presented of precision automatic control systems which make use of electronic computers, taking into account the existing possibilities for an employment of computers in automatic control systems, approaches and studies required for including a computer in such control systems, and an analysis of the structure of automatic control systems with computers. Attention is also given to functional blocks in the considered systems.

  12. Forming different planetary systems

    NASA Astrophysics Data System (ADS)

    Zhou, Ji-Lin; Xie, Ji-Wei; Liu, Hui-Gen; Zhang, Hui; Sun, Yi-Sui

    2012-08-01

    With the increasing number of detected exoplanet samples, the statistical properties of planetary systems have become much clearer. In this review, we summarize the major statistical results that have been revealed mainly by radial velocity and transiting observations, and try to interpret them within the scope of the classical core-accretion scenario of planet formation, especially in the formation of different orbital architectures for planetary systems around main sequence stars. Based on the different possible formation routes for different planet systems, we tentatively classify them into three major catalogs: hot Jupiter systems, standard systems and distant giant planet systems. The standard system can be further categorized into three sub-types under different circumstances: solar-like systems, hot Super-Earth systems, and subgiant planet systems. We also review the theory of planet detection and formation in binary systems as well as planets in star clusters.

  13. Hot Spot Removal System: System description

    SciTech Connect

    1997-09-01

    Hazardous wastes contaminated with radionuclides, chemicals, and explosives exist across the Department of Energy complex and need to be remediated due to environmental concerns. Currently, an opportunity is being developed to dramatically reduce remediation costs and to assist in the acceleration of schedules associated with these wastes by deploying a Hot Spot Removal System. Removing the hot spot from the waste site will remove risk driver(s) and enable another, more cost effective process/option/remedial alternative (i.e., capping) to be applied to the remainder of the site. The Hot Spot Removal System consists of a suite of technologies that will be utilized to locate and remove source terms. Components of the system can also be used in a variety of other cleanup activities. This Hot Spot Removal System Description document presents technologies that were considered for possible inclusion in the Hot Spot Removal System, technologies made available to the Hot Spot Removal System, industrial interest in the Hot Spot Removal System`s subsystems, the schedule required for the Hot Spot Removal System, the evaluation of the relevant technologies, and the recommendations for equipment and technologies as stated in the Plan section.

  14. Space Launch and Temperature System: Avionics System

    NASA Technical Reports Server (NTRS)

    Gillis, Amelia; Luna, Steve; Schrock, Ken; Howard, Ricky; Kilpatrick, John (Technical Monitor)

    2001-01-01

    This paper outlines the approach needed to develop the avionics system for a Space Launch and Transportation System. Avionics systems development, power, range safety, and simulations considerations are covered. Each of these topics includes the project design inputs that must be considered on the outset. Process steps are then provided to obtain the desired outputs. This paper discusses the importance of starting and staying with an overall systems plan that ensures that all avionics internal and external requirements are fulfilled. Key design, development, testing and implementations considerations are provided.

  15. Novel central nervous system drug delivery systems.

    PubMed

    Stockwell, Jocelyn; Abdi, Nabiha; Lu, Xiaofan; Maheshwari, Oshin; Taghibiglou, Changiz

    2014-05-01

    For decades, biomedical and pharmaceutical researchers have worked to devise new and more effective therapeutics to treat diseases affecting the central nervous system. The blood-brain barrier effectively protects the brain, but poses a profound challenge to drug delivery across this barrier. Many traditional drugs cannot cross the blood-brain barrier in appreciable concentrations, with less than 1% of most drugs reaching the central nervous system, leading to a lack of available treatments for many central nervous system diseases, such as stroke, neurodegenerative disorders, and brain tumors. Due to the ineffective nature of most treatments for central nervous system disorders, the development of novel drug delivery systems is an area of great interest and active research. Multiple novel strategies show promise for effective central nervous system drug delivery, giving potential for more effective and safer therapies in the future. This review outlines several novel drug delivery techniques, including intranasal drug delivery, nanoparticles, drug modifications, convection-enhanced infusion, and ultrasound-mediated drug delivery. It also assesses possible clinical applications, limitations, and examples of current clinical and preclinical research for each of these drug delivery approaches. Improved central nervous system drug delivery is extremely important and will allow for improved treatment of central nervous system diseases, causing improved therapies for those who are affected by central nervous system diseases. PMID:24325540

  16. Intelligent inspection system

    NASA Astrophysics Data System (ADS)

    May, Jeniece; Dale, Ken; Holloway, Mike; Gaby, Willard

    1997-01-01

    The intelligent inspection system is an advanced controller and analysis system for dimensional measuring machines dedicated to measuring surface of revolution mechanical parts. IIS was developed by the Lockheed Martin Energy Systems, Inc. Oak Ridge Y-12 plant because no commercial product was available to replace the obsolete computing systems on these important machines.

  17. Coaches as System Leaders

    ERIC Educational Resources Information Center

    Fullan, Michael; Knight, Jim

    2011-01-01

    The role of school leadership--of principals and coaches--must be played out on a systems level to get widespread and sustainable improvement. Successful, whole-system education reform relies on capacity building, teamwork, pedagogy, and systemic reform. The strategies of good coaches and the right drivers for whole-system reform go hand in hand.…

  18. Computer Center: CIBE Systems.

    ERIC Educational Resources Information Center

    Crovello, Theodore J.

    1982-01-01

    Differentiates between computer systems and Computers in Biological Education (CIBE) systems (computer system intended for use in biological education). Describes several CIBE stand alone systems: single-user microcomputer; single-user microcomputer/video-disc; multiuser microcomputers; multiuser maxicomputer; and local and long distance computer…

  19. Program (systems) engineering

    NASA Technical Reports Server (NTRS)

    Baroff, Lynn E.; Easter, Robert W.; Pomphrey, Richard B.

    2004-01-01

    Program Systems Engineering applies the principles of Systems Engineering at the program level. Space programs are composed of interrelated elements which can include collections of projects, advanced technologies, information systems, etc. Some program elements are outside traditional engineering's physical systems, such as education and public outreach, public relations, resource flow, and interactions within the political environments.

  20. Imaging systems and applications.

    PubMed

    Bennett, Gisele; Catrysse, Peter B; Farrell, Joyce E; Fowler, Boyd; Mait, Joseph N

    2012-02-01

    Imaging systems are used in consumer, medical, and military applications. Designing, developing, and building imaging systems requires a multidisciplinary approach. This issue features current research in imaging systems that ranges from fundamental theories to novel applications. Although the papers collected are diverse, their unique compilation provides a systems perspective to imaging. PMID:22307134

  1. Broad Bandwidth Telecommunications Systems.

    ERIC Educational Resources Information Center

    Sodolski, John

    Broad bandwidth transmission systems have been around for years. They include microwave, assorted cable systems, and recently, satellites. With the exception of some privately owned systems, broadband services have been furnished by the common carriers. Recently, a new element has been added--Cable Antenna Television (CATV) distribution systems.…

  2. Microsphere insulation systems

    NASA Technical Reports Server (NTRS)

    Allen, Mark S. (Inventor); Willen, Gary S. (Inventor); Mohling, Robert A. (Inventor)

    2005-01-01

    A new insulation system is provided that contains microspheres. This insulation system can be used to provide insulated panels and clamshells, and to insulate annular spaces around objects used to transfer, store, or transport cryogens and other temperature-sensitive materials. This insulation system provides better performance with reduced maintenance than current insulation systems.

  3. Medical imaging systems

    DOEpatents

    Frangioni, John V

    2013-06-25

    A medical imaging system provides simultaneous rendering of visible light and diagnostic or functional images. The system may be portable, and may include adapters for connecting various light sources and cameras in open surgical environments or laparascopic or endoscopic environments. A user interface provides control over the functionality of the integrated imaging system. In one embodiment, the system provides a tool for surgical pathology.

  4. Electronic Document Supply Systems.

    ERIC Educational Resources Information Center

    Cawkell, A. E.

    1991-01-01

    Describes electronic document delivery systems used by libraries and document image processing systems used for business purposes. Topics discussed include technical specifications; analogue read-only laser videodiscs; compact discs and CD-ROM; WORM; facsimile; ADONIS (Article Delivery over Network Information System); DOCDEL; and systems at the…

  5. Regulation of hypothalamic renin-angiotensin system and oxidative stress by aldosterone

    PubMed Central

    Huang, Bing S; Zheng, Hong; Tan, Junhui; Patel, Kaushik P; Leenen, Frans HH

    2011-01-01

    In rats with salt-induced hypertension or post myocardial infarction (MI), AT1 receptor (AT1R) densities and oxidative stress increase and neuronal nitric oxide synthase (nNOS) levels decrease in the paraventricular nucleus (PVN). The present study was designed to determine whether these changes may depend on activation of the aldosterone – “ouabain” neuromodulatory pathway. After intracerebroventricular (icv) infusion of aldosterone (20ng/h) for 14 days, blood pressure (BP) and heart rate (HR) were recorded in conscious Wistar rats, and mRNA and protein for nNOS, endothelial NOS (eNOS), AT1R and NADPH oxidase subunits were assessed in brain tissue. BP and HR were significantly increased by aldosterone. Aldosterone significantly increased mRNA and protein of AT1R, P22phox, P47phox, P67phox and Nox2, and decreased nNOS but not eNOS mRNA and protein in the PVN, and increased angiotensin converting enzyme (ACE) and AT1R binding densities in the PVN and SON. The increases in BP and HR as well as changes in mRNA, proteins and ACE and AT1R binding densities were all largely prevented by concomitant icv infusion of Digibind (to bind “ouabain”) or benzamil (to block presumably epithelial sodium channels). These data indicate that aldosterone via “ouabain” increases in the PVN ACE, AT1R and oxidative stress but decreases nNOS, and suggest that endogenous aldosterone may cause this similar pattern of changes observed in salt sensitive hypertension and heart failure post MI. PMID:21824999

  6. Identification of propulsion systems

    NASA Technical Reports Server (NTRS)

    Merrill, Walter; Guo, Ten-Huei; Duyar, Ahmet

    1991-01-01

    This paper presents a tutorial on the use of model identification techniques for the identification of propulsion system models. These models are important for control design, simulation, parameter estimation, and fault detection. Propulsion system identification is defined in the context of the classical description of identification as a four step process that is unique because of special considerations of data and error sources. Propulsion system models are described along with the dependence of system operation on the environment. Propulsion system simulation approaches are discussed as well as approaches to propulsion system identification with examples for both air breathing and rocket systems.

  7. On generalized Volterra systems

    NASA Astrophysics Data System (ADS)

    Charalambides, S. A.; Damianou, P. A.; Evripidou, C. A.

    2015-01-01

    We construct a large family of evidently integrable Hamiltonian systems which are generalizations of the KM system. The algorithm uses the root system of a complex simple Lie algebra. The Hamiltonian vector field is homogeneous cubic but in a number of cases a simple change of variables transforms such a system to a quadratic Lotka-Volterra system. We present in detail all such systems in the cases of A3, A4 and we also give some examples from higher dimensions. We classify all possible Lotka-Volterra systems that arise via this algorithm in the An case.

  8. What is systems engineering?

    SciTech Connect

    Bahill, A.T.

    1995-08-01

    Systems Engineering is an interdisciplinary process that ensures that the customers` needs are satisfied throughout a system`s entire life cycle. This process includes: understanding customer needs; stating the problem; specifying requirements; defining performance and cost measures, prescribing tests, validating requirements, conducting design reviews, exploring alternative concepts, sensitivity analyses, functional decomposition, system design, designing and managing interfaces, system integration, total system test, configuration management, risk management, reliability analysis; total quality management; project management; and documentation. Material for this paper was gathered from senior Systems Engineers at Sandia National Laboratories.

  9. Advanced information processing system: Local system services

    NASA Technical Reports Server (NTRS)

    Burkhardt, Laura; Alger, Linda; Whittredge, Roy; Stasiowski, Peter

    1989-01-01

    The Advanced Information Processing System (AIPS) is a multi-computer architecture composed of hardware and software building blocks that can be configured to meet a broad range of application requirements. The hardware building blocks are fault-tolerant, general-purpose computers, fault-and damage-tolerant networks (both computer and input/output), and interfaces between the networks and the computers. The software building blocks are the major software functions: local system services, input/output, system services, inter-computer system services, and the system manager. The foundation of the local system services is an operating system with the functions required for a traditional real-time multi-tasking computer, such as task scheduling, inter-task communication, memory management, interrupt handling, and time maintenance. Resting on this foundation are the redundancy management functions necessary in a redundant computer and the status reporting functions required for an operator interface. The functional requirements, functional design and detailed specifications for all the local system services are documented.

  10. Decentralized Modular Systems Versus Centralized Systems.

    ERIC Educational Resources Information Center

    Crossey, R. E.

    Building design, planning, and construction programing for modular decentralized mechanical building systems are outlined in terms of costs, performance, expansion and flexibility. Design strategy, approach, and guidelines for implementing such systems for buildings are suggested, with emphasis on mechanical equipment and building element…

  11. ENVIRONMENTAL SYSTEMS MANAGEMENT AND SUSTAINABLE SYSTEMS THEORY

    EPA Science Inventory

    Environmental Systems Management is the management of environmental problems at the systems level fully accounting for the multi-dimensional nature of the environment. This includes socio-economic dimensions as well as the usual physical and life science aspects. This is importa...

  12. Performance, Performance System, and High Performance System

    ERIC Educational Resources Information Center

    Jang, Hwan Young

    2009-01-01

    This article proposes needed transitions in the field of human performance technology. The following three transitions are discussed: transitioning from training to performance, transitioning from performance to performance system, and transitioning from learning organization to high performance system. A proposed framework that comprises…

  13. EPICS system: system structure and user interface

    SciTech Connect

    West, R.E.; Bartlett, J.F.; Bobbitt, J.S.; Lahey, T.E.; Kramper, B.J.; MacKinnon, B.A.

    1984-02-01

    This paper present the user's view of and the general organization of the EPICS control system at Fermilab. Various subsystems of the EPICS control system are discussed. These include the user command language, software protection, the device database, remote computer interfaces, and several application utilities. This paper is related to two other papers on EPICS: an overview paper and a detailed implementation paper.

  14. Efficient Evaluation System for Learning Management Systems

    ERIC Educational Resources Information Center

    Cavus, Nadire

    2009-01-01

    A learning management system (LMS) provides the platform for web-based learning environment by enabling the management, delivery, tracking of learning, testing, communication, registration process and scheduling. There are many LMS systems on the market that can be obtained for free or through payment. It has now become an important task to choose…

  15. Local hospital systems: forerunners of regional systems?

    PubMed

    Luke, R D

    1992-01-01

    Over the past several decades, the hospital industry has been undergoing a major organizational change that has until now been little examined. Local hospital systems (LHSs) are combinations of two or more hospitals that are in the same company and located in or around the same metropolitan areas in this country. This article presents the first detailed examination of the 402 such systems that have been identified to date. LHSs offer great potential for achieving the cost, quality, and access benefits that are often attributable to regional systems. The degree to which LHSs have attained some basic structural features expected of regional systems are examined. Differences are compared within ownership categories. Issues and challenges facing leaders in the field, should they hope to achieve the potential of regional systems, are discussed. PMID:10122669

  16. Photovoltaic systems and applications

    SciTech Connect

    Not Available

    1982-01-01

    Abstracts are given of presentations given at a project review meeting held at Albuquerque, NM. The proceedings cover the past accomplishments and current activities of the Photovoltaic Systems Research, Balance-of-System Technology Development and System Application Experiments Projects at Sandia National Laboratories. The status of intermediate system application experiments and residential system analysis is emphasized. Some discussion of the future of the Photovoltaic Program in general, and the Sandia projects in particular is also presented.

  17. Residential photovoltaic system designs

    SciTech Connect

    Russell, M. C.

    1981-01-01

    A project to develop Residential Photovoltaic Systems has begun at Massachusetts Institute of Technology Lincoln Laboratory with the construction and testing of five Prototype Systems. All of these systems utilize a roof-mounted photovoltaic array and allow excess solar-generated electric energy to be fed back to the local utility grid, eliminating the need for on-site storage. Residential photovoltaic system design issues are discussed and specific features of the five Prototype Systems now under test are presented.

  18. Satellite services system overview

    NASA Technical Reports Server (NTRS)

    Rysavy, G.

    1982-01-01

    The benefits of a satellite services system and the basic needs of the Space Transportation System to have improved satellite service capability are identified. Specific required servicing equipment are discussed in terms of their technology development status and their operative functions. Concepts include maneuverable television systems, extravehicular maneuvering unit, orbiter exterior lighting, satellite holding and positioning aid, fluid transfer equipment, end effectors for the remote manipulator system, teleoperator maneuvering system, and hand and power tools.

  19. Data Acquisition Systems

    NASA Technical Reports Server (NTRS)

    1989-01-01

    Technology developed during a joint research program with Langley and Kinetic Systems Corporation led to Kinetic Systems' production of a high speed Computer Automated Measurement and Control (CAMAC) data acquisition system. The study, which involved the use of CAMAC equipment applied to flight simulation, significantly improved the company's technical capability and produced new applications. With Digital Equipment Corporation, Kinetic Systems is marketing the system to government and private companies for flight simulation, fusion research, turbine testing, steelmaking, etc.

  20. FNAL system patching design

    SciTech Connect

    Schmidt, Jack; Lilianstrom, Al; Romero, Andy; Dawson, Troy; Sieh, Connie; /Fermilab

    2004-01-01

    FNAL has over 5000 PCs running either Linux or Windows software. Protecting these systems efficiently against the latest vulnerabilities that arise has prompted FNAL to take a more central approach to patching systems. Due to different levels of existing support infrastructures, the patching solution for linux systems differs from that of windows systems. In either case, systems are checked for vulnerabilities by Computer Security using the Nessus tool.

  1. Fluid infusion system

    NASA Technical Reports Server (NTRS)

    1974-01-01

    Performance testing carried out in the development of the prototype zero-g fluid infusion system is described and summarized. Engineering tests were performed in the course of development, both on the original breadboard device and on the prototype system. This testing was aimed at establishing baseline system performance parameters and facilitating improvements. Acceptance testing was then performed on the prototype system to verify functional performance. Acceptance testing included a demonstration of the fluid infusion system on a laboratory animal.

  2. Automated Pilot Advisory System

    NASA Technical Reports Server (NTRS)

    Parks, J. L., Jr.; Haidt, J. G.

    1981-01-01

    An Automated Pilot Advisory System (APAS) was developed and operationally tested to demonstrate the concept that low cost automated systems can provide air traffic and aviation weather advisory information at high density uncontrolled airports. The system was designed to enhance the see and be seen rule of flight, and pilots who used the system preferred it over the self announcement system presently used at uncontrolled airports.

  3. Evolvable synthetic neural system

    NASA Technical Reports Server (NTRS)

    Curtis, Steven A. (Inventor)

    2009-01-01

    An evolvable synthetic neural system includes an evolvable neural interface operably coupled to at least one neural basis function. Each neural basis function includes an evolvable neural interface operably coupled to a heuristic neural system to perform high-level functions and an autonomic neural system to perform low-level functions. In some embodiments, the evolvable synthetic neural system is operably coupled to one or more evolvable synthetic neural systems in a hierarchy.

  4. On evolutionary systems.

    PubMed

    Alvarez de Lorenzana, J M; Ward, L M

    1987-01-01

    This paper develops a metatheoretical framework for understanding evolutionary systems (systems that develop in ways that increase their own variety). The framework addresses shortcomings seen in other popular systems theories. It concerns both living and nonliving systems, and proposes a metahierarchy of hierarchical systems. Thus, it potentially addresses systems at all descriptive levels. We restrict our definition of system to that of a core system whose parts have a different ontological status than the system, and characterize the core system in terms of five global properties: minimal length interval, minimal time interval, system cycle, total receptive capacity, and system potential. We propose two principles through the interaction of which evolutionary systems develop. The Principle of Combinatorial Expansion describes how a core system realizes its developmental potential through a process of progressive differentiation of the single primal state up to a limit stage. The Principle of Generative Condensation describes how the components of the last stage of combinatorial expansion condense and become the environment for and components of new, enriched systems. The early evolution of the Universe after the "big bang" is discussed in light of these ideas as an example of the application of the framework. PMID:3689299

  5. A System of Systems Approach to the EU Energy System

    NASA Astrophysics Data System (ADS)

    Jess, Tom; Madani, Kaveh; Mahlooji, Maral; Ristic, Bora

    2016-04-01

    Around the world, measures to prevent dangerous climate change are being adopted and may change energy systems fundamentally. The European Union (EU) is committed to reducing greenhouse gas emission by 20% by 2020 and by 80-95% by 2050. In order to achieve this, EU member states aim to increase the share of renewables in the energy mix to 20% by 2020. This commitment comes as part of a series of other aims, principles, and policies to reform the EU's energy system. Cost-efficiency in the emissions reductions measures as well as strategic goals under the Resource Efficient Europe flagship initiative which would include a more prudent approach to other natural resources such as water and land. Using the "System of Systems Approach", as from Hadian and Madani (2015), energy sources' Relative Aggregate Footprints (RAF) in the EU are evaluated. RAF aggregates across four criteria: carbon footprint, water footprint, land footprint, and economic cost. The four criteria are weighted by resource availability across the EU and for each Member State. This provides an evaluation of the overall resource use efficiency of the EU's energy portfolio and gives insight into the differences in the desirability of energy sources across Member States. Broadly, nuclear, onshore wind, and geothermal are most desirable under equal criteria weights and EU average weighting introduces only small changes in the relative performance of only few technologies. The member state specific weightings show that most countries have similar energy technology preferences. However, the UK deviates most strongly from the average, with an even stronger preference for nuclear and coal. Sweden, Malta and Finland also deviate from the typical preferences indicating the complexity in play in reforming the EU energy system. Reference Hadian S, Madani K (2015) A System of Systems Approach to Energy Sustainability Assessment: Are All Renewables Really Green? Ecological Indicators, 52, 194-206.

  6. A protective role for endothelial nitric oxide synthase in glomerulonephritis.

    PubMed

    Heeringa, Peter; Steenbergen, Eric; van Goor, Harry

    2002-03-01

    In acute glomerulonephritis (GN), increased nitric oxide (NO) production occurs, suggesting a pathophysiological role for NO in the disease process. Although NO potentially could have both toxic as well as protective effects, its exact role in the pathophysiology of GN is unclear and may depend on the NOS isoform generating NO. The protective effects of NO such as prevention of leukocyte and platelet activation and adhesion have been attributed to NO generated by endothelial nitric oxide synthase (eNOS). Evidence for a beneficial role for eNOS includes the demonstration of reduced eNOS expression in experimental models of GN as well as human biopsy specimens that is mostly likely due to endothelial cell necrosis. Reduced NO production in GN also may occur through reaction of NO with superoxide anions or the myeloperoxidase (MPO)/hypochlorous acid (HOCL) system. Further evidence has been provided by the observation that in several experimental models of GN, glomerular injury is exacerbated following treatment with non-selective NO inhibitors. Finally, the development of GN is severely aggravated in mice lacking a functional gene for eNOS as compared to wild-type mice, providing direct support for a protective role of eNOS-derived NO in acute GN. PMID:11849432

  7. Intelligent systems technology infrastructure for integrated systems

    NASA Technical Reports Server (NTRS)

    Lum, Henry

    1991-01-01

    A system infrastructure must be properly designed and integrated from the conceptual development phase to accommodate evolutionary intelligent technologies. Several technology development activities were identified that may have application to rendezvous and capture systems. Optical correlators in conjunction with fuzzy logic control might be used for the identification, tracking, and capture of either cooperative or non-cooperative targets without the intensive computational requirements associated with vision processing. A hybrid digital/analog system was developed and tested with a robotic arm. An aircraft refueling application demonstration is planned within two years. Initially this demonstration will be ground based with a follow-on air based demonstration. System dependability measurement and modeling techniques are being developed for fault management applications. This involves usage of incremental solution/evaluation techniques and modularized systems to facilitate reuse and to take advantage of natural partitions in system models. Though not yet commercially available and currently subject to accuracy limitations, technology is being developed to perform optical matrix operations to enhance computational speed. Optical terrain recognition using camera image sequencing processed with optical correlators is being developed to determine position and velocity in support of lander guidance. The system is planned for testing in conjunction with Dryden Flight Research Facility. Advanced architecture technology is defining open architecture design constraints, test bed concepts (processors, multiple hardware/software and multi-dimensional user support, knowledge/tool sharing infrastructure), and software engineering interface issues.

  8. Systems Architecture for a Nationwide Healthcare System.

    PubMed

    Abin, Jorge; Nemeth, Horacio; Friedmann, Ignacio

    2015-01-01

    From a national level to give Internet technology support, the Nationwide Integrated Healthcare System in Uruguay requires a model of Information Systems Architecture. This system has multiple healthcare providers (public and private), and a strong component of supplementary services. Thus, the data processing system should have an architecture that considers this fact, while integrating the central services provided by the Ministry of Public Health. The national electronic health record, as well as other related data processing systems, should be based on this architecture. The architecture model described here conceptualizes a federated framework of electronic health record systems, according to the IHE affinity model, HL7 standards, local standards on interoperability and security, as well as technical advice provided by AGESIC. It is the outcome of the research done by AGESIC and Systems Integration Laboratory (LINS) on the development and use of the e-Government Platform since 2008, as well as the research done by the team Salud.uy since 2013. PMID:26262000

  9. Modeling Power Systems as Complex Adaptive Systems

    SciTech Connect

    Chassin, David P.; Malard, Joel M.; Posse, Christian; Gangopadhyaya, Asim; Lu, Ning; Katipamula, Srinivas; Mallow, J V.

    2004-12-30

    Physical analogs have shown considerable promise for understanding the behavior of complex adaptive systems, including macroeconomics, biological systems, social networks, and electric power markets. Many of today's most challenging technical and policy questions can be reduced to a distributed economic control problem. Indeed, economically based control of large-scale systems is founded on the conjecture that the price-based regulation (e.g., auctions, markets) results in an optimal allocation of resources and emergent optimal system control. This report explores the state-of-the-art physical analogs for understanding the behavior of some econophysical systems and deriving stable and robust control strategies for using them. We review and discuss applications of some analytic methods based on a thermodynamic metaphor, according to which the interplay between system entropy and conservation laws gives rise to intuitive and governing global properties of complex systems that cannot be otherwise understood. We apply these methods to the question of how power markets can be expected to behave under a variety of conditions.

  10. Rover waste assay system

    SciTech Connect

    Akers, D.W.; Stoots, C.M.; Kraft, N.C.; Marts, D.J.

    1997-11-01

    The Rover Waste Assay System (RWAS) is a nondestructive assay system designed for the rapid assay of highly-enriched {sup 235}U contaminated piping, tank sections, and debris from the Rover nuclear rocket fuel processing facility at the Idaho Chemical Processing Plant. A scanning system translates a NaI(Tl) detector/collimator system over the structural components where both relative and calibrated measurements for {sup 137}Cs are made. Uranium-235 concentrations are in operation and is sufficiently automated that most functions are performed by the computer system. These functions include system calibration, problem identification, collimator control, data analysis, and reporting. Calibration of the system was done through a combination of measurements on calibration standards and benchmarked modeling. A description of the system is presented along with the methods and uncertainties associated with the calibration and analysis of the system for components from the Rover facility. 4 refs., 2 figs., 4 tabs.

  11. NASA Systems Engineering Handbook

    NASA Technical Reports Server (NTRS)

    Shishko, Robert; Aster, Robert; Chamberlain, Robert G.; Mcduffee, Patrick; Pieniazek, Les; Rowell, Tom; Bain, Beth; Cox, Renee I.; Mooz, Harold; Polaski, Lou

    1995-01-01

    This handbook brings the fundamental concepts and techniques of systems engineering to NASA personnel in a way that recognizes the nature of NASA systems and environment. It is intended to accompany formal NASA training courses on systems engineering and project management when appropriate, and is designed to be a top-level overview. The concepts were drawn from NASA field center handbooks, NMI's/NHB's, the work of the NASA-wide Systems Engineering Working Group and the Systems Engineering Process Improvement Task team, several non-NASA textbooks and guides, and material from independent systems engineering courses taught to NASA personnel. Five core chapters cover systems engineering fundamentals, the NASA Project Cycle, management issues in systems engineering, systems analysis and modeling, and specialty engineering integration. It is not intended as a directive. Superseded by: NASA/SP-2007-6105 Rev 1 (20080008301).

  12. Alkaline etch system qualification

    SciTech Connect

    Goldammer, S.E.; Pemberton, S.E.; Tucker, D.R.

    1997-04-01

    Based on the data from this qualification activity, the Atotech etch system, even with minimum characterization, was capable of etching production printed circuit products as good as those from the Chemcut system. Further characterization of the Atotech system will improve its etching capability. In addition to the improved etch quality expected from further characterization, the Atotech etch system has additional features that help reduce waste and provide for better consistency in the etching process. The programmable logic controller and computer will allow operators to operate the system manually or from pre-established recipes. The evidence and capabilities of the Atotech system made it as good as or better than the Chemcut system for etching WR products. The Printed Wiring Board Engineering Department recommended that the Atotech system be released for production. In December 1995, the Atotech system was formerly qualified for production.

  13. Open systems storage platforms

    NASA Technical Reports Server (NTRS)

    Collins, Kirby

    1992-01-01

    The building blocks for an open storage system includes a system platform, a selection of storage devices and interfaces, system software, and storage applications CONVEX storage systems are based on the DS Series Data Server systems. These systems are a variant of the C3200 supercomputer with expanded I/O capabilities. These systems support a variety of medium and high speed interfaces to networks and peripherals. System software is provided in the form of ConvexOS, a POSIX compliant derivative of 4.3BSD UNIX. Storage applications include products such as UNITREE and EMASS. With the DS Series of storage systems, Convex has developed a set of products which provide open system solutions for storage management applications. The systems are highly modular, assembled from off the shelf components with industry standard interfaces. The C Series system architecture provides a stable base, with the performance and reliability of a general purpose platform. This combination of a proven system architecture with a variety of choices in peripherals and application software allows wide flexibility in configurations, and delivers the benefits of open systems to the mass storage world.

  14. A systems analysis of longwall mining systems

    SciTech Connect

    Ramani, R.V.; Kovach, T.S.

    1983-03-01

    In many instances, the actual production from a longwall face does not equal the planned capacity. General problem areas which have been identified include face length and panel depth, face area and gate entry roof support, face conveyor and shearer wear, outby haulage system failures, number of entries in longwall gate development and longwall move time. The performance of a longwall face is totally dependent on the interaction of these and many other factors. To explore fully these interactions, a systems analysis of longwalls has been performed. In this paper, the systems approach, the factors considered in the analysis, and the results of the analysis are presented.

  15. Digital wireless control system

    NASA Astrophysics Data System (ADS)

    Smith, R.

    1993-08-01

    The Digital Wireless Control System (DWCS) is designed to initiate high explosives safely while using a wireless remote control system. Numerous safety features have been designed into the fire control system to mitigate the hazards associated with remote initiation of high explosives. These safety features range from a telemetry (TM) fire control status system to mechanical timers and keyed power lockout switches. The environment, safety, and health (ES&H) Standard Operating Procedure (SOP) SP471970 is intended as a guide when working with the DWCS. This report describes the Digital Wireless Control System and outlines each component's theory of operation and its relationship to the system.

  16. Continuous system modeling

    NASA Technical Reports Server (NTRS)

    Cellier, Francois E.

    1991-01-01

    A comprehensive and systematic introduction is presented for the concepts associated with 'modeling', involving the transition from a physical system down to an abstract description of that system in the form of a set of differential and/or difference equations, and basing its treatment of modeling on the mathematics of dynamical systems. Attention is given to the principles of passive electrical circuit modeling, planar mechanical systems modeling, hierarchical modular modeling of continuous systems, and bond-graph modeling. Also discussed are modeling in equilibrium thermodynamics, population dynamics, and system dynamics, inductive reasoning, artificial neural networks, and automated model synthesis.

  17. Flash evaporator systems test

    NASA Technical Reports Server (NTRS)

    Dietz, J. B.

    1976-01-01

    A flash evaporator heat rejection system representative of that proposed for the space shuttle orbiter underwent extensive system testing at the NASA Johnson Space Center (JSC) to determine its operational suitability and to establish system performance/operational characteristics for use in the shuttle system. During the tests the evaporator system demonstrated its suitability to meet the shuttle requirements by: (1) efficient operation with 90 to 95% water evaporation efficiency, (2) control of outlet temperature to 40 + or - 2 F for partial heat load operation, (3) stability of control system for rapid changes in Freon inlet temperature, and (4) repeated dormant-to-active device operation without any startup procedures.

  18. Space shuttle avionics system

    NASA Technical Reports Server (NTRS)

    Hanaway, John F.; Moorehead, Robert W.

    1989-01-01

    The Space Shuttle avionics system, which was conceived in the early 1970's and became operational in the 1980's represents a significant advancement of avionics system technology in the areas of systems and redundacy management, digital data base technology, flight software, flight control integration, digital fly-by-wire technology, crew display interface, and operational concepts. The origins and the evolution of the system are traced; the requirements, the constraints, and other factors which led to the final configuration are outlined; and the functional operation of the system is described. An overall system block diagram is included.

  19. Concepts, states, and systems

    NASA Astrophysics Data System (ADS)

    Wolff, Karl Erich

    2000-05-01

    Mathematical System Theory is extended to Conceptual System Theory using Formal Concept Analysis (Wille 1982). States are defined as formal concepts and `points of time' are generalized to `time granules,' interpreted as `pieces' of time needed for the realization of measurements. As a generalization of classical time systems we define conceptual time systems, their state spaces and phase spaces. Time dependent relations among the parts of a conceptual time system are introduced in `relational conceptual time systems.' Applications in psychology and industry, including `conceptual films' are mentioned.

  20. Cooperating systems: Layered MAS

    NASA Technical Reports Server (NTRS)

    Rochowiak, Daniel

    1990-01-01

    Distributed intelligent systems can be distinguished by the models that they use. The model developed focuses on layered multiagent system conceived of as a bureaucracy in which a distributed data base serves as a central means of communication. The various generic bureaus of such a system is described and a basic vocabulary for such systems is presented. In presenting the bureaus and vocabularies, special attention is given to the sorts of reasonings that are appropriate. A bureaucratic model has a hierarchy of master system and work group that organizes E agents and B agents. The master system provides the administrative services and support facilities for the work groups.

  1. Data Acquisition Systems

    NASA Technical Reports Server (NTRS)

    1994-01-01

    In the mid-1980s, Kinetic Systems and Langley Research Center determined that high speed CAMAC (Computer Automated Measurement and Control) data acquisition systems could significantly improve Langley's ARTS (Advanced Real Time Simulation) system. The ARTS system supports flight simulation R&D, and the CAMAC equipment allowed 32 high performance simulators to be controlled by centrally located host computers. This technology broadened Kinetic Systems' capabilities and led to several commercial applications. One of them is General Atomics' fusion research program. Kinetic Systems equipment allows tokamak data to be acquired four to 15 times more rapidly. Ford Motor company uses the same technology to control and monitor transmission testing facilities.

  2. Experiment support system

    NASA Technical Reports Server (NTRS)

    Shannon, A. V.

    1977-01-01

    The Experiment Support System is a switchboard system with displays and controls. It routes electrical power to experiments M092, M093, and M171 equipment; gaseous nitrogen to the Blood Pressure Measurement System; receives biomedical data from all related equipment; routes the conditioned data signals to the Airlock Module Telemetry System and also displays (in digital or analog from) portions of that data which the crewmen must see to complete the experiment successfully. The Experiment Support System is interfaced to the M131 control panel to transfer conditioned data to the Airlock Module Telemetry System.

  3. MLS: Airplane system modeling

    NASA Technical Reports Server (NTRS)

    Thompson, A. D.; Stapleton, B. P.; Walen, D. B.; Rieder, P. F.; Moss, D. G.

    1981-01-01

    Analysis, modeling, and simulations were conducted as part of a multiyear investigation of the more important airplane-system-related items of the microwave landing system (MLS). Particular emphasis was placed upon the airplane RF system, including the antenna radiation distribution, the cabling options from the antenna to the receiver, and the overall impact of the airborne system gains and losses upon the direct-path signal structure. In addition, effort was expended toward determining the impact of the MLS upon the airplane flight management system and developing the initial stages of a fast-time MLS automatic control system simulation model. Results ot these studies are presented.

  4. EPICS system: an overview

    SciTech Connect

    Bartlett, J.F.; Bobbitt, J.S.; Kramper, B.J.; Lahey, T.E.; MacKinnon, B.A.; West, R.E.

    1984-02-01

    This paper presents an overview of the EPICS control system at FERMILAB. EPICS is a distributed, multi-user, interactive system for the control and monitoring of particle beamlines at a high-energy experimental physics laboratory. The overview discusses the operating environment of the control system, the requirements which determined the design decisions, the hardware and software configurations, and plans for the future growth and enhancement of the present system. This paper is the first of three related papers on the EPICS system. The other two cover (1) the system structure and user interface and (2) RSX implementation issues.

  5. Verification of Adaptive Systems

    SciTech Connect

    Pullum, Laura L; Cui, Xiaohui; Vassev, Emil; Hinchey, Mike; Rouff, Christopher; Buskens, Richard

    2012-01-01

    Adaptive systems are critical for future space and other unmanned and intelligent systems. Verification of these systems is also critical for their use in systems with potential harm to human life or with large financial investments. Due to their nondeterministic nature and extremely large state space, current methods for verification of software systems are not adequate to provide a high level of assurance for them. The combination of stabilization science, high performance computing simulations, compositional verification and traditional verification techniques, plus operational monitors, provides a complete approach to verification and deployment of adaptive systems that has not been used before. This paper gives an overview of this approach.

  6. Precision Pointing System Development

    SciTech Connect

    BUGOS, ROBERT M.

    2003-03-01

    The development of precision pointing systems has been underway in Sandia's Electronic Systems Center for over thirty years. Important areas of emphasis are synthetic aperture radars and optical reconnaissance systems. Most applications are in the aerospace arena, with host vehicles including rockets, satellites, and manned and unmanned aircraft. Systems have been used on defense-related missions throughout the world. Presently in development are pointing systems with accuracy goals in the nanoradian regime. Future activity will include efforts to dramatically reduce system size and weight through measures such as the incorporation of advanced materials and MEMS inertial sensors.

  7. Weather Information System

    NASA Technical Reports Server (NTRS)

    1995-01-01

    WxLink is an aviation weather system based on advanced airborne sensors, precise positioning available from the satellite-based Global Positioning System, cockpit graphics and a low-cost datalink. It is a two-way system that uplinks weather information to the aircraft and downlinks automatic pilot reports of weather conditions aloft. Manufactured by ARNAV Systems, Inc., the original technology came from Langley Research Center's cockpit weather information system, CWIN (Cockpit Weather INformation). The system creates radar maps of storms, lightning and reports of surface observations, offering improved safety, better weather monitoring and substantial fuel savings.

  8. Airborne oceanographic lidar system

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Specifications and preliminary design of an Airborne Oceanographic Lidar (AOL) system, which is to be constructed for installation and used on a NASA Wallops Flight Center (WFC) C-54 research aircraft, are reported. The AOL system is to provide an airborne facility for use by various government agencies to demonstrate the utility and practicality of hardware of this type in the wide area collection of oceanographic data on an operational basis. System measurement and performance requirements are presented, followed by a description of the conceptual system approach and the considerations attendant to its development. System performance calculations are addressed, and the system specifications and preliminary design are presented and discussed.

  9. Power system interface and umbilical system study

    NASA Technical Reports Server (NTRS)

    1980-01-01

    System requirements and basic design criteria were defined for berthing or docking a payload to the 25 kW power module which will provide electrical power and attitude control, cooling, data transfer, and communication services to free-flying and Orbiter sortie payloads. The selected umbilical system concept consists of four assemblies and command and display equipment to be installed at the Orbiter payload specialist station: (1) a movable platen assembly which is attached to the power system with EVA operable devices; (2) a slave platen assembly which is attached to the payload with EVA operable devices; (3) a fixed secondary platen permanently installed in the power system; and (4) a fixed secondary platen permanently installed on the payload. Operating modes and sequences are described.

  10. Business System Planning Project System Requirements Specification

    SciTech Connect

    NELSON, R.E.

    2000-09-08

    The purpose of the Business Systems Planning Project System Requirements Specification (SRS) is to provide the outline and contents of the requirements for the CH2M HILL Hanford Group, Inc. (CHG) integrated business and technical information systems. The SRS will translate proposed objectives into the statement of the functions that are to be performed and data and information flows that they require. The requirements gathering methodology will use (1) facilitated group requirement sessions; (2) individual interviews; (3) surveys; and (4) document reviews. The requirements will be verified and validated through coordination of the technical requirement team and CHG Managers. The SRS document used the content and format specified in Lockheed Martin Services, Inc. Organization Standard Software Practices in conjunction with the Institute of Electrical and Electronics Engineers Standard 8340-1984 for Systems Requirements Documents.

  11. NASA's SPICE System Models the Solar System

    NASA Technical Reports Server (NTRS)

    Acton, Charles

    1996-01-01

    SPICE is NASA's multimission, multidiscipline information system for assembling, distributing, archiving, and accessing space science geometry and related data used by scientists and engineers for mission design and mission evaluation, detailed observation planning, mission operations, and science data analysis.

  12. User Registration Systems for Distributed Systems

    NASA Astrophysics Data System (ADS)

    Murphy, K. J.; Cechini, M.; Pilone, D.; Mitchell, A.

    2010-12-01

    As NASA’s Earth Observing System Data and Information System (EOSDIS) systems have evolved over the years, most of the EOSDIS data are now available to users via anonymous on-line access. Although the changes have improved the dissemination efficiency of earth science data, the anonymous access has made it difficult to characterize users, capture metrics on the value of EOSDIS and provide customized services that benefit users. As the number of web-based applications continues to grow, data centers and application providers have implemented their own user registration systems and provided new tools and interfaces for their registered users. This has led to the creation of independent registration systems for accessing data and interacting with online tools and services. The user profile information maintained at each of these registration systems is not consistent and the registration enforcement varies by system as well. This problem is in no way unique to EOSDIS and represents a general challenge to the distributed computing community. In a study done in 2007(http://www2007.org/papers/paper620.pd), the average user has approximately 7 passwords for about 25 accounts and enters a password 8 times a day. These numbers have only increased in the last three years. To try and address this, a number of solutions have been offered including Single Sign-On solutions using a common backend like Microsoft Active Directory or an LDAP server, trust based identity providers like OpenID, and various forms of authorization delegation like OAuth or SAML/XACML. This talk discusses the differences between authentication and authorization, the state of the more popular user registration solutions available for distributed use, and some of the technical and policy drivers that need to be considered when incorporating a user registration system into your application.

  13. Enabling Systems Biology Approaches Through Microfabricated Systems

    PubMed Central

    Zhan, Mei; Chingozha, Loice; Lu, Hang

    2014-01-01

    With the experimental tools and knowledge that have accrued from a long history of reductionist biology, we can now start to put the pieces together and begin to understand how biological systems function as an integrated whole. Here, we describe how microfabricated tools have demonstrated promise in addressing experimental challenges in throughput, resolution and sensitivity to support systems-based approaches to biological understanding. PMID:23984862

  14. System and method for creating expert systems

    NASA Technical Reports Server (NTRS)

    Hughes, Peter M. (Inventor); Luczak, Edward C. (Inventor)

    1998-01-01

    A system and method provides for the creation of a highly graphical expert system without the need for programming in code. An expert system is created by initially building a data interface, defining appropriate Mission, User-Defined, Inferred, and externally-generated GenSAA (EGG) data variables whose data values will be updated and input into the expert system. Next, rules of the expert system are created by building appropriate conditions of the rules which must be satisfied and then by building appropriate actions of rules which are to be executed upon corresponding conditions being satisfied. Finally, an appropriate user interface is built which can be highly graphical in nature and which can include appropriate message display and/or modification of display characteristics of a graphical display object, to visually alert a user of the expert system of varying data values, upon conditions of a created rule being satisfied. The data interface building, rule building, and user interface building are done in an efficient manner and can be created without the need for programming in code.

  15. Integrated Systems Health Management for Intelligent Systems

    NASA Technical Reports Server (NTRS)

    Figueroa, Fernando; Melcher, Kevin

    2011-01-01

    The implementation of an integrated system health management (ISHM) capability is fundamentally linked to the management of data, information, and knowledge (DIaK) with the purposeful objective of determining the health of a system. Management implies storage, distribution, sharing, maintenance, processing, reasoning, and presentation. ISHM is akin to having a team of experts who are all individually and collectively observing and analyzing a complex system, and communicating effectively with each other in order to arrive at an accurate and reliable assessment of its health. In this chapter, concepts, procedures, and approaches are presented as a foundation for implementing an ISHM capability relevant to intelligent systems. The capability stresses integration of DIaK from all elements of a system, emphasizing an advance toward an on-board, autonomous capability. Both ground-based and on-board ISHM capabilities are addressed. The information presented is the result of many years of research, development, and maturation of technologies, and of prototype implementations in operational systems.

  16. Immune System (For Parents)

    MedlinePlus

    ... lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has ... can't be prevented, you can help your child's immune system stay stronger and fight illnesses by ...

  17. System status display evaluation

    NASA Technical Reports Server (NTRS)

    Summers, Leland G.

    1988-01-01

    The System Status Display is an electronic display system which provides the crew with an enhanced capability for monitoring and managing the aircraft systems. A flight simulation in a fixed base cockpit simulator was used to evaluate alternative design concepts for this display system. The alternative concepts included pictorial versus alphanumeric text formats, multifunction versus dedicated controls, and integration of the procedures with the system status information versus paper checklists. Twelve pilots manually flew approach patterns with the different concepts. System malfunctions occurred which required the pilots to respond to the alert by reconfiguring the system. The pictorial display, the multifunction control interfaces collocated with the system display, and the procedures integrated with the status information all had shorter event processing times and lower subjective workloads.

  18. Central nervous system

    MedlinePlus

    The central nervous system is composed of the brain and spinal cord. Your brain and spinal cord serve as the main "processing center" for your entire nervous system. They control all the workings of your body.

  19. Leasing Residential PV Systems

    SciTech Connect

    Rutberg, Michael; Bouza, Antonio

    2013-11-01

    The article discusses the adoption, consequences and current market status of the leasing of residential photovoltaic systems. It addresses attributed energy savings and market potential of residential system leasing.

  20. School System Empires

    ERIC Educational Resources Information Center

    Huberman, Michael

    1972-01-01

    Although most educational systems are resistant to change, there are some features of the community, of the teachers, of government, and of the system that enable one to predict the likelihood of an innovation being accepted and implemented. (AL)

  1. Henry Ford Health Systems

    Cancer.gov

    Henry Ford Health Systems evolved from a hospital into a system delivering care to 2.5 million patients and includes the Cancer Epidemiology, Prevention and Control Program, which focuses on epidemiologic and public health aspects of cancer.

  2. Highly Autonomous Systems Workshop

    NASA Technical Reports Server (NTRS)

    Doyle, R.; Rasmussen, R.; Man, G.; Patel, K.

    1998-01-01

    It is our aim by launching a series of workshops on the topic of highly autonomous systems to reach out to the larger community interested in technology development for remotely deployed systems, particularly those for exploration.

  3. Double Degenerate Binary Systems

    SciTech Connect

    Yakut, K.

    2011-09-21

    In this study, angular momentum loss via gravitational radiation in double degenerate binary (DDB)systems (NS + NS, NS + WD, WD + WD, and AM CVn) is studied. Energy loss by gravitational waves has been estimated for each type of systems.

  4. Torque control system

    NASA Technical Reports Server (NTRS)

    Studenick, D. K.; Tyler, A. L.; Squillari, W.

    1975-01-01

    System stabilizes aximuth of gondolas which are carried by high-altitude balloons as platforms for tracking telescopes. When telescopes must be constantly aimed at specific targets, control system stabilizes gondola to within 5 arc-seconds.

  5. Immune System and Disorders

    MedlinePlus

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  6. Pneumonia - weakened immune system

    MedlinePlus

    ... medlineplus.gov/ency/article/000093.htm Pneumonia - weakened immune system To use the sharing features on this page, ... fighting off infection because of problems with the immune system. This type of disease is called "pneumonia in ...

  7. Male Reproductive System

    MedlinePlus

    ... gamete, the egg or ovum , meet in the female's reproductive system to create a new individual. Both the male and female reproductive systems are essential for reproduction. Humans, like other organisms, ...

  8. Male Reproductive System

    MedlinePlus

    ... gamete, the egg or ovum, meet in the female's reproductive system to create a baby. Both the male and female reproductive systems are essential for reproduction. Humans pass certain characteristics ...

  9. Power system stability

    SciTech Connect

    Not Available

    1984-03-01

    The following papers are included: exact Lagrangians for linear nonconservative systems; linear nonconservative systems with asymmetric parameters derivable from a Lagrangian; some remarks on the derivability of linear nonconservative systems from a Lagrangian; dynamic response by means of functions of matrices; a direct construction of first integrals for certain nonlinear dynamical systems; derivation of the Brayton-Moser equations from a topological mixed potential function; quadratic integrals for linear nonconservative systems and their connection with the inverse problem of Lagrangian dynamics; generalized Lagrangian and conservation law for the damped harmonic oscillator; connections between the generalized Hamilton-Lagrange and Brayton-Moser equations; time-dependent linear systems derivable from a variational principle; the generalized Lagrange formulation for nonlinear RLC networks; the Helmholtz conditions revisited - a new approach to the inverse problem of Lagrangian dynamics; time-dependent linear systems derivable from a variational principle II; and conservation laws for some separable gyroscopic dynamical systems.

  10. Silver recovery system data

    SciTech Connect

    Boulineau, B.

    1991-08-26

    In August of 1990 the Savannah River Site Photography Group began testing on a different type of silver recovery system. This paper describes the baseline study and the different phases of installation and testing of the system.

  11. Absorption heat pump system

    DOEpatents

    Grossman, Gershon

    1984-01-01

    The efficiency of an absorption heat pump system is improved by conducting liquid from a second stage evaporator thereof to an auxiliary heat exchanger positioned downstream of a primary heat exchanger in the desorber of the system.

  12. JT-60 Control System

    SciTech Connect

    Yonekawa, I.; Kawamata, Y.; Totsuka, T.; Akasaka, H.; Sueoka, M.; Kurihara, K.; Kimura, T.

    2002-09-15

    The present status of the JT-60U control system is reported including its original design concept, the progress of the system, and various modifications since the JT-60 upgrade. This control system has features of a functionally distributed and hierarchical structure, using CAMAC interfaces initially, which have been replaced by versatile module Europe (VME)-bus interfaces, and a protective interlock system composed of both software and hard-wired interlock logics. Plant monitoring and control are performed by efficient data communication through CAMAC highways and Ethernet with TCP/IP protocols. Sequential control of plasma discharges is executed by a combination of a remodeled VME-bus system and a timing system. A real-time plasma control system and a human interface system have been continuously modified corresponding to the progress of JT-60U experiments.

  13. Human Resource Accounting System

    ERIC Educational Resources Information Center

    Cerullo, Michael J.

    1974-01-01

    Main objectives of human resource accounting systems are to satisfy the informational demands made by investors and by operating managers. The paper's main concern is with the internal uses of a human asset system. (Author)

  14. Secondary power systems

    SciTech Connect

    Not Available

    1985-01-01

    In aeronautical engineering secondary power systems have long played second fiddle to the airframe, the engine, and indeed, the avionics. This collection of papers is thus timely, and its publication by the Institution of Mechanical Engineers appropriate, as secondary power systems in modern aircraft present challenging mechanical engineering problems. In military aircraft demands for electrical and hydraulic power and high pressure air have grown over the past two decades. To these basic needs are added requirements for emergency power, ground power, and independent engine starting. Additionally increased reliability and maintainability is demanded from all secondary power systems. Complete contents: What is a secondary power system. Modern technology secondary power systems for next generation military aircraft; Integrated power units; Secondary power system gearbox; Starting the system - air turbine starters; Auxiliary and emergency power system; Secondary hydraulic power generation; Advanced technology electrical power generation equipment.

  15. Alarm Notification System

    Energy Science and Technology Software Center (ESTSC)

    1995-03-12

    AN/EMS, the Alarm Notification Energy Management System, is used to monitor digital sensors in PETC buildings and to notify the safety/security operator by both a video and an audio system when a possibly hazardous condition arises.

  16. Biomedical recording system

    NASA Technical Reports Server (NTRS)

    Vick, H. A.

    1970-01-01

    System collects medical data directly from patients and permanently records and displays several parameters - electrocardiograph, electroencephalograph, heart rate, respiration rate, auscultatory blood pressure, leg circumference changes, body temperature, and time. Components and operation of the system are described.

  17. Male Reproductive System

    MedlinePlus

    ... Surveillance Modules » Anatomy & Physiology » Reproductive System » Male Reproductive System Cancer Registration & Surveillance Modules Anatomy & Physiology Intro to the Human Body Body Functions & Life Process Anatomical Terminology Review Quiz ...

  18. Modular optical detector system

    DOEpatents

    Horn, Brent A.; Renzi, Ronald F.

    2006-02-14

    A modular optical detector system. The detector system is designed to detect the presence of molecules or molecular species by inducing fluorescence with exciting radiation and detecting the emitted fluorescence. Because the system is capable of accurately detecting and measuring picomolar concentrations it is ideally suited for use with microchemical analysis systems generally and capillary chromatographic systems in particular. By employing a modular design, the detector system provides both the ability to replace various elements of the detector system without requiring extensive realignment or recalibration of the components as well as minimal user interaction with the system. In addition, the modular concept provides for the use and addition of a wide variety of components, including optical elements (lenses and filters), light sources, and detection means, to fit particular needs.

  19. Gleason grading system

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000920.htm Gleason grading system To use the sharing features on this page, ... score of between 5 and 7. Gleason Grading System Sometimes, it can be hard to predict how ...

  20. Multiple system atrophy

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/000757.htm Multiple system atrophy To use the sharing features on this page, please enable JavaScript. Multiple system atrophy (MSA) is a rare condition that causes ...

  1. Semiotic labelled deductive systems

    SciTech Connect

    Nossum, R.T.

    1996-12-31

    We review the class of Semiotic Models put forward by Pospelov, as well as the Labelled Deductive Systems developed by Gabbay, and construct an embedding of Semiotic Models into Labelled Deductive Systems.

  2. Immune System and Disorders

    MedlinePlus

    ... substances that are usually not harmful Immune deficiency diseases - disorders in which the immune system is missing one or more of its parts Autoimmune diseases - diseases causing your immune system to attack your ...

  3. Avian respiratory system disorders

    USGS Publications Warehouse

    Olsen, G.H.

    1989-01-01

    Diagnosing and treating respiratory diseases in avian species requires a basic knowledge about the anatomy and physiology of this system in birds. Differences between mammalian and avian respiratory system function, diagnosis, and treatment are highlighted.

  4. Absorption heat pump system

    DOEpatents

    Grossman, G.

    1982-06-16

    The efficiency of an absorption heat pump system is improved by conducting liquid from a second stage evaporator thereof to an auxiliary heat exchanger positioned downstream of a primary heat exchanger in the desorber of the system.

  5. Information retrieval system

    NASA Technical Reports Server (NTRS)

    Berg, R. F.; Holcomb, J. E.; Kelroy, E. A.; Levine, D. A.; Mee, C., III

    1970-01-01

    Generalized information storage and retrieval system capable of generating and maintaining a file, gathering statistics, sorting output, and generating final reports for output is reviewed. File generation and file maintenance programs written for the system are general purpose routines.

  6. Intensive care alarm system

    NASA Technical Reports Server (NTRS)

    Christensen, J. L.; Herbert, A. L.

    1973-01-01

    Inductive loop has been added to commercially available call system fitted with earphone receiver. System transmits high frequency signals to nurse's receiver to announce patient's need for help without disturbing others.

  7. INL Autonomous Navigation System

    Energy Science and Technology Software Center (ESTSC)

    2005-03-30

    The INL Autonomous Navigation System provides instructions for autonomously navigating a robot. The system permits high-speed autonomous navigation including obstacle avoidance, waypoing navigation and path planning in both indoor and outdoor environments.

  8. Portable Dental System

    NASA Technical Reports Server (NTRS)

    1980-01-01

    Portable dental system provides dental care in isolated communities. System includes a patient's chair and a dentist's stool, an X-ray machine and a power unit, all of which fold into compact packages. A large yellow "pumpkin" is a collapsible compressed air tank. Portable system has been used successfully in South America in out of the way communities with this back-packable system, and in American nursing homes. This product is no longer manufactured.

  9. Space shuttle revitalization system

    NASA Technical Reports Server (NTRS)

    Quattrone, P. D.

    1985-01-01

    The Space Shuttle air revitalization system is discussed. The sequential steps in loop closure are examined and a schematic outline of the regenerative air revitalization system is presented. Carbon dioxide reduction subsystem concepts are compared. Schemes are drawn for: static feedwater electrolysis cell, solid polymer electrolyte water electrolysis cell, air revitalization system, nitrogen generation reactions, nitrogen subsystem staging, vapor compression distillation subsystem, thermoelectric integrated membrane evaporation subsystem, catalytic distillation water reclamation subsystem, and space shuttle solid waste management system.

  10. Modular integrated video system

    SciTech Connect

    Gaertner, K.J.; Heaysman, B.; Holt, R.; Sonnier, C.

    1986-01-01

    The Modular Integrated Video System (MIVS) is intended to provide a simple, highly reliable closed circuit television (CCTV) system capable of replacing the IAEA Twin Minolta Film Camera Systems in those safeguards facilities where mains power is readily available, and situations where it is desired to have the CCTV camera separated from the CCTV recording console. This paper describes the MIVS and the Program Plan which is presently being followed for the development, testing, and implementation of the system.

  11. Linear system theory

    NASA Technical Reports Server (NTRS)

    Callier, Frank M.; Desoer, Charles A.

    1991-01-01

    The aim of this book is to provide a systematic and rigorous access to the main topics of linear state-space system theory in both the continuous-time case and the discrete-time case; and the I/O description of linear systems. The main thrusts of the work are the analysis of system descriptions and derivations of their properties, LQ-optimal control, state feedback and state estimation, and MIMO unity-feedback systems.

  12. Intermediate water recovery system

    NASA Technical Reports Server (NTRS)

    Deckman, G.; Anderson, A. R. (Editor)

    1973-01-01

    A water recovery system for collecting, storing, and processing urine, wash water, and humidity condensates from a crew of three aboard a spacecraft is described. The results of a 30-day test performed on a breadboard system are presented. The intermediate water recovery system produced clear, sterile, water with a 96.4 percent recovery rate from the processed urine. Recommendations for improving the system are included.

  13. Visual Alert System

    NASA Technical Reports Server (NTRS)

    1985-01-01

    A visual alert system resulted from circuitry developed by Applied Cybernetics Systems for Langley as part of a space related telemetry system. James Campman, Applied Cybernetics president, left the company and founded Grace Industries, Inc. to manufacture security devices based on the Langley technology. His visual alert system combines visual and audible alerts for hearing impaired people. The company also manufactures an arson detection device called the electronic nose, and is currently researching additional applications of the NASA technology.

  14. Lithium battery management system

    DOEpatents

    Dougherty, Thomas J.

    2012-05-08

    Provided is a system for managing a lithium battery system having a plurality of cells. The battery system comprises a variable-resistance element electrically connected to a cell and located proximate a portion of the cell; and a device for determining, utilizing the variable-resistance element, whether the temperature of the cell has exceeded a predetermined threshold. A method of managing the temperature of a lithium battery system is also included.

  15. Space power systems technology

    NASA Technical Reports Server (NTRS)

    Coulman, George A.

    1994-01-01

    Reported here is a series of studies which examine several potential catalysts and electrodes for some fuel cell systems, some materials for space applications, and mathematical modeling and performance predictions for some solid oxide fuel cells and electrolyzers. The fuel cell systems have a potential for terrestrial applications in addition to solar energy conversion in space applications. Catalysts and electrodes for phosphoric acid fuel cell systems and for polymer electrolyte membrane (PEM) fuel cell and electrolyzer systems were examined.

  16. Automated RTOP Management System

    NASA Technical Reports Server (NTRS)

    Hayes, P.

    1984-01-01

    The structure of NASA's Office of Aeronautics and Space Technology electronic information system network from 1983 to 1985 is illustrated. The RTOP automated system takes advantage of existing hardware, software, and expertise, and provides: (1) computerized cover sheet and resources forms; (2) electronic signature and transmission; (3) a data-based information system; (4) graphics; (5) intercenter communications; (6) management information; and (7) text editing. The system is coordinated with Headquarters efforts in codes R,E, and T.

  17. Nonsurvivable momentum exchange system

    NASA Technical Reports Server (NTRS)

    Roder, Russell (Inventor); Ahronovich, Eliezer (Inventor); Davis, III, Milton C. (Inventor)

    2007-01-01

    A demiseable momentum exchange system includes a base and a flywheel rotatably supported on the base. The flywheel includes a web portion defining a plurality of web openings and a rim portion. The momentum exchange system further includes a motor for driving the flywheel and a cover for engaging the base to substantially enclose the flywheel. The system may also include components having a melting temperature below 1500 degrees Celsius. The momentum exchange system is configured to demise on reentry.

  18. Digital communication systems

    NASA Astrophysics Data System (ADS)

    Peebles, Peyton Z., Jr.

    The fundamental principles of digital communication and the design of practical digital communication systems are explored in an introductory textbook for senior and graduate students of electrical engineering. Chapters are devoted to sampling principles, baseband digital waveforms, baseband digital systems, bandpass binary digital systems, and M-ary digital systems. Deterministic signals, networks, and random-signal theory are reviewed in extensive appendices, and graphs, flow charts, diagrams, and problems are provided.

  19. Space station power system

    NASA Technical Reports Server (NTRS)

    Baraona, Cosmo R.

    1987-01-01

    The major requirements and guidelines that affect the space station configuration and power system are explained. The evolution of the space station power system from the NASA program development-feasibility phase through the current preliminary design phase is described. Several early station concepts are described and linked to the present concept. Trade study selections of photovoltaic system technologies are described in detail. A summary of present solar dynamic and power management and distribution systems is also given.

  20. Goddard Ground System Environment

    NASA Technical Reports Server (NTRS)

    Liu, Ben

    2009-01-01

    This slide presentation reviews the Goddard Mission Services Evolution Center's work in providing the Ground System Infrastructure to allow for standard interfaces, and allow for a mix of heritage and new components. This software has been used by NASA and other Government users. Telemetry and command services are also provided as are mission planning and scheduling systems. Other areas that the presentation covers are work on trending systems, and data management system.