298 research outputs found

    A first analysis of the mean motion of CHAMP

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    The present study consists in studying the mean orbital motion of the CHAMP satellite, through a single long arc on a period of time of 200 days in 2001. We actually investigate the sensibility of its mean motion to its accelerometric data, as measures of the surface forces, over that period. In order to accurately determine the mean motion of CHAMP, we use “observed&quot; mean orbital elements computed, by filtering, from 1-day GPS orbits. On the other hand, we use a semi-analytical model to compute the arc. It consists in numerically integrating the effects of the mean potentials (due to the Earth and the Moon and Sun), and the effects of mean surfaces forces acting on the satellite. These later are, in case of CHAMP, provided by an averaging of the Gauss system of equations. Results of the fit of the long arc give a relative sensibility of about 10<sup>-3</sup>, although our gravitational mean model is not well suited to describe very low altitude orbits. This technique, which is purely dynamical, enables us to control the decreasing of the trajectory altitude, as a possibility to validate accelerometric data on a long term basis.<br><br><b>Key words.</b> Mean orbital motion, accelerometric dat

    Involvement of β3-Adrenoceptor in Altered β-Adrenergic Response in Senescent Heart: Role of Nitric Oxide Synthase 1–derived Nitric Oxide

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    Background: In senescent heart, β-adrenergic response is altered in parallel with β1- and β2-adrenoceptor down-regulation. A negative inotropic effect of β3-adrenoceptor could be involved. In this study, the authors tested the hypothesis that β3-adrenoceptor plays a role in β-adrenergic dysfunction in senescent heart.Methods: β-Adrenergic responses were investigated in vivo (echocardiography–dobutamine, electron paramagnetic resonance) and in vitro (isolated left ventricular papillary muscle, electron paramagnetic resonance) in young adult (3-month-old) and senescent (24-month-old) rats. Nitric oxide synthase (NOS) immunolabeling (confocal microscopy), nitric oxide production (electron paramagnetic resonance) and β-adrenoceptor Western blots were performed in vitro. Data are mean percentages of baseline ± SD. Results: An impaired positive inotropic effect (isoproterenol) was confirmed in senescent hearts in vivo (117 ± 23 vs. 162 ± 16%; P &lt; 0.05) and in vitro (127 ± 10 vs. 179 ± 15%; P &lt; 0.05). In the young adult group, the positive inotropic effect was not significantly modified by the nonselective NOS inhibitor NG-nitro-l-arginine methylester (l-NAME; 183 ± 19%), the selective NOS1 inhibitor vinyl-l-N-5(1-imino-3-butenyl)-l-ornithine (l-VNIO; 172 ± 13%), or the selective NOS2 inhibitor 1400W (183 ± 19%). In the senescent group, in parallel with β3-adrenoceptor up-regulation and increased nitric oxide production, the positive inotropic effect was partially restored by l-NAME (151 ± 8%; P &lt; 0.05) and l-VNIO (149 ± 7%; P &lt; 0.05) but not by 1400W (132 ± 11%; not significant). The positive inotropic effect induced by dibutyryl-cyclic adenosine monophosphate was decreased in the senescent group with the specific β3-adrenoceptor agonist BRL 37344 (167 ± 10 vs. 142 ± 10%; P &lt; 0.05). NOS1 and NOS2 were significantly up-regulated in the senescent rat. Conclusions: In senescent cardiomyopathy, β3-adrenoceptor overexpression plays an important role in the altered β-adrenergic response via induction of NOS1-nitric oxide

    MicroRNA-24 regulates vascularity after myocardial infarction

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    BACKGROUND: Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood. METHODS AND RESULTS: Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2-associated death promoter) and Sirtuin1 were identified by transcriptome, protein arrays, and chromatin immunoprecipitation analyses. Overexpression of miR-24 or silencing of its targets significantly impaired angiogenesis in zebrafish embryos. Blocking of endothelial miR-24 limited myocardial infarct size of mice via prevention of endothelial apoptosis and enhancement of vascularity, which led to preserved cardiac function and survival. CONCLUSIONS: Our findings indicate that miR-24 acts as a critical regulator of endothelial cell apoptosis and angiogenesis and is suitable for therapeutic intervention in the setting of ischemic heart disease. [KEYWORDS: Animals, Apoptosis/drug effects, Arterioles/pathology, Capillaries/pathology, Cell Hypoxia, Cells, Cultured/drug effects/metabolism, Collagen, Drug Combinations, Drug Evaluation, Preclinical, Endothelial Cells/ metabolism/pathology, GATA2 Transcription Factor/biosynthesis/genetics, Gene Expression Profiling, Heart Failure/etiology, Heme Oxygenase-1/biosynthesis/genetics, Laminin, Male, Mice, Mice, Inbred C57BL, MicroRNAs/antagonists & inhibitors/genetics/ physiology, Myocardial Infarc

    Query Answering in Normal Logic Programs under Uncertainty

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    We present a simple, yet general top-down query answering procedure for normal logic programs over lattices and bilattices, where functions may appear in the rule bodies. Its interest relies on the fact that many approaches to paraconsistency and uncertainty in logic programs with or without non-monotonic negation are based on bilattices or lattices, respectively
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