Abstract-Impaired response to catecholamines contributes to the altered hemodynamics in sepsis, which has been attributed to excessive NO formation. We have studied the systemic hemodynamic and local forearm responses and inducible NO synthase (iNOS) expression during experimental endotoxemia in humans. Escherichia coli endotoxin (lipopolysaccharide [LPS]) was administered at doses of 1 or 2 ng/kg to healthy volunteers. In 10 subjects, the systemic pressor effect of phenylephrine was assessed before and after the administration of LPS. In 9 further subjects, forearm blood flow responses to intra-arterial noradrenaline, acetylcholine, glyceryl trinitrate, and N G -monomethyl-L-arginine (L-NMMA) were studied at baseline and after LPS administration. Peripheral blood was collected and analyzed for iNOS mRNA and protein. Four hours after LPS, the response of systolic blood pressure (PϽ0.0005) and heart rate (PϽ0.05) to phenylephrine was significantly reduced. In the forearm, noradrenaline-induced vasoconstriction was also reduced by Ϸ50% (PϽ0.01), but L-NMMA responsiveness was unchanged. iNOS mRNA or protein was not increased. Marked vascular adrenoceptor hyporeactivity is detectable in the absence of increased NO activity or iNOS expression in endotoxemia, arguing against major involvement of vascular iNOS activity in the acute systemic vasodilation to LPS. Key Words: inducible nitric oxide synthase Ⅲ nitric oxide Ⅲ sepsis Ⅲ lipopolysaccharide Ⅲ adrenoceptors S epsis is still associated with a high mortality rate and remains a major therapeutic challenge despite improved intensive care therapy. 1 One of the key clinical aspects of sepsis, which is responsible for the poor hemodynamic state of these patients, is inappropriate vasodilation and impaired response to catecholamines, 2 resulting in hemodynamic instability and shock.A variety of substances and mediators is released by activated blood cells and endothelial cells during sepsis. 2,3 Many in vitro and in vivo animal experiments have indicated that excess formation of nitric NO in the vasculature may play the key role in the systemic vasodilation in sepsis and endotoxemia. These data suggest that most of the NO produced is formed after the induction of an inducible form of NO synthase (iNOS), which is not expressed in the vasculature under normal conditions. 4 iNOS can be induced in a variety of cells, such as vascular endothelial cells, vascular smooth muscle cells, and white blood cells (WBCs) after in vitro stimulation with endotoxin 5 and remains present for several days. Inhibition of NO synthesis in animals by NO synthase inhibitors reduces Escherichia coli endotoxin (lipopolysaccharide [LPS])-induced hypotension and vascular leakage and improves mortality. 6 -8 Experiments with iNOS knockout animals 9 and animals treated with iNOS antisense oligonucleotides 10 corroborated these pharmacological studies.Data on iNOS expression in humans are limited. A recent study did not detect iNOS in cells or vessels of the systemic circulation in septic patients but...

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The Vienna VLBI and Satellite Software (VieVS) is state-of-the-art Very Long Baseline Interferometry (VLBI) analysis software for geodesy and astrometry. VieVS has been developed at Technische Universität Wien (TU Wien) since 2008, where it is used for research purposes and for teaching space geodetic techniques. In the past decade, it has been successfully applied on Very Long Baseline Interferometry (VLBI) observations for the determination of celestial and terrestrial reference frames as well as for the estimation of celestial pole offsets, universal Time (UT1-UTC), and polar motion based on least-squares adjustment. Furthermore, VieVS is equipped with tools for scheduling and simulating VLBI observations to extragalactic radio sources as well as to satellites and spacecraft, features which proved to be very useful for a variety of applications. VieVS is now available as version 3.0 and we do provide the software to all interested persons and institutions. A wiki with more information about VieVS is available at http://vievswiki.geo.tuwien.ac.at/.

In connection with the work for the next generation VLBI2010 Global Observing System (VGOS) of the International VLBI Service for Geodesy and Astrometry, a new scheduling package (Vie_Sched) has been developed at the Vienna University of Technology as a part of the Vienna VLBI Software. In addition to the classical station-based approach it is equipped with a new scheduling strategy based on the radio sources to be observed. We introduce different configurations of source-based scheduling options and investigate the implications on present and future VLBI2010 geodetic schedules. By comparison to existing VLBI schedules of the continuous campaign CONT11, we find that the source-based approach with two sources has a performance similar to the station-based approach in terms of number of observations, sky coverage, and geodetic parameters. For an artificial 16 station VLBI2010 network, the source-based approach with four sources provides an improved distribution of source observations on the celestial sphere. Monte Carlo simulations yield slightly better repeatabilities of station coordinates with the source-based approach with two sources or four sources than the classical strategy. The new VLBI scheduling software with its alternative scheduling strategy offers a promising option with respect to applications of the VGOS.