886 research outputs found

    Nucleoside diphosphate kinase B is required for the formation of heterotrimeric G protein containing caveolae.

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    Caveolae are flask-shaped invaginations in the plasma membrane that serve to compartmentalize and organize signal transduction processes, including signals mediated by G protein-coupled receptors and heterotrimeric G proteins. Herein we report evidence for a close association of the nucleoside diphosphate kinase B (NDPK B) and caveolin proteins which is required for G protein scaffolding and caveolae formation. A concomitant loss of the proteins NDPK B, caveolin isoforms 1 (Cav1) and 3, and heterotrimeric G proteins occurred when one of these proteins was specifically depleted in zebrafish embryos. Co-immunoprecipitation of Cav1 with the G protein Gβ-subunit and NDPK B from zebrafish lysates corroborated the direct association of these proteins. Similarly, in embryonic fibroblasts from the respective knockout (KO) mice, the membrane content of the Cav1, Gβ, and NDPK B was found to be mutually dependent on one another. A redistribution of Cav1 and Gβ from the caveolae containing fractions of lower density to other membrane compartments with higher density could be detected by means of density gradient fractionation of membranes derived from NDPK A/B KO mouse embryonic fibroblasts (MEFs) and after shRNA-mediated NDPK B knockdown in H10 cardiomyocytes. This redistribution could be visualized by confocal microscopy analysis showing a decrease in the plasma membrane bound Cav1 in NDPK A/B KO cells and vice versa and a decrease in the plasma membrane pool of NDPK B in Cav1 KO cells. Consequently, ultrastructural analysis revealed a reduction of surface caveolae in the NDPK A/B KO cells. To prove that the disturbed subcellular localization of Cav1 in NDPK A/B KO MEFs as well as NDPK B in Cav1 KO MEFs is a result of the loss of NDPK B and Cav1, respectively, we performed rescue experiments. The adenoviral re-expression of NDPK B in NDPK A/B KO MEFs rescued the protein content and the plasma membrane localization of Cav1. The expression of an EGFP-Cav1 fusion protein in Cav1-KO cells induced a restoration of NDPK B expression levels and its appearance at the plasma membrane. We conclude from these findings that NDPK B, heterotrimeric G proteins, and caveolins are mutually dependent on each other for stabile localization and caveolae formation at the plasma membrane. The data point to a disturbed transport of caveolin/G protein/NDPK B complexes from intracellular membrane compartments if one of the components is missing

    An introduction to description logics and query rewriting

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    This chapter gives an overview of the description logics underlying the OWL 2 Web Ontology Language and its three tractable profiles, OWL 2 RL, OWL 2 EL and OWL 2 QL. We consider the syntax and semantics of these description logics as well as main reasoning tasks and their computational complexity. We also discuss the semantical foundations for fist-order and datalog rewritings of conjunctive queries over knowledge bases given in the OWL2 profiles, and outline the architecture of the ontology-based data access system Ontop

    Performance of the CREAM calorimeter in accelerator beam test

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    The CREAM calorimeter, designed to measure the spectra of cosmic-ray nuclei from under 1 TeV to 1000 TeV, is a 20 radiation length (X0) deep sampling calorimeter. The calorimeter is comprised of 20 layers of tungsten interleaved with 20 layers of scintillating fiber ribbons, and is preceded by a pair of graphite interaction targets providing about 0.42 proton interaction lengths (\lambda int). The calorimeter was placed in one of CERN's SPS accelerator beams for calibration and testing. Beams of 150 GeV electrons were used for calibration, and a variety of electron, proton, and nuclear fragment beams were used to test the simulation model of the detector. In this paper we discuss the performance of the calorimeter in the electron beam and compare electron beam data with simulation results.The CREAM calorimeter, designed to measure the spectra of cosmic-ray nuclei from under 1 TeV to 1000 TeV, is a 20 radiation length (X0) deep sampling calorimeter. The calorimeter is comprised of 20 layers of tungsten interleaved with 20 layers of scintillating fiber ribbons, and is preceded by a pair of graphite interaction targets providing about 0.42 proton interaction lengths (\lambda int). The calorimeter was placed in one of CERN's SPS accelerator beams for calibration and testing. Beams of 150 GeV electrons were used for calibration, and a variety of electron, proton, and nuclear fragment beams were used to test the simulation model of the detector. In this paper we discuss the performance of the calorimeter in the electron beam and compare electron beam data with simulation results

    No evidence for an association of plasma homocysteine levels and refractive error - Results from the population-based Gutenberg Health Study (GHS)

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    Purpose There is a strong association between severe hyperhomocysteinemia and myopia. Thus we studied the hypothesis that even moderately increased levels of homocysteine (Hcy) might be a potentially treatable risk factor for myopia. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74 at recruitment. The baseline examination was conducted from 2007-2012. Refraction was measured using autorefraction (HARK 599, Carl Zeiss AG, Jena, Germany). Hcy was measured by an immunoassay. We included only phakic participants without a history of corneal surgery or corneal laser treatment. We used linear regression models to evaluate the potential association between Hcy and refraction at baseline, and between Hcy and change in refraction between baseline and 5-year-follow-up examination. We used generalized estimating equation models to account for the correlation between fellow eyes. Results We included 13,749 participants, categorized as having no myopia (spherical equivalent > -0.75 D, 65.2%), low myopia (-0.75 D-2.75 D, 21.5%), moderate myopia (-3.00 D- 5.75 D, 9.8%) and high myopia (≤ -6

    The Layer 0 Inner Silicon Detector of the D0 Experiment

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    This paper describes the design, fabrication, installation and performance of the new inner layer called Layer 0 (L0) that was inserted in the existing Run IIa Silicon Micro-Strip Tracker (SMT) of the D0 experiment at the Fermilab Tevatron collider. L0 provides tracking information from two layers of sensors, which are mounted with center lines at a radial distance of 16.1 mm and 17.6 mm respectively from the beam axis. The sensors and readout electronics are mounted on a specially designed and fabricated carbon fiber structure that includes cooling for sensor and readout electronics. The structure has a thin polyimide circuit bonded to it so that the circuit couples electrically to the carbon fiber allowing the support structure to be used both for detector grounding and a low impedance connection between the remotely mounted hybrids and the sensors.Comment: 28 pages, 9 figure

    Factors Affecting European Farmers’Participation in Biodiversity Policies

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    This article reports the major findings from an interdisciplinary research project that synthesises key insights into farmers’ willingness and ability to co-operate with biodiversity policies. The results of the study are based on an assessment of about 160 publications and research reports from six EU member states and from international comparative research.We developed a conceptual framework to systematically review the existent literature relevant for our purposes. This framework provides a common structure for analysing farmers’ perspectives regarding the introduction into farming practices of measures relevant to biodiversity. The analysis is coupled and contrasted with a survey of experts. The results presented above suggest that it is important to view support for practices oriented towards biodiversity protection not in a static sense – as a situation determined by one or several influencing factors – but rather as a process marked by interaction. Financial compensation and incentives function as a necessary, though clearly not sufficient condition in this process

    A complex proinflammatory cascade mediates the activation of HSCs upon LPS exposure in vivo

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    Infections are a key source of stress to the hematopoietic system. While infections consume short-lived innate immune cells, their recovery depends on quiescent hematopoietic stem cells (HSCs) with long-term self-renewal capacity. Both chronic inflammatory stress and bacterial infections compromise competitive HSC capacity and cause bone marrow failure. However, our understanding of how HSCs act during acute and contained infections remains incomplete. Here, we used advanced chimeric and genetic mouse models in combination with pharmacological interventions to dissect the complex nature of the acute systemic response of HSCs to lipopolysaccharide (LPS), a well-established model for inducing inflammatory stress. Acute LPS challenge transiently induced proliferation of quiescent HSCs in vivo. This response was not only mediated via direct LPS-TLR4 conjugation on HSCs, but also involved indirect TLR4 signaling in CD115+ monocytic cells, inducing a complex pro-inflammatory cytokine cascade in the bone marrow. Downstream of LPS-TLR4 signaling, the combined action of pro-inflammatory cytokines such as IFNα, IFNγ, TNFα, IL-1α, IL-1β and many others is required to mediate full HSC activation in vivo. Together, our study reveals detailed mechanistic insights into the interplay of proinflammatory cytokine-induced molecular pathways and cell types that jointly orchestrate the complex process of emergency hematopoiesis and HSC activation upon LPS exposure in vivo

    Photoproduction of phi mesons from nuclei

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    We investigate the consequences of possible medium modifications of the phi meson at finite nuclear matter density on the K+K- mass distribution in photonuclear reactions. The inclusive cross sections for K+K- pair production are calculated within a semi--classical BUU transport model, which combines the initial state interaction of the incoming photon with the final state interactions of the produced particles. The effects of final state interactions on the invariant mass distribution of the observed K+K- pairs are discussed in detail. In addition we calculate the Coulomb correction and possible effects of hadronic kaon potentials on the K+K- mass spectrum. Due to the large cross sections for reactions of the final state particles with the surrounding nuclear medium and the influence of the Coulomb potential we find no measurable sensitivity of the observables to the phi properties at finite baryon density.Comment: revtex4, 24 page

    Search for composite and exotic fermions at LEP 2

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    A search for unstable heavy fermions with the DELPHI detector at LEP is reported. Sequential and non-canonical leptons, as well as excited leptons and quarks, are considered. The data analysed correspond to an integrated luminosity of about 48 pb^{-1} at an e^+e^- centre-of-mass energy of 183 GeV and about 20 pb^{-1} equally shared between the centre-of-mass energies of 172 GeV and 161 GeV. The search for pair-produced new leptons establishes 95% confidence level mass limits in the region between 70 GeV/c^2 and 90 GeV/c^2, depending on the channel. The search for singly produced excited leptons and quarks establishes upper limits on the ratio of the coupling of the excited fermio
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