626 research outputs found

    Focal adhesion kinase regulates the activity of the osmosensitive transcription factor TonEBP/NFAT5 under hypertonic conditions

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    Ton EBP/NFAT5 is a major regulator of the urinary concentrating process and is essential for the osmoadaptation of renal medullary cells. Focal adhesion kinase (FAK) is a mechanosensitive non-receptor protein tyrosine kinase expressed abundantly in the renal medulla. Since osmotic stress causes cell shrinkage, the present study investigated the contribution of FAK on TonEBP/NFAT5 activation. Osmotic stress induced time-dependent activation of FAK as evidenced by phosphorylation at Tyr-397, and furosemide reduces FAK Tyr-397 phosphorylation in the rat renal medulla. Both pharmacological inhibition of FAK and siRNA-mediated knockdown of FAK drastically reduced TonEBP/NFAT5 transcriptional activity and target gene expression in HEK293 cells. This effect was not mediated by impaired nuclear translocation or by reduced transactivating activity of TonEBP/NFAT5. However, TonEBP/NFAT5 abundance under hypertonic conditions was diminished by 50% by FAK inhibition or siRNA knockdown of FAK. FAK inhibition only marginally reduced transcription of the TonEBP/NFAT5 gene. Rather, TonEBP/NFAT5 mRNA stability was diminished significantly by FAK inhibition, which correlated with reduced reporter activity of the TonEBP/NFAT5 mRNA 3' untranslated region (3'-UTR). In conclusion, FAK is a major regulator of TonEBP/NFAT5 activity by increasing its abundance via stabilization of the mRNA. This in turn, depends on the presence of the TonEBP/NFAT5 3'-UTR

    QCD Analysis of Polarized Deep Inelastic Data and Parton Distributions

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    A QCD analysis of the world data on polarized deep inelastic scattering is presented in leading and next-to-leading order. New parameterizations are derived for the quark and gluon distributions for the kinematic range x \epsilon [10^{-9},1], Q^2 \epsilon [1,10^6] \GeV^2. The extrapolation far outside the domain of the current measurements is given both to allow for applications at higher values of Q2Q^2 and to be able to calculate integral properties of the present distributions. The values of ΛQCD\Lambda_{\rm QCD} and αs(Mz)\alpha_s(M_z) are determined. Emphasis is put on the derivation of the fully correlated 1σ1\sigma error bands for these distributions, which are also given in terms of parameterizations and are directly applicable to determine experimental errors of other polarized observables. The impact of the variation of both the renormalization and factorization scales on the value of αs\alpha_s is studied. Finally we perform a factorization--scheme invariant QCD analysis based on the observables g1(x,Q2)g_1(x,Q^2) and dg1(x,Q2)/dlog(Q2)d g_1(x,Q^2)/d \log(Q^2) in next-to-leading order, which is compared to the standard analysis. A series of low moments of parton densities, accounting for error correlation, are given to allow for comparison with results from lattice simulations.Comment: 43 pages LATEX, 1 style files, 13 eps-figures, final version, Nucl. Phys. B in prin

    Financial Evaluation of Different Vaccination Strategies for Controlling the Bluetongue Virus Serotype 8 Epidemic in the Netherlands in 2008

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    Background: Bluetongue (BT) is a vector-borne disease of ruminants caused by bluetongue virus that is transmitted by biting midges (Culicoides spp.). In 2006, the introduction of BTV serotype 8 (BTV-8) caused a severe epidemic in Western and Central Europe. The principal effective veterinary measure in response to BT was believed to be vaccination accompanied by other measures such as movement restrictions and surveillance. As the number of vaccine doses available at the start of the vaccination campaign was rather uncertain, the Dutch Ministry of Agriculture, Nature and Food Quality and the Dutch agricultural industry wanted to evaluate several different vaccination strategies. This study aimed to rank eight vaccination strategies based on their efficiency (i.e. net costs in relation to prevented losses or benefits) for controlling the bluetongue virus serotype 8 epidemic in 2008 Methodology/Principal Findings: An economic model was developed that included the Dutch professional cattle, sheep and goat sectors together with the hobby farms. Strategies were evaluated based on the least cost - highest benefit frontier, the benefit-cost ratio and the total net returns. Strategy F, where all adult sheep at professional farms in the Netherlands would be vaccinated was very efficient at lowest costs, whereas strategy D, where additional to all adult sheep at professional farms also all adult cattle in the four Northern provinces would be vaccinated, was also very efficient but at a little higher costs. Strategy C, where all adult sheep and cattle at professional farms in the whole of the Netherlands would be vaccinated was also efficient but again at higher costs. Conclusions/Significance: This study demonstrates that a financial analysis differentiates between vaccination strategies and indicates important decision rules based on efficienc

    The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae

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    Gross R, Guzman CA, Sebaihia M, et al. The missing link: Bordetella petrii is endowed with both the metabolic versatility of environmental bacteria and virulence traits of pathogenic Bordetellae. BMC Genomics. 2008;9(1): 449.Background: Bordetella petrii is the only environmental species hitherto found among the otherwise host-restricted and pathogenic members of the genus Bordetella. Phylogenetically, it connects the pathogenic Bordetellae and environmental bacteria of the genera Achromobacter and Alcaligenes, which are opportunistic pathogens. B. petrii strains have been isolated from very different environmental niches, including river sediment, polluted soil, marine sponges and a grass root. Recently, clinical isolates associated with bone degenerative disease or cystic fibrosis have also been described. Results: In this manuscript we present the results of the analysis of the completely annotated genome sequence of the B. petrii strain DSMZ12804. B. petrii has a mosaic genome of 5,287,950 bp harboring numerous mobile genetic elements, including seven large genomic islands. Four of them are highly related to the clc element of Pseudomonas knackmussii B13, which encodes genes involved in the degradation of aromatics. Though being an environmental isolate, the sequenced B. petrii strain also encodes proteins related to virulence factors of the pathogenic Bordetellae, including the filamentous hemagglutinin, which is a major colonization factor of B. pertussis, and the master virulence regulator BvgAS. However, it lacks all known toxins of the pathogenic Bordetellae. Conclusion: The genomic analysis suggests that B. petrii represents an evolutionary link between free-living environmental bacteria and the host-restricted obligate pathogenic Bordetellae. Its remarkable metabolic versatility may enable B. petrii to thrive in very different ecological niches

    Qualification of laser optics for high-power LIDAR space missions

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    Space environment presents unique challenges for the operation of optics and optical coatings as part of laser systems. This talk summarizes the test technology status for qualifying single component laser optics for space applications and lessons learned from these tests. Tests involve the measurement of laser-induced damage thresholds (LIDT) according to the S-on-1 test procedure detailed in ISO 21254-2 [1] as well as raster scans to test large surface areas. Another topic is the investigation of laser-induced molecular contamination (LIMC), which can degrade optical components and furthermore dramatically lower the LIDT. We recently developed an ISO technical report [2] describing the systematic measurement of LIMC. Methods to prevent and clean laser-induced deposits are also presented. Finally, the degradation of non-linear optical crystals due to ionizing radiation (space radiation) and methods for ground-based testing are discussed. [1] ISO 21254 (all parts), Lasers and laser-related equipment, Test methods for laser-induced damage threshold [2] ISO/TR 20811:2017(E), Optics and photonics, Lasers and laser-related equipment, Laser-induced molecular contaminatio
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