48 research outputs found

    The INF Treaty of 1987

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    Der von Ronald Reagan und Michail Gorbatschow am 8. Dezember 1987 unterzeichnete »Intermediate-Range Nuclear Forces Treaty«, kurz INF-Vertrag, stellte einen Meilenstein der nuklearen Abrüstungsverhandlungen zwischen den Vereinigten Staaten von Amerika und der Sowjetunion dar. Im Jahr 2019 wurde er von Russland und den USA gekündigt. Der englischsprachige Band untersucht die Vorgeschichte des Abkommens, dessen Implementierung und Folgen sowohl in den beiden Supermächten als auch in den mit ihnen verbündeten Staaten. Er ist damit die erste umfassende Darstellung eines der wichtigsten Abrüstungsabkommen der jüngsten Zeit

    Methionine Sulfoxide Reductases Are Essential for Virulence of Salmonella Typhimurium

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    Production of reactive oxygen species represents a fundamental innate defense against microbes in a diversity of host organisms. Oxidative stress, amongst others, converts peptidyl and free methionine to a mixture of methionine-S- (Met-S-SO) and methionine-R-sulfoxides (Met-R-SO). To cope with such oxidative damage, methionine sulfoxide reductases MsrA and MsrB are known to reduce MetSOs, the former being specific for the S-form and the latter being specific for the R-form. However, at present the role of methionine sulfoxide reductases in the pathogenesis of intracellular bacterial pathogens has not been fully detailed. Here we show that deletion of msrA in the facultative intracellular pathogen Salmonella (S.) enterica serovar Typhimurium increased susceptibility to exogenous H2O2, and reduced bacterial replication inside activated macrophages, and in mice. In contrast, a ΔmsrB mutant showed the wild type phenotype. Recombinant MsrA was active against free and peptidyl Met-S-SO, whereas recombinant MsrB was only weakly active and specific for peptidyl Met-R-SO. This raised the question of whether an additional Met-R-SO reductase could play a role in the oxidative stress response of S. Typhimurium. MsrC is a methionine sulfoxide reductase previously shown to be specific for free Met-R-SO in Escherichia (E.) coli. We tested a ΔmsrC single mutant and a ΔmsrBΔmsrC double mutant under various stress conditions, and found that MsrC is essential for survival of S. Typhimurium following exposure to H2O2, as well as for growth in macrophages, and in mice. Hence, this study demonstrates that all three methionine sulfoxide reductases, MsrA, MsrB and MsrC, facilitate growth of a canonical intracellular pathogen during infection. Interestingly MsrC is specific for the repair of free methionine sulfoxide, pointing to an important role of this pathway in the oxidative stress response of Salmonella Typhimurium

    Synergism between particle-based multiplexing and microfluidics technologies may bring diagnostics closer to the patient

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    In the field of medical diagnostics there is a growing need for inexpensive, accurate, and quick high-throughput assays. On the one hand, recent progress in microfluidics technologies is expected to strongly support the development of miniaturized analytical devices, which will speed up (bio)analytical assays. On the other hand, a higher throughput can be obtained by the simultaneous screening of one sample for multiple targets (multiplexing) by means of encoded particle-based assays. Multiplexing at the macro level is now common in research labs and is expected to become part of clinical diagnostics. This review aims to debate on the “added value” we can expect from (bio)analysis with particles in microfluidic devices. Technologies to (a) decode, (b) analyze, and (c) manipulate the particles are described. Special emphasis is placed on the challenges of integrating currently existing detection platforms for encoded microparticles into microdevices and on promising microtechnologies that could be used to down-scale the detection units in order to obtain compact miniaturized particle-based multiplexing platforms

    Picking up the pieces Schroder's working programme for the European Communities and the solution of the 1963 crisis

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    Includes bibliographical referencesSIGLEAvailable from British Library Document Supply Centre- DSC:DX220208 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

    Nigel Ashton, Kennedy, Macmillan and the Cold War: The Irony of Interdependence

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