551 research outputs found

    Confronting Grand Challenges in environmental fluid mechanics

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    Environmental fluid mechanics underlies a wealth of natural, industrial and, by extension, societal challenges. In the coming decades, as we strive towards a more sustainable planet, there are a wide range of grand challenge problems that need to be tackled, ranging from fundamental advances in understanding and modeling of stratified turbulence and consequent mixing, to applied studies of pollution transport in the ocean, atmosphere and urban environments. A workshop was organized in the Les Houches School of Physics in France in January 2019 with the objective of gathering leading figures in the field to produce a road map for the scientific community. Five subject areas were addressed: multiphase flow, stratified flow, ocean transport, atmospheric and urban transport, and weather and climate prediction. This article summarizes the discussions and outcomes of the meeting, with the intent of providing a resource for the community going forward

    Confronting Grand Challenges in Environmental Fluid Dynamics

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    Environmental fluid dynamics underlies a wealth of natural, industrial and, by extension, societal challenges. In the coming decades, as we strive towards a more sustainable planet, there are a wide range of grand challenge problems that need to be tackled, ranging from fundamental advances in understanding and modeling of stratified turbulence and consequent mixing, to applied studies of pollution transport in the ocean, atmosphere and urban environments. A workshop was organized in the Les Houches School of Physics in France in January 2019 with the objective of gathering leading figures in the field to produce a road map for the scientific community. Five subject areas were addressed: multiphase flow, stratified flow, ocean transport, atmospheric and urban transport, and weather and climate prediction. This article summarizes the discussions and outcomes of the meeting, with the intent of providing a resource for the community going forward

    Joint effect of phosphorus limitation and temperature on alkaline phosphatase activity and somatic growth in Daphnia magna

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    Alkaline phosphatase (AP) is a potential biomarker for phosphorus (P) limitation in zooplankton. However, knowledge about regulation of AP in this group is limited. In a laboratory acclimation experiment, we investigated changes in body AP concentration for Daphnia magna kept for 6 days at 10, 15, 20 and 25°C and fed algae with 10 different molar C:P ratios (95–660). In the same experiment, we also assessed somatic growth of the animals since phosphorus acquisition is linked to growth processes. Overall, non-linear but significant relationships of AP activity with C:P ratio were observed, but there was a stronger impact of temperature on AP activity than of P limitation. Animals from the lowest temperature treatment had higher normalized AP activity, which suggests the operation of biochemical temperature compensation mechanisms. Body AP activity increased by a factor of 1.67 for every 10°C decrease in temperature. These results demonstrate that temperature strongly influences AP expression. Therefore, using AP as a P limitation marker in zooplankton needs to consider possible confounding effects of temperature. Both temperature and diet affected somatic growth. The temperature effect on somatic growth, expressed as the Q10 value, responded non-linearly with C:P, with Q10 ranging between 1.9 for lowest food C:P ratio and 1.4 for the most P-deficient food. The significant interaction between those two variables highlights the importance of studying temperature-dependent changes of growth responses to food quality

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Engineering the surface properties of a human monoclonal antibody prevents self-association and rapid clearance in vivo

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    Uncontrolled self-association is a major challenge in the exploitation of proteins as therapeutics. Here we describe the development of a structural proteomics approach to identify the amino acids responsible for aberrant self-association of monoclonal antibodies and the design of a variant with reduced aggregation and increased serum persistence in vivo. We show that the human monoclonal antibody, MEDI1912, selected against nerve growth factor binds with picomolar affinity, but undergoes reversible self-association and has a poor pharmacokinetic profile in both rat and cynomolgus monkeys. Using hydrogen/deuterium exchange and cross-linking-mass spectrometry we map the residues responsible for self-association of MEDI1912 and show that disruption of the self-interaction interface by three mutations enhances its biophysical properties and serum persistence, whilst maintaining high affinity and potency. Immunohistochemistry suggests that this is achieved via reduction of non-specific tissue binding. The strategy developed represents a powerful and generic approach to improve the properties of therapeutic proteins
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