85 research outputs found

    Шум и его влияние на организм человека

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    Рассмотрены основные понятия, связанные с шумом, обозначено влияние на организм человека и его последствия

    Climate change impacts on critical international transportation assets of Caribbean Small Island Developing States (SIDS): the case of Jamaica and Saint Lucia

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    This contribution presents an assessment of the potential vulnerabilities to climate variability and change (CV & C) of the critical transportation infrastructure of Caribbean Small Island Developing States (SIDS). It focuses on potential operational disruptions and coastal inundation forced by CV & C on four coastal international airports and four seaports in Jamaica and Saint Lucia which are critical facilitators of international connectivity and socioeconomic development. Impact assessments have been carried out under climatic conditions forced by a 1.5 °C specific warming level (SWL) above pre-industrial levels, as well as for different emission scenarios and time periods in the twenty-first century. Disruptions and increasing costs due to, e.g., more frequent exceedance of high temperature thresholds that could impede transport operations are predicted, even under the 1.5 °C SWL, advocated by the Alliance of Small Island States (AOSIS) and reflected as an aspirational goal in the Paris Climate Agreement. Dynamic modeling of the coastal inundation under different return periods of projected extreme sea levels (ESLs) indicates that the examined airports and seaports will face increasing coastal inundation during the century. Inundation is projected for the airport runways of some of the examined international airports and most of the seaports, even from the 100-year extreme sea level under 1.5 °C SWL. In the absence of effective technical adaptation measures, both operational disruptions and coastal inundation are projected to increasingly affect all examined assets over the course of the century

    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

    Prostaglandin E2 Signals Through PTGER2 to Regulate Sclerostin Expression

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    The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost) produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E2 (PGE2), a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE2 is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE2 receptor EP2 mimic the effect of PGE2 upon Sost, and siRNA reduction in Ptger2 prevents PGE2-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/β-catenin signaling pathway in bone

    The distribution and amount of carbon in the largest peatland complex in Amazonia

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    Peatlands in Amazonian Peru are known to store large quantities of carbon, but there is high uncertainty in the spatial extent and total carbon stocks of these ecosystems. Here, we use a multi-sensor (Landsat, ALOS PALSAR and SRTM) remote sensing approach, together with field data including 24 forest census plots and 218 peat thickness measurements, to map the distribution of peatland vegetation types and calculate the combined above- and below-ground carbon stock of peatland ecosystems in the Pastaza-Marañon foreland basin in Peru. We find that peatlands cover 35 600 ± 2133 km2 and contain 3.14 (0.44–8.15) Pg C. Variation in peat thickness and bulk density are the most important sources of uncertainty in these values. One particular ecosystem type, peatland pole forest, is found to be the most carbon-dense ecosystem yet identified in Amazonia (1391 ± 710 Mg C ha−1). The novel approach of combining optical and radar remote sensing with above- and below-ground carbon inventories is recommended for developing regional carbon estimates for tropical peatlands globally. Finally, we suggest that Amazonian peatlands should be a priority for research and conservation before the developing regional infrastructure causes an acceleration in the exploitation and degradation of these ecosystems

    Application of a distributed physically-based hydrological model to a medium size catchment

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    International audiencePhysically based distributed models are rarely calibrated and validated thoroughly because of lack of data. In practice, validation is limited to comparison of simulated and predicted discharges in a catchment, or of simulated and observed piezometric levels in some calibrated wells. Rarely, internal noncalibrated wells or discharge stations are included in model evaluation. In this study, the fully distributed physically based MIKE SHE model was applied to the 600-km2 catchment of the Grote and the Kleine Gete, Belgium. Firstly, the MIKE SHE model was calibrated against both daily discharge measurements and observed water levels and then validated using a simple split-sample test. The observed discharges were simulated successfully in both the calibration and the validation period, while results for the piezometric levels differed considerably among the wells. In addition, a multi-site validation test for 2 internal discharge stations and 6 observation wells showed inferior results for the discharge stations and comparable results for the water table wells. As in the calibration and the split-sample test validation, water table fluctuations were predicted well in some wells, but with little agreement in others. This may be due to scale effects and to the poor quality of the data in certain areas of the catchment. Mainly, the lack of data made it difficult to simulate time series of internal catchment variables with acceptable accuracy so that even the calibrated and validated model could not provide reliable predictions of the water table over the entire catchment. Keywords: integral hydrological modelling; distributed code; MIKE-SHE; model performance; model calibration; model validatio

    Simulating Glass Cockpit Displays in a General Aviation Flight Environment

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    Development of a research platform that replicates the basic flight functions of a light, general aviation aircraft is described. This involved retrofitting an actual aircraft cockpit with computer displays to emulate an aircraft environment. The hardware and software used in this research platform are described, as well as issues and problems regarding implementation and use in research
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