348 research outputs found

    Regression calibration for Cox regression under heteroscedastic measurement error - Determining risk factors of cardiovascular diseases from error-prone nutritional replication data

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    For instance nutritional data are often subject to severe measurement error, and an adequate adjustment of the estimators is indispensable to avoid deceptive conclusions. This paper discusses and extends the method of regression calibration to correct for measurement error in Cox regression. Special attention is paid to the modelling of quadratic predictors, the role of heteroscedastic measurement error, and the efficient use of replicated measurements of the surrogates. The method is used to analyze data from the German part of the MONICA cohort study on cardiovascular diseases. The results corroborate the importance of taking into account measurement error carefully

    Study of the Hot-Spot Temperature During Quench in the Nonplanar Coils of W7-X

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    The quench protection system of the nonplanar coils of the Wendelstein 7-X stellarator was laid out over 15 years ago. At that time, the assessment of the hot-spot temperature by a basic adiabatic model was done using design values for material and operation parameters. After the operating experience in 2016, the hot-spot temperature is reassessed with the thermal-hydraulic program THEA, using the actual values for delay and dump time. The electrical resistivity of the conduit alloy ismeasured over the whole range of temperatures and in magnetic fields on relevant samples of a conductor, exposed to the hardening heat treatment after winding. The results were fed into THEA. Parametric variations are studied in the calculations, e.g., testing the effect of the quench initiation zone, delay time, and dump resistor. The results suggest that the hot-spot temperature of the conduit in the case of quench is safely within the allowable values even when the dump voltage is reduced compared to the initial design value

    New ultrahigh-resolution picture of Earth's gravity field

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    We provide an unprecedented ultrahigh resolution picture of Earth’s gravity over all continents and numerous islands within ±60° latitude. This is achieved through augmentation of new satellite and terrestrial gravity with topography data and use of massive parallel computation techniques, delivering local detail at ~200 m spatial resolution. As such, our work is the first-of-its-kind to model gravity at unprecedented fine scales yet with near-global coverage. The new picture of Earth’s gravity encompasses a suite of gridded estimates of gravity accelerations, radial and horizontal field components, and quasi-geoid heights at over 3 billion points covering 80% of Earth’s land masses. We identify new candidate locations of extreme gravity signals, suggesting that the Committee on Data for Science and Technology standard for peak-to-peak variations in free-fall gravity is too low by about 40%. The new models are beneficial for a wide range of scientific and engineering applications and freely available to the public

    Modelling chemistry in the nocturnal boundary layer above tropical rainforest and a generalised effective nocturnal ozone deposition velocity for sub-ppbv NOx conditions

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    Measurements of atmospheric composition have been made over a remote rainforest landscape. A box model has previously been demonstrated to model the observed daytime chemistry well. However the box model is unable to explain the nocturnal measurements of relatively high [NO] and [O3], but relatively low observed [NO2]. It is shown that a one-dimensional (1-D) column model with simple O3 -NOx chemistry and a simple representation of vertical transport is able to explain the observed nocturnal concentrations and predict the likely vertical profiles of these species in the nocturnal boundary layer (NBL). Concentrations of tracers carried over from the end of the night can affect the atmospheric chemistry of the following day. To ascertain the anomaly introduced by using the box model to represent the NBL, vertically-averaged NBL concentrations at the end of the night are compared between the 1-D model and the box model. It is found that, under low to medium [NOx] conditions (NOx <1 ppbv), a simple parametrisation can be used to modify the box model deposition velocity of ozone, in order to achieve good agreement between the box and 1-D models for these end-of-night concentrations of NOx and O3. This parametrisation would could also be used in global climate-chemistry models with limited vertical resolution near the surface. Box-model results for the following day differ significantly if this effective nocturnal deposition velocity for ozone is implemented; for instance, there is a 9% increase in the following day’s peak ozone concentration. However under medium to high [NOx] conditions (NOx > 1 ppbv), the effect on the chemistry due to the vertical distribution of the species means no box model can adequately represent chemistry in the NBL without modifying reaction rate constants

    Henchir Bourgou (Djerba, Tunesien): Stratigraphie und Fundvorlage einer Sondage im Zentrum der antiken Siedlung (8. Jh. v. Chr. – 2. Jh. n. Chr.)

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    Die antike Siedlung Henchir Bourgou auf Djerba (Tunesien) ist seit 2017 Gegenstand gemeinsamer Forschungen des tunesischen Institut National du Patrimoine (INP) und des Deutschen Archäologischen Instituts (DAI). Der vorliegende Beitrag ist die Publikation der Ergebnisse einer ersten Sondage im Zentrum des Siedlungsareals. Die Schichtenabfolge und die Baubefunde von den ersten Siedlungsphasen im 8. Jh. v. Chr. bis zu den letzten Spuren einer intensiven Besiedlung an der höchsten Stelle des Siedlungsareals in der letzten Hälfte des 2. Jhs. n. Chr., geben gemeinsam mit der vorgelegten Fundkeramik und begleitenden naturwissenschaftlichen Untersuchungen einen ersten Überblick über die Siedlungs- und Wirtschaftsgeschichte von Henchir Bourgou.The ancient settlement of Henchir Bourgou/Djerba (Tunisia) has been the focus of joint research by the Tunisian Institut National du Patrimoine (INP) and the German Archaeological Institute (DAI) since 2017. The article summarizes the results of a first sondage in the centre of the settlement area. The sequence of layers and the building features from the first settlement phases in the 8th century B.C. to the last traces of intensive occupation at the highest point of the settlement area in the last half of the 2nd century A.D., together with the find pottery and accompanying scientific investigations, provide a first overview of the settlement and economic history of Henchir Bourgou

    Clostridial Neurotoxins: Mechanism of SNARE Cleavage and Outlook on Potential Substrate Specificity Reengineering

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    The clostridial neurotoxin family consists of tetanus neurotoxin and seven distinct botulinum neurotoxins which cause the diseases tetanus and botulism. The extreme potency of these toxins primarily relies not only on their ability to specifically enter motoneurons but also on the activity their catalytic domains display inside presynaptic motoneuronal terminals. Subsequent to neurotoxin binding and endocytosis the catalytic domains become translocated across endosomal membranes and proteolyze unique peptide bonds of one of three soluble N-ethylmaleimide-sensitive fusion protein attachment receptors (SNAREs), vesicle associated membrane protein/synaptobrevin, synaptosome associated protein of 25 kDa, or syntaxin. As these substrate proteins are core components of the vesicular membrane fusion apparatus, cleavage of any of the substrate molecules results in the blockade of neurotransmitter release. This review summarizes the present knowledge about the molecular basis of the specific substrate recognition and cleavage mechanism and assesses the feasibility of reengineering catalytic domains to hydrolyze non-substrate members of the three SNARE families in order to expand the therapeutic application of botulinum neurotoxins

    Innovative and Highly Sensitive Detection of Clostridium perfringens Enterotoxin Based on Receptor Interaction and Monoclonal Antibodies

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    Clostridium perfringens enterotoxin (CPE) regularly causes food poisoning and antibioticassociated diarrhea; therefore, reliable toxin detection is crucial. To this aim, we explored stationary and mobile strategies to detect CPE either exclusively by monoclonal antibodies (mAbs) or, alternatively, by toxin-enrichment via the cellular receptor of CPE, claudin-4, and mAb detection. Among the newly generated mAbs, we identified nine CPE-specific mAbs targeting five distinct epitopes, among them mAbs recognizing CPE bound to claudin-4 or neutralizing CPE activity in vitro. In surface plasmon resonance experiments, all mAbs and claudin-4 revealed excellent affinities towards CPE, ranging from 0.05 to 2.3 nM. Integrated into sandwich enzyme-linked immunosorbent assays (ELISAs), the most sensitive mAb/mAb and claudin-4/mAb combinations achieved similar detection limits of 0.3 pg/mL and 1.0 pg/mL, respectively, specifically detecting recombinant CPE from spiked feces and native CPE from 30 different C. perfringens culture supernatants. The implementation of mAb- and receptor-based ELISAs into a mobile detection platform enabled the fast detection of CPE, which will be helpful in clinical laboratories to diagnose diarrhea of assumed bacterial origin. In conclusion, we successfully employed an endogenous receptor and novel high affinity mAbs for highly sensitive and specific CPE-detection. These tools will be useful for both basic and applied research.Peer Reviewe
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