154 research outputs found

    Coupling a model of human thermoregulation with computational fluid dynamics for predicting human-environment interaction

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    This paper describes the methods developed to couple a commercial CFD program with a multi-segmented model of human thermal comfort and physiology. A CFD model is able to predict detailed temperatures and velocities of airflow around a human body, whilst a thermal comfort model is able to predict the response of a human to the environment surrounding it. By coupling the two models and exchanging information about the heat transfer at the body surface the coupled system can potentially predict the response of a human body to detailed local environmental conditions. This paper presents a method of exchanging data, using shared files, to provide a means of dynamically exchanging simulation data with the IESD-Fiala model during the CFD solution process. Additional code is used to set boundary conditions for the CFD simulation at the body surface as determined by the IESD-Fiala model and to return information about local environmental conditions adjacent to the body surface as determined by the CFD simulation. The coupled system is used to model a human subject in a naturally ventilated environment. The resulting ventilation flow pattern agrees well with other numerical and experimental work

    Backward bending structure of Phillips Curve in Japan, France, Turkey and the U.S.A.

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    This work aims to analyse the cointegration and the causality relationship between inflation and unemployment by using nonlinear A.R.D.L. and two popular nonlinear causality tests for the period from 1960 to 2016 in Japan, Turkey, the U.S.A. and from 1970 to 2016 in France. This study complements the previous empirical papers. However, it differs from the existing literature with simultaneous use of nonlinear A.R.D.L. and causality methods. Nonlinear A.R.D.L. determined that there is a long run relationship between inflation and unemployment; between economic growth and unemployment for Japan, France, the U.S.A. and Turkey

    Multicentre evaluation of the NaĂ­da Ci Q70 sound processor: Feedback from cochlear implant users and professionals

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    The aim of this survey was to gather data from both implant recipients and professionals on the ease of use of the NaĂ­da CI Q70 (NaĂ­da CI) sound processor from Advanced Bionics and on the usefulness of the new functions and features available. A secondary objective was to investigate fitting practices with the new processor. A comprehensive user satisfaction survey was conducted in a total of 186 subjects from 24 centres. In parallel, 23 professional questionnaires were collected from 11 centres. Overall, there was high satisfaction with the NaĂ­da CI processor from adults, children, experienced and new CI users as well as from professionals. The NaĂ­da CI processor was shown as being easy to use by all ages of recipients and by professionals. The majority of experienced CI users rated the NaĂ­da CI processor as being similar or better than their previous processor in all areas surveyed. The NaĂ­da CI was recommended by the professionals for fitting in all populations. Features like UltraZoom, ZoomControl and DuoPhone would not be fitted to very young children in contrast to adults. Positive ratings were obtained for ease of use, comfort and usefulness of the new functions and features of the NaĂ­da CI sound processor. Seventy-seven percent of the experienced CI users rated the new processor as being better than their previous sound processor from a general point of view. The survey also showed that fitting practices were influenced by the age of the user

    Toxoplasma DJ-1 Regulates Organelle Secretion by a Direct Interaction with Calcium-Dependent Protein Kinase 1

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    Human DJ-1 is a highly conserved and yet functionally enigmatic protein associated with a heritable form of Parkinson’s disease. It has been suggested to be a redox-dependent regulatory scaffold, binding to proteins to modulate their function. Here we present the X-ray crystal structure of the Toxoplasma orthologue Toxoplasma gondii DJ-1 (TgDJ-1) at 2.1-Å resolution and show that it directly associates with calcium-dependent protein kinase 1 (CDPK1). The TgDJ-1 structure identifies an orthologously conserved arginine dyad that acts as a phospho-gatekeeper motif to control complex formation. We determined that the binding of TgDJ-1 to CDPK1 is sensitive to oxidation and calcium, and that this interaction potentiates CDPK1 kinase activity. Finally, we show that genetic deletion of TgDJ-1 results in upregulation of CDPK1 expression and that disruption of the CDPK1/TgDJ-1 complex in vivo prevents normal exocytosis of parasite virulence-associated organelles called micronemes. Overall, our data suggest that TgDJ-1 functions as a noncanonical kinase-regulatory scaffold that integrates multiple intracellular signals to tune microneme exocytosis in T. gondii. IMPORTANCE Apicomplexan parasites such as Toxoplasma and Plasmodium are obligate intracellular parasites that require the protective environment of a host cell in order to replicate and survive within a host organism. These parasites secrete effector proteins from specialized apical organelles to select and invade a chosen host cell. The secretion of these organelles is a tightly regulated process coordinated by endogenous small molecules and calcium-dependent protein kinases. We previously identified the Toxoplasma orthologue of the highly conserved protein DJ-1 as a regulator of microneme secretion, but the molecular basis for this was not known. We have now identified the molecular mechanism for how TgDJ-1 regulates microneme secretion. TgDJ-1 interacts with the kinase responsible for the secretion of these organelles (calcium-dependent kinase 1) and synergizes with calcium to potentiate kinase activity. This interaction is direct, phosphodependent, and necessary for the normal secretion of these important organelles

    UnterstĂĽtzung kommunalplanerischer Prozesse mit CityGLM-basierter Anbindung Modelica-getriebener Quartierssimulationen

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    Eine integrale Planung städtischer (Energie-)Systeme bedarf einer planungsbegleitenden Unterstützung durch IT-basierte Planungs- und Simulationswerkzeuge. Die durchgängige Anwendung dieser digitalen Planungshilfsmittel wird allerdings bislang insbesondere durch den sehr hohen Aufwand bei der Spezifizierung und Erfassung benötigter Datengrundlagen sowie eine mangelhafte Interoperabilität zwischen den Systemen gehemmt. Im Rahmen eines Forschungsverbundprojektes wird dieses Problemfeld mittels praxisbezogener Prozessanalysen genauer spezifiziert und die technische und fachliche Integration durch die prozessbezogene Spezifikation relevanter Informationsbedarfe sowie die Entwicklung einer darauf aufbauenden, bidirektionalen Schnittstelle auf Basis des etablierten virtuellen Stadtmodellstandards CityGML verbessert. Als exemplarisches Anwendungsszenario innerhalb kommunaler Planungsprozesse wurde die Ausweisung von Vorranggebieten der Fernwärmenutzung basierend auf einer räumlichen Analyse des Wärmebedarfs für verschiedene Entwicklungsszenarien mittels einer bidirektionalen standard-basierten Koppelung von CityGML und Modelica ausgearbeitet

    Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

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    Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery
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