2,663 research outputs found

    Formation of Giant Quasibound Cold Diatoms by Strong Atom-Cavity Coupling

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    We show that giant quasi-bound diatomic complexes, whose size is typically hundreds of nm, can be formed by intra-cavity cold diatom photoassociation or photodissociation in the strong atom-cavity coupling regime.Comment: 4 pages, 3 figure

    Mouse models for preeclampsia: disruption of redox-regulated signaling

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    The concept that oxidative stress contributes to the development of human preeclampsia has never been tested in genetically-defined animal models. Homozygous deletion of catechol-Omethyl transferase (Comt-/-) in pregnant mice leads to human preeclampsia-like symptoms (high blood pressure, albuminurea and preterm birth) resulting from extensive vasculo-endothelial pathology, primarily at the utero-fetal interface where maternal cardiac output is dramatically increased during pregnancy. Comt converts estradiol to 2-methoxyestradiol 2 (2ME2) which counters angiogenesis by depleting hypoxia inducible factor-1 alpha (HIF-1 alpha) at late pregnancy. We propose that in wild type (Comt++) pregnant mice, 2ME2 destabilizes HIF-1 alpha by inhibiting mitochondrial superoxide dismutase (MnSOD). Thus, 2ME2 acts as a pro-oxidant, disrupting redox-regulated signaling which blocks angiogenesis in wild type (WT) animals in physiological pregnancy. Further, we suggest that a lack of this inhibition under normoxic conditions in mutant animals (Comt-/-) stabilises HIF-1 alpha by inactivating prolyl hydroxlases (PHD). We predict that a lack of inhibition of MnSOD, leading to persistent accumulation of HIF-1 alpha, would trigger inflammatory infiltration and endothelial damage in mutant animals. Critical tests of this hypothesis would be to recreate preeclampsia symptoms by inducing oxidative stress in WT animals or to ameliorate by treating mutant mice with Mn-SOD-catalase mimetics or activators of PHD

    Physics–Dynamics Coupling in weather, climate and Earth system models: Challenges and recent progress

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    This is the final version. Available from American Meteorological Society via the DOI in this record.Numerical weather, climate, or Earth system models involve the coupling of components. At a broad level, these components can be classified as the resolved fluid dynamics, unresolved fluid dynamical aspects (i.e., those represented by physical parameterizations such as subgrid-scale mixing), and nonfluid dynamical aspects such as radiation and microphysical processes. Typically, each component is developed, at least initially, independently. Once development is mature, the components are coupled to deliver a model of the required complexity. The implementation of the coupling can have a significant impact on the model. As the error associated with each component decreases, the errors introduced by the coupling will eventually dominate. Hence, any improvement in one of the components is unlikely to improve the performance of the overall system. The challenges associated with combining the components to create a coherent model are here termed physics–dynamics coupling. The issue goes beyond the coupling between the parameterizations and the resolved fluid dynamics. This paper highlights recent progress and some of the current challenges. It focuses on three objectives: to illustrate the phenomenology of the coupling problem with references to examples in the literature, to show how the problem can be analyzed, and to create awareness of the issue across the disciplines and specializations. The topics addressed are different ways of advancing full models in time, approaches to understanding the role of the coupling and evaluation of approaches, coupling ocean and atmosphere models, thermodynamic compatibility between model components, and emerging issues such as those that arise as model resolutions increase and/or models use variable resolutions.Natural Environment Research Council (NERC)National Science FoundationDepartment of Energy Office of Biological and Environmental ResearchPacific Northwest National Laboratory (PNNL)DOE Office of Scienc

    Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

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    Fe d'errates disponible a: http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, ÎČ=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity

    Work functions, ionization potentials, and in-between: Scaling relations based on the image charge model

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    We revisit a model in which the ionization energy of a metal particle is associated with the work done by the image charge force in moving the electron from infinity to a small cut-off distance just outside the surface. We show that this model can be compactly, and productively, employed to study the size dependence of electron removal energies over the range encompassing bulk surfaces, finite clusters, and individual atoms. It accounts in a straightforward manner for the empirically known correlation between the atomic ionization potential (IP) and the metal work function (WF), IP/WF∌\sim2. We formulate simple expressions for the model parameters, requiring only a single property (the atomic polarizability or the nearest neighbor distance) as input. Without any additional adjustable parameters, the model yields both the IP and the WF within ∌\sim10% for all metallic elements, as well as matches the size evolution of the ionization potentials of finite metal clusters for a large fraction of the experimental data. The parametrization takes advantage of a remarkably constant numerical correlation between the nearest-neighbor distance in a crystal, the cube root of the atomic polarizability, and the image force cutoff length. The paper also includes an analytical derivation of the relation of the outer radius of a cluster of close-packed spheres to its geometric structure.Comment: Original submission: 8 pages with 7 figures incorporated in the text. Revised submission (added one more paragraph about alloy work functions): 18 double spaced pages + 8 separate figures. Accepted for publication in PR

    Second Generation Leptoquark Search in p\bar{p} Collisions at s\sqrt{s} = 1.8 TeV

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    We report on a search for second generation leptoquarks with the D\O\ detector at the Fermilab Tevatron ppˉp\bar{p} collider at s\sqrt{s} = 1.8 TeV. This search is based on 12.7 pb−1^{-1} of data. Second generation leptoquarks are assumed to be produced in pairs and to decay into a muon and quark with branching ratio ÎČ\beta or to neutrino and quark with branching ratio (1−ÎČ)(1-\beta). We obtain cross section times branching ratio limits as a function of leptoquark mass and set a lower limit on the leptoquark mass of 111 GeV/c2^{2} for ÎČ=1\beta = 1 and 89 GeV/c2^{2} for ÎČ=0.5\beta = 0.5 at the 95%\ confidence level.Comment: 18 pages, FERMILAB-PUB-95/185-
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