2,550 research outputs found

    Stationary wave patterns generated by an impurity moving with supersonic velocity through a Bose-Einstein condensate

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    Formation of stationary 3D wave patterns generated by a small point-like impurity moving through a Bose-Einstein condensate with supersonic velocity is studied. Asymptotic formulae for a stationary far-field density distribution are obtained. Comparison with three-dimensional numerical simulations demonstrates that these formulae are accurate enough already at distances from the obstacle equal to a few wavelengths.Comment: 7 pages, 3 figure

    The sleep-inducing lipid oleamide deconvolutes gap junction communication and calcium wave transmission in glial cells.

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    Oleamide is a sleep-inducing lipid originally isolated from the cerebrospinal fluid of sleep-deprived cats. Oleamide was found to potently and selectively inactivate gap junction-mediated communication between rat glial cells. In contrast, oleamide had no effect on mechanically stimulated calcium wave transmission in this same cell type. Other chemical compounds traditionally used as inhibitors of gap junctional communication, like heptanol and 18beta-glycyrrhetinic acid, blocked not only gap junctional communication but also intercellular calcium signaling. Given the central role for intercellular small molecule and electrical signaling in central nervous system function, oleamide- induced inactivation of glial cell gap junction channels may serve to regulate communication between brain cells, and in doing so, may influence higher order neuronal events like sleep induction

    Members of the chloride intracellular ion channel protein family demonstrate glutaredoxin-like enzymatic activity

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    © 2015 Al Khamici et al. The Chloride Intracellular Ion Channel (CLIC) family consists of six evolutionarily conserved proteins in humans. Members of this family are unusual, existing as both monomeric soluble proteins and as integral membrane proteins where they function as chloride selective ion channels, however no function has previously been assigned to their soluble form. Structural studies have shown that in the soluble form, CLIC proteins adopt a glutathione S-transferase (GST) fold, however, they have an active site with a conserved glutaredoxin monothiol motif, similar to the omega class GSTs. We demonstrate that CLIC proteins have glutaredoxin-like glutathione-dependent oxidoreductase enzymatic activity. CLICs 1, 2 and 4 demonstrate typical glutaredoxin-like activity using 2-hydroxyethyl disulfide as a substrate. Mutagenesis experiments identify cysteine 24 as the catalytic cysteine residue in CLIC1, which is consistent with its structure. CLIC1 was shown to reduce sodium selenite and dehydroascorbate in a glutathione-dependent manner. Previous electrophysiological studies have shown that the drugs IAA-94 and A9C specifically block CLIC channel activity. These same compounds inhibit CLIC1 oxidoreductase activity. This work for the first time assigns a functional activity to the soluble form of the CLIC proteins. Our results demonstrate that the soluble form of the CLIC proteins has an enzymatic activity that is distinct from the channel activity of their integral membrane form. This CLIC enzymatic activity may be important for protecting the intracellular environment against oxidation. It is also likely that this enzymatic activity regulates the CLIC ion channel function

    Predicting the long-term impact of antiretroviral therapy scale-up on population incidence of tuberculosis.

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    OBJECTIVE: To investigate the impact of antiretroviral therapy (ART) on long-term population-level tuberculosis disease (TB) incidence in sub-Saharan Africa. METHODS: We used a mathematical model to consider the effect of different assumptions about life expectancy and TB risk during long-term ART under alternative scenarios for trends in population HIV incidence and ART coverage. RESULTS: All the scenarios we explored predicted that the widespread introduction of ART would initially reduce population-level TB incidence. However, many modelled scenarios projected a rebound in population-level TB incidence after around 20 years. This rebound was predicted to exceed the TB incidence present before ART scale-up if decreases in HIV incidence during the same period were not sufficiently rapid or if the protective effect of ART on TB was not sustained. Nevertheless, most scenarios predicted a reduction in the cumulative TB incidence when accompanied by a relative decline in HIV incidence of more than 10% each year. CONCLUSIONS: Despite short-term benefits of ART scale-up on population TB incidence in sub-Saharan Africa, longer-term projections raise the possibility of a rebound in TB incidence. This highlights the importance of sustaining good adherence and immunologic response to ART and, crucially, the need for effective HIV preventive interventions, including early widespread implementation of ART

    Charmed meson decay constants in three-flavor lattice QCD

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    We present the first lattice QCD calculation with realistic sea quark content of the D^+ meson decay constant f_{D^+}. We use the MILC Collaboration's publicly available ensembles of lattice gauge fields, which have a quark sea with two flavors (up and down) much lighter than a third (strange). We obtain f_{D^+} = 201 +/- 3 +/- 17 MeV, where the errors are statistical and a combination of systematic errors. We also obtain f_{D_s} = 249 +/- 3 +/- 16 MeV for the D_s meson.Comment: note added on recent CLEO measurement; PRL versio

    Numerical Integration of the Master Equation in Some Models of Stochastic Epidemiology

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    The processes by which disease spreads in a population of individuals are inherently stochastic. The master equation has proven to be a useful tool for modeling such processes. Unfortunately, solving the master equation analytically is possible only in limited cases (e.g., when the model is linear), and thus numerical procedures or approximation methods must be employed. Available approximation methods, such as the system size expansion method of van Kampen, may fail to provide reliable solutions, whereas current numerical approaches can induce appreciable computational cost. In this paper, we propose a new numerical technique for solving the master equation. Our method is based on a more informative stochastic process than the population process commonly used in the literature. By exploiting the structure of the master equation governing this process, we develop a novel technique for calculating the exact solution of the master equation – up to a desired precision – in certain models of stochastic epidemiology. We demonstrate the potential of our method by solving the master equation associated with the stochastic SIR epidemic model. MATLAB software that implements the methods discussed in this paper is freely available as Supporting Information S1

    The regulatory subunit of PKA-I remains partially structured and undergoes β-aggregation upon thermal denaturation

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    Background: The regulatory subunit (R) of cAMP-dependent protein kinase (PKA) is a modular flexible protein that responds with large conformational changes to the binding of the effector cAMP. Considering its highly dynamic nature, the protein is rather stable. We studied the thermal denaturation of full-length RIα and a truncated RIα(92-381) that contains the tandem cyclic nucleotide binding (CNB) domains A and B. Methodology/Principal Findings: As revealed by circular dichroism (CD) and differential scanning calorimetry, both RIα proteins contain significant residual structure in the heat-denatured state. As evidenced by CD, the predominantly α-helical spectrum at 25°C with double negative peaks at 209 and 222 nm changes to a spectrum with a single negative peak at 212-216 nm, characteristic of β-structure. A similar α→β transition occurs at higher temperature in the presence of cAMP. Thioflavin T fluorescence and atomic force microscopy studies support the notion that the structural transition is associated with cross-β-intermolecular aggregation and formation of non-fibrillar oligomers. Conclusions/Significance: Thermal denaturation of RIα leads to partial loss of native packing with exposure of aggregation-prone motifs, such as the B' helices in the phosphate-binding cassettes of both CNB domains. The topology of the β-sandwiches in these domains favors inter-molecular β-aggregation, which is suppressed in the ligand-bound states of RIα under physiological conditions. Moreover, our results reveal that the CNB domains persist as structural cores through heat-denaturation. © 2011 Dao et al

    Dark solitons in atomic Bose-Einstein condensates: from theory to experiments

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    This review paper presents an overview of the theoretical and experimental progress on the study of matter-wave dark solitons in atomic Bose-Einstein condensates. Upon introducing the general framework, we discuss the statics and dynamics of single and multiple matter-wave dark solitons in the quasi one-dimensional setting, in higher-dimensional settings, as well as in the dimensionality crossover regime. Special attention is paid to the connection between theoretical results, obtained by various analytical approaches, and relevant experimental observations.Comment: 82 pages, 13 figures. To appear in J. Phys. A: Math. Theor

    Computer-Aided Lead Optimization: Improved Small-Molecule Inhibitor of the Zinc Endopeptidase of Botulinum Neurotoxin Serotype A

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    Optimization of a serotype-selective, small-molecule inhibitor of botulinum neurotoxin serotype A (BoNTA) endopeptidase is a formidable challenge because the enzyme-substrate interface is unusually large and the endopeptidase itself is a large, zinc-binding protein with a complex fold that is difficult to simulate computationally. We conducted multiple molecular dynamics simulations of the endopeptidase in complex with a previously described inhibitor (Kiapp of 7±2.4 µM) using the cationic dummy atom approach. Based on our computational results, we hypothesized that introducing a hydroxyl group to the inhibitor could improve its potency. Synthesis and testing of the hydroxyl-containing analog as a BoNTA endopeptidase inhibitor showed a twofold improvement in inhibitory potency (Kiapp of 3.8±0.8 µM) with a relatively small increase in molecular weight (16 Da). The results offer an improved template for further optimization of BoNTA endopeptidase inhibitors and demonstrate the effectiveness of the cationic dummy atom approach in the design and optimization of zinc protease inhibitors

    La consulta previa y su influencia en los proyectos de interés nacional estratégico en Colombia

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    Artículo de investigaciónLa consulta previa es un derecho fundamental que consiste en un mecanismo de participación de las comunidades étnicas e indígenas sobre las medidas administrativas o legislativas que pueden afectar su integridad social, cultural y económica, entre otros. El desarrollo que este mecanismo ha presentado en Colombia, según cifras del Ministerio del Interior (2018) puede calificarse como desmedido. En este sentido, es necesario realizar un análisis acerca del exceso de consultas previas presentadas hoy en día en Colombia. Lo anterior, tiene como finalidad identificar las posibles mejoras que pueden desarrollarse a través de la reglamentación consiente de los procesos de consulta previa, a partir de la identificación real de las afectaciones que puede constituir cada proyecto (PINES). Ponderando el interés general y la necesidad de los proyectos que se encuentran en marcha.1. INTRODUCCIÓN 2. LA CONSULTA PREVIA COMO DERECHO FUNDAMENTAL 3. FUNDAMENTO CONSTITUCIONAL DE LA CONSULTA PREVIA 4. AUTODETERMINACIÓN, CONSENTIMIENTO PREVIO LIBRE E INFORMADO DE LAS COMUNIDADES ÉTNICAS CONCLUSIONES REFERENCIAS 5. PROYECTOS DE INTERÉS NACIONAL Y ESTRATÉGICOS – PINES 6. LA CONSULTA PREVIA Y LOS PROYECTOS DE INTERÉS NACIONAL Y ESTRATÉGICOS – PINES. 7. LA CONSULTA PREVIA Y LA CONSULTA POPULAR Y SU INFLUENCIA EN EL DESARROLLO DEL PAÍSPregradoAbogad
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