1,979 research outputs found

    Association between two CHRNA3 variants and susceptibility of lung cancer: a meta-analysis

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    Exploring the Effect of Crowd Management Measures on Passengers’ Behaviour at Metro Stations

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    To reduce problems of interaction at the platform train interface (PTI) platform edge doors (PEDs) and markings on the platform are used as door positions indicators. The common methods to study the effect of these measures are based on average values of density using Fruin’s Level of Service (LOS), however identification cannot be made of which part of the PTI is more congested. To solve this problem, a new method is proposed. The method included a conceptual model in which the PTI was discretised into 40 cm square cells to identify which part of the platform is more congested. Passengers’ behaviour was recorded considering two situations before the train arrives: i) passengers waiting in front of the doors; ii) passengers waiting beside the doors. Observation was done at existing stations at Metro de Santiago and London Underground. Results show that PEDs changed the behaviour of passengers as they were located beside the doors rather than in front of them. In addition, when markings were used on the platform, then this behaviour was reinforced. Therefore, it is recommended to use this method to better design the PTI rather than the LOS which is used to design the whole platform. Further research is needed to study the effect of PEDs on passengers with reduced mobility

    Two-dimensional universal conductance fluctuations and the electron-phonon interaction of topological surface states in Bi2Te2Se nanoribbons

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    The universal conductance fluctuations (UCFs), one of the most important manifestations of mesoscopic electronic interference, have not yet been demonstrated for the two-dimensional surface state of topological insulators (TIs). Even if one delicately suppresses the bulk conductance by improving the quality of TI crystals, the fluctuation of the bulk conductance still keeps competitive and difficult to be separated from the desired UCFs of surface carriers. Here we report on the experimental evidence of the UCFs of the two-dimensional surface state in the bulk insulating Bi2Te2Se nanoribbons. The solely-B\perp-dependent UCF is achieved and its temperature dependence is investigated. The surface transport is further revealed by weak antilocalizations. Such survived UCFs of the topological surface states result from the limited dephasing length of the bulk carriers in ternary crystals. The electron-phonon interaction is addressed as a secondary source of the surface state dephasing based on the temperature-dependent scaling behavior

    Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

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    Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

    Structural Basis and Kinetics of Force-Induced Conformational Changes of an αA Domain-Containing Integrin

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    Integrin α(L)β₂ (lymphocyte function-associated antigen, LFA-1) bears force upon binding to its ligand intercellular adhesion molecule 1 (ICAM-1) when a leukocyte adheres to vascular endothelium or an antigen presenting cell (APC) during immune responses. The ligand binding propensity of LFA-1 is related to its conformations, which can be regulated by force. Three conformations of the LFA-1 αA domain, determined by the position of its α₇-helix, have been suggested to correspond to three different affinity states for ligand binding.The kinetics of the force-driven transitions between these conformations has not been defined and dynamically coupled to the force-dependent dissociation from ligand. Here we show, by steered molecular dynamics (SMD) simulations, that the αA domain was successively transitioned through three distinct conformations upon pulling the C-terminus of its α₇-helix. Based on these sequential transitions, we have constructed a mathematical model to describe the coupling between the αA domain conformational changes of LFA-1 and its dissociation from ICAM-1 under force. Using this model to analyze the published data on the force-induced dissociation of single LFA-1/ICAM-1 bonds, we estimated the force-dependent kinetic rates of interstate transition from the short-lived to intermediate-lived and from intermediate-lived to long-lived states. Interestingly, force increased these transition rates; hence activation of LFA-1 was accelerated by pulling it via an engaged ICAM-1.Our study defines the structural basis for mechanical regulation of the kinetics of LFA-1 αA domain conformational changes and relates these simulation results to experimental data of force-induced dissociation of single LFA-1/ICAM-1 bonds by a new mathematical model, thus provided detailed structural and kinetic characterizations for force-stabilization of LFA-1/ICAM-1 interaction

    Detection of regulator genes and eQTLs in gene networks

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    Genetic differences between individuals associated to quantitative phenotypic traits, including disease states, are usually found in non-coding genomic regions. These genetic variants are often also associated to differences in expression levels of nearby genes (they are "expression quantitative trait loci" or eQTLs for short) and presumably play a gene regulatory role, affecting the status of molecular networks of interacting genes, proteins and metabolites. Computational systems biology approaches to reconstruct causal gene networks from large-scale omics data have therefore become essential to understand the structure of networks controlled by eQTLs together with other regulatory genes, and to generate detailed hypotheses about the molecular mechanisms that lead from genotype to phenotype. Here we review the main analytical methods and softwares to identify eQTLs and their associated genes, to reconstruct co-expression networks and modules, to reconstruct causal Bayesian gene and module networks, and to validate predicted networks in silico.Comment: minor revision with typos corrected; review article; 24 pages, 2 figure
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