214 research outputs found

    Organization of Cellular Receptors into a Nanoscale Junction during HIV-1 Adhesion

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    The fusion of the human immunodeficiency virus type 1 (HIV-1) with its host cell is the target for new antiretroviral therapies. Viral particles interact with the flexible plasma membrane via viral surface protein gp120 which binds its primary cellular receptor CD4 and subsequently the coreceptor CCR5. However, whether and how these receptors become organized at the adhesive junction between cell and virion are unknown. Here, stochastic modeling predicts that, regarding binding to gp120, cellular receptors CD4 and CCR5 form an organized, ring-like, nanoscale structure beneath the virion, which locally deforms the plasma membrane. This organized adhesive junction between cell and virion, which we name the viral junction, is reminiscent of the well-characterized immunological synapse, albeit at much smaller length scales. The formation of an organized viral junction under multiple physiopathologically relevant conditions may represent a novel intermediate step in productive infection

    Feasibility of using Grindr™ to distribute HIV self-test kits to men who have sex with men in Los Angeles, California

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    Background: Our study aimed to determine if Grindr™ is an effective means of reaching high-risk men who have sex with men (MSM) for HIV testing. In Los Angeles (LA), Black and Latino MSM have the highest rate of HIV infection, and Black MSM in LA are four-fold more likely than white MSM to not know they are infected with HIV. Those MSM are also major users of social networking apps. Grindr™ was used to provide access to free HIV self-testing. Methods: Free HIV self-test kits were advertised on Grindr™ from 13 October to 11 November 2014, consisting of 300 000 banner ads and three broadcast messages targeting a high-risk HIV population in LA. Eligible participants, Black or Latino, MSM and who were aged ≥18 years of age, were invited to take a survey 2 weeks after test delivery. Results: The website received 4389 unique visitors and 333 test requests, of which 247 (74%) were requests for mailed tests, 58 (17%) were for vouchers and 28 (8%) were for vending machines. Of the 125 participants, 74% reported at least one episode of condomless anal intercourse in the past 3 months, 29% last tested for HIV over 1 year ago and 9% had never been tested. Conclusions: It was feasible to use Grindr™ to distribute HIV self-test kits. Users are willing to provide personal information in exchange for a free self-test and found self-tests acceptable and easy to use. HIV self-testing promotion through apps has a high potential to reach untested high-risk populations

    Observation of low-lying isomeric states in 136^{136}Cs: a new avenue for dark matter and solar neutrino detection in xenon detectors

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    We report on new measurements establishing the existence of low-lying isomeric states in 136^{136}Cs using γ\gamma rays produced in 136^{136}Xe(p,n)136^{136}Cs reactions. Two states with O(100)\mathcal{O}(100)~ns lifetimes are placed in the decay sequence of the 136^{136}Cs levels that are populated in charged-current interactions of solar neutrinos and fermionic dark matter with 136^{136}Xe. Xenon-based experiments can therefore exploit a delayed-coincidence tag of these interactions, greatly suppressing backgrounds to enable spectroscopic studies of solar neutrinos and dark matter.Comment: Supplemental material available upon request. Version accepted by Phys.Rev.Let

    “What’s on the Test?”: The Impact of Giving Students a Concept-List Study Guide

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    Students frequently request concept-list study guides prior to exams, but the benefits of instructors providing such resources are unclear. Research on memory and comprehension has suggested that some challenges in learning are associated with benefits to performance. In the context of an introductory psychology course, a study was conducted to investigate the impact of providing a concept-list study guide on exam performance, as opposed to having students create a study guide. Additionally, student preferences for various types of study guides were examined. Results indicated that although students greatly prefer that the instructors provide a study guide (as opposed to making their own), providing a concept-list study guide resulted in poorer exam performance. These results call for future research on the influence of study guides on student performance

    Experimental investigation of electron heating modes in capacitively coupled radio-frequency oxygen discharge

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    A Langmuir probe has been used to investigate electron heating mechanisms in a capacitively coupled oxygen discharge over a wide pressure range (50 – 800 mTorr) at a fixed applied power (200 W). Evidence presented here from experimentally obtained electron energy distribution functions (EEDFs) illustrates discharge transition from collisionless (stochastic) to collisional (ohmic) dominant regime with increasing oxygen pressure. The discharge exhibited a bi-Maxwellian EEDF in the collisionless regime, dominated by stochastic heating whereas Druyvesteyn-like EEDFs in the collisional dominant regime. Moreover, in the transition between these two regimes, parameters such as electron density, effective electron temperature and electron-neutral collision frequency exhibited significant variations

    RIPK3 activation leads to cytokine synthesis that continues after loss of cell membrane integrity

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    Necroptosis is a form of programmed cell death that is defined by activation of the kinase RIPK3 and subsequent cell membrane permeabilization by the effector MLKL. RIPK3 activation can also promote immune responses via production of cytokines and chemokines. How active cytokine production is coordinated with the terminal process of necroptosis is unclear. Here, we report that cytokine production continues within necroptotic cells even after they have lost cell membrane integrity and irreversibly committed to death. This continued cytokine production is dependent on mRNA translation and requires maintenance of endoplasmic reticulum integrity that remains after plasma membrane integrity is lost. The continued translation of cytokines by cellular corpses contributes to necroptotic cell uptake by innate immune cells and priming of adaptive immune responses to antigens associated with necroptotic corpses. These findings imply that cell death and production of inflammatory mediators are coordinated to optimize the immunogenicity of necroptotic cells

    Battery Earth: using the subsurface at Boulby underground laboratory to investigate energy storage technologies

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    Renewable energy provides a low-carbon alternative to power generation in the UK. However, the resultant supply varies on daily, weekly and seasonal cycles, such that for green energies to be fully exploited new grid-scale energy storage systems must be implemented. Two pilot facilities in Germany and the United States have demonstrated the potential of the Earth as a battery to store compressed air, using off-peak surplus energy. Natural accumulations of salt (halite deposits) in the UK represent a large and untapped natural storage reservoir for compressed air with the ability to provide instantaneous green energy to meet peak demand. To realise the potential of this emerging technology, a detailed knowledge of the relationship between mechanics, chemistry and geological properties is required to optimise cavern design, storage potential and economic feasibility. The variable stresses imposed on the rock matrix by gas storage, combined with the cyclic nature of cavern pressurisation are barriers to deployment that need to be addressed to enable large-scale adoption of schemes. Well-designed field experiments are a lynchpin for advancing research in this area, especially when supported by state-of-the-art characterisation and modelling techniques. The research facility at STFC’s Boulby Underground Laboratory presents the ideal location to tackle these fundamental issues to optimise “Battery Earth”
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