559 research outputs found

    Rivalry, Exclusion and Coalitions

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    Coalition formation, exclusion contest, tragedy of the commons

    How can the study of action kinematics inform our understanding of human social interaction?

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    The kinematics of human actions are influenced by the social context in which they are performed. Motion-capture technology has allowed researchers to build up a detailed and complex picture of how action kinematics vary across different social contexts. Here we review three task domains-point-to-point imitation tasks, motor interference tasks and reach-to-grasp tasks-to critically evaluate how these tasks can inform our understanding of social interactions. First, we consider how actions within these task domains are performed in a non-social context, before highlighting how a plethora of social cues can perturb the baseline kinematics. We show that there is considerable overlap in the findings from these different tasks domains but also highlight the inconsistencies in the literature and the possible reasons for this. Specifically, we draw attention to the pitfalls of dealing with rich, kinematic data. As a way to avoid these pitfalls, we call for greater standardisation and clarity in the reporting of kinematic measures and suggest the field would benefit from a move towards more naturalistic tasks

    A novel framework for engineering protein loops exploring length and compositional variation

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    Insertions and deletions (indels) are known to affect function, biophysical properties and substrate specificity of enzymes, and they play a central role in evolution. Despite such clear significance, this class of mutation remains an underexploited tool in protein engineering with few available platforms capable of systematically generating and analysing libraries of varying sequence composition and length. We present a novel DNA assembly platform (InDel assembly), based on cycles of endonuclease restriction digestion and ligation of standardised dsDNA building blocks, that can generate libraries exploring both composition and sequence length variation. In addition, we developed a framework to analyse the output of selection from InDel-generated libraries, combining next generation sequencing and alignment-free strategies for sequence analysis. We demonstrate the approach by engineering the well-characterized TEM-1 β-lactamase Ω-loop, involved in substrate specificity, identifying multiple novel extended spectrum β-lactamases with loops of modified length and composition—areas of the sequence space not previously explored. Together, the InDel assembly and analysis platforms provide an efficient route to engineer protein loops or linkers where sequence length and composition are both essential functional parameters

    Effects of Antiplatelet Therapy After Stroke Caused by Intracerebral Hemorrhage Extended Follow-up of the RESTART Randomized Clinical Trial

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    Importance: The Restart or Stop Antithrombotics Randomized Trial (RESTART) found that antiplatelet therapy appeared to be safe up to 5 years after intracerebral hemorrhage (ICH) that had occurred during antithrombotic (antiplatelet or anticoagulant) therapy. Objectives: To monitor adherence, increase duration of follow-up, and improve precision of estimates of the effects of antiplatelet therapy on recurrent ICH and major vascular events. Design, Setting and Participants: From May 22, 2013, through May 31, 2018, this prospective, open, blinded end point, parallel-group randomized clinical trial studied 537 participants at 122 hospitals in the UK. Participants were individuals 18 years or older who had taken antithrombotic therapy for the prevention of occlusive vascular disease when they developed ICH, discontinued antithrombotic therapy, and survived for 24 hours. After initial follow-up ended on November 30, 2018, annual follow-up was extended until November 30, 2020, for a median of 3.0 years (interquartile range [IQR], 2.0-5.0 years) for the trial cohort. Interventions: Computerized randomization that incorporated minimization allocated participants (1:1) to start or avoid antiplatelet therapy. Main Outcomes and Measures: Participants were followed up for the primary outcome (recurrent symptomatic ICH) and secondary outcomes (all major vascular events) for up to 7 years. Data from all randomized participants were analyzed using Cox proportional hazards regression, adjusted for minimization covariates. Results: A total of 537 patients (median age, 76.0 years; IQR, 69.0-82.0 years; 360 [67.0%] male; median time after ICH onset, 76.0 days; IQR, 29.0-146.0 days) were randomly allocated to start (n = 268) or avoid (n = 269 [1 withdrew]) antiplatelet therapy. The primary outcome of recurrent ICH affected 22 of 268 participants (8.2%) allocated to antiplatelet therapy compared with 25 of 268 participants (9.3%) allocated to avoid antiplatelet therapy (adjusted hazard ratio, 0.87; 95% CI, 0.49-1.55; P = .64). A major vascular event affected 72 participants (26.8%) allocated to antiplatelet therapy compared with 87 participants (32.5%) allocated to avoid antiplatelet therapy (hazard ratio, 0.79; 95% CI, 0.58-1.08; P = .14). Conclusions and Relevance: Among patients with ICH who had previously taken antithrombotic therapy, this study found no statistically significant effect of antiplatelet therapy on recurrent ICH or all major vascular events. These findings provide physicians with some reassurance about the use of antiplatelet therapy after ICH if indicated for secondary prevention of major vascular events

    Jets and Broad Emission Line Regions

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    Wetensch. publicatieFaculteit der Wiskunde en Natuurwetenschappe

    Extragalactic Radio Continuum Surveys and the Transformation of Radio Astronomy

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    Next-generation radio surveys are about to transform radio astronomy by discovering and studying tens of millions of previously unknown radio sources. These surveys will provide new insights to understand the evolution of galaxies, measuring the evolution of the cosmic star formation rate, and rivalling traditional techniques in the measurement of fundamental cosmological parameters. By observing a new volume of observational parameter space, they are also likely to discover unexpected new phenomena. This review traces the evolution of extragalactic radio continuum surveys from the earliest days of radio astronomy to the present, and identifies the challenges that must be overcome to achieve this transformational change.Comment: To be published in Nature Astronomy 18 Sept 201

    Insertion and translocation of proteins into and through membranes

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    AbstractIn prokaryotic and eukaryotic organisms proteins are efficiently sorted to reach their final destinations in a whole range of subcellular compartments. Targeting is mediated by Hydrophobie signal sequences or hydrophilic targeting sequences depending upon the compartment, these sequences being often processed. Proteins cannot be translocated through a membrane in a tightly folded stage, they must have a loose conformation, the so-called ‘translocation competent state’, which is usually kept through interactions with chaperones. In addition to these cytosolic receptor-like components, receptors are also present on the target membranes. Depending upon the organelles and organisms, two different energy sources have been identified, energy rich phosphate bonds (ATP and GTP) and a potential across the target membrane. Besides the signal peptides various classes of signals have been identified to account for topologies of membrane proteins. Protein secretion in bacterial organisms has been extensively studied. Various classes of proteins use different strategies some of these may also be used in eukaryotic cells
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