507 research outputs found

    The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and haemostasis

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    Objective: Heat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering haemostasis and thrombosis, in this study we sought to characterise the role of HSP47 on these cells. Approach and Results: The deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP-XL), but responses to thrombin were unaltered. In the absence of functional HSP47, the interaction of collagen with platelets was reduced, and this was associated with reduced GPVI-collagen binding, signalling and platelet activation. Thrombus formation on collagen, under arterial flow conditions was also decreased following the inhibition or deletion of HSP47, in the presence or absence of the eptifibatide, consistent with a role for HSP47 in enhancing platelet adhesion to collagen. Platelet adhesion under flow to von Willebrand Factor was unaltered following HSP47 inhibition. Laser-induced thrombosis in cremaster muscle arterioles was reduced and bleeding time was prolonged in HSP47 deficient mice or following inhibition of HSP47. Conclusions: Our study demonstrates the presence of HSP47 on the platelet surface where it interacts with collagen, stabilises platelet adhesion and increases collagen mediated signalling and therefore thrombus formation and haemostasis

    Motivation of UK school pupils towards foreign languages: a large-scale survey at Key Stage 3

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    Motivation is one of the most significant predictors of success in foreign language learning. While individual and governmental commitment to the learning of foreign languages is growing throughout most of Europe and across the globe, it is stuttering in the United Kingdom. An entitlement to language learning in primary school is not yet fully in place, whilst the removal of language from the core curriculum at Key Stage 4 (ages 14 to 16) has led to a dramatic fall in numbers of language learners. Among national initiatives seeking to enhance learners’ interest in languages among school pupils are Specialist Language Colleges and the Languages Ladder. The latter, by certifying achievement through its associated accreditation scheme Asset Languages, seeks to engender a sense of success and motivate continuation of language study. This article reports on a study conducted in 2005-06 of the language learning motivation of over ten thousand school pupils at Key Stage 3 – the only group currently obliged to study a foreign language. The study analyses the nature of learner motivation and its relationship with gender, level of study (Years 7, 8 and 9) and type of school, and thus provides evidence for possible measures to increase numbers of teenagers studying a foreign language, and a baseline against which the success of policy initiatives can be measured in the future

    Asymmetric rolling of interstitial-free steel using differential roll diameters. Part II : microstructure and annealing effects

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    The effects of annealing on the microstructure, texture, tensile properties, and R value evolution of an IF steel sheet after room-temperature symmetric and asymmetric rolling were examined. Simulations were carried out to obtain R values from the experimental textures using the viscoplastic self-consistent polycrystal plasticity model. The investigation revealed the variations in the textures due to annealing and symmetric/asymmetric rolling and showed that the R values correlate strongly with the evolution of the texture. An optimum heat treatment for the balance of strength, ductility, and deep drawability was found to be at 873 K (600 _C) for 30 minutes

    Explaining motivation in language learning: a framework for evaluation and research

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    Researching motivation in language learning is complex and multi-faceted. Various models of learner motivation have been proposed in the literature, but no one model supplies a complex and coherent framework for investigating a range of motivational characteristics. Building on previous models I propose such a methodological framework, based on a complex dynamic systems perspective, which re-conceptualises the investigation of motivation in SLA in qualitative and mixed method approaches by offering one flexible tool for case study approaches. This new framework has been tried and tested in three locations in England and reported as case studies. The study aimed to address the following research questions: (1) in what ways does CLIL impact on learner motivation? (2) what are the main elements of CLIL that enhance motivation? Overall analysis of the results found that where expectations of success were high and where the teaching was effective, CLIL had a positive impact on motivation and progress. The framework is designed to be flexible enough to be used to investigate language learning in a range of national contexts. It is hoped that the proposed framework, reported here together with exemplification and commentary from the English study, will enable researchers in a wide range of language learning contexts to investigate learner motivation in a systematic and in-depth manner

    Searches for lepton-flavour-violating decays of the Higgs boson into eτ and μτ in \sqrt{s} = 13 TeV pp collisions with the ATLAS detector

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    Abstract This paper presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ, performed using data collected with the ATLAS detector at the LHC. The searches are based on a data sample of proton-proton collisions at a centre-of-mass energy s s \sqrt{s} = 13 TeV, corresponding to an integrated luminosity of 138 fb−1. Leptonic (τ → ℓνℓντ) and hadronic (τ → hadrons ντ) decays of the τ-lepton are considered. Two background estimation techniques are employed: the MC-template method, based on data-corrected simulation samples, and the Symmetry method, based on exploiting the symmetry between electrons and muons in the Standard Model backgrounds. No significant excess of events is observed and the results are interpreted as upper limits on lepton-flavour-violating branching ratios of the Higgs boson. The observed (expected) upper limits set on the branching ratios at 95% confidence level, B B \mathcal{B} (H → eτ) < 0.20% (0.12%) and B B \mathcal{B} (H → μτ ) < 0.18% (0.09%), are obtained with the MC-template method from a simultaneous measurement of potential H → eτ and H → μτ signals. The best-fit branching ratio difference, B B \mathcal{B} (H → μτ) → B B \mathcal{B} (H → eτ), measured with the Symmetry method in the channel where the τ-lepton decays to leptons, is (0.25 ± 0.10)%, compatible with a value of zero within 2.5σ