94 research outputs found

    Fibromodulin Interacts with Collagen Cross-linking Sites and Activates Lysyl Oxidase

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    The hallmark of fibrotic disorders is a highly cross-linked and dense collagen matrix, a property driven by the oxidative action of lysyl oxidase. Other fibrosis-associated proteins also contribute to the final collagen matrix properties, one of which is fibromodulin - its interactions with collagen affect collagen cross-linking, packing, and fibril diameter. We investigated the possibility that a specific relationship exists between fibromodulin and lysyl oxidase, potentially imparting a specific collagen matrix phenotype. We mapped the fibromodulin-collagen interaction sites using the Collagen II and III Toolkit peptide libraries. Fibromodulin interacted with the peptides containing the known collagen cross-linking sites and the MMP-1 cleavage site in collagens I and II. Interestingly, the interaction sites are closely aligned within the quarter-staggered collagen fibril, suggesting a multivalent interaction between fibromodulin and several collagen helices. Furthermore, we detected an interaction between fibromodulin and lysyl oxidase - a major collagen cross-linking enzyme - and mapped the interaction site to 12 N-terminal amino acids on fibromodulin. This interaction also increases the activity of lysyl oxidase. Altogether, the data suggest a fibromodulin-modulated collagen cross-linking mechanism, where fibromodulin binds to a specific part of the collagen domain and also forms a complex together with lysyl oxidase, targeting the enzyme towards specific cross-linking sites.SK and KR were supported by grants from the Swedish Cancer Foundation, the Swedish Research Council, the Alfred Österlund Foundation, the Crafoord Foundation, the Magnus Bergvall Foundation, and the Åke Wiberg Foundation; AB, DB and RWF by grants from the Wellcome Trust (094470/Z/10/Z) and British Heart Foundation (RG/15/4/31268).This is the final version of the article. It first appeared from the American Society for Biochemistry and Molecular Biology] via http://dx.doi.org/10.1074/jbc.M115.69340

    Ecological direct action and the nature of anarchism : explorations from 1992 to 2005

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    In this thesis I study the radical environmental movement, of which I am part, by combining the analysis of texts and the textual record of discussions with my own extensive participant observation. More specifically, I look at the direct action undertaken by radical eco-activists and examine the relationship between this and the anarchist tradition. My research demonstrates, first, that anarchism is alive and well, albeit in a somewhat modified form from the `classical anarchism' of the 19th and early 20th centuries. In researching today's direct activists, therefore, I have also been examining the nature of anarchism itself. I show that anarchism is to be found most strongly in the dialogue that takes place between activists on the ground, engaged in practical struggles. It is from here, in the strategic debates, self-produced pamphlets, and open-ended discussions of radical environmentalists focussed on practical and immediate issues, that I draw much of my data and ideas. In pursuing this project, I present an understanding of anarchism as a pluralistic and dynamic discourse in which there is no single, correct line on each issue. Instead, the vigour of anarchism is revealed through the dissent and reflexive debate of its practitioners. This understanding of anarchism, while contrary to a static project of ideological mapping or comprehensive summary of a tradition, may be in keeping with both contemporary theory, and also the anarchist tradition itself. To pursue this understanding of anarchism, I elaborate an `anarchist methodology of research' which is both collective and subjective, ethically-bounded and reflexive. This draws on the experience of politically engaged researchers who have sought to draw lines of consistency between their ideals and the practice of research. The various forms of ecological direct action manifested in the UK between 1992 and 2005 provide the main source material for this thesis. I survey the practice and proclamations of anti-roads protesters, Earth First!, GM crop-trashers, peat saboteurs, Reclaim the Streets and others, particularly my own local group, `Tyneside Action for People and Planet'. Also considered are the explicitly anarchist organisations of the UK, and the direct action wings of related social movements. Comparison with these non-ecological movements serves to highlight influences, alternatives and criticisms across the cultures of anarchistic direct action, and contributes to the overall diversity of the anarchism studied.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

    This is the future: A reconstruction of the UK business web space (1996–2001)

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    This is the author accepted manuscript. The final version is available from SAGE via http://dx.doi.org/10.1177/1461444816643791Institute of Historical Researc

    Generalized super-resolution 4D Flow MRI \unicode{x2013} using ensemble learning to extend across the cardiovascular system

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    4D Flow Magnetic Resonance Imaging (4D Flow MRI) is a non-invasive measurement technique capable of quantifying blood flow across the cardiovascular system. While practical use is limited by spatial resolution and image noise, incorporation of trained super-resolution (SR) networks has potential to enhance image quality post-scan. However, these efforts have predominantly been restricted to narrowly defined cardiovascular domains, with limited exploration of how SR performance extends across the cardiovascular system; a task aggravated by contrasting hemodynamic conditions apparent across the cardiovasculature. The aim of our study was to explore the generalizability of SR 4D Flow MRI using a combination of heterogeneous training sets and dedicated ensemble learning. With synthetic training data generated across three disparate domains (cardiac, aortic, cerebrovascular), varying convolutional base and ensemble learners were evaluated as a function of domain and architecture, quantifying performance on both in-silico and acquired in-vivo data from the same three domains. Results show that both bagging and stacking ensembling enhance SR performance across domains, accurately predicting high-resolution velocities from low-resolution input data in-silico. Likewise, optimized networks successfully recover native resolution velocities from downsampled in-vivo data, as well as show qualitative potential in generating denoised SR-images from clinical level input data. In conclusion, our work presents a viable approach for generalized SR 4D Flow MRI, with ensemble learning extending utility across various clinical areas of interest.Comment: 10 pages, 5 figure

    Coercion against patients with dementia – A literature review about the dilemma between autonomy and restraints in healthcare

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    Introduktion: I arbetet kan sjuksköterskor komma i kontakt med patienter med demenssjukdom. Demenssjuka patienter har enligt svensk lagstiftning samma rätt till självbestämmande som övriga patienter. Dock kan de svikta i sjukdomsinsikt och tenderar därför att vägra sjukvårdsinsatser som sätts in för patientens eget beskydd. I dessa fall kan vårdpersonal känna behov av att tillgripa tvångsåtgärder i form av lugnande läkemedel eller fysiska restriktioner för att skydda patienten från skada, vilket juridiskt sett ses som ett övergrepp. Syfte: Syftet med litteraturöversikten är att belysa sjuksköterskans användande av tvångsåtgärder och tankarna detta väcker, samt att även redovisa möjliga metoder för att minska användandet av tvångsåtgärder. Metod: Litteraturöversikt baserat på sex kvalitativa och tre kvantitativa vetenskapligt granskade forskningsartiklar. Resultat: Tvångsåtgärder används i större utsträckning på avdelningar med fysiskt mer krävande patienter. Det har dessutom visat sig att tvångsåtgärderna inte endast används för patientens bästa, utan även till förmån för personal och andra patienter. Dock känner vårdpersonal ofta obehag inför utförandet av tvångsåtgärderna och använder ett antal olika “ursäkter” eller copingstrategier för att hantera detta. Vårdpersonalen funderar även på ifall det vore möjligt att använda sig av andra metoder, men säger sig inte ha resurser för detta. Ytterligare forskning visar att det ofta saknas lokala riktlinjer för dessa situationer och att kunskapsnivån på området är för låg. Sammantaget leder det till ökad användning av tvångsåtgärder. Slutsats: Det behövs ökad bemanning och personalen bör ha högre kunskap om geriatrisk vård, alternativa metoder samt vad tvångsåtgärderna gör med patienterna. Dessutom är det viktigt att det finns lokala riktlinjer för hantering av situationer där tvångsåtgärder riskerar att använda

    Multidimensional MRI of Cardiac Motion Acquisition, Reconstruction and Visualization

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    Left ventricular volume measured for all combination
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