6,308 research outputs found

    The observable structure of persistence modules

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    In persistent topology, q-tame modules appear as a natural and large class of persistence modules indexed over the real line for which a persistence diagram is definable. However, unlike persistence modules indexed over a totally ordered finite set or the natural numbers, such diagrams do not provide a complete invariant of q-tame modules. The purpose of this paper is to show that the category of persistence modules can be adjusted to overcome this issue. We introduce the observable category of persistence modules: a localization of the usual category, in which the classical properties of q-tame modules still hold but where the persistence diagram is a complete isomorphism invariant and all q-tame modules admit an interval decomposition

    Pathogenicity of anti-ADAMTS13 autoantibodies in acquired thrombotic thrombocytopenic purpura.

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    BACKGROUND: Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency. ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor multimeric size and platelet-tethering function, which results in the formation of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13 autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity generally < 10%) has not been formally investigated. METHODS: We analysed 92 acquired TTP episodes at presentation, through treatment and remission/relapse using epitope mapping and functional analyses to understand the pathogenic mechanisms of anti-ADAMTS13 IgG. RESULTS: 89/92 of TTP episodes had IgG recognising the ADAMTS13 N-terminal domains. The central spacer domain was the only N-terminal antigenic target detected. 38/92 TTP episodes had autoantibodies recognising the N-terminal domains alone; 54/92 TTP episodes also had antibodies against the ADAMTS13 C-terminal domains (TSP2-8 and/or CUB domains). Changes in autoantibody specificity were detected in 9/16 patients at relapse, suggesting a continued development of the disease. Functional analyses on IgG from 43 patients revealed inhibitory IgG were limited to anti-spacer domain antibodies. However, 15/43 patients had autoantibodies with no detectable inhibitory action and as many as 32/43 patients had autoantibodies with inhibitory function that was insufficient to account for the severe deficiency state, suggesting that in many patients there is an alternative pathogenic mechanism. We therefore analysed plasma ADAMTS13 antigen levels in 91 acquired TTP presentation samples. We demonstrated markedly reduced ADAMTS13 antigen levels in all presentation samples, median 6% normal (range 0-47%), with 84/91 patients having < 25% ADAMTS13 antigen. ADAMTS13 antigen in the lowest quartile at first presentation was associated with increased mortality (odds ratio 5.7). CONCLUSIONS: Anti-spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP. However, depletion of ADAMTS13 antigen (rather than enzyme inhibition) is a dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have prognostic significance. Taken together, our results provide new insights into the pathophysiology of acquired TTP

    Gender and the heat pump transition

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    Decarbonisation in moderate and cold climates is reliant on the replacement of existing heating technologies with electric heat pumps. Heat pumps work differently from incumbent technologies, including in how they are controlled, their distribution of heat around the home and their space requirements. Despite evidence that domestic practices and interests associated with women played an important role in previous heating transitions, policy and research have not yet considered how heat pumps might interact with traditionally gendered needs and concerns. This could have significant implications for the success of the heat pump transition. This synthesis uses a framework of evidenced heating needs, incorporating wellbeing, resources, ease of use and relational dynamics, to structure a narrative literature review on how experiences of heat pumps may be gendered. Indicative evidence suggests that heat pumps have the potential to improve female thermal comfort, but that other possibly gendered heating needs such as minimising perceived waste and easy controllability are not always addressed. Amidst a lack of empirical studies exploring women’s needs, and whether they are met by heat pumps, a series of recommendations is provided for multidisciplinary research on the topic and to enhance consideration of gendered needs and experiences in policy development

    Dependency structure matrix modelling for stakeholder value networks

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    This paper develops a qualitative/quantitative network approach, namely a “Stakeholder Value Network”, to understand the impacts of both direct and indirect relationships between stakeholders on the success of large engineering projects. Specifically, this paper explores the feasibility and benefit of applying the Dependency Structure Matrix (DSM) as the modelling platform for Stakeholder Value Networks. Further, an efficient algorithm is designed for computing indirect stakeholder influence and implemented in a case study for a multinational energy project. The results derived from this analysis are able to answer three fundamental questions for stakeholder management: What are the critical paths/themes for a project to engage other stakeholders? Who are the most important stakeholders for a project? How can the complexity of a large relationship network be reasonably managed

    Experimental evolution reveals high insecticide tolerance in Daphnia inhabiting farmland ponds

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    Exposure of nontarget populations to agricultural chemicals is an important aspect of global change. We quantified the capacity of natural Daphnia magna populations to locally adapt to insecticide exposure through a selection experiment involving carbaryl exposure and a control. Carbaryl tolerance after selection under carbaryl exposure did not increase significantly compared to the tolerance of the original field populations. However, there was evolution of a decreased tolerance in the control experimental populations compared to the original field populations. The magnitude of this decrease was positively correlated with land use intensity in the neighbourhood of the ponds from which the original populations were sampled. The genetic change in carbaryl tolerance in the control rather than in the carbaryl treatment suggests widespread selection for insecticide tolerance in the field associated with land use intensity and suggests that this evolution comes at a cost. Our data suggest a strong impact of current agricultural land use on nontarget natural Daphnia populations
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