632 research outputs found

    Combating barriers to inclusive design – Evaluation of an inclusive design toolkit

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    This research is based on a number of studies of barriers to inclusive design [1-4], in particular the authors ’ own investigation of drivers for, and barriers to, inclusive design within the UK consumer product industry [4], where two mail surveys were conducted: one with 177 industrial design consultancies, and the other with 152 consumer produc

    Development of modelling method selection tool for health services management: from problem structuring methods to modelling and simulation methods.

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    BACKGROUND: There is an increasing recognition that modelling and simulation can assist in the process of designing health care policies, strategies and operations. However, the current use is limited and answers to questions such as what methods to use and when remain somewhat underdeveloped. AIM: The aim of this study is to provide a mechanism for decision makers in health services planning and management to compare a broad range of modelling and simulation methods so that they can better select and use them or better commission relevant modelling and simulation work. METHODS: This paper proposes a modelling and simulation method comparison and selection tool developed from a comprehensive literature review, the research team's extensive expertise and inputs from potential users. Twenty-eight different methods were identified, characterised by their relevance to different application areas, project life cycle stages, types of output and levels of insight, and four input resources required (time, money, knowledge and data). RESULTS: The characterisation is presented in matrix forms to allow quick comparison and selection. This paper also highlights significant knowledge gaps in the existing literature when assessing the applicability of particular approaches to health services management, where modelling and simulation skills are scarce let alone money and time. CONCLUSIONS: A modelling and simulation method comparison and selection tool is developed to assist with the selection of methods appropriate to supporting specific decision making processes. In particular it addresses the issue of which method is most appropriate to which specific health services management problem, what the user might expect to be obtained from the method, and what is required to use the method. In summary, we believe the tool adds value to the scarce existing literature on methods comparison and selection

    Multi-domain design assessment for aerospace components including weld accessibility

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    AbstractAeroengine manufacturers need to better include assessment of risk and cost for realising the novel products needed to meet the ambitions sustainability driven targets for air transport. Radical technologies are needed that simultaneously require critical manufacturing processes to be assessed already in conceptual design.In this paper, a multi-domain framework for conceptual design and evaluation is proposed that provide the ability to interactively explore the concepts that simultaneously allow a wider range of architectures can be assessed and still include weldability of the concepts.It has been demonstrated how high level, and function driven conceptual design alternatives can be modelled and evaluated to analyse risk and resilience of architectures. Geometrical concepts generated for the most interesting regimes using design of experiments covering a desired design space. For each CAD-model the welding process can be simulated to assess feasibility and lead time for welding, and return quantified results to be included in an integrated results data set for interactive decision making. The paper is the first report from a research project that improve concurrent design of product and production concepts.Clean Sky 2 Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme. Grant agreement No 887174

    The effects of theaflavin-enriched black tea extract on muscle soreness, oxidative stress, inflammation, and endocrine responses to acute anaerobic interval training: a randomized, double-blind, crossover study

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    <p>Abstract</p> <p>Background</p> <p>Muscle soreness and decreased performance often follow a bout of high-intensity exercise. By reducing these effects, an athlete can train more frequently and increase long-term performance. The purpose of this study is to examine whether a high-potency, black tea extract (BTE) alters the delayed onset muscle soreness (DOMS), oxidative stress, inflammation, and cortisol (CORT) responses to high-intensity anaerobic exercise.</p> <p>Methods</p> <p>College-age males (N = 18) with 1+ yrs of weight training experience completed a double-blind, placebo-controlled, crossover study. Subjects consumed the BTE (1,760 mg BTE·d<sup>-1</sup>) or placebo (PLA) for 9 days. Each subject completed two testing sessions (T1 & T2), which occurred on day 7 of the intervention. T1 & T2 consisted of a 30 s Wingate Test plus eight 10 s intervals. Blood samples were obtained before, 0, 30 & 60 min following the interval sessions and were used to analyze the total to oxidized glutathione ratio (GSH:GSSG), 8-isoprostane (8-iso), CORT, and interleukin 6 (IL-6) secretion. DOMS was recorded at 24 & 48 h post-test using a visual analog scale while BTE or PLA continued to be administered. Significance was set at <it>P < 0.05</it>.</p> <p>Results</p> <p>Compared to PLA, BTE produced significantly higher average peak power (<it>P = 0.013</it>) and higher average mean power (<it>P = 0.067</it>) across nine WAnT intervals. BTE produced significantly lower DOMS compared to PLA at 24 h post test (<it>P < 0.001</it>) and 48 h post test (<it>P < 0.001</it>). Compared to PLA, BTE had a slightly higher GSH:GSSG ratio at baseline which became significantly higher at 30 and 60 min post test (<it>P < 0.002</it>). AUC analysis revealed BTE to elicit significantly lower GSSG secretion (<it>P = 0.009</it>), significantly higher GSH:GSSG ratio (<it>P = 0.001</it>), and lower CORT secretion (<it>P = 0.078</it>) than PLA. AUC analysis did not reveal a significant difference in total IL-6 response (<it>P = 0.145</it>) between conditions.</p> <p>Conclusions</p> <p>Consumption of theaflavin-enriched black tea extract led to improved recovery and a reduction in oxidative stress and DOMS responses to acute anaerobic intervals. An improved rate of recovery can benefit all individuals engaging in high intensity, anaerobic exercise as it facilitates increased frequency of exercise.</p

    Transiting extrasolar planetary candidates in the Galactic bulge

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    More than 200 extrasolar planets have been discovered around relatively nearby stars, primarily through the Doppler line shifts owing to the reflex motions of their host stars, and more recently through transits of some planets across the face of the host stars. The detection of planets with the shortest known periods, 1.2 to 2.5 days, has mainly resulted from transit surveys which have generally targeted stars more massive than 0.75 M_sun. Here we report the results from a planetary transit search performed in a rich stellar field towards the Galactic bulge. We discovered 16 candidates with orbital periods between 0.4 and 4.2 days, five of which orbit stars of 0.44 to 0.75 M_sun. In two cases, radial-velocity measurements support the planetary nature of the companions. Five candidates have orbital periods below 1.0 day, constituting a new class of ultra-short-period planets (USPPs), which occur only around stars of less than 0.88 M_sun. This indicates that those orbiting very close to more luminous stars might be evaporatively destroyed, or that jovian planets around lower-mass stars might migrate to smaller radii.Comment: To appear in October 5, 2006 issue of Natur

    Metallothionein genes: no association with Crohn's disease in a New Zealand population

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    Metallothioneins (MTs) are excellent candidate genes for Inflammatory Bowel Disease (IBD) and have previously been shown to have altered expression in both animal and human studies of IBD. This is the first study to examine genetic variants within the MT genes and aims to determine whether such genetic variants have an important role in this disease. 28 tag SNPs in genes MT1 (subtypes A, B, E, F, G, H, M, X), MT2, MT3 and MT4 were selected for genotyping in a well-characterized New Zealand dataset consisting of 406 patients with Crohn's Disease and 638 controls. We did not find any evidence of association for MT genetic variation with CD. The lack of association indicates that genetic variants in the MT genes do not play a significant role in predisposing to CD in the New Zealand population

    The use of phylogeny to interpret cross-cultural patterns in plant use and guide medicinal plant discovery: an example from Pterocarpus (Leguminosae)

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    The study of traditional knowledge of medicinal plants has led to discoveries that have helped combat diseases and improve healthcare. However, the development of quantitative measures that can assist our quest for new medicinal plants has not greatly advanced in recent years. Phylogenetic tools have entered many scientific fields in the last two decades to provide explanatory power, but have been overlooked in ethnomedicinal studies. Several studies show that medicinal properties are not randomly distributed in plant phylogenies, suggesting that phylogeny shapes ethnobotanical use. Nevertheless, empirical studies that explicitly combine ethnobotanical and phylogenetic information are scarce.In this study, we borrowed tools from community ecology phylogenetics to quantify significance of phylogenetic signal in medicinal properties in plants and identify nodes on phylogenies with high bioscreening potential. To do this, we produced an ethnomedicinal review from extensive literature research and a multi-locus phylogenetic hypothesis for the pantropical genus Pterocarpus (Leguminosae: Papilionoideae). We demonstrate that species used to treat a certain conditions, such as malaria, are significantly phylogenetically clumped and we highlight nodes in the phylogeny that are significantly overabundant in species used to treat certain conditions. These cross-cultural patterns in ethnomedicinal usage in Pterocarpus are interpreted in the light of phylogenetic relationships.This study provides techniques that enable the application of phylogenies in bioscreening, but also sheds light on the processes that shape cross-cultural ethnomedicinal patterns. This community phylogenetic approach demonstrates that similar ethnobotanical uses can arise in parallel in different areas where related plants are available. With a vast amount of ethnomedicinal and phylogenetic information available, we predict that this field, after further refinement of the techniques, will expand into similar research areas, such as pest management or the search for bioactive plant-based compounds

    Structure and Dynamics of the G121V Dihydrofolate Reductase Mutant: Lessons from a Transition-State Inhibitor Complex

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    It is well known that enzyme flexibility is critical for function. This is due to the observation that the rates of intramolecular enzyme motions are often matched to the rates of intermolecular events such as substrate binding and product release. Beyond this role in progression through the reaction cycle, it has been suggested that enzyme dynamics may also promote the chemical step itself. Dihydrofolate reductase (DHFR) is a model enzyme for which dynamics have been proposed to aid in both substrate flux and catalysis. The G121V mutant of DHFR is a well studied form that exhibits a severe reduction in the rate of hydride transfer yet there remains dispute as to whether this defect is caused by altered structure, dynamics, or both. Here we address this by presenting an NMR study of the G121V mutant bound to reduced cofactor and the transition state inhibitor, methotrexate. NMR chemical shift markers demonstrate that this form predominantly adopts the closed conformation thereby allowing us to provide the first glimpse into the dynamics of a catalytically relevant complex. Based on 15N and 2H NMR spin relaxation, we find that the mutant complex has modest changes in ps-ns flexibility with most affected residues residing in the distal adenosine binding domain rather than the active site. Thus, aberrant ps-ns dynamics are likely not the main contributor to the decreased catalytic rate. The most dramatic effect of the mutation involves changes in µs-ms dynamics of the F-G and Met20 loops. Whereas loop motion is quenched in the wild type transition state inhibitor complex, the F-G and Met20 loops undergo excursions from the closed conformation in the mutant complex. These excursions serve to decrease the population of conformers having the correct active site configuration, thus providing an explanation for the G121V catalytic defect
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