4,678 research outputs found
Degradation of two novel congenital TTP ADAMTS13 mutants by the cell proteasome prevents ADAMTS13 secretion
INTRODUCTION: Over 150 mutations have been identified in the ADAMTS13 gene in patients with congenital thrombotic thrombocytopenic purpura (TTP). The majority of these (86%), lead to reduced (<50%) secretion of mutant recombinant ADAMTS13. The mechanism by which this occurs has not been investigated in vitro. Two novel ADAMTS13 mutations (p.I143T and p.Y570C) identified in two congenital adolescence onset TTP patients were studied, to investigate their effects on ADAMTS13 secretion and subcellular localisation. MATERIALS AND METHODS: HEK293T cells were transiently transfected with wild type or mutant ADAMTS13 cDNA. Immunofluorescence and confocal microscopy were used to study localisation within the endoplasmic reticulum (ER) and Golgi. The cell proteasome and lysosomes were inhibited in cells stably expressing ADAMTS13 to investigate degradation of ADAMTS13 by either organelle. RESULTS: Both mutations severely impaired secretion and both mutants localised within the ER and Golgi. Proteasome inhibition led to the intracellular accumulation of both mutants, suggesting proteasome degradation. Lysosome inhibition on the other hand did not lead to increased intracellular accumulation of the mutants. CONCLUSIONS: Proteasome degradation of these ADAMTS13 mutants contributed to their reduced secretion
The impact of broadband in schools
The report reviews evidence for the impact of broadband in English schools, exploring; Variations in provision in level of broadband connectivity; Links between the level of broadband activity and nationally accessible performance data; Aspects of broadband connectivity and the school environment that contribute to better outcomes for pupils and teachers; Academic and motivational benefits associated with educational uses of this technology
Development of an interatomic potential for the simulation of defects, plasticity, and phase transformations in titanium
New interatomic potentials describing defects, plasticity, and high temperature phase transitions for Ti are presented. Fitting the martensitic hcp-bcc phase transformation temperature requires an efficient and accurate method to determine it. We apply a molecular dynamics method based on determination of the melting temperature of competing solid phases, and Gibbs-Helmholtz integration, and a lattice-switch Monte Carlo method: these agree on the hcp-bcc transformation temperatures to within 2 K. We were able to develop embedded atom potentials which give a good fit to either low or high temperature data, but not both. The first developed potential (Ti1) reproduces the hcp-bcc transformation and melting temperatures and is suitable for the simulation of phase transitions and bcc Ti. Two other potentials (Ti2 and Ti3) correctly describe defect properties and can be used to simulate plasticity or radiation damage in hcp Ti. The fact that a single embedded atom method potential cannot describe both low and high temperature phases may be attributed to neglect of electronic degrees of freedom, notably bcc has a much higher electronic entropy. A temperature-dependent potential obtained from the combination of potentials Ti1 and Ti2 may be used to simulate Ti properties at any temperature.</p
Cauchy's formulas for random walks in bounded domains
Cauchy's formula was originally established for random straight paths
crossing a body and basically relates the average
chord length through to the ratio between the volume and the surface of the
body itself. The original statement was later extended in the context of
transport theory so as to cover the stochastic paths of Pearson random walks
with exponentially distributed flight lengths traversing a bounded domain. Some
heuristic arguments suggest that Cauchy's formula may also hold true for
Pearson random walks with arbitrarily distributed flight lengths. For such a
broad class of stochastic processes, we rigorously derive a generalized
Cauchy's formula for the average length travelled by the walkers in the body,
and show that this quantity depends indeed only on the ratio between the volume
and the surface, provided that some constraints are imposed on the entrance
step of the walker in . Similar results are obtained also for the average
number of collisions performed by the walker in , and an extension to
absorbing media is discussed.Comment: 12 pages, 6 figure
Prevalence and impact of chronic widespread pain in the Bangladeshi and White populations of Tower Hamlets, East London
The prevalence and impact of chronic pain differ between ethnic groups. We report a study of the comparative prevalence and impact of chronic pain in Bangladeshi, British Bangladeshi and White British/Irish people. We posted a short questionnaire to a random sample of 4,480 patients registered with 16 general practices in the London Borough of Tower Hamlets and conducted a longer questionnaire with patients in the waiting areas at those practices. We distinguished between Bangladeshi participants who were born in the UK or had arrived in the UK at the age of 14 or under (British Bangladeshi) and those who arrived in UK at the age of over 14 (Bangladeshi). We obtained 1,223/4,480 (27 %) responses to the short survey and 600/637 (94 %) to the long survey. From the former, the prevalence of chronic pain in the White, British Bangladeshi and Bangladeshi groups was 55, 54 and 72 %, respectively. The corresponding figures from the long survey were 49, 45 and 70 %. Chronic widespread pain was commoner in the Bangladeshi (16 %) than in the White (10 %) or British Bangladeshi (9 %) groups. People with chronic pain experienced poorer quality of life (odds ratio for scoring best possible health vs. good health (or good vs. poor health) 5.6 (95 % confidence interval 3.4 to 9.8)), but we found no evidence of differences between ethnic groups in the impact of chronic pain on the quality of life. Chronic pain is commoner and, of greater severity, in Bangladeshis than in Whites. On most measures in this study, British Bangladeshis resembled the Whites more than the Bangladeshis
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Tablet PCs in schools: Case study report: A report for Becta by the Open University
The publication provides an analysis of twelve case studies involving schools in England that were using Tablet PCs. The analysis is complemented by brief individual reports describing aspects of how each of these schools was using Tablet PCs
Changes in microphytobenthos fluorescence over a tidal cycle: implications for sampling designs
Intertidal microphytobenthos (MPB) are important primary producers and provide food for herbivores in soft sediments and on rocky shores. Methods of measuring MPB biomass that do not depend on the time of collection relative to the time of day or tidal conditions are important in any studies that need to compare temporal or spatial variation, effects of abiotic factors or activity of grazers. Pulse amplitude modulated (PAM) fluorometry is often used to estimate biomass of MPB because it is a rapid, non-destructive method, but it is not known how measures of fluorescence are altered by changing conditions during a period of low tide. We investigated this experimentally using in situ changes in minimal fluorescence (F) on a rocky shore and on an estuarine mudflat around Sydney (Australia), during low tides. On rocky shores, the time when samples are taken during low tide had little direct influence on measures of fluorescence as long as the substratum is dry. Wetness from wave-splash, seepage from rock pools, run-off, rainfall, etc., had large consequences for any comparisons. On soft sediments, fluorescence was decreased if the sediment dried out, as happens during low-spring tides on particularly hot and dry days. Surface water affected the response of PAM and therefore measurements used to estimate MPB, emphasising the need for care to ensure that representative sampling is done during low tide
Sharks of the order Carcharhiniformes from the British Coniacian, Santonian and Campanian (Upper Cretaceous).
Bulk sampling of phosphate-rich horizons within the British Coniacian to Campanian (Upper Cretaceous) yielded very large samples of shark and ray teeth. All of these samples yielded teeth of diverse members of the Carcharhiniformes, which commonly dominate the fauna. The following species are recorded and described: Pseudoscyliorhinus reussi (Herman, 1977) comb. nov., Crassescyliorhinus germanicus (Herman, 1982) gen. nov., Scyliorhinus elongatus (Davis, 1887), Scyliorhinus brumarivulensis sp. nov., ? Palaeoscyllium sp., Prohaploblepharus riegrafi (Müller, 1989) gen. nov., ? Cretascyliorhinus sp., Scyliorhinidae inc. sedis 1, Scyliorhinidae inc. sedis 2, Pteroscyllium hermani sp. nov., Protoscyliorhinus sp., Leptocharias cretaceus sp. nov., Palaeogaleus havreensis Herman, 1977, Paratriakis subserratus sp. nov., Paratriakis tenuis sp. nov., Paratriakis sp. indet. and ? Loxodon sp. Taxa belonging to the families ?Proscylliidae, Leptochariidae, and Carcharhinidae are described from the Cretaceous for the first time. The evolutionary and palaeoecological implications of these newly recognised faunas are discussed
An elementary algorithm to evaluate trigonometric functions to high precision
Evaluation of the cosine function is done via a simple Cordic-like algorithm, together with a package for handling arbitrary-precision arithmetic in the computer program Matlab. Approximations to the cosine function having hundreds of correct decimals are presented with a discussion around errors and implementation
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