1,683 research outputs found

    Vulnerabilities in first-generation RFID-enabled credit cards

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    Credit cards ; Radio frequency identification systems

    Insulin-like growth factor-1 induces hyperproliferation of PKD1 cystic cells via a Ras/Raf dependent signalling pathway

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    Autosomal dominant polycystic kidney disease (ADPKD) largely results from mutations in the PKD1 gene leading to hyperproliferation of renal tubular epithelial cells and consequent cyst formation. Rodent models of PKD suggest that the multifunctional hormone insulin-like growth factor-1 (IGF-1) could play a pathogenic role in renal cyst formation. In order to test this possibility, conditionally immortalized renal epithelial cells were prepared from normal individuals and from ADPKD patients with known germline mutations in PKD1. All patient cell lines had a decreased or absence of polycystin-1 but not polycystin-2. These cells had an increased sensitivity to IGF-1 and to cyclic AMP, which required phosphatidylinositol-3 (PI3)-kinase and the mitogen-activated protein kinase, extracellular signal-regulated protein kinase (ERK) for enhanced growth. Inhibition of Ras or Raf abolished the stimulated cell proliferation. Our results suggest that haploinsufficiency of polycystin-1 lowers the activation threshold of the Ras/Raf signalling system leading to growth factor-induced hyperproliferation. Inhibition of Ras or Raf activity may be a therapeutic option for decreasing tubular cell proliferation in ADPKD

    Phosphorylation and SCF-mediated degradation regulate CREB-H transcription of metabolic targets.

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    CREB‑H, an endoplasmic reticulum–anchored transcription factor, plays a key role in regulating secretion and in metabolic and inflammatory pathways, but how its activity is modulated remains unclear. We examined processing of the nuclear active form and identified a motif around S87–S90 with homology to DSG-type phosphodegrons. We show that this region is subject to multiple phosphorylations, which regulate CREB-H stability by targeting it to the SCF(Fbw1a) E3 ubiquitin ligase. Data from phosphatase treatment, use of phosophospecific antibody, and substitution of serine residues demonstrate phosphorylation of candidate serines in the region, with the core S87/S90 motif representing a critical determinant promoting proteasome-mediated degradation. Candidate kinases CKII and GSK-3b phosphorylate CREB-H in vitro with specificities for different serines. Prior phosphorylation with GSK-3 at one or more of the adjacent serines substantially increases S87/S90-dependent phosphorylation by CKII. In vivo expression of a dominant-negative Cul1 enhances steady-state levels of CREB‑H, an effect augmented by Fbw1a. CREB-H directly interacts with Fbw1a in a phosphorylation-dependent manner. Finally, mutations within the phosphodegron, when incorporated into the full-length protein, result in increased levels of constitutively cleaved nuclear protein and increased transcription and secretion of a key endogenous target gene, apolipoprotein A IV

    Effectiveness of enhanced diabetes care to patients of South Asian ethnicity : the United Kingdom Asian Diabetes Study (UKADS) : a cluster randomised controlled trial

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    Background: Delivering high quality and evidence based healthcare to deprived sectors of the community is a major goal for society. We investigated the effectiveness of a culturally sensitive enhanced care package in UK general practice in improving cardiovascular risk factors in South Asian patients with type 2 diabetes. Methods: 21 inner city practices were randomised to intervention (enhanced practice nurse time, link worker and diabetes specialist nurse support) (n=868) or control (standard care) (n=618) groups. Prescribing algorithms with clearly defined targets were provided for all practices. Main outcome measures comprised changes in blood pressure, total cholesterol and glycaemic control (HbA1c) after 2 years. Findings: At baseline, groups were similar with respect to age, sex and cardiovascular risk factors. Comparing treatment groups, after adjustment for confounders, and clustering, differences in diastolic blood pressure (1.91mmHg, P=0.0001) and mean arterial pressure (1.36mmHg, P=0.0180) were significant. There were no significant differences between groups for total cholesterol or HbA1c. Economic analysis indicates the nurse-led intervention was not cost-effective. Across the whole study population systolic blood pressure, diastolic blood pressure and cholesterol decreased significantly by 4.9mmHg, 3.8mmHg and 0.45mmol/L respectively, but there was no change in HbA1c. Interpretation: Additional, although limited, benefits were observed from our culturally enhanced care package over and above the secular changes achieved in the UK in recent years. Stricter targets in general practice and further measures to motivate patients are needed to maximise healthcare outcomes in South Asian patients with diabetes

    Biodegradation of wool by bacteria and fungi and enhancement of wool quality by biosurfactant washing

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    Biodegradation of Ryeland and Shetland wool by Bacillus subtilis W3 and Streptomyces albidoflavus were investigated. The effect of treating raw wool with Rhamnolipid was also studied. It is shown that the wool surface morphology is improved with effective displacement of surface contaminants revealing a smooth outer cuticle layer after just 2 days. These results have important practical implications for the establishment of a quick and easy biodegradable process for wool scouring finishing in textile industry or for the pre-treatment of keratinous waste materials before degradation by bacteria or fungi. This methodology provides an environmentally friendly alternative to conventional chemical pre-treatments

    Dispersion insensitive, high-speed optical clock recovery based on a mode-locked laser diode

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    An investigation into the effects of varying levels of chromatic dispersion on a mode- locked laser diode optical clock recovery process is presented. Results demonstrate that this technique is invariant to input dispersion varying between +75 ps/nm

    Search Behaviour On Photo Sharing Platforms

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    The behaviour, goals, and intentions of users while searching for images in large scale online collections are not well understood, with image search log analysis providing limited insights, in part because they tend only to have access to user search and result click information. In this paper we study user search behaviour in a large photo-sharing platform, analyzing all user actions during search sessions (i.e. including post result-click pageviews). Search accounts for a significant part of user interactions with such platforms, and we show differences between the queries issued on such platforms and those on general image search. We show that search behaviour is influenced by the query type, and also depends on the user. Finally, we analyse how users behave when they reformulate their queries, and develop URL class prediction models for image search, showing that query-specific models significantly outperform query-agnostic models. The insights provided in this paper are intended as a launching point for the design of better interfaces and ranking models for image search. © 2013 IEEE.published_or_final_versio

    AEGIS:Agent oriEnted orGanISations

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    Today's enterprises are faced with highly dynamic, sometimes even hostile environments. This paper dicovers that the two most prominent organizational strategies addressing these challenges, namely that of widespread decentralization and of business process orientation, are inherently conflicting. We argue that cooperative knowledge processing technology can contribute to dissolve this conflict. For this purpose, we introduce the reader into the field of Distributed Artificial Intelligence. On that basis we then develop the concept of Agent oriEnted orGanISations (AEGIS), in order to support the flexible modeling and management of business processes in decentralized organizational settings. Applying to methods of Distributed Planning a set of process modeling and process interaction operators is defined. These operators also permit to automatically create and customize computerized configurations of business processes. The concepts are presented in the context of an application in private banking, namely that of a Credit Advisory System.<br
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