621 research outputs found

    Diffusion coefficient and shear viscosity of rigid water models

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    We report the diffusion coefficient and viscosity of popular rigid water models: Two non polarizable ones (SPC/E with 3 sites, and TIP4P/2005 with 4 sites) and a polarizable one (Dang-Chang, 4 sites). We exploit the dependence of the diffusion coefficient on the system size [Yeh and Hummer, J. Phys. Chem. B 108, 15873 (2004)] to obtain the size-independent value. This also provides an estimate of the viscosity of all water models, which we compare to the Green-Kubo result. In all cases, a good agreement is found. The TIP4P/2005 model is in better agreement with the experimental data for both diffusion and viscosity. The SPC/E and Dang-Chang water overestimate the diffusion coefficient and underestimate the viscosity.Comment: 10 pages, 2 figures. To be published in J. Phys.: Condens. Matte

    Revisiting G3BP1 as a RasGAP binding protein: sensitization of tumor cells to chemotherapy by the RasGAP 317-326 sequence does not involve G3BP1.

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    RasGAP is a multifunctional protein that controls Ras activity and that is found in chromosomal passenger complexes. It also negatively or positively regulates apoptosis depending on the extent of its cleavage by caspase-3. RasGAP has been reported to bind to G3BP1 (RasGAP SH3-domain-binding protein 1), a protein regulating mRNA stability and stress granule formation. The region of RasGAP (amino acids 317-326) thought to bind to G3BP1 corresponds exactly to the sequence within fragment N2, a caspase-3-generated fragment of RasGAP, that mediates sensitization of tumor cells to genotoxins. While assessing the contribution of G3BP1 in the anti-cancer function of a cell-permeable peptide containing the 317-326 sequence of RasGAP (TAT-RasGAP₃₁₇₋₃₂₆), we found that, in conditions where G3BP1 and RasGAP bind to known partners, no interaction between G3BP1 and RasGAP could be detected. TAT-RasGAP₃₁₇₋₃₂₆ did not modulate binding of G3BP1 to USP10, stress granule formation or c-myc mRNA levels. Finally, TAT-RasGAP₃₁₇₋₃₂₆ was able to sensitize G3BP1 knock-out cells to cisplatin-induced apoptosis. Collectively these results indicate that G3BP1 and its putative RasGAP binding region have no functional influence on each other. Importantly, our data provide arguments against G3BP1 being a genuine RasGAP-binding partner. Hence, G3BP1-mediated signaling may not involve RasGAP

    Le médicament générique au Maroc: le point de vue du consommateur

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    Introduction: Le mĂ©dicament gĂ©nĂ©rique est souvent une origine de prĂ©jugĂ©s nĂ©gatifs et de mĂ©fiance chez les professionnels de santĂ© et les patients. Ceci pourrait ĂȘtre dĂ» Ă  plusieurs facteurs entre autre le manque des connaissances du patient sur ces mĂ©dicaments. Le but de notre Ă©tude Ă©tait d'Ă©valuer l'information du consommateur sur les mĂ©dicaments gĂ©nĂ©riques et apprĂ©cier leur utilisation de ces mĂ©dicaments. MĂ©thodes: Il s'agit d'une Ă©tude transversale rĂ©alisĂ©e de Janvier Ă  Mars 2010 auprĂšs de 251 sujets. Un questionnaire comprenant dix questions fermĂ©es a Ă©tĂ© utilisĂ©. Les questions concernaient l'Ă©valuation des connaissances sur les mĂ©dicaments gĂ©nĂ©riques, les sources d'information, le degrĂ© de confiance et d'information des patients sur ces mĂ©dicaments. Une analyse descriptive simple des diffĂ©rentes variables a Ă©tĂ© rĂ©alisĂ©e. RĂ©sultats: Dans notre Ă©tude, 126 sujets (50,2%) ont rĂ©pondu connaĂźtre les mĂ©dicaments gĂ©nĂ©riques. Parmi eux, 52,3% les utilisaient et 67,4% estimaient qu'ils Ă©taient insuffisamment informĂ©s sur ces mĂ©dicaments. Les cadres supĂ©rieurs et les Ă©tudiants ont reprĂ©sentĂ© la catĂ©gorie qui utilisait le plus les mĂ©dicaments gĂ©nĂ©riques (respectivement dans 40,9% et 25,7%) et qui Ă©tait la mieux informĂ©e (respectivement dans 61,9% et 23,81%). Le faible coĂ»t a Ă©tĂ© la principale motivation d'utilisation du mĂ©dicament gĂ©nĂ©rique (93,9%). Les mĂ©dias ont reprĂ©sentĂ© la premiĂšre source d'information (59,5%). AprĂšs sensibilisation, 88,8% des sujets qui ne connaissaient pas le mĂ©dicament gĂ©nĂ©rique ont Ă©tĂ© favorable Ă  son utilisation.Conclusion: Une promotion efficace par une politique d'information soutenue auprĂšs des consommateurs et par des mesures incitatrices Ă  la prescription et Ă  la dĂ©livrance du gĂ©nĂ©rique par les mĂ©decins et les pharmaciens, pourront amĂ©liorer l'utilisation de ces mĂ©dicaments dans notre pays.Key words: MĂ©dicament gĂ©nĂ©rique, consommateur, perception, Maro

    Remission of hypertension after treatment of giant simple renal cyst: a case report

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    Renal cysts are common in old patients, and usually remain untreated. Giant renal cysts measuring more than 15 cm in greatest diameter are uncommon and the association with hypertension is very rare. We present a case of a 25-year-old woman with a giant right renal cyst associated with hypertension that was treated by laparoscopic excision, followed by resolution hypertension

    Monitoring and Evaluating Fiscal Solvency in times of Crisis: Framework for Enhancing Revenue Generating Capacity in Nigeria

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    This study contributes to the existing literature on the ​fundamentals of public finance management efforts by sub-national governments in developing economies. The paper's primary contribution is finding that choice of public policy intervention by a central government requires establishing frameworks that first monitors individual efforts of sub-national government before approval of such interventions are made. It also suggests the application of certain methodologies for performance measurement in public finance section of the government

    Metastatic collecting duct carcinoma of the kidney treated with sunitinib

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    Collecting duct carcinoma (CDC) of the kidney is a rare and aggressive malignant tumor arising from the distal collecting tubules which has been shown to have a poor response to several kinds of systemic therapy. We present a case of metastatic CDC that responded favorably to a multiple tyrosine kinase inhibitor, sunitinib, achieving a partial response in both lung and skeletal metastases. To our knowledge, this is the first report showing therapeutic activity of sunitinib against CDC. Considering these findings, it would be worthwhile prospectively investigating the role of multiple tyrosine kinase inhibitors, particularly sunitinib, in the management of metastatic CDC

    Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFÎČ signalling and EMT

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    Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFß-dependent biological outputs such as epithelial–mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isoforms (N-terminal, WWP2-N; C-terminal WWP2-C), as novel Smad-binding partners. We show that WWP2-FL interacts exclusively with Smad2, Smad3 and Smad7 in the TGFß pathway. Interestingly, the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7. In addition, WWP2-FL and WWP2-C have a preference for Smad7 based on protein turnover and ubiquitination studies. Unexpectedly, we also find that WWP2-N, which lacks the HECT ubiquitin ligase domain, can also interact with WWP2-FL in a TGFß-regulated manner and activate endogenous WWP2 ubiquitin ligase activity causing degradation of unstimulated Smad2 and Smad3. Consistent with our protein interaction data, overexpression and knockdown approaches reveal that WWP2 isoforms differentially modulate TGFß-dependent transcription and EMT. Finally, we show that selective disruption of WWP2 interactions with inhibitory Smad7 can stabilise Smad7 protein levels and prevent TGFß-induced EMT. Collectively, our data suggest that WWP2-N can stimulate WWP2-FL leading to increased activity against unstimulated Smad2 and Smad3, and that Smad7 is a preferred substrate for WWP2-FL and WWP2-C following prolonged TGFß stimulation. Significantly, this is the first report of an interdependent biological role for distinct HECT E3 ubiquitin ligase isoforms, and highlights an entirely novel regulatory paradigm that selectively limits the level of inhibitory and activating Smads

    Effect of Wood Fillers on the Viscoelastic and Thermophysical Properties of HDPE-Wood Composite

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    Wood polymer composites (WPC) have well proven their applicability in several fields of the plasturgy sector, due to their aesthetics and low maintenance costs. However, for plasturgy applications, the characterization of viscoelastic behavior and thermomechanical and thermophysical properties of WPC with the temperature and wood filler contents is essential. Therefore, the processability of polymer composites made up with different percentage of wood particles needs a better understanding of materials behaviors in accordance with temperature and wood particles contents. To this end, a numerical analysis of the viscoelastic, mechanical, and thermophysical properties of composite composed of high density polyethylene (HDPE) reinforced with soft wood particles is evaluated
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