3,780 research outputs found

    A Limited area model intercomparison on the "Montserrat-2000" flash-flood event using statistical and deterministic methods

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    In the scope of the European project Hydroptimet, INTERREG IIIB-MEDOCC programme, limited area model (LAM) intercomparison of intense events that produced many damages to people and territory is performed. As the comparison is limited to single case studies, the work is not meant to provide a measure of the different models' skill, but to identify the key model factors useful to give a good forecast on such a kind of meteorological phenomena. This work focuses on the Spanish flash-flood event, also known as "Montserrat-2000" event. The study is performed using forecast data from seven operational LAMs, placed at partners' disposal via the Hydroptimet ftp site, and observed data from Catalonia rain gauge network. To improve the event analysis, satellite rainfall estimates have been also considered. For statistical evaluation of quantitative precipitation forecasts (QPFs), several non-parametric skill scores based on contingency tables have been used. Furthermore, for each model run it has been possible to identify Catalonia regions affected by misses and false alarms using contingency table elements. Moreover, the standard "eyeball" analysis of forecast and observed precipitation fields has been supported by the use of a state-of-the-art diagnostic method, the contiguous rain area (CRA) analysis. This method allows to quantify the spatial shift forecast error and to identify the error sources that affected each model forecasts. High-resolution modelling and domain size seem to have a key role for providing a skillful forecast. Further work is needed to support this statement, including verification using a wider observational data set

    Electrocardiographic features, mapping and ablation of idiopathic outflow tract ventricular arrhythmias

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    Idiopathic outflow tract ventricular arrhythmias are ventricular tachycardias or premature ventricular contractions presumably not related to myocardial scar or disorders of ion channels. These arrhythmias have focal origin and display characteristic electrocardiographic features. The purpose of this article is to review the state of the art of diagnosis and treatment of idiopathic outflow tract ventricular arrhythmias

    The 8 and 9 September 2002 flash flood event in France: a model intercomparison

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    Within the framework of the European Interreg IIIb Medocc program, the HYDROPTIMET project aims at the optimization of the hydrometeorological forecasting tools in the context of intense precipitation within complex topography. Therefore, some meteorological forecast models and hydrological models were tested on four Mediterranean flash-flood events. One of them occured in France where the South-eastern ridge of the French “Massif Central”, the Gard region, experienced a devastating flood on 8 and 9 September 2002. 24 people were killed during this event and the economic damage was estimated at 1.2 billion euros. To built the next generation of the hydrometeorological forecasting chain that will be able to capture such localized and fast events and the resulting discharges, the forecasted rain fields might be improved to be relevant for hydrological purposes. In such context, this paper presents the results of the evaluation methodology proposed by Yates et al. (2005) that highlights the relevant hydrological scales of a simulated rain field. Simulated rain fields of 7 meteorological model runs concerning with the French event are therefore evaluated for different accumulation times. The dynamics of these models are either based on non-hydrostatic or hydrostatic equation systems. Moreover, these models were run under different configurations (resolution, initial conditions). The classical score analysis and the areal evaluation of the simulated rain fields are then performed in order to put forward the main simulation characteristics that improve the quantitative precipitation forecast. The conclusions draw some recommendations on the value of the quantitative precipitation forecasts and way to use it for quantitative discharge forecasts within mountainous areas

    Chemotherapy-resistant osteosarcoma is highly susceptible to IL-15-activated allogeneic and autologous NK cells

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    High-grade osteosarcoma occurs predominantly in adolescents and young adults and has an overall survival rate of about 60%, despite chemotherapy and surgery. Therefore, novel treatment modalities are needed to prevent or treat recurrent disease. Natural killer (NK) cells are lymphocytes with cytotoxic activity toward virus-infected or malignant cells. We explored the feasibility of autologous and allogeneic NK cell–mediated therapies for chemotherapy-resistant and chemotherapy-sensitive high-grade osteosarcoma. The expression by osteosarcoma cells of ligands for activating NK cell receptors was studied in vitro and in vivo, and their contribution to NK cell–mediated cytolysis was studied by specific antibody blockade. Chromium release cytotoxicity assays revealed chemotherapy-sensitive and chemotherapy-resistant osteosarcoma cell lines and osteosarcoma primary cultures to be sensitive to NK cell–mediated cytolysis. Cytolytic activity was strongly enhanced by IL-15 activation and was dependent on DNAM-1 and NKG2D pathways. Autologous and allogeneic activated NK cells lysed osteosarcoma primary cultures equally well. Osteosarcoma patient–derived NK cells were functionally and phenotypically unimpaired. In conclusion, osteosarcoma cells, including chemoresistant variants, are highly susceptible to lysis by IL-15-induced NK cells from both allogeneic and autologous origin. Our data support the exploitation of NK cells or NK cell–activating agents in patients with high-grade osteosarcoma

    Structure-Based Screen Identifies a Potent Small Molecule Inhibitor of Stat5a/b with Therapeutic Potential for Prostate Cancer and Chronic Myeloid Leukemia.

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    Bypassing tyrosine kinases responsible for Stat5a/b phosphorylation would be advantageous for therapy development for Stat5a/b-regulated cancers. Here, we sought to identify small molecule inhibitors of Stat5a/b for lead optimization and therapy development for prostate cancer and Bcr-Abl-driven leukemias. In silico screening of chemical structure databases combined with medicinal chemistry was used for identification of a panel of small molecule inhibitors to block SH2 domain-mediated docking of Stat5a/b to the receptor-kinase complex and subsequent phosphorylation and dimerization. We tested the efficacy of the lead compound IST5-002 in experimental models and patient samples of two known Stat5a/b-driven cancers, prostate cancer and chronic myeloid leukemia (CML). The lead compound inhibitor of Stat5-002 (IST5-002) prevented both Jak2 and Bcr-Abl-mediated phosphorylation and dimerization of Stat5a/b, and selectively inhibited transcriptional activity of Stat5a (IC50 = 1.5μmol/L) and Stat5b (IC50 = 3.5 μmol/L). IST5-002 suppressed nuclear translocation of Stat5a/b, binding to DNA and Stat5a/b target gene expression. IST5-002 induced extensive apoptosis of prostate cancer cells, impaired growth of prostate cancer xenograft tumors, and induced cell death in patient-derived prostate cancers when tested ex vivo in explant organ cultures. Importantly, IST5-002 induced robust apoptotic death not only of imatinib-sensitive but also of imatinib-resistant CML cell lines and primary CML cells from patients. IST5-002 provides a lead structure for further chemical modifications for clinical development for Stat5a/b-driven solid tumors and hematologic malignancies

    Economic predictors of differences in interview faking between countries : economic inequality matters, not the state of economy

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    Many companies recruit employees from different parts of the globe, and faking behavior by potential employees is a ubiquitous phenomenon. It seems that applicants from some countries are more prone to faking compared to others, but the reasons for these differences are largely unexplored. This study relates country-level economic variables to faking behavior in hiring processes. In a cross-national study across 20 countries, participants (N = 3839) reported their faking behavior in their last job interview. This study used the random response technique (RRT) to ensure participants anonymity and to foster honest answers regarding faking behavior. Results indicate that general economic indicators (gross domestic product per capita [GDP] and unemployment rate) show negligible correlations with faking across the countries, whereas economic inequality is positively related to the extent of applicant faking to a substantial extent. These findings imply that people are sensitive to inequality within countries and that inequality relates to faking, because inequality might actuate other psychological processes (e.g., envy) which in turn increase the probability for unethical behavior in many forms

    Performance of the CMS Cathode Strip Chambers with Cosmic Rays

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    The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns
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