1,179 research outputs found
Pyk2 and Cyr61 at the cross-road of cAMP-dependent signalling in invasiveness and neuroendocrine differentiation of prostate cancer
The european flood alert system EFAS – Part 2: Statistical skill assessment of probabilistic and deterministic operational forecasts
Since 2005 the European Flood Alert System (EFAS) has been producing probabilistic hydrological forecasts in pre-operational mode at the Joint Research Centre (JRC) of the European Commission. EFAS aims at increasing preparedness for floods in trans-national European river basins by providing medium-range deterministic and probabilistic flood forecasting information, from 3 to 10 days in advance, to national hydro-meteorological services. <br><br> This paper is Part 2 of a study presenting the development and skill assessment of EFAS. In Part 1, the scientific approach adopted in the development of the system has been presented, as well as its basic principles and forecast products. In the present article, two years of existing operational EFAS forecasts are statistically assessed and the skill of EFAS forecasts is analysed with several skill scores. The analysis is based on the comparison of threshold exceedances between proxy-observed and forecasted discharges. Skill is assessed both with and without taking into account the persistence of the forecasted signal during consecutive forecasts. <br><br> Skill assessment approaches are mostly adopted from meteorology and the analysis also compares probabilistic and deterministic aspects of EFAS. Furthermore, the utility of different skill scores is discussed and their strengths and shortcomings illustrated. The analysis shows the benefit of incorporating past forecasts in the probability analysis, for medium-range forecasts, which effectively increases the skill of the forecasts
The secondary KIT mutation p.Ala510Val in a cutaneous mast cell tumour carrying the activating mutation p.Asn508Ile confers resistance to masitinib in dogs
Background: Gain-of-function mutations in KIT are driver events of oncogenesis in mast cell tumours (MCTs) affecting companion animals. Somatic mutations of KIT determine the constitutive activation of the tyrosine kinase receptor leading to a worse prognosis and a shorter survival time than MCTs harbouring wild-type KIT. However, canine MCTs carrying KIT somatic mutations generally respond well to tyrosine kinase inhibitors; hence their presence represents a predictor of treatment effectiveness, and its detection allows implementing a stratified medical approach. Despite this, veterinary oncologists experience treatment failures, even with targeted therapies whose cause cannot be elucidated. The first case of an MCT-affected dog caused by a secondary mutation in the tyrosine kinase domain responsible for resistance has recently been reported. The knowledge of this and all the other mutations responsible for resistance would allow the effective bedside implementation of a deeply stratified and more effective medical approach. Case presentation: The second case of a canine MCT carrying a different resistance mutation is herein described. The case was characterised by aggressive behaviour and early metastasis unresponsive to both vinblastine- and masitinib-based treatments. Molecular profiling of the tumoural masses revealed two different mutations; other than the already known activating mutation p.Asn508Ile in KIT exon 9, which is tyrosine kinase inhibitor-sensitive, a nearly adjacent secondary missense mutation, p.Ala510Val, which had never before been described, was detected. In vitro transfection experiments showed that the secondary mutation did not cause the constitutive activation by itself but played a role in conferring resistance to masitinib. Conclusions: This study highlighted the importance of the accurate molecular profiling of an MCT in order to improve understanding of the molecular mechanism underlying tumourigenesis and reveal chemoresistance in MCTs for more effective therapies. The detection of the somatic mutations responsible for resistance should be included in the molecular screening of MCTs, and a systematic analysis of all the cases characterised by unexpected refractoriness to therapies should be investigated in depth at both the genetic and the phenotypic level
Deux cas d'infection humaine accidentelle par Plasmodium cynomolgi bastianellii : étude clinique et sérologique
Biomonitoring of metals in children living in an urban area and close to waste incinerators
The impact of waste incinerators is usually examined by measuring environmental pollutants. Biomonitoring has been limited, until now, to few metals and to adults. We explored accumulation of a comprehensive panel of metals in children free-living in an urban area hosting two waste incinerators. Children were divided by georeferentiation in exposed and control groups, and toenail concentrations of 23 metals were thereafter assessed. The percentage of children having toenail metal concentrations above the limit of detection was higher in exposed children than in controls for Al, Ba, Mn, Cu, and V. Exposed children had higher absolute concentrations of Ba, Mn, Cu, and V, as compared with those living in the reference area. The Tobit regression identified living in the exposed area as a significant predictor of Ba, Ni, Cu, Mn, and V concentrations, after adjusting for covariates. The concentrations of Ba, Mn, Ni, and Cu correlated with each other, suggesting a possible common source of emission. Exposure to emissions derived from waste incinerators in an urban setting can lead to body accumulation of specific metals in children. Toenail metal concentration should be considered a noninvasive and adequate biomonitoring tool and an early warning indicator which should integrate the environmental monitoring of pollutants
Nonlinear Gamow vectors in nonlocal optical propagation
Shock waves dominate in a wide variety of fields in physics dealing with nonlinear phenomena, nevertheless the description of their evolution is not resolved for the entire dynamics. Here we propose an analytical method based on Gamow vectors, which belong to irreversible quantum mechanics. We theoretically and experimentally show the appearance of these decaying states during shock evolution
allowing to describe the whole wave propagation. These results open new ways to the control of extreme nonlinear regimes such as supercontinuum generation or in the analogies of fundamental physical theories
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