Le mélanome et les polymorphismes associés au dysfonctionnement du système immunitaire

La recherche biomédicale profite de plus en plus au développement des techniques de séquençage et d'analyse de l'ADN. Les coûts du séquençage ont drastiquement baissés au cours de ces dernières années et les genomes-wides associations studies (GWAS) ont révolutionné l'approche de la recherche génétique en mettant en évidence associations et single-nucleotide-polymorphisms (SNPs) qui pourraient être importantes pour la susceptibilité à développer des maladies dites communes. La majorité des cancers appartiennent à cette définition de maladie commune, ils sont généralement causés par une accumulation de lésions/mutations de l'ADN aboutissant à une perte de contrôle de la prolifération et du cycle cellulaire. Ces mutations peuvent être héréditaires, acquises ou une combinaison des deux. Dans la plupart des cancers communs (cancers qui n'ont pas une hérédité familiale importante) les mutations de l'ADN sont souvent amenées par des facteurs tels que inflammation chronique, tabac, virus, exposition aux radiations, aux agents chimiques. Ceci est le cas pour le mélanome également, un cancer de la peau qui est corrélé à l'exposition des rayons UV solaires ou artificiels. Une hypothèse largement acceptée aujourd'hui est que les tumeurs, à travers leur accumulation progressive de mutations somatiques et d'anomalies chromosomiques, finissent par échapper au contrôle exercé par le système immunitaire. Il est par conséquence imaginable que des polymorphismes naturels puissent renforcer ou affaiblir la capacité du système immunitaire à freiner voir arrêter la progression tumorale

Statistical mechanics of Beltrami flows in axisymmetric geometry: Equilibria and bifurcations

We characterize the thermodynamical equilibrium states of axisymmetric Euler-Beltrami flows. They have the form of coherent structures presenting one or several cells. We find the relevant control parameters and derive the corresponding equations of state. We prove the coexistence of several equilibrium states for a given value of the control parameter like in 2D turbulence [Chavanis and Sommeria, J. Fluid Mech. 314, 267 (1996)]. We explore the stability of these equilibrium states and show that all states are saddle points of entropy and can, in principle, be destabilized by a perturbation with a larger wavenumber, resulting in a structure at the smallest available scale. This mechanism is therefore reminiscent of the 3D Richardson energy cascade towards smaller and smaller scales. Therefore, our system is truly intermediate between 2D turbulence (coherent structures) and 3D turbulence (energy cascade). We further explore numerically the robustness of the equilibrium states with respect to random perturbations using a relaxation algorithm in both canonical and microcanonical ensembles. We show that saddle points of entropy can be very robust and therefore play a role in the dynamics. We evidence differences in the robustness of the solutions in the canonical and microcanonical ensembles. A scenario of bifurcation between two different equilibria (with one or two cells) is proposed and discussed in connection with a recent observation of a turbulent bifurcation in a von Karman experiment [Ravelet et al., Phys. Rev. Lett. 93, 164501 (2004)].Comment: 25 pages; 16 figure

A novel approach to flood risk assessment: the Exposure-Vulnerability matrices

The classical approach to flood defence, focused on reducing the probability of flooding through hard defences, has been gradually substituted by flood risk management approach, which accepts the idea of coping with floods, and aims at reducing both probability and the consequences of flooding. In this view, the concept of vulnerability becomes central, such as the (non-structural) measures for its increment. However, the evaluations for the effectiveness and methods of non-structural measure and the vulnerability are less studied, compared to the structural solutions. In this paper, we adopted the Longano catchment in Sicily, Italy, as the case study. The methodology developed in the work enabled a qualitative evaluation of the consequences of floods, based on a crisscross analysis of vulnerability curves and classes of exposure for assets at risk. A GIS-based tool was used to evaluate each element at risk inside an Exposure-Vulnerability matrix. The construction of an E-V matrix allowed a better understanding of the actual situation within a catchment and the effectiveness of non-structural measures for a site. Referring directly to vulnerability can also estimate the possible consequences of an event even in those catchments where the damage data are absent. The instrument proposed can be useful for authorities responsible for development and periodical review of adaptive flood risk management plans

Flood risk assessment using a novel exposure-vulnerability matrices approach

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What if quality of damage data is poor: an exposure-vulnerability approach for flood vulnerability assessment

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Simultaneous 3D measurement of the translation and rotation of finite size particles and the flow field in a fully developed turbulent water flow

We report a novel experimental technique that measures simultaneously in three dimensions the trajectories, the translation, and the rotation of finite size inertial particles together with the turbulent flow. The flow field is analyzed by tracking the temporal evolution of small fluorescent tracer particles. The inertial particles consist of a super-absorbent polymer that renders them index and density matched with water and thus invisible. The particles are marked by inserting at various locations tracer particles into the polymer. Translation and rotation, as well as the flow field around the particle are recovered dynamically from the analysis of the marker and tracer particle trajectories. We apply this technique to study the dynamics of inertial particles much larger in size (Rp/{\eta} \approx 100) than the Kolmogorov length scale {\eta} in a von K\'arm\'an swirling water flow (R{\lambda} \approx 400). We show, using the mixed (particle/fluid) Eulerian second order velocity structure function, that the interaction zone between the particle and the flow develops in a spherical shell of width 2Rp around the particle of radius Rp. This we interpret as an indication of a wake induced by the particle. This measurement technique has many additional advantages that will make it useful to address other problems such as particle collisions, dynamics of non-spherical solid objects, or even of wet granular matter.Comment: 18 pages, 7 figures, submitted to "Measurement Science and Technology" special issue on "Advances in 3D velocimetry

194preal life utilization of genomic testing for invasive breast cancer patients in italy and france reduces chemotherapy recommendations

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Advanced pharmacological therapies for neurofibromatosis type 1-related tumors

Neurofibromatosis Type 1 (NF1) is an autosomal dominant tumor-predisposition disorder that is caused by a heterozygous loss of function variant in the NF1 gene, which encodes a protein called neurofi-bromin. The absence of neurofibromin causes increased activity in the Rat sarcoma protein (RAS) signalling pathway, which results in an increased growth and cell proliferation. As a result, both oncological and non-oncological comorbidities contribute to a high morbidity and mortality in these patients. Optic pathways gliomas, plexiform neurofibromas and malignant peripheral nerve sheath tumor (MPNST) are the most fre-quent NF1-associated tumors. The treatment of these complications is often challenging, since surgery may not be feasible due to the location, size, and infiltrative nature of these tumors, and standard chemotherapy or radiotherapy are burdened by significant toxicity and risk for secondary malignancies. For these reasons, following the novel discoveries of the pathophysiological mechanisms that lead to cell proliferation and tumori-genesis in NF1 patients, emerging drugs targeting specific signalling pathways (i.e. the MEK/ERK cascade), have been developed with promising results. (www.actabiomedica.it)