180 research outputs found

    An energy-consistent depth-averaged Euler system: derivation and properties

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    In this paper, we present an original derivation process of a non-hydrostatic shallow water-type model which aims at approximating the incompressible Euler and Navier-Stokes systems with free surface. The closure relations are obtained by aminimal energy constraint instead of an asymptotic expansion. The model slightly differs from thewell-known Green-Naghdi model and is confronted with stationary andanalytical solutions of the Euler system corresponding to rotationalflows. At the end of the paper, we givetime-dependent analytical solutions for the Euler system that are alsoanalytical solutions for the proposed model but that are not solutionsof the Green-Naghdi model. We also give and compare analytical solutions of thetwo non-hydrostatic shallow water models

    Les flux économiques de la paix et leur impact sur les connexions régionales de l'Égypte

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    Le système régional du Proche-Orient, défini par les champs de force des relations internationales, est en proie à de profondes mutations géopolitiques : des avancées significatives dans le règlement d'un conflit vieux d'un demi-siècle vont faire l'objet de redistributions territoriales et modifier la carte politique de la région syro-palestinienne. Les répercussions de cette nouvelle configuration, en particulier la fin de l'état de belligérance et l'intégration politique de deux entités éta..

    Sous les mines, la plage

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    Le premier regard porté sur le territoire de l'Égypte amène tout naturellement à focaliser son attention sur la répartition extraordinaire de la population, sa concentration sur un axe fluvial et ses ramifications. Fortes densités, structure linéaire à petite échelle, l'espace nilotique renvoie à un écoumène longtemps soumis à des contraintes naturelles prégnantes. Source de vie, la vallée est aussi un carcan dont les extensions ne font qu'agrandir un territoire intrinsèquement tourné vers le..

    Estimating nitrate and pesticide transfer mode within the unsaturated zone of a fluvioglacial aquifer and its implication on spatial and temporal concentration variability

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    International audienceThe Meyzieu fluvioglacial aquifer of 113 km 2 located at the eastern part of Lyon is intensively exploited and subject to multiple pressures (urban, industrial, agriculture). Nitrate concentrations are quite high while pesticides contamination is low considering the past and today's pressure. A project was initiated in 2011 with the objective of determining the role of the unsaturated zone in the transfer of NO 3 and pesticides from soil to groundwater. Monthly monitoring of major elements, some pesticides, and stable water isotopes is carried out at three sampling points located along the flow lines. Additional information such as hydrogeological functioning, pressure inventory was gathered and additional data from three water sampling campaigns was collected. The temporal variation of NO 3 , metolachlor and metabolites and atrazine and metabolites is quite different at the three monitoring points. At the sampling point located upstream, where the unsaturated zone has a thickness around 40m, the nitrate concentrations are comprised between 20 and 40 mg.l-1 from 2004 to mid-2013. From mid-2013 nitrate concentrations are increasing regularly and are now reaching 70 mg.l-1. This point presents the highest level in atrazine metabolites (DEA) of the area but with concentrations lower than 0.05 µg.l-1 and very low detection of metolachlor or its metabolites. In the centre of the basin, where agriculture pressure is the highest and unsaturated zone of up to 30m in depth, nitrate concentrations are above 50 mg.l-1 with low seasonal variations. Metolachlor is lower than 0.03 µg.l-1 but values of 0,39 µg.l-1 max. of ESA metolachlor (MESA) were reached. Downstream, just before the discharge area, the sampling point shows the lowest and more stable nitrate concentrations (around 40 mg.l-1). The water level in this sector is at less than 20 m deep. Metolachlor have been detected only once while MESA is nearly always detected and can reach 0.24 µg.l-1

    Specificity determinants for the two tRNA substrates of the cyclodipeptide synthase AlbC from Streptomyces noursei

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    International audienceCyclodipeptide synthases (CDPSs) use two aminoacyl-tRNA substrates in a sequential ping-pong mechanism to form a cyclodipeptide. The crystal structures of three CDPSs have been determined and all show a Rossmann-fold domain similar to the catalytic domain of class-I aminoacyl-tRNA synthetases (aaRSs). Structural features and mutational analyses however suggest that CDPSs and aaRSs interact differently with their tRNA substrates. We used AlbC from Streptomyces noursei that mainly produces cyclo(l-Phe-l-Leu) to investigate the interaction of a CDPS with its substrates. We demonstrate that Phe-tRNA Phe is the first substrate accommodated by AlbC. Its binding to AlbC is dependent on basic residues located in the helix ␣4 that form a basic patch at the surface of the protein. AlbC does not use all of the Leu-tRNA Leu isoacceptors as a second substrate. We show that the G 1-C 72 pair of the acceptor stem is essential for the recognition of the second substrate. Substitution of D163 located in the loop ␣6–␣7 or D205 located in the loop ␤6–␣8 affected Leu-tRNA Leu isoacceptors specificity, suggesting the involvement of these residues in the binding of the second substrate. This is the first demonstration that the two substrates of CDPSs are accommodated in different binding sites

    Comparison of climate change impacts on the recharge of two karst systems computing different modelling approaches

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    International audienceKarst systems constitute aquifers in which infiltration and groundwater flows are generally complex processes and are characterized by limited knowledge in terms of geometry and structure. Nonetheless, they often represent interesting groundwater resources, some of them being subjected to intensive exploitation and others non exploited due to their poor understanding. In the future, it is likely that climate change impact on water resources will increase the interest for such a kind of aquifers due to their strong infiltration and storage capacity, in a broad context of higher water scarcity.The Lez and the Lison karst systems in Southern and Eastern France, respectively, provide 2 examples of such systems of several km² under two contrasted climate conditions, the first one being heavily exploited. This study presents a comparative climate change assessment onboth karst systems. Nine climate scenarios corresponding to the Fourth assessment report of the IPCC (SRES A1B scenario), downscaled using weather-type methods by the CERFACS, have been applied to various recharge modelling approaches, as standard analytical solutions of recharge estimation and soil-water balance models. Results are compared and discussed in order to assess the influence on climate change impacts of i) the climate conditions(geographic location), ii) the groundwater exploitation and iii) the modelling approach

    FHR4-based immunoconjugates direct complement-dependent cytotoxicity and phagocytosis towards HER2-positive cancer cells

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    Directing selective complement activation towards tumour cells is an attractive strategy to promote their elimination. In the present work, we have generated heteromultimeric immunoconjugates that selectively activate the complement alternative pathway (AP) on tumour cells. We used the C4b-binding protein C-terminal-alpha-/beta-chain scaffold for multimerisation to generate heteromultimeric immunoconjugates displaying (a) a multivalent-positive regulator of the AP, the human factor H-related protein 4 (FHR4) with; (b) a multivalent targeting function directed against erbB2 (HER2); and (c) a monovalent enhanced GFP tracking function. Two distinct VHH targeting two different epitopes against HER2 and competing either with trastuzumab or with pertuzumab-recognising epitopes [VHH(T) or VHH(P)], respectively, were used as HER2 anchoring moieties. Optimised high-FHR4 valence heteromultimeric immunoconjugates [FHR4/VHH(T) or FHR4/VHH(P)] were selected by sequential cell cloning and a selective multistep His-Trap purification. Optimised FHR4-heteromultimeric immunoconjugates successfully overcame FH-mediated complement inhibition threshold, causing increased C3b deposition on SK-OV-3, BT474 and SK-BR3 tumour cells, and increased formation of lytic membrane attack complex densities and complement-dependent cytotoxicity (CDC). CDC varies according to the pattern expression and densities of membrane-anchored complement regulatory proteins on tumour cell surfaces. In addition, opsonised BT474 tumour cells were efficiently phagocytosed by macrophages through complement-dependent cell-mediated cytotoxicity. We showed that the degree of FHR4-multivalency within the multimeric immunoconjugates was the key element to efficiently compete and deregulate FH and FH-mediated convertase decay locally on tumour cell surface. FHR4 can thus represent a novel therapeutic molecule, when expressed as a multimeric entity and associated with an anchoring system, to locally shift the complement steady-state towards activation on tumour cell surface

    Governance traditions and narratives of public sector reform in contemporary France.

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    This article explores the basic traditions of governance in contemporary France and the narratives of public sector reform associated with them. It should be stressed right from the outset that this article does not aim to describe the set of public sector reforms that have been implemented in France in the last ten years or so. Instead, the aim is to demonstrate the similarities and differences between the narratives of the left and the right with regard to these reforms and to show how these narratives help to explain the types of reform that have been enacted. The basic argument is that there is a certain commonality to both the left and the right with regard to their narratives of public sector reform. At the same time, though, there are differences of emphasis both within each tradition and between the two main traditions themselves. Except where indicated, all translations are the author's own

    Imprint of Initial Education and Loss of Ly49C/I in Activated Natural Killer Cells of TAP1-KO and C57BL/6 Wildtype Mice

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    Natural killer (NK) cells are important effectors of the innate immune system and participate in the first line of defense against infections and tumors. Prior to being functional, these lymphocytes must be educated or licensed through interactions of their major histocompatibility complex class I molecules with self-specific inhibitory receptors that recognize them. In the absence of such contacts, caused by either the lack of expression of the inhibitory receptors or a very low level of major histocompatibility complex class I (MHC class I) proteins, NK cells are hypo-reactive at baseline ( ex vivo ). After stimulation (assessed through plate-bound antibodies against activating receptors or culture in the presence of cytokines such as interleukin (IL)-2 or IL-15) however, they can become cytotoxic and produce cytokines. This is particularly the case in transporter associated with antigen processing (TAP)-deficient mice, which we investigated in the present study. Transporter associated with antigen processing transports endogenous peptides from the cytosol to the endoplasmic reticulum, where they are loaded on nascent MHC class I molecules, which then become stable and expressed at the cell surface. Consequently, TAP-KO mice have very low levels of MHC class I expression. We present a study about phenotypic and functional aspects of NK cells in two mouse strains, C57BL/6 wildtype and TAP1-KO in spleen and lung. We observed that in both types of mice, on the same genetic background, the initial pattern of education, conferred to the cells via the inhibitory receptors Ly49C/I and NKG2A, was maintained even after a strong stimulation by the cytokines interleukin-2, interleukin-12, interleukin-15 and interleukin-18. Furthermore, the percentages of activated NK cells expressing Ly49C/I and Ly49I were strongly down-modulated under these conditions. We completed our investigations with phenotypic studies of NK cells from these mice
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