388 research outputs found

    Les épouses des hommes politiques français sous la cinquième République

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    L'apparition d'un phénomène nouveau en France depuis quelques années: la médiatisation croissante des épouses d'hommes politiques et l'attention particulière dont elles sont désormais l'objet, nous a poussé à réfléchir sur le rôle des Premières Dames en France sous la cinquième République auprès de leur époux. Ce mémoire a pour but de comprendre en quoi ces femmes, épouses d'hommes politiques ayant une influence certaine sur leur mari, sont partie intégrante ou non de la stratégie de communication de ces derniers.\ud Nous avons étudié divers concepts essentiels à notre recherche comme celui de la représentation du politique, du pouvoir, d'image, de la communication politique ou encore du marketing politique. Ces concepts très lourds de sens sont les clés qui nous ont permis de comprendre comment est pensée aujourd'hui une stratégie de communication politique.\ud Pour répondre à notre question de recherche, nous avons donc mené une étude qualitative, en faisant dans un premier temps la mise en lumière sur les divergences et les convergences entre la vie de trois Premières Dames de France sous la cinquième république. Choisies dans une perspective historique, les biographies d'Yvonne de Gaulle, Bernadette Chirac et Cécilia Sarkozy, nous ont permis de proposer des pistes de réflexion sur leur réelle fonction de \ud « ces femmes de » d'hier à aujourd'hui. Dans un deuxième temps, nous avons analysé les éléments les plus récurrents et pertinents de l'histoire de ces femmes. Ces constats et l'entretien avec Armelle Le Bras-Chopard que nous avons effectué, nous ont permis de pouvoir constater l'impact des Premières Dames sur la communication de leur époux. ______________________________________________________________________________ MOTS-CLÉS DE L’AUTEUR : Premières Dames, Cinquième République, Stratégie de communication, Communication politique, Pouvoir, Image, Marketing politique

    Effect of doping on the modification of polycrystalline silicon by spontaneous reduction of diazonium salts

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    International audienceThe chemical modification of doped polycrystalline silicon materials (N+, N++ and P++) and silicon (1 0 0) and (1 1 1) used as references is investigated by spontaneous reduction of diazonium salts. The effectiveness of the grafting process on all polySi surfaces is shown by AFM and XPS analyses. The effect of substrate doping on the efficiency of the electrografting process is compared by using the thicknesses of the deposited organic films. For a better accuracy, two methods are used to estimate the thicknesses: XPS and the coupling of a O2 plasma etching with AFM measurement. Structural characteristics of the poly-Si films were investigated by Scanning Electron Microscopy and X-ray diffraction to find a correlation between the structure of the material and its reactivity. Different parameters that could have an impact on the efficiency of the grafting procedure are discussed. The observed differences between differently doped silicon surfaces is rather limited, this is in agreement with the radical character of the reacting species

    Mycophenolic Acid overcomes imatinib and nilotinib resistance of chronic myeloid leukemia cells by apoptosis or a senescent-like cell cycle arrest.

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    International audienceWe used K562 cells sensitive or generated resistant to imatinib or nilotinib to investigate their response to mycophenolic acid (MPA). MPA induced DNA damage leading to cell death with a minor contribution of apoptosis, as revealed by annexin V labeling (up to 25%). In contrast, cell cycle arrest and positive staining for senescence-associated β-galactosidase activity were detected for a large cell population (80%). MPA-induced cell death was potentialized by the inhibition of autophagy and this is associated to the upregulation of apoptosis. In contrast, senescence was neither decreased nor abrogated in autophagy deficient K562 cells. Primary CD34 cells from CML patients sensitive or resistant to imatinib or nilotinib respond to MPA although apoptosis is mainly detected. These results show that MPA is an interesting tool to overcome resistance in vitro and in vivo mainly in the evolved phase of the disease

    Identification of Cryptic MHC I–restricted Epitopes Encoded by HIV-1 Alternative Reading Frames

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    Human immunodeficiency virus (HIV) 1 major histocompatibility complex (MHC) I–restricted epitopes are widely believed to be derived from viral proteins encoded by primary open reading frames. However, the HIV-1 genome contains alternative reading frames (ARFs) potentially encoding small polypeptides. We have identified a panel of epitopes encoded by ARFs within the gag, pol, and env genes. The corresponding epitopic peptides were immunogenic in mice humanized for MHC-I molecules. In addition, cytotoxic T lymphocytes recognizing these epitopes were found in HIV-infected patients. These results reveal the existence of atypical mechanisms of HIV-1 epitope generation. They indicate that the repertoire of epitopes recognized by the cellular anti–HIV-1 immune response is broader than initially thought. This should be taken into account when designing vaccine strategies aimed at activating these responses

    A Cl- cotransporter selective for NH4+ over K+ in glial cells of bee retina

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    There appears to be a flux of ammonium (NH4+/NH3) from neurons to glial cells in most nervous tissues. In bee retinal glial cells, NH4+/NH3 uptake is at least partly by chloride-dependant transport of the ionic form NH4+. Transmembrane transport of NH4+ has been described previously on transporters on which NH4+ replaces K+, or, more rarely, Na+ or H+, but no transport system in animal cells has been shown to be selective for NH4+ over these other ions. To see if the NH4+-Cl− cotransporter on bee retinal glial cells is selective for NH4+ over K+ we measured ammonium-induced changes in intracellular pH (pHi) in isolated bundles of glial cells using a fluorescent indicator. These changes in pHi result from transmembrane fluxes not only of NH4+, but also of NH3. To estimate transmembrane fluxes of NH4+, it was necessary to measure several parameters. Intracellular pH buffering power was found to be 12 mM. Regulatory mechanisms tended to restore intracellular [H+] after its displacement with a time constant of 3 min. Membrane permeability to NH3 was 13 μm s−1. A numerical model was used to deduce the NH4+ flux through the transporter that would account for the pHi changes induced by a 30-s application of ammonium. This flux saturated with increasing [NH4+]o; the relation was fitted with a Michaelis-Menten equation with Km ≈ 7 mM. The inhibition of NH4+ flux by extracellular K+ appeared to be competitive, with an apparent Ki of ∼15 mM. A simple standard model of the transport process satisfactorily described the pHi changes caused by various experimental manipulations when the transporter bound NH4+ with greater affinity than K+. We conclude that this transporter is functionally selective for NH4+ over K+ and that the transporter molecule probably has a greater affinity for NH4+ than for K+

    SiGe derivatization by spontaneous reduction of aryl diazonium salts

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    International audienceGermanium semiconductors have interesting properties for FET-based biosensor applications since they possess high surface roughness allowing the immobilization of a high amount of receptors on a small surface area. Since SiGe combined low cost of Si and intrinsic properties of Ge with high mobility carriers, we focused the study on this particularly interesting material. The comparison of the efficiency of a functionalization process involving the spontaneous reduction of diazonium salts is studied on Si(1 0 0), SiGe and Ge semiconductors. XPS analysis of the functionalized surfaces reveals the presence of a covalent grafted layer on all the substrates that was confirmed by AFM. Interestingly, the modified Ge derivatives have still higher surface roughness after derivatization. To support the estimated thickness by XPS, a step measurement of the organic layers is done by AFM or by profilometer technique after a O2 plasma etching of the functionalized layer. This original method is well-adapted to measure the thickness of thin organic films on rough substrates such as germanium. The analyses show a higher chemical grafting on SiGe substrates compared with Si and Ge semiconductors

    DC Subsets Regulate Humoral Immune Responses by Supporting the Differentiation of Distinct Tfh Cells

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    To determine the contribution of skin DC subsets in the regulation of humoral immunity, we used a well-characterized antigen targeting system to limit antigen availability and presentation to certain skin-derived DC subsets. Here we show that delivery of foreign antigen to steady state Langerhans cells (LCs) and cDC1s through the same receptor (Langerin) led to, respectively, robust vs. minimal-to-null humoral immune response. LCs, unlike cDC1s, supported the formation of germinal center T follicular helper cells (GC-Tfh) antigen dose-dependently and then, likely licensed by these T cells, some of the LCs migrated to the B cell area to initiate B cell responses. Furthermore, we found that the cDC1s, probably through their superior T cell activation capacity, prevented the LCs from inducing GC-Tfh cells and humoral immune responses. We further show that targeted delivery of cytokines to DCs can be used to modulate DC-induced humoral immune responses, which has important therapeutic potential. Finally, we show that human LCs, unlike monocyte-derived DCs, can support GC Tfh generation in an in vitro autologous system; and in agreement with mouse data, we provide evidence in NHP studies that targeting LCs without adjuvants is an effective way to induce antibody responses, but does not trigger CD8+ T cell responses. Our findings suggest that the major limitations of some relatively ineffective vaccines currently in use or in development might be that (1) they are not formulated to specifically target a certain subset of DCs and/or (2) the antigen dose is not tailored to maximize the intrinsic/pre-programmed capabilities of the specific DC subset. This new and substantial departure from the status quo is expected to overcome problems that have hindered our ability to generate effective vaccines against some key pathogens

    CTL Escape Mediated by Proteasomal Destruction of an HIV-1 Cryptic Epitope

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    Cytotoxic CD8+ T cells (CTLs) play a critical role in controlling viral infections. HIV-infected individuals develop CTL responses against epitopes derived from viral proteins, but also against cryptic epitopes encoded by viral alternative reading frames (ARF). We studied here the mechanisms of HIV-1 escape from CTLs targeting one such cryptic epitope, Q9VF, encoded by an HIVgag ARF and presented by HLA-B*07. Using PBMCs of HIV-infected patients, we first cloned and sequenced proviral DNA encoding for Q9VF. We identified several polymorphisms with a minority of proviruses encoding at position 5 an aspartic acid (Q9VF/5D) and a majority encoding an asparagine (Q9VF/5N). We compared the prevalence of each variant in PBMCs of HLA-B*07+ and HLA-B*07- patients. Proviruses encoding Q9VF/5D were significantly less represented in HLA-B*07+ than in HLA-B*07- patients, suggesting that Q9FV/5D encoding viruses might be under selective pressure in HLA-B*07+ individuals. We thus analyzed ex vivo CTL responses directed against Q9VF/5D and Q9VF/5N. Around 16% of HLA-B*07+ patients exhibited CTL responses targeting Q9VF epitopes. The frequency and the magnitude of CTL responses induced with Q9VF/5D or Q9VF/5N peptides were almost equal indicating a possible cross-reactivity of the same CTLs on the two peptides. We then dissected the cellular mechanisms involved in the presentation of Q9VF variants. As expected, cells infected with HIV strains encoding for Q9VF/5D were recognized by Q9VF/5D-specific CTLs. In contrast, Q9VF/5N-encoding strains were neither recognized by Q9VF/5N- nor by Q9VF/5D-specific CTLs. Using in vitro proteasomal digestions and MS/MS analysis, we demonstrate that the 5N variation introduces a strong proteasomal cleavage site within the epitope, leading to a dramatic reduction of Q9VF epitope production. Our results strongly suggest that HIV-1 escapes CTL surveillance by introducing mutations leading to HIV ARF-epitope destruction by proteasomes

    Synthesis by extrusion: continuous, large-scale preparation of MOFs using little or no solvent

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    YesGrinding solid reagents under solvent-free or low-solvent conditions (mechanochemistry) is emerging as a general synthetic technique which is an alternative to conventional solvent-intensive methods. However, it is essential to find ways to scale-up this type of synthesis if its promise of cleaner manufacturing is to be realised. Here, we demonstrate the use of twin screw and single screw extruders for the continuous synthesis of various metal complexes, including Ni(salen), Ni(NCS)2(PPh3)2 as well as the commercially important metal organic frameworks (MOFs) Cu3(BTC)2 (HKUST-1), Zn(2-methylimidazolate)2 (ZIF-8, MAF-4) and Al(fumarate)(OH). Notably, Al(fumarate)(OH) has not previously been synthesised mechanochemically. Quantitative conversions occur to give products at kg h−1 rates which, after activation, exhibit surface areas and pore volumes equivalent to those of materials produced by conventional solvent-based methods. Some reactions can be performed either under completely solvent-free conditions whereas others require the addition of small amounts of solvent (typically 3–4 mol equivalents). Continuous neat melt phase synthesis is also successfully demonstrated by both twin screw and single screw extrusion for ZIF-8. The latter technique provided ZIF-8 at 4 kg h−1. The space time yields (STYs) for these methods of up to 144 × 103 kg per m3 per day are orders of magnitude greater than STYs for other methods of making MOFs. Extrusion methods clearly enable scaling of mechanochemical and melt phase synthesis under solvent-free or low-solvent conditions, and may also be applied in synthesis more generally.EPSRC (EP/L019655/1
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