210 research outputs found

    De l'île de Ré à l’île d’Arros:Récits, symboles et statistiques dans l'expérience du bouclier fiscal (2005-2011)

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    Comment expliquer que des responsables politiques puissent conduire des politiques fiscales à l’avantage des plus riches, tout en obtenant l’assentiment de la majorité de la population ? À travers l’étude de la genèse puis de la suppression du bouclier fiscal, entre 2005 et 2011, cet article montre comment ses promoteurs ont su utiliser les symboles, les récits et les statistiques pour maintenir un voile d’ignorance quant à la position sociale des bénéficiaires. D’instrument destiné à protéger les contribuables de l’impôt, ce dispositif est pourtant devenu en quelques années l’incarnation du clientélisme politique. Les symboles offrent des ressources pour la construction des problèmes publics, mais peuvent aussi devenir des stigmates lorsque la réalité se révèle trop éloignée de la fiction imaginée. Cette étude met ainsi en lumière la dimension dynamique et évolutive de la construction des problèmes publics.Political science has been struggling for a number of years with a democratic puzzle: how is it that upwardly-redistributive policies, which grant significant tax cuts to rich people, seem to be supported by a majority of voters? Is this due to misinformation, political obfuscation, or a shift in the moral attitudes towards taxation and redistribution? Through an analysis of the French ‘bouclier fiscal’ (tax shield), which was created in 2005 and abolished in 2011, we stress the major role played by symbols, narratives and numbers in the evolving representations of tax inequality. Initially conceived as a tool that would protect all taxpayers from excessive taxation, this measure became increasingly perceived as embodying client politics, especially after 2009-2010. We argue that symbols, when used in politics, may help frame public issues, but also lead to political weakness when reality appears to be too distanced from constructed narratives

    Coexpression of GM-CSF and antigen in DNA prime-adenoviral vector boost immunization enhances polyfunctional CD8+ T cell responses, whereas expression of GM-CSF antigen fusion protein induces autoimmunity

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    <p>Abstract</p> <p>Background</p> <p>Granulocyte-macrophage colony-stimulating factor (GM-CSF) has shown promising results as a cytokine adjuvant for antiviral vaccines and in various models of tumor gene therapy. To explore whether the targeting of antigens to GM-CSF receptors on antigen-presenting cells enhances antigen-specific CD8 T-cell responses, fusion proteins of GM-CSF and ovalbumin (OVA) were expressed by DNA and adenoviral vector vaccines. In addition, bicistronic vectors allowing independent expression of the antigen and the cytokine were tested in parallel.</p> <p>Results</p> <p><it>In vitro</it>, the GM-CSF ovalbumin fusion protein (GM-OVA) led to the better stimulation of OVA-specific CD8+ T cells by antigen-presenting cells than OVA and GM-CSF given as two separate proteins. However, prime-boost immunizations of mice with DNA and adenoviral vector vaccines encoding GM-OVA suppressed CD8+ T-cell responses to OVA. OVA-specific IgG2a antibody levels were also reduced, while the IgG1 antibody response was enhanced. Suppression of CD8+ T cell responses by GM-OVA vaccines was associated with the induction of neutralizing antibodies to GM-CSF. In contrast, the coexpression of GM-CSF and antigens in DNA prime adenoviral boost immunizations led to a striking expansion of polyfunctional OVA-specific CD8+ T cells without the induction of autoantibodies.</p> <p>Conclusion</p> <p>The induction of autoantibodies suggests a general note of caution regarding the use of highly immunogenic viral vector vaccines encoding fusion proteins between antigens and host proteins. In contrast, the expansion of polyfunctional OVA-specific CD8+ T cells after immunizations with bicistronic vectors further support a potential application of GM-CSF as an adjuvant for heterologous prime-boost regimens with genetic vaccines. Since DNA prime adenoviral vector boost regimenes are presently considered as one of the most efficient ways to induce CD8+ T cell responses in mice, non-human primates and humans, further enhancement of this response by GM-CSF is a striking observation.</p

    Shearographic non-destructive evaluation of space shuttle thermal protection systems

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    Preliminary results of shearographic inspections of the shuttle external tank (ET) spray-on foam insulation (SOFI) and solid rocket booster (SRB) Marshall sprayable ablative (MSA-2) epoxy-cork thermal protection systems (TPS) are presented. Debonding SOFI or MSA-2 damage the orbiter 'belly' tile and exposes the ET/SRB to thermal loading. Previous work with the ET/SRB showed promising results with shearography. The first area investigated was the jack pad close-out, one of many areas on the ET where foam is applied at KSC. Voids 0.375 inch were detected in 1.75 inch thick foam using a pressure reduction of less than 0.4 psi. Of primary interest are areas of the ET that directly face the orbiter tile TPS. It is estimated that 90% of tile TPS damage on the orbiter 'belly' results from debonding SOFI during ascent. Test panels modeling these areas were manufactured with programmed debonds to determine the sensitivity of shearography as a function of debond size, SOFI thickness and vacuum. Results show repeatable detection of debonds with a diameter approximately half the SOFI thickness at less than 0.4 psi pressure reduction. Preliminary results are also presented on inspections of MSA-2 and the remote manipulator system (RMS) honeycomb materia

    GagPol-specific CD4+ T-cells increase the antibody response to Env by intrastructural help

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    Background: Immunization of rhesus macaques against Gag of SIV resulted in a more rapid appearance of Env antibodies after infection with SIV or SHIV challenge viruses although the vaccines lacked an Env component. We therefore explored whether T helper cells specific for internal HIV proteins could provide intrastructural help for Env-specific B cells and thus increase the Env antibody response. Results: Mice were immunized by adenoviral vector or DNA vaccines against GagPol and then boosted with virus-like particles (VLP) containing GagPol and Env. Env-specific antibody levels after the VLP booster immunizations were significantly higher in GagPol-immunized mice than in mock-vaccinated controls. Adoptive transfer of CD4+ T cells from GagPol-immunized mice also enhanced the Env antibody response to VLP immunization in the recipient mice. Depending on the presence of VLPs, co-cultivation of CD4+ T cells from GagPol-primed mice with BCR transgenic B cells specific for a protein presented on the surface of the VLPs also resulted in the activation of the B and T cells. Conclusions: Our study indicates that GagPol-specific T helper cells may provide intrastructural help for Env antibody responses. This cross-talk between immune responses directed against different components of the retroviral particle may be relevant for the immunopathogenesis of retroviral infections and allow to improve virus like particle vaccine approaches against HIV

    Innate signalling molecules as genetic adjuvants do not alter the efficacy of a DNA-based influenza A vaccine

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    In respect to the heterogeneity among influenza A virus strains and the shortcomings of current vaccination programs, there is a huge interest in the development of alternative vaccines that provide a broader and more long-lasting protection. Gene-based approaches are considered as promising candidates for such flu vaccines. In our study, innate signalling molecules from the RIG-I and the NALP3 pathways were evaluated as genetic adjuvants in intramuscular DNA immunizations. Plasmids encoding a constitutive active form of RIG-I (cRIG-I), IPS-1, IL-1β, or IL-18 were co-administered with plasmids encoding the hemagglutinin and nucleoprotein derived from H1N1/Puerto Rico/8/1934 via electroporation in BALB/c mice. Immunogenicity was analysed in detail and efficacy was demonstrated in homologous and heterologous influenza challenge experiments. Although the biological activities of the adjuvants have been confirmed by in vitro reporter assays, their single or combined inclusion in the vaccine did not result in superior vaccine efficacy. With the exception of significantly increased levels of antigen-specific IgG1 after the co-administration of IL-1β, there were only minor alterations concerning the immunogenicity. Since DNA electroporation alone induced substantial inflammation at the injection site, as demonstrated in this study using Mx2-Luc reporter mice, it might override the adjuvants´ contribution to the inflammatory microenvironment and thereby minimizes the influence on the immunogenicity. Taken together, the DNA immunization was protective against subsequent challenge infections but could not be further improved by the genetic adjuvants analysed in this study

    Enhancement of the priming efficacy of DNA vaccines encoding dendritic cell-targeted antigens by synergistic toll-like receptor ligands

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    Abstract Background Targeting of protein antigens to dendritic cells (DC) via the DEC205 receptor enhances presentation of antigen-derived peptides on MHC-I and MHC-II molecules and, in the presence of costimulatory signals, antigen-specific immune responses. The immunogenicity and efficacy of DNA vaccination can also be enhanced by fusing the encoded antigen to single chain antibodies directed against DEC205. To further improve this strategy, we evaluated different toll-like receptor ligands (TLR) and CD40 ligands (CD40L) as adjuvants for DNA vaccines encoding a DEC205-single-chain antibody fused to the ovalbumin model antigen or HIV-1 Gag and assessed the priming efficacy of DNA in a DNA prime adenoviral vector boost immunization regimen. Results Mice were primed with the adjuvanted DEC-205 targeted DNA vaccines and boosted with adenoviral vectors encoding the same antigens. CD8+ T cell responses were determined after the adenoviral booster immunization, to determine how well the different DNA immunization regimens prime for the adenoviral boost. In the absence of adjuvants, targeting of DNA-encoded ovalbumin to DCs suppressed CD8+ T-cell responses after the adenoviral booster immunization. CD8+ T-cell responses to the DEC205 targeted DNA vaccines increased only slightly by adding either the TLR-9 ligand CpG, the TLR-3 ligand Poly I:C, or CD40 ligand expression plasmids. However, the combination of both TLR-ligands led to a strong enhancement of CD8+ T-cell responses compared to a non-targeted DNA vaccine. This finding was confirmed using HIV Gag as antigen. Conclusion Although DNA prime adenoviral vector boost immunizations belong to the strongest inducers of cytotoxic T cell responses in different animal models and humans, the CD8+ T cell responses can be further improved by targeting the DNA encoded antigen to DEC205 in the presence of synergistic TLR ligands CpG and Poly I:C

    anti-1′,6′,7′,8′,9′,14′,15′,16′-Octa­chloro­dispiro­[1,3-dioxolane-2,17′-penta­cyclo­[12.2.1.16,9.02,13.05,10]octa­decane-18′,2′′-1,3-dioxolane]-7′,15′-diene

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    The title compound, C22H20Cl8O4, was prepared as part of the synthesis of precursors for the preparation of fluorinated mol­ecular tweezers. The mol­ecule sits on an inversion center, thus requiring that the cyclo­octane ring adopt a chair conformation
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