Pasarela en Le Havre Francia

The longitudinal profile of this is a cubic parabola with a 6 m rise and a length of 105 m. Essentially this footbridge consists of a metal pier —that supports two unequal spans— situated at 3/10 of the length so as to utilize the pier of an old bridge; it has the shape of a capital A, the posts of which are pyramids with triangular section and which are formed by sheet plates joined together by welding. The spans, however, consist of: two lateral metal welded beams; a series of bridge ties also of metal, at a distance of 2.50 m from each other and joined to the beams by means of bolts; and resting upon these, a 10 cm thick reinforced concrete slab, protected by a greatly adhesive covering due to the strong slope of the accesses. The suspended solution does not allow any greater thickness of the footbridge and thus the views of the harbour are hardly obstructed. Its assymmetric shape along with the slender form of the pier contributes to making its location in the centre of the city very suitable.El perfil longitudinal de esta pasarela es el de una parábola cúbica con 6 m de flecha y 105 m de longitud. Esencialmente está constituida por una pila metálica —que soporta dos tramos desiguales— situada a 3/10 de la longitud con el fin de reutilizar, para su cimentación, la pila de un antiguo puente; tiene la forma de una gran A, cuyos montantes son pirámides de sección triangular formados por palastros soldados entre sí. Los tramos, a su vez, están formados por: dos vigas laterales metálicas, soldadas; una serie de traviesas, también metálicas, distanciadas 2,50 m y unidas a las vigas mediante bulones; y, apoyando sobre estas últimas, una losa de hormigón armado de 10 cm de espesor, protegida por un revestimiento de gran adherencia motivado por la fuerte pendiente de los accesos. La solución suspendida ha permitido dar un espesor muy pequeño a la pasarela, con lo que apenas se obstaculizan las perspectivas de la dársena. Su forma asimétrica, unida a la gran esbeltez de la pila, la hacen muy adecuada a su emplazamiento en pleno centro de la ciudad

DOCK8 Functions as an Adaptor that Links TLR–MyD88 Signaling to B Cell Activation

DOCK8 and MyD88 have been implicated in serologic memory. Here we report antibody responses were impaired and $CD27^+$ memory B cells were severely reduced in DOCK8-deficient patients. Toll-like receptor 9 (TLR9)- but not CD40-driven B cell proliferation and immunoglobulin production were severely reduced in DOCK8-deficient B cells. In contrast, TLR9-driven expression of AICDA, CD23 and CD86, and activation of NF-κB, p38 and Rac1 were intact. DOCK8 associated constitutively with MyD88 and the tyrosine kinase Pyk2 in normal B cells. Following TLR9 ligation, DOCK8 became tyrosine phosphorylated by Pyk2, bound the Src family kinase Lyn and linked TLR9 to a Src-Syk-STAT3 cascade essential for TLR9-driven B cell proliferation and differentiation. Thus, DOCK8 functions as an adaptor in a TLR9-MyD88 signaling pathway in B cells

Galectin-1, a gene preferentially expressed at the tumor margin, promotes glioblastoma cell invasion

BACKGROUND: High-grade gliomas, including glioblastomas (GBMs), are recalcitrant to local therapy in part because of their ability to invade the normal brain parenchyma surrounding these tumors. Animal models capable of recapitulating glioblastoma invasion may help identify mediators of this aggressive phenotype. METHODS: Patient-derived glioblastoma lines have been propagated in our laboratories and orthotopically xenografted into the brains of immunocompromized mice. Invasive cells at the tumor periphery were isolated using laser capture microdissection. The mRNA expression profile of these cells was compared to expression at the tumor core, using normal mouse brain to control for host contamination. Galectin-1, a target identified by screening the resulting data, was stably over-expressed in the U87MG cell line. Sub-clones were assayed for attachment, proliferation, migration, invasion, and in vivo tumor phenotype. RESULTS: Expression microarray data identified galectin-1 as the most potent marker (p-value 4.0 x 10(-8)) to identify GBM cells between tumor-brain interface as compared to the tumor core. Over-expression of galectin-1 enhanced migration and invasion in vitro. In vivo, tumors expressing high galectin-1 levels showed enhanced invasion and decreased host survival. CONCLUSIONS: In conclusion, cells at the margin of glioblastoma, in comparison to tumor core cells, have enhanced expression of mediators of invasion. Galectin-1 is likely one such mediator. Previous studies, along with the current one, have proven galectin-1 to be important in the migration and invasion of glioblastoma cells, in GBM neoangiogenesis, and also, potentially, in GBM immune privilege. Targeting this molecule may offer clinical improvement to the current standard of glioblastoma therapy, i.e. radiation, temozolomide, anti-angiogenic therapy, and vaccinotherapy

Pasarela en Le Havre Francia

The longitudinal profile of this is a cubic parabola with a 6 m rise and a length of 105 m. &#13; Essentially this footbridge consists of a metal pier —that supports two unequal spans— situated at 3/10 of the length so as to utilize the pier of an old bridge; it has the shape of a capital A, the posts of which are pyramids with triangular section and which are formed by sheet plates joined together by welding. &#13; The spans, however, consist of: two lateral metal welded beams; a series of bridge ties also of metal, at a distance of 2.50 m from each other and joined to the beams by means of bolts; and resting upon these, a 10 cm thick reinforced concrete slab, protected by a greatly adhesive covering due to the strong slope of the accesses.&#13; The suspended solution does not allow any greater thickness of the footbridge and thus the views of the harbour are hardly obstructed. Its assymmetric shape along with the slender form of the pier contributes to making its location in the centre of the city very suitable.<br><br>El perfil longitudinal de esta pasarela es el de una parábola cúbica con 6 m de flecha y 105 m de longitud. &#13; Esencialmente está constituida por una pila metálica —que soporta dos tramos desiguales— situada a 3/10 de la longitud con el fin de reutilizar, para su cimentación, la pila de un antiguo puente; tiene la forma de una gran A, cuyos montantes son pirámides de sección triangular formados por palastros soldados entre sí. &#13; Los tramos, a su vez, están formados por: dos vigas laterales metálicas, soldadas; una serie de traviesas, también metálicas, distanciadas 2,50 m y unidas a las vigas mediante bulones; y, apoyando sobre estas últimas, una losa de hormigón armado de 10 cm de espesor, protegida por un revestimiento de gran adherencia motivado por la fuerte pendiente de los accesos. &#13; La solución suspendida ha permitido dar un espesor muy pequeño a la pasarela, con lo que apenas se obstaculizan las perspectivas de la dársena. &#13; Su forma asimétrica, unida a la gran esbeltez de la pila, la hacen muy adecuada a su emplazamiento en pleno centro de la ciudad

Restriction fragment haplotypes in the human immunoglobulin IGHG locus and their correlation with the Gm polymorphism

International audienceOf the four human IgG subclass heavy chain (IGHG) genes, three--IGHG1, IGHG2 and IGHG3--have allelic forms which encode antigenic determinants called G1m, G2m and G3m allotypes for markers of the IgG1, IgG2 and IgG3 molecules. The alleles at these three closely linked loci are transmitted as Gm haplotypes, together with the IGHG4 and the IGHGP (or pseudo gamma) genes. Restriction Fragment Length Polymorphisms (RFLPs) have been described for all these IGHG genes, allowing us to define at least 15 RFLP alleles (N. Ghanem et al., Eur. J. Immunol. 1988. 18:1059). In this article, we determine unambiguously the Gm alleles and haplotypes and the associated RFLPs in French, Lebanese and Tunisian families, chosen for the various Gm phenotypes of their members, in order to correlate both these polymorphisms and to know the evolution of the IGHG multigene family. We were able to assign all the IGHG alleles to the Gm alleles and to their linked IGHG4 and IGHGP genes allowing us to define restriction fragment haplotypes of the IGHG gene family

Thymoquinone Potently Enhances the Activities of Classically Activated Macrophages Pulsed with Necrotic Jurkat Cell Lysates and the Production of Antitumor Th1-/M1-Related Cytokines

International audienceAntitumor activity of classically activated macrophage (Mϕ) may be impaired within the tumors, spleen, and bone marrow. Thus, it is possible to boost its antitumor activity after its pulsing with necrotic tumor cell lysates combined with an adjuvant. We set out to determine the potential adjuvant effects of thymoquinone (TQ; 2-isopropyl-5-methyl-1,4-benzoquinone, C10H12O2) on both functional activities of classically activated Mϕs, pulsed or not with necrotic Jurkat T cell line lysates (NecrJCL), and the balance of antitumor cytokines (ATCs) versus immunosuppressive cytokines (ISCs) during crosstalk with autologous human CD4+ T cells. We found that TQ treatment resulted in a significant upregulation of phagocytic activity, respiratory burst, the production of interleukin-2 (IL-2), IL-6, and IL-17 in NecrJCL-pulsed Mϕ co-culture system, and, conversely, in downregulation of the production of IL-6, IL-17, nitric oxide (NO), and arginase activity in nonpulsed TQ-treated Mϕs co-culture system. In addition, TQ has also shown low upregulation effect on the production of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and IL-1β, pathogen killing capacity and H2O2 in NecrJCL-pulsed Mϕs co-cultures. Moreover, TQ significantly downregulated arginase activity, and significantly upregulated inducible NO synthase (iNOS) activity-to-arginase activity ratio in NecrJCL-pulsed Mϕ co-cultures. Furthermore, TQ downregulated IL-10-to-IL-17 ratio and total cellular cholesterol content (ttcCHOL), but upregulated the ratios of IL-1β-to-IL-4, IL-1β-to-IL-10, IFN-γ-to-IL-4, IFN-γ-to-IL-10, TNF-α-to-IL-4, TNF-α-to-IL-10, and combined proinflammatory cytokines (PICs)-to-anti-inflammatory cytokines (AICs) in NecrJCL-pulsed Mϕs co-culture system, whereas significant differences were highlighted only for IL-10-to-IL-17, IFN-γ-to-IL-10, and PICs-to-AICs ratios. Our outcomes demonstrated that TQ can act as potent adjuvant for enhancing both the functional activities of NecrJCL-pulsed Mϕ and the production of ATCs during their interplay with CD4+ T cells

Design of cassette baculovirus vectors for the production of therapeutic antibodies in insect cells

International audienc

Design of cassette baculovirus vectors for the production of therapeutic antibodies in insect cells

International audienc

IMGT-choreography for immunogenetics and immunoinformatics

IMGT, the international ImMunoGeneTics information system® (http://imgt.cines.fr), was created in 1989 at Montpellier, France. IMGT is a high quality integrated knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune system (RPI) which belong to the immunoglobulin superfamily (IgSF) and MHC superfamily (MhcSF). IMGT provides a common access to standardized data from genome, proteome, genetics and three-dimensional structures. The accuracy and the consistency of IMGT data are based on IMGT-ONTOLOGY, a semantic specification of terms to be used in immunogenetics and immunoinformatics. IMGT-ONTOLOGY has been formalized using XML Schema (IMGT-ML) for interoperability with other information systems. We are developing Web services to automatically query IMGT databases and tools. This is the first step towards IMGT-Choreography which will trigger and coordinate dynamic interactions between IMGT Web services to process complex significant biological and clinical requests. IMGT-Choreography will further increase the IMGT leadership in immunogenetics and immunoinformatics for medical research (repertoire analysis of the IG antibody recognition sites and of the TR recognition sites in autoimmune and infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research (IG and TR repertoires in farm and wild life species), genome diversity and genome evolution studies of the adaptive immune responses, biotechnology related to antibody engineering (single chain Fragment variable (scFv), phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (detection and follow-up of residual diseases) and therapeutical approaches (grafts, immunotherapy, vaccinology). IMGT is freely available at http://imgt.cines.fr