Hal-Diderot
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    Radio and X-ray Diagnostics of Electron Beams in Solar Flares

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    Défense et illustration de la monarchie parlementaire néerlandaise dans le film Soldaat van Oranje de Paul Verhoeven

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    Soldaat van Oranje est un film de Paul Verhoeven sorti en 1977. Adaptations des mémoires de guerre d’Erik Hazelhoff Roefzelma, on y suit les aventures d’un groupe d’amis de 1939 à 1945. Certains d’entre eux réussissent à rejoindre Londres, d’où la reine Wilhelmina organise la résistance. La monarchie constitutionnelle y est dépeinte de façon très méliorative, si bien que le film, très populaire, semble avoir eu un impact positif sur sa préservation alors même qu’un certain nombre de scandales l’éclabousse la famille royale hollandaise dans les années 1970. PLAN : I. POSER LE DÉCOR : L’ÉLOQUENCE DE L’UNITÉ DE LIEU II. L’INCARNATION DE LA MONARCHIE PARLEMENTAIRE : LE THÈME DE LA NOUVELLE DÉMOCRATIE III. L’INFLUENCE DU FILM SUR L’IMAGINAIRE COLLECTIF HOLLANDAIS : LE RÉCIT DE LA REINE ET DE LA PATRI

    Grid is Good: Adaptive Refinement Algorithms for Off-the-Grid Total Variation Minimization: Grid is good

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    We propose an adaptive refinement algorithm to solve total variation regularized measure optimization problems. The method iteratively constructs dyadic partitions of the unit cube based on i) the resolution of discretized dual problems and ii) on the detection of cells containing points that violate the dual constraints. The detection is based on upper-bounds on the dual certificate, in the spirit of branch-and-bound methods. The interest of this approach is that it avoids the use of heuristic approaches to find the maximizers of dual certificates. We prove the convergence of this approach under mild hypotheses and a linear convergence rate under additional non-degeneracy assumptions. These results are confirmed by simple numerical experiments

    Association between recent methamphetamine use, antiretroviral therapy and HIV viral load; a mediation analysis from a cohort of HIV positive persons who inject drugs in Hai Phong, Vietnam

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    International audienceBackground There has been a significant increase in methamphetamine use among persons who use drugs in Vietnam in the last 5–10 years. We examined the degree to which adherence to antiretroviral therapy (ART) mediates the relationship between recent methamphetamine use and unsuppressed HIV viral load among people who inject drugs (PWID) in Hai Phong, Vietnam. Methods We recruited PWID from October 2016-October 2018 and enrolled HIV positive PWID into a cohort, with up to three years of total follow-up. We assessed relationships among recent methamphetamine use frequency, ART adherence and unsuppressed HIV viral load. Mediation analysis was used to estimate the total and natural direct effects of recent methamphetamine use on unsuppressed HIV viral load and the indirect effect proportion. Results We enrolled 792 HIV seropositive PWID into the cohort; approximately 75.9% reported high/perfect ART adherence at baseline and 81.3% were virally suppressed. In mediation analysis, the total effect for the association between methamphetamine use and unsuppressed HIV viral load (1000 copies/mL) was 3.94 (95% CI: 1.95, 7.96); the natural direct effect was 2.14 (95% CI: 1.29, 3.55); the proportion mediated by self-reported ART adherence was 0.444. Similar results were found when examining lower unsuppressed HIV viral load cutpoints of 250 copies/mL and 500 copies/mL. Conclusions Methamphetamine use is associated with unsuppressed HIV viral load among PWID despite high levels of ART adherence. Further research is needed to better understand these relationships, with emphasis on potential biological pathways that may interact with ART

    D-instantons in Calabi-Yau compactifications

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    International audienceEuclidean D-branes wrapped on non-trivial cycles of a Calabi-Yau threefold are known to affect the metric on the hypermultiplet moduli space determining the effective action of type II strings on such manifolds. After reviewing the existing results on the instanton corrected metric following from a combination of constraints imposed by supersymmetry and dualities, I'll show how the D-instanton effects can be computed by a direct worldsheet approach. This required solving several conceptual and technical problems, which also paved the way for extension of this approach to compactifications with lower supersymmetry. The talk is based on joint work with A. Sen and B. Stefanski

    Etude des mécanismes moléculaires impliqués dans le dialogue entre les cellules B tumorales de Leucémie Lymphoïde Chronique et leur microenvironnement

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    The tumor microenvironment plays an important role in the pathophysiology of chronic lymphocytic leukemia (CLL) as it promotes the survival and proliferation of malignant B cells either through direct cell-cell interactions or indirectly through soluble factors. In this study, we focused our attention on β-catenin as an effector of the cross-talk between CLL cells and the microenvironment using a co-culture model of tumor cells with a human bone marrow stromal cell line, HS-5. β-catenin is a known regulator of cell adhesion but it also behaves as a transcriptional co-activator in several signal transduction cascades induced by different stimuli, including Wnt and the BCR. When CLL and HS-5 cells are co-cultured, a fraction of CLL cells adhere to HS-5 whereas another fraction remain in suspension. We observed that the amount and distribution of β-catenin varies in the adherent versus suspension cells, suggesting a different role of β-catenin in these two cell fractions. Indeed, we observed that in suspension cells, β-catenin is stabilized, interacts with the kinase BTK and, regulates Cyclin D1 gene transcription. However, in adherent cells β-catenin is mainly in the cytosol/membrane compartments. When β-catenin is overexpressed in CLL cells, their adhesion to stromal cells is exacerbated without consequences on cell migration. Thesedata indicate that β-catenin, in association with BTK, plays a role in regulating the dialogue between tumor cells and their microenvironment. In the second part of this project, we analyzed the effect of CLL cells on the phenotypic and functional reprogramming of HS-5 cells. Our results suggest that CLL cells promote tumor immune evasion by secreting immunomodulatory cytokines (IFNγ, TNFα) to direct HS-5 cells to a FRC-like lymph node cell lineage. A better understanding of the mechanisms by which tumor cells increase their survival and escape immune surveillance could open new therapeutic avenues to block the harmful dialogue between leukemic cells and their microenvironment and restore effective immunity at sites of tumor proliferation.Le microenvironnement tumoral joue un rôle majeur dans la physiopathologie de la leucémie lymphoïde chronique (LLC) car il contribue à la survie et la prolifération des cellules B malignes par l’intermédiaire d’interactions directes intercellulaires ou indirectes via des facteurs solubles. Dans le cadre de l’étude du dialogue entre les cellules LLC et leur microenvironnement, nous avons porté notre attention sur la β-caténine pour sa capacité à réguler l’adhérence cellulaire mais également à induire une réponse transcriptionnelle de gènes pro-survie. La co-culture de cellules LLC (primaires ou lignées) avec des cellules stromales (la lignée HS-5) constitue un modèle de choix pour mimer les échanges avec le microenvironnement. Lors de leur co-culture, les cellules LLC se répartissent en deux fractions : une fraction adhérente et une fraction non adhérente aux cellules stromales. Dans les cellules LLC non-adhérentes, la β-caténine est fortement stabilisée, interagit avec la kinase BTK et régule la transcription du gène Cyclin D1. En revanche, cette stabilisation n’est pas observée dans les cellules adhérentes et la β-caténine est localisée à la membrane cellulaire. La surexpression dans les cellules LLC de la β-caténine augmente leur adhérence aux cellules stromales. Ces données indiquent que la β-caténine, en association avec BTK, joue un rôle de régulateur du dialogue entre les cellules tumorales et leur microenvironnement. Dans une deuxième partie, nous avons analysé l’impact des cellules LLC sur la reprogrammation phénotypique et fonctionnelle des cellules HS-5. Nos résultats montrent que les cellules LLC orientent les cellules HS-5 vers un profil de cellules ganglionnaires de type FRC via notamment la sécrétion de cytokines immunomodulatrices (IFNβγ, TNFα), favorisant ainsi l’échappement immunitaire de la tumeur. La description à l’échelle moléculaire du dialogue entre la cellule tumorale et son microenvironnement permettra de mieux comprendre la physiopathologie de la LLC mais également de mettre en évidence des cibles thérapeutiques alternatives aux stratégies actuelles afin de cibler et de bloquer le dialogue délétère que la tumeur établit avec son microenvironnement

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    Hal-Diderot is based in France
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