199 research outputs found
Sociologie du conflit
Michel Wieviorka, Hervé Le Bras, directeurs d’études Penser la crise Dans le passé, les sociologues se sont révélés peu capables d’analyser à chaud une grande crise. Il en a été ainsi notamment lors de la crise de 1929 qui a suscité une seule recherche marquante, celle de Jahoda, Lazarsfeld et Zeisel sur les chômeurs de Marienthal. La crise actuelle étant d’importance, il m’est apparu utile d’en faire l’objet du séminaire dès la rentrée 2008-2009 et j’ai proposé à Hervé Le Bras de se joindre ..
Sociologie du conflit
Michel Wieviorka, Hervé Le Bras, directeurs d’études Sociologie du conflit. Penser la crise Pour sa deuxième année, le séminaire « Penser la crise » a continué d’alterner séances « ouvertes », autour d’un invité, et séances « fermées », destinées à approfondir les analyses de ses deux animateurs. Il a reçu Pierre Cunéo, directeur de la stratégie ferroviaire et de la régulation à la SNCF, qui a traité de l’impact de la crise sur une grande entreprise comme la sienne ; Jean-Christophe Le Duigou..
Multi-mode analysis of Rayleigh-type Lg. Part 2. Application to southern California and the northwestern Sierra Nevada
The UC diagram technique described in the companion paper (Part 1), is applied to nine sets of Lg phases recorded through the CEDAR system in southern California, and two sets of Lg phases recorded along the northwestern margin of the Sierra Nevada. A clear image of the signal is obtained in time-frequency-wavenumber space, and we discuss in particular observations at 2.5-sec period, for events 200 to 300 km outside the profiles. From the gross features of UC diagrams we conclude that a representation of Lg as a single coherent multi-mode wave train is oversimplified in the case of southern California but is more appropriate for the Sierra block. In southern California, peaks observed at group velocities smaller than 3.2 km/sec are not predicted by realistic crustal models of the area, and are probably due to lateral heterogeneities effects such as mode conversion and multipathing. On the other hand, for group velocities between 3.2 and 3.6 km/sec, peaks observed in either area can generally be interpreted in terms of overtones excited at the source and propagating through spatially averaged structures, although care must be taken to monitor the stability of the algorithm on actual short-period records
Processing of blood samples influences PBMC viability and outcome of cell-mediated immune responses in antiretroviral therapy-naïve HIV-1-infected patients
AbstractIntracellular cytokine staining (ICS) assay is increasingly used in vaccine clinical trials to measure antigen-specific T-cell mediated immune (CMI) responses in cryopreserved peripheral blood mononuclear cells (PBMCs) and whole blood. However, recent observations indicate that several parameters involved in blood processing can impact PBMC viability and CMI responses, especially in antiretroviral therapy (ART)-naïve HIV-1-infected individuals.In this phase I study (NCT01610427), we collected blood samples from 22 ART-naïve HIV-1-infected adults. PBMCs were isolated and processed for ICS assay. The individual and combined effects of the following parameters were investigated: time between blood collection and PBMC processing (time-to-process: 2, 7 or 24h); time between PBMC thawing and initiation of in vitro stimulation with HIV-1 antigens (resting-time: 0, 2, 6 and 18h); and duration of antigen-stimulation in PBMC cultures (stimulation-time: 6h or overnight). The cell recovery after thawing, cell viability after ICS and magnitude of HIV-specific CD8+ T-cell responses were considered to determine the optimal combination of process conditions. The impact of time-to-process (2 or 4h) on HIV-specific CD8+ T-cell responses was also assessed in a whole blood ICS assay.A higher quality of cells in terms of recovery and viability (up to 81% and >80% respectively) was obtained with shorter time-to-process (less than 7h) and resting-time (less than 2h) intervals. Longer (overnight) rather than shorter (6h) stimulation-time intervals increased the frequency of CD8+-specific T-cell responses using ICS in PBMCs without change of the functionality. The CD8+ specific T-cell responses detected using fresh whole blood showed a good correlation with the responses detected using frozen PBMCs.Our results support the need of standardized procedures for the evaluation of CMI responses, especially in HIV-1-infected, ART-naïve patients
A global biodiversity observing system to unite monitoring and guide action
The rate and extent of global biodiversity change is surpassing our ability to measure, monitor and forecast trends. We propose an interconnected worldwide system of observation networks — a global biodiversity observing system (GBiOS) — to coordinate monitoring worldwide and inform action to reach international biodiversity targets.acceptedVersio
Defective lymphoid organogenesis underlies the immune deficiency caused by a heterozygous S32I mutation in IκBα.
Patients with ectodermal dysplasia with immunodeficiency (ED-ID) caused by mutations in the inhibitor of NF-κB α (IκBα) are susceptible to severe recurrent infections, despite normal T and B cell numbers and intact in vitro lymphocyte function. Moreover, the outcome of hematopoietic stem cell transplantation (HSCT) in these patients is poor despite good engraftment. Mice heterozygous for the IκBα S32I mutation found in patients exhibited typical features of ED-ID. Strikingly, the mice lacked lymph nodes, Peyer's patches, splenic marginal zones, and follicular dendritic cells and failed to develop contact hypersensitivity (CHS) or form germinal centers (GCs), all features not previously recognized in patients and typical of defective noncanonical NF-κB signaling. Lymphotoxin β receptor (LTβR)-driven induction of chemokines and adhesion molecules mediated by both canonical and noncanonical NF-κB pathways was impaired, and levels of p100 were markedly diminished in the mutant. IκBα mutant → Rag2(-/-), but not WT→IκBα mutant, bone marrow chimeras formed proper lymphoid organs and developed CHS and GCs. Defective architectural cell function explains the immunodeficiency and poor outcome of HSCT in patients with IκBα deficiency and suggests that correction of this niche is critical for reconstituting their immune function
A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction
Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acidinduced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5dihydroxybenzoic acid to a range of 2,5substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholineinduced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF2 and H2DCFDA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RTPCR and western blotting were utilized to measure Akt, eNOS, Nrf2, NQO1 and HO1 expression. Results: Ex vivo endotheliumdependent relaxation was significantly improved by the glycomimetics under palmitateinduced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitateinduced oxidative stress and enhanced NO production. We demonstrate that the protective effects of preincubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROSinduced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease
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