L'Occupation provoque le repli des bureaux d’études de cinq sociétés nationales de construction aéronautique à Cannes (en zone libre jusqu’à novembre 1942). Sous la tutelle maintenue des organismes ...de Vichy et des occupants, ainsi que de la Commission d’armistice de Wiesbaden, cette concentration est propice à l’innovation, par la conception et l’expérimentation de procédés et prototypes, alors que les autres usines doivent essentiellement produire du matériel allemand. Mais la pression des occupants (italiens et surtout allemands) amène certains ingénieurs à prendre des contacts durables avec la Résistance, la France libre et les Alliés, voire à partir. Les Allemands finissent donc par fermer Cannes. Si la transition de l’après-guerre a été difficile, il y a là, à certains égards, l’une des origines du redressement des capacités de conception de l’aéronautique française
The aptameric protective group strategy for the one-step regioselective transformation of aminoglycoside antibiotics was found to be compatible with diverse reagents and reaction conditions. New ...derivatives of neomycin B were synthesized with regioselectivities of >99%. This result extends the scope of applicability of APGs facilitating access to novel aminoglycoside derivatives.
Background Some but not all randomized controlled trials (RCT) have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents may be an acceptable alternative to coronary ...artery bypass grafting (CABG) surgery for the treatment of unprotected left main coronary artery disease (ULMCAD). We therefore aimed to compare the risk of all-cause mortality between PCI and CABG in patients with ULMCAD in a pairwise meta-analysis of RCT. Methods Randomized controlled trials comparing PCI vs CABG for the treatment of ULMCAD were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Results Six trials including 4,686 randomized patients were identified. After a median follow-up of 39 months, there were no significant differences between PCI vs CABG in the risk of all-cause mortality (hazard ratio HR 0.99, 95% CI 0.76-1.30) or cardiac mortality. However, a significant interaction for cardiac mortality ( Pinteraction = .03) was apparent between randomization arm and SYNTAX score, such that the relative risk for mortality tended to be lower with PCI compared with CABG among patients in the lower SYNTAX score tertile, similar in the intermediate tertile, and higher in the upper SYNTAX score tertile. Percutaneous coronary intervention compared with CABG was associated with a similar long-term composite risk of death, myocardial infarction, or stroke (HR 1.06, 95% CI 0.82-1.37), with fewer events within 30 days after PCI offset by fewer events after 30 days with CABG ( Pinteraction < .0001). Percutaneous coronary intervention was associated with greater rates of unplanned revascularization compared with CABG (HR 1.74, 95% CI 1.47-2.07). Conclusions In patients undergoing revascularization for ULMCAD, PCI was associated with similar rates of mortality compared with CABG at a median follow-up of 39 months, but with an interaction effect suggesting relatively lower mortality with PCI in patients with low SYNTAX score and relatively lower mortality with CABG in patients with high SYNTAX score. Both procedures resulted in similar long-term composite rates of death, myocardial infarction, or stroke, with PCI offering an early safety advantage and CABG demonstrating greater durability.
Microglia are brain macrophages and, as such, key immune-competent cells that can respond to environmental changes. Understanding the mechanisms of microglia-specific responses during pathologies is ...hence vital for reducing disease burden. The definition of microglial functions has so far been hampered by the lack of genetic in vivo approaches that allow discrimination of microglia from closely related peripheral macrophage populations in the body. Here we introduce a mouse experimental system that specifically targets microglia to examine the role of a mitogen-associated protein kinase kinase kinase (MAP3K), transforming growth factor (TGF)-β-activated kinase 1 (TAK1), during autoimmune inflammation. Conditional depletion of TAK1 in microglia only, not in neuroectodermal cells, suppressed disease, significantly reduced CNS inflammation and diminished axonal and myelin damage by cell-autonomous inhibition of the NF-κB, JNK and ERK1/2 pathways. Thus, we found TAK1 to be pivotal in CNS autoimmunity, and we present a tool for future investigations of microglial function in the CNS.
Year-to-year changes in carbon uptake by terrestrial ecosystems have an essential role in determining atmospheric carbon dioxide concentrations
. It remains uncertain to what extent temperature and ...water availability can explain these variations at the global scale
. Here we use factorial climate model simulations
and show that variability in soil moisture drives 90 per cent of the inter-annual variability in global land carbon uptake, mainly through its impact on photosynthesis. We find that most of this ecosystem response occurs indirectly as soil moisture-atmosphere feedback amplifies temperature and humidity anomalies and enhances the direct effects of soil water stress. The strength of this feedback mechanism explains why coupled climate models indicate that soil moisture has a dominant role
, which is not readily apparent from land surface model simulations and observational analyses
. These findings highlight the need to account for feedback between soil and atmospheric dryness when estimating the response of the carbon cycle to climatic change globally
, as well as when conducting field-scale investigations of the response of the ecosystem to droughts
. Our results show that most of the global variability in modelled land carbon uptake is driven by temperature and vapour pressure deficit effects that are controlled by soil moisture.
Purpose Lenalidomide maintenance therapy after autologous stem-cell transplantation (ASCT) demonstrated prolonged progression-free survival (PFS) versus placebo or observation in several randomized ...controlled trials (RCTs) of patients with newly diagnosed multiple myeloma (NDMM). All studies had PFS as the primary end point, and none were powered for overall survival (OS) as a primary end point. Thus, a meta-analysis was conducted to better understand the impact of lenalidomide maintenance in this setting. Patients and Methods The meta-analysis was conducted using primary-source patient-level data and documentation from three RCTs (Cancer and Leukemia Group B 100104, Gruppo Italiano Malattie Ematologiche dell'Adulto RV-MM-PI-209, and Intergroupe Francophone du Myélome 2005-02) that met the following prespecified inclusion criteria: an RCT in patients with NDMM receiving ASCT followed by lenalidomide maintenance versus placebo or observation with patient-level data available and achieved database lock for primary efficacy analysis. Results Overall, 1,208 patients were included in the meta-analysis (605 patients in the lenalidomide maintenance group and 603 in the placebo or observation group). The median PFS was 52.8 months for the lenalidomide group and 23.5 months for the placebo or observation group (hazard ratio, 0.48; 95% CI, 0.41 to 0.55). At a median follow-up time of 79.5 months for all surviving patients, the median OS had not been reached for the lenalidomide maintenance group, whereas it was 86.0 months for the placebo or observation group (hazard ratio, 0.75; 95% CI, 0.63 to 0.90; P = .001). The cumulative incidence rate of a second primary malignancy before disease progression was higher with lenalidomide maintenance versus placebo or observation, whereas the cumulative incidence rates of progression, death, or death as a result of myeloma were all higher with placebo or observation versus lenalidomide maintenance. Conclusion This meta-analysis demonstrates a significant OS benefit and confirms the PFS benefit with lenalidomide maintenance after ASCT in patients with NDMM when compared with placebo or observation.
PDF
