Synthesis Optimization and Catalytic Activity Screening of Industrially Relevant Ruthenium-Based Metathesis Catalysts

International audienceOlefin metathesis is a powerful catalytic reaction that has a huge potential in the pharmaceutical, polymer and specialty chemicals industries. Cost-effective industrial applications require large-scale availability of catalyst precursors which combine high activity, high selectivity and long life-time. Among the known numerous families of olefin metathesis catalysts, the Umicore M7-catalyst family represents a novel class of Hoveyda-type complexes showing excellent chemical stabilities and modular activity profiles. Relevant aspects related to their industrial synthesis as well as their catalytic performance in valuable olefin metathesis transformations are overviewed here

High-voltage pixel detectors in commercial CMOS technologies for ATLAS, CLIC and Mu3e experiments

High-voltage particle detectors in commercial CMOS technologies are a detector family that allows implementation of low-cost, thin and radiation-tolerant detectors with a high time resolution. In the R/D phase of the development, a radiation tolerance of 10 15 n eq = cm 2 , nearly 100% detection ef fi ciency and a spatial resolution of about 3 μ m were demonstrated. Since 2011 the HV detectors have fi rst applications: the technology is presently the main option for the pixel detector of the planned Mu3e experiment at PSI (Switzerland). Several prototype sensors have been designed in a standard 180 nm HV CMOS process and successfully tested. Thanks to its high radiation tolerance, the HV detectors are also seen at CERN as a promising alternative to the standard options for ATLAS upgrade and CLIC. In order to test the concept, within ATLAS upgrade R/D, we are currently exploring an active pixel detector demonstrator HV2FEI4; also implemented in the 180 nm HV proces

Innovative analytical methodologies for characterizing chemical exposure with a view to next-generation risk assessment

International audienceThe chemical burden on the environment and human population is increasing. Consequently, regulatory risk assessment must keep pace to manage, reduce, and prevent adverse impacts on human and environmental health associated with hazardous chemicals. Surveillance of chemicals of known, emerging, or potential future concern, entering the environment-food-human continuum is needed to document the reality of risks posed by chemicals on ecosystem and human health from a one health perspective, feed into early warning systems and support public policies for exposure mitigation provisions and safe and sustainable by design strategies. The use of less-conventional sampling strategies and integration of full-scan, high-resolution mass spectrometry and effect-directed analysis in environmental and human monitoring programmes have the potential to enhance the screening and identification of a wider range of chemicals of known, emerging or potential future concern. Here, we outline the key needs and recommendations identified within the European Partnership for Assessment of Risks from Chemicals (PARC) project for leveraging these innovative methodologies to support the development of next-generation chemical risk assessment

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old