Analytic and Gevrey Hypoellipticity for Perturbed Sums of Squares Operators

We prove a couple of results concerning pseudodifferential perturbations of differential operators being sums of squares of vector fields and satisfying H\"ormander's condition. The first is on the minimal Gevrey regularity: if a sum of squares with analytic coefficients is perturbed with a pseudodifferential operator of order strictly less than its subelliptic index it still has the Gevrey minimal regularity. We also prove a statement concerning real analytic hypoellipticity for the same type of pseudodifferential perturbations, provided the operator satisfies to some extra conditions (see Theorem 1.2 below) that ensure the analytic hypoellipticity

Sub-Riemannian Calculus on Hypersurfaces in Carnot Groups

We develope basic geometric quantities and properties of hypersurfaces in Carnot groups

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

Background: We 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 ~ 80% of cases. Methods: We 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. Results: No 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 = 1.1 × 10−4) 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 = 2.1 × 10−4). 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 = 3.4 × 10−3), 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 = 7.7 × 10−8). 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 = 1.68 × 10−5). Conclusions: Rare 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

Effect of a granulovirus larvicide, Madex®, on egg-laying of Cydia pomonella L. (Lepidoptera: Tortricidae) due to changes in chemical signalization on the apple leaf surface

Applications of Madex® (granulovirus) against the codling moth, Cydia pomonella, which targets neonate larvae before or during their initial entry into fruit, provide selective control of this key apple pest. Differences in the efficacy of Madex® treatment against C. pomonella larvae were observed in an experimental orchard in northern Italy on two apple tree cultivars, ‘Golden Delicious’ and ‘Red Chief’. The intensity of egg-laying by the moth may vary from one cultivar to another. The composition of a metabolite blend on the leaf surface consisting of glucose, fructose, sucrose, sorbitol, quebrachitol and myo-inositol is one of the factors that could explain these variations. Our hypothesis was therefore that variations in the efficacy of Madex® could be related to variations in egg numbers, itself related to the composition of metabolites on the leaf surface of each cultivar. Differences in egg-laying (number and localization) were recorded on the two cultivars, ‘Golden Delicious’ and ‘Red Chief’, untreated or treated with the larvicide. Madex® had the same efficacy on both cultivars in terms of the reduction of fruit damage due to larval feeding. Surprisingly, the effect ofMadex® on reducing damage seemed less tied to a lethal effect of the larvicide on the larvae than to egg-laying reduction, the latter being linked to changes in chemical signals of the leaf surface induced by applications of Madex®. This observation was verified by experiments on egg-laying on an artificial substrate. When the active metabolite blends mimicking the corymb leaf surface compositions of each cultivar (untreated and treated with Madex®) were applied to nylon cloth egg-laying substrates, significant reductions in acceptance (% of egg-laying females) and egg-laying stimulation (number of eggs per egg-laying female) were observed. The reduction of eggs on ‘Red Chief’ could be primarily explained by a drastic effect on egg-laying stimulation, whereas the reduction on ‘Golden Delicious’ was partly due to a lower acceptance. The number of eggs laid naturally differs from one apple tree cultivar to another. The effects of reduced egg-laying caused by applications ofMadex® were due to biochemical changes in surface blends, depending on the cultiva

Relation pharmacocinétique/pharmacodynamique entre la concentration sanguine de tétrahydrocannabinol et l’aptitude à conduire un véhicule chez des consommateurs occasionnels ou chroniques de cannabis

International audienceObjectiveThe pharmacokinetic/pharmacodynamic (PK/PD) relationship between blood tétrahydrocannabinol (THC) concentrations after smoking and the ability to drive is poorly documented.MethodsTHC and its metabolites were measured in the blood of chronic users (CC, 1–2 joints/day) and 15 occasional users (CO, 1–2 joints/week) 12 times over 24 h after randomized placebo-controlled smoking containing 10 mg or 30 mg of THC. The effects were evaluated 7 times by a vigilance test (reaction time) and a driving simulator during the same period.ResultsThere is no PK/PD relationship. The blood concentration for THC and 11-OH-THC is maximal at the end of the consumption whereas the effects are strongest about 5 h later. After the same dose consumed, the blood concentration of THC is almost twice as high in CC than in CO. CC always have THC in the blood (>1 ng/mL) after 24 h whereas it is 1 ng/mL) après 24 h alors qu’il est < 0,5 ng/mL chez les CO après 6 h environ. Les effets sur l’allongement du temps de réaction sont plus importants pour les CO (+19 % à 10 mg et +27 % à 30 mg) que pour les CC (+11 % à 10 mg et +19 % à 30 mg), de même sur l’aptitude à conduire où on ne retrouve pas d’effet dose (+25 % d’erreur pour les CC vs +34 % chez les CO). L’effet total sur la conduite dure environ 8 h chez les CC et jusqu’à 13 h chez les CO.ConclusionLe cannabis a un effet délétère sur la conduite, décalé dans le temps par rapport à la cinétique sanguine du THC