Origin of the Reactor Antineutrino Anomalies in Light of a New Summation Model with Parametrized ß

We investigate the possible origins of the reactor antineutrino anomalies in norm and shape within the framework of a summation model where ß^{-} transitions are simulated by a phenomenological model of Gamow-Teller decay strength. The general trends of divergence from the Huber-Mueller model on the antineutrino side can be reproduced in both norm and shape. From the exact electron-antineutrino correspondence of the summation model, we predict similar distortions in the electron spectra, suggesting that biases on the reference spectra of fission electrons could be the cause of the anomalies.

Observation of a Nuclear Recoil Peak at the 100 eV Scale Induced by Neutron Capture.

Coherent elastic neutrino-nucleus scattering and low-mass dark matter detectors rely crucially on the understanding of their response to nuclear recoils. We report the first observation of a nuclear recoil peak at around 112 eV induced by neutron capture. The measurement was performed with a CaWO_{4} cryogenic detector from the NUCLEUS experiment exposed to a ^{252}Cf source placed in a compact moderator. We identify the expected peak structure from the single-γ de-excitation of ^{183}W with 3σ and its origin by neutron capture with 6σ significance. This result demonstrates a new method for precise, in situ, and nonintrusive calibration of low-threshold experiments.

[Impact of positive surgical margins on prostate cancer prognosis]. / Impact carcinologique des marges positives après prostatectomie totale.

OBJECTIVE: To examine the impact of positive surgical margins (PSM) after radical prostatectomy (RP) for prostate cancer on oncological results. PATIENTS AND METHODS: We performed a study where all patients who underwent radical prostatectomy between January 2004 and December 2018 for prostate cancer were included. The preoperative, postoperative data and the carcinological results collected were analyzed. Data were analysed using Kaplan-Meier survival analysis and proportional hazards models. RESULTS: A total of 319 patients with a median age of 65 years (IQR : 62-69) were included. The median follow-up was 43.6 months (IQR: 19.4-79.3). The overall rate of PSM was 33.5%. PSM was associated with biochemical recurrence (P<0.001). Overall mortality was not associated with positive margins. A clinical stage> T1c was an independent predictor of PSM on multivariate analysis (P=0.01). CONCLUSION: PSM would increase the risk of biochemical recurrence with no impact on survival. Clinical stage>T1c was an adverse predictor for PSM. LEVEL OF EVIDENCE: 3.

[Impact of antiplatelet and anticoagulant treatments on bleeding complications in patients treated with HoLEP]. / Impact des anticoagulants et antiagrégants sur complications hémorragiques chez les patients traités par HoLEP.

INTRODUCTION: We aimed to assess the impact of antiplatelet and anticoagulation therapy for patients undergoing HoLEP. METHODS: We performed a study during the learning curve on a consecutive series of patients who underwent HoLEP surgery from 2015 to 2018. The patients were divided into 3 groups: a control group, patients with antiplatelet therapy and patients with anticoagulation therapy. RESULTS: A total of 223 patients underwent HoLEP surgery during this period: 124 in the control group, 63 in the antiplatelet group and 36 in the anticoagulant group. In the anticoagulant group, we observe significant differences with the control group for the catheterization time (2.05 days vs 5.17 days; P<0.001), the hospital length of stay (1.5 nights vs 4.49 nights; P<0.001) and complications (8.9% vs 58%; P<0.001). No difference between the control and antiplatelet groups in terms of catheterization time, hospital length of stay and complications (2.05 days vs 2.68 days; 1.5 nights vs 1.6 nights) but variation in terms of complications and bleeding complications (8.9% vs 21%; P<0,001; 8.1% vs 19%; P<0,001) CONCLUSION: Our study shows that HoLEP is therefore associated with a higher risk of bleeding for patients treated with anticoagulation therapy. Complications increase morbidity with longer catheterization time, hospitalization times and higher transfusion's rates, revision surgery and readmission. LEVEL OF EVIDENCE: 3.

Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates.

Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)-rich protein aggregates [termed "Lewy bodies" (LBs)], is a well-established characteristic of Parkinson's disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning-based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

A large HPGe detector for the non-destructive radioassay of an ultra-low-background counting facility.

We present the use of a low background counting facility, equipped with a p-type 80% relative efficiency HPGe detector, protected by active and passive shielding, and large enough to count a 10 in photo-multiplier tube (PMT). A GEANT4 Monte-Carlo of this detector was developed and tuned to 3% accuracy. We report the U, Th, and K content in three different types of PMTs used in current neutrino experiments, with accuracies of ~10ppb for U and Th and of ~15ppm for K.

Conversion of thymidylate synthase into an HIV protease substrate.

Thymidylate synthase (TS) is an essential enzyme of DNA metabolism. We have carried out an extensive insertional mutagenesis of the Escherichia coli TS gene (thyA) using three different methods. Insertion of exogenous sequences at unique restriction sites or at random positions produced defective mutants, whereas comparison of TS sequences from different species allowed us to identify six zones permissive for insertions of exogenous sequences. The insertion of Human immunodeficiency virus type 1 (HIV-1) protease substrate sequences into the permissive sites converted TS to an HIV-1 protease substrate, and the in vivo cleavage of these insertions by the cloned HIV-1 protease conferred a thymidylate synthase-deficient phenotype in some of our E. coli mutant strains. In agreement with crystallographic data, these results show that the permissive sites are located in regions of the TS protein not essential for enzyme activity and accessible to cleavage by HIV protease. These results also show that it is possible to control a growth phenotype in E. coli through the protease-mediated destruction of an essential metabolic enzyme. Because both wild type and thymidylate synthase-deficient phenotypes are selectable on the appropriate growth medium, these thyA mutants could be used for genetic selections of protease inhibitors and analysis of protease specificities.

Variable constraints on the principal immunodominant domain of the transmembrane glycoprotein of human immunodeficiency virus type 1.

Lentiviruses have in their transmembrane glycoprotein (TM) a highly immunogenic structure referred to as the principal immunodominant domain (PID). The PID forms a loop of 5 to 7 amino acids between two conserved cysteines. Previous studies showed that envelope (Env) glycoprotein functions of feline immunodeficiency virus (FIV) could be retained after extensive mutation of the PID loop sequence, in spite of its high conservation. In order to compare Env function in different lentiviruses, either random mutations were introduced in the PID loop sequence of human immunodeficiency virus type 1 (HIV-1) or the entire HIV-1 PID loop was replaced by the corresponding PID loop of FIV or simian immunodeficiency virus (SIV). In the macrophage-tropic HIV-1 ADA Env, mutations impaired the processing of the gp160 Env precursor, thereby abolishing viral infectivity. However, 6 of the 108 random Env mutants that were screened retained the capacity to induce cell membrane fusion. The SIV and FIV sequences and five random mutations were then introduced in the context of T-cell-line-adapted HIV-1 LAI which, although phenotypically distant from HIV-1 ADA, has an identical PID loop sequence. In contrast to the situation for HIV-1 ADA mutants, the cleavage of the Env precursor was unaffected in most HIV-1 LAI mutants. Such mutations, however, resulted in increased shedding of the gp120 surface glycoprotein (SU) from the gp41 TM. The HIV-1 LAI Env mutants showed high fusogenic efficiency. Three Env mutants retained the capacity to mediate virus entry in target cells, although less efficiently than the wild-type Env, and allowed the reconstitution of infectious molecular clones. These results indicated that in HIV-1, like FIV, the conserved PID sequence can be changed without impairing Env function. However, functional constraints on the PID of HIV-1 vary depending on the structural context of Env, presumably in relation to the role of the PID in the interaction of the SU and TM subunits and the stability of the Env complex.

Apparent enhancement of perinatal transmission of human immunodeficiency virus type 1 by high maternal anti-gp160 antibody titer.

The presence of antibodies able to enhance infection in vitro in sera from human immunodeficiency virus (HIV)-1-infected patients raises the possibility that antibodies exert a deleterious activity during natural infection. The anti-HIV-1 humoral response and plasma HIV-1 RNA were measured in a cohort of 98 infected mothers, included in the French Prospective Study on Pediatric HIV Infection, 49 of whom transmitted HIV to their children. Transmission from mother to child was associated with antibody responses to the envelope gp160 (P = .009 for serum dilution of 1/400) and to a highly conserved domain of the transmembrane glycoprotein (P = .055 for serum dilution of 1/400) and with plasma HIV-1 RNA levels (P < .0001). Multivariate logistic regression indicated that a high anti-gp160 response and a high plasma virus load are independent risk factors for perinatal transmission of HIV-1 (odds ratio, 3.4; 95% confidence interval, 1.1-9.9 for anti-gp160; odds ratio, 2.8; 95% confidence interval, 1.6-5.0 for virus load).

Shared usage of the chemokine receptor CXCR4 by primary and laboratory-adapted strains of feline immunodeficiency virus.

Strains of the feline immunodeficiency virus (FIV) presently under investigation exhibit distinct patterns of in vitro tropism. In particular, the adaptation of FIV for propagation in Crandell feline kidney (CrFK) cells results in the selection of strains capable of forming syncytia with cell lines of diverse species origin. The infection of CrFK cells by CrFK-adapted strains appears to require the chemokine receptor CXCR4 and is inhibited by its natural ligand, stromal cell-derived factor 1alpha (SDF-1alpha). Here we found that inhibitors of CXCR4-mediated infection by human immunodeficiency virus type I (HIV-1), such as the bicyclam AMD3100 and short peptides derived from the amino-terminal region of SDF-1alpha, also blocked infection of CrFK by FIV. Nevertheless, we observed differences in the ranking order of the peptides as inhibitors of FIV and HIV-1 and showed that such differences are related to the species origin of CXCR4 and not that of the viral envelope. These results suggest that, although the envelope glycoproteins of FIV and HIV-1 are substantially divergent, FIV and HIV-1 interact with CXCR4 in a highly similar manner. We have also addressed the role of CXCR4 in the life cycle of primary isolates of FIV. Various CXCR4 ligands inhibited infection of feline peripheral blood mononuclear cells (PBMC) by primary FIV isolates in a concentration-dependent manner. These ligands also blocked the viral transduction of feline PBMC by pseudotyped viral particles when infection was mediated by the envelope glycoprotein of a primary FIV isolate but not by the G protein of vesicular stomatitis virus, indicating that they act at an envelope-mediated step and presumably at viral entry. These findings strongly suggest that primary and CrFK-adapted strains of FIV, despite disparate in vitro tropisms, share usage of CXCR4.