Monte Carlo methods for linear and non-linear Poisson-Boltzmann equation

The electrostatic potential in the neighborhood of a biomolecule can be computed thanks to the non-linear divergence-form elliptic Poisson-Boltzmann PDE. Dedicated Monte-Carlo methods have been developed to solve its linearized version (see e.g.Bossy et al 2009, Mascagni & Simonov 2004}). These algorithms combine walk on spheres techniques and appropriate replacements at the boundary of the molecule. In the first part of this article we compare recent replacement methods for this linearized equation on real size biomolecules, that also require efficient computational geometry algorithms. We compare our results with the deterministic solver APBS. In the second part, we prove a new probabilistic interpretation of the nonlinear Poisson-Boltzmann PDE. A Monte Carlo algorithm is also derived and tested on a simple test case

La distribution de synérèse/diérèse dans la phonologie du français contemporain & perspectives de codage

Conference programme at https://www.projet-pfc.net/journees-floral-ipfc-2019/

Low spatial autocorrelation in mountain biodiversity data and model residuals

Spatial autocorrelation (SAC) is a common feature of ecological data where observations tend to be more similar at some geographic distance(s) than expected by chance. Despite the implications of SAC for data dependencies, its impact on the performance of species distribution models (SDMs) remains controversial, with reports of both strong and negligible impacts on inference. Yet, no study has comprehensively assessed the prevalence and the strength of SAC in the residuals of SDMs over entire geographic areas. Here, we used a large-scale spatial inventory in the western Swiss Alps to provide a thorough assessment of the importance of SAC for (1) 850 species belonging to nine taxonomic groups, (2) six predictors commonly used for modeling species distributions, and (3) residuals obtained from SDMs fitted with two algorithms with the six predictors included as covariates. We used various statistical tools to evaluate (1) the global level of SAC, (2) the spatial pattern and spatial extent of SAC, and (3) whether local clusters of SAC can be detected. We further investigated the effect of the sampling design on SAC levels. Overall, while environmental predictors expectedly displayed high SAC levels, SAC in biodiversity data was rather low overall and vanished rapidly at a distance of similar to 5-10 km. We found low evidence for the existence of local clusters of SAC. Most importantly, model residuals were not spatially autocorrelated, suggesting that inferences derived from SDMs are unlikely to be affected by SAC. Further, our results suggest that the influence of SAC can be reduced by a careful sampling design. Overall, our results suggest that SAC is not a major concern for rugged mountain landscapes.Peer reviewe

Neurophysiological changes induced by music-supported therapy for recovering upper extremity function after stroke: a case series

Music-supported therapy (MST) follows the best practice principles of stroke rehabilitation and has been proven to instigate meaningful enhancements in motor recovery post-stroke. The existing literature has established that the efficacy and specificity of MST relies on the reinforcement of auditory-motor functional connectivity in related brain networks. However, to date, no study has attempted to evaluate the underlying cortical network nodes that are key to the efficacy of MST post-stroke. In this case series, we evaluated changes in connectivity within the auditory-motor network and changes in upper extremity function following a 3-week intensive piano training in two stroke survivors presenting different levels of motor impairment. Connectivity was assessed pre- and post-training in the α- and the β-bands within the auditory-motor network using magnetoencephalography while participants were passively listening to a standardized melody. Changes in manual dexterity, grip strength, movement coordination, and use of the upper extremity were also documented in both stroke survivors. After training, an increase in the clinical measures was accompanied by enhancements in connectivity between the auditory and motor network nodes for both the α- and the β-bands, especially in the affected hemisphere. These neurophysiological changes associated with the positive effects of post-stroke MST on motor outcomes delineate a path for a larger scale clinical trial

The Euratom Safeguards On-site Laboratories at the Reprocessing Plants of La Hague and Sellafield

In the European Union, nuclear material is reprocessed from irradiated power reactor fuel at two sites ¿ La Hague in France and Sellafield in the United Kingdom. These are the largest nuclear sites within the EU, processing many hundreds of tons of nuclear material in a year. Under the Euratom Treaty, the European Commission has the duty to assure that the nuclear material is only used for declared purposes. The Directorate General for Energy (DG ENER), acting for the Commission, assures itself that the terms of Article 77 of Chapter VII of the Treaty have been complied with. In contrast to the Non Proliferation Treaty, the Euratom Treaty requires to safeguard all civil nuclear material in all EU member states ¿ including the nuclear weapons states. The considerable amount of fissile material separated per year (several tonnes) calls for a stringent system of safeguards measures. The aim of safeguards is to deter diversion of nuclear material from peaceful use by maximizing the chance of early detection. At a broader level, it provides assurance to the public that the European nuclear industry, the EU member states and the European Union honour their legal duties under the Euratom Treaty and their commitments to the Non-Proliferation Treaty. Efficient and effective safeguards measures are essential for the public acceptance of nuclear activities.JRC.E.7-Nuclear Safeguards and Forensic

Profiling the landscape of transcription, chromatin accessibility and chromosome conformation of cattle, pig, chicken and goat genomes [FAANG pilot project]

Functional annotation of livestock genomes is a critical and obvious next step to derive maximum benefit for agriculture, animal science, animal welfare and human health. The aim of the Fr-AgENCODE project is to generate multi-species functional genome annotations by applying high-throughput molecular assays on three target tissues/cells relevant to the study of immune and metabolic traits. An extensive collection of stored samples from other tissues is available for further use (FAANG Biosamples ‘FR-AGENCODE’). From each of two males and two females per species (pig, cattle, goat, chicken), strand-oriented RNA-seq and chromatin accessibility ATAC-seq assays were performed on liver tissue and on two T-cell types (CD3+CD4+&CD3+CD8+) sorted from blood (mammals) or spleen (chicken). Chromosome Conformation Capture (in situ Hi-C) was also carried out on liver. Sequencing reads from the 3 assays were processed using standard processing pipelines. While most (50–70%) RNA-seq reads mapped to annotated exons, thousands of novel transcripts and genes were found, including extensions of annotated protein-coding genes and new lncRNAs (see abstract #69857). Consistency of ATAC-seq results was confirmed by the significant proportion of called peaks in promoter regions (36–66%) and by the specific accumulation pattern of peaks around gene starts (TSS) v. gene ends (TTS). Principal Component Analyses for RNA-seq (based on quantified gene expression) and ATAC-seq (based on quantified chromatin accessibility) highlighted clusters characterised by cell type and sex in all species. From Hi-C data, we generated 40kb-resolution interaction maps, profiled a genome-wide Directionality Index and identified from 4,100 (chicken) to 12,100 (pig) topologically-associating do- mains (TADs). Correlations were reported between RNA-seq and ATAC-seq results (see abstract #71581). In summary, we present here an overview of the first multi-species and -tissue annotations of chromatin accessibility and genome architecture related to gene expression for farm animals

Readiness in HIV Treatment Adherence: A Matter of Confidence. An Exploratory Study§

Adherence to treatment is recognized as the essence of a successful HIV combination therapy. Optimal adherence implies a readiness to begin the treatment on the part of the patient. A better understanding of the "readiness phenomenon" will become an asset for optimizing HIV treatment. However, few studies have focused on understanding the process underlying the choice to adhere. The aim of this study is to understand the readiness process that leads to adhering to the HIV treatment, from both patient and professional perspectives. Twenty-seven in-depth interviews, with a qualitative exploratory design, were the source of our data. Participants were recruited in two hospitals in Paris. Throughout the data-collection process, analysed data were supplied to all participants and the research team, thus allowing for shared constructions. Four themes, interrelated with a constitutive pattern, emerged from the data we collected. Being ready to begin and adhere to treatment is a matter of confidence in oneself, as well as in relatives, in the treatment and in the health professional team. These themes are not constant and unvarying; instead, they constitute a picture moving across time and life events. Results of this study show that adherence that goes beyond “complying with” the medical instructions, but depends on how much of an active role the patient plays in the choice to adhere

Structures of DPAGT1 explain glycosylation disease mechanisms and advance TB antibiotic design

Summary: Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 (GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic “lipid-altered” tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P \u3c .001), and a steeper rate of decline through the first 5 days (P \u3c .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978