Grandes déformations multi-domaines par une approche monolithique pour le calcul massivement parallèle

National audienceLe développement d'une approche performante au niveau du calcul massivement parallèle, capable de simuler des applications complexes ( multi domaine) est l'un des intérêts essentiels de l'industrie. Dans cet article, le sujet des grandes déformations est abordé tout en utilisant une approche eulérienne monolithique. Une méthode level set convective est utilisée afin de définir les différents domaines présents et leur évolution au cours du temps. Ainsi, un seul maillage est considéré sur lequel un ensemble d'équations est résolu dont les propriétés physiques sont gérées par des lois de mélange. Le maillage est adapté afin d'avoir une précision plus élevée au niveau du calcul. L'utilisation d'un maillage unique permet d'obtenir une très bonne performance parallèle de l'approche

Modélisation des problèmes de grandes déformations multi-domaines par une approche Eulérienne monolithique massivement parallèle

Modeling of multi-domain problems is addressed in a Purely Eulerian framework. A single mesh is used all over the domain. The evolution of the different interacting bodies is described using numerical tools such as the Level Set method. The characteristics of the subdomains, considered as heterogeneities in the mesh, are determined using mixture laws.This work is one of the first attempts applying fully Eulerian Approach to Model large deformation problems. Therefore, the capacity of this approach is tested to determine necessary developments. The friction between the different objects is managed by adding a boundary layer implying the presence of a lubricant. Combined with an identification technique, a new quadratic mixture Law is introduced to determine the lubricant viscosity. Comparisons have been performed with Forge® and results were found satisfactory. To treat the contact problem between the different objects, a directional solver was developed. Despite the interesting results, it remains the topic of further improvements. The scalability of the approach in a massively parallel environment is tested as well. Several recommendations were proposed to ensure an optimal performance. The technique of a single mesh guarantees a very good scalability since the efficiency of parallelism depends of the partition of a single mesh (unlike the Lagrangian Methods). The proposed method presents undeniable capacities but remains far from being complete. Ideas for future Improvements are proposed accordingly.La modélisation des problèmes multi-domaine est abordée dans un cadre purement Eulérien. Un maillage unique, ne représentant plus la matière, est utilisé. Les différentes frontières et leur évolution sont décrites via des outils numériques tels que la méthode Level Set. Les caractéristiques locales de chaque sous domaines sont déterminées par des lois de mélange.Ce travail est une des premières tentations appliquant une approche Eulérienne pour modéliser de problèmes de grandes déformations. Dans un premier temps, la capacité de l'approche est testée afin de déterminer les développements nécessaires.Le frottement entre les différents objets est géré par un lubrifiant ajouté dans une couche limite. Combinée avec une technique d'identification, une nouvelle loi de mélange quadratique est introduite pour décrire la viscosité du lubrifiant. Des comparaisons ont été effectuées avec Forge® et les résultats sont trouvés satisfaisants. Pour traiter le contact entre les différents objets, un solveur directionnel a été développé. Malgré que les résultats soient intéressants, il reste le sujet de nouvelles améliorations. La scalabilité de l'approche dans un environnement massivement parallèle est testée aussi. Plusieurs recommandations ont été proposées pour s'assurer d'une performance optimale. La technique du maillage unique permet d'obtenir une très bonne scalabilité. L'efficacité du parallélisme ne dépend que de la partition d'un seul maillage (contrairement aux méthodes Lagrangiennes). La méthode proposée présente des capacités indéniables mais reste loin d'être complète. Des pistes d'amélioration sont proposées en conséquence

Clinical Data on Daptomycin plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus aureus Bacteremia

Vancomycin (VAN) and daptomycin (DAP) are approved as a monotherapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A regimen of daptomycin plus ceftaroline (DAP+CPT) has shown promise in published case series of MRSA salvage therapy, but no comparative data exist to compare up-front DAP+CPT head-to-head therapy versus standard monotherapy as an initial treatment. In a pilot study, we evaluated 40 adult patients who were randomized to receive 6 to 8 mg/kg of body weight per day of DAP and 600 mg intravenous (i.v.) CPT every 8 h (q8h) (n = 17) or standard monotherapy (n = 23) with vancomycin (VAN; dosed to achieve serum trough concentrations of 15 to 20 mg/liter; n = 21) or 6 to 8 mg/kg/day DAP (n = 2). Serum drawn on the first day of bacteremia was sent to a reference laboratory post hoc for measurement of interleukin-10 (IL-10) concentrations and correlation to in-hospital mortality. Sources of bacteremia, median Pitt bacteremia scores, Charlson comorbidity indices, and median IL-10 serum concentrations were similar in both groups. Although the study was initially designed to examine bacteremia duration, we observed an unanticipated in-hospital mortality difference of 0% (0/17) for combination therapy and 26% (6/23) for monotherapy (P = 0.029), causing us to halt the study. Among patients with an IL-10 concentration of \u3e5 pg/ml, 0% (0/14) died in the DAP+CPT group versus 26% (5/19) in the monotherapy group (P = 0.057). Here, we share the full results of this preliminary (but aborted) assessment of early DAP+CPT therapy versus standard monotherapy in MRSA bacteremia, hoping to encourage a more definitive clinical trial of its potential benefits against this leading cause of infection-associated mortality. (The clinical study discussed in this paper has been registered at ClinicalTrials.gov under identifier NCT02660346.

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Beiträge zum 28. Darmstädter Geotechnik-Kolloquium am 09. März 2022

Themenschwerpunkte: 1. Modell- und Feldversuche 2. Digitalisierung und künstliche Intelligenz in der Geotechnik 3. Nationale und internationale Großprojekte 4. Normung und Rechtliche