Design and Analysis of a Task-based Parallelization over a Runtime System of an Explicit Finite-Volume CFD Code with Adaptive Time Stepping

FLUSEPA (Registered trademark in France No. 134009261) is an advanced simulation tool which performs a large panel of aerodynamic studies. It is the unstructured finite-volume solver developed by Airbus Safran Launchers company to calculate compressible, multidimensional, unsteady, viscous and reactive flows around bodies in relative motion. The time integration in FLUSEPA is done using an explicit temporal adaptive method. The current production version of the code is based on MPI and OpenMP. This implementation leads to important synchronizations that must be reduced. To tackle this problem, we present the study of a task-based parallelization of the aerodynamic solver of FLUSEPA using the runtime system StarPU and combining up to three levels of parallelism. We validate our solution by the simulation (using a finite-volume mesh with 80 million cells) of a take-off blast wave propagation for Ariane 5 launcher.Comment: Accepted manuscript of a paper in Journal of Computational Scienc

Political Astuteness of Nurse Educators

Nurses comprise the largest segment of the healthcare workforce. Although nurses have advocated for patients since Florence Nightingale’s time, advocating for changes in health policies that affect populations on a larger scale has not changed over time (Rasheed et al., 2020). Professional nursing associations, nurse educators, and the Institute of Medicine have all identified the need to educate nurses in advocacy and health policy. With the recent revision of the American Association of Colleges of Nursing’s Essentials publication, health policy has moved from an essential to a featured concept that is found in the competencies and subcompetencies of the domains. Therefore, it is imperative that nurse educators have the knowledge, or political astuteness, to teach health policy to the future nursing workforce. This study explored the political astuteness level from a national sample of 72 nurse educators teaching in pre-licensure programs. An electronic survey containing the Political Astuteness Inventory (Clark, 1984, 2008) and a demographics questionnaire that also included questions seeking comfort and enthusiasm levels when teaching health policy content was distributed via network and social media approaches. Although the results showed no significant difference in the political astuteness score mean between educators who are teaching health policy and educators who have not taught health policy in 24 months, there were statistically significant findings with political astuteness scores, comfort, and enthusiasm. This study contributes to the existing body of knowledge regarding levels of political astuteness in nurses. Recommendations for future research and implications for nursing education are included

MPMD parallelization of an aerodynamic code with bodies in relative motion

International audienceFLUSEPA is an advanced simulation tool which performs a large panel of aerodynamic studies. It is the unstructured finite-volume solver developed by Airbus Defence & Space company to calculate compressible, multidimensional, unsteady, viscous and reactive flows around bodies in relative motion. The numerical strategy in FLUSEPA is designed for highly compressible flows and keeps its accuracy in non-Cartesian grids. According the desired accuracy, a second-order accurate shock-capturing scheme is generally used for RANS and URANS simulations and a fourth order accurate vortex-centered scheme is used for hybrid RANS/LES simulations. The meshing strategy is based on multi-overlapping grid intersection which is conservative and allows to quickly and properly mesh 3D complex geometries. It can be seen as a CHIMERA strategy without interpolation. Each body is meshed independently and immersed in background grids.MPMD parallelisation of this code is presented

Task-based parallelization of a CFD code over a Runtime System

International audienceFLUSEPA is an advanced simulation tool which performs a large panel of aerodynamic studies. It is the unstructured nite-volume solver developed by Airbus Defence & Space company to calculate compressible, multidimensional, unsteady, viscous and reactive flows around bodies in relative motion [2](Figure 1). The numerical strategy in FLUSEPA is designed for highly compressible tlows and to remain accurate when using non-Cartesian grids. The meshing strategy is based on multi-overlapping grid intersection which is conservative and allows to quickly mesh 3D complex geometries. The time integration in FLUSEPA is done using an explicit temporal adaptive method [3]. Instead of using a time step imposed by the slowest cell, cells are grouped inside temporal classes according to their maximum allowed time step. This method allows to perform a fewer number of operations at the expense of some complexity. An iteration of the aerodynamic solver is separated into several sub-iterations. Every cell is not integrated during each sub-iteration but cells which share a face with a slower one are interpolated. At the end of the iteration, each cell has reached the same time. Between iterations, temporal classes can evolve.The current version of FLUSEPA is parallelized using a classical MPI-OpenMP approach and domain decomposition: border faces are duplicated and ghost cells are used. However, the way the time is integrated leads to important time wasted in synchronization despite computation-communication overlapping. The time integration implies an order for the cells to be processed depending on their temporal class: neighbor cells must be at the same time during processing. This locality information is partially lost with the current parallelization. In this paper, we present a way to overcome this issue by working on sub-domains inside each process. We capture the dependencies more precisely through the use of a task-based parallel expression with the help of a well suited runtime system

Towards an efficient Task-based Parallelization over a Runtime System of an Explicit Finite-Volume CFD Code with Adaptive Time Stepping

International audienceFLUSEPA is an advanced simulation tool which performs a large panel of aerodynamic studies. It is the unstruc-tured finite-volume solver developed by Airbus Defence & Space company to calculate compressible, multidimensional, unsteady, viscous and reactive flows around bodies in relative motion. The time integration in FLUSEPA is done using an explicit temporal adaptive method. The current production version of the code is based on MPI and OpenMP. This implementation leads to important synchronizations that must be reduced. To tackle this problem, we present a first study of a task-based parallelization of the solver part of FLUSEPA using the runtime system StarPU and combining up to three levels of parallelism. We validate our solution on the simulation of a takeoff blast wave propagation for Ariane 5 launcher

Selective degradation permits a feedback loop controlling Annexin A6 and cholesterol levels in endolysosomes of NPC1 mutant cells

We recently identified elevated annexin A6 (AnxA6) protein levels in Niemann-Pick-type C1 (NPC1) mutant cells. In these cells, AnxA6 depletion rescued the cholesterol accumulation associated with NPC1 deficiency. Here, we demonstrate that elevated AnxA6 protein levels in NPC1 mutants or upon pharmacological NPC1 inhibition, using U18666A, were not due to upregulated AnxA6 mRNA expression, but caused by defects in AnxA6 protein degradation. Two KFERQ-motifs are believed to target AnxA6 to lysosomes for chaperone-mediated autophagy (CMA), and we hypothesized that the cholesterol accumulation in endolysosomes (LE/Lys) triggered by the NPC1 inhibition could interfere with the CMA pathway. Therefore, AnxA6 protein amounts and cholesterol levels in the LE/Lys (LE-Chol) compartment were analyzed in NPC1 mutant cells ectopically expressing lysosome-associated membrane protein 2A (Lamp2A), which is well known to induce the CMA pathway. Strikingly, AnxA6 protein amounts were strongly decreased and coincided with significantly reduced LE-Chol levels in NPC1 mutant cells upon Lamp2A overexpression. Therefore, these findings suggest Lamp2A-mediated restoration of CMA in NPC1 mutant cells to lower LE-Chol levels with concomitant lysosomal AnxA6 degradation. Collectively, we propose CMA to permit a feedback loop between AnxA6 and cholesterol levels in LE/Lys, encompassing a novel mechanism for regulating cholesterol homeostasis in NPC1 disease

Vacuolar ATPase Is a Possible Therapeutic Target in Acute Myeloid Leukemia: Focus on Patient Heterogeneity and Treatment Toxicity

Vacuolar ATPase (V-ATPase) is regarded as a possible target in cancer treatment. It is expressed in primary acute myeloid leukemia cells (AML), but the expression varies between patients and is highest for patients with a favorable prognosis after intensive chemotherapy. We therefore investigated the functional effects of two V-ATPase inhibitors (bafilomycin A1, concanamycin A) for primary AML cells derived from 80 consecutive patients. The V-ATPase inhibitors showed dose-dependent antiproliferative and proapoptotic effects that varied considerably between patients. A proteomic comparison of primary AML cells showing weak versus strong antiproliferative effects of V-ATPase inhibition showed a differential expression of proteins involved in intracellular transport/cytoskeleton functions, and an equivalent phosphoproteomic comparison showed a differential expression of proteins that regulate RNA processing/function together with increased activity of casein kinase 2. Patients with secondary AML, i.e., a heterogeneous subset with generally adverse prognosis and previous cytotoxic therapy, myeloproliferative neoplasia or myelodysplastic syndrome, were characterized by a strong antiproliferative effect of V-ATPase inhibition and also by a specific mRNA expression profile of V-ATPase interactome proteins. Furthermore, the V-ATPase inhibition altered the constitutive extracellular release of several soluble mediators (e.g., chemokines, interleukins, proteases, protease inhibitors), and increased mediator levels in the presence of AML-supporting bone marrow mesenchymal stem cells was then observed, especially for patients with secondary AML. Finally, animal studies suggested that the V-ATPase inhibitor bafilomycin had limited toxicity, even when combined with cytarabine. To conclude, V-ATPase inhibition has antileukemic effects in AML, but this effect varies between patients.publishedVersio

CD1b Tetramers Bind αβ\alpha \beta T Cell Receptors to Identify a Mycobacterial Glycolipid-Reactive T Cell Repertoire in Humans

Microbial lipids activate T cells by binding directly to CD1 and T cell receptors (TCRs) or by indirect effects on antigen-presenting cells involving induction of lipid autoantigens, CD1 transcription, or cytokine release. To distinguish among direct and indirect mechanisms, we developed fluorescent human CD1b tetramers and measured T cell staining. CD1b tetramer staining of T cells requires glucose monomycolate (GMM) antigens, is specific for TCR structure, and is blocked by a recombinant clonotypic TCR comprised of TRAV17 and TRBV4-1, proving that CD1b-glycolipid complexes bind the TCR. GMM-loaded tetramers brightly stain a small subpopulation of blood-derived cells from humans infected with Mycobacterium tuberculosis, providing direct detection of a CD1b-reactive T cell repertoire. Polyclonal T cells from patients sorted with tetramers are activated by GMM antigens presented by CD1b. Whereas prior studies emphasized CD8$^+$ and CD4$^-$CD8$^-$ CD1b-restricted clones, CD1b tetramer-based studies show that nearly all cells express the CD4 co-receptor. These findings prove a cognate mechanism whereby CD1b-glycolipid complexes bind to TCRs. CD1b tetramers detect a natural CD1b-restricted T cell repertoire ex vivo with unexpected features, opening a new investigative path to study the human CD1 system

Incidence, mortality and survival patterns of prostate cancer among residents in Singapore from 1968 to 2002

<p>Abstract</p> <p>Background</p> <p>From 1968 to 2002, Singapore experienced an almost four-fold increase in prostate cancer incidence. This paper examines the incidence, mortality and survival patterns for prostate cancer among all residents in Singapore from 1968 to 2002.</p> <p>Methods</p> <p>This is a retrospective population-based cohort study including all prostate cancer cases aged over 20 (n = 3613) reported to the Singapore Cancer Registry from 1968 to 2002. Age-standardized incidence, mortality rates and 5-year Relative Survival Ratios (RSRs) were obtained for each 5-year period. Follow-up was ascertained by matching with the National Death Register until 2002. A weighted linear regression was performed on the log-transformed age-standardized incidence and mortality rates over period.</p> <p>Results</p> <p>The percentage increase in the age-standardized incidence rate per year was 5.0%, 5.6%, 4.0% and 1.9% for all residents, Chinese, Malays and Indians respectively. The percentage increase in age-standardized mortality rate per year was 5.7%, 6.0%, 6.6% and 2.5% for all residents, Chinese, Malays and Indians respectively. When all Singapore residents were considered, the RSRs for prostate cancer were fairly constant across the study period with slight improvement from 1995 onwards among the Chinese.</p> <p>Conclusion</p> <p>Ethnic differences in prostate cancer incidence, mortality and survival patterns were observed. There has been a substantial improvement in RSRs since the 1990s for the Chinese.</p

Anticancer chemotherapy and radiotherapy trigger both non-cell-autonomous and cell-autonomous death.

Even though cell death modalities elicited by anticancer chemotherapy and radiotherapy have been extensively studied, the ability of anticancer treatments to induce non-cell-autonomous death has never been investigated. By means of multispectral imaging flow-cytometry-based technology, we analyzed the lethal fate of cancer cells that were treated with conventional anticancer agents and co-cultured with untreated cells, observing that anticancer agents can simultaneously trigger cell-autonomous and non-cell-autonomous death in treated and untreated cells. After ionizing radiation, oxaliplatin, or cisplatin treatment, fractions of treated cancer cell populations were eliminated through cell-autonomous death mechanisms, while other fractions of the treated cancer cells engulfed and killed neighboring cells through non-cell-autonomous processes, including cellular cannibalism. Under conditions of treatment with paclitaxel, non-cell-autonomous and cell-autonomous death were both detected in the treated cell population, while untreated neighboring cells exhibited features of apoptotic demise. The transcriptional activity of p53 tumor-suppressor protein contributed to the execution of cell-autonomous death, yet failed to affect the non-cell-autonomous death by cannibalism for the majority of tested anticancer agents, indicating that the induction of non-cell-autonomous death can occur under conditions in which cell-autonomous death was impaired. Altogether, these results reveal that chemotherapy and radiotherapy can induce both non-cell-autonomous and cell-autonomous death of cancer cells, highlighting the heterogeneity of cell death responses to anticancer treatments and the unsuspected potential contribution of non-cell-autonomous death to the global effects of anticancer treatment