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International audience; This paper presents an erosion interpretation of cohesive granular materials stressed by an impinging jet based on the results of a micromechanical simulation model. The numerical techniques are briefly described, relying on a two-dimensional Lattice Boltzmann Method coupled with a Discrete Element Methods including a simple model of solid intergranular cohesion.These are then used to perform a parametric study of a planar jet in the laminar regime impinging the surface of granular samples with different degrees of cohesive strength. The results show the pertinence of using a generalized form of the Shields criterion for the quantification of the erosion threshold, which is valid for cohesionless samples, through empirical calibration, and also for cohesive ones. Furthermore, the scouring kinetics are analysed here from the perspective of a self-similar expansion of the eroded crater leading to the identification of a characteristic erosion time and the quantification of the classical erosion coefficient. However, the presented results also challenge the postulate of a local erosion law including erodibility parameters as intrinsic material properties. The paper then reviews the main limitations of the simulation and current interpretation models, and discusses the potential causes for the observed discrepancies, questioning the pertinenceof using time-averaged macroscopic relations to correctly describe soil erosion. The paper concludes addressing this question with a complementary study of the presented simulations re-assessed at the particle-scale. The resulting local critical shear stress of single grains reveals a very wide dispersion of the data but nevertheless appears to confirm the general macroscopic trend derived for the cohesionless samples, while the introduction of cohesion implies a significant but systematic quantitative deviation between the microscopic and macroscopic estimates. Nevertheless, the micro data still shows consistently that the critical shear stress does actually vary approximately in linear proportion of the adhesive force.

Endo-lysosomes transport along microtubules and clustering in the perinuclear area are two necessary steps for microbes to activate specialized phagocyte functions. We report that RUN and FYVE domain-containing protein 3 exists as two alternative isoforms distinguishable by the presence of a C-terminal FYVE domain and by their affinity for PtdIns(3)P on endosomal membranes. The FYVE domain-bearing isoform (iRUFY3) is preferentially expressed in immune cells and up-regulated upon activation by microbes and cytokines. iRUFY3 is necessary for ARL8b+/LAMP1+ endo-lysosomes positioning in the pericentriolar organelles cloud of LPS-activated macrophages. We show that iRUFY3 controls macrophages migration, MHC II presentation and responses to Interferon-γ while being required for Intracellular Salmonella replication. Specific inactivation of Rufy3 in phagocytes leads to aggravated pathologies in mouse upon LPS injection or bacterial pneumonia. This study highlights iRUFY3 function, as a novel modulator of immunity, controlling endo-lysosomes dynamics, and ultimately regulating the function of activated phagocytes.

Cellular metabolism underpins immune cell functionality, yet our understanding of metabolic influences in human dendritic cell biology and their ability to orchestrate immune responses is poorly developed. Here, we map single-cell metabolic states and immune profiles of inflammatory and tolerogenic monocytic dendritic cells using recently developed multiparametric approaches. Single-cell metabolic pathway activation scores reveal simultaneous engagement of multiple metabolic pathways in distinct monocytic dendritic cell differentiation stages. GM-CSF/IL4-induce rapid reprogramming of glycolytic monocytes and transient co-activation of mitochondrial pathways followed by TLR4-dependent maturation of dendritic cells. Skewing of the mTOR:AMPK phosphorylation balance and upregulation of OXPHOS, glycolytic and fatty acid oxidation metabolism underpin metabolic hyperactivity and an immunosuppressive phenotype of tolerogenic dendritic cells, which exhibit maturation-resistance and a de-differentiated immune phenotype marked by unique immunoregulatory receptor signatures. This single-cell dataset provides important insights into metabolic pathways impacting the immune profiles of human dendritic cells.

Background Founder populations that have recently undergone important genetic bottlenecks such as French-Canadians and Ashkenazi Jews can harbor some pathogenic variants at a higher carrier rate than the general population, putting them at a higher risk for certain genetic diseases. In these populations, there can be considerable benefit to performing ethnic-based or expanded preconception carrier screening, which can help in the prevention or early diagnosis and management of some genetic diseases. Acadians are descendants of French immigrants who settled in the Atlantic Coast of Canada in the seventeenth century. Yet, the Acadian population has never been investigated for the prevalence/frequency of disease-causing genetic variants. Methods An exome sequencing panel for 312 autosomal recessive and 30 X-linked diseases was designed and specimens from 60 healthy participants were sequenced to assess carrier frequency for the targeted diseases. Results In this study, we show that a sample population of Acadians in South-East New Brunswick harbor variants for 28 autosomal recessive and 1 X-linked diseases, some of which are significantly more frequent in comparison to reference populations. Conclusion Results from this pilot study suggests a need for further investigation of genomic variation in this population and possibly implementation of targeted carrier and neonatal screening programs.

Forced answering (FA) is a frequent answer format in online surveys that forces respondents to answer each question in order to proceed through the questionnaire. The underlying rationale is to decrease the amount of missing data. Despite its popularity, empirical research on the impact of FA on respondents’ answering behavior is scarce and has generated mixed findings. In fact, some quasi-experimental studies showed that FA has detrimental consequences such as increased survey dropout rates and faking behavior. Notably, a theoretical psychological process driving these effects has hitherto not been identified. Therefore, the aim of the present study was twofold: First, we sought to experimentally replicate detrimental effects of FA on online questionnaire data quality. Second, we tried to uncover an explanatory psychological mechanism. Specifically, we hypothesized that FA effects are mediated through reactance. Zero-order effects showed that FA increased state reactance and questionnaire dropout as well as reduced answer length in open-ended questions. Results of survival and mediation analyses corroborate negative FA effects on data quality and the proposed psychological process.

Abstract. General self-efficacy is a central personality trait often evaluated in surveys as context variable. It can be interpreted as a personal coping resource reflecting individual belief in one’s overall competence to perform across a variety of situations. The German-language Allgemeine-Selbstwirksamkeit-Kurzskala (ASKU) is a reliable and valid instrument to assess this disposition in the German-speaking countries based on a three-item equation. This study develops a French version of the ASKU and tests this French version for measurement invariance compared to the original ASKU. A reliable and valid French instrument would make it easy to collect data in the French-speaking countries and allow comparisons between the French and German results. Data were collected on a sample of 1,716 adolescents. Confirmatory factor analysis resulted in a good fit for a single-factor model of the data (in total, French, and German version). Additionally, construct validity was assessed by elucidating intercorrelations between the ASKU and different factors that should theoretically be related to ASKU. Furthermore, we confirmed configural and metric as well as scalar invariance between the different language versions, meaning that all forms of statistical comparison between the developed French version and the original German version are allowed.

When performing western blots for protein detection using the classical Laemmli method, experimenters often encounter difficulties with the detection of transmembrane proteins involved in lipid or fatty acid metabolism. A crucial phase in sample preparation is heating the samples to 100 °C in a Laemmli sample buffer containing SDS before separation by polyacrylamide gel electrophoresis (PAGE). In the current study, the analysis of several proteins was performed following modifications of the heating step during sample preparation. Multiple samples of the human Jurkat cell line were prepared using commercial or homemade Laemmli sample buffer. Samples were subjected to incubation at different temperatures for varying periods of time prior to separation by SDS-PAGE, transfer onto PVDF membranes and detection with specific antibodies. In samples incubated at temperatures of 25 °C, 40 °C, 70 °C and 100 °C, detection of the transmembrane protein elongase of long chain fatty acids 5 (ELOVL5) significantly decreased with temperature to a near total absence of signal at 100 °C. Heating (100 °C) the samples even for 1 min resulted in significant loss of ELOVL5 band intensity that was associated with the appearance of higher molecular weight immunoreactive materials. Loss of ELOVL5 band intensity was also observed with heating of samples at 100 °C prepared from HepG2, HEK293, MCF-7 and SKRB cells. The robust induction of ELOVL5 in stimulated primary T cells was not detected when sample were heated. The detection of fatty acid-metabolizing enzymes stearoyl-CoA desaturase-1 and long-chain-fatty-acid-CoA ligases 3 and 4 showed bands with significantly less intensity after heating at 100 °C compared to samples prepared at room temperature. Heating samples at 100 °C did not affect the detection of transmembrane proteins ERBB2 and five-lipoxygenase activating protein, or the soluble 5-lipoxygenase protein. Overall, the number of transmembrane passes of a protein was not predictive of loss of band intensity after heating, however this study indicates that sample heating can drastically affect the ability to detect proteins following separation by SDS-PAGE. This has implications for any detection methods that follow SDS-PAGE.

Additional file 2. Figure S1. Probability of detecting at least one variant as a function of allele frequency for a sample of 60 individuals. The minor allele frequencies in the reference population for the variants observed in our sample range from 9 × 10-6to 0.5.

This paper explores dynamic load balancing algorithms used by asynchronous many-task (AMT), or ‘taskbased’, programming models to optimize task placement for scientific applications with dynamic workload imbalances. AMT programming models use overdecomposition of the computational domain. Overdecompostion provides a natural mechanism for domain developers to expose concurrency and break their computational domain into pieces that can be remapped to different hardware. This paper explores fully distributed load balancing strategies that have shown great promise for exascale-level computing but are challenging to theoretically reason about and implement effectively. We present a novel theoretical analysis of a gossip-based load balancing protocol and use it to build an efficient implementation with fast convergence rates and high load balancing quality. We demonstrate our algorithm in a next-generation plasma physics application (EMPIRE) that induces time-varying workload imbalance due to spatial non-uniformity in particle density across the domain. Our highly scalable, novel load balancing algorithm, achieves over a 3x speedup (particle work) compared to a bulk-synchronous MPI implementation without load balancing.

Leukotriene B4 (LTB4) plays a prominent role in innate immunity as it induces phagocyte recruitment, the release of antimicrobial effectors, and as it potentiates the ingestion and killing of pathogens. In humans, LTB4 has a short half-life and is rapidly metabolized by leukocytes, notably into 20-OH- and 20-COOH-LTB4 by neutrophils. Although these LTB4 metabolites bind to the BLT1 receptor with high affinity, they activate neutrophils to a much lower extent than LTB4. We thus postulated that LTB4 metabolites could dampen BLT1-mediated responses, therefore limiting the impact of LTB4 on human neutrophil functions. We found that 20-OH-LTB4 and 20-COOH-LTB4 inhibited all of the LTB4-mediated neutrophil responses we tested (migration, degranulation, leukotriene biosynthesis). The potencies of the different compounds at inhibiting LTB4-mediated responses were 20-OH-LTB4 = CP 105,696 (BLT1 antagonist) > > 20-COOH-LTB4 ≥ resolvin E1 (RVE1). In contrast, the fMLP- and IL-8-mediated responses we tested were not affected by the LTB4 metabolites or RVE1. 20-OH-LTB4 and 20-COOH-LTB4 also inhibited the LTB4-mediated migration of human eosinophils but not that induced by 5-KETE. Moreover, using 20-COOH-LTB4, LTB4, and LTB4-alkyne, we show that LTB4 is a chemotactic, rather than a chemokinetic factor for both human neutrophils and eosinophils. In conclusion, our data indicate that LTB4 metabolites and RVE1 act as natural inhibitors of LTB4-mediated responses. Thus, preventing LTB4 ω-oxidation might result in increased innate immunity and granulocyte functions.

PAX5 and EBF1 work synergistically to regulate genes that are involved in B lymphocyte differentiation. We used the KIS-1 diffuse large B cell lymphoma cell line, which is reported to have elevated levels of PAX5 expression, to investigate the mechanism of EBF1- and PAX5-regulated gene expression. We demonstrate the lack of expression of hallmark B cell genes, including CD19, CD79b, and EBF1, in the KIS-1 cell line. Upon restoration of EBF1 expression we observed activation of CD19, CD79b and other genes with critical roles in B cell differentiation. Mass spectrometry analyses of proteins co-immunoprecipitated with PAX5 in KIS-1 identified components of the MLL H3K4 methylation complex, which drives histone modifications associated with transcription activation. Immunoblotting showed a stronger association of this complex with PAX5 in the presence of EBF1. Silencing of KMT2A, the catalytic component of MLL, repressed the ability of exogenous EBF1 to activate transcription of both CD19 and CD79b in KIS-1 cells. We also find association of PAX5 with the MLL complex and decreased CD19 expression following silencing of KMT2A in other human B cell lines. These data support an important role for the MLL complex in PAX5-mediated transcription regulation.

The main objective of the German Emigration and Remigration Panel Study (GERPS) is to establish a longitudinal data set that provides information on life trajectories of international migrants. However, a large amount of paradata were also collected in order to obtain meta-information on respondents’ survey participation. This auxiliary information can help to optimize data quality at all stages of the survey process. By continuing the existing discussion in the field of online surveys, this chapter pursues a twofold objective: it reflects device usage (mobile vs. computer) and elucidates determinants of device choice. In particular, it analyses whether selectivity effects due to respondent’s device choices bias the sample. Moreover, this chapter investigates differences in response time between devices to detect differences in response burden. The analysis of response burden differences by device is an important issue, since an increased device-specific response burden can be a predictor of actual and further panel dropouts. In both device-specific selectivity and survey burden, only slight differences were found between mobile and desktop devices. Using these data, the following paper addresses the need to analyse potential sources of survey error and provides evidence that GERPS data do not appear to contain noteworthy bias attributed to device usage.

After an initial phase of low reactivity from the French public health authorities, in the face of the emergence of SARS-CoV-2 in February 2020, various Non Pharmaceutical Interventions (NPIs) were put in place (strict stay-at-home orders, followed by mandatory mask wearing in public places, curfews, partial lockdowns, etc.). In our knowledge, no study has independently assessed their respective effectiveness in an independent manner nor a synergistic manner. Our study has retrospectively studied (from 03/01/2020 to 30/01/2021), using metropolitan France data, the association strength (using normalized mutual information) as well as the linear correlation (using Pearson’s correlation) between more restrictive NPIs (mrNPIs) and epidemiological markers of COVID-19. All mrNPIs were moderately associated with a viral reproduction rate decrease but were associated neither with a decrease in COVID-19 daily hospitalizations, nor with COVID-19 daily ICU admissions. This paper is only for academic discussion, conclusions need to be confirmed by further research. Data and codes were available here http://gitlab.com/covid-data-2/lockdown-and-curfew.

Natural soil deposits such as carbonate sands in the marine environment may show an effective cohesion due to intergranular solid bridges formed by calcareous precipitation. Such cementation effect endows the granular material with the ability to resist some degree of tensile stress in addition to the compressive and shearing resistance proper of uncemented frictional sands. tensile resistance of such materials may be quantified based on measures of debonding force at the micro-scale and using appropriate homogenization techniques. However, it is still a challenge to assess the influence of solid intergranular cohesion on the mechanical behaviour of soils in many practical engineering problems. Recent advances both in computational hardware and parallelization strategies make it nowadays possible to address such problems from a micromechanical perspective. Here we introduce a simple model for solid cohesion and its implementation within a 3D discrete element framework. The model involves a classical viscoelastic bond rheology and specific debonding modes for tensile, shearing, bending and torsional solicitations. We finally present a calibration of the model to match experimental data from an artificial granular soil made out of cemented glass beads and a validation of the approach with a macro-mechanical application.

Moving–particularly to a new country–is fraught with risks as migrants leave familiar legal frameworks and cultural institutions behind them. To date, little is known about the psychological determinants of international migration. This chapter helps to fill this gap by analysing data from the first wave of the German Emigration and Remigration Panel Study (GERPS) in combination with data on non-mobile individuals from the German Socio-Economic Panel Study (SOEP). The analyses presented examine whether the risk attitudes of internationally mobile Germans (‘movers’) differ from those of their non-mobile counterparts (‘stayers’). The results show that–with control for key socio-demographic and socio-economic determinants of risk affinity–both emigrants and remigrants report a significantly higher willingness to take risks than stayers. Risk affinity differs within the group of internationally mobile individuals: Emigrants moving to geographically and culturally distant non-European countries report higher risk affinity than those moving to Germany’s neighbouring countries. Emigrants with multiple previous emigration periods are also more willing to take risks. These findings suggest that voluntary emigration from wealthy countries like Germany is only partly a matter of living conditions. Rather, (repeated) emigration seems to be a matter of personality and an expression of a more adventurous lifestyle.

The development of high-throughput technologies revealed the existence of non-canonical short open reading frames (sORFs) on most eukaryotic RNAs. They are ubiquitous genetic elements highly conserved across species and suspected to be involved in numerous cellular processes. MetamORF (http://metamorf.hb.univ-amu.fr/) aims to provide a repository of unique sORFs identified in the human and mouse genomes with both experimental and computational approaches. By gathering publicly available sORF data, normalizing it and summarizing redundant information, we were able to identify a total of 1,162,675 unique sORFs. Despite the usual characterization of ORFs as short, upstream or downstream, there is currently no clear consensus regarding the definition of these categories. Thus, the data has been reprocessed using a normalized nomenclature. MetamORF enables new analyses at loci, gene, transcript and ORF levels, that should offer the possibility to address new questions regarding sORF functions in the future. The repository is available through an user-friendly web interface, allowing easy browsing, visualization, filtering over multiple criteria and export possibilities. sORFs could be searched starting from a gene, a transcript, an ORF ID, or looking in a genome area. The database content has also been made available through track hubs at UCSC Genome Browser.

We present the execution model of Virtual Transport (VT) a new, Asynchronous Many-Task (AMT) runtime system that provides unprecedented integration and interoperability with MPI. We have developed VT in conjunction with large production applications to provide a highly incremental, high-value path to AMT adoption in the dominant ecosystem of MPI applications, libraries, and developers. Our aim is that the `MPI+X' model of hybrid parallelism can smoothly extend to become `MPI+VT +X'. We illustrate a set of design and implementation techniques that have been useful in building VT. We believe that these ideas and the code embodying them will be useful to others building similar systems, and perhaps provide insight to how MPI might evolve to better support them. We motivate our approach with two applications that are adopting VT and have begun to benefit from increased asynchrony and dynamic load balancing.

In stressed cells, phosphorylation of eukaryotic initiation factor 2α (eIF2α) controls transcriptome-wide changes in mRNA translation and gene expression known as the integrated stress response (ISR). We show here that dendritic cells (DCs) display unusually high eIF2α phosphorylation, which is mostly caused by a developmentally regulated activation of the ER kinase PERK (EIF2AK3). Despite high p-eIF2α levels, differentiated DCs display active protein synthesis and no signs of a chronic ISR. eIF2α phosphorylation does not majorly impact DC differentiation nor cytokines production. It is however important to adapt protein homeostasis to the variations imposed on DCs by the immune or physiological contexts. This biochemical specificity prevents translation arrest and expression of the transcription factor ATF4 during ER-stress induction by subtilase cytotoxin or upon DC stimulation with bacterial lipopolysaccharides. This is also exemplified by the influence of the actin cytoskeleton dynamics on eIF2α phosphorylation and the migratory deficit observed in PERK-deficient DCs.

© The Author(s), under exclusive licence to Springer Nature America, Inc. 2021, Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here, we found that γδ T cell subsets making either interferon-γ (IFN-γ) or interleukin (IL)-17 have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during thymic development and were stably maintained in the periphery and within tumors. Moreover, pro-tumoral IL-17+ γδ T cells selectively showed high lipid uptake and intracellular lipid storage and were expanded in obesity and in tumors of obese mice. Conversely, glucose supplementation enhanced the antitumor functions of IFN-γ+ γδ T cells and reduced tumor growth upon adoptive transfer. These findings have important implications for the differentiation of effector γδ T cells and their manipulation in cancer immunotherapy., This work was supported by the Wellcome Trust (092973/Z/10/Z to D.J.P.), Biotechnology and Biological Sciences Research Council (BBSRC) UK (BB/R017808/1 to D.J.P.), European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 646701 to B.S.-S.; StG_679173 to L.L.), Science Foundation Ireland (SFI) (16/FRL/3865 to L.L.), NIH (NS115064, HG008155, AG062377 to M.K.), NIH (R01 AI134861 and metabolic core grant S10 OD020100 to L.L.), Fundação Astrazeneca (Prémio FAZ Ciência 2019 to B.S.-S. and N.L.) and PAC-PRECISE LISBOA-01-0145-FEDER-016394, co-funded by FEDER (POR Lisboa 2020 (Programa Operacional Regional de Lisboa, do Portugal 2020)) and Fundação para a Ciência e a Tecnologia (Portugal). N.L. is supported by a postdoctoral fellowship from EMBO (ALTF 752-2018); S.M. was supported by a studentship from the Medical Research Council (MRC) UK; G.F. is supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 752932; and A.D., S.C., L.D. and H.P. are supported by Irish Research Council fellowships.

International migration between economically highly developed countries is a central component of global migration flows. Still, surprisingly little is known about the international mobility of the populations of these affluent societies. The aim of the German Emigration and Remigration Panel Study (GERPS) is to collect data to analyse the individual consequences of international migration as well as the consequences for the country of origin. GERPS is based on an origin-based multistage probability sample using the German population registers as a sampling frame. The realised net sample includes more than 11,000 persons who recently moved abroad from Germany and persons returning to Germany after having lived abroad. The study follows a multi-destination country design and allows comparative analyses of migrants and non-migrants who stayed in the country of origin. GERPS is a panel study with at least four waves during a period of at least 24 months. This documentation, however, presents the methodology and the data for the first wave providing the baseline survey. Detailed information is provided to invite external researchers to apply the new data infrastructure to their own research and to disseminate the innovative research design to construct migrant samples.

PUFAs are important constituents of membrane glycerophospholipids. However, changes in the capacities to incorporate and metabolize PUFAs when cells enter the cell cycle have not been thoroughly studied. In this study, differences in the incorporation and metabolism of exogenous PUFAs in resting and proliferating primary human T-cells and in the Jurkat cell line were measured. Overall, proliferating T-cells and Jurkat cells had a greater capacity to incorporate and elongate exogenous 18- and 20-carbon PUFAs compared with resting T-cells. Proliferating T-cells and Jurkat cells also showed a greater capacity to desaturate 18-carbon PUFA substrates. Consistent with these observations, a significant increase in the expression of fatty acid desaturase (FADS) 1, FADS2, and elongation of very long chain fatty acids protein (ELOVL) 5 was measured in proliferating T-cells compared with resting T-cells. No quantifiable ELOVL2 was measured. Knockdown of ELOVL5 in T-cells and Jurkat cells significantly affected cellular monounsaturated and PUFA profiles and strongly impaired the elongation of 18- and 20-carbon PUFAs. In conclusion, the induction of proliferation in human T-cells is associated with a significant increase in the capacity to take up and metabolize exogenous PUFAs, and ELOVL5 is responsible for the elongation of 18- and 20-carbon PUFAs in these cells.

The article investigates the political discourse on youth in the aftermath of the economic crisis. Based on the EU Youth Strategy, the article analyses how the concept of youth is shaped by political discourse and agenda setting. The authors show that the EU Youth Strategy is highly focussed on activating young people as entrepreneurs who are supposed to become active and productive members of society. They argue that the Strategy represents specific meanings about young people and thus reframes the concept of youth as an “entrepreneurial self”.

DNA methylation has garnered much attention in recent years for its diagnostic potential in multiple conditions including cancer and neurodegenerative diseases. Conversely, advances regarding the potential diagnostic relevance of DNA methylation status have been sparse in the field of amyotrophic lateral sclerosis (ALS) even though patients diagnosed with this condition would significantly benefit from improved molecular assays aimed at furthering the current diagnostic and therapeutic options available. This review will provide an overview of the current diagnostic approaches available for ALS diagnosis and discuss the potential clinical usefulness of DNA methylation. We will also present examples of DNA methylation as a diagnostic tool in various types of cancer and neurodegenerative conditions and expand on how circulating cfDNA methylation may be leveraged for the early detection of ALS. In general, this article will reinforce the importance of cfDNA methylation as diagnostic tools and will further highlight its clinical relevance for persons diagnosed with ALS.

Formulas for incremental or parallel computation of second order central moments have long been known, and recent extensions of these formulas to univariate and multivariate moments of arbitrary order have been developed. Such formulas are of key importance in scenarios where incremental results are required and in parallel and distributed systems where communication costs are high. We survey these recent results, and improve them with arbitrary-order, numerically stable one-pass formulas which we further extend with weighted and compound variants. We also develop a generalized correction factor for standard two-pass algorithms that enables the maintenance of accuracy over nearly the full representable range of the input, avoiding the need for extended-precision arithmetic. We then empirically examine algorithm correctness for pairwise update formulas up to order four as well as condition number and relative error bounds for eight different central moment formulas, each up to degree six, to address the trade-offs between numerical accuracy and speed of the various algorithms. Finally, we demonstrate the use of the most elaborate among the above mentioned formulas, with the utilization of the compound moments for a practical large-scale scientific application.

International audience; Energetic metabolism reprogramming is critical for cancer and immune responses. Current methods to functionally profile the global metabolic capacities and dependencies of cells are performed in bulk. We designed a simple method for complex metabolic profiling called SCENITH, for single-cell energetic metabolism by profiling translation inhibition. SCENITH allows for the study of metabolic responses in multiple cell types in parallel by flow cytometry. SCENITH is designed to perform metabolic studies ex vivo, particularly for rare cells in whole blood samples, avoiding metabolic biases introduced by culture media. We analyzed myeloid cells in solid tumors from patients and identified variable metabolic profiles, in ways that are not linked to their lineage or their activation phenotype. SCENITH's ability to reveal global metabolic functions and determine complex and linked immune-phenotypes in rare cell subpopulations will contribute to the information needed for evaluating therapeutic responses or patient stratification.

The novel COVID-19 disease is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a new virus of the coronavirus family, SARS-CoV-2. Alike with other coronaviruses, some studies show a COVID-19 neurotropism, inducing de-myelination lesions as encountered in Guillain-Barré syndrome. In particular, an Italian report concluded that there is a significant vitamin D deficiency in COVID-19 infected patients. In the current study, we applied a Pearson correlation test to public health as well as weather data, in order to assess the linear relationship between COVID-19 mortality rate and the sunlight exposure. For instance in continental metropolitan France, average annual sunlight hours are significantly (for a p-value of 1.532 × 10−32) correlated to the COVID-19 mortality rate, with a Pearson coefficient of -0.636. This correlation hints at a protective effect of sunlight exposure against COVID-19 mortality. This paper is proposed to foster academic discussion and its hypotheses and conclusions need to be confirmed by further research.

Polyunsaturated fatty acids (PUFA) are important components of cellular membranes, serving both structural and signaling functions. Investigation of the functional responses of cells to various PUFA often involves cell culture experiments, which can then inform or guide subsequent in vivo and clinical investigations. In this study, human carcinoma and leukemia cell lines (MCF-7, HepG2, THP-1, Jurkat) were incubated for 3 days in the presence of up to 150 μM of exogenous arachidonic or eicosapentaenoic acids. At concentrations up to 20 μM these PUFA were enriched in cellular phospholipids, but at concentrations of 20 μM or higher cells accumulated large quantities of these PUFA and their elongation products into triglycerides. This coincided with decreased cell proliferation and enhanced apoptosis. Inhibition of DGAT1 but not DGAT2 enhanced the cytotoxic effect of exogenous PUFA suggesting a protective role of PUFA sequestration into TGs. Lower (10 μM) and higher (50 μM) exogenous PUFA concentrations also had different impacts on the expression of PUFA metabolizing enzymes. Overall, these results indicate that caution must be exercised when planning in vitro experiments since elevated concentrations of PUFA can lead to dysfunctional cellular responses that are not predictive of in vivo responses to dietary PUFA.

Leukotriene B

Global collectives (reductions/aggregations) are ubiquitous and feature in nearly every application of distributed high-performance computing (HPC). While it is advisable to devise algorithms by placing collectives off the critical path of execution, they are sometimes unavoidable for correctness, numerical convergence and analyses purposes. Scalable algorithms for distributed collectives are well studied and have become an integral part of MPI, but new and emerging distributed computing frameworks and paradigms such as Asynchronous Many-Task (AMT) models lack the same sophistication for distributed collectives. Since the central promise of AMT runtimes is that they automatically discover, and expose, task dependencies in the underlying program and can schedule work optimally to minimize idle time and hide data movement, a naively designed collectives protocol can completely offset any gains made from asynchronous execution. In this study we demonstrate that scalable distributed collectives are indispensable for performance in AMT models. We design, implement and test the performance of a scalable collective algorithm in Legion, an exemplar data-centric AMT programming model. Our results show that AMT systems contain the necessary primitives that allow for fully scalable collectives without breaking the transparent data movement abstractions. Scalability tests of an integrated Legion 1D stencil mini-application show the clear benefit of implementing scalable collectives and the performance degradation when a naive collectives alternative is used instead.

Major histocompatibility complex (MHC) molecules present peptide antigens to T lymphocytes and initiate immune responses. The peptides loaded onto MHC class I or MHC class II molecules can be derived from cytosolic proteins, both self and foreign. A variety of cellular processes, including endocytosis, vesicle trafficking, and autophagy, play critical roles in presentation of these antigens. We discuss the role of autophagy, a major intracellular degradation system that delivers cytoplasmic constituents to lysosomes in both MHC class I and II-restricted antigen presentation. We propose the new term "Type 2 cross-presentation" (CP2) to define the autophagy-dependent processes leading to MHC II-restricted presentation of intracellular antigens by professional antigen presenting cells. A better understanding of Type 2 cross-presentation may guide future efforts to control the immune system through autophagy manipulation.

Due to the principle of risk pooling exercised by life and health insurers, the latter have the right to select and segment the risks they cover. While this legitimate approach on principle protects them from penal proceedings related to discrimination based on health status, it can now be observed that the imperatives of public solidarity or, respectively, the requirement to furnish justifications relevant to the differentiated treatment of insured persons produce more and more numerous exceptions to the above-mentioned rule.

Les assureurs de personnes, du fait de la mutualisation d'assurance, disposent du droit de selectionner et de segmenter les risques qu'ils couvrent. Si cette demarche legitime les abrite en principe des poursuites penales pour discrimination fondees sur l'etat de sante, on observe dorenavant que les imperatifs de solidarite publique ou l'exigence de justifications pertinentes au traitement differencie des assures produisent des exceptions de plus en plus nombreuses a la regle ci-dessus rappelee.

Wenn du etwas wissen willst, frage! – Was im Alltag so einfach klingt, ist in der Methodenforschung ein aufwendiger Prozess. Sowohl das Formulieren von Fragen als auch die Gestaltung des Fragebogens bedarf der Berucksichtigung unterschiedlicher Regeln, ohne die durch Befragungen gewonnene Daten schnell unbrauchbar werden konnen. So spielen in einem systematischen Frage-Antwort-Vorgang zentrale Kommunikationsregeln und psychologische Ablaufe eine Rolle, die es als Forscher dringend zu beachten gilt. Aufbauend auf diesen zentralen Erkenntnissen befasst sich der folgende Beitrag mit unterschiedlichen Aspekten, die die Qualitat von Fragebogen beeinflussen. Anhand von praxisbezogenen Beispielen, die aus Erfahrungen mit diversen Befragungen sowie einer systematischen Methodenforschung resultieren, werden dabei dem Leser Leitlinien zur Optimierung von eigenen Fragebogen an die Hand gegeben. Gleichwohl gilt es dabei zu beachten, dass es allgemeingultige Regeln, die auf jede Forschungsfrage, Untersuchungspopulation oder auch Erhebungsart anwendbar sind, nicht geben kann. Die hier erarbeiteten Instruktionen dienen vielmehr der Vermittlung wesentlicher Kenntnisse, die zum Vermeiden grober Fehler fuhren sollen und es dem Forscher zugleich erlauben, bei Bedarf die Leitlinien nach kritischer Betrachtung eigenstandig anzupassen.

Recognition of pathogen derived molecules by Pattern Recognition Receptors (PRR) induces the production of cytokines (i.e. type I interferons) that stimulate the surrounding cells to transcribe and translate hundreds of genes, in order to prevent further infection and organize the immune response. Here, we report on the rising matter that metabolism sensing and gene expression control at the level of mRNA translation, allow swift responses that mobilize host defenses and coordinate innate responses to infection.