Ocelotl: Large Trace Overviews Based on Multidimensional Data Aggregation

International audiencePerformance analysis of parallel applications is commonly based on execution traces that might be investigated through visualization techniques. The weak scalability of such techniques appears when traces get larger both in time (many events registered) and space (many processing elements), a very common situation for current large-scale HPC applications. In this paper we present an approach to tackle such scenarios in order to give a correct overview of the behavior registered in very large traces. Two configurable and controlled aggregation-based techniques are presented: one based exclusively on the temporal aggregation, and another that consists in a spatiotemporal aggregation algorithm. The paper also details the implementation and evaluation of these techniques in Ocelotl, a performance analysis and visualization tool that overcomes the current graphical and interpretation limitations by providing a concise overview registered on traces. The experimental results show that Ocelotl helps in detecting quickly and accurately anomalies in 8 GB traces containing up to two hundred million of events

Bistable Cell Fate Specification as a Result of Stochastic Fluctuations and Collective Spatial Cell Behaviour

BACKGROUND: In culture, isogenic mammalian cells typically display enduring phenotypic heterogeneity that arises from fluctuations of gene expression and other intracellular processes. This diversity is not just simple noise but has biological relevance by generating plasticity. Noise driven plasticity was suggested to be a stem cell-specific feature. RESULTS: Here we show that the phenotypes of proliferating tissue progenitor cells such as primary mononuclear muscle cells can also spontaneously fluctuate between different states characterized by the either high or low expression of the muscle-specific cell surface molecule CD56 and by the corresponding high or low capacity to form myotubes. Although this capacity is a cell-intrinsic property, the cells switch their phenotype under the constraints imposed by the highly heterogeneous microenvironment created by their own collective movement. The resulting heterogeneous cell population is characterized by a dynamic equilibrium between "high CD56" and "low CD56" phenotype cells with distinct spatial distribution. Computer simulations reveal that this complex dynamic is consistent with a context-dependent noise driven bistable model where local microenvironment acts on the cellular state by encouraging the cell to fluctuate between the phenotypes until the low noise state is found. CONCLUSIONS: These observations suggest that phenotypic fluctuations may be a general feature of any non-terminally differentiated cell. The cellular microenvironment created by the cells themselves contributes actively and continuously to the generation of fluctuations depending on their phenotype. As a result, the cell phenotype is determined by the joint action of the cell-intrinsic fluctuations and by collective cell-to-cell interactions

Investigation of grain orientations of melt-textured HTSC with addition of uranium oxide, Y2O3 and Y2BaCuO5

Local grain orientations were studied in melt-textured YBCO samples processed with various amounts of depleted uranuim oxide (DU) and Y 2O3 by means of electron backscatter diffraction (EBSD) analysis. The addition of DU leads to the formation of Ucontaining nanoparticles (Y2Ba4CuUOx) with sizes of around 200 nm, embedded in the superconducting Y-123 matrix. The orientation of the Y 2BaCuO5 (Y-211) particles, which are also present in the YBCO bulk microstructure, is generally random as is the case in other melttextured Y-123 samples. The presence of Y-211 particles, however, also affects the orientation of the Y-123 matrix in these samples

Pre-clinical Development of a Lentiviral Vector Expressing the Anti-sickling \u3b2AS3 Globin for Gene Therapy for Sickle Cell Disease

Sickle cell disease (SCD) is caused by a mutation (E6V) in the hemoglobin (Hb) \u3b2-chain that induces polymerization of Hb tetramers, red blood cell deformation, ischemia, anemia, and multiple organ damage. Gene therapy is a potential alternative to human leukocyte antigen (HLA)-matched allogeneic hematopoietic stem cell transplantation, available to a minority of patients. We developed a lentiviral vector expressing a \u3b2-globin carrying three anti-sickling mutations (T87Q, G16D, and E22A) inhibiting axial and lateral contacts in the HbS polymer, under the control of the \u3b2-globin promoter and a reduced version of the \u3b2-globin locus-control region. The vector (GLOBE-AS3) transduced 60%\u201380% of mobilized CD34+ hematopoietic stem-progenitor cells (HSPCs) and drove \u3b2AS3-globin expression at potentially therapeutic levels in erythrocytes differentiated from transduced HSPCs from SCD patients. Transduced HSPCs were transplanted in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG)-immunodeficient mice to analyze biodistribution, chimerism, and transduction efficiency in bone marrow (BM), spleen, thymus, and peripheral blood 12\u201314 weeks after transplantation. Vector integration site analysis, performed in pre-transplant HSPCs and post-transplant BM cells from individual mice, showed a normal lentiviral integration pattern and no evidence of clonal dominance. An in vitro immortalization (IVIM) assay showed the low genotoxic potential of GLOBE-AS3. This study enables a phase I/II clinical trial aimed at correcting the SCD phenotype in juvenile patients by transplantation of autologous hematopoietic stem cells (HSC) transduced by GLOBE-AS3

Genetics of Dispersal

Dispersal is a process of central importance for the ecological and evolutionary dynamics of populations and communities, because of its diverse consequences for gene flow and demography. It is subject to evolutionary change, which begs the question, what is the genetic basis of this potentially complex trait? To address this question, we (i) review the empirical literature on the genetic basis of dispersal, (ii) explore how theoretical investigations of the evolution of dispersal have represented the genetics of dispersal, and (iii) discuss how the genetic basis of dispersal influences theoretical predictions of the evolution of dispersal and potential consequences. Dispersal has a detectable genetic basis in many organisms, from bacteria to plants and animals. Generally, there is evidence for significant genetic variation for dispersal or dispersal-related phenotypes or evidence for the micro-evolution of dispersal in natural populations. Dispersal is typically the outcome of several interacting traits, and this complexity is reflected in its genetic architecture: while some genes of moderate to large effect can influence certain aspects of dispersal, dispersal traits are typically polygenic. Correlations among dispersal traits as well as between dispersal traits and other traits under selection are common, and the genetic basis of dispersal can be highly environment-dependent. By contrast, models have historically considered a highly simplified genetic architecture of dispersal. It is only recently that models have started to consider multiple loci influencing dispersal, as well as non-additive effects such as dominance and epistasis, showing that the genetic basis of dispersal can influence evolutionary rates and outcomes, especially under non-equilibrium conditions. For example, the number of loci controlling dispersal can influence projected rates of dispersal evolution during range shifts and corresponding demographic impacts. Incorporating more realism in the genetic architecture of dispersal is thus necessary to enable models to move beyond the purely theoretical towards making more useful predictions of evolutionary and ecological dynamics under current and future environmental conditions. To inform these advances, empirical studies need to answer outstanding questions concerning whether specific genes underlie dispersal variation, the genetic architecture of context-dependent dispersal phenotypes and behaviours, and correlations among dispersal and other traits.Peer reviewe

Planck pre-launch status : The Planck mission

Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

The worldwide C3S CORDEX grand ensemble: A major contribution to assess regional climate change in the IPCC AR6 Atlas

peer reviewedAbstract The collaboration between the Coordinated Regional Climate Downscaling Experiment (CORDEX) and the Earth System Grid Federation (ESGF) provides open access to an unprecedented ensemble of Regional Climate Model (RCM) simulations, across the 14 CORDEX continental-scale domains, with global coverage. These simulations have been used as a new line of evidence to assess regional climate projections in the latest contribution of the Working Group I (WGI) to the IPCC Sixth Assessment Report (AR6), particularly in the regional chapters and the Atlas. Here, we present the work done in the framework of the Copernicus Climate Change Service (C3S) to assemble a consistent worldwide CORDEX grand ensemble, aligned with the deadlines and activities of IPCC AR6. This work addressed the uneven and heterogeneous availability of CORDEX ESGF data by supporting publication in CORDEX domains with few archived simulations and performing quality control. It also addressed the lack of comprehensive documentation by compiling information from all contributing regional models, allowing for an informed use of data. In addition to presenting the worldwide CORDEX dataset, we assess here its consistency for precipitation and temperature by comparing climate change signals in regions with overlapping CORDEX domains, obtaining overall coincident regional climate change signals. The C3S CORDEX dataset has been used for the assessment of regional climate change in the IPCC AR6 (and for the interactive Atlas) and is available through the Copernicus Climate Data Store (CDS)

Hétérogénéité phénotypique dans les populations d’origine clonale : Origine et conséquences

According to the actual paradigm, isogenic cells inthe same environment must display the same behavior as they share the same genetic program. In consequences, the clonal origin of cells is considered as the best guaranty of their homogeneity. Nevertheless, observing differences between isogenic cells, grown in the same environment is not a rare event as observed in different studies. The main objective of this work is to understand how those differences between genetically identical cells appear and to quantify the dynamics of these changes. The first part is dedicated to the study of long term variations in cells’ phenotype. Starting from single cells, we monitored the emergence of cell-to-cell variations in the resulting populations by weekly analysis during several weeks. We show that the establishment of cell-to-cell heterogeneity in our system is a long lasting process, suffering a memory effect which slowed the diversification of phenotype. Nevertheless, several weeks after subcloning individual cells, a relaxation process is observed in the resulting populations and their variability reached the same level as in the original population. In the second part, we quantified rapid changes in gene expression at the level of single cells. Based on video-microscopy experiments coupled with images analysis and signal processing, we highlight different single-cell dynamics that could explain the emergence of cell-to-cell differences in isogenic cells populations. We also show that a competition effect appears between similar transgenic constructs when they are close to each other. Finally, we highlight the limitations of the use oflong-life proteins for the study of gene expression dynamics.Le paradigme actuel de la biologie soutient que descellules possédant le même programme génétique doivent se comporter de façon similaire lorsqu’elles évoluent dans le même environnement. L'origine clonale de cellules est alors une garantie de grande homogénéité pour de nombreuses applications. Néanmoins, des observations montrent que malgré leur identité génétique, certaines cellules arborent des caractères différents dans le même environnement. L’objectif principal de ce travail est d’étudier la dynamique des fluctuations qui conduit à la diversification de ces cellules. Dans un premier temps, nous avons étudié la dynamique qui permet d’obtenir une population clonale hétérogène, à partir d’une cellule. En isolant des cellules et en analysant leurs descendants pendant plusieurs semaines, nous avons montré que ce processus est relativement long. Il semble subir uneffet mémoire à l’échelle cellulaire qui ralentie la diversification phénotypique. Néanmoins, après plusieurs semaines, un retour à l’équilibre s’opère et la variabilité des populations obtenues atteint celle de la population d’origine. Par la suite, nous avons quantifié les changements d’expression génique à l’échelle cellulaire. Cette seconde étape, basée sur la vidéo-microscopie couplée à l’analyse d’images et au traitement du signal, a permis d’estimer la dynamique qui aboutie à l’hétérogénéité observée dans la première partie. Nous avons aussi mis en évidence qu’une proximité spatiale entre deux constructions transgéniques pouvait entraîner une compétition entreelles. Enfin, nous avons identifié une limite à l’utilisation de certains gènes rapporteurs dans les études dynamiques de l’expression génique