Distributed Management of Massive Data: an Efficient Fine-Grain Data Access Scheme

This paper addresses the problem of efficiently storing and accessing massive data blocks in a large-scale distributed environment, while providing efficient fine-grain access to data subsets. This issue is crucial in the context of applications in the field of databases, data mining and multimedia. We propose a data sharing service based on distributed, RAM-based storage of data, while leveraging a DHT-based, natively parallel metadata management scheme. As opposed to the most commonly used grid storage infrastructures that provide mechanisms for explicit data localization and transfer, we provide a transparent access model, where data are accessed through global identifiers. Our proposal has been validated through a prototype implementation whose preliminary evaluation provides promising results

Optimization in a Self-Stabilizing Service Discovery Framework for Large Scale Systems

Ability to find and get services is a key requirement in the development of large-scale distributed sys- tems. We consider dynamic and unstable environments, namely Peer-to-Peer (P2P) systems. In previous work, we designed a service discovery solution called Distributed Lexicographic Placement Table (DLPT), based on a hierar- chical overlay structure. A self-stabilizing version was given using the Propagation of Information with Feedback (PIF) paradigm. In this paper, we introduce the self-stabilizing COPIF (for Collaborative PIF) scheme. An algo- rithm is provided with its correctness proof. We use this approach to improve a distributed P2P framework designed for the services discovery. Significantly efficient experimental results are presented

Towards an efficient process placement policy for MPI applications in multicore environments

International audienceThis paper presents a method to efficiently place MPI processes on multicore machines. Since MPI implementations often feature efficient supports for both shared-memory and network communication, an adequate placement policy is a crucial step to improve applications performance. As a case study, we show the results obtained for several NAS computing kernels and explain how the policy influences overall performance. In particular, we found out that a policy merely increasing the intranode communication ratio is not enough and that cache utilization is also an influential factor. A more sophisticated policy (eg. one taking into account the architecture's memory structure) is required to observe performance improvements

FASTLens (FAst STatistics for weak Lensing) : Fast method for Weak Lensing Statistics and map making

With increasingly large data sets, weak lensing measurements are able to measure cosmological parameters with ever greater precision. However this increased accuracy also places greater demands on the statistical tools used to extract the available information. To date, the majority of lensing analyses use the two point-statistics of the cosmic shear field. These can either be studied directly using the two-point correlation function, or in Fourier space, using the power spectrum. But analyzing weak lensing data inevitably involves the masking out of regions or example to remove bright stars from the field. Masking out the stars is common practice but the gaps in the data need proper handling. In this paper, we show how an inpainting technique allows us to properly fill in these gaps with only $N \log N$ operations, leading to a new image from which we can compute straight forwardly and with a very good accuracy both the pow er spectrum and the bispectrum. We propose then a new method to compute the bispectrum with a polar FFT algorithm, which has the main advantage of avoiding any interpolation in the Fourier domain. Finally we propose a new method for dark matter mass map reconstruction from shear observations which integrates this new inpainting concept. A range of examples based on 3D N-body simulations illustrates the results.Comment: Final version accepted by MNRAS. The FASTLens software is available from the following link : http://irfu.cea.fr/Ast/fastlens.software.ph

Many-core Branch-and-Bound for GPU accelerators and MIC coprocessors

International audienceCoprocessors are increasingly becoming key building blocks of High Performance Computing platforms. These many-core energy-efficient devices boost the performance of traditional processors. On the other hand, Branch-and-Bound (B&B) algorithms are tree-based exact methods for solving to optimality combinatorial optimization problems (COPs). Solving large COPs results in the generation of a very large pool of subproblems and the evaluation of their associated lower bounds. Generating and evaluating those subproblems on coprocessors raises several issues including processor-coprocessor data transfer optimization, vectorization, thread divergence, and so on. In this paper, we investigate the offload-based parallel design and implementation of B&B algorithms for coprocessors addressing these issues. Two major many-core architectures are considered and compared: Nvidia GPU and Intel MIC. The proposed approaches have been experimented using the Flow-Shop scheduling problem and two hardware configurations equivalent in terms of energy consumption: Nvidia Tesla K40 and Intel Xeon Phi 5110P. The reported results show that the GPU-accelerated approach outperforms the MIC offload-based one even in its vectorized version. Moreover, vectorization improves the efficiency of the MIC offload-based approach with a factor of two

Direct AMPK activation corrects NASH in rodents through metabolic effects and direct action on inflammation and fibrogenesis

No approved therapies are available for nonalcoholic steatohepatitis (NASH). Adenosine monophosphate–activated protein kinase (AMPK) is a central regulator of cell metabolism; its activation has been suggested as a therapeutic approach to NASH. Here we aimed to fully characterize the potential for direct AMPK activation in preclinical models and to determine mechanisms that could contribute to efficacy for this disease. A novel small-molecule direct AMPK activator, PXL770, was used. Enzyme activity was measured with recombinant complexes. De novo lipogenesis (DNL) was quantitated in vivo and in mouse and human primary hepatocytes. Metabolic efficacy was assessed in ob/ob and high-fat diet–fed mice. Liver histology, biochemical measures, and immune cell profiling were assessed in diet-induced NASH mice. Direct effects on inflammation and fibrogenesis were assessed using primary mouse and human hepatic stellate cells, mouse adipose tissue explants, and human immune cells. PXL770 directly activated AMPK in vitro and reduced DNL in primary hepatocytes. In rodent models with metabolic syndrome, PXL770 improved glycemia, dyslipidemia, and insulin resistance. In mice with NASH, PXL770 reduced hepatic steatosis, ballooning, inflammation, and fibrogenesis. PXL770 exhibited direct inhibitory effects on pro-inflammatory cytokine production and activation of primary hepatic stellate cells. Conclusion: In rodent models, direct activation of AMPK is sufficient to produce improvements in all core components of NASH and to ameliorate related hyperglycemia, dyslipidemia, and systemic inflammation. Novel properties of direct AMPK activation were also unveiled: improved insulin resistance and direct suppression of inflammation and fibrogenesis. Given effects also documented in human cells (reduced DNL, suppression of inflammation and stellate cell activation), these studies support the potential for direct AMPK activation to effectively treat patients with NASH

SPOT: a web-based tool for using biological databases to prioritize SNPs after a genome-wide association study

SPOT (http://spot.cgsmd.isi.edu), the SNP prioritization online tool, is a web site for integrating biological databases into the prioritization of single nucleotide polymorphisms (SNPs) for further study after a genome-wide association study (GWAS). Typically, the next step after a GWAS is to genotype the top signals in an independent replication sample. Investigators will often incorporate information from biological databases so that biologically relevant SNPs, such as those in genes related to the phenotype or with potentially non-neutral effects on gene expression such as a splice sites, are given higher priority. We recently introduced the genomic information network (GIN) method for systematically implementing this kind of strategy. The SPOT web site allows users to upload a list of SNPs and GWAS P-values and returns a prioritized list of SNPs using the GIN method. Users can specify candidate genes or genomic regions with custom levels of prioritization. The results can be downloaded or viewed in the browser where users can interactively explore the details of each SNP, including graphical representations of the GIN method. For investigators interested in incorporating biological databases into a post-GWAS SNP selection strategy, the SPOT web tool is an easily implemented and flexible solution

A Mild Form of SLC29A3 Disorder: A Frameshift Deletion Leads to the Paradoxical Translation of an Otherwise Noncoding mRNA Splice Variant

We investigated two siblings with granulomatous histiocytosis prominent in the nasal area, mimicking rhinoscleroma and Rosai-Dorfman syndrome. Genome-wide linkage analysis and whole-exome sequencing identified a homozygous frameshift deletion in SLC29A3, which encodes human equilibrative nucleoside transporter-3 (hENT3). Germline mutations in SLC29A3 have been reported in rare patients with a wide range of overlapping clinical features and inherited disorders including H syndrome, pigmented hypertrichosis with insulin-dependent diabetes, and Faisalabad histiocytosis. With the exception of insulin-dependent diabetes and mild finger and toe contractures in one sibling, the two patients with nasal granulomatous histiocytosis studied here displayed none of the many SLC29A3-associated phenotypes. This mild clinical phenotype probably results from a remarkable genetic mechanism. The SLC29A3 frameshift deletion prevents the expression of the normally coding transcripts. It instead leads to the translation, expression, and function of an otherwise noncoding, out-of-frame mRNA splice variant lacking exon 3 that is eliminated by nonsense-mediated mRNA decay (NMD) in healthy individuals. The mutated isoform differs from the wild-type hENT3 by the modification of 20 residues in exon 2 and the removal of another 28 amino acids in exon 3, which include the second transmembrane domain. As a result, this new isoform displays some functional activity. This mechanism probably accounts for the narrow and mild clinical phenotype of the patients. This study highlights the ‘rescue’ role played by a normally noncoding mRNA splice variant of SLC29A3, uncovering a new mechanism by which frameshift mutations can be hypomorphic

Altered translation of GATA1 in Diamond-Blackfan anemia

Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA)[superscript 1, 2], congenital asplenia[superscript 3] and T cell leukemia[superscript 4]. Yet, how mutations in genes encoding ubiquitously expressed proteins such as these result in cell-type– and tissue-specific defects remains unknown[superscript 5]. Here, we identify mutations in GATA1, encoding the critical hematopoietic transcription factor GATA-binding protein-1, that reduce levels of full-length GATA1 protein and cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the more common cause of DBA, can lead to decreased GATA1 mRNA translation, possibly resulting from a higher threshold for initiation of translation of this mRNA in comparison with other mRNAs. In primary hematopoietic cells from patients with mutations in RPS19, encoding ribosomal protein S19, the amplitude of a transcriptional signature of GATA1 target genes was globally and specifically reduced, indicating that the activity, but not the mRNA level, of GATA1 is decreased in patients with DBA associated with mutations affecting ribosomal proteins. Moreover, the defective hematopoiesis observed in patients with DBA associated with ribosomal protein haploinsufficiency could be partially overcome by increasing GATA1 protein levels. Our results provide a paradigm by which selective defects in translation due to mutations affecting ubiquitous ribosomal proteins can result in human disease.National Institutes of Health (U.S.) (Grant P01 HL32262)National Institutes of Health (U.S.) (Grant U54 HG003067-09

Modeling of Intermediate Structures and Chain Conformation in Silica-Latex Nanocomposites Observed by SANS During Annealing

The evolution of the polymer structure during nanocomposite formation and annealing of silica-latex nanocomposites is studied using contrast-variation small angle neutron scattering. The experimental system is made of silica nanoparticles (Rsi \approx 8 nm) and a mixture of purpose-synthesized hydrogenated and deuterated nanolatex (Rlatex \approx 12.5 nm). The progressive disappearance of the latex beads by chain interdiffusion and release in the nanocomposites is analyzed quantitatively with a model for the scattered intensity of hairy latex beads and an RPA description of the free chains. In silica-free matrices and nanocomposites of low silica content (7%v), the annealing procedure over weeks at up to Tg + 85 K results in a molecular dispersion of chains, the radius of gyration of which is reported. At higher silica content (20%v), chain interdiffusion seems to be slowed down on time-scales of weeks, reaching a molecular dispersion only at the strongest annealing. Chain radii of gyration are found to be unaffected by the presence of the silica filler