Exploring Fully Offloaded GPU Stream-Aware Message Passing

Modern heterogeneous supercomputing systems are comprised of CPUs, GPUs, and high-speed network interconnects. Communication libraries supporting efficient data transfers involving memory buffers from the GPU memory typically require the CPU to orchestrate the data transfer operations. A new offload-friendly communication strategy, stream-triggered (ST) communication, was explored to allow offloading the synchronization and data movement operations from the CPU to the GPU. A Message Passing Interface (MPI) one-sided active target synchronization based implementation was used as an exemplar to illustrate the proposed strategy. A latency-sensitive nearest neighbor microbenchmark was used to explore the various performance aspects of the implementation. The offloaded implementation shows significant on-node performance advantages over standard MPI active RMA (36%) and point-to-point (61%) communication. The current multi-node improvement is less (23% faster than standard active RMA but 11% slower than point-to-point), but plans are in progress to purse further improvements.Comment: 12 pages, 17 figure

Nonblocking collectives for scalable Java communications

This is the peer reviewed version of the following article: Ramos, S., Taboada, G. L., Expósito, R. R., & Touriño, J. (2015). Nonblocking collectives for scalable Java communications. Concurrency and Computation: Practice and Experience, 27(5), 1169-1187, which has been published in final form at https://doi.org/10.1002/cpe.3279. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.[Abstract] This paper presents a Java implementation of the recently published MPI 3.0 nonblocking message passing collectives in order to analyze and assess the feasibility of taking advantage of these operations in shared memory systems using Java. Nonblocking collectives aim to exploit the overlapping between computation and communication for collective operations to increase scalability of message passing codes, as it has been carried out for nonblocking point‐to‐point primitives. This scalability has become crucial not only for clusters but also for shared memory systems because of the current trend of increasing the number of cores per chip, which is leading to the generalization of multi‐core and many‐core processors. Message passing libraries based on remote direct memory access, thread‐based progression, or implementing pure multi‐threading shared memory support could potentially benefit from the lack of imposed synchronization by nonblocking collectives. But, although the distributed memory scenario has been well studied, the shared memory one has not been tackled yet. Hence, nonblocking collectives support has been included in FastMPJ, a Message Passing in Java (MPJ) implementation, and evaluated on a representative shared memory system, obtaining significant improvements because of overlapping and lack of implicit synchronization, and with barely any overhead imposed over common blocking operations.Ministerio de Ciencia e Innovación; TIN2010-16735Xunta de Galicia; CN2012/211Xunta de Galicia; GRC2013/05

M-CSF instructs myeloid lineage fate in single haematopoietic stem cells

Under stress conditions such as infection or inflammation the body rapidly needs to generate new blood cells that are adapted to the challenge. Haematopoietic cytokines are known to increase output of specific mature cells by affecting survival, expansion and differentiation of lineage-committed progenitors, but it has been debated whether long-term haematopoietic stem cells (HSCs) are susceptible to direct lineage-specifying effects of cytokines. Although genetic changes in transcription factor balance can sensitize HSCs to cytokine instruction, the initiation of HSC commitment is generally thought to be triggered by stochastic fluctuation in cell-intrinsic regulators such as lineage-specific transcription factors, leaving cytokines to ensure survival and proliferation of the progeny cells. Here we show that macrophage colony-stimulating factor (M-CSF, also called CSF1), a myeloid cytokine released during infection and inflammation, can directly induce the myeloid master regulator PU.1 and instruct myeloid cell-fate change in mouse HSCs, independently of selective survival or proliferation. Video imaging and single-cell gene expression analysis revealed that stimulation of highly purified HSCs with M-CSF in culture resulted in activation of the PU.1 promoter and an increased number of PU.1(+) cells with myeloid gene signature and differentiation potential. In vivo, high systemic levels of M-CSF directly stimulated M-CSF-receptor-dependent activation of endogenous PU.1 protein in single HSCs and induced a PU.1-dependent myeloid differentiation preference. Our data demonstrate that lineage-specific cytokines can act directly on HSCs in vitro and in vivo to instruct a change of cell identity. This fundamentally changes the current view of how HSCs respond to environmental challenge and implicates stress-induced cytokines as direct instructors of HSC fate

A Comparison of Different Methods for Rna and Dna Extraction From Formalin – Fixed Paraffin-Embedded Tissues From Different Cancer Samples

RNA and DNA extracted from formalin-fixed paraffin-embedded (FFPE) tissue is problematic due to chemical modifications and continued degradation over time. we compared quantity of RNA extracted by two different protocols from 14 recently archived from patients suffered from different cancers distributed among formalin-fixed paraffin-embedded (FFPE) breast cancer tissues ,thyroid cancer tissues and Cervical uterus carcinoma tissues by using Guanidine isothiocyanate (GTC)with phenol-chloroform (protocol-1) and Silica Gel Column(SGC) dependent on spin column purification-based ( protocol- 2), to assess, which technique is the most efficient and reproducible in terms of total yield and purity.  The results showed RNA isolated with SGC technique was characterized by higher mean concentration in a range (80-180) µg/ml ,but it  give positive results to 12 sample with degradation in comparison with RNA isolated by the (GTC) technique (protocol-1), comparison with total RNA extraction from human blood ( two distinguished bands ) .In this study comparative methods have been performed to analyze the efficiency for extraction and purification of Genomic DNA from six selective FFPE Tissues samples, revealing that the extraction of DNA by using  extraction  modified method give good result  with yield  higher mean concentration of DNA in a range (160-260) µg/ml.The lysis of FFPE Tissues  was enhanced by increased the concentration of proteinase K to30 mg\ml for 2 hour at 65C, which considered the best time for lysis tissues  and heated comparable with results that obtained from lysis tissues by using 20mg\ml for (24 -48 hours) at 55

Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

<p>Abstract</p> <p>Background</p> <p>Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies.</p> <p>Methods</p> <p>Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders.</p> <p>Results</p> <p>The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both <it>in vitro </it>and <it>in vivo </it>after transplantation into regenerating muscle of immunodeficient mice.</p> <p>Conclusions</p> <p>Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess <it>in vivo </it>the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.</p

Human muscle progenitors (participation of quiescent cells in muscle regeneration)

Les cellules satellites (progéniteurs musculaires) sont responsables de la capacité de régénération des fibres du muscle squelettique. Localisées entre la lame basale et la membrane plasmique des fibres musculaires, elles sont à l état normal dans un état de quiescence dans le muscle adulte, et sont activées après exercice ou une lésion d origine traumatique ou pathologique (dystrophie musculaire). Une fois le processus de régénération terminé, une minorite des cellules satellites non-engagés dans le processus de différenciation retournent à un état quiescent. Il a été montré chez la souris que la transplantation intra-musculaire de fibres isolées avec leurs cellules satellites résidentes était beaucoup plus efficace que tout autre type de greffe cellulaire, qu il s agisse de myoblastes (cellules satellite amplifiées) ou de cellules souches myogéniques, ce qui pourrait suggérer que c est l état de quiescence qui confère cette efficacité élevée. Les expériences décrites dans le premier chapitre de cette thèse ont été menées pour tester cette hypothèse dans un contexte humain. Les cellules satellites étant activées lors de leur isolation, elles se prêtent mal à cette étude. Par conséquent, nous avons comparé des modèles de culture cellulaire pour générer des cellules quiescentes, proches des cellules satellites : cultures en suspension et modèle de cellules réserves (RC). La viabilité des cellules étant bien meilleure dans le modèle RC, nous l avons utilisée pour évaluer (1) in vitro : l expression de marqueurs myogéniques, la capacité proliférative, la fusion, ainsi que le profil du cycle cellulaire de ces cellules réserves et (2) in vivo: leur efficacité à participer à la régénération musculaire après transplantation dans des souris immunodéficientes. Les résultats obtenus sur les RC ont ensuite été comparés avec ceux obtenus avec des myoblastes contrôles, et nous n avons pas observé de différence significative entre les deux types cellulaires comparés dans cette étude, ce qui suggère que la quiescence n a pas d effet sur la capacité régénérative des myoblastes humains. Le groupe de G. Goldspink a montré que les fibres musculaires soumises à une déformation mécanique produisent un facteur de croissance appelé MGF (Mecano Growth Factor). Des études ont montré que le MGF protège contre les dommages des radicaux libres d'oxygène et joue un rôle au cours de la réparation et de l'adaptation musculaire. De plus on observe une diminution du MGF dans des muscles de souris âgées associée à une perte de masse et de force musculaire. Les expériences décrites dans la seconde partie de cette thèse ont été réalisées pour étudier les effets du peptide E de MGF, issu d épissage alternatif, sur la prolifération et la différenciation des myoblastes humains isolés de biopsies de sujets nouveaux-nés, adultes jeunes et âgés. Nous avons comparé dans ces trois groupes, la capacité proliférative, la différenciation, ainsi que le pourcentage de cellules réserves, en présence ou en absence du peptide MGF. Les données obtenues indiquent que le MGF pourrait avoir un rôle important dans la réparation des muscles et l'adaptation au cours du vieillissementPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Volumetric determination of tetraalkyl thiuram disulphides

A method for the volumetric determination of tetraalkyl thiuram disulphide is developed. It is based on its reaction with potassium cyanide in aqueous acetonitrile medium, when the corresponding tetraalkyl thiuram monosulphide and thiocyanate are formed. The former is removed by extraction with benzene and the latter converted into cyanogen bromide, which is estimated iodometrically