DZero data-intensive computing on the Open Science Grid

International audienceHigh energy physics experiments periodically reprocess data, in order to take advantage of improved understanding of the detector and the data processing code. Between February and May 2007, the DZero experiment has reprocessed a substantial fraction of its dataset. This consists of half a billion events, corresponding to about 100 TB of data, organized in 300,000 files. The activity utilized resources from sites around the world, including a dozen sites participating to the Open Science Grid consortium (OSG). About 1,500 jobs were run every day across the OSG, consuming and producing hundreds of Gigabytes of data. Access to OSG computing and storage resources was coordinated by the SAM-Grid system. This system organized job access to a complex topology of data queues and job scheduling to clusters, using a SAM-Grid to OSG job forwarding infrastructure. For the first time in the lifetime of the experiment, a data intensive production activity was managed on a general purpose grid, such as OSG. This paper describes the implications of using OSG, where all resources are granted following an opportunistic model, the challenges of operating a data intensive activity over such large computing infrastructure, and the lessons learned throughout the project

ReSS: A Resource Selection Service for the Open Science Grid

The Open Science Grid offers access to hundreds of computing and storage resources via standard Grid interfaces. Before the deployment of an automated resource selection system, users had to submit jobs directly to these resources. They would manually select a resource and specify all relevant attributes in the job description prior to submitting the job. The necessity of a human intervention in resource selection and attribute specification hinders automated job management components from accessing OSG resources and it is inconvenient for the users. The Resource Selection Service (ReSS) project addresses these shortcomings. The system integrates condor technology, for the core match making service, with the gLite CEMon component, for gathering and publishing resource information in the Glue Schema format. Each one of these components communicates over secure protocols via web services interfaces. The system is currently used in production on OSG by the DZero Experiment, the Engagement Virtual Organization, and the Dark Energy. It is also the resource selection service for the Fermilab Campus Grid, FermiGrid. ReSS is considered a lightweight solution to push-based workload management. This paper describes the architecture, performance, and typical usage of the system

ReSS: Resource Selection Service for National and Campus Grid Infrastructure

The Open Science Grid (OSG) offers access to around hundred Compute elements (CE) and storage elements (SE) via standard Grid interfaces. The Resource Selection Service (ReSS) is a push-based workload management system that is integrated with the OSG information systems and resources. ReSS integrates standard Grid tools such as Condor, as a brokering service and the gLite CEMon, for gathering and publishing resource information in GLUE Schema format. ReSS is used in OSG by Virtual Organizations (VO) such as Dark Energy Survey (DES), DZero and Engagement VO. ReSS is also used as a Resource Selection Service for Campus Grids, such as FermiGrid. VOs use ReSS to automate the resource selection in their workload management system to run jobs over the grid. In the past year, the system has been enhanced to enable publication and selection of storage resources and of any special software or software libraries (like MPI libraries) installed at computing resources. In this paper, we discuss the Resource Selection Service, its typical usage on the two scales of a National Cyber Infrastructure Grid, such as OSG, and of a campus Grid, such as FermiGrid

Identification of Ecdysone Hormone Receptor Agonists as a Therapeutic Approach for Treating Filarial Infections

Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets. Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. A B. malayi ecdysone receptor ligand-binding domain was developed and used to study the ligand-receptor interactions of these agonists. An excellent correlation between the virtual screening results and the screening assay was observed. Based on both of these approaches, steroidal ecdysone agonists and the diacylhydrazine family of compounds were identified as a fruitful source of potential receptor agonists. In further confirmation of the modeling and screening results, Ponasterone A and Muristerone A, two compounds predicted to be strong ecdysone agonists stimulated expulsion of microfilaria and immature stages from adult parasites. Conclusions The studies validate the potential of the B. malayi ecdysone receptor as a drug target and provide a means to rapidly evaluate compounds for development of a new class of drugs against the human filarial parasites

Phenotypic and Molecular Analysis of the Effect of 20-hydroxyecdysone on the Human Filarial Parasite Brugia malayi

A homologue of the ecdysone receptor has been identified and shown to be responsive to 20- hydroxyecdysone in Brugia malayi. However, the role of this master regulator of insect development has not been delineated in filarial nematodes. Gravid adult female B. malayi cultured in the presence of 20-hydroxyecdysone produced significantly more microfilariae and abortive immature progeny than control worms, implicating the ecdysone receptor in regulation of embryogenesis and microfilarial development. Transcriptome analyses identified 30 genes whose expression was significantly up-regulated in 20-hydroxyecdysone-treated parasites compared with untreated controls. Of these, 18% were identified to be regulating transcription. A comparative proteomic analysis revealed 932 proteins to be present in greater amounts in extracts of 20- hydroxyecdysone-treated adult females than in extracts prepared from worms cultured in the absence of the hormone. Of the proteins exhibiting a greater than two-fold difference in the 20- hydroxyecdysone-treated versus untreated parasite extracts, 16% were involved in transcriptional regulation. RNA interference (RNAi) phenotype analysis of Caenorhabditis elegans orthologs revealed that phenotypes involved in developmental processes associated with embryogenesis were significantly over-represented in the transcripts and proteins that were up-regulated by exposure to 20-hydroxyecdysone. Taken together, the transcriptomic, proteomic and phenotypic data suggest that the filarial ecdysone receptor may play a role analogous to that in insects, where it serves as a regulator of egg development

DZero data-intensive computing on the Open Science Grid

High energy physics experiments periodically reprocess data, in order to take advantage of improved understanding of the detector and the data processing code. Between February and May 2007, the DZero experiment has reprocessed a substantial fraction of its dataset. This consists of half a billion events, corresponding to about 100 TB of data, organized in 300,000 files. The activity utilized resources from sites around the world, including a dozen sites participating to the Open Science Grid consortium (OSG). About 1,500 jobs were run every day across the OSG, consuming and producing hundreds of Gigabytes of data. Access to OSG computing and storage resources was coordinated by the SAM-Grid system. This system organized job access to a complex topology of data queues and job scheduling to clusters, using a SAM-Grid to OSG job forwarding infrastructure. For the first time in the lifetime of the experiment, a data intensive production activity was managed on a general purpose grid, such as OSG. This paper describes the implications of using OSG, where all resources are granted following an opportunistic model, the challenges of operating a data intensive activity over such large computing infrastructure, and the lessons learned throughout the project

Expression of Functional Anti-p24 scFv 183-H12-5C in HEK293T and Jurkat T Cells

Purpose: More than half of the diagnostic and therapeutic recombinant protein production depends on mammalian-based expression system. However, the generation of recombinant antibodies remains a challenge in mammalian cells due to the disulfide bond formation and reducing cytoplasm. Therefore, the production of functional recombinant antibodies in target cell line is necessary to be evaluated before used in therapeutic application such intrabodies against HIV-1. Methods: The work was to test expression of a single-chain variable fragment (scFv) antibody against HIV-1 Capsid p24 protein in a human mammalian-based expression system using HEK293T and Jurkat T cells as a model. Three expression plasmid vectors expressing scFv 183-H12-5C were generated and introduced into HEK293T. Expression of the scFv was analyzed, while ELISA and immunoblotting analysis verified its binding. The evaluation of the recombinant antibody was confirmed by HIV-1 replication and MAGI infectivity assay in Jurkat T cells. Results: Three plasmid vectors expressing scFv 183-H12-5C was successfully engineered in this study. Recombinant antibodies scFv (~29 kDa) and scFv-Fc (~52 kDa) in the cytoplasm of HEK293T were effectively obtained by transfected the cells with engineered pCDNA3.3-mu-IgGk-scFv 183-H12-5C and pCMX2.5-scFv 183-H12-5C-hIgG1-Fc plasmid vectors respectively. scFv and scFv-Fc are specifically bound recombinant p24, and HIV-1 derived p24 (gag) evaluated by ELISA and Western blot. Jurkat T cells transfected by pCDNA3.3-scFv 183-H12-5C inhibit the replication-competent NL4-3 viral infectivity up to 60%. Conclusion: Anti-p24 scFv 183-H12-5C antibody generated is suitable to be acted as intrabodies and may serve as a valuable tool for the development of antibody-based biotherapeutics against HIV-1

Molecular Mechanisms Governing IL-24 Gene Expression

Interleukin-24 (IL-24) belongs to the IL-10 family of cytokines and is well known for its tumor suppressor activity. This cytokine is released by both immune and nonimmune cells and acts on non-hematopoietic tissues such as skin, lung and reproductive tissues. Apart from its ubiquitous tumor suppressor function, IL-24 is also known to be involved in the immunopathology of autoimmune diseases like psoriasis and rheumatoid arthritis. Although the cellular sources and functions of IL-24 are being increasingly investigated, the molecular mechanisms of IL-24 gene expression at the levels of signal transduction, epigenetics and transcription factor binding are still unclear. Understanding the specific molecular events that regulate the production of IL-24 will help to answer the remaining questions that are important for the design of new strategies of immune intervention involving IL-24. Herein, we briefly review the signaling pathways and transcription factors that facilitate, induce, or repress production of this cytokine along with the cellular sources and functions of IL-24