WLCG Input to Pisa workshop on Resilience-Explicit Computing in Grids

This document summarizes the input from the Worldwide LHC Computing Grid (WLCG) to the workshop held on Resilience-Explicit Computing in Grids in Pisa, July 14th 2008. The techniques on which WLCG services have been built have been described in numerous papers, including [1][2][3]. They are based on many years of experience in delivering reliable services, using knowledge gained from the LEP era and from other High Energy Physics experiments around the world

Robust and Resilient Services â How to design, build and operate them

Grid infrastructures require a high degree of fault tolerance and reliability. This can only be achieved by careful planning and detailed implementation. We describe on-going work within the WLCG project to build and run highly reliable services. Following the "a priori" analysis based on the services and service levels listed in the Memorandum of Understanding that sites participating in WLCG have signed[1], this paper provides an "a posteriori" analysis following over 2 years of production service. This work covers not only the services deployed at the Tier0 centre at CERN - which has the most stringent service requirements related to the acquisition of the raw data, the initial processing phase and the distribution of raw and processed data to Tier1 sites, but also a similar analysis for Tier1 and major Tier2 sites. The latter will be covered at a workshop that will take place shortly before the EELA conference and so will be very up-to-date

Methadone, Buprenorphine, and Street Drug Interactions with Antiretroviral Medications

While street drugs appear unlikely to alter the metabolism of antiretroviral (ARV) medications, several ARVs may induce or inhibit metabolism of various street drugs. However, research on these interactions is limited. Case reports have documented life-threatening overdoses of ecstasy and gamma-hydroxybutyrate after starting ritonavir, an ARV that inhibits several metabolic enzymes. For opioid addiction, methadone or buprenorphine are the treatments of choice. Because a number of ARVs decrease or increase methadone levels, patients should be monitored for methadone withdrawal or toxicity when they start or stop ARVs. Most ARVs do not cause buprenorphine withdrawal or toxicity, even if they alter buprenorphine levels, with rare exceptions to date including atazanavir/ritonavir associated with significant increases in buprenorphine and adverse events related to sedation and mental status changes in some cases. There are newer medications yet to be studied with methadone or buprenorphine. Further, there are many frequently used medications in treatment of complications of HIV disease that have not been studied. There is need for continuing research to define these drug interactions and their clinical significance

Identification of a BRCA1-mRNA Splicing Complex Required for Efficient DNA Repair and Maintenance of Genomic Stability

Mutations within BRCA1 predispose carriers to a high risk of breast and ovarian cancers. BRCA1 functions to maintain genomic stability through the assembly of multiple protein complexes involved in DNA repair, cell-cycle arrest, and transcriptional regulation. Here, we report the identification of a DNA damage-induced BRCA1 protein complex containing BCLAF1 and other key components of the mRNA-splicing machinery. In response to DNA damage, this complex regulates pre-mRNA splicing of a number of genes involved in DNA damage signaling and repair, thereby promoting the stability of these transcripts/proteins. Further, we show that abrogation of this complex results in sensitivity to DNA damage, defective DNA repair, and genomic instability. Interestingly, mutations in a number of proteins found within this complex have been identified in numerous cancer types. These data suggest that regulation of splicing by the BRCA1-mRNA splicing complex plays an important role in the cellular response to DNA damage

A Stakeholder-Informed Approach to the Identification of Criteria for the Prioritization of Zoonoses in Canada

Background: Zoonotic diseases account for over 60 % of all communicable diseases causing illness in humans and 75 % of recently emerging infectious diseases. As limited resources are available for the control and prevention of zoonotic diseases, it is necessary to prioritize diseases in order to direct resources into those with the greatest needs. The selection of criteria for prioritization has traditionally been on the basis of expert opinion; however, details of the methods used to identify criteria from expert opinion often are not published and a full range of criteria may not be captured by expert opinion. Methodology/Principal Findings: This study used six focus groups to identify criteria for the prioritization of zoonotic diseases in Canada. Focus groups included people from the public, animal health professionals and human health professionals. A total of 59 criteria were identified for prioritizing zoonotic diseases. Human-related criteria accounted for the highest proportion of criteria identified (55%), followed by animal-related criteria (26%) then pathogen/disease-related criteria (19%). Similarities and differences were observed in the identification and scoring of criteria for disease prioritization between groups; the public groups were strongly influenced by the individual-level of disease burden, the responsibility of the scientific community in disease prioritization and the experiences of recent events while the professional groups were influenced by the societal- and population-level of disease burden and political and public pressure