ScotGrid: Providing an Effective Distributed Tier-2 in the LHC Era

ScotGrid is a distributed Tier-2 centre in the UK with sites in Durham, Edinburgh and Glasgow. ScotGrid has undergone a huge expansion in hardware in anticipation of the LHC and now provides more than 4MSI2K and 500TB to the LHC VOs. Scaling up to this level of provision has brought many challenges to the Tier-2 and we show in this paper how we have adopted new methods of organising the centres, from fabric management and monitoring to remote management of sites to management and operational procedures, to meet these challenges. We describe how we have coped with different operational models at the sites, where Glagsow and Durham sites are managed "in house" but resources at Edinburgh are managed as a central university resource. This required the adoption of a different fabric management model at Edinburgh and a special engagement with the cluster managers. Challenges arose from the different job models of local and grid submission that required special attention to resolve. We show how ScotGrid has successfully provided an infrastructure for ATLAS and LHCb Monte Carlo production. Special attention has been paid to ensuring that user analysis functions efficiently, which has required optimisation of local storage and networking to cope with the demands of user analysis. Finally, although these Tier-2 resources are pledged to the whole VO, we have established close links with our local physics user communities as being the best way to ensure that the Tier-2 functions effectively as a part of the LHC grid computing framework..Comment: Preprint for 17th International Conference on Computing in High Energy and Nuclear Physics, 7 pages, 1 figur

The cellular redox environment alters antigen presentation

Cysteine-containing peptides represent an important class of T cell epitopes, yet their prevalence remains underestimated. We have established and interrogated a database of around 70,000 naturally processed MHC-bound peptides and demonstrate that cysteine-containing peptides are presented on the surface of cells in an MHC allomorph-dependent manner and comprise on average 5-10% of the immunopeptidome. A significant proportion of these peptides are oxidatively modified, most commonly through covalent linkage with the antioxidant glutathione. Unlike some of the previously reported cysteine-based modifications, this represents a true physiological alteration of cysteine residues. Furthermore, our results suggest that alterations in the cellular redox state induced by viral infection are communicated to the immune system through the presentation of S-glutathionylated viral peptides, resulting in altered T cell recognition. Our data provide a structural basis for how the glutathione modification alters recognition by virus-specific T cells. Collectively, these results suggest that oxidative stress represents a mechanism for modulating the virus-specific T cell response.This work was supported, in whole or in part, by National Institutes of Health Grant R01 NS036592. This work was also supported by an infrastructure grant (Grant LE100100036) from the Australian Research Council (ARC) and a project grant from the Juvenile Diabetes Research Foundation (17-2012-134)

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

American Military Culture and the Strategic Seduction of Remote Warfare

This essay endeavours to answer the question of why the US National Security establishment puts such ever-expanding faith in remotely piloted drones in a strategic bombing role in fighting twenty-first-century wars. This essay argues, one: the use of strategic air power has been shaped by long-term historical factors surrounding an imbalanced emphasis on the science of warfare in the United States military beginning in the nineteenth century stretching back to the founding of the US Military Academy at West Point. Two, twenty-first-century drone warfare fits into the larger historical context surrounding the development of a uniquely American version of strategic bombing theory during the inter-war period and carried out in World War II. That theory promoted a technological determinism that lives on despite the repeated failure of strategic bombing to live up to expectations largely because the creation of the independent Air Force in 1947 rested upon the perceived achievements of US strategic bombing during the war