High Resolution BPM Upgrade for the ATF Damping Ring at KEK

A beam position monitor (BPM) upgrade at the KEK Accelerator Test Facility (ATF) damping ring has been accomplished, carried out by a KEK/FNAL/SLAC collaboration under the umbrella of the global ILC R&D effort. The upgrade consists of a high resolution, high reproducibility read-out system, based on analog and processing, and also implements a new automatic gain error correction schema. The technical concept and realization as well as results of beam studies are presented.Comment: 3 pp. 10th European Workshop on Beam Diagnostics and Instrumentation for Particle Accelerators DIPAC 2011, 16-18 May 2011. Hamburg, German

High resolution BPMS with integrated gain correction system

High resolution beam position monitors (BPM) are an essential tool to achieve and reproduce a low vertical beam emittance at the KEK Accelerator Test Facility (ATF) damping ring. The ATF damping ring (DR) BPMs are currently upgraded with new high resolution read-out electronics. Based on analog and digital down-conversion techniques, the upgrade includes an automatic gain calibration system to correct for slow drift effects and ensure high reproducible beam position readings. The concept and its technical realization, as well as preliminary results of beam studies are presented

Intra- and inter-individual genetic differences in gene expression

Genetic variation is known to influence the amount of mRNA produced by a gene. Given that the molecular machines control mRNA levels of multiple genes, we expect genetic variation in the components of these machines would influence multiple genes in a similar fashion. In this study we show that this assumption is correct by using correlation of mRNA levels measured independently in the brain, kidney or liver of multiple, genetically typed, mice strains to detect shared genetic influences. These correlating groups of genes (CGG) have collective properties that account for 40-90% of the variability of their constituent genes and in some cases, but not all, contain genes encoding functionally related proteins. Critically, we show that the genetic influences are essentially tissue specific and consequently the same genetic variations in the one animal may up-regulate a CGG in one tissue but down-regulate the same CGG in a second tissue. We further show similarly paradoxical behaviour of CGGs within the same tissues of different individuals. The implication of this study is that this class of genetic variation can result in complex inter- and intra-individual and tissue differences and that this will create substantial challenges to the investigation of phenotypic outcomes, particularly in humans where multiple tissues are not readily available.

&#xa

Improving Metabolic Health Through Precision Dietetics in Mice

The incidence of diet-induced metabolic disease has soared over the last half-century, despite national efforts to improve health through universal dietary recommendations. Studies comparing dietary patterns of populations with health outcomes have historically provided the basis for healthy diet recommendations. However, evidence that population-level diet responses are reliable indicators of responses across individuals is lacking. This study investigated how genetic differences influence health responses to several popular diets in mice, which are similar to humans in genetic composition and the propensity to develop metabolic disease, but enable precise genetic and environmental control. We designed four human-comparable mouse diets that are representative of those eaten by historical human populations. Across four genetically distinct inbred mouse strains, we compared the American diet’s impact on metabolic health to three alternative diets (Mediterranean, Japanese, and Maasai/ketogenic). Furthermore, we investigated metabolomic and epigenetic alterations associated with diet response. Health effects of the diets were highly dependent on genetic background, demonstrating that individualized diet strategies improve health outcomes in mice. If similar genetic-dependent diet responses exist in humans, then a personalized, or “precision dietetics,” approach to dietary recommendations may yield better health outcomes than the traditional one-size-fits-all approach

Saint or Sinner?: A Reconsideration of the Career of Prince Alexandre de Merode, Chair of the International Olympic Committee’s Medical Commission, 1967-2002

This article explores the role of Prince Alexandre de Merode in heading the IOC’s fight against drugs from the 1960s to 2002. History has not served de Merode very well. He has been presented in simplistic ways that emerge from context rather than evidence – as either a saint or a sinner. IOC-sanctioned accounts cast him in the mould of the saint: a moral and intelligent man who saved sports from doping. In contrast, sports academics have tended to portray him as a sinner: an ineffectual leader who did not develop either the testing systems or the punishments required to prevent doping and who deliberately concealed evidence of high-profile doping cases. This article assesses both representations before presenting information to support a richer and more complicated interpretation

Current anti-doping policy: a critical appraisal

BACKGROUND: Current anti-doping in competitive sports is advocated for reasons of fair-play and concern for the athlete's health. With the inception of the World Anti Doping Agency (WADA), anti-doping effort has been considerably intensified. Resources invested in anti-doping are rising steeply and increasingly involve public funding. Most of the effort concerns elite athletes with much less impact on amateur sports and the general public. DISCUSSION: We review this recent development of increasingly severe anti-doping control measures and find them based on questionable ethical grounds. The ethical foundation of the war on doping consists of largely unsubstantiated assumptions about fairness in sports and the concept of a "level playing field". Moreover, it relies on dubious claims about the protection of an athlete's health and the value of the essentialist view that sports achievements reflect natural capacities. In addition, costly antidoping efforts in elite competitive sports concern only a small fraction of the population. From a public health perspective this is problematic since the high prevalence of uncontrolled, medically unsupervised doping practiced in amateur sports and doping-like behaviour in the general population (substance use for performance enhancement outside sport) exposes greater numbers of people to potential harm. In addition, anti-doping has pushed doping and doping-like behaviour underground, thus fostering dangerous practices such as sharing needles for injection. Finally, we argue that the involvement of the medical profession in doping and anti-doping challenges the principles of non-maleficience and of privacy protection. As such, current anti-doping measures potentially introduce problems of greater impact than are solved, and place physicians working with athletes or in anti-doping settings in an ethically difficult position. In response, we argue on behalf of enhancement practices in sports within a framework of medical supervision. SUMMARY: Current anti-doping strategy is aimed at eradication of doping in elite sports by means of all-out repression, buttressed by a war-like ideology similar to the public discourse sustaining international efforts against illicit drugs. Rather than striving for eradication of doping in sports, which appears to be an unattainable goal, a more pragmatic approach aimed at controlled use and harm reduction may be a viable alternative to cope with doping and doping-like behaviour

Geometric Interpretation of Gene Coexpression Network Analysis

The merging of network theory and microarray data analysis techniques has spawned a new field: gene coexpression network analysis. While network methods are increasingly used in biology, the network vocabulary of computational biologists tends to be far more limited than that of, say, social network theorists. Here we review and propose several potentially useful network concepts. We take advantage of the relationship between network theory and the field of microarray data analysis to clarify the meaning of and the relationship among network concepts in gene coexpression networks. Network theory offers a wealth of intuitive concepts for describing the pairwise relationships among genes, which are depicted in cluster trees and heat maps. Conversely, microarray data analysis techniques (singular value decomposition, tests of differential expression) can also be used to address difficult problems in network theory. We describe conditions when a close relationship exists between network analysis and microarray data analysis techniques, and provide a rough dictionary for translating between the two fields. Using the angular interpretation of correlations, we provide a geometric interpretation of network theoretic concepts and derive unexpected relationships among them. We use the singular value decomposition of module expression data to characterize approximately factorizable gene coexpression networks, i.e., adjacency matrices that factor into node specific contributions. High and low level views of coexpression networks allow us to study the relationships among modules and among module genes, respectively. We characterize coexpression networks where hub genes are significant with respect to a microarray sample trait and show that the network concept of intramodular connectivity can be interpreted as a fuzzy measure of module membership. We illustrate our results using human, mouse, and yeast microarray gene expression data. The unification of coexpression network methods with traditional data mining methods can inform the application and development of systems biologic methods