Instrument Front-Ends at Fermilab During Run II

The optimization of an accelerator relies on the ability to monitor the behavior of the beam in an intelligent and timely fashion. The use of processor-driven front-ends allowed for the deployment of smart systems in the field for improved data collection and analysis during Run II. This paper describes the implementation of the two main systems used: National Instruments LabVIEW running on PCs, and WindRiver's VxWorks real-time operating system running in a VME crate processor.Comment: 8 p

Extracting Gene Networks for Low-Dose Radiation Using Graph Theoretical Algorithms

Genes with common functions often exhibit correlated expression levels, which can be used to identify sets of interacting genes from microarray data. Microarrays typically measure expression across genomic space, creating a massive matrix of co-expression that must be mined to extract only the most relevant gene interactions. We describe a graph theoretical approach to extracting co-expressed sets of genes, based on the computation of cliques. Unlike the results of traditional clustering algorithms, cliques are not disjoint and allow genes to be assigned to multiple sets of interacting partners, consistent with biological reality. A graph is created by thresholding the correlation matrix to include only the correlations most likely to signify functional relationships. Cliques computed from the graph correspond to sets of genes for which significant edges are present between all members of the set, representing potential members of common or interacting pathways. Clique membership can be used to infer function about poorly annotated genes, based on the known functions of better-annotated genes with which they share clique membership (i.e., “guilt-by-association”). We illustrate our method by applying it to microarray data collected from the spleens of mice exposed to low-dose ionizing radiation. Differential analysis is used to identify sets of genes whose interactions are impacted by radiation exposure. The correlation graph is also queried independently of clique to extract edges that are impacted by radiation. We present several examples of multiple gene interactions that are altered by radiation exposure and thus represent potential molecular pathways that mediate the radiation response

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.

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Exercise-induced bronchoconstriction and atopy in Tunisian athletes

<p>Abstract</p> <p>Background</p> <p>This study is a cross sectional analysis, aiming to evaluate if atopy is as a risk factor for exercise induced bronchoconstriction (EIB) among Tunisian athletes.</p> <p>Methods</p> <p>Atopy was defined by a skin prick test result and EIB was defined as a decrease of at least 15% in forced expiratory volume in one second (FEV1) after 8-min running at 80–85% HRmaxTheo. The study population was composed of 326 athletes (age: 20.8 ± 2.7 yrs – mean ± SD; 138 women and 188 men) of whom 107 were elite athletes.</p> <p>Results</p> <p>Atopy was found in 26.9% (88/326) of the athletes. Post exercise spirometry revealed the presence of EIB in 9.8% of the athletes including 13% of the elite athletes. Frequency of atopy in athletes with EIB was significantly higher than in athletes without EIB [62.5% vs 23.1%, respectively].</p> <p>Conclusion</p> <p>This study showed that atopic Tunisian athletes presented a higher risk of developing exercise induced bronchoconstriction than non-atopic athletes.</p

The Collaborative Cross at Oak Ridge National Laboratory: developing a powerful resource for systems genetics

Complex traits and disease comorbidity in humans and in model organisms are the result of naturally occurring polymorphisms that interact with each other and with the environment. To ensure the availability of resources needed to investigate biomolecular networks and systems-level phenotypes underlying complex traits, we have initiated breeding of a new genetic reference population of mice, the Collaborative Cross. This population has been designed to optimally support systems genetics analysis. Its novel and important features include a high level of genetic diversity, a large population size to ensure sufficient power in high-dimensional studies, and high mapping precision through accumulation of independent recombination events. Implementation of the Collaborative Cross has been ongoing at the Oak Ridge National Laboratory (ORNL) since May 2005. Production has been systematically managed using a software-assisted breeding program with fully traceable lineages, performed in a controlled environment. Currently, there are 650 lines in production, and close to 200 lines are now beyond their seventh generation of inbreeding. Retired breeders enter a high-throughput phenotyping protocol and DNA samples are banked for analyses of recombination history, allele drift and loss, and population structure. Herein we present a progress report of the Collaborative Cross breeding program at ORNL and a description of the kinds of investigations that this resource will support

Genome-wide patterns of promoter sharing and co-expression in bovine skeletal muscle

Background: Gene regulation by transcription factors (TF) is species, tissue and time specific. To better understand how the genetic code controls gene expression in bovine muscle we associated gene expression data from developing Longissimus thoracis et lumborum skeletal muscle with bovine promoter sequence information.Results: We created a highly conserved genome-wide promoter landscape comprising 87,408 interactions relating 333 TFs with their 9,242 predicted target genes (TGs). We discovered that the complete set of predicted TGs share an average of 2.75 predicted TF binding sites (TFBSs) and that the average co-expression between a TF and its predicted TGs is higher than the average co-expression between the same TF and all genes. Conversely, pairs of TFs sharing predicted TGs showed a co-expression correlation higher that pairs of TFs not sharing TGs. Finally, we exploited the co-occurrence of predicted TFBS in the context of muscle-derived functionally-coherent modules including cell cycle, mitochondria, immune system, fat metabolism, muscle/glycolysis, and ribosome. Our findings enabled us to reverse engineer a regulatory network of core processes, and correctly identified the involvement of E2F1, GATA2 and NFKB1 in the regulation of cell cycle, fat, and muscle/glycolysis, respectively.Conclusion: The pivotal implication of our research is two-fold: (1) there exists a robust genome-wide expression signal between TFs and their predicted TGs in cattle muscle consistent with the extent of promoter sharing; and (2) this signal can be exploited to recover the cellular mechanisms underpinning transcription regulation of muscle structure and development in bovine. Our study represents the first genome-wide report linking tissue specific co-expression to co-regulation in a non-model vertebrate

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

ON THE USE OF REGGE-POLE ANALYSES TO EXTRACT POSSIBLE QUASI MOLECULAR ROTATIONAL BANDS FROM ELASTIC HEAVY ION CROSS SECTIONS

Si une bande de rotation s'étend au-dessus du seuil d'émission de particule, ses membres sont des résonances plutôt que des états liés. S'ils sont en outre suffisamment larges pour se recouvrir, leurs phases et amplitudes relatives déterminent la façon dont ils interfèrent entre eux dans les sections efficaces de diffusion et de réaction. On montre qu'un pôle de Regge permet une paramétrisation commode et économique de ces amplitudes.If a rotational band extends above a breakup threshold, its members will be resonances rather than bound states. If in addition they are sufficiently broad to overlap, their relative phases and amplitudes will determine the way in which they interfere with one another in scattering and reaction cross sections. It is pointed out that a Regge pole provides a convenient and economical parametrization of these amplitudes