Allelic expression mapping across cellular lineages to establish impact of non-coding SNPs

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On Charged Lifshitz Black Holes

We obtain exact solutions of charged asymptotically Lifshitz black holes in arbitrary (d+2) dimensions, generalizing the four dimensional solution investigated in 0908.2611[hep-th]. We find that both the conventional Hamiltonian approach and the recently proposed method for defining mass in non-relativistic backgrounds do not work for this specific example. Thus the mass of the black hole can only be determined by the first law of thermodynamics. We also obtain perturbative solutions in five-dimensional Gauss-Bonnet gravity. The ratio of shear viscosity over entropy density and the DC conductivity are calculated in the presence of Gauss-Bonnet corrections.Comment: 24 pages, no figures, to appear in JHE

Calogero-Sutherland Approach to Defect Blocks

Extended objects such as line or surface operators, interfaces or boundaries play an important role in conformal field theory. Here we propose a systematic approach to the relevant conformal blocks which are argued to coincide with the wave functions of an integrable multi-particle Calogero-Sutherland problem. This generalizes a recent observation in 1602.01858 and makes extensive mathematical results from the modern theory of multi-variable hypergeometric functions available for studies of conformal defects. Applications range from several new relations with scalar four-point blocks to a Euclidean inversion formula for defect correlators.Comment: v2: changes for clarit

A new metric for quantifying the relative impact of risk factors on loss of working life illustrated in a population of working dogs

In a resource-limited world, organisations attempting to reduce the impact of health or behaviour issues need to choose carefully how to allocate resources for the highest overall impact. However, such choices may not always be obvious. Which has the biggest impact? A large change to a small number of individuals, or a small change to a large number of individuals? The challenge is identifying the issues that have the greatest impact on the population so potential interventions can be prioritised. We addressed this by developing a score to quantify the impact of health conditions and behaviour problems in a population of working guide dogs using data from Guide Dogs, UK. The cumulative incidence of different issues was combined with information about their impact, in terms of reduction in working life, to create a work score. The work score was created at population-level to illustrate issues with the greatest impact on the population and to understand contributions of breeds or crossbreeds to the workforce. An individual work deficit score was also created and means of this score used to illustrate the impact on working life within a subgroup of the population such as a breed, or crossbreed generation. The work deficit scores showed that those removed for behavioural issues had a greater impact on the overall workforce than those removed for health reasons. Additionally trends over time illustrated the positive influence of interventions Guide Dogs have made to improve their workforce. Information highlighted by these scores is pertinent to the effort of Guide Dogs to ensure partnerships are lasting. Recognising that the scores developed here could be transferable to a wide variety of contexts and species, most notably human work force decisions; we discuss possible uses and adaptations such as reduction in lifespan, quality of life and yield in production animals

A New Stalked Filter-Feeder from the Middle Cambrian Burgess Shale, British Columbia, Canada

Burgess Shale-type deposits provide invaluable insights into the early evolution of body plans and the ecological structure of Cambrian communities, but a number of species, continue to defy phylogenetic interpretations. Here we extend this list to include a new soft-bodied animal, Siphusauctum gregarium n. gen. and n. sp., from the Tulip Beds (Campsite Cliff Shale Member, Burgess Shale Formation) of Mount Stephen (Yoho National Park, British Columbia). With 1,133 specimens collected, S. gregarium is clearly the most abundant animal from this locality

Immunoseq: the identification of functionally relevant variants through targeted capture and sequencing of active regulatory regions in human immune cells

$\textbf{BACKGROUND}$: The observation that the genetic variants identified in genome-wide association studies (GWAS) frequently lie in non-coding regions of the genome that contain cis-regulatory elements suggests that altered gene expression underlies the development of many complex traits. In order to efficiently make a comprehensive assessment of the impact of non-coding genetic variation in immune related diseases we emulated the whole-exome sequencing paradigm and developed a custom capture panel for the known DNase I hypersensitive site (DHS) in immune cells - "Immunoseq". $\textbf{RESULTS}$: We performed Immunoseq in 30 healthy individuals where we had existing transcriptome data from T cells. We identified a large number of novel non-coding variants in these samples. Relying on allele specific expression measurements, we also showed that our selected capture regions are enriched for functional variants that have an impact on differential allelic gene expression. The results from a replication set with 180 samples confirmed our observations. $\textbf{CONCLUSIONS}$: We show that Immunoseq is a powerful approach to detect novel rare variants in regulatory regions. We also demonstrate that these novel variants have a potential functional role in immune cells.This work was supported by grants from the Canadian Institute of Health Research (CIHR), the UK Medical Research Council (G1100125), the Swedish Research Council (DO283001) and Knut and Alice Wallenberg Foundation (KAW). We also acknowledge the use of subjects from the Cambridge BioResource and the support of the Cambridge NIHR Biomedical Research Centre. AM was supported by the Fond de Recherche Santé Québec Doctoral training award. TP and CL holds a Canada Research Chair

A soft-bodied mollusc with radula from the Middle Cambrian Burgess Shale

Author Posting. © Nature Publishing Group, 2006. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature 442 (2006): 159-163, doi:10.1038/nature04894.Odontogriphus omalus was originally described as a problematic non-biomineralized lophophorate organism. Here we reinterpret Odontogriphus based on 189 new specimens including numerous exceptionally well-preserved individuals from the Burgess Shale collections of the Royal Ontario Museum. This additional material provides compelling evidence that the feeding apparatus in Odontogriphus is a radula of molluscan architecture comprising two primary bipartite tooth rows attached to a radular membrane and showing replacement by posterior addition. Further characters supporting molluscan affinity include a broad foot bordered by numerous ctenidia located in a mantle groove and a stiffened cuticular dorsum. Odontogriphus has a radula similar to Wiwaxia corrugata but lacks a scleritome. We interpret these animals to be members of an early stem-group mollusc lineage that likely originated in the Neoproterozoic Ediacaran Period, providing support for the retention of a biomat-based grazing community from the late Precambrian until at least the Middle Cambrian.Our research was in part supported by a Post-Doctoral Natural Sciences and Engineering Research Council of Canada grant (to JBC-2005) and by a Swedish Research Council grant (to CS)

Meta-analysis of cancer gene expression signatures reveals new cancer genes, SAGE tags and tumor associated regions of co-regulation

Cancer is among the major causes of human death and its mechanism(s) are not fully understood. We applied a novel meta-analysis approach to multiple sets of merged serial analysis of gene expression and microarray cancer data in order to analyze transcriptome alterations in human cancer. Our methodology, which we denote ‘COgnate Gene Expression patterNing in tumours’ (COGENT), unmasked numerous genes that were differentially expressed in multiple cancers. COGENT detected well-known tumor-associated (TA) genes such as TP53, EGFR and VEGF, as well as many multi-cancer, but not-yet-tumor-associated genes. In addition, we identified 81 co-regulated regions on the human genome (RIDGEs) by using expression data from all cancers. Some RIDGEs (28%) consist of paralog genes while another subset (30%) are specifically dysregulated in tumors but not in normal tissues. Furthermore, a significant number of RIDGEs are associated with GC-rich regions on the genome. All assembled data is freely available online (www.oncoreveal.org) as a tool implementing COGENT analysis of multi-cancer genes and RIDGEs. These findings engender a deeper understanding of cancer biology by demonstrating the existence of a pool of under-studied multi-cancer genes and by highlighting the cancer-specificity of some TA-RIDGEs

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration