185 research outputs found

    Effective action in a higher-spin background

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    We consider a free massless scalar field coupled to an infinite tower of background higher-spin gauge fields via minimal coupling to the traceless conserved currents. The set of Abelian gauge transformations is deformed to the non-Abelian group of unitary operators acting on the scalar field. The gauge invariant effective action is computed perturbatively in the external fields. The structure of the various (divergent or finite) terms is determined. In particular, the quadratic part of the logarithmically divergent (or of the finite) term is expressed in terms of curvatures and related to conformal higher-spin gravity. The generalized higher-spin Weyl anomalies are also determined. The relation with the theory of interacting higher-spin gauge fields on anti de Sitter spacetime via the holographic correspondence is discussed.Comment: 40 pages, Some errors and typos corrected, Version published in JHE

    Fermionic Coset, Critical Level W^(2)_4-Algebra and Higher Spins

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    The fermionic coset is a limit of the pure spinor formulation of the AdS5xS5 sigma model as well as a limit of a nonlinear topological A-model, introduced by Berkovits. We study the latter, especially its symmetries, and map them to higher spin algebras. We show the following. The linear A-model possesses affine \AKMSA{pgl}{4}{4}_0 symmetry at critical level and its \AKMSA{psl}{4}{4}_0 current-current perturbation is the nonlinear model. We find that the perturbation preserves W4(2)\mathcal{W}^{(2)}_4-algebra symmetry at critical level. There is a topological algebra associated to \AKMSA{pgl}{4}{4}_0 with the properties that the perturbation is BRST-exact. Further, the BRST-cohomology contains world-sheet supersymmetric symplectic fermions and the non-trivial generators of the W4(2)\mathcal{W}^{(2)}_4-algebra. The Zhu functor maps the linear model to a higher spin theory. We analyze its \SLSA{psl}{4}{4} action and find finite dimensional short multiplets.Comment: 25 page

    Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection

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    Approximately three quarters of acute hepatitis C (HCV) infections evolve to a chronic state, while one quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development of chronicity. We have conducted a genome-wide association study to identify genomic variants underlying HCV spontaneous clearance using ImmunoChip in European and African ancestries. We confrmed two previously reported signifcant associations, in the IL28B/IFNL4 and the major histocompatibility complex (MHC) regions, with spontaneous clearance in the European population. We further fne-mapped the association in the MHC to a region of about 50 kilo base pairs, down from 1 mega base pairs in the previous study. Additional analyses suggested that the association in MHC is stronger in samples from North America than those from Europe

    Ordinary-derivative formulation of conformal totally symmetric arbitrary spin bosonic fields

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    Conformal totally symmetric arbitrary spin bosonic fields in flat space-time of even dimension greater than or equal to four are studied. Second-derivative (ordinary-derivative) formulation for such fields is developed. We obtain gauge invariant Lagrangian and the corresponding gauge transformations. Gauge symmetries are realized by involving the Stueckelberg and auxiliary fields. Realization of global conformal boost symmetries on conformal gauge fields is obtained. Modified de Donder gauge condition and de Donder-Stueckelberg gauge condition are introduced. Using the de Donder-Stueckelberg gauge frame, equivalence of the ordinary-derivative and higher-derivative approaches is demonstrated. On-shell degrees of freedom of the arbitrary spin conformal field are analyzed. Ordinary-derivative light-cone gauge Lagrangian of conformal fields is also presented. Interrelations between the ordinary-derivative gauge invariant formulation of conformal fields and the gauge invariant formulation of massive fields are discussed.Comment: 51 pages, v2: Results and conclusions of v1 unchanged. In Sec.3, brief review of higher-derivative approaches added. In Sec.4, new representations for Lagrangian, modified de Donder gauge, and de Donder-Stueckelberg gauge added. In Sec.5, discussion of interrelations between the ordinary-derivative and higher-derivative approaches added. Appendices A,B,C,D and references adde

    Discovering functional modules by identifying recurrent and mutually exclusive mutational patterns in tumors

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    <p>Abstract</p> <p>Background</p> <p>Assays of multiple tumor samples frequently reveal recurrent genomic aberrations, including point mutations and copy-number alterations, that affect individual genes. Analyses that extend beyond single genes are often restricted to examining pathways, interactions and functional modules that are already known.</p> <p>Methods</p> <p>We present a method that identifies functional modules without any information other than patterns of recurrent and mutually exclusive aberrations (RME patterns) that arise due to positive selection for key cancer phenotypes. Our algorithm efficiently constructs and searches networks of potential interactions and identifies significant modules (RME modules) by using the algorithmic significance test.</p> <p>Results</p> <p>We apply the method to the TCGA collection of 145 glioblastoma samples, resulting in extension of known pathways and discovery of new functional modules. The method predicts a role for <it>EP300 </it>that was previously unknown in glioblastoma. We demonstrate the clinical relevance of these results by validating that expression of <it>EP300 </it>is prognostic, predicting survival independent of age at diagnosis and tumor grade.</p> <p>Conclusions</p> <p>We have developed a sensitive, simple, and fast method for automatically detecting functional modules in tumors based solely on patterns of recurrent genomic aberration. Due to its ability to analyze very large amounts of diverse data, we expect it to be increasingly useful when applied to the many tumor panels scheduled to be assayed in the near future.</p

    An integrated analysis of molecular aberrations in NCI-60 cell lines

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    <p>Abstract</p> <p>Background</p> <p>Cancer is a complex disease where various types of molecular aberrations drive the development and progression of malignancies. Large-scale screenings of multiple types of molecular aberrations (e.g., mutations, copy number variations, DNA methylations, gene expressions) become increasingly important in the prognosis and study of cancer. Consequently, a computational model integrating multiple types of information is essential for the analysis of the comprehensive data.</p> <p>Results</p> <p>We propose an integrated modeling framework to identify the statistical and putative causal relations of various molecular aberrations and gene expressions in cancer. To reduce spurious associations among the massive number of probed features, we sequentially applied three layers of logistic regression models with increasing complexity and uncertainty regarding the possible mechanisms connecting molecular aberrations and gene expressions. Layer 1 models associate gene expressions with the molecular aberrations on the same loci. Layer 2 models associate expressions with the aberrations on different loci but have known mechanistic links. Layer 3 models associate expressions with nonlocal aberrations which have unknown mechanistic links. We applied the layered models to the integrated datasets of NCI-60 cancer cell lines and validated the results with large-scale statistical analysis. Furthermore, we discovered/reaffirmed the following prominent links: (1)Protein expressions are generally consistent with mRNA expressions. (2)Several gene expressions are modulated by composite local aberrations. For instance, CDKN2A expressions are repressed by either frame-shift mutations or DNA methylations. (3)Amplification of chromosome 6q in leukemia elevates the expression of MYB, and the downstream targets of MYB on other chromosomes are up-regulated accordingly. (4)Amplification of chromosome 3p and hypo-methylation of PAX3 together elevate MITF expression in melanoma, which up-regulates the downstream targets of MITF. (5)Mutations of TP53 are negatively associated with its direct target genes.</p> <p>Conclusions</p> <p>The analysis results on NCI-60 data justify the utility of the layered models for the incoming flow of cancer genomic data. Experimental validations on selected prominent links and application of the layered modeling framework to other integrated datasets will be carried out subsequently.</p

    Unifying generative and discriminative learning principles

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    <p>Abstract</p> <p>Background</p> <p>The recognition of functional binding sites in genomic DNA remains one of the fundamental challenges of genome research. During the last decades, a plethora of different and well-adapted models has been developed, but only little attention has been payed to the development of different and similarly well-adapted learning principles. Only recently it was noticed that discriminative learning principles can be superior over generative ones in diverse bioinformatics applications, too.</p> <p>Results</p> <p>Here, we propose a generalization of generative and discriminative learning principles containing the maximum likelihood, maximum a posteriori, maximum conditional likelihood, maximum supervised posterior, generative-discriminative trade-off, and penalized generative-discriminative trade-off learning principles as special cases, and we illustrate its efficacy for the recognition of vertebrate transcription factor binding sites.</p> <p>Conclusions</p> <p>We find that the proposed learning principle helps to improve the recognition of transcription factor binding sites, enabling better computational approaches for extracting as much information as possible from valuable wet-lab data. We make all implementations available in the open-source library Jstacs so that this learning principle can be easily applied to other classification problems in the field of genome and epigenome analysis.</p
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