4,133 research outputs found

    Gravity Dual of Gauge Theory on S^2 x S^1 x R

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    We (numerically) construct new static, asymptotically AdS solutions where the conformal infinity is the product of time and S^2 x S^1. There always exist a family of solutions in which the S^1 is not contractible and, for small S^1, there are two additional families of solutions in which the S^1 smoothly pinches off. This shows that (when fermions are antiperiodic around the S^1) there is a quantum phase transition in the gauge theory as one decreases the radius of the S^1 relative to the S^2. We also compare the masses of our solutions and argue that the one with lowest mass should minimize the energy among all solutions with conformal boundary S^2 x S^1 x R. This provides a new positive energy conjecture for asymptotically locally AdS metrics. A simple analytic continuation produces AdS black holes with topology S^2 x S^1.Comment: 17 pages, 4 figures, v2: minor changes, added reference

    Calibrating genomic and allelic coverage bias in single-cell sequencing

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    Artifacts introduced in whole-genome amplification (WGA) make it difficult to derive accurate genomic information from single-cell genomes and require different analytical strategies from bulk genome analysis. Here, we describe statistical methods to quantitatively assess the amplification bias resulting from whole-genome amplification of single-cell genomic DNA. Analysis of single-cell DNA libraries generated by different technologies revealed universal features of the genome coverage bias predominantly generated at the amplicon level (1–10 kb). The magnitude of coverage bias can be accurately calibrated from low-pass sequencing (∼0.1 × ) to predict the depth-of-coverage yield of single-cell DNA libraries sequenced at arbitrary depths. We further provide a benchmark comparison of single-cell libraries generated by multi-strand displacement amplification (MDA) and multiple annealing and looping-based amplification cycles (MALBAC). Finally, we develop statistical models to calibrate allelic bias in single-cell whole-genome amplification and demonstrate a census-based strategy for efficient and accurate variant detection from low-input biopsy samples.National Cancer Institute (U.S.) (Grant P30-CA14051

    Minimal Flavour Violation for Leptoquarks

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    Scalar leptoquarks, with baryon and lepton number conserving interactions, could have TeV scale masses, and be produced at colliders or contribute to a wide variety of rare decays. In pursuit of some insight as to the most sensitive search channels, We assume that the leptoquark-lepton-quark coupling can be constructed from the known mass matrices. We estimate the rates for selected rare processes in three cases: leptoquarks carrying lepton and quark flavour, leptoquarks with quark flavour only, and unflavoured leptoquarks. We find that leptoquark decay to top quarks is an interesting search channel.Comment: 17 pages, 2 figures, minor changes and references adde

    Mechanism of age-dependent susceptibility and novel treatment strategy in glutaric acidemia type I

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    Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. The mechanisms underlying injury and age-dependent susceptibility have been unknown, and lack of a diagnostic marker heralding brain injury has impeded intervention efforts. Using a mouse model of GA-I, we show that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic marker. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings provide what we believe are new monitoring and treatment strategies that may translate for use in human GA-I

    Study of measured pulsar masses and their possible conclusions

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    We study the statistics of 61 measured masses of neutron stars (NSs) in binary pulsar systems, including 18 double NS (DNS) systems, 26 radio pulsars (10 in our Galaxy) with white dwarf (WD) companions, 3 NSs with main-sequence companions, 13 NSs in X-ray binaries, and one undetermined system. We derive a mean value of M = 1.46 +/- 0.30 solar masses. When the 46 NSs with measured spin periods are divided into two groups at 20 milliseconds, i.e., the millisecond pulsar (MSP) group and others, we find that their mass averages are, respectively, M=1.57 +/- 0.35 solar masses and M=1.37+/- 0.23 solar masses. In the framework of the pulsar recycling hypothesis, this suggests that an accretion of approximately 0.2 solar mass is sufficient to spin up a neutron star and place it in the millisecond pulsar group. An empirical relation between the accreting mass and MSP spin period is \Delta M=0.43 (solar mass)(P/1 ms)^{-2/3}. UNlike the standard recycling process, if a MSP is formed by the accretion induced collapse (AIC) of a white dwarf with a mass less than Chandrasekha limit, e.g. 1.35 solar mass, then the binary MSPs involved in AICs is not be higher than 20%, which imposes a constraint on the AIC origin of MSPs.Comment: 6 pages, 5 figures, in press, Astronomy and Astrophysics 2011, 527, 8

    Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer

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    Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies

    Fermi-LAT Search for Pulsar Wind Nebulae around gamma-ray Pulsars

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    The high sensitivity of the Fermi-LAT (Large Area Telescope) offers the first opportunity to study faint and extended GeV sources such as pulsar wind nebulae (PWNe). After one year of observation the LAT detected and identified three pulsar wind nebulae: the Crab Nebula, Vela-X and the PWN inside MSH 15-52. In the meantime, the list of LAT detected pulsars increased steadily. These pulsars are characterized by high energy loss rates from ~3 \times 10^{33} erg s1^{-1} to 5 \times 1038^{38} erg s1^{-1} and are therefore likely to power a PWN. This paper summarizes the search for PWNe in the off-pulse windows of 54 LAT-detected pulsars using 16 months of survey observations. Ten sources show significant emission, seven of these likely being of magnetospheric origin. The detection of significant emission in the off-pulse interval offers new constraints on the gamma-ray emitting regions in pulsar magnetospheres. The three other sources with significant emission are the Crab Nebula, Vela-X and a new pulsar wind nebula candidate associated with the LAT pulsar PSR J1023-5746, coincident with the TeV source HESS J1023-575. We further explore the association between the H.E.S.S. and the Fermi source by modeling its spectral energy distribution. Flux upper limits derived for the 44 remaining sources are used to provide new constraints on famous PWNe that have been detected at keV and/or TeV energies.Comment: Accepted for publication in Astrophysical Journal, 42 pages, 17 figure

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
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