Classical aspects of Hawking radiation verified in analogue gravity experiment

There is an analogy between the propagation of fields on a curved spacetime and shallow water waves in an open channel flow. By placing a streamlined obstacle into an open channel flow we create a region of high velocity over the obstacle that can include wave horizons. Long (shallow water) waves propagating upstream towards this region are blocked and converted into short (deep water) waves. This is the analogue of the stimulated Hawking emission by a white hole (the time inverse of a black hole). The measurements of amplitudes of the converted waves demonstrate that they appear in pairs and are classically correlated; the spectra of the conversion process is described by a Boltzmann-distribution; and the Boltzmann-distribution is determined by the determined by the change in flow across the white hole horizon.Comment: 17 pages, 10 figures; draft of a chapter submitted to the proceedings of the IX'th SIGRAV graduate school: Analogue Gravity, Lake Como, Italy, May 201

Mining Energy from a Black Hole by Strings

We discuss how cosmic strings can be used to mine energy from black holes. A string attached to the black hole gives rise to an additional channel for the energy release. It is demonstrated that when a string crosses the event horizon, its transverse degrees of freedom are thermally excited and thermal string perturbations propagate along the string to infinity. The internal metric induced on the 2D worldsheet of the static string crossing the horizon describes a 2D black hole. For this reason thermal radiation of string excitations propagating along the string can be interpreted as Hawking radiation of the 2D black hole. It is shown that the rate of energy emission through the string channel is of the same order of magnitude as the bulk radiation of the black hole. Thus, for N strings attached to the black hole the efficiency of string channels is increased by factor N. We discuss restrictions on N which exist because of the finite thickness of strings, the gravitational backreaction and quantum fluctuations. Our conclusion is that the energy emission rate by strings can be increased as compared to the standard emission in the bulk by the factor 10^3 for GUT strings and up to the factor 10^{31} for electroweak strings.Comment: 13 pages, no figures, final version to appear in Physical Revie

VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Search for R-parity Violating Decays of Supersymmetric Particles in e+e−e^+ e^- Collisions at LEP

A search, in $e^+ e^-$ collisions, for chargino, neutralino, scalar lepton and scalar quark pair-production is performed, without assuming R-parity conservation in decays, in the case that only one of the coupling constants $\lambda_{ijk}$ or $\lambda''_{ ijk}$ is non-negligible. No signal is found in data up to a centre-of-mass energy of 208 \GeV. Limits on the production cross sections and on the masses of supersymmetric particles are derived.A search, in e + e − collisions, for chargino, neutralino, scalar lepton and scalar quark pair-production is performed, without assuming R-parity conservation in decays, in the case that only one of the coupling constants λ or λ ″ is non-negligible. No signal is found in data up to a centre-of-mass energy of 208 GeV. Limits on the production cross sections and on the masses of supersymmetric particles are derived.A search, in e^+e^- collisions, for chargino, neutralino, scalar lepton and scalar quark pair-production is performed, without assuming R-parity conservation in decays, in the case that only one of the coupling constants lambda_ijk or lambda''_ijk is non-negligible. No signal is found in data up to a centre-of-mass energy of 208GeV. Limits on the production cross sections and on the masses of supersymmetric particles are derived

A Modified Progressive Supranuclear Palsy Rating Scale

Background: The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status. Objective: The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones. Methods: Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy. Results: The modified scale retained 14 items (yielding 0–2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months). Conclusions: The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine

Driver Fusions and Their Implications in the Development and Treatment of Human Cancers.

Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types. Our study suggests that fusions drive the development of 16.5% of cancer cases and function as the sole driver in more than 1% of them. Finally, we identified druggable fusions involving genes such as TMPRSS2, RET, FGFR3, ALK, and ESR1 in 6.0% of cases, and we predicted immunogenic peptides, suggesting that fusions may provide leads for targeted drug and immune therapy