775 research outputs found

    A seemingly unrelated regression analysis of regulator selection and electricity prices

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    Includes bibliographical references (p. 21-22)

    Integrated Resource Planning and Incentive Regulation

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    HDAC1 interacts with the p50 NF-κB subunit via its nuclear localization sequence to constrain inflammatory gene expression

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    The NF-κB p50 subunit is an important regulator of inflammation, with recent experimental evidence to support it also having a tumor suppressor role. Classically, p50 functions in heterodimeric form with the RelA (p65) NF-κB subunit to activate inflammatory genes. However, p50 also forms homodimers which actively repress NF-κB-dependent inflammatory gene expression and exert an important brake on the inflammatory process. This repressive activity of p50:p50 is thought to be in part mediated by an interaction with the epigenetic repressor protein Histone Deacetylase 1 (HDAC1). However, neither the interaction of p50 with HDAC1 nor the requirement of HDAC1 for the repressive activities of p50 has been well defined. Here we employed in silico prediction with in vitro assays to map sites of interaction of HDAC1 on the p50 protein. Directed mutagenesis of one such region resulted in almost complete loss of HDAC1 binding to p50. Transfected mutant p50 protein lacking the putative HDAC1 docking motif resulted in enhanced cytokine and chemokine expression when compared with cells expressing a transfected wild type p50. In addition, expression of this mutant p50 was associated with enhanced chemoattraction of neutrophils and acetylation of known inflammatory genes demonstrating the likely importance of the p50:HDAC1 interaction for controlling inflammation. These new insights provide an advance on current knowledge of the mechanisms by which NF-κB-dependent gene transcription are regulated and highlight the potential for manipulation of p50:HDAC1 interactions to bring about experimental modulation of chronic inflammation and pathologies associated with dysregulated neutrophil accumulation and activation

    The ACS Virgo Cluster Survey III. Chandra and HST Observations of Low-Mass X-Ray Binaries and Globular Clusters in M87

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    The ACIS instrument on board the Chandra X-ray Observatory has been used to carry out the first systematic study of low-mass X-ray binaries (LMXBs) in M87. We identify 174 X-ray point-sources, of which ~150 are likely LMXBs. This LMXB catalog is combined with deep F475W and F850LP images taken with ACS on HST to examine the connection between LMXBs and globular clusters in M87. Of the 1688 globular clusters in our catalog, f_X = 3.6 +- 0.5% contain a LMXB and we find that the metal-rich clusters are 3 +- 1 times more likely to harbor a LMXB than their metal-poor counterparts. In agreement with previous findings for other galaxies, we find that brighter, more metal-rich clusters are more likely to contain a LMXB. For the first time, however, we are able to demonstrate that the probability, p_X, that a given cluster will contain a LMXB depends sensitively on the dynamical properties of the host cluster. Specifically, we use the HST images to measure the half-light radius, concentration index and central density, \rho_0, for each globular, and define a parameter, \Gamma, which is related to the tidal capture and binary-neutron star exchange rate. Our preferred form for p_X is then p_X \propto \Gamma \rho_0^{-0.42\pm0.11} (Z/Z_{\odot})^{0.33\pm0.1}. We argue that if the form of p_X is determined by dynamical processes, then the observed metallicity dependence is a consequence of an increased number of neutron stars per unit mass in metal-rich globular clusters. Finally, we find no compelling evidence for a break in the luminosity distribution of resolved X-ray point sources. Instead, the LMXB luminosity function is well described by a power law with an upper cutoff at L_X ~ 10^39 erg/s. (abridged)Comment: 23 pages, 21 figures. Accepted for publication in ApJ. Also available at http://www.physics.rutgers.edu/~pcote/acs/publications.htm

    Reproduction of Twentieth Century Intradecadal to Multidecadal Surface Temperature Variability in Radiatively Forced Coupled Climate Models

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    [1] Coupled Model Intercomparison Project 3 simulations that included time-varying radiative forcings were ranked according to their ability to consistently reproduce twentieth century intradecadal to multidecadal (IMD) surface temperature variability at the 5° by 5° spatial scale. IMD variability was identified using the running Mann-Whitney Z method. Model rankings were given context by comparing the IMD variability in preindustrial control runs to observations and by contrasting the IMD variability among the ensemble members within each model. These experiments confirmed that the inclusion of time-varying external forcings brought simulations into closer agreement with observations. Additionally, they illustrated that the magnitude of unforced variability differed between models. This led to a supplementary metric that assessed model ability to reproduce observations while accounting for each model\u27s own degree of unforced variability. These two metrics revealed that discernable differences in skill exist between models and that none of the models reproduced observations at their theoretical optimum level. Overall, these results demonstrate a methodology for assessing coupled models relative to each other within a multimodel framework

    Marine seismic surveys and ocean noise : time for coordinated and prudent planning

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    Marine seismic surveys use intense (eg >= 230 decibel [dB] root mean square [RMS]) sound impulses to explore the ocean bottom for hydrocarbon deposits, conduct geophysical research, and establish resource claims under the United Nations Convention on the Law of the Sea. The expansion of seismic surveys necessitates greater regional and international dialogue, partnerships, and planning to manage potential environmental risks. Data indicate several reasons for concern about the negative impacts of anthropogenic noise on numerous marine species, including habitat displacement, disruption of biologically important behaviors, masking of communication signals, chronic stress, and potential auditory damage. The sound impulses from seismic surveys - spanning temporal and spatial scales broader than those typically considered in environmental assessments - may have acute, cumulative, and chronic effects on marine organisms. Given the international and transboundary nature of noise from marine seismic surveys, we suggest the creation of an international regulatory instrument, potentially an annex to the existing International Convention on the Prevention of Pollution from Ships, to address the issue.Publisher PDFPeer reviewe

    MINERvA neutrino detector response measured with test beam data

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    The MINERvA collaboration operated a scaled-down replica of the solid scintillator tracking and sampling calorimeter regions of the MINERvA detector in a hadron test beam at the Fermilab Test Beam Facility. This article reports measurements with samples of protons, pions, and electrons from 0.35 to 2.0 GeV/c momentum. The calorimetric response to protons, pions, and electrons are obtained from these data. A measurement of the parameter in Birks' law and an estimate of the tracking efficiency are extracted from the proton sample. Overall the data are well described by a Geant4-based Monte Carlo simulation of the detector and particle interactions with agreements better than 4%, though some features of the data are not precisely modeled. These measurements are used to tune the MINERvA detector simulation and evaluate systematic uncertainties in support of the MINERvA neutrino cross section measurement program.Comment: as accepted by NIM

    A proteomic approach based on peptide affinity chromatography, 2-dimensional electrophoresis and mass spectrometry to identify multiprotein complexes interacting with membrane-bound receptors

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    There is accumulating evidence that membrane-bound receptors interact with many intracellular proteins. Multiprotein complexes associated with ionotropic receptors have been extensively characterized, but the identification of proteins interacting with G protein-coupled receptors (GPCRs) has so far only been achieved in a piecemeal fashion, focusing on one or two protein species. We describe a method based on peptide affinity chromatography, two-dimensional electrophoresis, mass spectrometry and immunoblotting to identify the components of multiprotein complexes interacting directly or indirectly with intracellular domains of GPCRs or, more generally, any other membrane-bound receptor. Using this global approach, we have characterized multiprotein complexes that bind to the carboxy-terminal tail of the 5-hydroxytryptamine type 2C receptor and are important for its subcellular localization in CNS cells (Bécamel et al., EMBO J., 21(10): 2332, 2002)

    Ethnic inequalities and pathways to care in psychosis in England: a systematic review and meta-analysis

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    © The Author(s). 2018Background: As part of a national programme to tackle ethnic inequalities, we conducted a systematic review and meta-analysis of research on ethnic inequalities in pathways to care for adults with psychosis living in England and/or Wales. Methods: Nine databases were searched from inception to 03.07.17 for previous systematic reviews, including forward and backward citation tracking and a PROSPERO search to identify ongoing reviews. We then carried forward relevant primary studies from included reviews (with the latest meta-analyses reporting on research up to 2012), supplemented by a search on 18.10.17 in MEDLINE, Embase, PsycINFO and CINAHL for primary studies between 2012 and 2017 that had not been covered by previous meta-analyses. Results: Forty studies, all conducted in England, were included for our updated meta-analyses on pathways to care. Relative to the White reference group, elevated rates of civil detentions were found for Black Caribbean (OR = 3.43, 95% CI = 2.68 to 4.40, n = 18), Black African (OR = 3.11, 95% CI = 2.40 to 4.02, n = 6), and South Asian patients (OR = 1.50, 95% CI 1.07 to 2.12, n = 10). Analyses of each Mental Health Act section revealed significantly higher rates for Black people under (civil) Section 2 (OR = 1.53, 95% CI = 1.11 to 2.11, n = 3). Rates in repeat admissions were significantly higher than in first admission for South Asian patients (between-group difference p < 0.01). Some ethnic groups had more police contact (Black African OR = 3.60, 95% CI = 2.15 to 6.05, n = 2; Black Caribbean OR = 2.64, 95% CI = 1.88 to 3.72, n = 8) and criminal justice system involvement (Black Caribbean OR = 2.76, 95% CI = 2.02 to 3.78, n = 5; Black African OR = 1.92, 95% CI = 1.32 to 2.78, n = 3). The White Other patients also showed greater police and criminal justice system involvement than White British patients (OR = 1.49, 95% CI = 1.03 to 2.15, n = 4). General practitioner involvement was less likely for Black than the White reference group. No significant variations over time were found across all the main outcomes. Conclusions: Our updated meta-analyses reveal persisting but not significantly worsening patterns of ethnic inequalities in pathways to psychiatric care, particularly affecting Black groups. This provides a comprehensive evidence base from which to inform policy and practice amidst a prospective Mental Health Act reform. Trial registration: CRD42017071663Peer reviewedFinal Published versio
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