842 research outputs found

    Measurement of Cosmic-ray Muons and Muon-induced Neutrons in the Aberdeen Tunnel Underground Laboratory

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    We have measured the muon flux and production rate of muon-induced neutrons at a depth of 611 m water equivalent. Our apparatus comprises three layers of crossed plastic scintillator hodoscopes for tracking the incident cosmic-ray muons and 760 L of gadolinium-doped liquid scintillator for producing and detecting neutrons. The vertical muon intensity was measured to be Iμ=(5.7±0.6)×106I_{\mu} = (5.7 \pm 0.6) \times 10^{-6} cm2^{-2}s1^{-1}sr1^{-1}. The yield of muon-induced neutrons in the liquid scintillator was determined to be Yn=(1.19±0.08(stat)±0.21(syst))×104Y_{n} = (1.19 \pm 0.08 (stat) \pm 0.21 (syst)) \times 10^{-4} neutrons/(μ\mu\cdotg\cdotcm2^{-2}). A fit to the recently measured neutron yields at different depths gave a mean muon energy dependence of Eμ0.76±0.03\left\langle E_{\mu} \right\rangle^{0.76 \pm 0.03} for liquid-scintillator targets.Comment: 14 pages, 17 figures, 3 table

    OGLE-2012-BLG-0455/MOA-2012-BLG-206: Microlensing event with ambiguity in planetary interpretations caused by incomplete coverage of planetary signal

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    Characterizing a microlensing planet is done from modeling an observed lensing light curve. In this process, it is often confronted that solutions of different lensing parameters result in similar light curves, causing difficulties in uniquely interpreting the lens system, and thus understanding the causes of different types of degeneracy is important. In this work, we show that incomplete coverage of a planetary perturbation can result in degenerate solutions even for events where the planetary signal is detected with a high level of statistical significance. We demonstrate the degeneracy for an actually observed event OGLE-2012-BLG-0455/MOA-2012-BLG-206. The peak of this high-magnification event (Amax400)(A_{\rm max}\sim400) exhibits very strong deviation from a point-lens model with Δχ24000\Delta\chi^{2}\gtrsim4000 for data sets with a total number of measurement 6963. From detailed modeling of the light curve, we find that the deviation can be explained by four distinct solutions, i.e., two very different sets of solutions, each with a two-fold degeneracy. While the two-fold (so-called "close/wide") degeneracy is well-understood, the degeneracy between the radically different solutions is not previously known. The model light curves of this degeneracy differ substantially in the parts that were not covered by observation, indicating that the degeneracy is caused by the incomplete coverage of the perturbation. It is expected that the frequency of the degeneracy introduced in this work will be greatly reduced with the improvement of the current lensing survey and follow-up experiments and the advent of new surveys.Comment: 5 pages, 3 figures, ApJ accepte

    B and T cells are not required for the viable motheaten phenotype.

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    Comparative analysis of homology models of the Ah receptor ligand binding domain: Verification of structure-function predictions by site-directed mutagenesis of a nonfunctional receptor

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    The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates the biological and toxic effects of a wide variety of structurally diverse chemicals, including the toxic environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). While significant interspecies differences in AHR ligand binding specificity, selectivity, and response have been observed, the structural determinants responsible for those differences have not been determined, and homology models of the AHR ligand-binding domain (LBD) are available for only a few species. Here we describe the development and comparative analysis of homology models of the LBD of 16 AHRs from 12 mammalian and nonmammalian species and identify the specific residues contained within their ligand binding cavities. The ligand-binding cavity of the fish AHR exhibits differences from those of mammalian and avian AHRs, suggesting a slightly different TCDD binding mode. Comparison of the internal cavity in the LBD model of zebrafish (zf) AHR2, which binds TCDD with high affinity, to that of zfAHR1a, which does not bind TCDD, revealed that the latter has a dramatically shortened binding cavity due to the side chains of three residues (Tyr296, Thr386, and His388) that reduce the amount of internal space available to TCDD. Mutagenesis of two of these residues in zfAHR1a to those present in zfAHR2 (Y296H and T386A) restored the ability of zfAHR1a to bind TCDD and to exhibit TCDD-dependent binding to DNA. These results demonstrate the importance of these two amino acids and highlight the predictive potential of comparative analysis of homology models from diverse species. The availability of these AHR LBD homology models will facilitate in-depth comparative studies of AHR ligand binding and ligand-dependent AHR activation and provide a novel avenue for examining species-specific differences in AHR responsiveness. © 2013 American Chemical Society

    MOA-2011-BLG-293Lb: A test of pure survey microlensing planet detections

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    Because of the development of large-format, wide-field cameras, microlensing surveys are now able to monitor millions of stars with sufficient cadence to detect planets. These new discoveries will span the full range of significance levels including planetary signals too small to be distinguished from the noise. At present, we do not understand where the threshold is for detecting planets. MOA-2011-BLG-293Lb is the first planet to be published from the new surveys, and it also has substantial followup observations. This planet is robustly detected in survey+followup data (Delta chi^2 ~ 5400). The planet/host mass ratio is q=5.3+/- 0.2*10^{-3}. The best fit projected separation is s=0.548+/- 0.005 Einstein radii. However, due to the s-->s^{-1} degeneracy, projected separations of s^{-1} are only marginally disfavored at Delta chi^2=3. A Bayesian estimate of the host mass gives M_L = 0.43^{+0.27}_{-0.17} M_Sun, with a sharp upper limit of M_L < 1.2 M_Sun from upper limits on the lens flux. Hence, the planet mass is m_p=2.4^{+1.5}_{-0.9} M_Jup, and the physical projected separation is either r_perp = ~1.0 AU or r_perp = ~3.4 AU. We show that survey data alone predict this solution and are able to characterize the planet, but the Delta chi^2 is much smaller (Delta chi^2~500) than with the followup data. The Delta chi^2 for the survey data alone is smaller than for any other securely detected planet. This event suggests a means to probe the detection threshold, by analyzing a large sample of events like MOA-2011-BLG-293, which have both followup data and high cadence survey data, to provide a guide for the interpretation of pure survey microlensing data.Comment: 29 pages, 6 figures, Replaced 7/3/12 with the version accepted to Ap

    Immunotherapy targeting isoDGR-protein damage extends lifespan in a mouse model of protein deamidation

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    \ua9 2023 The Authors. Published under the terms of the CC BY 4.0 license. Aging results from the accumulation of molecular damage that impairs normal biochemical processes. We previously reported that age-linked damage to amino acid sequence NGR (Asn-Gly-Arg) results in “gain-of-function” conformational switching to isoDGR (isoAsp-Gly-Arg). This integrin-binding motif activates leukocytes and promotes chronic inflammation, which are characteristic features of age-linked cardiovascular disorders. We now report that anti-isoDGR immunotherapy mitigates lifespan reduction of Pcmt1−/− mouse. We observed extensive accumulation of isoDGR and inflammatory cytokine expression in multiple tissues from Pcmt1−/− and naturally aged WT animals, which could also be induced via injection of isoDGR-modified plasma proteins or synthetic peptides into young WT animals. However, weekly injection of anti-isoDGR mAb (1 mg/kg) was sufficient to significantly reduce isoDGR-protein levels in body tissues, decreased pro-inflammatory cytokine concentrations in blood plasma, improved cognition/coordination metrics, and extended the average lifespan of Pcmt1−/− mice. Mechanistically, isoDGR-mAb mediated immune clearance of damaged isoDGR-proteins via antibody-dependent cellular phagocytosis (ADCP). These results indicate that immunotherapy targeting age-linked protein damage may represent an effective intervention strategy in a range of human degenerative disorders
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