A First Comparison of the responses of a He4-based fast-neutron detector and a NE-213 liquid-scintillator reference detector

A first comparison has been made between the pulse-shape discrimination characteristics of a novel $^{4}$He-based pressurized scintillation detector and a NE-213 liquid-scintillator reference detector using an Am/Be mixed-field neutron and gamma-ray source and a high-resolution scintillation-pulse digitizer. In particular, the capabilities of the two fast neutron detectors to discriminate between neutrons and gamma-rays were investigated. The NE-213 liquid-scintillator reference cell produced a wide range of scintillation-light yields in response to the gamma-ray field of the source. In stark contrast, due to the size and pressure of the $^{4}$He gas volume, the $^{4}$He-based detector registered a maximum scintillation-light yield of 750~keV$_{ee}$ to the same gamma-ray field. Pulse-shape discrimination for particles with scintillation-light yields of more than 750~keV$_{ee}$ was excellent in the case of the $^{4}$He-based detector. Above 750~keV$_{ee}$ its signal was unambiguously neutron, enabling particle identification based entirely upon the amount of scintillation light produced.Comment: 23 pages, 7 figures, Nuclear Instruments and Methods in Physics Research Section A review addresse

Circulating Small Non-coding RNAs as Biomarkers for Recovery After Exhaustive or Repetitive Exercise

Circulating microRNAs have proven to be reliable biomarkers, due to their high stability, both in vivo in the circulation, and ex vivo during sample preparation and storage. Small nucleolar RNAs (snoRNAs) are a different type of small non-coding RNAs that can also be reliably measured in plasma, but have only been studied sporadically. In this study, we aimed to identify RNA-biomarkers that can distinguish between different exercise regimes and that entail clues about muscle repair and recovery after prolonged exhaustive endurance exercise. We compared plasma microRNA profiles between two cohorts of elite cyclists, subjected to two different types of exercise regimes, as well as a cohort of patients with peripheral artery disease (PAD) that were scheduled to undergo lower limb amputation, due to critical limb ischemia. In elite athletes, muscle tissue recovers quickly even after exhaustive exercise, whereas in PAD patients, recovery is completely impaired. Furthermore, we measured levels of a specific group of snoRNAs in the plasma of both elite cyclists and PAD patients. Using a multiplex qPCR screening, we detected a total of 179 microRNAs overall, of which, on average, 161 microRNAs were detected per sample. However, only 30 microRNAs were consistently expressed in all samples. Of these, two microRNAs, miR-29a-3p and miR193a-5p, that responded differently two different types of exercise, namely exhaustive exercise and non-exhaustive endurance exercise. Using individual rt/qPCR, we also identified a snoRNA, SNORD114.1, which was significantly upregulated in plasma in response to endurance exercise. Furthermore, two microRNAs, miR-29a-3p and miR-495-3p, were significantly differentially expressed in athletes compared to PAD patients, but only following exercise. We suggest that these two microRNAs could function as markers of impaired muscle repair and recovery. In conclusion, microRNAs miR-29a-3p and miR-193a-5p may help us distinguish between repeated exhaustive and non-exhaustive endurance exercise. MicroRNA miR-29a-3p, as well as miR-495-3p, may further mark impaired muscle recovery in patients with severe critical limb ischemia. Furthermore, we showed for the first time that a circulating snoRNA, SNORD114.1, is regulated in response to exercise and may be used as biomarker

A Search for Very High-Energy Gamma Rays from the Missing Link Binary Pulsar J1023+0038 with VERITAS

The binary millisecond radio pulsar PSR J1023+0038 exhibits many characteristics similar to the gamma-ray binary system PSR B1259--63/LS 2883, making it an ideal candidate for the study of high-energy non-thermal emission. It has been the subject of multi-wavelength campaigns following the disappearance of the pulsed radio emission in 2013 June, which revealed the appearance of an accretion disk around the neutron star. We present the results of very high-energy gamma-ray observations carried out by VERITAS before and after this change of state. Searches for steady and pulsed emission of both data sets yield no significant gamma-ray signal above 100 GeV, and upper limits are given for both a steady and pulsed gamma-ray flux. These upper limits are used to constrain the magnetic field strength in the shock region of the PSR J1023+0038 system. Assuming that very high-energy gamma rays are produced via an inverse-Compton mechanism in the shock region, we constrain the shock magnetic field to be greater than $\sim$2 G before the disappearance of the radio pulsar and greater than $\sim$10 G afterwards.Comment: 7 pages, 3 figures, accepted for publication in Ap

Very-High-Energy γ\gamma-Ray Observations of the Blazar 1ES 2344+514 with VERITAS

We present very-high-energy $\gamma$-ray observations of the BL Lac object 1ES 2344+514 taken by the Very Energetic Radiation Imaging Telescope Array System (VERITAS) between 2007 and 2015. 1ES 2344+514 is detected with a statistical significance above background of $20.8\sigma$ in $47.2$ hours (livetime) of observations, making this the most comprehensive very-high-energy study of 1ES 2344+514 to date. Using these observations the temporal properties of 1ES 2344+514 are studied on short and long times scales. We fit a constant flux model to nightly- and seasonally-binned light curves and apply a fractional variability test, to determine the stability of the source on different timescales. We reject the constant-flux model for the 2007-2008 and 2014-2015 nightly-binned light curves and for the long-term seasonally-binned light curve at the $> 3\sigma$ level. The spectra of the time-averaged emission before and after correction for attenuation by the extragalactic background light are obtained. The observed time-averaged spectrum above 200 GeV is satisfactorily fitted (${\chi^2/NDF = 7.89/6}$) by a power-law function with index $\Gamma = 2.46 \pm 0.06_{stat} \pm 0.20_{sys}$ and extends to at least 8 TeV. The extragalactic-background-light-deabsorbed spectrum is adequately fit (${\chi^2/NDF = 6.73/6}$) by a power-law function with index $\Gamma = 2.15 \pm 0.06_{stat} \pm 0.20_{sys}$ while an F-test indicates that the power-law with exponential cutoff function provides a marginally-better fit ($\chi^2/NDF$ = $2.56 / 5$) at the 2.1$\sigma$ level. The source location is found to be consistent with the published radio location and its spatial extent is consistent with a point source.Comment: 7 pages, 2 figures. Published in Monthly Notices of the Royal Astronomical Societ

Tagging fast neutrons from an 241Am/9Be source

We report on an investigation of the fast-neutron spectrum emitted by 241Am/9Be. Well-understood shielding, coincidence, and time-of-flight measurement techniques are employed to produce a continuous, polychromatic, energy-tagged neutron beam.Comment: 17 pages, 7 figures, submitted to Journal of Applied Radiation and Isotope

Dark Matter Constraints from a Joint Analysis of Dwarf Spheroidal Galaxy Observations with VERITAS

We present constraints on the annihilation cross section of WIMP dark matter based on the joint statistical analysis of four dwarf galaxies with VERITAS. These results are derived from an optimized photon weighting statistical technique that improves on standard imaging atmospheric Cherenkov telescope (IACT) analyses by utilizing the spectral and spatial properties of individual photon events. We report on the results of $\sim$230 hours of observations of five dwarf galaxies and the joint statistical analysis of four of the dwarf galaxies. We find no evidence of gamma-ray emission from any individual dwarf nor in the joint analysis. The derived upper limit on the dark matter annihilation cross section from the joint analysis is $1.35\times 10^{-23} {\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the bottom quark ($b\bar{b}$) final state, $2.85\times 10^{-24}{\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the tau lepton ($\tau^{+}\tau^{-}$) final state and $1.32\times 10^{-25}{\mathrm{ cm^3s^{-1}}}$ at 1 TeV for the gauge boson ($\gamma\gamma$) final state.Comment: 14 pages, 9 figures, published in PRD, Ascii tables containing annihilation cross sections limits are available for download as ancillary files with readme.txt file description of limit

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Estrogen-Like Effects of Cadmium in Vivo Do Not Appear to be Mediated via the Classical Estrogen Receptor Transcriptional Pathway

Cadmium is a toxic metal classified as human carcinogen and ubiquitously found in our environment mainly from anthropogenic activities. Exposure to cadmium has been associated with increased risk of certain hormone-dependent cancers in humans, and the metal has been proposed to possess endocrine disruptive properties by mimicking the physiological actions of estrogens. However, the mechanisms behind these effects are unclear. The overall aim of this thesis was to provide mechanistic insights into the estrogenicity of cadmium that may have implications for the human health. To achieve this aim, investigations on the estrogen-like effects of cadmium as well as possible involvement of classical/non-classical estrogen receptor signaling was studied in mice, and these mechanisms were further scrutinized in cell-based models. Furthermore, associations of biomarker of cadmium exposure with endogenous circulating sex hormones were evaluated in a population-based study of women. Results presented here indicate that exposure to cadmium does not affect the genomic estrogen response in vivo in mice, suggesting that classical estrogen signaling is not targeted by cadmium. However, some estrogen-like effects were observed in cadmium exposed mice, i.e. significant thickening of uterine epithelia, in the absence of uterine weight increase, and activation of ERK1/2 MAPKs in the liver. This suggests the existence of alternative signaling pathways modulated by cadmium. In addition, exposure to a wide dose range of cadmium, dose-dependently increased the expression of the endogenous genes Mt1, Mt2, p53, c-fos, and Mdm2 in mouse liver, with p53 being the most sensitive gene. However, phosphorylation of ERK1/2 was already induced at the lowest exposure level (0.5µg/kg body weight), rendering ERK1/2 a more sensitive marker of exposure than any change in gene expression. Furthermore, in vivo findings suggest that cadmium-induced effects are markedly concentration dependent: low-level exposure activates protein-kinases whereas high-level exposure turns on cellular stress responses. The data from in vitro studies indicate that cadmium at regular human exposure levels activates protein-kinase signaling through Raf-MEK-ERK/MAPKs, and we identified EGFR and GPR30 as the mediating receptors. This cadmium-induced activation of protein-kinases further leads to a disturbance in Mdm2/p53 balance, with a significant increase in the Mdm2/p53 ratio in the presence of genotoxic compounds, which in turn suggest that cadmium may disrupt stress response to genotoxins. In 438 postmenopausal women, a positive association was observed between the concentrations of cadmium in blood and testosterone in serum, while an inverse association was observed with estradiol. This may suggest that cadmium affects steroidogenesis. In conclusion, data presented in this thesis collectively suggests that cadmium-induced estrogen-like effects do not involve classical estrogen receptor signaling but rather appear to be mediated via membrane-associated signaling. The activation/ transactivation of GPR30/EGFR-Raf-MEK-ERK/MAPKs and Mdm2 represent a general mechanism by which cadmium may exert its effects. Since EGFR, ERK and Mdm2 are all known key players in cancer promotion, cadmium-induced activation of these and disturbance in the estradiol/testosterone balance in women may have implications for the promotion/development of hormone-related cancers

A search for spectral hysteresis and energy-dependent time lags from X-ray and TeV gamma-ray observations of Mrk 421

Blazars are variable emitters across all wavelengths over a wide range of timescales, from months down to minutes. It is therefore essential to observe blazars simultaneously at different wavelengths, especially in the X-ray and gamma-ray bands, where the broadband spectral energy distributions usually peak. In this work, we report on three "target-of-opportunity" (ToO) observations of Mrk 421, one of the brightest TeV blazars, triggered by a strong flaring event at TeV energies in 2014. These observations feature long, continuous, and simultaneous exposures with XMM-Newton (covering X-ray and optical/ultraviolet bands) and VERITAS (covering TeV gamma-ray band), along with contemporaneous observations from other gamma-ray facilities (MAGIC and Fermi-LAT) and a number of radio and optical facilities. Although neither rapid flares nor significant X-ray/TeV correlation are detected, these observations reveal subtle changes in the X-ray spectrum of the source over the course of a few days. We search the simultaneous X-ray and TeV data for spectral hysteresis patterns and time delays, which could provide insight into the emission mechanisms and the source properties (e.g. the radius of the emitting region, the strength of the magnetic field, and related timescales). The observed broadband spectra are consistent with a one-zone synchrotron self-Compton model. We find that the power spectral density distribution at $\gtrsim 4\times 10^{-4}$ Hz from the X-ray data can be described by a power-law model with an index value between 1.2 and 1.8, and do not find evidence for a steepening of the power spectral index (often associated with a characteristic length scale) compared to the previously reported values at lower frequencies.Comment: 45 pages, 15 figure