Searching for axion dark matter, the ADMX Collaboration acquired data from January to October 2018, over the mass range 2.81–3.31 μeV, corresponding to the frequency range 680–790 MHz. Using an ...axion haloscope consisting of a microwave cavity in a strong magnetic field, the ADMX experiment excluded Dine-Fischler-Srednicki-Zhitnisky (DFSZ) axions at 90% confidence level and 100% dark matter density over this entire frequency range, except for a few gaps due to mode crossings. This paper explains the full ADMX analysis for run 1B, motivating analysis choices informed by details specific to this run.
Atrial fibrillation (AF) is the most common arrhythmia and is associated with worsened morbidity and mortality. The prevalence of AF is estimated to increase with an ageing population resulting in an ...ever‐increasing burden on the healthcare system. Despite improvements in AF treatment, several questions remain unanswered in relation to the development and progression of AF. In this review, we discuss the evidence supporting the presence of vascular dysfunction in the development of AF, but also as a final common pathway explaining why AF constitutes a markedly increased risk of cardiovascular morbidity and mortality. Specifically, we summarise the work performed in humans related to the impact of AF on vascular structure and function, and whether measures of vascular function predict AF progression and the development of cardiovascular events. Subsequently, we discuss the potential mechanisms linking AF to the development of vascular dysfunction. Finally, we propose future perspectives of vascular health and AF, advocating a strong focus on regular exercise training as a safe and effective strategy to improve vascular function and, hence, reduce the risk for development and progression of AF and its associated risk for cardiovascular events.
Atrial fibrillation (AF) is the most common cardiac arrhythmia, characterized by irregular atrial activity. AF is related to increased risk of thromboembolic events, heart failure, and premature ...mortality. Recent advances in our understanding of its pathophysiology include a potentially central role for inflammation and presence of cardiovascular risk factors. The role of physical activity and exercise in the development and progression of AF, however, are not yet fully understood. Physical activity is protective for modifiable cardiovascular risk factors, including those associated with AF. Indeed, emerging research has demonstrated beneficial effects of exercise on AF-specific outcomes, including AF recurrence postablation. Counterintuitively, the prevalence of AF in veteran endurance athletes seems higher compared with the general population. In this review, we discuss the novel evidence and underlying mechanisms underpinning the role of exercise as medicine in the development and management of AF but also the counterintuitive detrimental role of excessive endurance exercise. Finally, we advocate regular (but not long-term high-intensity endurance) exercise training as a safe and effective strategy to reduce the risk of incident AF and to minimize the associated risk of secondary cardiovascular events.
In this paper, we present the analysis and results of a direct measurement of the cosmic-ray proton spectrum with the CALET instrument onboard the International Space Station, including the detailed ...assessment of systematic uncertainties. The observation period used in this analysis is from October 13, 2015 to August 31, 2018 (1054 days). We have achieved the very wide energy range necessary to carry out measurements of the spectrum from 50 GeV to 10 TeV covering, for the first time in space, with a single instrument the whole energy interval previously investigated in most cases in separate subranges by magnetic spectrometers (BESS-TeV, PAMELA, and AMS-02) and calorimetric instruments (ATIC, CREAM, and NUCLEON). The observed spectrum is consistent with AMS-02 but extends to nearly an order of magnitude higher energy, showing a very smooth transition of the power-law spectral index from -2.81±0.03 (50-500 GeV) neglecting solar modulation effects (or -2.87±0.06 including solar modulation effects in the lower energy region) to -2.56±0.04 (1-10 TeV), thereby confirming the existence of spectral hardening and providing evidence of a deviation from a single power law by more than 3σ.
Extended results on the cosmic-ray electron + positron spectrum from 11 GeV to 4.8 TeV are presented based on observations with the Calorimetric Electron Telescope (CALET) on the International Space ...Station utilizing the data up to November 2017. The analysis uses the full detector acceptance at high energies, approximately doubling the statistics compared to the previous result. CALET is an all-calorimetric instrument with a total thickness of 30 X_{0} at normal incidence and fine imaging capability, designed to achieve large proton rejection and excellent energy resolution well into the TeV energy region. The observed energy spectrum in the region below 1 TeV shows good agreement with Alpha Magnetic Spectrometer (AMS-02) data. In the energy region below ∼300 GeV, CALET's spectral index is found to be consistent with the AMS-02, Fermi Large Area Telescope (Fermi-LAT), and Dark Matter Particle Explorer (DAMPE), while from 300 to 600 GeV the spectrum is significantly softer than the spectra from the latter two experiments. The absolute flux of CALET is consistent with other experiments at around a few tens of GeV. However, it is lower than those of DAMPE and Fermi-LAT with the difference increasing up to several hundred GeV. The observed energy spectrum above ∼1 TeV suggests a flux suppression consistent within the errors with the results of DAMPE, while CALET does not observe any significant evidence for a narrow spectral feature in the energy region around 1.4 TeV. Our measured all-electron flux, including statistical errors and a detailed breakdown of the systematic errors, is tabulated in the Supplemental Material in order to allow more refined spectral analyses based on our data.
ABSTRACT
We present a blind time-delay cosmographic analysis for the lens system DES J0408−5354. This system is extraordinary for the presence of two sets of multiple images at different redshifts, ...which provide the opportunity to obtain more information at the cost of increased modelling complexity with respect to previously analysed systems. We perform detailed modelling of the mass distribution for this lens system using three band Hubble Space Telescope imaging. We combine the measured time delays, line-of-sight central velocity dispersion of the deflector, and statistically constrained external convergence with our lens models to estimate two cosmological distances. We measure the ‘effective’ time-delay distance corresponding to the redshifts of the deflector and the lensed quasar $D_{\Delta t}^{\rm eff}=$$3382_{-115}^{+146}$ Mpc and the angular diameter distance to the deflector Dd = $1711_{-280}^{+376}$ Mpc, with covariance between the two distances. From these constraints on the cosmological distances, we infer the Hubble constant H0= $74.2_{-3.0}^{+2.7}$ km s−1 Mpc−1 assuming a flat ΛCDM cosmology and a uniform prior for Ωm as $\Omega _{\rm m} \sim \mathcal {U}(0.05, 0.5)$. This measurement gives the most precise constraint on H0 to date from a single lens. Our measurement is consistent with that obtained from the previous sample of six lenses analysed by the H0 Lenses in COSMOGRAIL’s Wellspring (H0LiCOW) collaboration. It is also consistent with measurements of H0 based on the local distance ladder, reinforcing the tension with the inference from early Universe probes, for example, with 2.2σ discrepancy from the cosmic microwave background measurement.
We present a detailed analysis of week-long simultaneous observations of the blazar Mrk 421 at 2-60 keV X-rays (RXTE) and TeV -rays (Whipple and HEGRA) in 2001. Accompanying optical monitoring was ...performed with the Mt. Hopkins 48 inch telescope. The unprecedented quality of this data set enables us to establish the existence of the correlation between the TeV and X-ray luminosities, and also to start unveiling some of its characteristics, in particular its energy dependence and time variability. The source shows strong variations in both X-ray and -ray bands, which are highly correlated. No evidence of an X-ray/-ray interband lag tau is found on the full week data set, with tau image 3 ks. A detailed analysis of the March 19 flare, however, reveals that data are not consistent with the peak of the outburst in the 2-4 keV X-ray and TeV band being simultaneous. We estimate a image ks TeV lag. The amplitudes of the X-ray and -ray variations are also highly correlated, and the TeV luminosity increases more than linearly with respect to the X-ray one. The high degree of correlation lends further support to the standard model in which a unique electron population produces the X-rays by synchrotron radiation and the -ray component by inverse Compton scattering. However, the finding that for the individual best observed flares the -ray flux scales approximately quadratically with respect to the X-ray flux poses a serious challenge to emission models for TeV blazars, as it requires rather special conditions and/or fine tuning of the temporal evolution of the physical parameters of the emission region. We briefly discuss the astrophysical consequences of these new findings in the context of the competing models for the jet emission in blazars.
MicroRNAs (miRNAs) contribute to the pathogenesis of many forms of cancer, including the pediatric cancer neuroblastoma, but the underlying mechanisms leading to altered miRNA expression are often ...unknown. Here, a novel integrated approach for analyzing DNA methylation coupled with miRNA and mRNA expression data sets identified 67 epigenetically regulated miRNA in neuroblastoma. A large proportion (42%) of these miRNAs was associated with poor patient survival when underexpressed in tumors. Moreover, we demonstrate that this panel of epigenetically silenced miRNAs targets a large set of genes that are overexpressed in tumors from patients with poor survival in a highly redundant manner. The genes targeted by the epigenetically regulated miRNAs are enriched for a number of biological processes, including regulation of cell differentiation. Functional studies involving ectopic overexpression of several of the epigenetically silenced miRNAs had a negative impact on neuroblastoma cell viability, providing further support to the concept that inactivation of these miRNAs is important for neuroblastoma disease pathogenesis. One locus, miR-340, induced either differentiation or apoptosis in a cell context dependent manner, indicating a tumor suppressive function for this miRNA. Intriguingly, it was determined that miR-340 is upregulated by demethylation of an upstream genomic region that occurs during the process of neuroblastoma cell differentiation induced by all-trans retinoic acid (ATRA). Further biological studies of miR-340 revealed that it directly represses the SOX2 transcription factor by targeting of its 3'-untranslated region, explaining the mechanism by which SOX2 is downregulated by ATRA. Although SOX2 contributes to the maintenance of stem cells in an undifferentiated state, we demonstrate that miR-340-mediated downregulation of SOX2 is not required for ATRA induced differentiation to occur. In summary, our results exemplify the dynamic nature of the miRNA epigenome and identify a remarkable network of miRNA/mRNA interactions that significantly contribute to neuroblastoma disease pathogenesis.
The Pluto system was recently explored by NASA's New Horizons spacecraft, making closest approach on 14 July 2015. Pluto's surface displays diverse landforms, terrain ages, albedos, colors, and ...composition gradients. Evidence is found for a water-ice crust, geologically young surface units, surface ice convection, wind streaks, volatile transport, and glacial flow. Pluto's atmosphere is highly extended, with trace hydrocarbons, a global haze layer, and a surface pressure near 10 microbars. Pluto's diverse surface geology and long-term activity raise fundamental questions about how small planets remain active many billions of years after formation. Pluto's large moon Charon displays tectonics and evidence for a heterogeneous crustal composition; its north pole displays puzzling dark terrain. Small satellites Hydra and Nix have higher albedos than expected.
We present constraints on the annihilation cross section of weakly interacting massive particles 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 ∼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 1.35×10−23 cm3 s−1 at 1 TeV for the bottom quark (bb¯) final state, 2.85×10−24 cm3 s−1 at 1 TeV for the tau lepton (τ+τ−) final state and 1.32×10−25 cm3 s−1 at 1 TeV for the gauge boson (γγ) final state.
PDF
