We present a study of γ-ray emission from the core-collapse supernova remnant Cas A in the energy range from 0.1 GeV to 10 TeV. We used 65 hr of the Very Energetic Radiation Imaging Telescope Array ...System (VERITAS) data to cover 200 GeV-10 TeV, and 10.8 yr of Fermi-Large Area Telescope (LAT) data to cover 0.1-500 GeV. The spectral analysis of Fermi-LAT data shows a significant spectral curvature around 1.3 0.4stat GeV that is consistent with the expected spectrum from pion decay. Above this energy, the joint spectrum from Fermi-LAT and VERITAS deviates significantly from a simple power law, and it is best described by a power law with a spectral index of 2.17 0.02stat and a cutoff energy of 2.3 0.5stat TeV. These results, along with radio, X-ray, and γ-ray data, are interpreted in the context of leptonic and hadronic models. Assuming a one-zone model, we exclude a purely leptonic scenario and conclude that proton acceleration up to at least 6 TeV is required to explain the observed γ-ray spectrum. From modeling of the entire multiwavelength spectrum, a minimum magnetic field inside the remnant of Bmin 150 G is deduced.
KCNMA1 forms the pore of BK K
channels, which regulate neuronal and muscle excitability. Recently, genetic screening identified heterozygous
variants in a subset of patients with debilitating ...paroxysmal non-kinesigenic dyskinesia, presenting with or without epilepsy (PNKD3). However, the relevance of
mutations and the basis for clinical heterogeneity in PNKD3 has not been established. Here, we evaluate the relative severity of three
patient variants in BK channels, neurons, and mice. In heterologous cells, BK
and BK
channels displayed gain-of-function (GOF) properties, whereas BK
channels showed loss-of-function (LOF) properties. The relative degree of channel activity was BK
> BK
>WT > BK
. BK currents and action potential firing were increased, and seizure thresholds decreased, in
and
transgenic mice but not
mice. In a novel behavioral test for paroxysmal dyskinesia, the more severely affected
mice became immobile after stress. This was abrogated by acute dextroamphetamine treatment, consistent with PNKD3-affected individuals. Homozygous
mice showed similar immobility, but in contrast, homozygous
mice displayed hyperkinetic behavior. These data establish the relative pathogenic potential of patient alleles as N999S>D434G>H444Q and validate
mice as a model for PNKD3 with increased seizure propensity.
Abstract
The Breakthrough Listen Initiative is conducting a program using multiple telescopes around the world to search for “technosignatures”: artificial transmitters of extraterrestrial origin ...from beyond our solar system. The Very Energetic Radiation Imaging Telescope Array System (VERITAS) Collaboration joined this program in 2018 and provides the capability to search for one particular technosignature: optical pulses of a few nanoseconds in duration detectable over interstellar distances. We report here on the analysis and results of dedicated VERITAS observations of Breakthrough Listen targets conducted in 2019 and 2020 and of archival VERITAS data collected since 2012. Thirty hours of dedicated observations of 136 targets and 249 archival observations of 140 targets were analyzed and did not reveal any signals consistent with a technosignature. The results are used to place limits on the fraction of stars hosting transmitting civilizations. We also discuss the minimum pulse sensitivity of our observations and present VERITAS observations of CALIOP: a space-based pulsed laser on board the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations. The detection of these pulses with VERITAS, using the analysis techniques developed for our technosignature search, allows a test of our analysis efficiency and serves as an important proof of principle.
KCNMA1 encodes the voltage- and calcium-activated K+ (BK) channel, which regulates suprachiasmatic nucleus (SCN) neuronal firing and circadian behavioral rhythms. Gain-of-function (GOF) and ...loss-of-function (LOF) alterations in BK channel activity disrupt circadian behavior, but the effect of human disease-associated KCNMA1 channelopathy variants has not been studied on clock function. Here, we assess circadian behavior in two GOF and one LOF mouse lines. Heterozygous Kcnma1N999S/WT and homozygous Kcnma1D434G/D434G mice are validated as GOF models of paroxysmal dyskinesia (PNKD3), but whether circadian rhythm is affected in this hypokinetic locomotor disorder is unknown. Conversely, homozygous LOF Kcnma1H444Q/H444Q mice do not demonstrate PNKD3. We assessed circadian behavior by locomotor wheel running activity. All three mouse models were rhythmic, but Kcnma1N999S/WT and Kcnma1D434G/D434G showed reduced circadian amplitude and decreased wheel activity, corroborating prior studies focused on acute motor coordination. In addition, Kcnma1D434G/D434G mice had a small decrease in period. However, the phase-shifting sensitivity for both GOF mouse lines was abnormal. Both Kcnma1N999S/WT and Kcnma1D434G/D434G mice displayed increased responses to light pulses and took fewer days to re-entrain to a new light:dark cycle. In contrast, the LOF Kcnma1H444Q/H444Q mice showed no difference in any of the circadian parameters tested. The enhanced sensitivity to phase-shifting stimuli in Kcnma1N999S/WT and Kcnma1D434G/D434G mice was similar to other Kcnma1 GOF mice. Together with previous studies, these results suggest that increasing BK channel activity decreases circadian clock robustness, without rhythm ablation.
The variability of the blazar Markarian 421 in TeV gamma rays over a 14-year time period has been explored with the Whipple 10m telescope. It is shown that the dynamic range of its flux variations is ...large and similar to that in X-rays. A correlation between the X-ray and TeV energy bands is observed during some bright flares and when the complete data sets are binned on long timescales. The main database consists of 878.4h of observation with the Whipple telescope, spread over 783 nights. The peak energy response of the telescope was 400GeV with 20% uncertainty. This is the largest database of any TeV-emitting active galactic nucleus (AGN) and hence was used to explore the variability profile of Markarian 421. The time-averaged flux from Markarian 421 over this period was 0.446±0.008Crab flux units. The flux exceeded 10Crab flux units on three separate occasions. For the 2000–2001 season the average flux reached 1.86Crab units, while in the 1996–1997 season the average flux was only 0.23Crab units.
On 2015 March 23, the Very Energetic Radiation Imaging Telescope Array System (VERITAS) responded to a Swift-Burst Alert Telescope (BAT) detection of a gamma-ray burst, with observations beginning ...270 s after the onset of BAT emission, and only 135 s after the main BAT emission peak. No statistically significant signal is detected above 140 GeV. The VERITAS upper limit on the fluence in a 40-minute integration corresponds to about 1% of the prompt fluence. Our limit is particularly significant because the very-high-energy (VHE) observation started only ∼2 minutes after the prompt emission peaked, and Fermi-Large Area Telescope observations of numerous other bursts have revealed that the high-energy emission is typically delayed relative to the prompt radiation and lasts significantly longer. Also, the proximity of GRB 150323A (z = 0.593) limits the attenuation by the extragalactic background light to ∼50% at 100-200 GeV. We conclude that GRB 150323A had an intrinsically very weak high-energy afterglow, or that the GeV spectrum had a turnover below ∼100 GeV. If the GRB exploded into the stellar wind of a massive progenitor, the VHE non-detection constrains the wind density parameter to be A 3 × 1011 g cm−1, consistent with a standard Wolf-Rayet progenitor. Alternatively, the VHE emission from the blast wave would be weak in a very tenuous medium such as the interstellar medium, which therefore cannot be ruled out as the environment of GRB 150323A.
ABSTRACT Transient X-ray binaries produce major outbursts in which the X-ray flux can increase over the quiescent level by factors as large as 107. The low-mass X-ray binary V 404 Cyg and the ...high-mass system 4U 0115+634 underwent such major outbursts in 2015 June and October, respectively. We present here observations at energies above hundreds of GeV with the VERITAS observatory taken during some of the brightest X-ray activity ever observed from these systems. No gamma-ray emission has been detected by VERITAS in 2.5 hr of observations of the microquasar V 404 Cyg from 2015, June 20-21. The upper flux limits derived from these observations on the gamma-ray flux above 200 GeV of F cm−2 s−1 correspond to a tiny fraction (about 10−6) of the Eddington luminosity of the system, in stark contrast to that seen in the X-ray band. No gamma-rays have been detected during observations of 4U 0115+634 in the period of major X-ray activity in 2015 October. The flux upper limit derived from our observations is F cm−2 s−1 for gamma-rays above 300 GeV, setting an upper limit on the ratio of gamma-ray to X-ray luminosity of less than 4%.
This study tested the hypothesis that site-specific estrogen receptor alpha (ERα) expression is a critical factor in the expression of male prosocial behavior and aggression. Previous studies have ...shown that in the socially monogamous prairie vole (Microtus ochrogaster) low levels of ERα expression, in the medial amygdala (MeA), play an essential role in the expression of high levels of male prosocial behavior and that increasing ERα expression reduced male prosocial behavior. We used an shRNA adeno-associated viral vector to knock down/inhibit ERα in the MeA of the polygynous male meadow vole (M. pennsylvanicus), which displays significantly higher levels of ERα in the MeA than its monogamous relative. Control males were transfected with a luciferase expressing AAV vector. After treatment males participated in three social behavior tests, a same-sex dyadic encounter, an opposite-sex social preference test and an alloparental test. We predicted that decreasing MeA ERα would increase male meadow vole’s prosocial behavior and reduce aggression. The results generally supported the hypothesis. Specifically, MeA knockdown males displayed lower levels of defensive aggression during dyadic encounters and increased levels of overall side-x-side physical contact with females during the social preference test, eliminating the partner preference observed in controls. There was no effect on pup interactions, with both treatments expressing low levels of alloparental behavior. Behaviors affected were similar to those in male prairie voles with increased ERα in the BST rather than the MeA, suggesting that relative changes of expression within these nuclei may play a critical role in regulating prosocial behavior.
This study tested the hypotheses that maternal and paternal effects differentially influence expression of their offspring's adult behavior and underlying neural mechanisms. We predicted that ...maternal influences would be greater than paternal influences on male offspring. We tested these hypotheses by cross-breeding two phenotypically-, behaviorally- and neuroanatomically-distinct populations of prairie voles (Microtus ochrogaster) from Illinois, which are highly prosocial, and Kansas, which are significantly less prosocial. Females from each population were crossed with males from the other population. F1 crosses were tested as adults to determine the effect of parentage on the expression of prosocial behavior and aggression, using a same-sex dyadic encounter and a heterosexual partner preference test, and for the expression of oxytocin (OT) and arginine vasopressin (AVP) in the paraventricular nucleus of the hypothalamus (PVN). As predicted, all significant differences in males, behavioral, OT and AVP immunoreactivity, were associated exclusively with maternal influences. There was a significant effect of treatment in the OT immunoreactivity of females. The effect of treatment in females’ OT was associated with an interaction of population and sex, while same-sex social interactions differences were associated with population. Finally, in females, paternity influenced heterosexual bonds, with females with Illinois sires forming a partner preference. The results indicate that maternal influences dominate in male offspring, suggesting a parent-of-origin effect, while paternal effects are limited to selected prosocial behavioral expression in daughters.
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