BATSE Observations of Gamma-Ray Burst Spectra. IV. Time-Resolved High-Energy Spectroscopy

We report on the temporal behavior of the high-energy power law continuum component of gamma-ray burst spectra with data obtained by the Burst and Transient Source Experiment. We have selected 126 high fluence and high flux bursts from the beginning of the mission up until the present. Much of the data were obtained with the Large Area Detectors, which have nearly all-sky coverage, excellent sensitivity over two decades of energy and moderate energy resolution, ideal for continuum spectra studies of a large sample of bursts at high time resolution. At least 8 spectra from each burst were fitted with a spectral form that consisted of a low-energy power law, a spectral break at middle energies and a high-energy continuum. In most bursts (122), the high-energy continuum was consistent with a power law. The evolution of the fitted high-energy power-law index over the selected spectra for each burst is inconsistent with a constant for 34% of the total sample. The sample distribution of the average value for the index from each burst is fairly narrow, centered on -2.12. A linear trend in time is ruled out for only 20% of the bursts, with hard-to-soft evolution dominating the sample (100 events). The distribution for the total change in the power-law index over the duration of a burst peaks at the value -0.37, and is characterized by a median absolute deviation of 0.39, arguing that a single physical process is involved. We present analyses of the correlation of the power-law index with time, burst intensity and low-energy time evolution. In general, we confirm the general hard-to-soft spectral evolution observed in the low-energy component of the continuum, while presenting evidence that this evolution is different in nature from that of the rest of the continuum.Comment: 30 pages, with 2 tables and 9 figures To appear in The Astrophysical Journal, April 1, 199

State-Dependent Effects of Ventromedial Prefrontal Cortex Continuous Thetaburst Stimulation on Cocaine Cue Reactivity in Chronic Cocaine Users

Cue-induced craving is a significant barrier to obtaining abstinence from cocaine. Neuroimaging research has shown that cocaine cue exposure evokes elevated activity in a network of frontal-striatal brain regions involved in drug craving and drug seeking. Prior research from our laboratory has demonstrated that when targeted at the medial prefrontal cortex (mPFC), continuous theta burst stimulation (cTBS), an inhibitory form of non-invasive brain stimulation, can decrease drug cue-related activity in the striatum in cocaine users and alcohol users. However, it is known that there are individual differences in response to repetitive transcranial magnetic stimulation (rTMS), with some individuals being responders and others non-responders. There is some evidence that state-dependent effects influence response to rTMS, with baseline neural state predicting rTMS treatment outcomes. In this single-blind, active sham-controlled crossover study, we assess the striatum as a biomarker of treatment response by determining if baseline drug cue reactivity in the striatum influences striatal response to mPFC cTBS. The brain response to cocaine cues was measured in 19 cocaine-dependent individuals immediately before and after real and sham cTBS (110% resting motor threshold, 3600 total pulses). Group independent component analysis (ICA) revealed a prominent striatum network comprised of bilateral caudate, putamen, and nucleus accumbens, which was modulated by the cocaine cue reactivity task. Baseline drug cue reactivity in this striatal network was inversely related to change in striatum reactivity after real (vs. sham) cTBS treatment (ρ = -.79; p < .001; R2Adj = .58). Specifically, individuals with a high striatal response to cocaine cues at baseline had significantly attenuated striatal activity after real but not sham cTBS (t9 = -3.76; p ≤ .005). These data demonstrate that the effects of mPFC cTBS on the neural circuitry of craving are not uniform and may depend on an individual’s baseline frontal-striatal reactivity to cues. This underscores the importance of assessing individual variability as we develop brain stimulation treatments for addiction

Human rabies postexposure prophylaxis during a raccoon rabies epizootic in New York, 1993 and 1994.

We describe the epidemiology of human rabies postexposure prophylaxis (PEP) in four upstate New York counties during the 1st and 2nd year of a raccoon rabies epizootic. We obtained data from records of 1,173 persons whose rabies PEP was reported to local health departments in 1993 and 1994. Mean annual PEP incidence rates were highest in rural counties, in summer, and in patients 10 to 14 and 35 to 44 years of age. PEP given after bites was primarily associated with unvaccinated dogs and cats, but most (70%) was not attributable to bites. Although pet vaccination and stray animal control, which target direct exposure, remain the cornerstones of human rabies prevention, the risk for rabies by the nonbite route (e. g., raccoon saliva on pet dogs' and cats' fur) should also be considered

Panoramic SETI: Program Update and High-Energy Astrophysics Applications

Optical SETI (Search for Extraterrestrial Intelligence) instruments that can explore the very fast time domain, especially with large sky coverage, offer an opportunity for new discoveries that can complement multimessenger and time domain astrophysics. The Panoramic SETI experiment (PANOSETI) aims to observe optical transients with nanosecond to second duration over a wide field-of-view ($\thicksim$2,500 sq.deg.) by using two assemblies of tens of telescopes to reject spurious signals by coincidence detection. Three PANOSETI telescopes, connected to a White Rabbit timing network used to synchronize clocks at the nanosecond level, have been deployed at Lick Observatory on two sites separated by a distance of 677 meters to distinguish nearby light sources (such as Cherenkov light from particle showers in the Earth's atmosphere) from astrophysical sources at large distances. In parallel to this deployment, we present results obtained during four nights of simultaneous observations with the four 12-meter VERITAS gamma-ray telescopes and two PANOSETI telescopes at the Fred Lawrence Whipple Observatory. We report PANOSETI's first detection of astrophysical gamma rays, comprising three events with energies in the range between $\thicksim$15 TeV and $\thicksim$50 TeV. These were emitted by the Crab Nebula, and identified as gamma rays using joint VERITAS observations.Comment: 9 pages, 5 figures, SPIE Astronomical Telescopes + Instrumentation conference, 2022, Montr\'eal, Qu\'ebec, Canad

Comparison of an anti-rabies human monoclonal antibody combination with human polyclonal anti-rabies immune globulin

The World Health Organization estimates human mortality from endemic canine rabies to be 55,000 deaths/ year. Limited supply hampers the accessibility of appropriate lifesaving treatment, particularly in areas where rabies is endemic. Anti-rabies antibodies are key to protection against lethal rabies. Currently, only human and equine polyclonal anti-rabies immune globulin (HRIG and ERIG) is available. Replacement of HRIG and ERIG with a safer and more widely available product is recommended. We have recently identified a combination of 2 human monoclonal antibodies (MAbs), CR57 and CR4098, that has high potential. We here describe a head-to-head comparison between an CR57/CR4098 MAb cocktail and HRIG. The MAb cocktail neutralized all viruses from a panel of 26 representative street rabies virus isolates. In combination with vaccine, the MAb cocktail protected Syrian hamsters against lethal rabies when administered 24 h after exposure, comparable with the results obtained with HRIG. Furthermore, the MAb cocktail did not interfere with rabies vaccine differently from HRIG. These results demonstrate that the human MAb cocktail of CR57 and CR4098 is a safe and efficacious alternative to RIG in rabies postexposure prophylaxis. A recent World Health Organization publication estimated human mortality from endemic canine rabies to be 55,000 deaths/year Mouse MAbs, as well as human MAbs, have been shown to protect rodents from lethal RV challeng

Gamma secretase inhibition promotes hypoxic necrosis in mouse pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease that is refractory to medical intervention. Notch pathway antagonism has been shown to prevent pancreatic preneoplasia progression in mouse models, but potential benefits in the setting of an established PDA tumor have not been established. We demonstrate that the gamma secretase inhibitor MRK003 effectively inhibits intratumoral Notch signaling in the KPC mouse model of advanced PDA. Although MRK003 monotherapy fails to extend the lifespan of KPC mice, the combination of MRK003 with the chemotherapeutic gemcitabine prolongs survival. Combination treatment kills tumor endothelial cells and synergistically promotes widespread hypoxic necrosis. These results indicate that the paucivascular nature of PDA can be exploited as a therapeutic vulnerability, and the dual targeting of the tumor endothelium and neoplastic cells by gamma secretase inhibition constitutes a rationale for clinical translation

A VERITAS/Breakthrough Listen Search for Optical Technosignatures

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 VERITAS Collaboration joined this program in 2018, and provides the capability to search for one particular technosignature: optical pulses of a few nanoseconds 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 onboard the CALIPSO satellite. 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.Comment: 15 pages, 7 figure

VERITAS discovery of very high energy gamma-ray emission from S3 1227+25 and multiwavelength observations

We report the detection of very high energy gamma-ray emission from the blazar S3 1227+25 (VER J1230+253) with the Very Energetic Radiation Imaging Telescope Array System (VERITAS). VERITAS observations of the source were triggered by the detection of a hard-spectrum GeV flare on May 15, 2015 with the Fermi-Large Area Telescope (LAT). A combined five-hour VERITAS exposure on May 16th and May 18th resulted in a strong 13$\sigma$ detection with a differential photon spectral index, $\Gamma$ = 3.8 $\pm$ 0.4, and a flux level at 9% of the Crab Nebula above 120 GeV. This also triggered target of opportunity observations with Swift, optical photometry, polarimetry and radio measurements, also presented in this work, in addition to the VERITAS and Fermi-LAT data. A temporal analysis of the gamma-ray flux during this period finds evidence of a shortest variability timescale of $\tau_{obs}$ = 6.2 $\pm$ 0.9 hours, indicating emission from compact regions within the jet, and the combined gamma-ray spectrum shows no strong evidence of a spectral cut-off. An investigation into correlations between the multiwavelength observations found evidence of optical and gamma-ray correlations, suggesting a single-zone model of emission. Finally, the multiwavelength spectral energy distribution is well described by a simple one-zone leptonic synchrotron self-Compton radiation model.Comment: 18 pages, 6 figures. Accepted for publication in the Astrophysical Journal (ApJ