Evolution of Novel Signal Traits in the Absence of Female Preferences in Neoconocephalus Katydids (Orthoptera, Tettigoniidae)

Background Significance: Communication signals that function to bring together the sexes are important for maintaining reproductive isolation in many taxa. Changes in male calls are often attributed to sexual selection, in which female preferences initiate signal divergence. Natural selection can also influence signal traits if calls attract predators or parasitoids, or if calling is energetically costly. Neutral evolution is often neglected in the context of acoustic communication. Methodology/Principal Findings: We describe a signal trait that appears to have evolved in the absence of either sexual or natural selection. In the katydid genus Neoconocephalus, calls with a derived pattern in which pulses are grouped into pairs have evolved five times independently. We have previously shown that in three of these species, females require the double pulse pattern for call recognition, and hence the recognition system of the females is also in a derived state. Here we describe the remaining two species and find that although males produce the derived call pattern, females use the ancestral recognition mechanism in which no pulse pattern is required. Females respond equally well to the single and double pulse calls, indicating that the derived trait is selectively neutral in the context of mate recognition. Conclusions/Significance: These results suggest that 1) neutral changes in signal traits could be important in the diversification of communication systems, and 2) males rather than females may be responsible for initiating signa

An Archival Search for Neutron-Star Mergers in Gravitational Waves and Very-High-Energy Gamma Rays

The recent discovery of electromagnetic signals in coincidence with neutron-star mergers has solidified the importance of multimessenger campaigns in studying the most energetic astrophysical events. Pioneering multimessenger observatories, such as LIGO/Virgo and IceCube, record many candidate signals below the detection significance threshold. These sub-threshold event candidates are promising targets for multimessenger studies, as the information provided by them may, when combined with contemporaneous gamma-ray observations, lead to significant detections. Here we describe a new method that uses such candidates to search for transient events using archival very-high-energy gamma-ray data from imaging atmospheric Cherenkov telescopes (IACTs). We demonstrate the application of this method to sub-threshold binary neutron star (BNS) merger candidates identified in Advanced LIGO's first observing run. We identify eight hours of archival VERITAS observations coincident with seven BNS merger candidates and search them for TeV emission. No gamma-ray emission is detected; we calculate upper limits on the integral flux and compare them to a short gamma-ray burst model. We anticipate this search method to serve as a starting point for IACT searches with future LIGO/Virgo data releases as well as in other sub-threshold studies for multimessenger transients, such as IceCube neutrinos. Furthermore, it can be deployed immediately with other current-generation IACTs, and has the potential for real-time use that places minimal burden on experimental operations. Lastly, this method may serve as a pilot for studies with the Cherenkov Telescope Array, which has the potential to observe even larger fields of view in its divergent pointing mode

VERITAS Observations of the Galactic Center Region at Multi-TeV Gamma-Ray Energies

The Galactic Center (GC) region hosts a variety of powerful astronomical sources and rare astrophysical processes that emit a large flux of non-thermal radiation. The inner 375 pc x 600 pc region, called the Central Molecular Zone, is home to the supermassive black hole Sagittarius A*, massive cloud complexes, and particle accelerators such as supernova remnants. We present the results of our improved analysis of the very-high-energy (VHE) gamma-ray emission above 2 TeV from the GC using 125 hours of data taken with the VERITAS imaging-atmospheric Cherenkov telescope between 2010 and 2018. The central source VER J1745-290, consistent with the position of Sagittarius A*, is detected at a significance of 38 standard deviations above the background level $(38\sigma)$, and we report its spectrum and light curve. Its differential spectrum is consistent with a power law with exponential cutoff, with a spectral index of $2.12^{+0.22}_{-0.17}$, a flux normalization at 5.3 TeV of $1.27^{+0.22}_{-0.23}\times 10^{-13}$ TeV-1 cm-2 s-1, and cutoff energy of $10.0^{+4.0}_{-2.0}$ TeV. We also present results on the diffuse emission near the GC, obtained by combining data from multiple regions along the GC ridge which yield a cumulative significance of $9.5\sigma$. The diffuse GC ridge spectrum is best fit by a power law with a hard index of 2.19 $\pm$ 0.20, showing no evidence of a cutoff up to 40 TeV. This strengthens the evidence for a potential accelerator of PeV cosmic rays being present in the GC. We also provide spectra of the other sources in our field of view with significant detections, composite supernova remnant G0.9+0.1 and HESS J1746-285.Comment: 19 pages, 8 figures, Accepted for publication in Astrophysical Journa

Demonstration of stellar intensity interferometry with the four VERITAS telescopes

High angular resolution observations at optical wavelengths provide valuable insights in stellar astrophysics, directly measuring fundamental stellar parameters, and probing stellar atmospheres, circumstellar disks, elongation of rapidly rotating stars, and pulsations of Cepheid variable stars. The angular size of most stars are of order one milli-arcsecond or less, and to spatially resolve stellar disks and features at this scale requires an optical interferometer using an array of telescopes with baselines on the order of hundreds of meters. We report on the successful implementation of a stellar intensity interferometry system developed for the four VERITAS imaging atmospheric-Cherenkov telescopes. The system was used to measure the angular diameter of the two sub-mas stars $\beta$ Canis Majoris and $\epsilon$ Orionis with a precision better than 5%. The system utilizes an off-line approach where starlight intensity fluctuations recorded at each telescope are correlated post-observation. The technique can be readily scaled onto tens to hundreds of telescopes, providing a capability that has proven technically challenging to current generation optical amplitude interferometry observatories. This work demonstrates the feasibility of performing astrophysical measurements with imaging atmospheric-Cherenkov telescope arrays as intensity interferometers and the promise for integrating an intensity interferometry system within future observatories such as the Cherenkov Telescope Array.Comment: Accepted for publication in Nature Astronomy (2020

Efficacious Intermittent Dosing of a Novel JAK2 Inhibitor in Mouse Models of Polycythemia Vera

A high percentage of patients with the myeloproliferative disorder polycythemia vera (PV) harbor a Val617→Phe activating mutation in the Janus kinase 2 (JAK2) gene, and both cell culture and mouse models have established a functional role for this mutation in the development of this disease. We describe the properties of MRLB-11055, a highly potent inhibitor of both the WT and V617F forms of JAK2, that has therapeutic efficacy in erythropoietin (EPO)-driven and JAK2V617F-driven mouse models of PV. In cultured cells, MRLB-11055 blocked proliferation and induced apoptosis in a manner consistent with JAK2 pathway inhibition. MRLB-11055 effectively prevented EPO-induced STAT5 activation in the peripheral blood of acutely dosed mice, and could prevent EPO-induced splenomegaly and erythrocytosis in chronically dosed mice. In a bone marrow reconstituted JAK2V617F-luciferase murine PV model, MRLB-11055 rapidly reduced the burden of JAK2V617F-expressing cells from both the spleen and the bone marrow. Using real-time in vivo imaging, we examined the kinetics of disease regression and resurgence, enabling the development of an intermittent dosing schedule that achieved significant reductions in both erythroid and myeloid populations with minimal impact on lymphoid cells. Our studies provide a rationale for the use of non-continuous treatment to provide optimal therapy for PV patients

Low BMI-1 expression is associated with an activated BMI-1-driven signature, vascular invasion, and hormone receptor loss in endometrial carcinoma

We studied the expression of polycomb group (PcG) protein BMI-1 in a large population-based patient series of endometrial carcinomas in relation to clinical and molecular phenotype. Also, 57 fresh frozen endometrial carcinomas were studied for the relationship between BMI-1 protein expression, BMI-1 mRNA level, and activation of an 11-gene signature reported to represent a BMI-1-driven pathway. BMI-1 protein expression was significantly weaker in tumours with vascular invasion (P<0.0001), deep myometrial infiltration (P=0.004), and loss of oestrogen receptor (ER) (P<0.0001) and progesterone receptors (PR) (P=0.03). Low BMI-1 protein expression was highly associated with low BMI-1 mRNA expression (P=0.002), and similarly low BMI-1 mRNA expression correlated significantly with vascular invasion, ER and PR loss, and histologic grade 3. In contrast, activation of the reported 11-gene signature, supposed to represent a BMI-1-driven pathway, correlated with low mRNA expression of BMI-1 (P<0.001), hormone receptor loss, presence of vascular invasion, and poor prognosis. We conclude that BMI-1 protein and mRNA expression are significantly correlated and that BMI-1 expression is inversely associated with activation of the 11-gene signature. Loss of BMI-1 seems to be associated with an aggressive phenotype in endometrial carcinomas

Interleukin-6 Is a Potential Biomarker for Severe Pandemic H1N1 Influenza A Infection

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data

Multiwavelength Observations of the Blazar VER J0521+211 during an Elevated TeV Gamma-Ray State

We report on a long-lasting, elevated gamma-ray flux state from VER J0521+211 observed by VERITAS, MAGIC, and Fermi-LAT in 2013 and 2014. The peak integral flux above 200 GeV measured with the nightly binned light curve is (8.8 ± 0.4) × 10-7 photons m-2 s-1, or ∼37% of the Crab Nebula flux. Multiwavelength observations from X-ray, UV, and optical instruments are also presented. A moderate correlation between the X-ray and TeV gamma-ray fluxes was observed, and the X-ray spectrum appeared harder when the flux was higher. Using the gamma-ray spectrum and four models of the extragalactic background light (EBL), a conservative 95% confidence upper limit on the redshift of the source was found to be z ≤ 0.31. Unlike the gamma-ray and X-ray bands, the optical flux did not increase significantly during the studied period compared to the archival low-state flux. The spectral variability from optical to X-ray bands suggests that the synchrotron peak of the spectral energy distribution (SED) may become broader during flaring states, which can be adequately described with a one-zone synchrotron self-Compton model varying the high-energy end of the underlying particle spectrum. The synchrotron peak frequency of the SED and the radio morphology of the jet from the MOJAVE program are consistent with the source being an intermediate-frequency-peaked BL Lac object

Combined dark matter searches towards dwarf spheroidal galaxies with Fermi-LAT, HAWC, H.E.S.S., MAGIC, and VERITAS

Cosmological and astrophysical observations suggest that 85% of the total matter of the Universe is made of Dark Matter (DM). However, its nature remains one of the most challenging and fundamental open questions of particle physics. Assuming particle DM, this exotic form of matter cannot consist of Standard Model (SM) particles. Many models have been developed to attempt unraveling the nature of DM such as Weakly Interacting Massive Particles (WIMPs), the most favored particle candidates. WIMP annihilations and decay could produce SM particles which in turn hadronize and decay to give SM secondaries such as high energy \u1d6fe rays. In the framework of indirect DM search, observations of promising targets are used to search for signatures of DM annihilation. Among these, the dwarf spheroidal galaxies (dSphs) are commonly favored owing to their expected high DM content and negligible astrophysical background. In this work, we present the very first combination of 20 dSph observations, performed by the Fermi-LAT, HAWC, H.E.S.S., MAGIC, and VERITAS collaborations in order to maximize the sensitivity of DM searches and improve the current results. We use a joint maximum likelihood approach combining each experiment’s individual analysis to derive more constraining upper limits on the WIMP DM self-annihilation cross-section as a function of DM particle mass. We present new DM constraints over the widest mass range ever reported, extending from 5 GeV to 100 TeV thanks to the combination of these five different \u1d6fe-ray instruments

Searching for VHE gamma-ray emission associated with IceCube neutrino alerts using FACT, H.E.S.S., MAGIC, and VERITAS

The realtime follow-up of neutrino events is a promising approach to search for astrophysical neutrino sources. It has so far provided compelling evidence for a neutrino point source: the flaring gamma-ray blazar TXS 0506+056 was observed in coincidence with the high-energy neutrino IceCube-170922A detected by IceCube. The detection of very-high-energy gamma rays (VHE, E > 100 GeV) from this source helped establish the coincidence and constrained the modeling of the blazar emission at the time of the IceCube event. The four major imaging atmospheric Cherenkov telescope arrays (IACTs) - FACT, H.E.S.S., MAGIC, and VERITAS - operate an active follow-up program of target-of-opportunity observations of neutrino alerts sent by IceCube. This program has two main components. One are the observations of known gamma-ray sources around which a cluster of candidate neutrino events has been identified by IceCube (Gamma-ray Follow-Up, GFU). The second one is the follow-up of single high-energy neutrino candidate events of potential astrophysical origin such as IceCube-170922A. GFU has been recently upgraded by IceCube in collaboration with the IACT groups. We present here recent results from the IACT follow-up programs of IceCube neutrino alerts and a description of the upgraded IceCube GFU system