House dust mite-driven neutrophilic airway inflammation in mice with TNFAIP3-deficient myeloid cells is IL-17-independent

Background: Asthma is a heterogeneous disease of the airways that involves several types of granulocytic inflammation. Recently, we have shown that the activation status of myeloid cells regulated by TNFAIP3/A20 is a crucial determinant of eosinophilic or neutrophilic airway inflammation. However, whether neutrophilic inflammation observed in this model is dependent on IL-17 remains unknown. Objective: In this study, we investigated whether IL-17RA-signalling is essential for eosinophilic or neutrophilic inflammation in house dust mite (HDM)-driven airway inflammation. Methods: Tnfaip3fl/flxLyz2+/cre (Tnfaip3LysM-KO) mice were crossed to Il17raKO mice, generating Tnfaip3LysMIl17raKO mice and subjected to an HDM-driven airway inflammation model. Results: Both eosinophilic and neutrophilic inflammation observed in HDM-exposed WT and Tnfaip3LysM-KO mice respectively were unaltered in the absence of IL-17RA. Production of IL-5, IL-13 and IFN-γ by CD4+ T cells was similar between WT, Tnfaip3LysM-KO and Il17raKO mice, whereas mucus-producing cells in Tnfaip3LysM-KOIl17raKO mice were reduced compared to controls. Strikingly, spontaneous accumulation of pulmonary Th1, Th17 and γδ-17 T cells was observed in Tnfaip3LysM-KOIl17raKO mice, but not in the other genotypes. Th17 cell-associated cytokines such as GM-CSF and IL-22 were increased in the lungs of HDM-exposed Tnfaip3LysM-KOIl17raKO mice, compared to IL-17RA-sufficient controls. Moreover, neutrophilic chemo-attractants CXCL1, CXCL2, CXCL12 and Th17-promoting cytokines IL-1β and IL-6 were unaltered between Tnfaip3LysM-KO and Tnfaip3LysM-KOIl17raKO mice. Conclusion and Clinical Relevance: These findings show that neutrophilic airway inflammation induced by activated TNFAIP3/A20-deficient myeloid cells can develop in the absence of IL-17RA-signalling. Neutrophilic inflammation is likely maintained by similar quantities of pro-inflammatory cytokines IL-1β and IL-6 that can, independently of IL-17-signalling, induce the expression of neutrophil chemo-attractants

GROWTH on S190510g: DECam Observation Planning and Follow-Up of a Distant Binary Neutron Star Merger Candidate

The first two months of the third Advanced LIGO and Virgo observing run (2019 April–May) showed that distant gravitational-wave (GW) events can now be readily detected. Three candidate mergers containing neutron stars (NS) were reported in a span of 15 days, all likely located more than 100 Mpc away. However, distant events such as the three new NS mergers are likely to be coarsely localized, which highlights the importance of facilities and scheduling systems that enable deep observations over hundreds to thousands of square degrees to detect the electromagnetic counterparts. On 2019 May 10 02:59:39.292 UT the GW candidate S190510g was discovered and initially classified as a binary neutron star (BNS) merger with 98% probability. The GW event was localized within an area of 3462 deg^2, later refined to 1166 deg^2 (90%) at a distance of 227 ± 92 Mpc. We triggered Target-of-Opportunity observations with the Dark Energy Camera (DECam), a wide-field optical imager mounted at the prime focus of the 4 m Blanco Telescope at Cerro Tololo Inter-American Observatory in Chile. This Letter describes our DECam observations and our real-time analysis results, focusing in particular on the design and implementation of the observing strategy. Within 24 hr of the merger time, we observed 65% of the total enclosed probability of the final skymap with an observing efficiency of 94%. We identified and publicly announced 13 candidate counterparts. S190510g was reclassified 1.7 days after the merger, after our observations were completed, with a "BNS merger" probability reduced from 98% to 42% in favor of a "terrestrial classification

Cross-modal visuo-haptic mental rotation: comparing objects between senses

The simple experience of a coherent percept while looking and touching an object conceals an intriguing issue: different senses encode and compare information in different modality-specific reference frames. We addressed this problem in a cross-modal visuo-haptic mental rotation task. Two objects in various orientations were presented at the same spatial location, one visually and one haptically. Participants had to identify the objects as same or different. The relative angle between viewing direction and hand orientation was manipulated (Aligned versus Orthogonal). In an additional condition (Delay), a temporal delay was introduced between haptic and visual explorations while the viewing direction and the hand orientation were orthogonal to each other. Whereas the phase shift of the response time function was close to 0° in the Aligned condition, we observed a consistent phase shift in the hand’s direction in the Orthogonal condition. A phase shift, although reduced, was also found in the Delay condition. Counterintuitively, these results mean that seen and touched objects do not need to be physically aligned for optimal performance to occur. The present results suggest that the information about an object is acquired in separate visual and hand-centered reference frames, which directly influence each other and which combine in a time-dependent manner

The Tidal Disruption Event AT2021ehb : Evidence of Relativistic Disk Reflection, and Rapid Evolution of the Disk-Corona System

© 2022. The Author(s). Published by the American Astronomical Society. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: https://creativecommons.org/licenses/by/4.0/We present X-ray, UV, optical, and radio observations of the nearby ($\approx78$ Mpc) tidal disruption event (TDE) AT2021ehb/ZTF21aanxhjv during its first 430 days of evolution. AT2021ehb occurs in the nucleus of a galaxy hosting a $\approx 10^{7}\,M_\odot$ black hole ($M_{\rm BH}$ inferred from host galaxy scaling relations). High-cadence Swift and NICER monitoring reveals a delayed X-ray brightening. The spectrum first undergoes a gradual ${\rm soft }\rightarrow{\rm hard}$ transition and then suddenly turns soft again within 3 days at $\delta t\approx 272$ days during which the X-ray flux drops by a factor of ten. In the joint NICER+NuSTAR observation ($\delta t =264$ days, harder state), we observe a prominent non-thermal component up to 30 keV and an extremely broad emission line in the iron K band. The bolometric luminosity of AT2021ehb reaches a maximum of $6.0^{+10.4}_{-3.8}\% L_{\rm Edd}$ when the X-ray spectrum is the hardest. During the dramatic X-ray evolution, no radio emission is detected, the UV/optical luminosity stays relatively constant, and the optical spectra are featureless. We propose the following interpretations: (i) the ${\rm soft }\rightarrow{\rm hard}$ transition may be caused by the gradual formation of a magnetically dominated corona; (ii) hard X-ray photons escape from the system along solid angles with low scattering optical depth ($\sim\,$a few) whereas the UV/optical emission is likely generated by reprocessing materials with much larger column density -- the system is highly aspherical; (iii) the abrupt X-ray flux drop may be triggered by the thermal-viscous instability in the inner accretion flow leading to a much thinner disk.Peer reviewe

Fast-transient Searches in Real Time with ZTFReST: Identification of Three Optically Discovered Gamma-Ray Burst Afterglows and New Constraints on the Kilonova Rate

The most common way to discover extragalactic fast transients, which fade within a few nights in the optical, is via follow-up of gamma-ray burst and gravitational-wave triggers. However, wide-field surveys have the potential to identify rapidly fading transients independently of such external triggers. The volumetric survey speed of the Zwicky Transient Facility (ZTF) makes it sensitive to objects as faint and fast fading as kilonovae, the optical counterparts to binary neutron star mergers, out to almost 200 Mpc. We introduce an open-source software infrastructure, the ZTF REaltime Search and Triggering, ZTFReST, designed to identify kilonovae and fast transients in ZTF data. Using the ZTF alert stream combined with forced point-spread-function photometry, we have implemented automated candidate ranking based on their photometric evolution and fitting to kilonova models. Automated triggering, with a human in the loop for monitoring, of follow-up systems has also been implemented. In 13 months of science validation, we found several extragalactic fast transients independently of any external trigger, including two supernovae with post-shock cooling emission, two known afterglows with an associated gamma-ray burst (ZTF20abbiixp, ZTF20abwysqy), two known afterglows without any known gamma-ray counterpart (ZTF20aajnksq, ZTF21aaeyldq), and three new fast-declining sources (ZTF20abtxwfx, ZTF20acozryr, ZTF21aagwbjr) that are likely associated with GRB200817A, GRB201103B, and GRB210204A. However, we have not found any objects that appear to be kilonovae. We constrain the rate of GW170817-like kilonovae to R < 900 Gpc-3 yr-1 (95% confidence). A framework such as ZTFReST could become a prime tool for kilonova and fast-transient discovery with the Vera Rubin Observatory

Constraining the Kilonova Rate with Zwicky Transient Facility Searches Independent of Gravitational Wave and Short Gamma-Ray Burst Triggers

The first binary neutron star merger, GW170817, was accompanied by a radioactivity-powered optical/infrared transient called a kilonova. To date, no compelling kilonova has been found in all-sky optical surveys, independently of short gamma-ray burst and gravitational-wave triggers. In this work, we searched the first 23 months of the Zwicky Transient Facility (ZTF) data stream for candidate kilonovae in the form of rapidly evolving transients. We combined ZTF alert queries with forced point-spread-function photometry and nightly flux stacking to increase our sensitivity to faint and fast transients. Automatic queries yielded >11,200 candidates, 24 of which passed quality checks and selection criteria based on a grid of kilonova models tailored for both binary neutron star and neutron star–black hole mergers. None of the candidates in our sample was deemed a possible kilonova after thorough vetting. The sources that passed our selection criteria are dominated by Galactic cataclysmic variables. We identified two fast transients at high Galactic latitude, one of which is the confirmed afterglow of long-duration GRB 190106A, the other is a possible cosmological afterglow. Using a survey simulation code, we constrained the kilonova rate for a range of models including top-hat, linearly decaying light curves, and synthetic light curves obtained with radiative transfer simulations. For prototypical GW170817-like kilonovae, we constrain the rate to be R < 1775 Gpc⁻³ yr⁻¹ (95% confidence). By assuming a population of kilonovae with the same geometry and composition of GW170817 observed under a uniform viewing angle distribution, we obtained a constraint on the rate of R < 4029 Gpc⁻³ yr⁻¹

Constraining the Kilonova Rate with Zwicky Transient Facility Searches Independent of Gravitational Wave and Short Gamma-ray Burst Triggers

The first binary neutron star merger, GW170817, was accompanied by a radioactivity-powered optical/infrared transient called a kilonova. To date, no compelling kilonova has been found during optical surveys of the sky, independent of gravitational-wave triggers. In this work, we searched the first 23 months of the Zwicky Transient Facility (ZTF) data stream for candidate kilonovae in the form of rapidly evolving transients. We combined ZTF alert queries with forced point-spread-function photometry and nightly flux stacking to increase our sensitivity to faint and fast transients. Automatic queries yielded $>11,200$ candidates, 24 of which passed quality checks and strict selection criteria based on a grid of kilonova models tailored for both binary neutron star and neutron star-black hole mergers. None of the candidates in our sample was deemed a possible kilonova after thorough vetting, catalog cross-matching, and study of their color evolution. The sources that passed our selection criteria are dominated by Galactic cataclysmic variables. In addition, we identified two fast transients at high Galactic latitude, one of which is the confirmed afterglow of long-duration GRB190106A, and the other is a possible cosmological afterglow. Using a survey simulation code, we constrained the kilonova rate for a range of models including top-hat and linearly decaying light curves and synthetic light curves obtained with radiative transfer simulations. For prototypical GW170817-like kilonovae, we constrain the rate to be $R < 1775$ Gpc$^{-3}$ yr$^{-1}$ at 95% confidence level by requiring at least 2 high-significance detections. By assuming a population of kilonovae with the same geometry and composition of GW170817 observed under a uniform viewing angle distribution, we obtained a constraint on the rate of $R < 4029$ Gpc$^{-3}$ yr$^{-1}$.Comment: Submitted for publication in Ap