p97 is a AAA-ATPase with multiple cellular functions, one of which is critical regulation of protein homeostasis pathways. We describe the characterization of CB-5083, a potent, selective, and orally bioavailable inhibitor of p97. Treatment of tumor cells with CB-5083 leads to accumulation of poly-ubiquitinated proteins, retention of endoplasmic reticulum-associated degradation (ERAD) substrates, and generation of irresolvable proteotoxic stress, leading to activation of the apoptotic arm of the unfolded protein response. In xenograft models, CB-5083 causes modulation of key p97-related pathways, induces apoptosis, and has antitumor activity in a broad range of both hematological and solid tumor models. Molecular determinants of CB-5083 activity include expression of genes in the ERAD pathway, providing a potential strategy for patient selection.

We present high-cadence UV, optical, and near-infrared data on the luminous Type II-P supernova SN 2017gmr from hours after discovery through the first 180 days. SN 2017gmr does not show signs of narrow, high-ionization emission lines in the early optical spectra, yet the optical light-curve evolution suggests that an extra energy source from circumstellar medium (CSM) interaction must be present for at least 2 days after explosion. Modeling of the early light curve indicates a ∼500 R o progenitor radius, consistent with a rather compact red supergiant, and late-time luminosities indicate that up to 0.130 ± 0.026 M o of 56Ni are present, if the light curve is solely powered by radioactive decay, although the 56Ni mass may be lower if CSM interaction contributes to the post-plateau luminosity. Prominent multipeaked emission lines of Hα and [O i] emerge after day 154, as a result of either an asymmetric explosion or asymmetries in the CSM. The lack of narrow lines within the first 2 days of explosion in the likely presence of CSM interaction may be an example of close, dense, asymmetric CSM that is quickly enveloped by the spherical supernova ejecta.

Wide-field optical surveys have begun to uncover large samples of fast (trise ≲ 5 d), luminous (Mpeak < -18), blue transients. While commonly attributed to the breakout of a supernova shock into a dense wind, the great distances to the transients of this class found so far have hampered detailed investigation of their properties. We present photometry and spectroscopy from a comprehensive worldwide campaign to observe AT 2018cow (ATLAS 18qqn), the first fast-luminous optical transient to be found in real time at lowredshift. Our first spectra (<2 days after discovery) are entirely featureless. A very broad absorption feature suggestive of nearrelativistic velocities develops between 3 and 8 days, then disappears. Broad emission features of H and He develop after >10 days. The spectrum remains extremely hot throughout its evolution, and the photospheric radius contracts with time (receding below R < 1014 cm after 1 month). This behaviour does not match that of any known supernova, although a relativistic jet within a fallback supernova could explain some of the observed features. Alternatively, the transient could originate from the disruption of a star by an intermediate-mass black hole, although thiswould require long-lasting emission of highly super-Eddington thermal radiation. In either case, AT 2018cow suggests that the population of fast luminous transients represents a new class of astrophysical event. Intensive follow-up of this event in its late phases, and of any future events found at comparable distance, will be essential to better constrain their origins.

We investigate the prompt emission and the afterglow properties of short-duration gamma-ray burst (sGRB) 130603B and another eight sGRB events during 2012-2015, observed by several multiwavelength facilities including the Gran Canarias Telescope 10.4 m telescope. Prompt emission high energy data of the events were obtained by INTEGRAL-SPI-ACS, Swift-BAT, and Fermi-GBM satellites. The prompt emission data by INTEGRAL in the energy range of 0.1-10 MeV for sGRB 130603B, sGRB 140606A, sGRB 140930B, sGRB 141212A, and sGRB 151228A do not show any signature of the extended emission or precursor activity and their spectral and temporal properties are similar to those seen in case of other short bursts. For sGRB 130603B, our new afterglow photometric data constrain the pre-jet-break temporal decay due to denser temporal coverage. For sGRB 130603B, the afterglow light curve, containing both our new and previously published photometric data is broadly consistent with the ISM afterglow model. Modeling of the host galaxies of sGRB 130603B and sGRB 141212A using the LePHARE software supports a scenario in which the environment of the burst is undergoing moderate star formation activity. From the inclusion of our late-time data for eight other sGRBs we are able to: place tight constraints on the non-detection of the afterglow, host galaxy, or any underlying 'kilonova' emission. Our late-time afterglow observations of the sGRB 170817A/GW170817 are also discussed and compared with the sub-set of sGRBs.

We present a systematic search for optical counterparts to 13 gravitational wave (GW) triggers involving at least one neutron star during LIGO/Virgo's third observing run (O3). We searched binary neutron star (BNS) and neutron star black hole (NSBH) merger localizations with the Zwicky Transient Facility (ZTF) and undertook follow-up with the Global Relay of Observatories Watching Transients Happen (GROWTH) collaboration. The GW triggers had a median localization area of 4480 deg2, a median distance of 267 Mpc, and false-alarm rates ranging from 1.5 to 10-25 yr-1. The ZTF coverage in the g and r bands had a median enclosed probability of 39%, median depth of 20.8 mag, and median time lag between merger and the start of observations of 1.5 hr. The O3 follow-up by the GROWTH team comprised 340 UltraViolet/Optical/InfraRed (UVOIR) photometric points, 64 OIR spectra, and three radio images using 17 different telescopes. We find no promising kilonovae (radioactivity-powered counterparts), and we show how to convert the upper limits to constrain the underlying kilonova luminosity function. Initially, we assume that all GW triggers are bona fide astrophysical events regardless of false-alarm rate and that kilonovae accompanying BNS and NSBH mergers are drawn from a common population; later, we relax these assumptions. Assuming that all kilonovae are at least as luminous as the discovery magnitude of GW170817 (-16.1 mag), we calculate that our joint probability of detecting zero kilonovae is only 4.2%. If we assume that all kilonovae are brighter than-16.6 mag (the extrapolated peak magnitude of GW170817) and fade at a rate of 1 mag day-1 (similar to GW170817), the joint probability of zero detections is 7%. If we separate the NSBH and BNS populations based on the online classifications, the joint probability of zero detections, assuming all kilonovae are brighter than-16.6 mag, is 9.7% for NSBH and 7.9% for BNS mergers. Moreover, no more than <57% (<89%) of putative kilonovae could be brighter than-16.6 mag assuming flat evolution (fading by 1 mag day-1) at the 90% confidence level. If we further take into account the online terrestrial probability for each GW trigger, we find that no more than <68% of putative kilonovae could be brighter than-16.6 mag. Comparing to model grids, we find that some kilonovae must have M ej < 0.03 M o˙, X lan > 10-4, or φ > 30° to be consistent with our limits. We look forward to searches in the fourth GW observing run; even 17 neutron star mergers with only 50% coverage to a depth of-16 mag would constrain the maximum fraction of bright kilonovae to <25%.