Discovery of a Druggable, Cryptic Pocket in SARS-CoV-2 nsp16 Using Allosteric Inhibitors
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Publications and source records attributed to Brown, Peter J..
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We present constraints on cosmological parameters from the Pantheon+ analysis of 1701 light curves of 1550 distinct Type Ia supernovae (SNe Ia) ranging in redshift from z = 0.001 to 2.26. This work features an increased sample size from the addition of multiple cross-calibrated photometric systems of SNe covering an increased redshift span, and improved treatments of systematic uncertainties in comparison to the original Pantheon analysis, which together result in a factor of 2 improvement in cosmological constraining power. For a flat ΛCDM model, we find Ω M = 0.334 ± 0.018 from SNe Ia alone. For a flat w 0 CDM model, we measure w 0 = –0.90 ± 0.14 from SNe Ia alone, H 0 = 73.5 ± 1.1 km s –1 Mpc –1 when including the Cepheid host distances and covariance (SH0ES), and w 0 = $-{0.978}_{-0.031}^{+0.024}$ when combining the SN likelihood with Planck constraints from the cosmic microwave background (CMB) and baryon acoustic oscillations (BAO); both w 0 values are consistent with a cosmological constant. We also present the most precise measurements to date on the evolution of dark energy in a flat w 0 w a CDM universe, and measure w a = $-{0.1}_{-2.0}^{+0.9}$ from Pantheon+ SNe Ia alone, H 0 = 73.3 ± 1.1 km s –1 Mpc –1 when including SH0ES Cepheid distances, and w a = $-{0.65}_{-0.32}^{+0.28}$ when combining Pantheon+ SNe Ia with CMB and BAO data. Finally, we find that systematic uncertainties in the use of SNe Ia along the distance ladder comprise less than one-third of the total uncertainty in the measurement of H 0 and cannot explain the present "Hubble tension" between local measurements and early universe predictions from the cosmological model.
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There are currently many large-field surveys that are operational and are being planned including the powerful Vera C. Rubin Observatory Legacy Survey of Space and Time. These surveys will increase the number and diversity of transients dramatically. However, for some transients, like supernovae (SNe), we can gain more understanding by directed observations (e.g., shock breakout and γ-ray detections) than by simply increasing the sample size. For example, the initial emission from these transients can be a powerful probe of these explosions. Upcoming ground-based detectors are not ideally suited to observing the initial emission (shock emergence) of these transients. These observations require a large field-of-view X-ray mission with a UV follow-up within the first hour of shock breakout. The emission in the first 1 hr to even 1 day provides strong constraints on the stellar radius and asymmetries in the outer layers of stars, the properties of the circumstellar medium (e.g., inhomogeneities in the wind for core-collapse SNe and accreting companions in thermonuclear SNe), and the transition region between these two areas. This paper describes a simulation for the number of SNe that could be seen by a large field-of-view lobster-eye X-ray and UV observatory.
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Protein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 results in drastically reduced levels of arginine monomethylated HSP70 family stress-associated proteins. Structural and biochemical analyses reveal that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibits methylation of both constitutive and inducible forms of HSP70, and leads to decreased tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors. These results demonstrate a role for PRMT7 and arginine methylation in stress response.
We present and discuss ultraviolet and optical photometry from the Ultraviolet/Optical Telescope, X-ray limits from the X-Ray Telescope on Swift, and imaging polarimetry and ultraviolet/optical spectroscopy with the Hubble Space Telescope, all from observations of ASASSN-15lh. It has been classified as a hydrogen-poor superluminous supernova (SLSN I), making it more luminous than any other supernova observed. ASASSN-15lh is not detected in the X-rays in individual or co-added observations. From the polarimetry we determine that the explosion was only mildly asymmetric. We find the flux of ASASSN-15lh to increase strongly into the ultraviolet, with an ultraviolet luminosity 100 times greater than the hydrogen-rich, ultraviolet-bright SLSN II SN2008es. We find that objects as bright as ASASSN-15lh are easily detectable beyond redshifts of ∼4 with the single-visit depths planned for the Large Synoptic Survey Telescope. Deep near-infrared surveys could detect such objects past a redshift of ∼20, enabling a probe of the earliest star formation. A late rebrightening-most prominent at shorter wavelengths -is seen about two months after the peak brightness, which is itself as bright as an SLSN. The ultraviolet spectra during the rebrightening are dominated by the continuum without the broad absorption or emission lines seen in SLSNe or tidal disruption events (TDEs) and the early optical spectra of ASASSN-15lh. Our spectra show no strong hydrogen emission, showing only Lyα absorption near the redshift previously found by optical absorption lines of the presumed host. The properties of ASASSN-15lh are extreme when compared to either SLSNe or TDEs.
We present an observational study of the Type IIn supernovae (SNe IIn) 2005ip and 2006jd. Broad-band UV, optical and near-IR photometry, and visual-wavelength spectroscopy of SN 2005ip complement and extend upon published observations to 6.5 years past discovery. Our observations of SN 2006jd extend from UV to mid-infrared wavelengths, and like SN 2005ip, are compared to reported X-ray measurements to understand the nature of the progenitor. Both objects display a number of similarities with the 1988Z-like subclass of SN IIn including: (i) remarkably similar early- and late-phase optical spectra, (ii) a variety of high ionization coronal lines, (iii) long-duration optical and near-IR emission and, (iv) evidence of cold and warm dust components. However, diversity is apparent including an unprecedented late-time r-band excess in SN 2006jd. The observed di erences are attributed to di erences between the mass-loss history of the progenitor stars. We conclude that the progenitor of SN 2006jd likely experienced a signi cant mass-loss event during its pre-SN evolution akin to the great 19th century eruption of eta Carinae. Contrarily, as advocated by Smith et al. (2009), we nd the circumstellar environment of SN 2005ip to be more consistent with a clumpy wind progenitor.
We present the earliest ultraviolet (UV) observations of the bright Type Ia supernova SN 2011fe/PTF11kly in the nearby galaxy M101 at a distance of only 6.4 Mpc. It was discovered shortly after explosion by the Palomar Transient Factory and first observed by Swift/UVOT about a day after explosion. The early UV light is well-defined, with approx. 20 data points per filter in the 5 days after explosion. With these early UV observations, we extend the near-UV template of SNe Ia to earlier times for comparison with observations at low and high redshift and report fits from semiempirical models of the explosion. We find the early UV count rates to be well fit by the superposition of two parabolic curves. Finally, we use the early UV flux measurements to examine a possible shock interaction with a non-degenerate companion. We find that even a solar mass companion at a distance of a few solar radii is unlikely at more than 95% confidence.