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At least 37 records · Page 2

3C-like protease inhibitors block coronavirus replication in vitro and improve survival in MERS-CoV–infected mice

Pathogenic coronaviruses are a major threat to global public health, as exemplified by severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and the newly emerged SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19). We describe herein the structure-guided optimization of a series of inhibitors of the coronavirus 3C-like protease (3CLpro), an enzyme essential for viral replication. The optimized compounds were effective against several human coronaviruses including MERS-CoV, SARS-CoV, and SARS-CoV-2 in an enzyme assay and in cell-based assays using Huh-7 and Vero E6 cell lines. Two selected compounds showed antiviral effects against SARS-CoV-2 in cultured primary human airway epithelial cells. In a mouse model of MERS-CoV infection, administration of a lead compound 1 day after virus infection increased survival from 0 to 100% and reduced lung viral titers and lung histopathology. These results suggest that this series of compounds has the potential to be developed further as antiviral drugs against human coronaviruses.

60 APPLIED LIFE SCIENCES↗

Seismic Monitoring at the Farnsworth CO2-EOR Field Using Time-Lapse Elastic-Waveform Inversion of 3D-3C VSP Data

During the Development Phase of the U.S. Southwest Regional Partnership on Carbon Sequestration, supercritical CO2 was continuously injected into the deep oil-bearing Morrow B formation of the Farnsworth Unit in Texas for Enhanced Oil Recovery (EOR). The project injected approximately 94 kilotons of CO2 to study geologic carbon storage during CO2-EOR. A three-dimensional (3D) surface seismic dataset was acquired in 2013 to characterize the subsurface structures of the Farnsworth site. Following this data acquisition, the baseline and three time-lapse three-dimensional three-component (3D-3C) vertical seismic profiling (VSP) data were acquired at a narrower surface area surrounding the CO2 injection and oil/gas production wells between 2014 and 2017 for monitoring CO2 injection and migration. With these VSP datasets, we inverted for subsurface velocity models to quantitatively monitor the CO2 plume within the Morrow B formation. We first built 1D initial P-wave (Vp) and S-wave (Vs) velocity models by upscaling the sonic logs. We improved the deep region of the Vp and Vs models by incorporating the deep part of a migration velocity model derived from the 3D surface seismic data. We improved the shallow region of 3D Vp and Vs models using 3D traveltime tomography of first arrivals of VSP downgoing waves. We further improved the 3D baseline velocity models using elastic-waveform inversion (EWI) of the 3D baseline VSP upgoing data. Our advanced EWI method employs alternative tomographic and conventional gradients and total-variation-based regularization to ensure the high-fidelity updates of the 3D baseline Vp and Vs models. We then sequentially applied our 3D EWI method to the three time-lapse datasets to invert for spatiotemporal changes of Vp and Vs in the reservoir. Our inversion results reveal the volumetric changes of the time-lapse Vp and Vs models and show the evolution of the CO2 plume from the CO2 injection well to the oil/gas production wells.

42 ENGINEERING↗

The Energetics of the Central Engine in the Powerful Quasar 3C 298

The compact steep-spectrum radio source 3C 298 (redshift of 1.44) has the largest 178 MHz luminosity in the Third Cambridge Revised Catalogue (3CR); its radio lobes are among the most luminous in the universe. The plasma state of the radio lobes is modeled with the aid of interferometric radio observations (in particular, the new Low Frequency Array observation and archival MERLIN data) and archival single-station data. It is estimated that the long-term time-averaged jet power required to fill these lobes with leptonic plasma is $\overline{Q}\,\approx 1.28\pm 0.51\times {10}^{47}\,\mathrm{erg}\,{{\rm{s}}}^{-1}$, rivaling the largest time-averaged jet powers from any quasar. Supporting this notion of extraordinary jet power is a 0.5–10 keV luminosity of ≈ 5.2 × 10 46 erg s –1 , comparable to luminous blazars, yet there is no other indication of strong relativistic beaming. We combine two new high signal-to-noise ratio optical spectroscopic observations from the Hobby-Eberly Telescope with archival Hubble Space Telescope, Two Micron All Sky Survey, and Galaxy Evolutionary Explorer data to compute a bolometric luminosity from the accretion flow of L bol ≈ 1.55 ± 0.15 × 10 47 erg s –1 . The ratio, $\overline{Q}/{L}_{\mathrm{bol}}\approx 1$, is the approximate upper limit for quasars. Characteristic of a large $\overline{Q}/{L}_{\mathrm{bol}}$, we find an extreme-ultraviolet (EUV) spectrum that is very steep (the "EUV deficit" of powerful radio quasars relative to radio-quiet quasars), and this weak ionizing continuum is likely a contributing factor to the relatively small equivalent widths of the broad emission lines in this quasar.

79 ASTRONOMY AND ASTROPHYSICS↗

Overview of the 2021 SDP 3C Citation Context Classification Shared Task

This paper provides an overview of the 2021 3C Citation Context Classification shared task. The second edition of the shared task was organised as part of the 2nd Workshop on Scholarly Document Processing (SDP 2021). The task is composed of two subtasks: classifying citations based on their (Subtask A) purpose and (Subtask B) influence. As in the previous year, both tasks were hosted on Kaggle and used a portion of the new ACT dataset. A total of 22 teams participated in Subtask A, and 19 teams competed in Subtask B. All the participated systems were ranked based on their achieved macro f-score. The highest scores of 0.26973 and 0.60025 were reported for sub-task A and B, respectively.

Kunnath, Suchetha N.↗

Effects of point defects on oxidation of 3C–SiC

The influence of implantation-induced point defects (PDs) on SiC oxidation is investigated via molecular dynamics simulations. PDs generally increase the oxidation rate of crystalline grains. Particularly, accelerations caused by Si antisites and vacancies are comparable, and followed by Si interstitials, which are higher than those by C antisites and C interstitials. However, in the grain boundary (GB) region, defect contribution to oxidation is more complex, with C antisites decelerating oxidation. Here, the underlying reason is the formation of a C-rich region along the oxygen diffusion pathway that blocks the access of O to Si and thus reduces the oxidation rate, as compared to the oxidation along a GB without defects.

36 MATERIALS SCIENCE↗

Electronic stopping in molecular dynamics simulations of cascades in 3C–SiC

Here, we investigate the effect of the electronic stopping power on defect production due to ion irradiation of cubic silicon carbide using molecular dynamics simulations. We simulate 20 keV and 30 keV Si and C ions, with and without the electronic energy loss. The results show that the electronic stopping effects are more profound in the case of C irradiation, where the ratio of the electronic energy loss S e to the nuclear energy loss S n is much larger compared to the ratio for Si ions. These findings indicate that this ratio plays a role in the effect of the electronic stopping on ion irradiation.

36 MATERIALS SCIENCE↗

Photoelectrochemically Self Improving Si/GaN Photocathode: Figure 3c Raw Data

XPS after 0hr of chronoampometry. Surface chemical composition and valence band structure of GaN were obtained by X-ray photoemission spectroscopy (XPS) on a Kratos Axis Ultra DLD system at a takeoff angle of 0° relative to the surface normal. An Al Kα source (hν = 1486.6 eV) was used to excite the core level electrons. Pass energy of 20 eV was used for the narrow scan of core levels and valence band spectra, and step size of 0.05 eV and 0.025 eV, respectively. The Spectral fitting was conducted using CasaXPS analysis software. The binding energy scales of all core levels were corrected to the N 1s of Ga – N bond at 397.8 eV. XPS O1s core level spectra from as-received Si/GaN sample, and deconvolution shows O - Ga bond and OH - H2O bond.

photocathode↗

Evaluation of DNA Vaccine Candidates against Foot-and-Mouth Disease Virus in Cattle

We evaluated four DNA vaccine candidates for their ability to produce virus-like particles (VLPs) and elicit a protective immune response against Foot-and-mouth disease virus (FMDV) in cattle. Two traditional DNA plasmids and two DNA minicircle constructs were evaluated. Both the pTarget O1P1-3C plasmid and O1P1-3C minicircle encoded a wild-type FMDV 3C protease to process the P1-2A polypeptide, whereas the O1P1-HIV-3CT minicircle used an HIV-1 ribosomal frameshift to down-regulate expression of a mutant 3C protease. A modified pTarget plasmid with a reduced backbone size, mpTarget O1P1-3C LT , used a 3C protease containing two mutations reported to enhance expression. All constructs produced mature FMDV P1 cleavage products in transfected cells, as seen by western blot analysis. Three constructs, O1P1-3C minicircles, pTarget O1P1-3C, and mpTarget O1P1-3C LT plasmids, produced intracellular VLP crystalline arrays detected by electron microscopy. Despite VLP formation in vitro, none of the DNA vaccine candidates elicited protection from clinical disease when administered independently. Administration of pTarget O1P1-3C plasmid enhanced neutralizing antibody titers when used as a priming dose prior to administration of a conditionally licensed adenovirus-vectored FMD vaccine. Further work is needed to develop these DNA plasmid-based constructs into standalone FMD vaccines in cattle.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

High thermal conductivity in wafer-scale cubic silicon carbide crystals

High thermal conductivity electronic materials are critical components for high-performance electronic and photonic devices as both active functional materials and thermal management materials. We report an isotropic high thermal conductivity exceeding 500 W m –1 K –1 at room temperature in high-quality wafer-scale cubic silicon carbide (3C-SiC) crystals, which is the second highest among large crystals (only surpassed by diamond). Furthermore, the corresponding 3C-SiC thin films are found to have record-high in-plane and cross-plane thermal conductivity, even higher than diamond thin films with equivalent thicknesses. Our results resolve a long-standing puzzle that the literature values of thermal conductivity for 3C-SiC are lower than the structurally more complex 6H-SiC. We show that the observed high thermal conductivity in this work arises from the high purity and high crystal quality of 3C-SiC crystals which avoids the exceptionally strong defect-phonon scatterings. Moreover, 3C-SiC is a SiC polytype which can be epitaxially grown on Si. We show that the measured 3C-SiC-Si thermal boundary conductance is among the highest for semiconductor interfaces. These findings provide insights for fundamental phonon transport mechanisms, and suggest that 3C-SiC is an excellent wide-bandgap semiconductor for applications of next-generation power electronics as both active components and substrates.

42 ENGINEERING↗