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Wang, Jun

Publications and source records attributed to Wang, Jun.

At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Development of the Safe and Broad‐Spectrum Aldehyde and Ketoamide Mpro inhibitors Derived from the Constrained α, γ‐AA Peptide Scaffold

Abstract SARS‐CoV‐2 is still wreaking havoc all over the world with surging morbidity and high mortality. The main protease (M pro ) is essential in the replication of SARS‐CoV‐2, enabling itself an active target for antiviral development. Herein, we reported the design and synthesis of a new class of peptidomimetics‐constrained α, γ‐AA peptides, based on which a series of aldehyde and ketoamide inhibitors of the M pro of SARS‐CoV‐2 were prepared. The lead compounds showed excellent inhibitory activity in the FRET‐based M pro enzymatic assay not only for the M pro of SARS‐CoV‐2 but also for SARS‐CoV and MERS‐CoV, along with HCoVs like HCoV‐OC43, HCoV‐229E, HCoV‐NL63 and HKU1. The X‐ray crystallographic results demonstrated that our compounds form a covalent bond with the catalytic Cys145. They also demonstrated effective antiviral activity against live SARS‐CoV‐2. Overall, the results suggest that α, γ‐AA peptide could be a promising molecular scaffold in designing novel M pro inhibitors of SARS‐CoV‐2 and other coronaviruses.

Chemistry↗
DOE OSTI2023

Divergent accumulation of amino sugars and lignins mediated by soil functional carbon pools under tropical forest conversion

Tropical primary forests are being destroyed at an alarming rate and converted for other land uses which is expected to greatly influence soil carbon (C) cycling. However, our understanding of how tropical forest conversions affect the accumulation of compounds in soil functional C pools remains unclear. Here, we collected soils from primary forests (PF), secondary forests (SF), oil-palm (OP), and rubber plantations (RP), and assessed the accumulation of plant- and microbial-derived compounds within soil organic carbon (SOC), particulate (POC) and mineral-associated (MAOC) organic C. PF conversion to RP greatly decreased SOC, POC, and MAOC concentrations, whereas conversion to SF increased POC concentrations and decreased MAOC concentrations, and conversion to OP only increased POC concentrations. PF conversion to RP decreased lignin concentrations and increased amino sugar concentrations in SOC pools which increased the stability of SOC, whereas conversion to SF only increased the lignin concentrations in POC, and conversion to OP just increased lignin concentrations in POC and decreased it in MAOC. We observed divergent dynamics of amino sugars (decrease) and lignin (increase) in SOC with increasing SOC. Only lignin concentrations increased in POC with increasing POC and amino sugars concentrations decreased in MAOC with increasing MAOC. Conversion to RP significantly decreased soil enzyme activities and microbial biomasses. Lignin accumulation was associated with microbial properties, whereas amino sugar accumulation was mainly associated with soil nutrients and stoichiometries. These results suggest that the divergent accumulation of plant- and microbial-derived C in SOC was delivered by the distribution and original composition of functional C pools under forest conversions. Forest conversions changed the formation and stabilization processes of SOC in the long run which was associated with converted plantations and management. As a result, the important roles of soil nutrients and stoichiometry also provide a natural-based solution to enhance SOC sequestration via nutrient management in tropical forests.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

A Robust Estimate of Continental-Scale Terrestrial Carbon Sinks Using GOSAT XCO 2 Retrievals

Satellite XCO 2 retrievals could improve the estimates of surface carbon fluxes, but it remains unknown on what scales these estimates are robust. Here, we use the time-dependent Bayesian synthesis top-down method and prior net ecosystem exchanges (NEEs) from 12 terrestrial biosphere models (TBMs) to infer the monthly carbon fluxes of 51 land regions with constraints by GOSAT XCO 2 retrievals. We find that the uncertainty (standard deviation of 12 TBMs) reduction rates (uncertainty reduction rate (URR)) decrease significantly at decreasing spatial scales. On the continental-scale, the mean URR is about 57%, and the annual and seasonal cycle estimates of NEE are rather robust. The evaluation shows that the posterior CO 2 concentrations are significantly improved at the continental scale. Our study suggests that the GOSAT XCO 2 can only promise a robust continental-scale NEE estimate and improving the XCO 2 accuracy is an effective way to achieve robust estimates on smaller scales under current spatial coverage.

58 GEOSCIENCES↗
DOE OSTI2022

Detecting faults in wind turbines

A wind turbine generator fault detection method is described. The method includes obtaining a first signal from a generator of a wind turbine and a second signal from a vibration sensor coupled to the wind turbine, the first signal representing an output current of the generator, and the second signal being a time-sampled signal representing vibrations of a bearing in the wind turbine. Determining a shaft rotation frequency signal from the first signal, the shaft rotation frequency signal representing a time-varying rotational speed of a shaft of the wind turbine. Resampling an envelope of the second signal based on the shaft rotation frequency signal to provide a third signal, the third signal being an angular sampled signal. Detecting, by the at least one processor, a fault in the bearing of the wind turbine by identifying a characteristic signature of a bearing fault in the third signal.

Qiao, Wei↗
DOE OSTI2022

A unique class of Zn 2+ -binding serine-based PBPs underlies cephalosporin resistance and sporogenesis in Clostridioides difficile

Treatment with β-lactam antibiotics, particularly cephalosporins, is a major risk factor for Clostridioides difficile infection. These broad-spectrum antibiotics irreversibly inhibit penicillin-binding proteins (PBPs), which are serine-based enzymes that assemble the bacterial cell wall. However, C. difficile has four different PBPs (PBP1-3 and SpoVD) with various roles in growth and spore formation, and their specific links to β-lactam resistance in this pathogen are underexplored. Here, we show that PBP2 (known to be essential for vegetative growth) is the primary bactericidal target for β-lactams in C. difficile. PBP2 is insensitive to cephalosporin inhibition, and this appears to be the main basis for cephalosporin resistance in this organism. We determine crystal structures of C. difficile PBP2, alone and in complex with β-lactams, revealing unique features including ligand-induced conformational changes and an active site Zn 2+ -binding motif that influences β-lactam binding and protein stability. The Zn 2+ -binding motif is also present in C. difficile PBP3 and SpoVD (which are known to be essential for sporulation), as well as in other bacterial taxa including species living in extreme environments and the human gut. We speculate that this thiol-containing motif and its cognate Zn 2+ might function as a redox sensor to regulate cell wall synthesis for survival in adverse or anaerobic environments.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Chemical and structural evolutions of Li–Mn-rich layered electrodes at different current densities

Although the two active redox centers in Li-rich cathodes, including the anionic and cationic contributions, can enable Li-ion batteries to achieve outstanding specific energy, their behaviors at different current densities have not been clarified. In this report we provide a comparative study of transition metals (TMs) and oxygen redox activities by directly accessing their oxidation states in Li-rich materials operated at very different current rates. Our data reveal that the oxidation of oxygen in the near-surface region is at the same level for electrodes cycled with a wide range of current rates, indicating a reaction gradient of lattice oxygen redox reactions. The oxidation process of lattice oxygen is found to be dynamically compatible with that of the TMs. Combining the results of first principles calculations and complementary experimental findings, we propose a detailed mechanism of structural distortion from octahedral Li to tetrahedral Li and the role of oxygen vacancy in Li + diffusion. It is found that fast delithiation occurring at high current densities can easily cause local structural transformation, leading to a limited Li + diffusion rate and consequently suppressing rate capability.

25 ENERGY STORAGE↗
DOE OSTI2022

MELCOR Model Development of the General Atomics Fast Modular Reactor

General Atomics Electromagnetic Systems (GA-EMS) is currently developing a fast modular reactor (FMR) capable of providing safe, carbon-free electricity by 2035. As part of the development process, researchers at the University of Wisconsin-Madison (UWM) use MELCOR 2.2 to develop a simulation model of the proposed design to perform accident analyses. This paper summarizes the efforts of researchers at UWM in the creation of the FMR model. This model was built based on initial FMR design parameters. The design parameters will change as the design evolves and is refined.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗
DOE OSTI2022

$\mathrm{IH}$-$\mathrm{GAN}$: A conditional generative model for implicit surface-based inverse design of cellular structures

Variable-density cellular structures can overcome connectivity and manufacturability issues of topologically optimized structures, particularly those represented as discrete density maps. However, the optimization of such cellular structures is challenging due to the multiscale design problem. Past work addressing this problem generally either only optimizes the volume fraction of single-type unit cells but ignoring the effects of unit cell geometry on properties, or considers the geometry–property relation but builds this relation via heuristics. In contrast, we propose a simple yet more principled way to accurately model the property to geometry mapping using a conditional deep generative model, named Inverse Homogenization Generative Adversarial Network (IH-GAN). It learns the conditional distribution of unit cell geometries given properties and can realize the one-to-many mapping from properties to geometries. Here we further reduce the complexity of IH-GAN by using the implicit function parameterization to represent unit cell geometries. Results show that our method can 1) generate various unit cells that satisfy given material properties with high accuracy (R 2 -scores between target properties and properties of generated unit cells >98%) and 2) improve the optimized structural performance over the conventional variable-density single-type structure. In the minimum compliance example, our IH-GAN generated structure achieves a 79.7% reduction in concentrated stress and an extra 3.03% reduction in displacement. In the target deformation examples, our IH-GAN generated structure reduces the target matching error by 86.4% and 79.6% for two test cases, respectively. We also demonstrated that the connectivity issue for multi-type unit cells can be solved by transition layer blending.

42 ENGINEERING↗
DOE OSTI2022

“Water–in–Eutectogel” Electrolytes for Quasi–Solid–State Aqueous Lithium–Ion Batteries

The development of high safety lithium-ion batteries (LIBs) is greatly impeded by the flammability and leakage concerns of typical organic solvent-based electrolytes. As one of the alternative classes of electrolytes, hydrogel electrolytes exhibit high safety, high flexibility, low cost, and are benign to the environment. However, the narrow electrochemical stability window (ESW) of typical hydrogel electrolytes restricts the operating voltage of battery cells. Here, a new class of “water-in-eutectogel (WiETG)” electrolyte is reported, fabricated by combining a hydrogel with a “deep eutectic solvent” (LiTFSI in acetamide). The obtained WiETG electrolyte exhibits non-flammability, high ionic conductivity, and a wide ESW. LiMn 2 O 4 ||Li 4 Ti 5 O 12 cells with the WiETG electrolyte exhibit good cycling stability, high flexibility, and high safety. This newly developed WiETG electrolyte not only broadens the ESW of typical hydrogel electrolytes, but also opens a new perspective on future directions and guidance for the design of high safety electrolytes for flexible LIBs and beyond.

25 ENERGY STORAGE↗
DOE OSTI2022

Standard atomic weights of the elements 2021 (IUPAC Technical Report)

Following the reviews of atomic-weight determinations and other cognate data in 2015, 2017, 2019 and 2021, the IUPAC (International Union of Pure and Applied Chemistry) Commission on Isotopic Abundances and Atomic Weights (CIAAW) reports changes of standard atomic weights. The symbol A r°(E) was selected for standard atomic weight of an element to distinguish it from the atomic weight of an element E in a specific substance P, designated A r(E, P). The CIAAW has changed the values of the standard atomic weights of five elements based on recent determinations of terrestrial isotopic abundances. The standard atomic weight of argon and lead have changed to an interval to reflect that the natural variation in isotopic composition exceeds the measurement uncertainty of A r(Ar) and A r(Pb) in a specific substance. The standard atomic weights and/or the uncertainties of fourteen elements have been changed based on the Atomic Mass Evaluations 2016 and 2020 accomplished under the auspices of the International Union of Pure and Applied Physics (IUPAP). A r° of Ho, Tb, Tm and Y were changed in 2017 and again updated in 2021.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
DOE OSTI2022

Reaction Heterogeneity in LiFePO 4 Agglomerates and the Role of Intercalation-Induced Stress

As an important battery cathode material, reaction distribution in lithium iron phosphate (LiFePO4) has been extensively studied in dispersed particle systems, but remains poorly understood for mesoscopic agglomerates (or secondary particles) that are used in most commercial batteries. Herein, we apply three-dimensional X-ray spectroscopic imaging to characterize the two-phase structure in LiFePO4 secondary particles during electrochemical cycling. (De)lithiated domains are found to not form the commonly assumed core-shell structure but develop highly anisotropic filamentary morphology that is rate independent and symmetric between charging and discharging. Phase-field simulations elucidate that the observed 1D phase growth behavior is not caused by the 1D lithium diffusivity of LiFePO4 but the elastic interaction between primary particles, which gives rise to stronger reaction heterogeneity than dispersed nanoparticles. As a result, uniform lithium (de)intercalation does not occur on the secondary particle surface even at high cycling rates.

36 MATERIALS SCIENCE↗
DOE OSTI2022

The P132H mutation in the main protease of Omicron SARS-CoV-2 decreases thermal stability without compromising catalysis or small-molecule drug inhibition

The ongoing SARS-CoV-2 pandemic continues to be a significant threat to global health. First reported in November 2021, the Omicron variant (B.1.1.529) is more transmissible and can evade immunity better than previous SARS-CoV-2 variants, fueling an unprecedented surge in cases. To produce functional proteins from its polyprotein, SARS-CoV-2 relies on the cysteine proteases Nsp3/papain-like protease (PL pro ) and Nsp5/main protease (M pro )/3C-like protease to cleave at three and more than 11 sites, respectively. Therefore, M pro and PL pro inhibitors are considered to be one of the most promising SARS-CoV-2 antivirals. On December 22, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for PAXLOVID, a ritonavir-boosted formulation of nirmatrelvir. Nirmatrelvir is a first-in-class orally bioavailable SARS-CoV-2 M pro inhibitor. Thus, the scientific community must vigilantly monitor potential mechanisms of drug resistance, especially because SARS-CoV-2 is naïve to M pro inhibitors. Mutations have been well identified in variants to this point. Notably, Omicron M pro (OM pro ) harbors a single mutation—P132H. Here, we characterized the enzymatic activity, drug inhibition, and structure of OM pro while evaluating the past and future implications of M pro mutations.

59 BASIC BIOLOGICAL SCIENCES↗