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Wang, Lihua

Publications and source records attributed to Wang, Lihua.

14 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Plasma proteomics of SARS-CoV-2 infection and severity reveals impact on Alzheimer’s and coronary disease pathways

Identification of proteins dysregulated by COVID-19 infection is critically important for better understanding of its pathophysiology, building prognostic models, and identifying new targets. Plasma proteomic profiling of 4,301 proteins was performed in two independent datasets and tested for the association for three COVID-19 outcomes (infection, ventilation, and death). We identified 1,449 proteins consistently associated in both datasets with any of these three outcomes. We subsequently created highly accurate models that distinctively predict infection, ventilation, and death. These proteins were enriched in specific biological processes including cytokine signaling, Alzheimer’s disease, and coronary artery disease. Mendelian randomization and gene network analyses identified eight causal proteins and 141 highly connected hub proteins including 35 with known drug targets. Our findings provide distinctive prognostic biomarkers for two severe COVID-19 outcomes, reveal their relationship to Alzheimer’s disease and coronary artery disease, and identify potential therapeutic targets for COVID-19 outcomes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Programming PAM antennae for efficient CRISPR-Cas9 DNA editing

Bacterial CRISPR-Cas9 nucleases have been repurposed as powerful genome editing tools. Whereas engineering guide RNAs or Cas nucleases have proven to improve the efficiency of CRISPR editing, modulation of protospacer-adjacent motif (PAM), indispensable for CRISPR, has been less explored. Here, we develop a DNA origami–based platform to program a PAM antenna microenvironment and address its performance at the single-molecule level with submolecular resolution. To mimic spatially controlled in vivo PAM distribution as may occur in chromatin, we investigate the effect of PAM antennae surrounding target DNA. We find that PAM antennae effectively sensitize the DNA cleavage by recruiting Cas9 molecules. Super-resolution tracking of single single-guide RNA/Cas9s reveals localized translocation of Cas9 among spatially proximal PAMs. We find that the introduction of the PAM antennae effectively modulates the microenvironment for enhanced target cleavage (up to ~50%). These results provide insight into factors that promote more efficient genome editing.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2019

VISAGE - A Visualization and Exploration Framework for Environmental Data

Diverse airborne and ground-based environmental observations are important technologies for disaster assessment and response, as well as for the validation of environmental satellite observations and atmospheric models which can improve forecasts. The VISAGE (Visualization for Integrated Satellite, Airborne and Ground-based data Exploration) project is working to provide three-dimensional visualization and basic analytics capabilities for such datasets in an interactive user interface. The use of cloud-native, server less technologies for analysis optimized data storage will position VISAGE for integration with other technologies into a Data Analytic Center Framework.

Conover, Helen↗
DOE OSTI2018

Plant‐made E2 glycoprotein single‐dose vaccine protects pigs against classical swine fever

Abstract Classical Swine Fever Virus ( CSFV ) causes classical swine fever, a highly contagious hemorrhagic fever affecting both feral and domesticated pigs. Outbreaks of CSF in Europe, Asia, Africa and South America had significant adverse impacts on animal health, food security and the pig industry. The disease is generally contained by prevention of exposure through import restrictions ( e.g . banning import of live pigs and pork products), localized vaccination programmes and culling of infected or at‐risk animals, often at very high cost. Current CSFV ‐modified live virus vaccines are protective, but do not allow differentiation of infected from vaccinated animals ( DIVA ), a critical aspect of disease surveillance programmes. Alternatively, first‐generation subunit vaccines using the viral protein E2 allow for use of DIVA diagnostic tests, but are slow to induce a protective response, provide limited prevention of vertical transmission and may fail to block viral shedding. CSFV E2 subunit vaccines from a baculovirus/insect cell system have been developed for several vaccination campaigns in Europe and Asia. However, this expression system is considered expensive for a veterinary vaccine and is not ideal for wide‐spread deployment. To address the issues of scalability, cost of production and immunogenicity, we have employed an Agrobacterium ‐mediated transient expression platform in Nicotiana benthamiana and formulated the purified antigen in novel oil‐in‐water emulsion adjuvants. We report the manufacturing of adjuvanted, plant‐made CSFV E2 subunit vaccine. The vaccine provided complete protection in challenged pigs, even after single‐dose vaccination, which was accompanied by strong virus neutralization antibody responses.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Hyperoxia-mediated transcriptional activation of cytochrome P4501A1 (CYP1A1) and decreased susceptibility to oxygen-mediated lung injury in newborn mice

Highlights: • Hyperoxia causes enhanced transcriptional activation of human CYP1A1-Luciferase expression in newborn mice in vivo. • Transgenic mice carrying the human CYP1A1-luc promoter are less susceptible to hyperoxic lung in injury and in vivo. • CYP1A1-Luc mice display increased levels of endogenous hepatic and pulmonary CYP1A as well as NADP(H) quinone oxidoreductase (NQO1) expression after hyperoxia exposure, compared to wild type mice. • The increased endogenous expression of CYP1A1 and NQO1 contributes to the beneficial effects seens in CYP1A1-Luc mice. Hyperoxia contributes to the development of bronchopulmonary dysplasia (BPD) in premature infants. In this study, we tested the hypothesis that newborn transgenic mice carrying the human CYP1A1-Luc promoter will display transcriptional activation of the human CYP1A1 promoter in vivo upon exposure to hyperoxia, and that these mice will be less susceptible to hyperoxic lung injury and alveolar simplification than similarly exposed wild type (WT) mice. Newborn WT (CD-1) or transgenic mice carrying a 13.2 kb human CYP1A1 promoter and the luciferase (Luc) reporter gene (CYP1A1-luc) were maintained in room air or exposed to hyperoxia (85% O{sub 2}) for 7–14 days. Hyperoxia exposure of CYP1A1-Luc mice for 7 and 14 days resulted in 4- and 30-fold increases, respectively, in hepatic Luc (CYP1A1) expression, compared to room air controls. In lung, hyperoxia caused a 2-fold induction of reporter Luc at 7 days, but the induction declined after 14 days. The newborn CYP1A1-Luc mice were less susceptible to lung injury and alveolar simplification than similarly exposed wild type (WT) CD-1 mice. Also, the CYP1A1-Luc mice showed increased levels of hepatic and pulmonary CYP1A1 expression and hepatic CYP1A2 activity after hyperoxia exposure. Hyperoxia also increased NADP(H) quinone reductase (NQO1) pulmonary gene expression in both CD-1 and CYP1A1-Luc mice at both time points, but this was more pronounced in the latter at 14 days. Our results support the hypothesis that hyperoxia activates the human CYP1A1 promoter in newborn mice, and that increased endogenous expression of CYP1A1 and NADP(H) quinone reductase (NQO1) contributes to the decreased susceptibilities to hyperoxic lung injury in the transgenic animals. This is the first report providing evidence of hyperoxia-mediated transcriptional activation of the human CYP1A1 promoter in newborn mice, and this in conjunction with decreased lung injury, suggests that these phenomena have important implications for BPD.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

New twinning route in face-centered cubic nanocrystalline metals

Twin nucleation in a face-centered cubic crystal is believed to be accomplished through the formation of twinning partial dislocations on consecutive atomic planes. Twinning should thus be highly unfavorable in face-centered cubic metals with high twin-fault energy barriers, such as Al, Ni, and Pt, but instead is often observed. Here, we report an in situ atomic-scale observation of twin nucleation in nanocrystalline Pt. Unlike the classical twinning route, deformation twinning initiated through the formation of two stacking faults separated by a single atomic layer, and proceeded with the emission of a partial dislocation in between these two stacking faults. Through this route, a three-layer twin was nucleated without a mandatory layer-by-layer twinning process. Furthermore, this route is facilitated by grain boundaries, abundant in nanocrystalline metals, that promote the nucleation of separated but closely spaced partial dislocations, thus enabling an effective bypassing of the high twin-fault energy barrier.

36 MATERIALS SCIENCE↗
NASA NTRS2017

Quantifying TOLNet Ozone Lidar Accuracy During the 2014 DISCOVER-AQ and FRAPPE Campaigns

The Tropospheric Ozone Lidar Network (TOLNet) is a unique network of lidar systems that measure high-resolution atmospheric profiles of ozone. The accurate characterization of these lidars is necessary to determine the uniformity of the network calibration. From July to August 2014, three lidars, the TROPospheric OZone (TROPOZ) lidar, the Tunable Optical Profiler for Aerosol and oZone (TOPAZ) lidar, and the Langley Mobile Ozone Lidar (LMOL), of TOLNet participated in the Deriving Information on Surface conditions from Column and Vertically Resolved Observations Relevant to Air Quality (DISCOVER-AQ) mission and the Front Range Air Pollution and Photochemistry Experiment (FRAPPA) to measure ozone variations from the boundary layer to the top of the troposphere. This study presents the analysis of the intercomparison between the TROPOZ, TOPAZ, and LMOL lidars, along with comparisons between the lidars and other in situ ozone instruments including ozonesondes and a P-3B airborne chemiluminescence sensor. The TOLNet lidars measured vertical ozone structures with an accuracy generally better than +/-15 % within the troposphere. Larger differences occur at some individual altitudes in both the near-field and far-field range of the lidar systems, largely as expected. In terms of column average, the TOLNet lidars measured ozone with an accuracy better than +/-5 % for both the intercomparison between the lidars and between the lidars and other instruments. These results indicate that these three TOLNet lidars are suitable for use in air quality, satellite validation, and ozone modeling efforts.

TOLNet↗
NASA NTRS2016

Understanding the Laminar Distribution of Tropospheric Ozone from Ground-Based, Airborne, Spaceborne, and Modeling Perspectives

Laminar ozone structure is a ubiquitous feature of tropospheric-ozone distributions resulting from dynamic and chemical atmospheric processes. Understanding the characteristics of these ozone laminae and the mechanisms responsible for producing them is important to outline the transport pathways of trace gases and to quantify the impact of different sources on tropospheric background ozone. In this study, we present a new method to detect ozone laminae to understand their climatological characteristics of occurrence frequency in terms of thickness and altitude. We employ both ground-based and airborne ozone lidar measurements and other synergistic observations and modeling to investigate the sources and mechanisms such as biomass burning transport, stratospheric intrusion, lightning-generated NOx, and nocturnal low-level jets that are responsible for depleted or enhanced tropospheric ozone layers. Spaceborne (e.g., OMI (Ozone Monitoring Instrument), TROPOMI (Tropospheric Monitoring Instrument), TEMPO (Tropospheric Emissions: Monitoring of Pollution)) measurements of these laminae will observe greater horizontal extent and lower vertical resolution than balloon-borne or lidar measurements will quantify. Using integrated ground-based, airborne, and spaceborne observations in a modeling framework affords insight into how to gain knowledge of both the vertical and horizontal evolution of these ubiquitous ozone laminae.

Tropospheric Ozone↗
NASA NTRS2015

Ozone Lidar Observations for Air Quality Studies

Tropospheric ozone lidars are well suited to measuring the high spatio-temporal variability of this important trace gas. Furthermore, lidar measurements in conjunction with balloon soundings, aircraft, and satellite observations provide substantial information about a variety of atmospheric chemical and physical processes. Examples of processes elucidated by ozone-lidar measurements are presented, and modeling studies using WRF-Chem, RAQMS, and DALES/LES models illustrate our current understanding and shortcomings of these processes.

Ozone↗
NASA NTRS2013

Stratosphere-to-Troposphere Transport Revealed by Ground-based Lidar and Ozonesonde at a Midlatitude Site

This paper presents ozone structures measured by a ground-based ozone lidar and ozonesonde at Huntsville, Alabama, on 27-29 April 2010 originating from a stratosphere-to-troposphere transport event associated with a cutoff cyclone and tropopause fold. In this case, the tropopause reached 6 km and the stratospheric intrusion resulted in a 2-km thick elevated ozone layer with values between 70 and 85 ppbv descending from the 306-K to 298-K isentropic surface at a rate of 5 km day1. The potential temperature was provided by a collocated microwave profiling radiometer. We examine the corresponding meteorological fields and potential vorticity (PV) structures derived from the analysis data from the North American Mesoscale model. The 2-PVU (PV unit) surface, defined as the dynamic tropopause, is able to capture the variations of the ozone tropopause estimated from the ozonesonde and lidar measurements. The estimated ozone/PV ratio, from the measured ozone and model derived PV, for the mixing layer between the troposphere and stratosphere is approximately 41 ppbv/PVU with an uncertainty of approximately 33%. Within two days, the estimated mass of ozone irreversibly transported from the stratospheric into the troposphere is between 0.07 Tg (0.9 10(exp33) molecules) and 0.11 Tg (1.3 10(exp33) molecules) with an estimated uncertainty of 59%. Tropospheric ozone exhibited enormous variability due to the complicated mixing processes. Low ozone and large variability were observed in the mid-troposphere after the stratospheric intrusion due to the westerly advection including the transition from a cyclonic system to an anticyclonic system. This study using high temporal and vertical-resolution measurements suggests that, in this case, stratospheric air quickly lost its stratospheric characteristics once it is irreversibly mixed down into the troposphere.

Kuang, Shi↗
NASA NTRS2011

The NASA Lightning Nitrogen Oxides Model (LNOM): Recent Updates and Applications

Improvements to the NASA Marshall Space Flight Center Lightning Nitrogen Oxides Model (LNOM) and its application to the Community Multiscale Air Quality (CMAQ) modeling system are presented. The LNOM analyzes Lightning Mapping Array (LMA) and National Lightning Detection Network(tm) (NLDN) data to estimate the raw (i.e., unmixed and otherwise environmentally unmodified) vertical profile of lightning NOx (= NO + NO2). Lightning channel length distributions and lightning 10-m segment altitude distributions are also provided. In addition to NOx production from lightning return strokes, the LNOM now includes non-return stroke lightning NOx production due to: hot core stepped and dart leaders, stepped leader corona sheath, K-changes, continuing currents, and M-components. The impact of including LNOM-estimates of lightning NOx for an August 2006 run of CMAQ is discussed.

Koshak, William↗
NASA NTRS2011

The NASA Lightning Nitrogen Oxides Model (LNOM): Application to Air Quality Modeling

Recent improvements to the NASA Marshall Space Flight Center Lightning Nitrogen Oxides Model (LNOM) and its application to the Community Multiscale Air Quality (CMAQ) modeling system are discussed. The LNOM analyzes Lightning Mapping Array (LMA) and National Lightning Detection Network(TradeMark)(NLDN) data to estimate the raw (i.e., unmixed and otherwise environmentally unmodified) vertical profile of lightning NO(x) (= NO + NO2). The latest LNOM estimates of lightning channel length distributions, lightning 1-m segment altitude distributions, and the vertical profile of lightning NO(x) are presented. The primary improvement to the LNOM is the inclusion of non-return stroke lightning NOx production due to: (1) hot core stepped and dart leaders, (2) stepped leader corona sheath, K-changes, continuing currents, and M-components. The impact of including LNOM-estimates of lightning NO(x) for an August 2006 run of CMAQ is discussed.

Koshak, William↗