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At least 379 records · Page 21

Towards Quantum-Chemical Level Calculations of SARS-CoV-2 Spike Protein Variants of Concern by First Principles Density Functional Theory

The spike protein (S-protein) is a crucial part of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with its many domains responsible for binding, fusion, and host cell entry. In this review we use the density functional theory (DFT) calculations to analyze the atomic-scale interactions and investigate the consequences of mutations in S-protein domains. We specifically describe the key amino acids and functions of each domain, which are essential for structural stability as well as recognition and fusion processes with the host cell; in addition, we speculate on how mutations affect these properties. Such unprecedented large-scale ab initio calculations, with up to 5000 atoms in the system, are based on the novel concept of amino acid–amino acid-bond pair unit (AABPU) that allows for an alternative description of proteins, providing valuable information on partial charge, interatomic bonding and hydrogen bond (HB) formation. In general, our results show that the S-protein mutations for different variants foster an increased positive partial charge, alter the interatomic interactions, and disrupt the HB networks. We conclude by outlining a roadmap for future computational research of biomolecular virus-related systems.

60 APPLIED LIFE SCIENCES↗

Understanding the Drivers of Mobility during the COVID-19 Pandemic in Florida, USA Using a Machine Learning Approach

As of March 2021, the State of Florida, U.S.A. had accounted for approximately 6.67% of total COVID-19 (SARS-CoV-2 coronavirus disease) cases in the U.S. The main objective of this research is to analyze mobility patterns during a three month period in summer 2020, when COVID-19 case numbers were very high for three Florida counties, Miami-Dade, Broward, and Palm Beach counties. To investigate patterns, as well as drivers, related to changes in mobility across the tri-county region, a random forest regression model was built using sociodemographic, travel, and built environment factors, as well as COVID-19 positive case data. Mobility patterns declined in each county when new COVID-19 infections began to rise, beginning in mid-June 2020. While the mean number of bar and restaurant visits was lower overall due to closures, analysis showed that these visits remained a top factor that impacted mobility for all three counties, even with a rise in cases. Our modeling results suggest that there were mobility pattern differences between counties with respect to factors relating, for example, to race and ethnicity (different population groups factored differently in each county), as well as social distancing or travel-related factors (e.g., staying at home behaviors) over the two time periods prior to and after the spike of COVID-19 cases.

60 APPLIED LIFE SCIENCES↗

Development of Masitinib Derivatives with Enhanced Mpro Ligand Efficiency and Reduced Cytotoxicity

Recently, a high-throughput screen of 1900 clinically used drugs identified masitinib, an orally bioavailable tyrosine kinase inhibitor, as a potential treatment for COVID-19. Masitinib acts as a broad-spectrum inhibitor for human coronaviruses, including SARS-CoV-2 and several of its variants. In this work, we rely on atomistic molecular dynamics simulations with advanced sampling methods to develop a deeper understanding of masitinib’s mechanism of M pro inhibition. To improve the inhibitory efficiency and to increase the ligand selectivity for the viral target, we determined the minimal portion of the molecule (fragment) that is responsible for most of the interactions that arise within the masitinib-Mpro complex. We found that masitinib forms highly stable and specific H-bond interactions with Mpro through its pyridine and aminothiazole rings. Importantly, the interaction with His 163 is a key anchoring point of the inhibitor, and its perturbation leads to ligand unbinding within nanoseconds. Based on these observations, a small library of rationally designed masitinib derivatives (M1–M5) was proposed. Our results show increased inhibitory efficiency and highly reduced cytotoxicity for the M3 and M4 derivatives compared to masitinib.

60 APPLIED LIFE SCIENCES↗

The Local Topological Free Energy of the SARS-CoV-2 Spike Protein

The novel coronavirus SARS-CoV-2 infects human cells using a mechanism that involves binding and structural rearrangement of its Spike protein. Understanding protein rearrangement and identifying specific amino acids where mutations affect protein rearrangement has attracted much attention for drug development. In this manuscript, we use a mathematical method to characterize the local topology/geometry of the SARS-CoV-2 Spike protein backbone. Our results show that local conformational changes in the FP, HR1, and CH domains are associated with global conformational changes in the RBD domain. The SARS-CoV-2 variants analyzed in this manuscript (alpha, beta, gamma, delta Mink, G614, N501) show differences in the local conformations of the FP, HR1, and CH domains as well. Finally, most mutations of concern are either in or in the vicinity of high local topological free energy conformations, suggesting that high local topological free energy conformations could be targets for mutations with significant impact of protein function. Namely, the residues 484, 570, 614, 796, and 969, which are present in variants of concern and are targeted as important in protein function, are predicted as such from our model.

60 APPLIED LIFE SCIENCES↗

Exploring the Role of Glycans in the Interaction of SARS-CoV-2 RBD and Human Receptor ACE2

COVID-19 is a highly infectious respiratory disease caused by the novel coronavirus SARS-CoV-2. It has become a global pandemic and its frequent mutations may pose new challenges for vaccine design. During viral infection, the Spike RBD of SARS-CoV-2 binds the human host cell receptor ACE2, enabling the virus to enter the host cell. Both the Spike and ACE2 are densely glycosylated, and it is unclear how distinctive glycan types may modulate the interaction of RBD and ACE2. Detailed understanding of these determinants is key for the development of novel therapeutic strategies. To this end, we perform extensive all-atom simulations of the (i) RBD-ACE2 complex without glycans, (ii) RBD-ACE2 with oligomannose MAN9 glycans in ACE2, and (iii) RBD-ACE2 with complex FA2 glycans in ACE2. These simulations identify the key residues at the RBD-ACE2 interface that form contacts with higher probabilities, thus providing a quantitative evaluation that complements recent structural studies. Notably, we find that this RBD-ACE2 contact signature is not altered by the presence of different glycoforms, suggesting that RBD-ACE2 interaction is robust. Applying our simulated results, we illustrate how the recently prevalent N501Y mutation may alter specific interactions with host ACE2 that facilitate the virus-host binding. Furthermore, our simulations reveal how the glycan on Asn90 of ACE2 can play a distinct role in the binding and unbinding of RBD. Finally, an energetics analysis shows that MAN9 glycans on ACE2 decrease RBD-ACE2 affinity, while FA2 glycans lead to enhanced binding of the complex. Together, our results provide a more comprehensive picture of the detailed interplay between virus and human receptor, which is much needed for the discovery of effective treatments that aim at modulating the physical-chemical properties of this virus.

60 APPLIED LIFE SCIENCES↗

Aerosol transport pathways and source attribution in China during the COVID-19 outbreak

Abstract. Due to the coronavirus disease 2019 (COVID-19) pandemic, human activities and industrial productions were strictly restricted during January–March 2020 in China. Despite the fact that anthropogenic aerosol emissions largely decreased, haze events still occurred. Characterization of aerosol transport pathways and attribution of aerosol sources from specific regions are beneficial to air quality and pandemic control strategies. This study establishes source–receptor relationships in various regions covering all of China during the COVID-19 outbreak based on the Community Atmosphere Model version 5 with Explicit Aerosol Source Tagging (CAM5-EAST). Our analysis shows that PM2.5 burden over the North China Plain between 30 January and 19 February is mostly contributed by local emissions (40 %–66 %). For other regions in China, PM2.5 burden is largely contributed from nonlocal sources. During the most polluted days of the COVID-19 outbreak, local emissions within the North China Plain and eastern China contributed 66 % and 87 % to the increase in surface PM2.5 concentrations, respectively. This is associated with the anomalous mid-tropospheric high pressure at the location of the climatological East Asia trough and the consequently weakened winds in the lower troposphere, leading to the local aerosol accumulation. The emissions outside China, especially those from South Asia and Southeast Asia, contribute over 50 % to the increase in PM2.5 concentration in southwestern China through transboundary transport during the most polluted day. As the reduction in emissions in the near future is desirable, aerosols from long-range transport and unfavorable meteorological conditions are increasingly important to regional air quality and need to be taken into account in clean-air plans.

54 ENVIRONMENTAL SCIENCES↗

Modeling the impact of COVID-19 on air quality in southern California: implications for future control policies

Abstract. In response to the coronavirus disease of 2019 (COVID-19), California issued statewide stay-at-home orders, bringing about abrupt and dramatic reductions in air pollutant emissions. This crisis offers us an unprecedented opportunity to evaluate the effectiveness of emission reductions in terms of air quality. Here we use the Weather Research and Forecasting model with Chemistry (WRF-Chem) in combination with surface observations to study the impact of the COVID-19 lockdown measures on air quality in southern California. Based on activity level statistics and satellite observations, we estimate the sectoral emission changes during the lockdown. Due to the reduced emissions, the population-weighted concentrations of fine particulate matter (PM2.5) decrease by 15 % in southern California. The emission reductions contribute 68 % of the PM2.5 concentration decrease before and after the lockdown, while meteorology variations contribute the remaining 32 %. Among all chemical compositions, the PM2.5 concentration decrease due to emission reductions is dominated by nitrate and primary components. For O3 concentrations, the emission reductions cause a decrease in rural areas but an increase in urban areas; the increase can be offset by a 70 % emission reduction in anthropogenic volatile organic compounds (VOCs). These findings suggest that a strengthened control on primary PM2.5 emissions and a well-balanced control on nitrogen oxides and VOC emissions are needed to effectively and sustainably alleviate PM2.5 and O3 pollution in southern California.

54 ENVIRONMENTAL SCIENCES↗

Three-Dimensional Human Bronchial-Tracheal Epithelial Tissue-Like Assemblies (TLAs) as Hosts for Severe Acute Respiratory Syndrome (SARS)-CoV Infection

A three-dimensional (3-D) tissue-like assembly (TLA) of human bronchial-tracheal mesenchymal (HBTC) cells with an overlay of human bronchial epithelial (BEAS-2B) cells was constructed using a NASA Bioreactor to survey the infectivity of SARS-CoV. This TLA was inoculated with a low passage number Urbani strain of SARS-CoV. At selected intervals over a 10-day period, media and cell aliquots of the 3-D TLA were harvested for viral titer assay and for light and electron microscopy examination. All viral titer assays were negative in both BEAS-2B two-dimensional monolayer and TLA. Light microscopy immunohistochemistry demonstrated antigen-antibody reactivity with anti-SARS-CoV polyclonal antibody to spike and nuclear proteins on cell membranes and cytoplasm. Coronavirus Group 2 cross-reactivity was demonstrated by positive reaction to anti-FIPV 1 and anti-FIPV 1 and 2 antibodies. TLA examination by transmission electron microscopy indicated increasing cytoplasmic vacuolation with numerous electron-dense bodies measuring 45 to 270 nm from days 4 through 10. There was no evidence of membrane blebbing, membrane duplication, or fragmentation of organelles in the TLAs. However, progressive disruption of endoplasmic reticulum was observed throughout the cells. Antibody response to SARS-CoV specific spike and nucleocapsid glycoproteins, cross-reactivity with FIPV antibodies, and the cytoplasmic pathology suggests this HBTE TLA model is permissive to SARS-CoV infection.

Suderman, M. T.↗

Building Supply Chain Visibility for Risk Management: Illuminating the COVID-19 Pandemic Impact Upon NASA Suppliers

NASA mission projects rely upon global supply chains subject to an array of risks that threaten to disrupt or deny the timely, affordable provision of products and services as required for mission success. Visibility into these supply chains is key to the management of risks, such as those stemming from the coronavirus pandemic and its associated effects upon suppliers. Accordingly, the Supplier Research and Analysis (SRA) Program within Goddard Space Flight Center’s Safety and Mission Assurance (SMA) Directorate produced the COVID-19 pandemic/NASA suppliers dashboard as part of the NASA Meta Information System. The dashboard provides visibility and situational awareness to aid risk assessment, planning and decision-making over the course of the pandemic recovery phase. The approach of integrating data and information into visual dashboard displays has also been employed by the SRA Program to focus on specific risks pertaining to foreign-based suppliers. This webinar is presented by the NASA Office of SMA and its Supply Chain Risk Management Program, in collaboration with the NASA Safety Center and Goddard’s SMA Directorate.

supplier research and analysis, supply chain risk ↗

Impact of Air Traffic Reductions during the COVID-19 Pandemic on Aircraft-induced Clouds and their Radiative Effects

Air travel restrictions due to the novel coronavirus 2019 (COVID-19) pandemic drastically reduced air travel internationally during the spring of 2020. Such an extraordinary disruption of air traffic may have a profound effect on contrail formation that could allow for better quantification and scientific understanding of the radiative impacts of aviation-induced clouds on climate. This investigation synergizes MODIS, CrIS, and GOES-16 satellite analyses with weather analyses, including those from GEOS and MERRA, to compare contrail formation conditions and radiative forcings of linear contrails and thin cirrus detected over the contiguous United States (CONUS) and the North Atlantic for the 2020 air traffic slowdown period with parallel analyses conducted for a baseline period from a previous year with normal air traffic. A consistent analysis system for contrail detection and cloud property retrievals (e.g. optical depth, particle size, and altitude) from satellites, coupled with radiative transfer modeling are applied to characterize and contrast contrail cirrus properties and radiative effects estimated during the pandemic and baseline periods. Temperature and humidity profiles from numerical weather models and hyperspectral infrared measurements are used to estimate the contrail formation potential (CFP) over the study areas in order to help choose the most appropriate baseline period and to account for potential impacts of differences in meteorology on contrail formation and coverage. This study, using NASA satellite data and other assets, is expected to improve our understanding of the relationship between air traffic, contrail cirrus coverage and related impacts in order to better quantify the need for contrail formation mitigation strategies that could reduce aviation effects on climate.

William L Smith↗

Spatiotemporal Associations Between Social Vulnerability, Environmental Measurements, and COVID-19 in the Conterminous United States

This study summarizes the results from fitting a Bayesian hierarchical spatiotemporal model to coronavirus disease 2019 (COVID-19) cases and deaths at the county level in the United States for the year 2020. Two models were created, one for cases and one for deaths, utilizing a scaled Besag, York, Mollié model with Type I spatial-temporal interaction. Each model accounts for 16 social vulnerability and 7 environmental variables as fixed effects. The spatial pattern between COVID-19 cases and deaths is significantly different in many ways. The spatiotemporal trend of the pandemic in the United States illustrates a shift out of many of the major metropolitan areas into the United States Southeast and Southwest during the summer months and into the upper Midwest beginning in autumn. Analysis of the major social vulnerability predictors of COVID-19 infection and death found that counties with higher percentages of those not having a high school diploma, having non-White status and being Age 65 and over to be significant. Among the environmental variables, above ground level temperature had the strongest effect on relative risk to both cases and deaths. Hot and cold spots, areas of statistically significant high and low COVID-19 cases and deaths respectively, derived from the convolutional spatial effect show that areas with a high probability of above average relative risk have significantly higher Social Vulnerability Index composite scores. The same analysis utilizing the spatiotemporal interaction term exemplifies a more complex relationship between social vulnerability, environmental measurements, COVID-19 cases, and COVID-19 deaths.

spatial epidemiology↗

Heliophysics Environmental & Radiation Measurement Experiment Suite (HERMES): A Small External Payload for Gateway with Big Challenges

Currently scheduled for liftoff in 2024, Gateway will be an outpost orbiting the moon for astronauts headed to and from the lunar surface and will serve as a staging point for deep space exploration. In January 2020, NASA Headquarters contacted Goddard Space Flight Center (GSFC) with a request that they provide a Heliophysics instrumentation package for Gateway. This package would later become known as the Heliophysics Environmental & Radiation Measurement Experiment Suite (HERMES). HERMES consists of four high-heritage instruments – a Miniaturized Electron pRoton Telescope (MERIT), an Electron Electrostatic Analyzer (EEA), a Solar Probe Analyzer-Ions (SPAN-I), and Noise Eliminating Magnetometer Instrument in a Small Integrated System (NEMISIS), which consists of one fluxgate and two magneto-inductive magnetometers. Launching HERMES with Gateway would provide an opportunity to conduct early science experiments on Gateway, but the plan to develop HERMES concurrently with Gateway and launch with the co-manifested vehicle brought numerous technical challenges for the pathfinder payload. HERMES was intended to be a low-cost, tailored Class-D mission, and maintaining that programmatic position proved difficult as the technical challenges grew. The effects of Coronavirus Disease 2019 (COVID-19) were not factored in from the beginning and also created programmatic challenges. This paper will discuss what’s being done to overcome the technical and programmatic challenges to put HERMES on track for a 2024 Launch Readiness Date (LRD).

Joe Burt↗

What Makes Hybrid Concurrent Engineering Teams Work and Not Work: A Theoretical Analysis

Aerospace concurrent engineering teams (CETs) have been around since 1995 and have evolved into various shapes and forms. Historically, CETs have been designed to function with all team members physically collocated. In order to continue operating during the coronavirus pandemic, these teams have had to become fully distributed in 2020. Previously, distributed CETs were predicted to be considerably less efficient than traditional CETs. However, at JPL studies are being successfully run at peak rate in a distributed mode. As nominal working conditions resume after the pandemic, a major question is whether these teams must go back to being fully collocated or if they can become successful hybrid teams, with half or more of the engineers working remotely. In order to address this question, it is important to understand the key characteristics that make a CET more likely to be successful in a remote mode. This paper revisits a framework for characterizing concurrent engineering teams, providing a means to describe and compare the behavior of concurrent engineering teams in various settings [1], and uses the framework to make recommendations for future hybrid teams.

Chattopadhyay, Debarati↗

Feasibility Study for Remote Psychoacoustic Testing of Human Response to Urban Air Mobility Vehicle Noise

NASA will remotely administer a psychoacoustic test in late summer of 2022 as the first of two phases of a cooperative Urban Air Mobility (UAM) vehicle noise human response study. This study relies on the cooperation of multiple government agencies, academia, and industry to assemble a wide range of UAM vehicle sounds. This database of sounds will be used to create a rich database of human response to UAM noise that would be challenging for a single organization to acquire. The development of the remote test method to study human response to aviation noise was prompted by the novel coronavirus pandemic. The feasibility portion of the study described in this work will demonstrate and refine the remote test method for use in the implementation phase. This paper details the method for remotely administering the psychoacoustic test and the sound stimuli to be used in the Feasibility Test. Comparisons of annoyance response data from previous in-person tests will be used to demonstrate the viability of the remote test method. The paper also describes an effort to determine if providing a contextual cue to test subjects influences the annoyance response.

UAM Vehicle Noise Human Response Study↗

New Hayabusa2 and OSIRIS REx Curation Facilities at Nasa Johnson Space Center

Asteroids are made up of rocky material that is left over from the formation of our solar system [1]. This material holds the key to unlocking information about the history of the planets and our sun. Hayabusa2 and OSIRIS-REx are two sample return missions that have collected rocky material from carbonaceous asteroids which are rich in water, carbon, and organic compounds [1]. Hayabusa2 is a spacecraft that collected samples from asteroid Ryugu launched by the Japan Aerospace Exploration Agency (JAXA). Samples were returned to Earth in December 2020 and 10 percent of the collected material is currently housed in a state-of-the-art laboratory at NASA Johnson Space Center (JSC) dedicated to Ryugu material [1]. OSIRIS-REx is a spacecraft launched by NASA that collected samples from asteroid Bennu. The samples are on their journey to Earth and will arrive in September 2023. They will be stored in a separate cleanroom dedicated to Bennu material. From these two missions, scientists will examine dust particles and rocky material to research clues on how the early solar system formed and how life began [2]. Because these samples are so precious and rare, it is important to keep them free from Earth contamination. In September of 2020, a massive construction project began to provide curation facilities to meet the needs of two incoming asteroid collections, Hayabusa2 and OSIRIS-REx. Despite numerous setbacks caused by the coronavirus pandemic, these facilities have been completed in the fall of 2021. Some of these setbacks included strict PPE requirements, keeping safe working distances as well as access to the facilities as NASA was operating under a Stage 3 condition in response to the pandemic. These facilities will provide curation laboratories to safely house the precious asteroid samples as well as facilities to manipulate samples, do sample preparation and process samples into and out of the labs for future studies by the scientific community. The lab suite consists of several different rooms including an initial anteroom (ISO 7), a staging area (ISO 7), two gowning areas (one for OSIRIS-REx and one for Hayabusa2; both ISO 6)), the Haybusa2 Curation Laboratory (ISO 5), the OSIRIS-REx Curation Laboratory (ISO 5), an ultramicrotomy laboratory (ISO 7) and a thin section laboratory (not a cleanroom). To maintain cleanliness levels necessary for these lab spaces quarterly to monthly Balazs organic and inorganic sampling has been conducted on a regular basis before, during and after the construction project to monitor the cleanliness levels in the new labs that will house the asteroid samples. These new facilities feature a Ruuvi (Grafana) monitoring system that measures temperature, humidity, and pressure of the lab suite. This is a small puck shaped sensor that sends signals to the Grafana cloud where the data can be plotted and set up on dashboards within the lab suite. These sensors are easy to set up and install and they run off a cell battery that is good for 3-5 years before needing replacement. This system can deliver text messages and emails to the appropriate personnel when values fall outside of set limits. In addition to the monitoring system, this new lab suite features viewing windows from several different locations and sliding motion censored doors. We have obtained some state-of-the-art equipment to outfit the lab spaces (desiccators, microscopes, ultramicrotome) and are in the process of outfitting the suite with additional items such as: nitrogen gloveboxes, additional desiccators, micromanipulators, etc. The Hayabusa2 samples provided to NASA by JAXA included 23 millimeter sized grains and 4 containers with finer material. OSIRIS-REx is expected to return as much as 400 grams of asteroid Bennu. Samples will be stored in a nitrogen glove box and separated into nitrogen sealed transfer containers. Small Bennu and Ryugu particles will be handled and prepared (e.g., ultra-thin sections for scanning electron microscopy (SEM) or transmission electron microscopy (TEM)) using an Axis Pro micromanipulator and Leica EM UC7 ultramicrotome. Analyzing samples at the atomic scale will provide greater insight to the origins of the solar system and life formation on Earth. All the curation preparation for these sample collections is essential to ongoing research and efforts to understand our solar system, both nowand for future generations.

Curation↗

Feasibility study for remote psychoacoustic testing of human response to urban air mobility vehicle noise

NASA will remotely administer a psychoacoustic test in late summer of 2022 as the first of two phases of a cooperative Urban Air Mobility (UAM) vehicle noise human response study. This study relies on the cooperation of multiple government agencies, academia, and industry to assemble a wide range of UAM vehicle sounds. This database of sounds will be used to create a rich database of human response to UAM noise that would be challenging for a single organization to acquire. The development of the remote test method to study human response to aviation noise was prompted by the novel coronavirus pandemic. The feasibility portion of the study described in this work will demonstrate and refine the remote test method for use in the implementation phase. This paper details the method for remotely administering the psychoacoustic test and the sound stimuli to be used in the Feasibility Test. Comparisons of annoyance response data from previous in-person tests will be used to demonstrate the viability of the remote test method. The paper also describes an effort to determine if providing a contextual cue to test subjects influences the annoyance response.

Remote psychoacoustic test↗

Global Reduction in Ship-tracks from Sulfur Regulations for Shipping Fuel

Ship-tracks are produced by ship-emitted aerosols interacting with low clouds. Here, we apply deep learning models on satellite data to produce the first global climatology map of ship-tracks. We show that ship-tracks are at the nexus of cloud physics, maritime shipping, and fuel regulation. Our map captures major shipping lanes while missing others because of background conditions. Ship-track frequency is more than 10 times higher than a previous survey, and its interannual fluctuations reflect variations in cross-ocean trade, shipping activity, and fuel regulations. Fuel regulation can alter both detected frequency and shipping routes due to cost. The 2020 fuel regulation, together with the coronavirus disease 2019 pandemic, reduced ship-track frequency to its lowest level in recent decades across the globe and may have ushered in an era of low frequency. The regulation reduces the aerosol indirect forcing from ship emissions by 46% or between 0.02 and 0.27 W m −2 given its current estimates.

ship tracks↗

Increasing Threat of Wildfires: the Year 2020 in Perspective: A Global Ecology and Biogeography Special Issue

Each year, wild and managed fires burn roughly 4 million km2 [~400 million hectares (Mha)] of savanna, forest, grassland and agricultural ecosystems. Land use and climate change have altered fire regimes throughout the world, with a trend toward higher-severity fires found from Australia, the Americas, Europe and Asia, to the Arctic. In 2020, there were notable catastrophic fires in Australia (in the 2019/20 Austral fire season), the Western United States, South America and Siberia. These fires defined much of the global fire year and were compounded by the socio-economic disruption of the Coronavirus 2019 (COVID-19) pandemic.

Rachael H Nolan↗