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DOE OSTI2015

Post-closure program streamlining at the Nevada national security site - 15290

More than 200 sites on the Nevada National Security Site (NNSS), Nevada Test and Training Range (NTTR), and Tonopah Test Range (TTR) have been closed in place. At these sites, contamination has been left in place, and protection of human health, safety, and the environment is ensured through the establishment of use restrictions (URs). Post-closure requirements were initially established in the Closure Report (CR) for each site and include a variety of inspection, monitoring, maintenance, and reporting commitments. Post-closure requirements and site controls (fences, monuments, soil covers, and postings) may vary depending on site location, accessibility, land use scenario, and the nature of contaminants left in place. Corrective Action Sites (CASs) on the NNSS, NTTR, and TTR have been identified for closure under the Federal Facility Agreement and Consent Order (FFACO), which was signed in 1996. Over 1,900 CASs have been closed under the framework of the FFACO, and more than 200 of those have URs. Many post-closure requirements have been modified over time. In addition, because the scope of the program has spanned almost 20 years, the post-closure requirements have varied due to changing strategies and expectations. Because of the number of sites closed over the course of the program, post-closure requirements are found in hundreds of closure documents, addendums, errata sheets, Records of Technical Change, inspection reports, permit modifications, and correspondence. Furthermore, resources such as personnel and funding necessary to conduct the post-closure program have diminished, while computer capabilities and configuration control principles have improved since closure activities under the FFACO began. Because of these factors, to effectively manage the post-closure program, ensure that all commitments are being met, and improve the ease of identifying the most current post-closure requirements for each UR, the current requirements for every use-restricted site under the purview of the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office will be consolidated into a single Post-Closure Plan. The Consolidated Post-Closure Plan will also outline a strategy and present possible criteria that may be used for future evaluation of post-closure requirements. Continual assessment of the post-closure program will ensure that the post-closure requirements for URs across the NNSS, NTTR, and TTR are consistently justifiable and sufficient to protect site workers, the public, and the environment while increasing efficiency. Future changes to post-closure requirements and justification for those changes will be recorded in revisions to the Consolidated Post-Closure Plan. This process will provide a comprehensive, consistent, and streamlined method for evaluation of post-closure requirements and implementation of changes. (authors)

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2019

Natural Gas Drilling near the Underground Nuclear Test Site of Rulison, Colorado - 19571

In 1969, the Project Rulison test was conducted in western Colorado using a nuclear device to stimulate natural gas production by fracturing low-permeability, gas-bearing rock. The presence of radionuclides (specifically tritium) in the produced gas persisted above acceptable levels, and the test was abandoned. Advances in hydrofracturing technology over the past 10-15 years have revolutionized the extraction of hydrocarbons from low-permeability formations, leading to a significant increase of drilling in the Rulison area. Drilling activity nearing the Rulison site has raised concerns that remnant radioactivity might be encountered. The site, now under the care of the US Department of Energy (DOE), is protected by a 16-hectare (40 acre) institutional control boundary (Lot 11) that prohibits drilling or extraction of materials below 1830 meters (6000 feet) within the lot boundary. Drilling within 0.8 kilometer (0.5 mile) of the site requires a hearing before the Colorado Oil and Gas Conservation Commission. DOE recommends that gas developers adopt a conservative, staged drilling approach, allowing gas reserves near the Rulison site to be recovered in a manner that minimizes the likelihood of encountering contamination. The staged approach calls for collecting data from wells away from the site before drilling closer. For instance, the wells 1.2 kilometer (0.75 mile) west of the site did not encounter any unexpected geologic conditions and now have 8 years of production without encountering any detonation-related radionuclides. The next set of wells would be 0.8 kilometer (0.5 mile) west of the site. This sequential method drills first at locations with a low probability of encountering contamination and then moves closer. This process protects public safety while allowing the collection of additional data to confirm that contamination has not migrated beyond the 16-hectare (40-acre) institutional control boundary. The staged drilling approach was simulated with a modeling effort that estimates the current extent of contamination and the potential for production-induced contaminant migration to nearby wells. The model incorporates geologic data from nearby wells and was calibrated to production data from both the reentry well production testing (1970-1971) and the wells 1.2 kilometer (0.75 mile) from the site that began producing in 2010. The geologic data include both sand/shale distribution statistics as well as the tendency of hydrofractures to preferentially propagate east and west due to the regional stress field. The model results indicate that it is unlikely that wells near the site would ever encounter site-related radionuclides. (authors)

03 NATURAL GAS↗

DOE OSTI2024

Dashboard for Marine Energy Site Assessment and Monitoring

The marine energy (ME) industry presently relies upon fragmented site assessment solutions that require high resource expenditure for deployment at each site and do not leverage the wealth of readily available tools and information. A wave energy resource assessment dashboard, currently in development, will substantially improve siting, permitting, operations, and maintenance of ME projects by providing an integrated solution that is a one-stop-shop for a developer’s needs. The Site Energy Assessment and MOnitoring Dashboard (SEAMOD) will be of commercial interest to anyone seeking to deploy an ME project and is easily expandable to include tidal and wind energy site assessments. The integrated dashboard is being developed using state-of-the-art database and cloud computing methods and data-assimilative modeling tools that can be coupled with low-cost, rapidly deployable wave buoys and environmental sensing hardware. The combined software and hardware dashboard will reduce wave energy site characterization and wave climate monitoring costs by more than 60 percent and provide assessments that meet international industry standards. To realize a thriving global ME industry, the physical environment at a potential deployment site must be understood, not only for resource characterization, but also for optimization of device and power conversion performance. SEAMOD directly addresses these needs with a commercially marketable product. SEAMOD is a low-cost solution that provides comprehensive ME resource assessments, baseline environmental monitoring, and offshore characterizations required for successful ME development. The key technical objectives for Phase I were a series of software development goals, which when implemented with monitoring solutions, produced an initial proof-of-concept low-cost wave energy resources dashboard. In Phase II, the development of the prototype SEAMOD continued. The basic framework employed was the development of a revised dashboard and monitoring tool customized for ME applications by focusing on IEC site assessment and method requirements. Development was focused on the integration of full hindcast metocean products to provide hindcast resource characterization and environmental information. The final integrated dashboard provides a low-cost solution that delivers comprehensive, scalable, industry-standard energy resource assessments and offshore characterizations required for successful ME development. The integrated dashboard offers visibility of the most recent site modeling, measurements, and historical data. The application and integration of consensus-based standards for wave energy resource assessment, as determined by the International Electrotechnical Commission (IEC), are crucial for the impact and value of SEAMOD. SEAMOD includes monthly, seasonal, and yearly statistics, as well as the total 30-year record, offering temporal resolution of the IEC parameters to aid potential developers in determining the available wave energy resources in their area of interest.

16 TIDAL AND WAVE POWER↗

DOE OSTI2025

Hyperspectral leaf reflectance of grasses varies with evolutionary lineage more than with site

Abstract To predict ecological responses at broad environmental scales, grass species are commonly grouped into two broad functional types based on photosynthetic pathway. However, closely related species may have distinctive anatomical and physiological attributes that influence ecological responses, beyond those related to photosynthetic pathway alone. Hyperspectral leaf reflectance can provide an integrated measure of covarying leaf traits that may result from phylogenetic trait conservatism and/or environmental conditions. Understanding whether spectra‐trait relationships are lineage specific or reflect environmental variation across sites is necessary for using hyperspectral reflectance to predict plant responses to environmental changes across spatial scales. We measured hyperspectral leaf reflectance (400–2400 nm) and 12 structural, biochemical, and physiological leaf traits from five grass‐dominated sites spanning the Great Plains of North America. We assessed if variation in leaf reflectance spectra among grass species is explained more by evolutionary lineage (as captured by tribes or subfamilies), photosynthetic pathway (C 3 or C 4 ), or site differences. We then determined whether leaf spectra can be used to predict leaf traits within and across lineages. Our results using redundancy analysis ordination (RDA) show that grass tribe identity explained more variation in leaf spectra (adjusted R 2 = 0.12) than photosynthetic pathway, which explained little variation in leaf spectra (adjusted R 2 = 0.00). Furthermore, leaf reflectance from the same tribe across multiple sites was more similar than leaf reflectance from the same site across tribes (adjusted R 2 = 0.12 and 0.08, respectively). Across all sites and species, trait predictions based on spectra ranged considerably in predictive accuracies ( R 2 = 0.65 to <0.01), but R 2 was >0.80 for certain lineages and sites. The relationship between Vc max , a measure of photosynthetic capacity, and spectra was particularly promising. Chloridoideae, a lineage more common at drier sites, appears to have distinct spectra‐trait relationships compared with other lineages. Overall, our results show that evolutionary relatedness explains more variation in grass leaf spectra than photosynthetic pathway or site, but consideration of lineage‐ and site‐specific trait relationships is needed to interpret spectral variation across large environmental gradients.

Pau, Stephanie [Department of Geography University↗

DOE OSTI2017

A Method to Recognize Anatomical Site and Image Acquisition View in X-ray Images

A method was developed to recognize anatomical site and image acquisition view automatically in 2D X-ray images that are used in image-guided radiation therapy. The purpose is to enable site and view dependent automation and optimization in the image processing tasks including 2D-2D image registration, 2D image contrast enhancement, and independent treatment site confirmation. The X-ray images for 180 patients of six disease sites (the brain, head-neck, breast, lung, abdomen, and pelvis) were included in this study with 30 patients each site and two images of orthogonal views each patient. A hierarchical multiclass recognition model was developed to recognize general site first and then specific site. Each node of the hierarchical model recognized the images using a feature extraction step based on principal component analysis followed by a binary classification step based on support vector machine. Given two images in known orthogonal views, the site recognition model achieved a 99% average F1 score across the six sites. If the views were unknown in the images, the average F1 score was 97%. If only one image was taken either with or without view information, the average F1 score was 94%. The accuracy of the site-specific view recognition models was 100%.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2014

Radiation Therapy to the Primary and Postinduction Chemotherapy MIBG-Avid Sites in High-Risk Neuroblastoma

Purpose: Although it is generally accepted that consolidation therapy for neuroblastoma includes irradiation of the primary site and any remaining metaiodobenzylguanidine (MIBG)-avid metastatic sites, limited information has been published regarding the efficacy of this approach. Methods and Materials: Thirty patients with high-risk neuroblastoma were treated at 1 radiation therapy (RT) department after receiving 5 cycles of induction chemotherapy and resection. All patients had at least a partial response after induction therapy, based upon international neuroblastoma response criteria. The primary sites were treated with 24 to 30 Gy whereas the MIBG-avid metastatic sites were treated with 24 Gy. RT was followed by high-dose chemotherapy with autologous stem cell rescue and 6 months of cis-retinoic acid. Results: The 5-year progression-free survival (PFS) and overall survival (OS) rates were 48% and 59%, respectively. The 5-year locoregional control at the primary site was 84%. There were no differences in locoregional control according to degree of primary surgical resection. The 5-year local control rate for metastatic sites was 74%. The 5-year PFS rates for patients with 0, 1, 2, and >3 postinduction MIBG sites were 66%, 57%, 20%, and 0% (P<.0001), respectively, whereas 5-year OS rates were 80%, 57%, 50%, and 0%, respectively (P<.0001). Conclusions: RT to the primary site and postinduction MIBG-positive metastatic sites was associated with 84% and 74% local control, respectively. The number of MIBG-avid sites present after induction chemotherapy and surgery was predictive of progression-free and overall survival.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2020

Rates of levoglucosanol hydrogenolysis over Brønsted and Lewis acid sites on platinum silica-alumina catalysts synthesized by atomic layer deposition

Nanoscale coatings of AlO x were deposited onto SiO 2 using atomic layer deposition (ALD) to synthesize amorphous silica-alumina (SiAl) catalysts, and these catalysts were investigated for levoglucosanol (Lgol) hydrogenolysis. With decreasing Al 2 O 3 loading, the ratio of Brønsted to Lewis acid sites, measured by NH 3 -TPD and pyridine-FTIR, systematically increases, while the Al coordination, measured by solid state 27 Al NMR, decreases. These structural changes correspond to an increasing mass-normalized rate of Lgol hydrogenolysis. We model the mass-normalized reaction rate as the sum of independent contributions from Brønsted and Lewis sites, showing that Brønsted acid sites on ALD-AlO x /SiO 2 catalysts have a 6-times higher turnover frequency (TOF) than Lewis acid sites on these catalysts. Additionally, Lewis acid sites on ALD-AlO x /SiO 2 catalysts (potentially related to Al(V) species) have a 4-times higher TOF than Lewis acid sites on bulk γ-Al 2 O 3 . The overall mass-normalized reactivity of ALD-AlO x /SiO 2 catalysts is due to Lewis acid sites at the highest Al 2 O 3 loading, while it is predominantly due to Brønsted acid sites at the lowest Al 2 O 3 loadings. In conclusion, this work provides a new approach to synthesize amorphous SiAls with tunable Brønsted/Lewis acid site ratio and reveals differences in the reactivity of Brønsted and Lewis acid sites on these materials.

36 MATERIALS SCIENCE↗

DOE OSTI2013

Persistence of uranium groundwater plumes: Contrasting mechanisms at two DOE sites in the groundwater-river interaction zone

We examine subsurface uranium (U) plumes at two U.S. Department of Energy sites that are located near large river systems and that are influenced by groundwater-river hydrologic interaction. Following surface excavation of contaminated materials, both sites were projected to naturally flush remnant uranium contamination to levels below regulatory limits (e.g., 30 µg/L or 0.126 µmol/L; U.S. EPA drinking water standard), with 10 years projected for the Hanford 300 Area (Columbia River) and 12 years for the Rifle site (Colorado River). The rate of observed uranium decrease was much lower than expected at both sites. While uncertainty remains, a comparison of current understanding suggests that the two sites have common, but also different mechanisms controlling plume persistence. At the Hanford 300 A, the persistent source is adsorbed U(VI) in the vadose zone that is released to the aquifer during spring water table excursions. The release of U(VI) from the vadose zone and its transport within the oxic, coarse-textured aquifer sediments is dominated by kinetically-limited surface complexation. Modeling implies that annual plume discharge volumes to the Columbia River are small (< one pore volume). At the Rifle site, slow oxidation of naturally reduced, contaminant U(IV) in the saturated zone and a continuous influx of U(VI) from natural, up-gradient sources influences plume persistence. Rate-limited mass transfer and surface complexation also control U(VI) migration velocity in the sub-oxic Rifle groundwater. Flux of U(VI) from the vadose zone at the Rifle site may be locally important, but it is not the dominant process that sustains the plume. A wide range in microbiologic functional diversity exists at both sites. Strains of Geobacter and other metal reducing bacteria are present at low natural abundance that are capable of enzymatic U(VI) reduction in localized zones of accumulated detrital organic carbon or after organic carbon amendment. Major differences between the sites include the geochemical nature of residual, contaminant U; the rates of current kinetic processes (both biotic and abiotic) influencing U(VI) solid-liquid distribution; the presence of detrital organic matter and the resulting spatial heterogeneity in microbially-driven redox properties; and the magnitude of groundwater hydrologic dynamics controlled by river-stage fluctuations, geologic structures, and aquifer hydraulic properties. The comparative analysis of these sites provides important guidance to the characterization, understanding, modeling, and remediation of groundwater contaminant plumes influenced by surface water interaction that are common world-wide.

Environmental Molecular Sciences Laboratory↗

DOE OSTI2020

Tuning Zr 12 O 22 Node Defects as Catalytic Sites in the Metal–Organic Framework hcp UiO-66

Defects in metal–organic frameworks (MOFs) play important roles in MOF reactivity and catalysis. Now, we report evidence of the reactivity and the quantitative characterization of the missing linker defects on the Zr 12 O 22 nodes in the MOF hcp UiO-66 (these are paired Zr 6 O 8 nodes bridged by OH groups) and those on the Zr 6 O 8 nodes of the MOF UiO-66. The defect sites catalyze the ring-opening reactions of epoxides with alcohols, and new sites formed by removal of bridging OH groups on the Zr 12 O 22 nodes also participate in the catalysis. The hcp UiO-66 was synthesized from UiO-66 and from molecular precursors, and, under various synthesis conditions, the nodes incorporated acetate ligands, where linkers were missing, and the number of these ligands was controlled by the synthesis conditions. These ligands are inhibitors of the catalytic reactions, and their removal by reaction with, for example, methanol (to form, for example, methyl acetate) preceded catalysis on the defect sites. The former MOF incorporated more defect sites than the latter, correspondingly being a more active catalyst. The defect sites on the Zr 12 O 22 nodes are 2–6 times more active per site than those on the isolated Zr 6 O 8 nodes, with the node-bridging OH groups increasing the catalytic activity of the neighboring node defect sites because new sites are formed by their removal. In conclusion, the results help point the way to the design and control of catalytic sites on metal oxide-like MOF nodes by tuning of the number and reactivity of the defect sites.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2015

Active Site and Remote Contributions to Catalysis in Methylthioadenosine Nucleosidases

5'-Methylthioadenosine/S-adenosyl-l-homocysteine nucleosidases (MTANs) catalyze the hydrolysis of 5'-methylthioadenosine to adenine and 5-methylthioribose. The amino acid sequences of the MTANs from Vibrio cholerae (VcMTAN) and Escherichia coli (EcMTAN) are 60% identical and 75% similar. Protein structure folds and kinetic properties are similar. However, binding of transition-state analogues is dominated by favorable entropy in VcMTAN and by enthalpy in EcMTAN. Catalytic sites of VcMTAN and EcMTAN in contact with reactants differ by two residues; Ala113 and Val153 in VcMTAN are Pro113 and Ile152, respectively, in EcMTAN. Here, we mutated the VcMTAN catalytic site residues to match those of EcMTAN in anticipation of altering its properties toward EcMTAN. Inhibition of VcMTAN by transition-state analogues required filling both active sites of the homodimer. However, in the Val153Ile mutant or double mutants, transition-state analogue binding at one site caused complete inhibition. Therefore, a single amino acid, Val153, alters the catalytic site cooperativity in VcMTAN. The transition-state analogue affinity and thermodynamics in mutant VcMTAN became even more unlike those of EcMTAN, the opposite of expectations from catalytic site similarity; thus, catalytic site contacts in VcMTAN are unable to recapitulate the properties of EcMTAN. X-ray crystal structures of EcMTAN, VcMTAN, and a multiple-site mutant of VcMTAN most closely resembling EcMTAN in catalytic site contacts show no major protein conformational differences. In conclusion, the overall protein architectures of these closely related proteins are implicated in contributing to the catalytic site differences.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2024

Dynamic Copper Site Redispersion through Atom Trapping in Zeolite Defects

Single-site copper-based catalysts have shown remarkable activity and selectivity for a variety of reactions. However, deactivation by sintering in high-temperature reducing environments remains a challenge and often limits their use due to irreversible structural changes to the catalyst. Here, we report zeolite-based copper catalysts in which copper oxide agglomerates formed after reaction can be repeatedly redispersed back to single sites using an oxidative treatment in air at 550 °C. Under different environments, single-site copper in Cu–Zn–Y/deAlBeta undergoes dynamic changes in structure and oxidation state that can be tuned to promote the formation of key active sites while minimizing deactivation through Cu sintering. For example, single-site Cu 2+ reduces to Cu 1+ after catalyst pretreatment (270 °C, 101 kPa H 2 ) and further to Cu0 nanoparticles under reaction conditions (270–350 °C, 7 kPa EtOH, 94 kPa H 2 ) or accelerated aging (400–450 °C, 101 kPa H 2 ). After regeneration at 550 °C in air, agglomerated CuO was dispersed back to single sites in the presence and absence of Zn and Y, which was verified by imaging, in situ spectroscopy, and catalytic rate measurements. Ab initio molecular dynamics simulations show that solvation of CuO monomers by water facilitates their transport through the zeolite pore, and condensation of the CuO monomer with a fully protonated silanol nest entraps copper and reforms the single-site structure. Importantly, the capability of silanol nests to trap and stabilize copper single sites under oxidizing conditions could extend the use of single-site copper catalysts to a wider variety of reactions and allows for a simple regeneration strategy for copper single-site catalysts.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2012

Substrate binds in the S1 site of the F253A mutant of LeuT, a neurotransmitter sodium symporter homologue

LeuT serves as the model protein for understanding the relationships between structure, mechanism and pharmacology in neurotransmitter sodium symporters (NSSs). At the present time, however, there is a vigorous debate over whether there is a single high-affinity substrate site (S1) located at the original, crystallographically determined substrate site or whether there are two high-affinity substrates sites, one at the primary or S1 site and the other at a second site (S2) located at the base of the extracellular vestibule. In an effort to address the controversy over the number of high-affinity substrate sites in LeuT, one group studied the F253A mutant of LeuT and asserted that in this mutant substrate binds exclusively to the S2 site and that 1 mM clomipramine entirely ablates substrate binding to the S2 site. Here we study the binding of substrate to the F253A mutant of LeuT using ligand binding and X-ray crystallographic methods. Both experimental methods unambiguously show that substrate binds to the S1 site of the F253A mutant and that binding is retained in the presence of 1 mM clomipramine. These studies, in combination with previous work, are consistent with a mechanism ofr LeuT that involves a single high-affinity substrate binding site.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2026

Author Correction: US oil and gas system emissions from nearly one million aerial site measurements

Correction to: Naturehttps://doi.org/10.1038/s41586-024-07117-5 Published online 13 March 2024 In the version of the article initially published, several errors were present and have been corrected in the HTML and PDF versions of the article and Supplementary Information. The main results, conclusions, and our interpretations of the data remain unchanged. See the new Supplementary Information Section S15 for a more detailed description of the errors corrected and the resulting effects on the analysis. Data processing and methods corrections Overflight count correction: We previously used pre-computed source coverage data for some Carbon Mapper campaigns that was computed differently than was required for our analysis. We have re-computed Carbon Mapper source coverage based on flightline polygons and source coordinates. Transition point computation, well sites: The updated version now correctly compares the cumulative emissions distribution of simulated well site emissions with that of aerially detected sources (rather than plumes) when computing the transition point. Transition point computation, midstream: Additionally, the transition point calculation has been corrected to exclude aerially detected midstream emissions below the transition point, which was previously leading to double counting of these emissions. This error was not present for upstream (well site) emissions. Calculation errors Unit error: We corrected a specific unit conversion error affecting well site emissions in the Kairos Fort Worth dataset. Across all datasets, we also correct the conversion factor for converting from standard volume to mass for midstream emissions. Sorting error: We correct code that was applying incorrect sorting when computing correction factors to account for partial detection at well sites. Small typographical corrections were made in Fig. 1b and SI Section S4.1. Data processing and methods corrections Overflight count correction: We previously used pre-computed source coverage data for some Carbon Mapper campaigns that was computed differently than was required for our analysis. We have re-computed Carbon Mapper source coverage based on flightline polygons and source coordinates. Transition point computation, well sites: The updated version now correctly compares the cumulative emissions distribution of simulated well site emissions with that of aerially detected sources (rather than plumes) when computing the transition point. Transition point computation, midstream: Additionally, the transition point calculation has been corrected to exclude aerially detected midstream emissions below the transition point, which was previously leading to double counting of these emissions. This error was not present for upstream (well site) emissions. Calculation errors Unit error: We corrected a specific unit conversion error affecting well site emissions in the Kairos Fort Worth dataset. Across all datasets, we also correct the conversion factor for converting from standard volume to mass for midstream emissions. Sorting error: We correct code that was applying incorrect sorting when computing correction factors to account for partial detection at well sites. Small typographical corrections were made in Fig. 1b and SI Section S4.1. The following practices may help researchers conducting similar analyses avoid making similar errors: 1, Clear, accessible documentation explaining the interpretation of all columns in data input tables and all internal variables within the model, 2, Simple cross-check calculations computed before and after unit conversions.

Sherwin, Evan D↗

DOE OSTI2023

Site specific N- and O-glycosylation mapping of the spike proteins of SARS-CoV-2 variants of concern

Abstract The glycosylation on the spike (S) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, modulates the viral infection by altering conformational dynamics, receptor interaction and host immune responses. Several variants of concern (VOCs) of SARS-CoV-2 have evolved during the pandemic, and crucial mutations on the S protein of the virus have led to increased transmissibility and immune escape. In this study, we compare the site-specific glycosylation and overall glycomic profiles of the wild type Wuhan-Hu-1 strain (WT) S protein and five VOCs of SARS-CoV-2: Alpha, Beta, Gamma, Delta and Omicron. Interestingly, both N- and O-glycosylation sites on the S protein are highly conserved among the spike mutant variants, particularly at the sites on the receptor-binding domain (RBD). The conservation of glycosylation sites is noteworthy, as over 2 million SARS-CoV-2 S protein sequences have been reported with various amino acid mutations. Our detailed profiling of the glycosylation at each of the individual sites of the S protein across the variants revealed intriguing possible association of glycosylation pattern on the variants and their previously reported infectivity. While the sites are conserved, we observed changes in the N- and O-glycosylation profile across the variants. The newly emerged variants, which showed higher resistance to neutralizing antibodies and vaccines, displayed a decrease in the overall abundance of complex-type glycans with both fucosylation and sialylation and an increase in the oligomannose-type glycans across the sites. Among the variants, the glycosylation sites with significant changes in glycan profile were observed at both the N -terminal domain and RBD of S protein, with Omicron showing the highest deviation. The increase in oligomannose-type happens sequentially from Alpha through Delta. Interestingly, Omicron does not contain more oligomannose-type glycans compared to Delta but does contain more compared to the WT and other VOCs. O-glycosylation at the RBD showed lower occupancy in the VOCs in comparison to the WT. Our study on the sites and pattern of glycosylation on the SARS-CoV-2 S proteins across the VOCs may help to understand how the virus evolved to trick the host immune system. Our study also highlights how the SARS-CoV-2 virus has conserved both N - and O - glycosylation sites on the S protein of the most successful variants even after undergoing extensive mutations, suggesting a correlation between infectivity/ transmissibility and glycosylation.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Oxygen and sulfur adsorption on vicinal surfaces of copper and silver: Preferred adsorption sites

We present an extensive density functional theory (DFT) study of adsorption site energetics for oxygen and sulfur adsorbed on two vicinal surfaces of Cu and Ag, with the goal of identifying the most stable adsorption site(s), identifying trends and common themes, and comparing with experimental work in the literature where possible. We also present benchmark calculations for adsorption on the flat (111) and (100) surfaces. The first vicinal surface is the (211), and results are similar for both metals. Here, we find that the step-doubling reconstruction is favored with both adsorbates and is driven by the creation of a special stable fourfold hollow (4fh) site at the reconstructed step. Zig-zag chain structures consisting of X–M–X units (X = chalcogen, M = metal) at the step edge are considered, in which the special 4fh site is partially occupied. The zig-zag configuration is energetically competitive for oxygen but not sulfur. DFT results for oxygen agree with experiment in terms of the stability of the reconstruction, but contradict the original site assignment. The second vicinal surface is the (410), where again results are similar for both metals. For oxygen, DFT predicts that step sites are filled preferentially even at lowest coverage, followed by terrace sites, consistent with the experiment. For sulfur, in contrast, DFT predicts that terrace sites fill first. Oxygen forms O–M–O rows on the top edge of the step, where it occupies incomplete 4fh sites. This resolves an experimental ambiguity in the site assignment. Finally, for both the (211) and (410) surfaces, the interaction energy that stabilizes the X–M–X chain or row correlates with the linearity of the X–M–X unit, which may explain key differences between oxygen and sulfur.

36 MATERIALS SCIENCE↗

DOE OSTI2016

Structural basis for nonneutralizing antibody competition at antigenic site II of the respiratory syncytial virus fusion protein

Palivizumab was the first antiviral monoclonal antibody (mAb) approved for therapeutic use in humans, and remains a prophylactic treatment for infants at risk for severe disease because of respiratory syncytial virus (RSV). Palivizumab is an engineered humanized version of a murine mAb targeting antigenic site II of the RSV fusion (F) protein, a key target in vaccine development. There are limited reported naturally occurring human mAbs to site II; therefore, the structural basis for human antibody recognition of this major antigenic site is poorly understood. Here, we describe a nonneutralizing class of site II-specific mAbs that competed for binding with palivizumab to postfusion RSV F protein. We also describe two classes of site II-specific neutralizing mAbs, one of which escaped competition with nonneutralizing mAbs. Here, an X-ray crystal structure of the neutralizing mAb 14N4 in complex with F protein showed that the binding angle at which human neutralizing mAbs interact with antigenic site II determines whether or not nonneutralizing antibodies compete with their binding. Fine-mapping studies determined that nonneutralizing mAbs that interfere with binding of neutralizing mAbs recognize site II with a pose that facilitates binding to an epitope containing F surface residues on a neighboring protomer. Neutralizing antibodies, like motavizumab and a new mAb designated 3J20 that escape interference by the inhibiting mAbs, avoid such contact by binding at an angle that is shifted away from the nonneutralizing site. Furthermore, binding to rationally and computationally designed site II helix–loop–helix epitope-scaffold vaccines distinguished neutralizing from nonneutralizing site II antibodies.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2018

MPS dose reconstruction for internal emitters: some site-specific issues and approaches

Background: As part of the Million Person Study (MPS), dose reconstructions for internal emitters have been performed for several U.S. facilities where large quantities of radionuclides were handled. The main challenges and dominant sources of potential error in retrospective dose estimates for internally exposed workers have been found to vary from site to site. Here in this paper, we discuss some important issues encountered in dose reconstructions performed for selected MPS sites and the approaches used to address those issues. The focus is on some foundational components of retrospective dose assessments that have received little attention in the literature. Methods: The discussion is built around illustrative exposure data and dose reconstructions for workers at selected facilities addressed in the MPS. Related findings at some non-MPS sites are also discussed. Results: Each of the following items has been found to be a major source of potential error in reconstructed tissue doses for some MPS sites: identification of all dosimetrically important internal emitters; the time pattern of intake; the mode(s) of intake; reliability of bioassay measurements; application of surrogate (coworker) information in lieu of, or in conjunction with, worker-specific monitoring data; the chemical and physical forms of inhaled radionuclide; and the relation of air monitoring data to actual intake. Conclusions: (1) Much of the dose reconstruction effort for internal emitters should be devoted to development of best feasible exposure scenarios. (2) Coworker data should be used to assign exposure scenarios or dose estimates to workers with missing exposure data only if there is compelling evidence of similar coworker exposure. (3) Bioassay data for some radionuclides and periods of operation at MPS sites are of questionable reliability due to sizable uncertainties associated with contamination, recovery, or background issues. (4) Dose estimates derived solely from air monitoring data should be treated as highly uncertain values in the absence of site-specific information demonstrating that the data are reasonably predictive of intake. (5) For intakes known or assumed to be via inhalation, the uncertainty in lung dose typically is much greater than the uncertainty in dose to systemic tissues, when dose estimates are based on urinary excretion data. (6) The lung dose estimate often can be improved through development of site-specific respiratory absorption parameter values. (7) There is generally insufficient site-specific information to justify development of site-specific systemic models.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2018

The Structure of Radiative Tunnel Recombination Sites in Emulsion Microcrystals of AgBr(I)

To identify the structure of emissive tunnel recombination sites in the emulsion microcrystals of silver bromide AgBr(I) with iodine contaminations and to determine the role of an emulsion medium in their formation, the temperature dependence of the luminescence spectra in the range from 77 to 120 K, the kinetics of the growth of the maximum luminescence intensity value at λ ≈ 560 nm, and the luminescence flash spectrum stimulated by the infrared light are investigated. Two types of the AgBr{sub 1–} {sub x}(I{sub x}) (x = 0.03) microcrystals—namely, obtained in an aqueous solution and on a gelatin substrate—are used in the studies. It is established that the emissive tunnel recombination sites with a luminescence maximum at λ ≈ 560 nm in AgBr{sub 1–} {sub x}(I{sub x}) (x = 0.03) are the {(I_a"-I_a"-)Ag_i"+} donor–acceptor complexes with the I{sub a}{sup -} iodine ions located in neighbor anionic sites of the AgBr(I) crystal lattice, next to which the Ag{sub i}{sup +} interstitial silver ion is positioned. With an increase in the temperature, the {(I_a"-I_a"-)Ag_i"+} sites undergo structural transformation into the {(I_a"-I_a"-)Ag_i_n"+} sites, where n = 2, 3, …. Moreover, the {(I_a"-I_a"-)Ag_i_n"+} sites (n = 2) after the capture of an electron and hole also provide the tunnel recombination with a luminescence maximum at λ ≈ 720 nm. The influence of an emulsion medium consists in that gelatin interacts with the surface electron-localization sites, i.e., the interstitial silver ions Ag{sub in}{sup +}, n = 1, 2, and forms the complexes {Ag_i_n"0 G"+} (n = 1, 2) with them. The latter are deeper electron traps with a small capture cross section as compared to the Ag{sub in}{sup +} sites (n = 1, 2) and that manifest themselves in that the kinetics of the luminescence growth in AgBr(I) to a stationary level at λ ≈ 560 nm is characterized by the presence of “flash firing.” At the same time, the luminescence flash stimulated by IR light, for which the Ag{sub in}{sup +}(n = 1, 2) electron-localization sites are responsible, is absent. It is supposed that the electrons localized on the {Ag_i_n"+G"+} complexes (n = 2) retain the capability for emissive tunnel recombination with holes localized on paired iodine sites with a luminescence maximum at λ ≈ 750 nm.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗