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Biosystems Design to Accelerate C 3 -to-CAM Progression

Global demand for food and bioenergy production has increased rapidly, while the area of arable land has been declining for decades due to damage caused by erosion, pollution, sea level rise, urban development, soil salinization, and water scarcity driven by global climate change. In order to overcome this conflict, there is an urgent need to adapt conventional agriculture to water-limited and hotter conditions with plant crop systems that display higher water-use efficiency (WUE). Crassulacean acid metabolism (CAM) species have substantially higher WUE than species performing C 3 or C 4 photosynthesis. CAM plants are derived from C 3 photosynthesis ancestors. However, it is extremely unlikely that the C 3 or C 4 crop plants would evolve rapidly into CAM photosynthesis without human intervention. Currently, there is growing interest in improving WUE through transferring CAM into C 3 crops. However, engineering a major metabolic plant pathway, like CAM, is challenging and requires a comprehensive deep understanding of the enzymatic reactions and regulatory networks in both C 3 and CAM photosynthesis, as well as overcoming physiometabolic limitations such as diurnal stomatal regulation. Recent advances in CAM evolutionary genomics research, genome editing, and synthetic biology have increased the likelihood of successful acceleration of C 3 -to-CAM progression. Here, we first summarize the systems biology-level understanding of the molecular processes in the CAM pathway. Then, we review the principles of CAM engineering in an evolutionary context. Lastly, we discuss the technical approaches to accelerate the C 3 -to-CAM transition in plants using synthetic biology toolboxes.

59 BASIC BIOLOGICAL SCIENCES↗

Thick filament activation is different in fast- and slow-twitch skeletal muscle

The contractile properties of fast-twitch and slow-twitch skeletal muscles are primarily determined by the myosin isoform content and modulated by a variety of sarcomere proteins. X-ray diffraction studies of regulatory mechanisms in muscle contraction have focused predominately on fast- or mixed-fibre muscle with slow muscle being much less studied. Here, we used time-resolved X-ray diffraction to investigate the dynamic behaviour of the myofilament proteins in relatively pure slow-twitch-fibre rat soleus (SOL) and pure fast-twitch-fibre rat extensor digitorum longus (EDL) muscle during twitch and tetanic contractions at optimal length. During twitch contractions the diffraction signatures indicating a transition in the myosin heads from ordered OFF states, where heads are held close to the thick filament backbone, to disordered ON states, where heads are free to bind to thin filaments, were found in EDL and not in SOL muscle. During tetanic contraction, changes in the disposition of myosin heads as active tension develops is a quasi-stepwise process in EDL muscle whereas in SOL muscle this relationship appears to be linear. The observed reduced extensibility of the thick filaments in SOL muscle as compared to EDL muscles indicates a molecular basis for this behaviour. These data indicate that for the EDL, thick filament activation is a cooperative strain-induced mechano-sensing mechanism, whereas for the SOL, thick filament activation has a more graded response. Further, these different approaches to thick filament regulation in fast- and slow-twitch muscles may be adaptations for short-duration, strong contractions versus sustained, finely controlled contractions, respectively.

59 BASIC BIOLOGICAL SCIENCES↗

Aquapv

This project brings together a multidisciplinary team to develop tools and analysis that will help U.S. industry accelerate deployment of floating PV on reservoirs and estuaries through producing: • A tool to assess potential environmental interactions of FPV on reservoirs and estuaries and thresholds for corresponding impacts. • A tailored FPV-specific techno-economic tool to guide users on financial performance and corresponding design considerations. • A synthesized tool, AquaPV, that combines the environmental and economic tools. • A set of case studies on an open-loop reservoir with a traditional hydropower plant (i.e., connected to a natural waterbody), closed-loop reservoir with a proposed pumped storage hydropower plant (i.e., manmade and disconnected from a natural waterbody), and a marine estuary (i.e., where a river meets the ocean), with an FPV system designed and modeled for each site. • A review of regulatory, environmental, and stakeholder opportunities and challenges to identify clear regulatory and environmental pathways to siting FPV on U.S. reservoirs. • A novel, high-fidelity geospatial resource assessment to estimate FPV technical potential on reservoirs in the United States.

Phillips, TylerB. [Idaho National Laboratory (INL)↗

Methods and Usability Enhancements in Shift for Non-LWR Applications

Several development and analysis tasks were undertaken in FY21 under the Nuclear Energy Advanced Modeling and Simulation program to enhance modeling of non light–water reactors (LWRs) with Shift. Specifically, these efforts targeted enhancements for tristructural isotropic (TRISO) fuel modeling. A new Shift user interface was developed that allows for much better usability and ease of modeling for non-LWR problems and TRISO fuel. Performance studies were conducted using an HTR-10 fuel pebble model by comparing different geometry packages in Shift, KENO-VI, and Serpent. These studies showed that the new geometry package in Shift performs well compared to Serpent for TRISO fuel modeling with consistent tracking options between both packages. The studies also identified the most critical areas of improvement for more efficiently performing Monte Carlo transport on TRISO fuel models with Shift. Tally calculations in Shift were optimized for non-LWR cross section generation and depletion calculations, and areas for further optimization and accuracy improvements were identified. Finally, initial collaboration efforts were formed between Idaho National Laboratory, Argonne National Laboratory, and the Nuclear Regulatory Commission to use Shift for Comprehensive Reactor Analysis Bundle support.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Addressing Regulatory Challenges to Tribal Solar Deployment: Preprint

Although Tribal land represents more than 5% of the solar photovoltaic technical potential in the United States, this resource is largely untapped due to a range of barriers, including complex project economics, Tribal technical and human resource capacity, project funding and financing obstacles, and regulatory challenges. To identify and better understand the regulatory barriers, the National Renewable Energy Laboratory (NREL) and the Midwest Tribal Energy Resources Association (MTERA) engaged Tribes, utilities, and regulators. Funded by the U.S. Department of Energy, the 3-year effort seeks to address regulatory challenges or barriers that affect Tribal solar projects differently - specifically or disproportionately because they are located on Tribal lands. This paper, largely excerpted from a comprehensive (draft) guidebook released by NREL and MTERA, provides an overview of 13 key regulatory barriers identified through this research, as well as potential short- and long-term solutions. In addition, the paper points to potential pathways for addressing key barriers through case studies highlighting successful Tribal solar projects along with considerations for stakeholders working with Tribes. These resources can support stakeholders in creating meaningful relationships and pursuing workable solar projects.

ENERGY PLANNING, POLICY, AND ECONOMY,SOLAR ENERGY↗

State Energy Justice Roundtable Series: Energy Justice Metrics

The National Association of Regulatory Utility Commissioners (NARUC), National Association of State Energy Officials (NASEO), and National Governors Association (NGA) hosted a State Energy Justice Roundtable (Roundtable) in April 2022. Participants included federal and state decision-makers, members of community-based organizations, and subject-matter experts. The Roundtable members explored current state efforts to articulate and incorporate energy justice concerns into energy-related decision-making. Participants established connections with one another to better understand the current landscape of existing resources, learn about emerging efforts, and identify ongoing support opportunities for advancing energy justice.This paper is one of five authored by the host organizations on topics that were the focus of the Roundtable. Each paper summarizes key themes, emerging efforts, and group takeaways that were discussed at the Roundtable and should assist state members in developing and meeting their own state goals around energy justice. The papers all include the same discussions of background, introduction, and reading list so they can be read separately. Each paper is written from the perspective of one association and includes options for its members to take actions that could support more equitable state energy policies and programs. The five papers cover: (1) Participation in decision making (NARUC), (2) Customer affordability and arrearages (NARUC), (3) Energy justice metrics (NARUC), (4) Equity in clean energy research and development (NASEO), and (5) Equitable distributed energy resource (DER) access (NGA). The resources and recommendations listed in these papers are not meant to be exhaustive, as this field of study continues to evolve. Although this brief is focused on electricity, energy justice considerations extend to all energy needs and services, including the impact of energy extraction, processing, and distribution functions.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Cyber Resilience and Social Equity: Twin Pillars of a Sustainable Energy Future

This paper examines the intersection of security and accessibility within energy systems amidst the rise of grid modernization and digitization, especially considering the regulatory changes and the imperatives of inclusive energy strategies. It addresses the dual need for secure, resilient infrastructure and a commitment to mitigate energy poverty while maintaining equitable access to energy. Amid escalating cybersecurity and physical threats, the paper advocates for sustainable energy delivery systems that ensure robust defenses without compromising the goals of reducing energy poverty and ensuring energy security. This paper identifies the pressing need for Cyber-Informed Engineering (CIE) and Secure-by-Design (SbD) principles, highlighting how these strategies can protect critical infrastructure and democratize access to secure energy, particularly for disadvantaged communities. The analysis underscores the challenges presented by the expansion of attack surfaces, interoperability requirements, and grid-edge analytics, offering innovative solutions that leverage advanced technologies and data-driven insights. Furthermore, this paper addresses the workforce development gap, emphasizing the necessity for public-private partnerships and vendor engagement in creating a skilled cybersecurity workforce. This paper has a dual focus on both the technological aspect of cybersecurity and the social dimension of equity within the context of sustainable energy development. It suggests a comprehensive examination of how these two critical elements interact and support the overarching goal of a sustainable energy future.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Zero Emission Cargo Transport (ZECT) II Demonstration: South Coast Air Quality Management District (Final Report)

The South Coast Air Quality Management District (South Coast AQMD), California Air Resources Board (CARB) and Southern California Association of Governments (SCAG) — the agencies responsible for preparing the State Implementation Plan required under the federal Clean Air Act — have agreed that attainment of federal air quality standards for the region will require a transition to the broad use of zero and near-zero emission energy sources in cars, trucks and other equipment. Accordingly, the 2012 South Coast AQMD Air Quality Management Plan, the SCAG 2012 Regional Transportation Plan, and the “Vision for Clean Air: A Framework for Air Quality and Climate Control Planning” all identify the need to immediately enact a phasing in of zero and near-zero emission technologies to meet air quality goals. In 2014, South Coast AQMD was awarded grant funding under the US Department of Energy Zero Emission Cargo Transport (ZECT) II Demonstration program to develop and demonstrate zero-emission drayage trucks for goods movement operations between the Port of Los Angeles (POLA) and Port of Long Beach (POLB) near dock rail yards and warehouses: 1) development and demonstration of zero-emission fuel cell range extended electric drayage trucks and 2) development and demonstration of hybrid electric drayage trucks. The purpose of this project was to accelerate deployment of zero emission cargo transport technologies to reduce harmful diesel emissions, petroleum consumption and greenhouse gases in the surrounding communities along the goods movement corridors that are impacted by heavy diesel traffic and the associated air pollution. Between 2014 – 2024, six ZECT II zero-emission fuel cell drayage truck platforms, including fuel cell range extended and CNG hybrid trucks, were successfully designed, developed, integrated, built, tested, and demonstrated with drayage fleet operators in transportation corridors within areas of the South Coast AQMD jurisdiction in Southern California such as in and around POLA and POLB. Portable hydrogen refueling was deployed to support the fuel cell vehicles. The project had real-time improvement with on-going debugging and optimizations while the vehicles were under demonstration. All platforms demonstrated sufficient or excess power, torque, and energy to support 82,000lbs Gross Vehicle Weight Rating and gradeability to perform their daily duty cycles. Collectively, the trucks drove over 23,000 miles during their respective demonstration phases. The ZECT II project was the first of its kind to demonstrate the commercial viability that supported the additional technology breakthroughs for Class 8 zero emission trucks and validations as well as the regulatory basis for all the zero-emission regulation that we know today, such as the Innovative Clean Transit regulation, Advanced Clean Trucks and Clean Fleet regulations.

08 HYDROGEN↗

The F-box protein gene exo-1 is a target for reverse engineering enzyme hypersecretion in filamentous fungi

Carbohydrate active enzymes (CAZymes) are vital for the lignocellulose-based biorefinery. The development of hypersecreting fungal protein production hosts is therefore a major aim for both academia and industry. However, despite advances in our understanding of their regulation, the number of promising candidate genes for targeted strain engineering remains limited. Here, we resequenced the genome of the classical hypersecreting Neurospora crassa mutant exo-1 and identified the causative point of mutation to reside in the F-box protein–encoding gene, NCU09899. The corresponding deletion strain displayed amylase and invertase activities exceeding those of the carbon catabolite derepressed strain ?cre-1, while glucose repression was still mostly functional in ?exo-1. Surprisingly, RNA sequencing revealed that while plant cell wall degradation genes are broadly misexpressed in ?exo-1, only a small fraction of CAZyme genes and sugar transporters are up-regulated, indicating that EXO-1 affects specific regulatory factors. Aiming to elucidate the underlying mechanism of enzyme hypersecretion, we found the high secretion of amylases and invertase in ?exo-1 to be completely dependent on the transcriptional regulator COL-26. Furthermore, misregulation of COL-26, CRE-1, and cellular carbon and nitrogen metabolism was confirmed by proteomics. Finally, we successfully transferred the hypersecretion trait of the exo-1 disruption by reverse engineering into the industrially deployed fungus Myceliophthora thermophila using CRISPR-Cas9. Our identification of an important F-box protein demonstrates the strength of classical mutants combined with next-generation sequencing to uncover unanticipated candidates for engineering. These data contribute to a more complete understanding of CAZyme regulation and will facilitate targeted engineering of hypersecretion in further organisms of interest.

Gabriel, Raphael↗

Using Systems Theoretic Process Analysis and Causal Analysis to Map and Manage Organizational Information to Enable Digitalization and Information Automation

The overarching goal of this Light Water Reactor Sustainability Program–supported research and development project is to provide planning tools and comprehensive guidance to utilities considering or undertaking full nuclear plant modernization. The results of this research will provide the nuclear industry with a comprehensive and usable solution, including guidance, lessons learned, methods, and planning tools. This research is currently working to provide guidance on digitalization and information automation to enable the evolution of data to information, insight, and action—thereby allowing utilities to operate safely and cost-competitively with all other electrical generation sources. Light Water Reactor Sustainability Program researchers have also recently started investigating how human and technology integration principles, information automation, and digitalization enable data evolution. These researchers are currently in the process of validating the use of System-Theoretic Process Analysis to define high-level safety constraints in the United States Nuclear Regulatory Commission’s problem identification and resolution process (i.e., a plant compliance information gathering activity). The next step in this research, which is described in the following sections of this report, is to map out data evolution in a use case to identify inefficiencies in another aspect of plant compliance information gathering and communication activities—event investigations and root cause analyses.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

State Energy Justice Roundtable Series: Customer Affordability and Arrearages

The National Association of Regulatory Utility Commissioners (NARUC), National Association of State Energy Officials (NASEO), and National Governors Association (NGA) hosted a State Energy Justice Roundtable (Roundtable) in April 2022. Participants included federal and state decision-makers, members of community-based organizations, and subject-matter experts. The Roundtable members explored current state efforts to articulate and incorporate energy justice concerns into energy-related decision-making. Participants established connections with one another to better understand the current landscape of existing resources, learn about emerging efforts, and identify ongoing support opportunities for advancing energy justice. This paper is one of five authored by the host organizations on topics that were the focus of the Roundtable. Each paper summarizes key themes, emerging efforts, and group takeaways that were discussed at the Roundtable and should assist state members in developing and meeting their own state goals around energy justice. The papers all include the same discussions of background, introduction, and reading list so they can be read separately. Each paper is written from the perspective of one association and includes options for its members to take actions that could support more equitable state energy policies and programs. The five papers cover: (1) Participation in decision making (NARUC) (2) Customer affordability and arrearages (NARUC) (3) Energy justice metrics (NARUC) (4) Equity in clean energy research and development (NASEO) (5) Equitable distributed energy resource (DER) access (NGA). The resources and recommendations listed in these papers are not meant to be exhaustive, as this field of study continues to evolve. Although this brief is focused on electricity, energy justice considerations extend to all energy needs and services, including the impact of energy extraction, processing, and distribution functions.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

State Energy Justice Roundtable Series: Participation in Decision Making

The National Association of Regulatory Utility Commissioners (NARUC), National Association of State Energy Officials (NASEO), and National Governors Association (NGA) hosted a State Energy Justice Roundtable (Roundtable) in April 2022. Participants included federal and state decision-makers, members of community-based organizations, and subject-matter experts. The Roundtable members explored current state efforts to articulate and incorporate energy justice concerns into energy-related decision-making. Participants established connections with one another to better understand the current landscape of existing resources, learn about emerging efforts, and identify ongoing support opportunities for advancing energy justice. This paper is one of five authored by the host organizations on topics that were the focus of the Roundtable. Each paper summarizes key themes, emerging efforts, and group takeaways that were discussed at the Roundtable and should assist state members in developing and meeting their own state goals around energy justice. The papers all include the same discussions of background, introduction, and reading list so they can be read separately. Each paper is written from the perspective of one association and includes options for its members to take actions that could support more equitable state energy policies and programs. The five papers cover: • Participation in decision making (NARUC) • Customer affordability and arrearages (NARUC) • Energy justice metrics (NARUC) • Equity in clean energy research and development (NASEO) • Equitable distributed energy resource (DER) access (NGA). The resources and recommendations listed in these papers are not meant to be exhaustive, as this field of study continues to evolve. Although this brief is focused on electricity, energy justice considerations extend to all energy needs and services, including the impact of energy extraction, processing, and distribution functions.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Assessment of CASL VERA for BWR analysis and application to accident tolerant SiC/SiC channel box

Application of the Virtual Environment for Reactor Applications (VERA) to BWR analysis is assessed in this paper by comparing results to those calculated using other widely-used modeling tools, namely the U.S. Nuclear Regulatory Commission’s PARCS/PATHS and the Serpent Monte Carlo particle transport code. Additionally, VERA is used to calculate 3-D temperature and fast neutron flux distributions in silicon carbide (SiC) fiber-reinforced, SiC matrix composite (SiC/SiC) BWR channel boxes, which are being studied as an Accident Tolerant Fuel core structural material concept. We found that the code-to-code comparisons were favorable, and the SiC/SiC channel box evaluation demonstrates the many advanced modeling features VERA provides while also highlighting the non-uniformity in fast neutron flux distributions that can play a role in potential SiC/SiC channel box deformation. Traditional BWR analysis tools do not have the calculation fidelity necessary for coupled assessment of flux and temperature gradients in a SiC/SiC channel box. VERA is a state-of-the-art modeling environment that was developed to increase the safety and economic competitiveness of nuclear power through improved modeling accuracy. While VERA has already been deployed in the nuclear industry for PWR applications, the current study is a vital initial step in the extensive development, validation, and verification that VERA must go through to be useful for BWR applications.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Small Nuclear Reactors for Maritime Ports

Maritime ports are entering a period of sharply rising electricity demand as operations are electrified, shore power adoption grows, and energy-intensive industries expand near ports. This report evaluates the feasibility of small nuclear reactors at U.S. ports, which could offer stable baseload power and reduced dependence on regional grids. The report describes the current state of advanced reactor technologies and other factors important for future deployment such as safety and operations, siting requirements, regulatory environments and policy, and other co-benefit considerations. A structured evaluation across a diverse group of U.S. ports highlights the wide variation in feasibility. Fifteen ports were analyzed through port interviews and data collection to assess the port-specific conditions that most impact advanced reactor deployment. The analysis found that the most feasible ports for deployment have favorable geotechnical stability, supportive regulatory environments, and substantial energy loads in a grid-constrained environment. Additionally, an initial reactor size matching was done for the ports based on their reported energy consumption across different modes of operation. However, further analysis and detailed data will be required in the future to determine the optimal reactor-port matching. The economic viability to adopt this technology will be dictated by competitive cost of nuclear-generated electricity compared to other alternatives. Overall, small nuclear reactors present a promising but highly site-dependent pathway for ports seeking resilient, high-capacity energy solutions that support future energy demands. This report identifies key areas for future research and highlights ports that warrant further evaluation to assess the viability of small nuclear reactor implementation. By establishing these priorities, the analysis provides support for the development of informed strategies for potential advanced nuclear technology deployment. The inclusion of ports in this report does not imply their endorsement of nuclear energy generation, and the authors are grateful for the information, expertise, and perspectives they contributed.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Natural Language Processing for Text Based Event Extraction: Identifying Events of Interest Related to Worldwide State-Sponsored Civil Nuclear Power

Beginning in FY20, SRNL was funded by the National Nuclear Security Administration’s Office of Defense Nuclear Non-Proliferation Research and Development to develop a prototype natural language processing/natural language understating machine learning-based modeling and analysis pipeline to extract and forecast events of interest from massive open data sources. The working hypothesis within the approach is that contextual shifts in key words and phrases act as indicators of events of interest over time. Therefore, by identifying points in time where contextual shifts occur, events of interest can be extracted along with explicit and implicit connections of entities and activities. The development of the preliminary prototype pipeline proved successful, meriting further testing of the pipeline on more broad topical domains and in a worldwide data environment. Therefore, SRNL, in collaboration with the Sanghani Center for Artificial Intelligence and Data Analytics at Virginia Tech, have continued development with a test case of identifying events of interest related to worldwide state-sponsored civil nuclear power in open data sources. In the first year of this follow-on effort, the team has curated domain-specific data corpuses using an automated scheme and applied the modeling and analysis pipeline. This robust, focused, and efficient approach consists of an ensemble of analyses applied to time dependent word embedding models that are trained on the data corpuses. In this report, the team has demonstrated the capability of the existing pipeline (as development has continued in parallel) by exploring several specific case-studies centered around Rosatom’s international activities regarding the planning, construction, operation, and/or shutdown of nuclear reactors. A basic timeline events has been generated by manually cataloging known “milestone” events that have occurred at reactors in Turkey, Finland, Hungary, and Egypt and compared with the output of the modeling pipeline. In this approach, the team has characterized the lead time using the prototype pipeline, as well as the ability to capture relevant information, which proved 100% successful. A deep dive example of the Akkuyu reactor (Turkey) is presented that shows the breadth of information that can be captured using the approach. In this case study, events were extracted pertaining to the planning/construction of Akkuyu including protests from the population, information campaigns in response to the protests, forged regulatory documents and lawsuits, budgetary/shareholder information, geopolitical tensions, and the various construction milestones. This has demonstrated the pipeline’s utility as a research aid or real-time event extraction tool, where summary-level information and detailed text extractions from millions of articles or Tweets across long time periods can be generated with significantly less effort than current techniques.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Homoeolog expression divergence contributes to time of day changes in transcriptomic and glucosinolate responses to prolonged water limitation in Brassica napus

SUMMARY Water availability is a major determinant of crop production, and rising temperatures from climate change are leading to more extreme droughts. To combat the effects of climate change on crop yields, we need to develop varieties that are more tolerant to water‐limited conditions. We aimed to determine how diverse crop types (winter/spring oilseed, tuberous, and leafy) of the allopolyploid Brassica napus , a species that contains the economically important rapeseed oilseed crop, respond to prolonged water limitation. We exposed plants to an 80% reduction in water and assessed growth and color on a high‐throughput phenotyping system over 4 weeks and ended the experiment with tissue collection for a time course transcriptomic study. We found an overall reduction in growth across cultivars but to varying degrees. Diel transcriptome analyses revealed significant accession‐specific changes in time‐of‐day regulation of photosynthesis, carbohydrate metabolism, and sulfur metabolism. Interestingly, there was extensive variation in which homoeologs from the two parental subgenomes responded to water limitation across crop types that could be due to differences in regulatory regions in these allopolyploid lines. Follow‐up experiments on select cultivars confirmed that plants maintained photosynthetic health during the prolonged water limitation while slowing growth. In two cultivars examined, we found significant time of day changes in levels of glucosinolates, sulfur‐ and nitrogen ‐rich specialized metabolites, consistent with the diel transcriptomic responses. These results suggest that these lines are adjusting their sulfur and nitrogen stores under water‐limited conditions through distinct time of day regulation.

Ricono, Angela [University of Minnesota St. Paul M↗

Pacific Northwest National Laboratory Facility Radionuclide Emission Points and Sampling Systems

Battelle–Pacific Northwest Division operates numerous research and development laboratories in Washington State. The U.S. Department of Energy (DOE) contracts to Battelle at Richland facilities on both the DOE Hanford Site and the Pacific Northwest National Laboratory (PNNL) Richland campus. These facilities have the potential for radionuclide air emissions. The PNNL contract with DOE also includes operations at the PNNL-Sequim campus in Sequim, where there is also the potential for radionuclide air emissions. This document is a periodic update that describes current PNNL facility emission units and sampling systems. The National Emission Standard for Hazardous Air Pollutants (NESHAP [40 Code of Federal Regulations 61, Subpart H]) requires an assessment of all emission units that have the potential for radionuclide air emissions. Emission units are registered with the State of Washington. Potential emissions from emission units are assessed annually by PNNL staff. Sampling, monitoring, and other regulatory compliance requirements are designated based on the potential to-emit dose criteria, a graded approach to facility-identified potential impact categories, and regulatory requirements. The purpose of this document is to describe the facility radionuclide air emission sampling program and provide current and historical facility emission unit system performance, operation, and design information. For sampled emission units, the building, exhaust unit, control technologies, and sample extraction details are provided. Additionally, applicable configuration drawings, figures, and photographs are included. For non-sampled emission units, emission estimation and radionuclide source details are provided. Site-wide permits for the lowest potential impact category are described. Deregistered/transitioned emission unit details are also provided as necessary for at least 5 years post-closure/transition. Currently, five emission units are sampled continuously for particulate radionuclides at PNNL managed facilities on the PNNL-Richland campus (3 of the 5) and on the Hanford Site (2 of the 5). Four of these units have sampling systems that comply with the American National Standards Institute/Health Physics Society (ANSI/HPS) N13.1–2011 standard for sampling from stacks and ducts of nuclear facilities, and the fifth is grandfathered and compliant with the older ANSI N13.1–1969 standard. In addition, the PNNL-managed Hanford Site 325 Building EP 325-01-S stack is sampled continuously for emissions of tritium. No emissions sampling is required for the single licensed emission unit on the PNNL-Sequim campus.

54 ENVIRONMENTAL SCIENCES↗

Comparison of Routes of Administration, Frequency, and Duration of Favipiravir Treatment in Mouse and Guinea Pig Models of Ebola Virus Disease

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013–2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.

60 APPLIED LIFE SCIENCES↗