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DOE OSTI2025

National User Resource for Biological Accelerator Mass Spectrometry (Final Report)

The National User Resource for Biological Accelerator Mass Spectrometry (User Resource) will provide isotopic analysis (primarily radiocarbon or 14C) by accelerator mass spectrometry (AMS) for NIH- funded researchers across the United States and will be the only User Resource of its type in the United States. The User Resource will provide measurement capability and expertise to a research community that requires highly sensitive, quantitative isotope analyses. Since commissioning a new accelerator mass spectrometer in June 2014, we have measured over 4000 samples a year for collaborators and service users. The User Resource will enable us to continue to meet these research needs, as well as provide for new users whose research programs would benefit from AMS as a measurement tool. The User Resource’s forte will be ultra-high sensitivity quantitation of radiocarbon and selected other radioisotopes for research studies where isotopes are required. Radioisotope labeling studies have been and will continue to be an important tool for addressing many complex biomedical science problems. AMS is a specialized and unique type of mass spectrometry that provides absolute quantitation of radiocarbon and other relevant radioisotopes with extreme sensitivity, having limits of detection in real samples on the order of a few attomol/mg of sample at measurement precisions of ~3%. It is the only instrumental method capable of quantifying radioisotope-labeled agents routinely in real-world samples with such precision and sensitivity. The sensitivity of AMS allows for the quantification of radiolabeled metabolites in extremely complex matrices of cells and organisms at very low concentrations and in small samples. AMS allows studies to be conducted without perturbing metabolism leading to more relevant quantification of metabolic rates and pathways. In addition, it enables quantification of pharmacokinetic and metabolic properties of toxicants at environmentally relevant concentrations in model systems as well as the ability to quantify pharmacokinetics and other molecular endpoints directly in humans. Such quantitative assessments can 1) improve risk assessment for toxicants, 2) address safety and efficacy considerations for therapeutic entities, 3) deepen understanding of xenobiotic and intermediary metabolism, 4) help understand the interactions between critical molecular pathways, and 5) improve efforts to model and predict various metabolic and biological states. These capabilities have been applied in a number of areas including research in carcinogenesis, toxicology, nutrition, pharmacology/drug development and basic biological science. As a NIGMS National Resource the National User Resource for Biological Accelerator Mass Spectrometry will help NIH funded scientists achieve a deeper understanding of the etiology of human health concerns by (1) enabling the quantification of pharmacokinetics and other molecular endpoints directly in humans; (2) offering the ability to conduct quantitative studies using biologics such as proteins or lipids, and thereby reducing the amount of radioisotope usage in biomedical labs; and (3) enabling more relevant studies of metabolic pathways in health and disease through the use of much lower, more biologically-relevant, concentrations of metabolic substrates in cells and intact organisms. Such studies support NIGMS’s basic biomedical research areas that contribute to the understanding of fundamental cellular and physiological principles and enable research supported by the Biophysics, Biomedical Technology, and Computational Biosciences (BBCB); Genetics and Molecular, Cellular, and Developmental Biology (GMCDB); Pharmacology, Physiology, Biological Chemistry (PPBC) and Training, Workforce Development, and Diversity (TWD) Divisions. Over the next five years, our goals are to: 1. Improve the efficiency of operation for AMS measurements through installation of new interfaces to our AMS systems, technical modifications to improve gas accepting ion source efficiency and upgrading our data analysis software for improved ease of use and data reporting. 2. Increase the accessibility and visibility of ultra-sensitive 14C measurements for the biomedical research community by training of new investigators and expanding our national user base. 3. Provide high throughput, ultra-sensitive 14C analysis for the NIGMS and NIH user community.

47 OTHER INSTRUMENTATION↗

DOE OSTI2026

YAP1 Dysfunction Promotes Molecular Properties Linked to Breast Cancer Susceptibility

YAP1 is a cotranscription factor that promotes malignant and stem cell properties in cancer. We previously found that YAP1 dysregulation is associated with aging in human mammary epithelia. With increased age, YAP1 expression changes in luminal epithelial cells, the prospective breast cancer cell of origin. Because age is a significant risk factor for breast cancer, we tested whether YAP1 dysregulation acted early in cancer progression by conferring cellular states associated with increased cancer susceptibility. In this study, we find that with increased age and genetic risk for developing cancer, human breast tissues showed significantly increased YAP1 expression, and cultured primary human mammary epithelial cells (HMEC) showed significantly increased expression of both YAP1 and its transcriptional targets. Increased YAP1 expression in cultured HMEC induced gene expression changes associated with increased cancer susceptibility, such as genes associated with stem cell states, increased telomerase activity, breast cancer progression, and increased age and genetic breast cancer risk. Furthermore, overexpression of YAP1 in post-stasis HMEC—finite lifespan cells that have bypassed a retinoblastoma-mediated senescence barrier—promoted properties related to increased growth potential. We found that YAP1 dysregulation in finite epithelial cells allows for access to gene programs and functions that are typically thought to be restricted to stem cells. We hypothesize that YAP1 acts early in breast cancer progression, long before the development of a tumor, to impose cancer-susceptible molecular states.

YAP1↗

DOE OSTI2025

Mondo: integrating disease terminology across communities

Precision medicine aims to enhance diagnosis, treatment, and prognosis by integrating multimodal data at the point of care. However, challenges arise due to the vast number of diseases, differing methods of classification, and conflicting terminological coding systems and practices used to represent molecular definitions of disease. This lack of interoperability artificially constrains the potential for diagnosis, clinical decision support, care outcome analysis, as well as data linkage across research domains to support the development or repurposing of therapeutics. There is a clear and pressing need for a unified system for managing disease entities⁠—including identifiers, synonyms, and definitions. To address these issues, we created the Mondo disease ontology—a community-driven, open-source, unified disease classification system that harmonizes diverse terminologies into a consistent, computable framework. Mondo integrates key medical and biomedical terminologies, including Online Mendelian Inheritance in Man (OMIM), Orphanet, Medical Subject Headings (MeSH), National Cancer Institute Thesaurus (NCIt), and more, to provide a comprehensive and accurate representation of disease concepts with fully provenanced and attributed links back to the sources. Mondo can be used as the handle for curation of gene–disease associations utilized in diagnostic applications, research applications such as computational phenotyping, and in clinical coding systems in clinical decision support by pointing the clinician to the numerous knowledge resources linked to the Mondo identifier. Mondo's community-centric approach, stewarded by the Monarch Initiative's expertise in ontologies, ensures that the ontology remains adaptable to the evolving needs of biomedical research and clinical communities, as well as the knowledge providers.

biomedical informatics↗

DOE OSTI2025

Emerging Per- and Polyfluoroalkyl Substances in Tap Water from the American Healthy Homes Survey II

Humans experience widespread exposure to anthropogenic per- and polyfluoroalkyl substances (PFAS) through various media, which can lead to a wide range of negative health impacts. Tap water is an important source of exposure in communities with any degree of contamination but routine or large-scale PFAS monitoring often depends on targeted analytical methods limited to measuring specific PFAS. We analyzed 680 tap water samples from the American Healthy Homes Survey II for PFAS using non-targeted analysis (NTA) to expand the range of detectable PFAS. Based on detection frequency and relative abundance, about half of the identified PFAS were found only by NTA. We identified (with varying degrees of confidence) 75 distinct PFAS, including 57 exclusively detected by NTA. The identified PFAS are members of seven structural subclasses differentiated by their head groups and degree of fluorination. Clustering analysis categorized the PFAS into four coabundance groups dominated by specific PFAS subclasses. One group uniquely identified by NTA contains zwitterionic PFAS and other PFAS transformation products which are likely associated with aqueous firefighting foam contaminants in a small number of spatially correlated samples. These results help further characterize the scope of exposure to emerging PFAS experienced by the U.S. population via tap water and augment nationwide targeted-PFAS monitoring programs.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI1995

Nuclear Safety [Vol. 36, No. 2, July-December 1995]

Nuclear Safety is a journal that covers significant issues in the field of nuclear safety. Its primary scope is safety in the design, construction, operation, and decommissioning of nuclear power reactors worldwide and the research and analysis activities that promote this goal, but it also encompasses the safety aspects of the entire nuclear fuel cycle, including fuel fabrication, spent-fuel processing and handling, and nuclear waste disposal, the handling of fissionable materials and radioisotopes, and the environmental effects of all these activities. Table of Contents for this issue follows. THE CHORNOBYL ACCIDENT: 195 The Chornobyl Accident Revisited, Part III: Chernobyl Source Term Release Dynamics and Reconstruction of Events During the Active Phase, A. R. Sich; GENERAL SAFETY CONSIDERATIONS: 218 Second ANS Workshop on the Safety of Soviet-Designed Nuclear Power Plants, R. A. Bari; 234 Elements of a Nuclear Criticality Safety Program, C. M. Hopper; 243 Rickover, Excellence, and Criticality Safety Programs, R. E. Wilson; ACCIDENT ANALYSIS: 249 Transient Analysis of the PIUS Advanced Reactor Design with the TRAC-PF1/MOD2 Code, B. E. Boyack, J. L Steiner, S. C. Harmony, H. J. Stumpf, and J. F. Lime; 278 The Hierarchy-By-Interval Approach to Identifying Important Models that Need Improvement in Severe-Accident Simulation Codes, T. J. Heames, M. Khatib-Rahbar, J. E. Kelly, R. P. Jenks-Johnson, and Y.-S. Chen; 290 RELAP5/MOD3 Code Coupling Model, R. P. Martin; 299 Missiles Caused by Severe Pressurized-Water Reactor Accidents, R. Krieg; DESIGN FEATURES: 310 Validation of COMMIX with Westinghouse AP-600 PCCS Test Data, J. G. Sun, T. H. Chien, J. Ding, and W T. Sha; ENVIRONMENTAL EFFECTS: 321 Spent Nuclear Fuel Characterization for a Bounding Reference Assembly for the Receiving Basin for Off-Site Fuel, S. D. Kahook, R. L. Garrett, L. R. Canas, and M J. Beckum; OPERATING EXPERIENCES: 332 Reactor Shutdown Experience, Compiled by J. W. Cletcher; U.S. NUCLEAR REGULATORY COMMISSION INFORMATION AND ANALYSES: 335 Reactor Coolant System Blowdown at Wolf Creek on September 17, 1994, J. V. Kauffman and S. L. Israel; RECENT DEVELOPMENTS: 344 Reports, Standards, and Safety Guides, D. S. Oueener; 349 Proposed Rule Changes as of June 30, 1995; ANNOUNCEMENTS: 320 Symposium on Acceptability of Risk From Radiation—Application to Manned Space Flight; 320 24th DOE/NRC Nuclear Air Cleaning and Treatment Conference; 361 Radiation Biology and Radiation Protection— Modern Developments and Tendencies in Radiation Biology; 362 1997 IEEE Sixth Conference on Human Factors and Power Plants; 354 The Authors; 360 Reviewers of Nuclear Safety, Vol. 36.

05 NUCLEAR FUELS↗

DOE OSTI1995

Nuclear Safety [Vol. 36, No. 2, July-December 1995]

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

DOE OSTI2025

Phenotypically anchored transcriptomics across diverse agrichemicals reveals conserved pathways and unique gene expression signatures in zebrafish

Agrichemicals such as herbicides, fungicides, insecticides, and biocides are widely used in agriculture, yet some are associated with adverse effects in humans and the environment. While many of these chemicals have been extensively studied in vitro and are included in the EPA’s ToxCast program, comprehensive in vivo comparisons using RNA sequencing across structurally diverse agrichemicals, in a single screening platform, are lacking. In this study, we examined structurally diverse agrichemicals found in the U.S. Environmental Protection Agency’s (EPA) Toxcast Phase I and II library by statically exposing early life stage zebrafish at 6 h post fertilization (hpf) until 120 hpf at concentrations ranging from 0.25 to 100 µM. Morphological outcomes were assessed at 120 hpf across 10 endpoints, including yolk sac edema, craniofacial malformations, and axis abnormalities. Chemicals that produced robust concentration-response relationships were selected for transcriptomic profiling. For transcriptomic analysis, zebrafish were statically exposed to each chemical and sampled at 48 hpf, prior to the onset of morphological effects observed at 120 hpf. Differential expression analysis identified between 0 and 4,538 differentially expressed genes (DEGs) per chemical, with no clear correlation to morphological severity. Both DEG and co-expression network analyses revealed chemical-specific expression patterns that converged on shared biological pathways, including neurodevelopment and cytoskeletal organization. Key regulatory genes such as mylpfa and krt4 were identified within co-expression modules, suggesting their potential role in conserved toxicity mechanisms. Semantic similarity analysis of enriched gene ontology (GO) terms, when compared to existing datasets, highlighted gaps in the annotation of neurodevelopmental processes, indicating that some in vivo effects may not be fully captured by current curated resources. The results provide new insights into the modes of action of diverse agrichemicals and establish a framework for understanding how agrichemical structure relates to biological function in a vertebrate model.

agrichemical↗

DOE OSTI2025

Advancing ocean monitoring and knowledge for societal benefit: the urgency to expand Argo to OneArgo by 2030

The ocean plays an essential role in regulating Earth’s climate, influencing weather conditions, providing sustenance for large populations, moderating anthropogenic climate change, encompassing massive biodiversity, and sustaining the global economy. Human activities are changing the oceans, stressing ocean health, threatening the critical services the ocean provides to society, with significant consequences for human well-being and safety, and economic prosperity. Effective and sustainable monitoring of the physical, biogeochemical state and ecosystem structure of the ocean, to enable climate adaptation, carbon management and sustainable marine resource management is urgently needed. The Argo program, a cornerstone of the Global Ocean Observing System (GOOS), has revolutionized ocean observation by providing real-time, freely accessible global temperature and salinity data of the upper 2,000m of the ocean (Core Argo) using cost-effective simple robotics. For the past 25 years, Argo data have underpinned many ocean, climate and weather forecasting services, playing a fundamental role in safeguarding goods and lives. Argo data have enabled clearer assessments of ocean warming, sea level change and underlying driving processes, as well as scientific breakthroughs while supporting public awareness and education. Building on Argo’s success, OneArgo aims to greatly expand Argo’s capabilities by 2030, expanding to full-ocean depth, collecting biogeochemical parameters, and observing the rapidly changing polar regions. Providing a synergistic subsurface and global extension to several key space-based Earth Observation missions and GOOS components, OneArgo will enable biogeochemical and ecosystem forecasting and new long-term climate predictions for which the deep ocean is a key component. Driving forward a revolution in our understanding of marine ecosystems and the poorly-measured polar and deep oceans, OneArgo will be instrumental to assess sea level change, ocean carbon fluxes, acidification and deoxygenation. Emerging OneArgo applications include new views of ocean mixing, ocean bathymetry and sediment transport, and ecosystem resilience assessment. Implementing OneArgo requires about $100 million annually, a significant increase compared to present Argo funding. OneArgo is a strategic and cost-effective investment which will provide decision-makers, in both government and industry, with the critical knowledge needed to navigate the present and future environmental challenges, and safeguard both the ocean and human wellbeing for generations to come.

ARGO↗

DOE OSTI2026

Aligning NASA Earth Science Data Stewardship with FAIR Principles: Outcomes, Recommendations, and Future Directions

The FAIR Principles—Findable, Accessible, Interoperable, and Reusable—offer a widely accepted framework for improving the sharing and reuse of digital scientific data by both human and machine users. Following these principles is critical for effective scientific data stewardship, broader scientific collaboration, and compliance with federal and agency data policies. This paper, based on the work of NASA’s Open, Free, and FAIR Working Group (O’FAIR WG) under the Earth Science Data Systems Program, presents an overview of how FAIR is being applied within NASA’s Earth science data landscape. It highlights ongoing progress and challenges, identifies FAIR-enabling resources, and offers recommendations and strategic actions to enhance the FAIRness of NASA-funded open and free Earth science data products. The FAIR-enabling resources identified underscore the vital role of NASA's existing enterprise processes, standards, tools, and infrastructures in supporting FAIR implementation. Our findings show strong performance in making NASA Earth science data more findable and accessible. However, further work is needed—especially in enhancing interoperability, so that different systems and tools can better understand and exchange data. This is especially important for enabling machine-driven discovery and analysis. We emphasize the importance of a balanced strategy that combines a centralized, top-down approach—focused on building enterprise-level capabilities and processes—with a decentralized, bottom-up approach driven by discipline-specific needs and community practices. We advocate for coordinated efforts to enhance (meta)data interoperability to facilitate seamless data and information sharing and exchange of Earth science data both within NASA and across other agencies managing Earth science data.

Data Product↗

DOE OSTI2024

Innovating the next generation of commercial smart building software

Nearly 30% of commercial building energy use is wasted due to equipment faults and HVAC controls problems. The result is increased emissions, compromised comfort and productivity, and less reliable coordination of building power needs with a clean grid. The energy impact alone represents $17 billion in potential savings. Today’s smart building software provides a robust solution to address these operational deficiencies. Energy management and information systems (EMIS) are saving up to 9% on average, with two-year paybacks. They are being incorporated into energy management processes, commissioning services, and utility programs. As effective as they are, two barriers prevent even deeper benefits; limited personnel to fix problems once they are identified, and the expense and time to manually implement changes in control systems. In partnership with the research community, the EMIS industry is developing new capabilities to overcome these barriers. Moving beyond siloed products for either fault detection and diagnostics, or optimal control, these new capabilities empower users to not only automatically identify faults, but also to push corrective action, and control improvements to their buildings. In this paper, several areas for enhancements are documented: ‘one-time’ correction of faults such as setpoints, schedules, and economizer lockouts; short-term active testing for automated proportional integral derivative (PID) loop tuning and functional testing; and continuous supervisory control for demand flexibility and year-round efficiency. Results are presented from a pair of partner implementations out of a dozen providers integrating these enhancements into their products, including field tests from across the country, and insights into operator acceptance and integration into operations and maintenance practices.

Casillas, Armando↗

DOE OSTI2024

Digitalization mapping and assessment process supporting ION strategic transformation activities

The existing fleet of commercial nuclear power plants (NPPs) are an important asset in the nation’s portfolio of electrical generating resources. Their continued safe and reliable operation are critical to providing a large source of carbon-free electricity to power the nation’s economy. The United States Department of Energy’s (DOE) Light Water Reactor Sustainability (LWRS) Program develops the scientific bases, methods, and tools, for the continued safe and economical operation of the nation's commercial NPPs. The Plant Modernization Pathway within LWRS Program focuses on providing guidance to industry on the full-scale implementation of modernization solutions for NPPs that significantly reduce the technical and financial risks associated with modernization. This research is focused on helping the nuclear industry understand how to digitize and digitalize their NPPs so that they can design their modernization solutions to be scalable, sustainable, and integrated both laterally and horizontally within their organization. That is, this research creates a digital transformation in NPPs by reshaping cultural mindsets and by identifying business efficiencies. In partnership with industry, and using four previously established guiding principles for digitalization, this research supported NPP modernization through assessing readiness for digitalization as a means to achieve integrated operations for nuclear. Specifically, this research created an assessment to review an entire organization’s work processes to gather information about the digitalization health of the plant. The assessment tools were administered to plant employees, and the results were used to develop a digitalization plan. The survey assessment identified the optimal candidate processes that would most benefit from a digitalization initiative which were revealed through analytical frameworks. One analysis calculated mean digitalization health indicator scores for all endorsed activities which allowed the researchers to rank and color code the results for easy identification. Individual health indicator scores are also provided, should our industry partner wish to understand these findings according to their own organizational priorities, business considerations and desired end-state. The results were also analyzed from the perspective that organizations are comprised of different types of innovators (e.g., generators, optimizers, conceptualizers, and implementers), which differentially affects the organization’s ability to comprehend and adapt to change (i.e., opportunities to innovate). Understanding the relative composition of innovator types at an NPP allows them to gather insights into the strengths and weaknesses they have in innovating how work is performed. For the utility that partnered with this research team, the results showed that implementers make up the largest portion of respondents and conceptualizers the smallest portion. Knowing the proportion of innovator types gave this organization insights on how they can effectively implement their innovation solutions. Additionally, the results were analyzed from a technical, economic, and risk perspective to identify and quantify work reduction opportunities (WROs). Recognizing that not all cost-saving opportunities are the same, a Technical, Economic and Risk Assessment (TERA) was performed to evaluate WROs to identify areas of greatest potential and lowest risk. The key results from TERA included a digitalization opportunity score for each activity, and a calculation of potential cost savings. These two outputs formed the bases for calculating a priority index and rank for the activities/processes assessed. From the prioritization calculations, TERA can then help the utility 1) decide what digitalization priorities to invest money in implementing and then 2) calculates how much should be invested in the digitalization initiatives selected to achieve cost savings and/or an acceptable return on investment. Last, onsite interviews revealed several inefficiencies in the standard work processes that occur cross-departmentally that are due to the absence of digitized and digitalized processes. Examples of these include time spent scanning paper documents and then uploading the documents electronically, obtaining signatures, and searching for desired information. This represents a digital but not digitalized process. Over 15 opportunities to improve work processes were identified through this multi-method digitalization assessment. The various analytical assessments used (e.g., TERA, digitalization health indicator scores), as well as discussions with the utility partner, corroborated that all the opportunities identified had a strong potential to make work processes more efficient and to improve overall performance of the NPP.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗