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At least 73 records · Page 4

Scaling open-weight large language models for hydropower regulatory information extraction: A systematic analysis

Information extraction from regulatory and technical documents using large language models (LLMs) involves practical trade-offs between extraction quality and computational cost. We evaluate eight open-weight LLMs spanning 0.6B–70B parameters on hydropower licensing documents and report deployment-oriented evidence under a unified extraction schema and evaluation protocol. Across the model set, we observe clear scale-dependent trends in both baseline extraction quality and the effectiveness of reflective reasoning (self-checking) under our fixed-prompt, no-augmentation setting. Mid-scale models often provide a favorable balance of accuracy and efficiency, whereas the smallest models show limited or inconsistent gains from the reasoning variants tested. Larger models achieve the highest overall F1 scores but incur substantially greater compute and infrastructure requirements. We further find that reliability failure modes can distort conventional metrics in this domain: in particular, high recall can coincide with systematic extraction errors when models fabricate values for fields that are absent from the source text, underscoring the importance of conservative null handling and evidence-grounded evaluation. Overall, our study provides a reproducible resource–performance comparison for open-weight LLM-based extraction in hydropower regulatory documentation and offers practical guidance for model selection under different deployment constraints.

Evaluation protocol↗

Non-LWR Regulatory Framework Modernization- Fiscal Year 2024

This report provides an end-of-year summary that reflects the progress and status of Idaho National Laboratory’s (INL’s) activities concerning the development of an advanced-reactor regulatory framework and its implementation in the United States (U.S.). The report also provides recommendations for work to be performed in Fiscal Year (FY)-25 and beyond. This work was completed in FY-24 and was supported by the U.S. Department of Energy (DOE) Regulatory Development sub-program. These activities are managed by INL on behalf of DOE.

22 - GENERAL STUDIES OF NUCLEAR REACTORS↗

AquaPV: Regulatory and Environmental Considerations for Floating Photovoltaic Projects Located on Federally Controlled Reservoirs in the United States

To meet the nation's decarbonization goals, the U.S. Department of Energy's Solar Futures study forecasts that installed solar photovoltaic (PV) capacity must increase nearly tenfold, from 80 gigawatts (GW) in 2020 to approximately 760 GW cumulative installed capacity by 2035. Ground-mounted PV is expected to dominate future solar deployment and will require more than 3.5 million acres of land to meet annual demand projections (of nearly 45 GW) by 2030. However, various competing demands for land (e.g., agricultural production, conservation) and high land acquisition costs in specific locations could be challenges to meeting future PV demand solely with ground-mounted PV deployment. Floating photovoltaics (FPV) may be an alternative in locations where ground-mounted PV is not feasible and aid in reaching the nation's PV deployment and decarbonization goals. FPV is a newer siting approach in which a PV array is affixed to a floating apparatus and sited on a water body like a reservoir behind a dam. FPV systems may be stand-alone or co-located at new or existing hydroelectric facilities or pumped storage hydropower (PSH) facility reservoirs. Co-located FPV systems may or may not be operationally paired and work in tandem with the hydroelectric or PSH facility. This report provides novel analysis to understand the opportunities and challenges associated with developing stand-alone and co-located FPV projects on reservoirs in the United States. Specifically, the report explores potential environmental and energy benefits and environmental impacts associated with the siting, construction, and operation of FPV projects. The report also identifies and analyzes U.S. federal- and state-issued permits and authorizations required by federal laws to understand the licensing pathways and regulatory requirements for FPV projects sited on reservoirs licensed by the Federal Energy Regulatory Commission and on powered and non-powered reservoirs owned by the Bureau of Reclamation or U.S. Army Corps of Engineers.

ENERGY PLANNING, POLICY, AND ECONOMY,SOLAR ENERGY↗

AquaPV: Regulatory and Environmental Considerations for Floating Photovoltaic Projects Located on Federally Controlled Reservoirs in the United States

To meet the nation's decarbonization goals, the U.S. Department of Energy's Solar Futures study forecasts that installed solar photovoltaic (PV) capacity must increase nearly tenfold, from 80 gigawatts (GW) in 2020 to approximately 760 GW cumulative installed capacity by 2035. Ground-mounted PV is expected to dominate future solar deployment and will require more than 3.5 million acres of land to meet annual demand projections (of nearly 45 GW) by 2030. However, various competing demands for land (e.g., agricultural production, conservation) and high land acquisition costs in specific locations could be challenges to meeting future PV demand solely with ground-mounted PV deployment. Floating photovoltaics (FPV) may be an alternative in locations where ground-mounted PV is not feasible and aid in reaching the nation's PV deployment and decarbonization goals. FPV is a newer siting approach in which a PV array is affixed to a floating apparatus and sited on a water body like a reservoir behind a dam. FPV systems may be stand-alone or co-located at new or existing hydroelectric facilities or pumped storage hydropower (PSH) facility reservoirs. Co-located FPV systems may or may not be operationally paired and work in tandem with the hydroelectric or PSH facility. This report provides novel analysis to understand the opportunities and challenges associated with developing stand-alone and co-located FPV projects on reservoirs in the United States. Specifically, the report explores potential environmental and energy benefits and environmental impacts associated with the siting, construction, and operation of FPV projects. The report also identifies and analyzes U.S. federal- and state-issued permits and authorizations required by federal laws to understand the licensing pathways and regulatory requirements for FPV projects sited on reservoirs licensed by the Federal Energy Regulatory Commission and on powered and non-powered reservoirs owned by the Bureau of Reclamation or U.S. Army Corps of Engineers.

ENERGY PLANNING, POLICY, AND ECONOMY,SOLAR ENERGY↗

Non-LWR Regulatory Framework Modernization

This report provides an end-of-year summary that reflects the progress and status of Idaho National Laboratory’s (INL) activities concerning the development of advanced reactor (AR) regulatory framework and its implementation in the United States (U.S.). The report also provides recommendations for work to be performed in Fiscal Year 2025 (FY-25) and beyond. This work was completed in Fiscal Year 2024 (FY-24) and was supported by the U.S. Department of Energy (DOE) Regulatory Development sub-program. These activities are managed by INL on behalf of DOE.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Regulatory Framework Modernization Program

This presentation discusses the work performed/being performed under the DOE Regulatory Development-Regulatory Framework Modernization Area in FY24

99 GENERAL AND MISCELLANEOUS↗

Change Agent: Energy Storage as a Driver of Regulatory Evolution

Purpose of Review Dividing the electric grid into the functions of generation, transmission, anddistribution enabled the drawing of jurisdictional lines and the application of the U.S.Constitution’s federalist system to energy regulation. Energy storage technologies,which can be placed throughout the grid to increase flexibility, can provide serviceacross all three of those functions. But the jurisdictional boundaries that have beendrawn around those functions have created barriers that restrict energy storagetechnologies from achieving their full potential. This review analyzes regulatory changes made to reduce barriers to storage deployment and their broader impacts on energy regulation in the U.S. Recent Findings Major energy regulations promulgated at the state and federal levels have generally focused on liberalizing the U.S. electric system through deregulation and increased competition. Paradoxically, however, these efforts have erected strict regulatory barriers that prevent energy storage technologies from providing service across multiple functions. A new wave of regulations in recent years has endeavored to reduce and remove those barriers. Summary Energy regulations adopted in recent years to reduce barriers to energy storage functionality in recent years have had deep and far-reaching impacts on U.S. electric regulation. These impacts go beyond storage and affect all energy technologies. This paper traces the development of energy regulation in U.S., the functional barriers that they created that impede energy storage functionality, recent efforts to remove those barriers, and the broader effects of those efforts. It concludes with a brief discussion of remaining barriers that prevent energy storage from reaching their full potential on the U.S. electric grid.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Evolution of storage monitoring – update in response to commercial and regulatory drivers

Carbon Capture and Storage (CCS) is in transition from first-of-a kind projects and research-orientated pilots to commercially-motivated applications. Monitoring results from many newly developed and planned large scale commercial projects are limited; however, it is worthwhile to assess their evolution and consider new strategies as part of an effort to assess and document best practices. Commercial monitoring is targeted to activities that comply with regulatory drivers and de-risk investments. Commercial monitoring also supports accounting that storage has occurred and is tied to project financing. It deals with long time frames and large volumes injected into multiple wells and multiple projects in favorable areas. We see developing trends toward reproducible workflows that systematically reduce risks and clarify expectations for oversight and long-term surveillance. Monitoring techniques showing increasing trends include injection zone pressure as a history-matching and compliance tool. To reduce cost and environmental impact of time-lapse seismic data collection, deploying new approaches and tools, such as use of fibre and installed sources are increasingly applied. Concern over the risk of induced seismicity by regulatory bodies and the general public has increased, which has also resulted in increased monitoring. Some techniques used in the early research phases have been sidelined or used only in restricted applications. For example, geochemical analyses in the injection zone as well as the environment are now being deployed less than it was in research-oriented programs, except in the US where it is required by the permitting process. Expectations of frequent area-wide near surface monitoring have also decreased.

25 ENERGY STORAGE↗

A cell type-aware framework for nominating non-coding variants in Mendelian regulatory disorders

Abstract Unsolved Mendelian cases often lack obvious pathogenic coding variants, suggesting potential non-coding etiologies. Here, we present a single cell multi-omic framework integrating embryonic mouse chromatin accessibility, histone modification, and gene expression assays to discover cranial motor neuron (cMN)cis-regulatory elements and subsequently nominate candidate non-coding variants in the congenital cranial dysinnervation disorders (CCDDs), a set of Mendelian disorders altering cMN development. We generate single cell epigenomic profiles for ~86,000 cMNs and related cell types, identifying ~250,000 accessible regulatory elements with cognate gene predictions for ~145,000 putative enhancers. We evaluate enhancer activity for 59 elements using an in vivo transgenic assay and validate 44 (75%), demonstrating that single cell accessibility can be a strong predictor of enhancer activity. Applying our cMN atlas to 899 whole genome sequences from 270 genetically unsolved CCDD pedigrees, we achieve significant reduction in our variant search space and nominate candidate variants predicted to regulate known CCDD disease genesMAFB, PHOX2A, CHN1, andEBF3– as well as candidates in recurrently mutated enhancers through peak- and gene-centric allelic aggregation. This work delivers non-coding variant discoveries of relevance to CCDDs and a generalizable framework for nominating non-coding variants of potentially high functional impact in other Mendelian disorders.

Science & Technology - Other Topics↗

Single-cell chromatin accessibility and cis -regulatory element analyses in plants using the scPlantReg platform

Understanding gene regulation is fundamental to plant improvement, but the lack of plant-specific single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) frameworks and cross-species databases has limited insights into cell-type-specific cellular regulation. Here we present ‘scPlantReg’, an integrated framework and database for plant scATAC-seq data. scPlantReg supports end-to-end analyses from raw data processing to biological interpretation and features ‘scATACtor’, a supervised machine-learning approach that outperforms existing tools for cell-type annotation. We applied scPlantReg to pearl millet to characterize cell-type-specific chromatin accessibility and identify validated activating and repressing accessible chromatin regions (ACRs), revealing WRKY transcription factors as potential regulators of xylem development. Furthermore, we reanalysed scATAC-seq datasets from 8 plant species, spanning 11 tissues and multiple developmental stages, enabling cross-species comparisons. Furthermore, these analyses uncovered conserved regulatory programmes, including AP2/EREBP-associated ACRs linked to cell wall development and cell-type-conserved TFs across grasses. Collectively, scPlantReg provides a general framework and resource for comparative regulatory analysis in plants.

Epigenomics↗

Integrating functional scoring and regulatory data to predict the effect of non-coding SNPs in a complex neurological disease

Abstract Most SNPs associated with complex diseases seem to lie in non-coding regions of the genome; however, their contribution to gene expression and disease phenotype remains poorly understood. Here, we established a workflow to provide assistance in prioritising the functional relevance of non-coding SNPs of candidate genes as susceptibility loci in polygenic neurological disorders. To illustrate the applicability of our workflow, we considered the multifactorial disorder migraine as a model to follow our step-by-step approach. We annotated the overlap of selected SNPs with regulatory elements and assessed their potential impact on gene expression based on publicly available prediction algorithms and functional genomics information. Some migraine risk loci have been hypothesised to reside in non-coding regions and to be implicated in the neurotransmission pathway. In this study, we used a set of 22 non-coding SNPs from neurotransmission and synaptic machinery-related genes previously suggested to be involved in migraine susceptibility based on our candidate gene association studies. After prioritising these SNPs, we focused on non-reported ones that demonstrated high regulatory potential: (1) VAMP2_rs1150 (3′ UTR) was predicted as a target of hsa-mir-5010-3p miRNA, possibly disrupting its own gene expression; (2) STX1A_rs6951030 (proximal enhancer) may affect the binding affinity of zinc-finger transcription factors (namely ZNF423) and disturb TBL2 gene expression; and (3) SNAP25_rs2327264 (distal enhancer) expected to be in a binding site of ONECUT2 transcription factor. This study demonstrated the applicability of our practical workflow to facilitate the prioritisation of potentially relevant non-coding SNPs and predict their functional impact in multifactorial neurological diseases.

Felício, Daniela↗

Single-cell and spatial omics in plants: from cellular atlases to regulatory mechanisms

Single-cell RNA sequencing (scRNA-seq) has transformed transcriptomic studies by enabling gene expression profiling at the resolution of individual cells within and across a broad range of tissue types, revealing cellular heterogeneity that is obscured in bulk tissue transcriptomes. Over the past decade, improvements in microfluidics and library preparation have drastically increased throughput, allowing tens of thousands of cells to be assayed in a single experiment. Although initially developed in animal systems, scRNA-seq has rapidly emerged as a powerful and widely adopted approach in plant biology. Beyond transcriptomics, the integration of single-cell data with chromatin accessibility, proteomics, metabolomics, and spatial omics is enabling a system-level understanding of plant gene regulation and cellular organization. Network-based analytical frameworks further support the reconstruction of gene regulatory networks and the interpretation of complex single-cell data. In this review, we summarize the current technological landscape of plant single-cell studies, discuss key experimental and analytical challenges, and review emerging strategies for validating single-cell discoveries. We also discuss future directions in applying single-cell technologies to woody perennials plants and bioenergy-relevant crops, emphasizing their potential to accelerate the discovery of cell type-specific regulatory mechanisms underlying growth, stress resilience, and biomass production.

Li, Miaomiao [ORNL] (ORCID:0000000321326168)↗

Clinical pharmacology information in regulatory submissions and labeling: A comparative analysis of orphan and non-orphan drugs approved by the FDA

Clinical pharmacology is an integral discipline supporting the development, regulatory evaluation, and clinical use of drugs for the treatment of both common and rare diseases. Here, we evaluated the recommendations and information available from select clinical pharmacology studies in the therapeutic product labeling of new molecular entities (NMEs) approved from 2017 to 2019 for both common and rare diseases. A total of 151 NMEs, including 72 orphan and 79 non-orphan drugs, were analyzed for recommendations and information available related to food–drug interaction, drug–drug interaction, renal impairment, hepatic impairment, QT assessment, and human radiolabeled mass balance studies using data collected from the original labeling and other regulatory documents. The analysis showed no statistically significant difference in the recommendations between orphan and non-orphan drugs except for renal impairment related recommendations in section 8 of the labeling. Although not significant, fewer hepatic impairment labeling recommendations were available for orphan drugs when compared with non-orphan drugs. At the time of initial approval, 79 postmarketing requirements (PMRs) and postmarketing commitments (PMCs) for 33 orphan drugs and 39 PMRs and PMCs for 19 non-orphan drugs were established; with most difference observed for drug–drug interaction, hepatic impairment, and QT assessment. Overall, although there was a trend for more labeling recommendations and fewer postmarketing studies and clinical trials for non-orphan drugs, there appeared to be no substantial differences in how these select clinical pharmacology studies are leveraged during the development and approval of orphan and non-orphan drugs.

60 APPLIED LIFE SCIENCES↗

Providing biological context for GWAS results using eQTL regulatory and co‐expression networks in Populus

Summary Our study utilized genome‐wide association studies (GWAS) to link nucleotide variants to traits in Populus trichocarpa , a species with rapid linkage disequilibrium decay. The aim was to overcome the challenge of interpreting statistical associations at individual loci without sufficient biological context, which often leads to reliance solely on gene annotations from unrelated model organisms. We employed an integrative approach that included GWAS targeting multiple traits using three individual techniques for lignocellulose phenotyping, expression quantitative trait loci (eQTL) analysis to construct transcriptional regulatory networks around each candidate locus and co‐expression analysis to provide biological context for these networks, using lignocellulose biosynthesis in Populus trichocarpa as a case study. The research identified three candidate genes potentially involved in lignocellulose formation, including one previously recognized gene (Potri.005G116800/VND1, a critical regulator of secondary cell wall formation) and two genes (Potri.012G130000/AtSAP9 and Potri.004G202900/BIC1) with newly identified putative roles in lignocellulose biosynthesis. Our integrative approach offers a framework for providing biological context to loci associated with trait variation, facilitating the discovery of new genes and regulatory networks.

59 BASIC BIOLOGICAL SCIENCES↗

Bioenergy sorghum stem growth regulation: intercalary meristem localization, development, and gene regulatory network analysis

SUMMARY Bioenergy sorghum is a highly productive drought tolerant C 4 grass that accumulates 80% of its harvestable biomass in approximately 4 m length stems. Stem internode growth is regulated by development, shading, and hormones that modulate cell proliferation in intercalary meristems (IMs). In this study, sorghum stem IMs were localized above the pulvinus at the base of elongating internodes using magnetic resonance imaging, microscopy, and transcriptome analysis. A change in cell morphology/organization occurred at the junction between the pulvinus and internode where LATERAL ORGAN BOUNDARIES ( SbLOB ), a boundary layer gene, was expressed. Inactivation of an AGCVIII kinase in DDYM ( dw2 ) resulted in decreased SbLOB expression, disrupted IM localization, and reduced internode cell proliferation. Transcriptome analysis identified approximately 1000 genes involved in cell proliferation, hormone signaling, and other functions selectively upregulated in the IM compared with a non‐meristematic stem tissue. This cohort of genes is expressed in apical dome stem tissues before localization of the IM at the base of elongating internodes. Gene regulatory network analysis identified connections between genes involved in hormone signaling and cell proliferation. The results indicate that gibberellic acid induces accumulation of growth regulatory factors (GRFs) known to interact with ANGUSTIFOLIA (SbAN3), a master regulator of cell proliferation. GRF:AN3 was predicted to induce SbARF3/ETT expression and regulate SbAN3 expression in an auxin‐dependent manner. GRFs and ARFs regulate genes involved in cytokinin and brassinosteroid signaling and cell proliferation. The results provide a molecular framework for understanding how hormone signaling regulates the expression of genes involved in cell proliferation in the stem IM.

59 BASIC BIOLOGICAL SCIENCES↗

Exploring Plant Cis –Regulatory Elements at Single–Cell Resolution: Overcoming Biological and Computational Challenges to Advance Plant Research

Cis-regulatory elements (CREs) are important sequences for gene expression and for plant biological processes such as development, evolution, domestication, and stress response. However, studying CREs in plant genomes has been challenging. The totipotent nature of plant cells, coupled with inability to maintain plant cell types in culture and the inherent technical challenges posed by the cell wall have limited our understanding of how plant cell types acquire and maintain their identities and respond to the environment via CRE usage. Furthermore, advances in single cell epigenomics have revolutionized the field identifying cell-type-specific CREs. These new technologies have the potential to significantly advance our understanding of plant CRE biology, and shed light on how the regulatory genome gives rise to diverse plant phenomena. However, there are significant biological and computational challenges associated with analyzing single cell epigenomic datasets. In this review, we discuss the historical and foundational underpinnings of plant single-cell research, challenges and common pitfalls in analysis of plant single-cell epigenomic data, and highlight biological challenges unique to plants. Additionally, we discuss how the application of single-cell epigenomic data in various contexts stands to transform our understanding of the importance of CREs in plant genomes.

59 BASIC BIOLOGICAL SCIENCES↗

Elucidating regulatory processes of intense physical activity by multi-omics analysis

Abstract Background Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment. Methods To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student’s t -test followed by pathway analysis and comparison between the different omics modalities. Results Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection. Conclusion This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.

59 BASIC BIOLOGICAL SCIENCES↗

Regulatory Treatment of Low Frequency External Events under a Risk-Informed Performance-Based Licensing Pathway: Enhanced SPRA-based Margins Assessment

Recently there has been development in the field of risk-informed performance-based (RIPB) design and licensing approaches, which leverage detailed risk assessments and performance-based metrics to allow flexibility and innovation. These RIPB approaches include the probabilistic treatment of external hazards, including low frequency events that are beyond the design basis. However, there are certain challenges that have been identified to the probabilistic treatment of low frequency external events, primarily due to uncertainty in the hazard curve and the associated plant response to rare, severe events. The NRC is currently developing 10 CFR Part 53 that would establish a technology-inclusive regulatory framework for use by applicants for new commercial advanced nuclear reactors. By examining the regulatory safety criteria contained within draft 10 CFR Part 53 and associated draft RIPB seismic design guidance, potential challenges were identified in demonstrating satisfaction of the safety criteria for low frequency external events, with specific difficulties associated with demonstrating compliance with the quantitative health objectives (QHOs). Non-LWRs are expected to utilize the direct calculation of offsite consequence, rather than use surrogates, for comparison to the QHOs, which can be particularly challenging as the previously identified uncertainties are compounded by uncertainties in the response of the neighboring population. The central recommendation from this effort is that it is necessary to develop an approach for demonstrating compliance with the safety criteria in draft Part 53 that addresses the key challenges while providing flexibility to applicants. This paper summarizes key findings, establishes a series of high-level goals, and reviews a newly developed approach to address the major challenges associated with assessing compliance with QHOs, with avenues to demonstrate compliance based on either the estimated consequence or the available margin to event occurrence, while also building on existing experience of seismic margins assessments. The paper also provides examples to demonstrate the application of the approach, as well as recommendations and potential future work.

external hazards↗