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A genomic regulatory network for development

Development of the body plan is controlled by large networks of regulatory genes. A gene regulatory network that controls the specification of endoderm and mesoderm in the sea urchin embryo is summarized here. The network was derived from large-scale perturbation analyses, in combination with computational methodologies, genomic data, cis-regulatory analysis, and molecular embryology. The network contains over 40 genes at present, and each node can be directly verified at the DNA sequence level by cis-regulatory analysis. Its architecture reveals specific and general aspects of development, such as how given cells generate their ordained fates in the embryo and why the process moves inexorably forward in developmental time.

Non-NASA Center↗

Advanced Reactor Regulatory Framework Development Activities for Fiscal Year 2023

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 summarizes some general updates on important topics in regulatory development. This work was completed in Fiscal Year 2023 (FY-23) 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.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Promoting regulatory acceptance of combined ion and neutron irradiation testing of nuclear reactor materials: Modeling and software considerations

As the needs for the nuclear energy industry continue to evolve in the 21st century, timely adoption of new technological solutions acceptable to regulatory agencies is critical. Quantitative prediction of radiation damage in materials and its impact on mechanical properties is a key component of licensing and regulatory decisions regarding nuclear power plants. Accelerated testing methodologies such as combined ion and neutron irradiation data sets are crucial for the development and deployment of new materials and new manufacturing methods (e.g., additive manufacturing). However, regulatory acceptance of accelerated testing methodologies is necessary for their adoption. Further, the present work discusses the fundamental basis for comparing ion- and neutron-induced material microstructures, the theory behind interpreting radiation damage across length and time scales and radiation types, and the codes, standards, and quality assurance concerns surrounding different modeling methods and software. In particular, recommendations are given as to the path forward that will enable national laboratories, academia, and industry to develop the modeling and software basis for regulatory acceptance of the combined use of ion and neutron irradiation for material performance evaluation.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

An expanded registry of candidate cis -regulatory elements

Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. Previously, the ENCODE consortium mapped biochemical signals across hundreds of cell types and tissues and integrated these data to develop a registry containing 0.9 million human and 300,000 mouse candidate cis-regulatory elements (cCREs) annotated with potential functions. Here we have expanded the registry to include 2.37 million human and 967,000 mouse cCREs, leveraging new ENCODE datasets and enhanced computational methods. This expanded registry covers hundreds of unique cell and tissue types, providing a comprehensive understanding of gene regulation. Functional characterization data from assays such as STARR-seq, massively parallel reporter assay, CRISPR perturbation and transgenic mouse assays have profiled more than 90% of human cCREs, revealing complex regulatory functions. We identified thousands of novel silencer cCREs and demonstrated their dual enhancer and silencer roles in different cellular contexts. Integrating the registry with other ENCODE annotations facilitates genetic variation interpretation and trait-associated gene identification, exemplified by the identification of KLF1 as a novel causal gene for red blood cell traits. This expanded registry is a valuable resource for studying the regulatory genome and its impact on health and disease.

Moore, Jill E. [Univ. of Massachusetts, Worchester↗

Carbon source–driven metabolic and regulatory remodeling defines phenomic states in Lipomyces starkeyi

Lipomyces is a genus of oleaginous yeasts with potential for contributing to reliable biomanufacturing supply chains. However, progress in advanced strain designs and engineering efforts are still constrained by a lack of understanding of the underlying molecular drivers of Lipomyces phenotypes. To address this gap, we collected a suite of multi-omic data to dissect how carbon source availability reshapes the metabolic network, lipid allocation, and regulatory architecture of Lipomyces starkeyi. We observed that glucose promotes biosynthetic and proliferative processes supported by abundant energy and carbon intermediates, xylose enhances redox-balancing mechanisms centered on the pentose phosphate pathway, and glycerol activates respiratory metabolism, ß-oxidation, and the glyoxylate cycle. Lipid species distributions remained consistent in both nitrogen replete and depleted conditions across the carbon sources, indicating robust production mechanisms. Regulatory protein identification and network analysis revealed glycerol-driven respiratory growth favors regulatory programs integrating stress tolerance, redox balance, and lipid-associated metabolism, whereas xylose growth activates compensatory transcriptional responses aimed at maintaining mitochondrial function. Nitrogen limitation modulates the strength of these responses but does not fundamentally alter their direction, reinforcing carbon source as the dominant driver of regulatory architecture. Taken together, this data enhances the understanding of Lipomyces molecular rearrangements and provides a foundation for further development of predictive phenotypic tools in this genus.

Biotechnology↗

Phytohormones in a universe of regulatory metabolites: lessons from jasmonate

Small-molecule phytohormones exert control over plant growth, development, and stress responses by coordinating the patterns of gene expression within and between cells. Increasing evidence indicates that currently recognized plant hormones are part of a larger group of regulatory metabolites that have acquired signaling properties during the evolution of land plants. This rich assortment of chemical signals reflects the tremendous diversity of plant secondary metabolism, which offers evolutionary solutions to the daunting challenges of sessility and other unique aspects of plant biology. A major gap in our current understanding of plant regulatory metabolites is the lack of insight into the direct targets of these compounds. Here, we illustrate the blurred distinction between classical phytohormones and other bioactive metabolites by highlighting the major scientific advances that transformed the view of jasmonate from an interesting floral scent to a potent transcriptional regulator. Lessons from jasmonate research generally apply to other phytohormones and thus may help provide a broad understanding of regulatory metabolite–protein interactions. In providing a framework that links small-molecule diversity to transcriptional plasticity, we hope to stimulate future research to explore the evolution, functions, and mechanisms of perception of a broad range of plant regulatory metabolites.

59 BASIC BIOLOGICAL SCIENCES↗

Addressing Regulatory Challenges to Tribal Solar Deployment: Key Findings

Tribal land in the United States represents approximately 2% of the country's total landmass and holds more than 5% of solar photovoltaic potential (Doris, Lopez, and Beckley 2013). This resource is largely untapped. Many Tribes note that regulatory challenges often are roadblocks to taking advantage of solar potential. This report serves as a summary of a larger project, Addressing Regulatory Challenges to Tribal Solar Deployment. The project seeks to unlock some of this potential by bringing Tribal, regulatory, utility, and other stakeholders together to articulate key barriers to Tribal solar adoption and develop replicable solutions. By increasing institutional capacity and developing frameworks, trainings, and a technical document repository for regulatory bodies, utilities, and Tribes, this project can help expand an emerging market.

14 SOLAR ENERGY↗

Recommendations to Improve the Nuclear Regulatory Commission Reactor Licensing and Approval Process

Due to the urgency around climate change and associated goals for clean energy transition, and Battelle Energy Alliance's (BEA) and Idaho National Laboratory's (INL) role as the nation's nuclear energy laboratory, numerous stakeholders have asked for BEA’s thoughts and recommendations to reduce the time and costs associated with licensing new reactors at the U.S. Nuclear Regulatory Commission (NRC). As an M&O contractor for an FFRDC, BEA is a long-term partner with the Government in seeking to achieve clean energy goals, yet has a level of independence needed to appropriately evaluate this topic. The views herein are informed by extensive BEA experience supporting nuclear energy endeavors including ongoing discussions with current and former regulators, applicants, and licensees. With this background in mind, the United States benefits from having an agency such as the NRC, which is viewed internationally as the leader in nuclear safety licensing and regulation. Nonetheless, while acknowledging the important nuclear safety role satisfied by the NRC, it is apparent that one of the most significant time and resource intensive activities for new reactor developers is the NRC licensing process. The time and cost to obtain NRC licenses add significant financial stress for new reactor projects and may result in abandonment of projects or failure to even begin new projects. The challenge is particularly acute for advanced reactors which may raise unique or new regulatory questions and may be smaller in size, resulting in a much higher proportional impact from regulatory and cost challenges. This situation presents a particularly troublesome risk for the nation given the urgency in which utilities are working to transition to clean, non-carbon-emitting energy sources like nuclear energy. Reforms to the NRC licensing process have the potential to greatly increase certainty and support the successful progress of new reactors. The NRC can retain its world-class nuclear safety reputation while becoming a world leader for regulatory efficiency and a critical enabler to the clean energy transition. This report describes potential NRC reforms, focusing on those with a statutory connection. Recognizing the potential tradeoffs with any proposed changes, the report attempts to highlight those considerations in the analysis of the reforms. The recommendations are presented as a set of options for consideration. Unless noted, they are independent options, offering stakeholders the option to select a subset for further consideration. Although difficult to calculate precise time improvements for some of the changes, the reforms have the potential for substantial improvements, perhaps even by a factor of two.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

Potential State Regulatory Pathways to Facilitate Low-Carbon Fuels

States and the federal government are increasingly engaged in the challenges around decarbonizing the electric grid. In particular, regulators, consumers, stakeholders, and utilities recognize the need to carefully consider the role natural gas will play in a decarbonized future. A variety of technology and policy options to reduce greenhouse gas emissions associated with natural gas use are available, including energy efficiency programs, demand reduction tools, strategic electrification, and strategies to reduce emissions from natural gas production, transportation, and consumption. Low-carbon fuels – mainly renewable natural gas (RNG) and clean hydrogen – are being considered an important component of decarbonization goals. RNG and hydrogen may be able to meaningfully reduce emissions from processes independent of geologic natural gas, displacing emissions of methane, a powerful greenhouse gas. Although RNG and hydrogen are not cost-competitive today with geologic natural gas and are smaller in scale and potential than other decarbonization options, they can be explored as potential critical tools to decarbonize sectors that are difficult to electrify or shift off of natural gas entirely, such as air travel, industrial processes, maritime transport, long-distance trucking, space heating on cold days, and railroads (Nadel, 2022). The role of this report is to provide informational context for state utility regulators to understand the impacts of and challenges associated with broader integration of low-carbon fuels, followed by examples of state regulatory actions taken to date to facilitate the development of low-carbon fuels. Setting clear guidance to calculate the environmental benefits of low-carbon fuels and continuing federal and state investments in research and development to reduce costs relative to fossil fuels will be important steps to take to signal the desire to grow the market for these fuels. State public utility commissions may play a key role in setting regulatory frameworks for low-carbon fuels and ensuring that ratepayer funds, if utilized, are done so to further the public interest. This report is intended to summarize decisions that states have made to date on low-carbon fuels. In the spirit of understanding the current market and sharing information, this report provides success stories, and lessons learned across states as regulators implement varying strategies to achieve decarbonization objectives while maintaining their focus on affordability, safety, and reliability of the energy system. The report begins with an introduction of the role of natural gas in the U.S. economy (Section I) and background information on natural gas use, decarbonization, and low-carbon fuels (Section II). Next, the report describes the current market by discussing the scale of current production, emissions intensity, resource potential, and costs of low-carbon fuels compared to geologic natural gas (Section III). Following these sections, the report describes four strategies states have employed to facilitate low-carbon fuels: opening exploratory dockets, approving voluntary tariffs for customers, approving interconnection tariffs for producers, and considering portfolio-wide procurement targets (Section IV). This section lists states that have taken actions in each category, citing utility filings, commission decisions, stakeholder comments, and other relevant sources. Finally, the report concludes with suggested questions regulators may wish to consider regarding low-carbon fuels, in the interest of preparing to make decisions in the future (Section V). These questions include: Are there existing regulatory or technical barriers to voluntary purchases of low-carbon fuels? Can customers work with utilities to procure low-carbon fuels; are producers able to interconnect projects without significant barriers to entry? Should the infrastructure and/or commodity costs of low-carbon fuels be socialized among all ratepayers, or borne solely by the large commercial and industrial (C&I) customers currently driving the market? Should regulated natural gas and/or electric utilities own and operate low-carbon fuel production? How should regulators consider the unique decarbonization potential of low-carbon fuels, particularly for hard-to-abate sectors, in decision-making? Is additional direction or clarity from state policymakers needed? What no-regrets approaches can help facilitate both near-term RNG development and long-term development of hydrogen and other zero-carbon fuels? We collectively wish to express our gratitude to the U.S. Department of Energy, Office of Fossil Energy and Carbon Management, for supporting this report and other technical assistance resources for state regulators on natural gas topics. State regulators operate under a variety of policy environments, and states have vastly different types of energy resources, infrastructure, and customers. While there is no optimal regulatory, policy, or technological solution that will be successful in every state, state regulators can benefit by exchanging lessons learned with their peers across the country. We look forward to continued engagement with our fellow commissioners, commission staff, NARUC, the U.S. Department of Energy, and other stakeholders to develop sound regulation in the public interest.

03 NATURAL GAS↗

Proactive Regulatory Approaches to Electrification and Load Growth: Workshop Report

On July 10 and 11, 2024, Pacific Northwest National Laboratory and RMI led a workshop in Aurora, Colorado, to explore novel and proactive approaches to electrification and load growth while minimizing risks and costs to customers. Over the next decade, a unique opportunity exists to invest strategically in the electricity system to enable electrification across the transportation, industrial, and building sectors and respond to data and technology-based load growth. However, current utility and regulatory planning practices are insufficient to identify and enable the right investments, and work must be done to reduce the risk and decisional uncertainty faced by utility regulatory commissions and utilities. Ensuring timely electrification investments may require new approaches to address risk, uncertainty, prudence, and cost recovery. Understanding the decision-making process and information needs of utilities and regulators is critical. New policies (or application of policies), financial tools, systems analysis, regulatory mechanisms, and enhanced process transparency may be required. The workshop's goal was to identify proactive regulatory approaches for electrification and load growth that minimize costs and risks to customers. Our intention was that the conversations and the resulting solutions and takeaways would be specific and tactical rather than general and theoretical and that together we would create actionable next steps for key actors in the system, including utilities, regulators, thought leaders, researchers, and the U.S. Department of Energy (DOE). This report is intended to provide workshop attendees with a record and summary of the discussion and proposals raised at the workshop and to provide interested entities who did not attend, such as other regulators, policymakers, utilities, and U.S. DOE offices, with an understanding of what was discussed and with ideas to explore in their organizations.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Regulatory Sandboxes and Other Processes to Expedite Utility Adoption of Advanced Grid Technologies

Advanced grid technologies are increasingly important to enable electric transmission and distribution systems to meet growing demands. However, traditional regulatory processes typically lag technological advancements. Regulatory sandboxes, which provide a structured environment for testing new technologies and business approaches under modified rules to increase the speed of adoption, aim to bridge the gap between grid needs and opportunities to deliver solutions at scale. This report examines the role of regulatory sandboxes in promoting utility innovation, highlights examples of successful sandbox mechanisms, and provides emerging best practices for designing and implementing regulatory sandboxes.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Dynamic Capacitive Wireless Power Transfer System for Electric Vehicles (CRADA Final Report)

Road transportation accounts for 23% of our nation's total energy consumption, 59% of our petroleum consumption and 22% of our total emissions. Electric vehicles (EVs) have much higher well-to-wheel efficiency compared to gasoline vehicles and can reduce our dependence on oil, minimize emissions, improve local air quality and provide a platform for technological innovation and economic growth. While major progress has been made in the development of electric vehicles, their penetration remains under 1 The main hurdles in their widespread adoption are high cost, limited range and long charging times, due to limitations in battery technology. An approach to overcome these hurdles is to substantially reduce the on-board energy storage and instead deliver power wirelessly to the vehicle while it is in motion dynamic wireless power transfer (WPT). For EV charging applications, researchers have traditionally focused on inductive WPT. An issue with inductive WPT systems is that for magnetic flux guidance and shielding, they require ferrite cores, making them expensive, bulky and difficult to embed in the roadway. Under an ARPA-E IDEAS grant, the CU Boulder team has recently developed an alternative approach to WPT based on capacitive coupling that is much smaller, lighter, less expensive, and easier to embed in the roadway than inductive WPT; and have demonstrated a 1.2-kW 6.78-MHz version of this capacitive WPT system on a stationary platform. Under this seed grant program, preliminary work will be carried out on a dynamic capacitive WPT system to prepare a strong proposal for the ARPA-E OPEN 2018 FOA.

33 ADVANCED PROPULSION SYSTEMS↗

A Community Guide to Regulatory Barriers Affecting Microgrids (Reports 1-3)

In response to growing risks of power outages from extreme weather and aging infrastructure, communities are increasingly exploring the potential of microgrids to provide reliable energy access. Microgrids offer promising solutions to meet this challenge but face a complex landscape of non-technical barriers, particularly regulations concerning the provision and distribution of energy. Most existing legal and regulatory frameworks were designed for a centralized, one-way power system, and are often poorly suited to handle systems that independently balance distributed energy resources with local load. This three-part report series provides a strategic analysis of existing regulatory and legal factors affecting microgrid deployments to help non-technical community leaders and decision-makers better understand the feasibility of a microgrid in their community. -Report No. 1: Foundational Issues Facing Microgrids details the universal policy barriers all microgrids face, including utility interconnection processes, rate structures, and local permitting. -Report No. 2: Single Property Microgrids outlines how direct asset ownership and operating behind-the-meter can bypass some regulatory oversight, using the Blue Lake Rancheria microgrid as a case study. -Report No. 3: Multi-Property Microgrids tackles the complex challenges of crossing public rights-of-way and navigating utility franchise rights, highlighting the Coventry microgrid project. The series equips decision-makers with phased frameworks to navigate financial and regulatory complexities, engage effectively with local utilities and Authorities Having Jurisdiction (AHJs), and structure successful microgrid projects.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Developmental gene regulatory network architecture across 500 million years of echinoderm evolution

Evolutionary change in morphological features must depend on architectural reorganization of developmental gene regulatory networks (GRNs), just as true conservation of morphological features must imply retention of ancestral developmental GRN features. Key elements of the provisional GRN for embryonic endomesoderm development in the sea urchin are here compared with those operating in embryos of a distantly related echinoderm, a starfish. These animals diverged from their common ancestor 520-480 million years ago. Their endomesodermal fate maps are similar, except that sea urchins generate a skeletogenic cell lineage that produces a prominent skeleton lacking entirely in starfish larvae. A relevant set of regulatory genes was isolated from the starfish Asterina miniata, their expression patterns determined, and effects on the other genes of perturbing the expression of each were demonstrated. A three-gene feedback loop that is a fundamental feature of the sea urchin GRN for endoderm specification is found in almost identical form in the starfish: a detailed element of GRN architecture has been retained since the Cambrian Period in both echinoderm lineages. The significance of this retention is highlighted by the observation of numerous specific differences in the GRN connections as well. A regulatory gene used to drive skeletogenesis in the sea urchin is used entirely differently in the starfish, where it responds to endomesodermal inputs that do not affect it in the sea urchin embryo. Evolutionary changes in the GRNs since divergence are limited sharply to certain cis-regulatory elements, whereas others have persisted unaltered.

NASA Program Fundamental Space Biology↗

Regulatory Compliance in Multi-Tier Supplier Networks

Over the years, avionics systems have increased in complexity to the point where 1st tier suppliers to an aircraft OEM find it financially beneficial to outsource designs of subsystems to 2nd tier and at times to 3rd tier suppliers. Combined with challenging schedule and budgetary pressures, the environment in which safety-critical systems are being developed introduces new hurdles for regulatory agencies and industry. This new environment of both complex systems and tiered development has raised concerns in the ability of the designers to ensure safety considerations are fully addressed throughout the tier levels. This has also raised questions about the sufficiency of current regulatory guidance to ensure: proper flow down of safety awareness, avionics application understanding at the lower tiers, OEM and 1st tier oversight practices, and capabilities of lower tier suppliers. Therefore, NASA established a research project to address Regulatory Compliance in a Multi-tier Supplier Network. This research was divided into three major study efforts: 1. Describe Modern Multi-tier Avionics Development 2. Identify Current Issues in Achieving Safety and Regulatory Compliance 3. Short-term/Long-term Recommendations Toward Higher Assurance Confidence This report presents our findings of the risks, weaknesses, and our recommendations. It also includes a collection of industry-identified risks, an assessment of guideline weaknesses related to multi-tier development of complex avionics systems, and a postulation of potential modifications to guidelines to close the identified risks and weaknesses.

Goossen, Emray R.↗

Best Practices for Regulatory Engagement and Relationship Building – 26129

In the initiation of a new project or facility, the management team should begin to engage with appropriate regulators, early and often. However, if this did not occur and new issues arise, new challenges develop, or regulatory impacts become a concern, the regulatory engagement process should be reconsidered and reevaluated. Regulators are key in the siting, construction, and continued operations of a new facility. Municipalities often seek to attract new initiatives, projects, or facilities that will have a significant positive impact on the community. Even though this is typically the goal, there are many hurdles along the path that may cause negative impacts leading to regulatory concerns and hurdles that may delay or stop work. Additionally, early and frequent engagement with regulators can have a significant positive impact on the successful siting, permitting, and construction of a facility, including meeting needed schedules that are important to economic viability. Further, it is essential for ongoing operations for regulators to be effectively and meaningfully engaged throughout the life of the project or facility due to the potential of changing factors during the construction and/or operation. Regular and consistent engagement builds relationships and helps ensure that potential topics of concern are addressed early before they become problems. In this paper, we will discuss best practices in engaging with regulators, how to initiate effective regulatory interactions, and building lasting relationships.

Jacobs, Stephanie [Savannah River National Laborat↗

Non-LWR Regulatory Framework Modernization

This report provides a summary of Fiscal Year 2025 activities performed in the Regulatory Framework Modernization work package through July 2025. This reflects the progress and status of Idaho National Laboratory?s activities concerning the development of an advanced reactor regulatory framework and its implementation in the United States. This report includes discussions of the progress that NRC has made on the ADVANCE Act requirements as well as the newly issued Presidential Executive Orders from May 2025. It provides a summary of the additional work packages added in July 2025 because of the executive orders. The report also provides recommendations for work to be performed in Fiscal Year 2026. This work was supported by the U.S. Department of Energy Office of Nuclear Energy Regulatory Development subprogram. These activities are managed by Idaho National Laboratory on behalf of the Department of Energy.

11 - NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Combinatorial transcription factor binding encodes cis -regulatory wiring of mouse forebrain GABAergic neurogenesis

Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as in vivo enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.

59 BASIC BIOLOGICAL SCIENCES↗