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At least 1,207 records · Page 67

The cis-regulatory codes of response to combined heat and drought stress in Arabidopsis thaliana

Abstract Plants respond to their environment by dynamically modulating gene expression. A powerful approach for understanding how these responses are regulated is to integrate information about cis-regulatory elements (CREs) into models called cis-regulatory codes. Transcriptional response to combined stress is typically not the sum of the responses to the individual stresses. However, cis-regulatory codes underlying combined stress response have not been established. Here we modeled transcriptional response to single and combined heat and drought stress in Arabidopsis thaliana. We grouped genes by their pattern of response (independent, antagonistic and synergistic) and trained machine learning models to predict their response using putative CREs (pCREs) as features (median F-measure = 0.64). We then developed a deep learning approach to integrate additional omics information (sequence conservation, chromatin accessibility and histone modification) into our models, improving performance by 6.2%. While pCREs important for predicting independent and antagonistic responses tended to resemble binding motifs of transcription factors associated with heat and/or drought stress, important synergistic pCREs resembled binding motifs of transcription factors not known to be associated with stress. These findings demonstrate how in silico approaches can improve our understanding of the complex codes regulating response to combined stress and help us identify prime targets for future characterization.

Azodi, Christina B.↗

U.S. Domestic Pebble Bed Reactor: Security-by-Design

U.S. nuclear power facilities face increasing challenges in meeting dynamic security requirements caused by evolving and expanding threats while keeping cost reasonable to make nuclear energy competitive. The past approach has often included implementing security features after a facility has been designed and without attention to optimization, which can lead to cost overruns. Incorporating security in the design process can provide robust, cost effective, and sufficient physical protection systems. The purpose of this work is both to develop a framework for the integration of security into the design phase of High Temperature Gas Reactors (HTGRs) that utilize pebble-based fuels and increase the use of modeling and simulation tools to optimize the design of physical protection systems. Specifically, this effort focuses on integrating security into the design phase of a model HTGR that meets current Nuclear Regulatory Commission (NRC) physical protection requirements and providing advanced solutions to improve physical protection and decrease costs. A suite of tools, including SCRIBE3D©, PATHTRACE© and Blender© were used to model a hypothetical, generic domestic HTGR facility. Physical protection elements such as sensors, cameras, barriers, and guard forces were added to the model based on best practices for physical protection systems. Multiple outsider sabotage scenarios were examined with four-to eight adversaries to determine security metrics. The results of this work will influence physical protection system designs and facility designs for U.S. domestic HTGRs. This work will also demonstrate how a series of experimental and modeling capabilities across the Department of Energy (DOE) Complex can impact the design of and complete Safeguards and Security by Design (SSBD) for SMRs. The conclusions and recommendations in this document may be applicable to all SMR designs.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Rapid tachyphylaxis to hemodynamic effects of PACAP-27 after inhibition of nitric oxide synthesis

The vasodilator effects of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 are subject to tachyphylaxis in rats treated with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). We examined whether this tachyphylaxis could be prevented by administration of the putative endothelium-derived nitrosyl factor S-nitroso-L-cysteine (L-SNC) and whether L-SNC may exert its effects via increases in cGMP levels in vascular smooth muscle. Five doses of PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats. These responses were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) in L-NAME-treated (50 micromol/kg iv) rats produced vasodilator responses similar to those in saline-treated rats, whereas subsequent injections produced progressively smaller responses. The injection of L-SNC (1,200 nmol/kg iv) before each injection of PACAP-27 prevented tachyphylaxis to the Gs protein-coupled receptor agonist in L-NAME-treated rats, whereas equihypotensive doses of the NO donor sodium nitroprusside (100 micrograms/kg iv) did not. The injection of the membrane-permeant cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-CPT-cGMP; 30 micromol/kg iv) to L-NAME-treated rats restored resting hemodynamic values to pre-L-NAME levels but did not prevent the development of tachyphylaxis to PACAP-27. These results suggest that nitrosyl factors prevent the development of tachyphylaxis to the hemodynamic actions of PACAP-27. These nitrosyl factors may act independently of their ability to generate cGMP in vascular smooth muscle.

NASA Discipline Regulatory Physiology↗

Fractal mechanisms and heart rate dynamics. Long-range correlations and their breakdown with disease

Under healthy conditions, the normal cardiac (sinus) interbeat interval fluctuates in a complex manner. Quantitative analysis using techniques adapted from statistical physics reveals the presence of long-range power-law correlations extending over thousands of heartbeats. This scale-invariant (fractal) behavior suggests that the regulatory system generating these fluctuations is operating far from equilibrium. In contrast, it is found that for subjects at high risk of sudden death (e.g., congestive heart failure patients), these long-range correlations break down. Application of fractal scaling analysis and related techniques provides new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as motivating development of novel physiologic models of systems that appear to be heterodynamic rather than homeostatic.

NASA Discipline Cardiopulmonary↗

Navigating Integration: Key Challenges for Data Centers, Nuclear Stakeholders, and Utility Operators

he exponential growth of data centers—driven by artificial intelligence and cloud computing—is reshaping the U.S. energy landscape, presenting urgent challenges and transformative opportunities for data center developers, nuclear energy providers, and utility operators. As data centers are projected to consume up to 12% of U.S. electricity by 2028, stakeholders must address rapid deployment needs, grid congestion, and the demand for reliable, high-quality power. This presentation explores the multifaceted barriers to integrating data centers with nuclear and utility infrastructure, including land use constraints, public perception, regulatory complexity, and workforce alignment. It highlights the distinct priorities and operational cultures of each sector, and the friction that arises from misaligned planning horizons and risk tolerances. We examine collaborative strategies such as co-siting, hybrid power-purchase agreements, unified community engagement, and innovative financing models.

22 - GENERAL STUDIES OF NUCLEAR REACTORS↗

Assessment of Adequacy and Completeness of Standards Endorsed by Regulatory Guides to Molten Salt Reactors

The benefits of using voluntary consensus standards and industry guidance documents and reports are evident in the design and licensing of the current generation of nuclear power plants. The use of voluntary consensus standards and industry guidance and reports facilitates the design and licensing of advanced reactors to improve the effectiveness and efficiency of the licensing and regulation of non-light-water reactor (non-LWR) technologies. Most of the regulations, guidance, and standards applicable to nuclear power plants were developed for water-cooled plants, so they may not adequately address factors such as the coolants, materials, temperatures, operations, testing, and maintenance proposed for advanced reactors.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

SCALE Modeling of the Sodium Cooled Fast-Spectrum Advanced Burner Test Reactor

This report documents the modeling and simulation of a sodium-cooled fast reactor (SFR) as part of a U.S. Nuclear Regulatory Commission–sponsored project to assess the modeling and simulation capabilities for accident progression, source term, and consequence analysis for advanced reactor technologies with the Oak Ridge National Laboratory code SCALE and the Sandia National Laboratories (SNL) code MELCOR. Based on publicly available benchmark specifications, a fully heterogeneous 3D SCALE model of the 250 MWth Advanced Burner Test Reactor (ABTR) was developed to demonstrate SCALE’s capabilities for full-core reactivity analysis, fuel inventory prediction, and decay heat analysis of an SFR. The benchmark specifications contain modeling details for the ABTR core at the beginning of equilibrium cycle (BOEC) at operating conditions; they were derived from a 2006 preconceptual design report produced by Argonne National Laboratory. The ABTR was designed to demonstrate reactor-based transmutation of transuranics, that is, to “burn” transuranics recovered from light-water reactor (LWR) spent fuel. The ABTR’s fuel is designed to operate in 4 month cycles using uranium/transuranic (U/TRU) metallic fuel, with a TRU content of approximately 20%, at a conversion ratio of approximately 0.6. Various reactivity calculations were performed with SCALE for the ABTR and, where possible, compared with results available in the open literature. Additionally, SCALE was used to perform a full-core depletion calculation over the 4 month cycle to obtain the nuclide inventory at the end of equilibrium cycle (EOEC). These nuclide inventories, decay heat, power profiles, and reactivity feedback coefficients at EOEC represent the initial conditions for analyzing severe accident scenarios with MELCOR.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Assessing kelp nutrient bioextraction capacity in aquaculture farms in the US with implications for conservation and management

This proposal aimed to assess the carbon and nitrogen bioextraction capabilities of sugar kelp farms across a broad geographic range encompassing both the East and West Coasts of the United States. To meet this objective, the project team first developed a cost-effective sampling toolkit using readily available materials and an illustrated protocol to guide kelp farmers in standardized sample collection. Farmers were trained to use the toolkit and prepare samples for shipment to the University of Alaska Fairbanks, where laboratory analyses were conducted to quantify carbon and nitrogen removal. Results were then shared with collaborating farmers, farm managers, regulatory agencies, and the general public to disseminate findings and gauge interest in the bioextraction services offered by kelp aquaculture. The project also investigated temporal and species-specific differences in carbon and nitrogen removal as a complementary objective.

54 ENVIRONMENTAL SCIENCES↗

Political and legal implications of developing and operating a satellite power system

A number of political and legal implications of developing and operating a satellite power system (SPS) are identified and studied in this report. These include the vulnerability of SPS to actions of adversaries, communications impacts, the legality of an SPS in orbit including on-orbit military protection, alleviation of political concerns about deployment and operation of SPS, programmatic planning for SPS and the interaction of SPS with federal regulatory agencies and major departments. In comparing SPS to terrestrial power stations, it is seen that the political problems are neither clearly larger nor clearly smaller--they are clearly different and they are international in nature. If SPS is to become a reality these problems must be dealt with. Five major issues are identified. These must be resolved in order to obtain international acceptance of SPS. However, this study has found no insurmountable obstacles that would clearly prohibit the deployment, operation and protection of an SPS fleet.

Hazelrigg, G. A., Jr.↗

Preliminary calculation of solar cosmic ray dose to the female breast in space mission

No regulatory dose limits are specifically assigned for the radiation exposure of female breasts during manned space flight. However, the relatively high radiosensitivity of the glandular tissue of the breasts and its potential exposure to solar flare protons on short- and long-term missions mandate a priori estimation of the associated risks. A model for estimating exposure within the breast is developed for use in future NASA missions. The female breast and torso geometry is represented by a simple interim model. A recently developed proton dose-buildup procedure is used for estimating doses. The model considers geomagnetic shielding, magnetic-storm conditions, spacecraft shielding, and body self-shielding. Inputs to the model include proton energy spectra, spacecraft orbital parameters, STS orbiter-shielding distribution at a given position, and a single parameter allowing for variation in breast size.

Shavers, Mark↗

Remediation Technology Collaboration Development

This slide presentation reviews programs at NASA aimed at development at Remediation Technology development for removal of environmental pollutants from NASA sites. This is challenging because there are many sites with different environments, and various jurisdictions and regulations. There are also multiple contaminants. There must be different approaches based on location and type of contamination. There are other challenges: such as costs, increased need for resources and the amount of resources available, and a regulatory environment that is increasing.

Mahoney, John↗

Correlation Between Weather Alerts and Grid Component Failures for Grid Alert

Weather events cause most grid failures. Often, we even get notifications on our phones to take cover or be prepared for an imminent event. If electric grid utilities had a similar warning that also included probable scenarios and the equipment involved, they could prepare and minimize the effects. Recent research at Idaho National Laboratory into electric grid risk analysis methods resulted in a tool that allows for the development of the most likely scenarios given failure probabilities of grid components. INL has a project with the U.S. Department of Energy’s Cybersecurity, Energy Security, and Emergency Response (CESER) program to develop a Grid Alert application that receives messages from the existing emergency alert system, filters and determines components possibly affected by the emergency event, calculates probable scenarios uses MASTERRI and then notifies the utility if there is significant risk. Historical failure data of elements that comprise the U.S. electric grid have been compiled by utilities and organizations such as the international regulatory body North American Electric Reliability Corporation (NERC). Nominal failure rates are obtained from this data. To make this tool possible, estimated failure rates are needed for different component types given the alert type, severity, and location. Historic weather-related grid element failures are correlated with historic weather events from Integrated Public Alert & Warning System (IPAWS). These correlated events and failures are used along with Bayesian updates from the historical norms to provide a modified failure rate for grid elements in the alert areas and calculate probable scenarios. This discusses the Grid Alert project plan but focuses on the data gathered and process used in determining failure rates for possible grid failure scenarios.

24 - POWER TRANSMISSION AND DISTRIBUTION↗

Development of Cable Aging Acceptance Criteria for Nuclear Facilities

The aging of nuclear power plant electrical cables has been the subject of substantial research and development (R&D) projects in the nuclear industry, national and international laboratories, universities, and vendor organizations for several years. More specifically, these R&D efforts were conducted to develop equipment and techniques for assessing age-related degradation of in-service cables in nuclear facilities including power plants, research reactors, waste facilities and fuel fabrication plants. In recent years, cable R&D efforts in the nuclear arena have also included work to develop new cables for the next generation of reactors. Over time, exposure to harsh environmental conditions such as elevated temperatures, radiation, and humidity in nuclear installations can result in age-related degradation and failure of cables. In the current fleet of nuclear reactors, there are thousands of miles of cabling installed in each plant and many of these cables are exposed to these harsh environmental conditions. For these cables, the jacket and insulation polymers harden and become brittle over time, making them more susceptible to crack formation and growth, moisture intrusion, and other mechanisms that can lead to cable failure. Moreover, the existing U.S. fleet of 98 nuclear reactors has an average operating age of 38 years. Many of these nuclear power plants have applied for and almost all have been granted regulatory approval for license renewals to operate for 60 years, 20 years beyond their original 40-year life. Further, subsequent license renewals (SLRs) are underway with a few commercial nuclear power sites already approved to operate up to 80 years. As these reactors pursue operating life extensions, utilities must find a way to address issues associated with age-related degradation of cables. Designers of small modular reactors are also in need of technologies to evaluate the performance of cables that will be installed in harsher environments (e.g. higher temperatures, radiation doses, dose rates, etc.) than those present in current-generation reactors. Today, a variety of cable condition monitoring (CM) techniques have been developed and successfully used in nuclear facilities. These techniques are used to identify age-related degradation and assess the condition of cables to determine if their performance characteristics have changed with age. However, objective criteria must be developed for these CM tests to help quantify cable condition and thereby develop repair and replacement schedules. With operating life extending to 80 years and more SLRs on the horizon, both nuclear facilities and regulators need an objective means to determine the aged condition of cables.

36 MATERIALS SCIENCE↗

Development of Cable Aging Acceptance Criteria for Nuclear Facilities

The aging of nuclear power plant electrical cables has been the subject of substantial research and development (R&D) projects in the nuclear industry, national and international laboratories, universities, and vendor organizations for several years. More specifically, these R&D efforts were conducted to develop equipment and techniques for assessing age-related degradation of in-service cables in nuclear facilities including power plants, research reactors, waste facilities and fuel fabrication plants. In recent years, cable R&D efforts in the nuclear arena have also included work to develop new cables for the next generation of reactors. Over time, exposure to harsh environmental conditions such as elevated temperatures, radiation, and humidity in nuclear installations can result in age-related degradation and failure of cables. In the current fleet of nuclear reactors, there are thousands of miles of cabling installed in each plant and many of these cables are exposed to these harsh environmental conditions. For these cables, the jacket and insulation polymers harden and become brittle over time, making them more susceptible to crack formation and growth, moisture intrusion, and other mechanisms that can lead to cable failure. Moreover, the existing U.S. fleet of 98 nuclear reactors has an average operating age of 38 years. Many of these nuclear power plants have applied for and almost all have been granted regulatory approval for license renewals to operate for 60 years, 20 years beyond their original 40-year life. Further, subsequent license renewals (SLRs) are underway with a few commercial nuclear power sites already approved to operate up to 80 years. As these reactors pursue operating life extensions, utilities must find a way to address issues associated with age-related degradation of cables. Designers of small modular reactors are also in need of technologies to evaluate the performance of cables that will be installed in harsher environments (e.g. higher temperatures, radiation doses, dose rates, etc.) than those present in current-generation reactors. Today, a variety of cable condition monitoring (CM) techniques have been developed and successfully used in nuclear facilities. These techniques are used to identify age-related degradation and assess the condition of cables to determine if their performance characteristics have changed with age. However, objective criteria must be developed for these CM tests to help quantify cable condition and thereby develop repair and replacement schedules. With operating life extending to 80 years and more SLRs on the horizon, both nuclear facilities and regulators need an objective means to determine the aged condition of cables.

36 MATERIALS SCIENCE↗

CoolPINNs: A physics-informed neural network modeling of active cooling in vascular systems

Emerging technologies like hypersonic aircraft, space exploration vehicles, and batteries avail fluid circulation in embedded microvasculatures for efficient thermal regulation. Modeling is vital during the design and operational phases of these engineered systems. However, many challenges exist in developing a modeling framework. What is lacking is an accurate framework that (i) captures sharp jumps in the thermal flux across complex vasculature layouts, (ii) deals with oblique derivatives (involving tangential and normal components), (iii) handles nonlinearity because of radiative heat transfer, (iv) provides a high-speed forecast for real-time monitoring, and (v) facilitates robust inverse modeling. Here, this paper addresses these challenges by availing the power of physics-informed neural networks (PINNs). We develop a fast, reliable, and accurate Scientific Machine Learning (SciML) framework for vascular-based thermal regulation—called CoolPINNs: a PINNs-based modeling framework for active cooling. The proposed mesh-less framework elegantly overcomes all the mentioned challenges. The significance of the reported research is multi-fold. First, the framework is valuable for real-time monitoring of thermal regulatory systems because of rapid forecasting. Second, researchers can address complex thermoregulation designs since the approach is meshless. Finally, the framework facilitates systematic parameter identification and inverse modeling studies, perhaps the most significant utility of the current framework.

97 MATHEMATICS AND COMPUTING↗

Atlas of Transcription Factor Binding Sites from ENCODE DNase Hypersensitivity Data across 27 Tissue Types

Characterizing the tissue-specific binding sites of transcription factors (TFs) is essential to reconstruct gene regulatory networks and predict functions for non-coding genetic variation. DNase-seq footprinting enables the prediction of genome-wide binding sites for hundreds of TFs simultaneously. Despite the public availability of high-quality DNase-seq data from hundreds of samples, a comprehensive, up-to-date resource for the locations of genomic footprints is lacking. Here, we develop a scalable footprinting workflow using two state-of-the-art algorithms: Wellington and HINT. We apply our workflow to detect footprints in 192 ENCODE DNase-seq experiments and predict the genomic occupancy of 1,515 human TFs in 27 human tissues. We validate that these footprints overlap true-positive TF binding sites from ChIP-seq. We demonstrate that the locations, depth, and tissue specificity of footprints predict effects of genetic variants on gene expression and capture a substantial proportion of genetic risk for complex traits.

59 BASIC BIOLOGICAL SCIENCES↗

Free Energy and Flexibility Analysis of Autoinhibited Human BRAF

The RAF serine/threonine protein kinases function as direct effectors of RAS in the intracellular transmission of extracellular growth signals, and they are key targets for drug discovery, given the high incidence of oncogenic mutations in RAF and other components of this signaling pathway. In its inactive state, RAF is held in an autoinhibited conformation in the cytosol through a combination of intramolecular interactions and binding to a regulatory 14−3−3 protein dimer. Activation of RAF is initiated by its interaction with membrane-localized GTP-bound RAS, which induces conformational changes that release RAF from its autoinhibited state. However, the molecular mechanisms governing RAF activation remain incomplete, largely due to the challenges in experimentally capturing the intermediate conformational states in this process. To address this gap, we developed a comprehensive all-atom model of BRAF based on existing cryo-EM structures. Using this model, we performed extensive molecular dynamics simulations to evaluate the stability and free energy landscape of autoinhibited BRAF in solution. Our analysis reveals conformational flexibility within the autoinhibited complex, suggesting that this dynamic behavior may play a role in facilitating BRAF activation upon engagement with the membrane-bound RAS.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Towards a dynamic photosynthesis model to guide yield improvement in C4 crops

Summary The most productive C4 food and biofuel crops, such as Saccharum officinarum (sugarcane), Sorghum bicolor (sorghum) and Zea mays (maize), all use NADP‐ME‐type C4 photosynthesis. Despite high productivities, these crops fall well short of the theoretical maximum solar conversion efficiency of 6%. Understanding the basis of these inefficiencies is key for bioengineering and breeding strategies to increase the sustainable productivity of these major C4 crops. Photosynthesis is studied predominantly at steady state in saturating light. In field stands of these crops light is continually changing, and often with rapid fluctuations. Although light may change in a second, the adjustment of photosynthesis may take many minutes, leading to inefficiencies. We measured the rates of CO 2 uptake and stomatal conductance of maize, sorghum and sugarcane under fluctuating light regimes. The gas exchange results were combined with a new dynamic photosynthesis model to infer the limiting factors under non‐steady‐state conditions. The dynamic photosynthesis model was developed from an existing C4 metabolic model for maize and extended to include: (i) post‐translational regulation of key photosynthetic enzymes and their temperature responses; (ii) dynamic stomatal conductance; and (iii) leaf energy balance. Testing the model outputs against measured rates of leaf CO 2 uptake and stomatal conductance in the three C4 crops indicated that Rubisco activase, the pyruvate phosphate dikinase regulatory protein and stomatal conductance are the major limitations to the efficiency of NADP‐ME‐type C4 photosynthesis during dark‐to‐high light transitions. We propose that the level of influence of these limiting factors make them targets for bioengineering the improved photosynthetic efficiency of these key crops.

59 BASIC BIOLOGICAL SCIENCES↗