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At least 1,081 records · Page 60

Fractal landscapes in biological systems: long-range correlations in DNA and interbeat heart intervals

Here we discuss recent advances in applying ideas of fractals and disordered systems to two topics of biological interest, both topics having common the appearance of scale-free phenomena, i.e., correlations that have no characteristic length scale, typically exhibited by physical systems near a critical point and dynamical systems far from equilibrium. (i) DNA nucleotide sequences have traditionally been analyzed using models which incorporate the possibility of short-range nucleotide correlations. We found, instead, a remarkably long-range power law correlation. We found such long-range correlations in intron-containing genes and in non-transcribed regulatory DNA sequences as well as intragenomic DNA, but not in cDNA sequences or intron-less genes. We also found that the myosin heavy chain family gene evolution increases the fractal complexity of the DNA landscapes, consistent with the intron-late hypothesis of gene evolution. (ii) The healthy heartbeat is traditionally thought to be regulated according to the classical principle of homeostasis, whereby physiologic systems operate to reduce variability and achieve an equilibrium-like state. We found, however, that under normal conditions, beat-to-beat fluctuations in heart rate display long-range power law correlations.

Non-NASA Center↗

Circadian and sleep-dependent regulation of hormone release in humans

Daily oscillations characterize the release of nearly every hormone. The circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, generates circadian, approximately 24-hour rhythms in many physiologic functions. However, the observed hormonal oscillations do not simply reflect the output of this internal clock. Instead, daily hormonal profiles are the product of a complex interaction between the output of the circadian pacemaker, periodic changes in behavior, light exposure, neuroendocrine feedback mechanisms, gender, age, and the timing of sleep and wakefulness. The interaction of these factors can affect hormonal secretory pulse frequency and amplitude, with each endocrine system differentially affected by these factors. This chapter examines recent advances in understanding the effects on endocrine rhythms of a number of these factors. Sleep exerts a profound effect on endocrine secretion. Sleep is a dynamic process that is characterized by periodic changes in electrophysiologic activity. These electrophysiologic changes, which are used to mark the state and depth of sleep, are associated with periodic, short-term variations in hormonal levels. The secretion of hormones such as renin and human growth hormone are strongly influenced by sleep or wake state, while melatonin and cortisol levels are relatively unaffected by sleep or wake state. In addition, sleep is associated with changes in posture, behavior, and light exposure, each of which is known to affect endocrine secretion. Furthermore, the tight concordance of habitual sleep and wake times with certain circadian phases has made it difficult to distinguish sleep and circadian effects on these hormones. Specific protocols, designed to extract circadian and sleep information semi-independently, have been developed and have yielded important insights into the effects of these regulatory processes. These results may help to account for changes in endocrine rhythms observed in circadian rhythm sleep disorders, including the dyssomnia of shift work and visual impairment. Yet to be fully investigated are the interactions of these factors with age and gender. Characterization of the factors governing hormone secretion is critical to understanding the temporal regulation of endocrine systems and presents many exciting areas for future research.

Non-NASA Center↗

Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature

In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.

Non-NASA Center↗

Molecular evidence of simian virus 40 infections in children

Recent studies have detected simian virus 40 (SV40) DNA in certain human tumors and normal tissues. The significance of human infections by SV40, which was first discovered as a contaminant of poliovirus vaccines used between 1955 and 1963, remains unknown. The occurrence of SV40 infections in unselected hospitalized children was evaluated. Polymerase chain reaction and DNA sequence analyses were done on archival tissue specimens from patients positive for SV40 neutralizing antibody. SV40 DNA was identified in samples from 4 of 20 children (1 Wilms' tumor, 3 transplanted kidney samples). Sequence variation among SV40 regulatory regions ruled out laboratory contamination of specimens. This study shows the presence of SV40 infections in pediatric patients born after 1982.

Non-NASA Center↗

Cell and molecular biology of simian virus 40: implications for human infections and disease

Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

Review↗

Regulation of body fluid volume and electrolyte concentrations in spaceflight

Despite a number of difficulties in performing experiments during weightlessness, a great deal of information has been obtained concerning the effects of spaceflight on the regulation of body fluid and electrolytes. Many paradoxes and questions remain, however. Although body mass, extracellular fluid volume, and plasma volume are reduced during spaceflight and remain so at landing, the changes in total body water are comparatively small. Serum or plasma sodium and osmolality have generally been unchanged or reduced during the spaceflight, and fluid intake is substantially reduced, especially during the first of flight. The diuresis that was predicted to be caused by weightlessness, has only rarely been observed as an increased urine volume. What has been well established by now, is the occurrence of a relative diuresis, where fluid intake decreases more than urine volume does. Urinary excretion of electrolytes has been variable during spaceflight, but retention of fluid and electrolytes at landing has been consistently observed. The glomerular filtration rate was significantly elevated during the SLS missions, and water and electrolyte loading tests have indicated that renal function is altered during readaptation to Earth's gravity. Endocrine control of fluid volumes and electrolyte concentrations may be altered during weightlessness, but levels of hormones in body fluids do not conform to predictions based on early hypotheses. Antidiuretic hormone is not suppressed, though its level is highly variable and its secretion may be affected by space motion sickness and environmental factors. Plasma renin activity and aldosterone are generally elevated at landing, consistent with sodium retention, but inflight levels have been variable. Salt intake may be an important factor influencing the levels of these hormones. The circadian rhythm of cortisol has undoubtedly contributed to its variability, and little is known yet about the influence of spaceflight on circadian rhythms. Atrial natriuretic peptide does not seem to play an important role in the control of natriuresis during spaceflight. Inflight activity of the sympathetic nervous system, assessed by measuring catecholamines and their metabolites and precursors in body fluids, generally seems to be no greater than on Earth, but this system is usually activated at landing. Collaborative experiments on the Mir and the International Space Station should provide more of the data needed from long-term flights, and perhaps help to resolve some of the discrepancies between U.S. and Russian data. The use of alternative methods that are easier to execute during spaceflight, such as collection of saliva instead of blood and urine, should permit more thorough study of circadian rhythms and rapid hormone changes in weightlessness. More investigations of dietary intake of fluid and electrolytes must be performed to understand regulatory processes. Additional hormones that may participate in these processes, such as other natriuretic hormones, should be determined during and after spaceflight. Alterations in body fluid volume and blood electrolyte concentrations during spaceflight have important consequences for readaptation to the 1-G environment. The current assessment of fluid and electrolyte status during weightlessness and at landing and our still incomplete understanding of the processes of adaptation to weightlessness and readaptation to Earth's gravity have resulted in the development of countermeasures that are only partly successful in reducing the postflight orthostatic intolerance experienced by astronauts and cosmonauts. More complete knowledge of these processes can be expected to produce countermeasures that are even more successful, as well as expand our comprehension of the range of adaptability of human physiologic processes.

NASA Discipline Number 18-10↗

A dual-input nonlinear system analysis of autonomic modulation of heart rate

Linear analyses of fluctuations in heart rate and other hemodynamic variables have been used to elucidate cardiovascular regulatory mechanisms. The role of nonlinear contributions to fluctuations in hemodynamic variables has not been fully explored. This paper presents a nonlinear system analysis of the effect of fluctuations in instantaneous lung volume (ILV) and arterial blood pressure (ABP) on heart rate (HR) fluctuations. To successfully employ a nonlinear analysis based on the Laguerre expansion technique (LET), we introduce an efficient procedure for broadening the spectral content of the ILV and ABP inputs to the model by adding white noise. Results from computer simulations demonstrate the effectiveness of broadening the spectral band of input signals to obtain consistent and stable kernel estimates with the use of the LET. Without broadening the band of the ILV and ABP inputs, the LET did not provide stable kernel estimates. Moreover, we extend the LET to the case of multiple inputs in order to accommodate the analysis of the combined effect of ILV and ABP effect on heart rate. Analyzes of data based on the second-order Volterra-Wiener model reveal an important contribution of the second-order kernels to the description of the effect of lung volume and arterial blood pressure on heart rate. Furthermore, physiological effects of the autonomic blocking agents propranolol and atropine on changes in the first- and second-order kernels are also discussed.

NASA Discipline Regulatory Physiology↗

Two cis elements collaborate to spatially repress transcription from a sea urchin promoter

The expression pattern of many territory-specific genes in metazoan embryos is maintained by an active process of negative spatial regulation. However, the mechanism of this strategy of gene regulation is not well understood in any system. Here we show that reporter constructs containing regulatory sequence for the SM30-alpha gene of Stronglyocentrotus purpuratus are expressed in a pattern congruent with that of the endogenous SM30 gene(s), largely as a result of active transcriptional repression in cell lineages in which the gene is not normally expressed. Chloramphenicol acetyl transferase assays of deletion constructs from the 2600-bp upstream region showed that repressive elements were present in the region from -1628 to -300. In situ hybridization analysis showed that the spatial fidelity of expression was severely compromised when the region from -1628 to -300 was deleted. Two highly repetitive sequence motifs, (G/A/C)CCCCT and (T/C)(T/A/C)CTTTT(T/A/C), are present in the -1628 to -300 region. Representatives of these elements were analyzed by gel mobility shift experiments and were found to interact specifically with protein in crude nuclear extracts. When oligonucleotides containing either sequence element were co-injected with a correctly regulated reporter as potential competitors, the reporter was expressed in inappropriate cells. When composite oligonucleotides, containing both sequence elements, were fused to a misregulated reporter, the expression of the reporter in inappropriate cells was suppressed. Comparison of composite oligonucleotides with oligonucleotides containing single constituent elements show that both sequence elements are required for effective spatial regulation. Thus, both individual elements are required, but only a composite element containing both elements is sufficient to function as a tissue-specific repressive element.

Non-NASA Center↗

The role of cytokines in immune changes induced by spaceflight

It has become apparent that spaceflight alters many immune responses. Among the regulatory components of the immune response that have been shown to be affected by spaceflight is the cytokine network. Spaceflight, as well as model systems of spaceflight, have been shown to affect the production and action of various cytokines including interferons, interleukins, colony stimulating factors, and tumor necrosis factors. These changes have been shown not to involve a general shutdown of the cytokine network but, rather, to involve selective alterations of specific cytokine functions by spaceflight. The full breadth of changes in cytokines induced by spaceflight, as well as mechanisms, duration, adaptation, reversibility, and significance to resistance to infection and neoplastic diseases, remains to be established.

NASA Discipline Number 18-10↗

Long-range correlations in nucleotide sequences

DNA sequences have been analysed using models, such as an n-step Markov chain, that incorporate the possibility of short-range nucleotide correlations. We propose here a method for studying the stochastic properties of nucleotide sequences by constructing a 1:1 map of the nucleotide sequence onto a walk, which we term a 'DNA walk'. We then use the mapping to provide a quantitative measure of the correlation between nucleotides over long distances along the DNA chain. Thus we uncover in the nucleotide sequence a remarkably long-range power law correlation that implies a new scale-invariant property of DNA. We find such long-range correlations in intron-containing genes and in nontranscribed regulatory DNA sequences, but not in complementary DNA sequences or intron-less genes.

NASA Discipline Cardiopulmonary↗

Public Safety: Fighting Crime and Terrorism; Border Security

This chapter discusses risks from unintentional or illicit movement of nuclear and radioactive material out of regulatory control through international border crossing points, summarizes international efforts to build capacity and support border security, and discusses how detection equipment can be used to screen for penetrating radiation at traditional border crossing points.

border security↗

A Circular Economy for Lithium-Ion Batteries Used in Mobile and Stationary Energy Storage: Drivers, Barriers, Enablers, and Policy Considerations

The demand for large-format lithium-ion batteries (LIB) is expected to continue in the U.S. to meet renewable energy and decarbonization goals. Total installed large-scale stationary battery energy storage is expected to increase almost 10-fold from 2021 to 2025 and LIBs account for 97% of the expected market share. Similarly, LIBs deployed in electric vehicles is expected to increase, with passenger electric vehicles alone expected to reach 16 million units on U.S. roads by 2030 and 46 million by 2025. The expected demand for LIBs brings supply chain concerns and a growing need for a circular economy for LIB materials. Domestic reuse and recycling is one potential circular economy solution for LIB. This presentation identifies drivers, barriers, and enablers to a circular economy for LIBs, as well as, the current U.S. law and regulatory landscape for the reuse and recycling of LIB materials, and how certain policy frameworks impact reuse and end-of-life management decisions for LIB materials.

barriers↗

Pathways to Overcome Geothermal Deployment Barriers

Geothermal resources represent a vast domestic energy supply that can provide a fexible and reliable source of electricity as well as contribute to clean energy goals. In the United States, geothermal exploration and development are subject to numerous permits, authorizations, and other regulatory requirements at the federal, state, and local level. These are necessary to address potential environmental and resource impacts at geothermal project sites, but may act as barriers to geothermal deployment, slowing timelines and raising costs. The 2022 NREL report, Non-Technical Barriers to Geothermal Development in California and Nevada, presents fndings of a study on non-technical barriers that may infuence geothermal project development.

geothermal↗

Mass Production of Microreactors: A Look at Potential Scenarios and Fabrication Facility Requirements

Microreactors may be able to be cost competitive in niche markets, but they are likely to be much more expensive than small modular reactors or large reactors in terms of levelized cost. The vision of microreactors being catered to larger markets relies heavily on their ability to be mass produced and cut costs. Since commercial nuclear reactors have not been mass produced before it is challenging to estimate what kind of manufacturing facilities will be needed, what they will cost, and how factory considerations influence the unit cost of microreactors. This summary attempts to imagine the various possible production layouts of microreactors and identify the different possible manufacturing facilities (factories) that might be required. Regulatory and economic considerations for these layouts and factories are then listed.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

A Simple Data-Centric Methodology for Producible Geothermal Well Determinations: Preprint

The Bureau of Land Management (BLM) has traditionally lacked a standardized methodology for determining if a newly drilled geothermal well is "producible," a designation essential for deciding whether a lease should be "held by production." This is a straightforward problem to solve in oil and gas: Demonstrate that a well is economically viable, meaning it produces sufficient oil or gas to exceed direct operating costs and lease-related expenses, such as rentals or minimum royalties. In geothermal, the problem is more complex: Geothermal wells are tightly coupled with the downstream infrastructure - specifically, the power plant, which is often not designed until well after a lease is deemed as "held by production." Although this designation is critical for advancing geothermal power plant development on BLM-managed lands, current geothermal well assessments often rely on ad hoc approaches that can be complex, operator-biased, and heavy in assumptions related to economic viability. To address this, we have developed two complementary methodologies: a minimum power requirement-based approach and a productivity index (PI)-based approach. These methods leverage key flow test data - pressure, temperature, flow rate, and specific enthalpy - to provide reliable and standardized producible well determinations. The minimum power requirement-based approach evaluates wells against specific power output thresholds informed by reservoir experts and the associated temperature requirements. The PI-based approach assesses well productivity using widely accepted reservoir engineering metrics, proposing a threshold of 2.5 kg/s/bar. Both methods are data-driven and grounded in empirical production data from operational geothermal wells, avoiding uncertain economic assumptions while maintaining decision-making accuracy. Wells falling below key performance thresholds (i.e., PI, specific power) are deemed non-producible. These methodologies aim to streamline BLM's decision-making process, reduce nontechnical barriers to geothermal energy adoption, and enable regulatory expansion into states lacking geothermal expertise. Preliminary results indicate clear trends and thresholds in production data that provide actionable insights for evaluating well producibility. Validation using well completion report (WCR) data is ongoing, with promising results demonstrating the potential for these standardized methodologies to impact geothermal development significantly.

15 GEOTHERMAL ENERGY↗

AI for Interpreting Nuclear Power Plant Documents for Power Uprates

To reduce the cost and time needed for regulatory compliance, nuclear power plants (NPPs) can utilize artificial intelligence (AI) to assist in interpreting complex and voluminous documents that typically span thousands of pages. Usually, the process of interpreting a plant’s technical specifications (TSs) and associated documents is labor intensive. This study aims to understand what processes state-of-the-art large language models (LLMs) can automate and to identify the pitfalls associated with using LLMs to reduce human labor costs and time. This research uses a recent AI technology called retrieval augmented generation (RAG), which retrieves pages of information from TSs and associated documents to assist with NPP power uprates (cleared to produce more power). LLMs are integral to RAG because they create human-like responses based on the retrieved information, aiding in the interpretation and application processes. A baseline case demonstrates how LLMs can operate successfully for a power uprate application. Then five use cases show five types of potential failures: (1) RAG retrieving the incorrect information, (2) RAG misinterpreting the retrieved information, (3) RAG relying on knowledge not contained in the retrieved information, (4) RAG hallucinating, and (5) RAG refusing to answer. The results of the five use cases suggest that automating the human interpretation of TSs and associated documents with AI should be approached with caution. A subject-matter expert reviewed the AI outputs from the five use cases and concluded that an LLM can produce technical information that is needed to produce power uprate applications in certain instances.

21 - SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLAN↗

BESS Digital Assurance, Supply Chain Risk Management, and Emerging Regulation Session One - Abridged

The TADA BESS Supply Chain Workshops are designed to equip participants with the knowledge and tools necessary to address the evolving challenges at the intersection of battery energy storage systems (BESS), cybersecurity, and supply chain vulnerabilities. The workshops emphasize the application of Cyber-Informed Engineering (CIE) principles using INL’s procurement guide and the CIE-BAT tool. Attendees will develop risk-based security strategies and actionable compliance roadmaps tailored to their BESS projects. Additionally, the program fosters a collaborative network of practitioners and provides guidance on navigating emerging regulatory requirements, including FEOC rules under the OBBB framework, to assess and enhance organizational readiness. This is Session 1 of 3.

25 - ENERGY STORAGE↗