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NASA NTRSDate not supplied

Radiation and Nuclear Technology in Planetary Cave Environments

Many technological and environmental challenges must be resolved to enable successful lunar habitation and exploration, and to maximize scientific return. This presentation is intended as a preliminary discussion on three such areas of interest with the intent to identify likely areas of mutual benefit for collaboration and data sharing between the space nuclear and radiological disciplines with the planetary cave community. First is the previously identified and studied possible application of lunar lava tubes or pits to reduce the solar and cosmic radiation environment burden on crew health and hardware reliability. This is an area of continued interest, and should be kept in the forefront of discussion during the selection of sites for potential exploration or long-term habitation. In theory, the prospect of using existing morphology presents an enticing opportunity to reduce the requirements on landed mass or construction while also reducing dose or fluence of harmful natural radiation. However, such discussions should also include the practical implications of relocating habitation hardware and personnel from a landing site to a subsurface location. Inherent risks associated with landing in proximity to the relevant terrain must also be considered and weighed against those imposed by the natural radiation environment. Second is a discussion on the means by which a long-term habitation module or base of operations may be powered throughout the lunar day-night cycle. Fission surface power presents an opportunity to establish round-the-clock power in any lunar surface environment, including permanently shadowed regions where solar panels cannot operate, or in any other non-polar region where solar radiation is available for no more than two weeks per four-week cycle. Among the drawbacks of fission surface power is the need to either land and co-locate a heavy shield to minimize radiological consequences to personnel or equipment, land and operate construction equipment capable of restructuring the in-situ regolith to provide appropriate shielding, or to make use of existing topology features (e.g. craters or pits) to serve as pre-formed radiation barriers. A realistic assessment of the practicality of this third option should involve the selection of candidate features from existing surveys, and assess the effectiveness of the approach using modern radiation transport methodologies. Consideration must be made for the needs to reject waste heat in the thermal power conversion process, which typically requires the use of large area radiators. Energy must be exchanged from the reactor and power conversion system to such radiators, and the impacts on thermal efficiency and secondary scatter of nuclear radiation must be considered. Further consideration should be made for the implications of placement of a power source such that it does not sacrifice valuable scientific opportunity. Placement of a reactor is likely to thereafter prevent personnel access within that feature. Third is a discussion on the use of portable radioisotope power systems (RPS) within confined spaces, both with respect to the dose effects of emitted nuclear radiation and also performance associated with emitted thermal radiation. Radioisotope power systems provide a unique capability to power objects with no reliance upon solar radiance. However, their useable power production relies upon the flow of heat from ‘hot side’ (decaying radioisotope) to ‘cold side’ (radiators emitting heat to space). In the case of a confined volume in vacuum such as a lunar lava tube, that radiated energy will absorb into the wall, which is already above the ‘cold background’ temperature of dark space, and then gradually rises in temperature. That temperature rise, and its implications on availability of useable electrical power, will depend upon factors such as enclosure volume, thermal emissivity/absorptivity, and thermal conductivity through the depth of absorbing media. The advantages of nuclear technology may prove to enable unique scientific exploration opportunities, both above the lunar surface and below. In turn, the unique advantages of lunar lava tubes or pits may present unique opportunities to enhance the application of these technologies and to mitigate the effects of radiation from both natural and technological sources. A discussion on these pairings may prove to be valuable to all, in our endeavor to explore our neighboring worlds.

Radiation↗

DOE OSTI2021

Experimental Evaluation of Deformation and Fracture Mechanisms in Highly Irradiated Austenitic Steels

The present report documents recent experimental results of analysis using scanning electron microscopy/electron backscatter diffraction (SEM-EBSD) of plastic deformation mechanisms and strain localization phenomena in austenitic steels irradiated by neutrons. Experiments were performed with specimens irradiated to 125 dpa and, additionally, with specimens that experienced radiation-induced swelling up to 3%. Section 1 briefly analyzes the deformation localization in irradiated steels and its consequences on the material performance. The section describes the advantages and importance of the SEM-EBSD approach combined with in situ mechanical testing capability. Section 2 briefly introduces the experimental tools and methods (i.e., SEM/EBSD in situ tensile frame, electric discharge machine to manufacture irradiated specimens) and describes the investigated materials (i.e., element composition, irradiation conditions, and general microstructure). Section 3 describes the key experimental results and provides a brief analysis and comparison with the datasets obtained earlier within the same task (i.e., low-dose specimens). The discussion focuses on EBSD microstructure maps with strain localization features, misorientation evolution as a function of strain, and observed deformation mechanisms. Section 4 evaluates data collected in recent years on highly irradiated steel and estimates the possible misorientation evolution under irradiation. The section introduces and discusses the concept of in-service-induced damage as an irradiation-assisted stress-corrosion cracking precursor. Section 5 summarizes the work performed. As expected, the present work results are beneficial for exploring and understanding degradation mechanisms in highly irradiated in-core materials found in light water reactors after long-term in-service life.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

NASA NTRS2002

Behavioral consequences of radiation exposure to simulated space radiation in the C57BL/6 mouse: open field, rotorod, and acoustic startle

Two experiments were carried out to investigate the consequences of exposure to proton radiation, such as might occur for astronauts during space flight. C57BL/6 mice were exposed, either with or without 15-g/cm2 aluminum shielding, to 0-, 3-, or 4-Gy proton irradiation mimicking features of a solar particle event. Irradiation produced transient direct deficits in open-field exploratory behavior and acoustic startle habituation. Rotorod performance at 18 rpm was impaired by exposure to proton radiation and was impaired at 26 rpm, but only for mice irradiated with shielding and at the 4-Gy dose. Long-term (>2 weeks) indirect deficits in open-field activity appeared as a result of impaired experiential encoding immediately following exposure. A 2-week recovery prior to testing decreased most of the direct effects of exposure, with only rotorod performance at 26 rpm being impaired. These results suggest that the performance deficits may have been mediated by radiation damage to hippocampal, cerebellar, and possibly, forebrain dopaminergic function.

Non-NASA Center↗

DOE OSTI2025

Plasmonic Ag nanocomposite phosphate glasses produced via γ-ray irradiation as reduction route

This paper reports on the impact of γ-ray irradiation (10, 100 kGy) on melt-quenched Ag + -doped phosphate glass and the effects of subsequent thermal processing leading to the production of plasmonic Ag nanocomposites. The γ-irradiated glasses were characterized alongside the pristine by differential scanning calorimetry (DSC), Raman spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, optical absorption, and photoluminescence (PL) spectroscopy. DSC characterization showed consistent glass transition temperatures (T g ) before and after γ-irradiation whereas the crystallization temperatures tended to decrease with increasing γ-ray dose. However, a lack of alteration of the glass network structure was supported by Raman spectroscopy. Room temperature EPR spectra clearly showed the formation of phosphorus oxygen hole center (POHC) defects in the undoped host, in addition to another doublet likely associated with a P 3 defect. The presence of paramagnetic silver species encompassing Ag 2+ and 107/109 Ag 0 atoms was also indicated in the silver-activated glass together with POHC defects. Optical absorption spectra were also consistent with the presence of various radiation-induced centers. Further analyzing the glass absorption edge via Tauc plots suggested the formation of electron center (EC) defects in γ-irradiated samples wherein the silver-doped glass exhibited decreasing band gap energies with increasing γ-ray dose. The PL characterization showed the silver-related radio-PL effect was induced exhibiting broad band emission with two maxima around 500 and 625 nm stemming from various molecular Ag$^{x+}_{n}$ clusters. Emission decay analyses revealed that the longer wavelength emission exhibited slower decay. The highest radiation dose of 100 kGy however resulted in weaker emission and faster decay kinetics attributed to energy transfer between the luminescent silver species and POHC defects. Finally subjecting the γ-irradiated Ag-doped glasses to heat treatment near the T g at 490 °C led to the development of the surface plasmon resonance of Ag nanoparticles (NPs) and the vanishing of the Ag$^{x+}_{n}$ clusters luminescence. In conclusion, the presence of the matrix-related EC defects was deemed accountable for the thermally induced reduction and consequent precipitation of Ag NPs making the plasmonic glasses attractive for photonic applications such as nonlinear optics.

36 MATERIALS SCIENCE↗

DOE OSTI2021

Modulating Electron Beam–Sample Interactions in Imaging and Diffraction Modes by Dose Fractionation with Low Dose Rates

Abstract Technological opportunities are explored to enhance detection schemes in transmission electron microscopy (TEM) that build on the detection of single-electron scattering events across the typical spectrum of interdisciplinary applications. They range from imaging with high spatiotemporal resolution to diffraction experiments at the window to quantum mechanics, where the wave-particle dualism of single electrons is evident. At the ultimate detection limit, where isolated electrons are delivered to interact with solids, we find that the beam current dominates damage processes instead of the deposited electron charge, which can be exploited to modify electron beam-induced sample alterations. The results are explained by assuming that all electron scattering are inelastic and include phonon excitation that can hardly be distinguished from elastic electron scattering. Consequently, a coherence length and a related coherence time exist that reflect the interaction of the electron with the sample and change linearly with energy loss. Phonon excitations are of small energy (<100 meV), but they occur frequently and scale with beam current in the irradiated area, which is why we can detect their contribution to beam-induced sample alterations and damage.

47 OTHER INSTRUMENTATION↗

NASA NTRSDate not supplied

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Health and Pharmacogenomics

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expand in duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to tailor medications for individual crewmembers and further examine appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique clinical and environmental history, genetic makeup, and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. A subset of this field is pharmacogenomics (PGX), the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on drug choice and dosing to avoid adverse events and maximize efficacy. The study goal was to identify which current space pharmacy drugs could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs on the ISS was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both astronauts’ personal medications, including supplements and over the counter drugs (n=151) contained in the ISS medical accessory kit (IMAK), and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in a total of 157 drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure (LxC). Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent ineffective treatment or impactful side effect events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost, or technical criteria and ranked from 1 (very low) to 5 (very high). An assessment of PGX reference laboratories is currently underway to evaluate sample requirements, benefit analysis (cost vs. utility of allele variant analysis), relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments (LxC 5x5 table) indicated 128 medications were in the green zone where risk is acceptable, with the remaining 29 of the medications in the yellow or red zone driven predominantly due to drug failure or safety concerns. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive preflight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve drug efficacy, and further open the door to countermeasure research. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more effective and efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing selection of the best treatment choice, and providing tailored countermeasures for individual crewmembers.

Pharmacogenomics↗

NASA NTRSDate not supplied

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Medicine and Pharmacogenomics for Human Deep Space Exploration

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expanding duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be even more essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to further tailor medications included in the spacecraft formulary and increased examination of appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of cutting-edge research and medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique factors and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. One example is the field of pharmacogenomics (PGX),the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on pharmaceutical choice and dosing to avoid adverse drug events and maximize pharmacological efficacy. The goal of this study was to evaluate which drugs in the current space pharmacy could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs onboard the International Space Station (ISS) was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both personal astronaut medications, including supplements and over the counter drugs (n=151) and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in 157 total drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure. Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent adverse events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost or technical and ranked from 1 (very low) to 5 (very high).A comprehensive assessment of commercially available PGX solutions is currently underway to evaluate specimen requirements, cost/benefit analysis (cost vs. number of alleles assessed), utility of variant analysis, relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments(LxC 5x5 table) indicated29medicationswere in the yellow or red zone driven predominantly by drug failure or safety concerns, with the remainder(n=128)of the medications in the green zone where risk is acceptable. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive pre-flight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve targeting drug efficacy and safety, and further open the door to countermeasure research exploring PGX-related allelic variants. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more cost effective and more efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing crew autonomy and providing tailored countermeasures

Alice R W Tang↗

DOE OSTI2021

Validation of the Public Radiation Exposure Calculation for the Incident at the National Institute of Standards and Technology Center for Neutron Research on February 3, 2021

The Department of Energy/National Nuclear Security Administration Consequence Management Program was contacted by the Health Physics Chief of the National Institute of Standards and Technology Center for Neutron Research (NCNR) to review public radiation exposure calculations for an event that occurred on its Gaithersburg, Maryland, campus on February 3, 2021. Subject matter experts from the Nuclear Emergency Support Team (NEST) assets, specifically the Consequence Management Home Team (CMHT) and the National Atmospheric Release Advisory Center (NARAC), were selected to provide support. CMHT used three separate modeling codes to validate the results the scientists at NCNR calculated using the HotSpot model. The analyses were performed using NARAC’s in-house Lagrangian dispersion codes known as LODI and Aeolus, as well as the Turbo FRMAC software from Sandia National Laboratories. The team used parameters provided by the NCNR scientists regarding the site, applicable observable meteorological data, and environmental survey and sampling data to estimate public exposure. Each model estimated public dose at much less than 0.5 mrem. CMHT concurs with the NCNR public radiation exposure calculations which state that members of the public at the 400-meter boundary would have received a radiological dose of less than 0.5 mrem.

61 RADIATION PROTECTION AND DOSIMETRY↗

NASA NTRS2008

Logic Gates Made of N-Channel JFETs and Epitaxial Resistors

Prototype logic gates made of n-channel junction field-effect transistors (JFETs) and epitaxial resistors have been demonstrated, with a view toward eventual implementation of digital logic devices and systems in silicon carbide (SiC) integrated circuits (ICs). This development is intended to exploit the inherent ability of SiC electronic devices to function at temperatures from 300 to somewhat above 500 C and withstand large doses of ionizing radiation. SiC-based digital logic devices and systems could enable operation of sensors and robots in nuclear reactors, in jet engines, near hydrothermal vents, and in other environments that are so hot or radioactive as to cause conventional silicon electronic devices to fail. At present, current needs for digital processing at high temperatures exceed SiC integrated circuit production capabilities, which do not allow for highly integrated circuits. Only single to small number component production of depletion mode n-channel JFETs and epitaxial resistors on a single substrate is possible. As a consequence, the fine matching of components is impossible, resulting in rather large direct-current parameter distributions within a group of transistors typically spanning multiples of 5 to 10. Add to this the lack of p-channel devices to complement the n-channel FETs, the lack of precise dropping diodes, and the lack of enhancement mode devices at these elevated temperatures and the use of conventional direct coupled and buffered direct coupled logic gate design techniques is impossible. The presented logic gate design is tolerant of device parameter distributions and is not hampered by the lack of complementary devices or dropping diodes. In addition to n-channel JFETs, these gates include level-shifting and load resistors (see figure). Instead of relying on precise matching of parameters among individual JFETS, these designs rely on choosing the values of these resistors and of supply potentials so as to make the circuits perform the desired functions throughout the ranges over which the parameters of the JFETs are distributed. The supply rails V(sub dd) and V(sub ss) and the resistors R are chosen as functions of the distribution of direct-current operating parameters of the group of transistors used.

Krasowski, Michael J.↗

DOE OSTI2020

Dynamic clay microstructures emerge via ion complexation waves

Clays control carbon, water and nutrient transport in the lithosphere, promote cloud formation5 and lubricate fault slip through interactions among hydrated mineral interfaces. Clay mineral properties are difficult to model because their structures are disordered, curved and dynamic. Consequently, interactions at the clay mineral-aqueous interface have been approximated using electric double layer models based on single crystals of mica and atomistic simulations. We discover that waves of complexation dipoles at dynamically curving interfaces create an emergent long-range force that drives exfoliation and restacking over time- and length-scales that are not captured in existing models. Curvature delocalizes electrostatic interactions in ways that fundamentally differ from planar surfaces, altering the ratio of ions bound to the convex and concave sides of a layer. Multiple-scattering reconstruction of low-dose energy-filtered cryo electron tomography enabled direct imaging of ion complexes and electrolyte distributions at hydrated and curved mineral interfaces with {\aa}ngstrom resolution over micron length scales. Layers exfoliate and restack abruptly and repeatedly over timescales that depend strongly on the counterion identity, demonstrating that the strong coupling between elastic, electrostatic and hydration forces in clays promote collective reorganization previously thought to be a feature only of active matter.

Whittaker, Michael L↗

NASA NTRS2003

A short pulse of mechanical force induces gene expression and growth in MC3T3-E1 osteoblasts via an ERK 1/2 pathway

Physiological mechanical loading is crucial for maintenance of bone integrity and architecture. We have calculated the strain caused by gravity stress on osteoblasts and found that 4-30g corresponds to physiological levels of 40-300 microstrain. Short-term gravity loading (15 minutes) induced a 15-fold increase in expression of growth-related immediate early gene c-fos, a 5-fold increase in egr-1, and a 3-fold increase in autocrine bFGF. The non-growth-related genes EP-1, TGF-beta, and 18s were unaffected by gravity loading. Short-term physiological loading induced extracellular signal-regulated kinase (ERK 1/2) phosphorylation in a dose-dependent manner with maximum phosphorylation saturating at mechanical loading levels of 12g (p < 0.001) with no effect on total ERK. The phosphorylation of focal adhesion kinase (FAK) was unaffected by mechanical force. g-Loading did not activate P38 MAPK or c-jun N-terminal kinase (JNK). Additionally, a gravity pulse resulted in the localization of phosphorylated ERK 1/2 to the nucleus; this did not occur in unloaded cells. The induction of c-fos was inhibited 74% by the MEK1/2 inhibitor U0126 (p < 0.001) but was not affected by MEK1 or p38 MAPK-specific inhibitors. The long-term consequence of a single 15-minute gravity pulse was a 64% increase in cell growth (p < 0.001). U0126 significantly inhibited gravity-induced growth by 50% (p < 0.001). These studies suggest that short periods of physiological mechanical stress induce immediate early gene expression and growth in MC3T3-E1 osteoblasts primarily through an ERK 1/2-mediated pathway.

NASA Discipline Cell Biology↗

NASA NTRS2005

Developing OSL Geological Dating Techniques for Use on Future Missions to Mars

The surface of Mars has been subject to aeolian, fluvial, and periglacial activity in the (relatively) recent past. Unfortunately, chronological dating of recent events on Mars is difficult as the errors associated with crater counting are comparable to younger ages (approx. 1 Ma). Consequently, techniques to quantify the ages of geological processes on Mars have become an important area of research. Optically stimulated luminescence (OSL) dating is one candidate technique for in-situ dating of the deposition of Martian surface sediments. This method can aid in developing a geological and climatic history of the last million years on Mars. The current paper addresses some of the challenges and progress associated with developing OSL as a viable in-situ dating technique for Mars. Some of the challenges include the mineral composition, the effectiveness of solar resetting under Martian conditions, the temperature regime, and determining the natural dose rate on Mars. All of these topics are currently under investigation, and some preliminary results are presented.

Blair, M. W.↗

DOE OSTI2024

Transfer functions for Q A /Q B international regulatory limits for the safe transport of radioactive materials

This paper presents a proposed revision of the International Atomic Energy Agency transport regulations, related to the A 1 and A 2 limit values used to determine the radioactive transport classification. Based on the 'Q system', a novel methodology was introduced to derive Q A and Q B values related to scenarios involving external exposure from a distant source. These values are key parameters that respectively represent the total effective dose and total equivalent dose to the skin, from all primary and secondary particles contributing to radiation exposure. The International Working Group (WG A 1 /A 2 ) is established and associated with the TRANSSC Technical Expert Group on Radiation Protection. A review of the A 1 and A 2 values is performed in response to identified limitations within the existing Q system. The followed approach is based on Monte Carlo simulations that enabled the development of transfer functions aimed at reducing computational time and increasing the flexibility of dose evaluations for any radionuclide with known particle emission spectra. This method allows updating the Q A and Q B values to account for future data evolutions (decay data, fluence-to-dose conversion coefficients) and standardizing the calculation of regulation limits across all referenced radionuclides and scenarios related to external exposure. The transfer functions are established using three Monte Carlo simulation codes—FLUKA, Geant4, and MCNP—and address the previous limitations of the 'Q system', reflecting the latest International Commission for Radiation Protection recommendations and improvements in calculation techniques. The results of the WG show consistent agreement across the codes, with minor discrepancies observed at low primary energies due to statistical uncertainties and different handling of stopping power for electrons/positrons in the codes. This revised approach aligns with current standards and recommendations, ensuring that the radiological consequences of transport accidents are acceptable for the new A 1 and A 2 limits from a radiological protection perspective.

61 RADIATION PROTECTION AND DOSIMETRY↗

NASA NTRS1992

Ionizing radiation exposure of LDEF (pre-recovery estimates)

The long duration exposure facility (LDEF), launched into a 258 nautical mile orbit with an inclination of 28.5 degrees, remained in space for nearly 6 yr. The 21,500 lb NASA satellite was one of the largest payloads ever deployed by the Space Shuttle. LDEF completed 32,422 orbits and carried 57 major experiments representing more than 200 investigators from 33 private companies, 21 universities and nine countries. The experiments covered a wide range of disciplines including basic science, electronics, optics, materials, structures and power and propulsion. A number of the experiments were specifically designed to measure the radiation environment. These experiments are of specific interest, since the LDEF orbit is essentially the same as that of the Space Station Freedom. Consequently, the radiation measurements on LDEF will play a significant role in the design of radiation shielding of the space station. The contributions of the various authors presented here attempt to predict the major aspects of the radiation exposure received by the various LDEF experiments and therefore should be helpful to investigators who are in the process of analyzing experiments which may have been affected by exposure to ionizing radiation. The paper discusses the various types and sources of ionizing radiation including cosmic rays, trapped particles (both protons and electrons) and secondary particles (including neutrons, spallation products and high-LET recoils), as well as doses and LET spectra as a function of shielding. Projections of the induced radioactivity of LDEF are also discussed.

Flight Experiment↗

NASA NTRS2007

Utility of DF-1 for Radioprotection in Lymphocytes

The development of degenerative changes in the vasculature, such as atherosclerosis, is a known consequence of exposure to ionizing radiation, and is thus a concern for astronaut health following long duration space flight. Cellular damage caused by radiation is due to free radical generation and DNA damage. The goal of this project was to assess the ability of a C60-derivative, DF-1, to mitigate cellular damage resulting from radiation exposure in primary human lymphocytes. DF-1 is a water-soluble C60 fullerene encapsulated in dendrimeric functional groups that is proposed to exhibit antioxidant properties. Human lymphocytes are radiosensitive and travel throughout the body potentially causing bystander effects in any tissues they contact. These cells were subjected to varying doses of gamma radiation in the presence or absence of DF-1. Cells were collected at 48 hours post-irradiation for chromosomal aberration studies and at 72 hours post-irradiation for micronuclei studies. These studies showed that the irradiated cells contained more chromosomal aberrations and micronuclei than the control cells. Addition of the DF-1 reduced the amount of observed DNA damage in the irradiated cells. Growth curves were measured for the lymphocytes exposed to 0 and 4 Gray gamma irradiations, and we observed less growth in the cells irradiated at 4 Gy. 2,7-dichlorofluorescein diacetate was used to detect reactive oxygen species production, and increased production of ROS was observed in the irradiated lymphocytes. Human lymphocytes were subjected to varying doses of gamma or photon radiation in the presence and absence of DF-1 and a known radioprotectant, amifostine. After irradiation, the production of reactive oxygen species, growth curves and cell viability were measured. These cells were also collected to quantify chromosomal aberrations and micronuclei formation. We predict that irradiated cells will show the most damage and that DF-1 will provide protective effects similar to those of amifostine, an established radioprotectant.

Reynolds, Julia↗

DOE OSTI2023

Trends in Light and Temperature Sensitivity Recommendations among Licensed Biotechnology Drug Products

Inherent structural and functional properties of biotechnology-derived therapeutic biologics make them susceptible to light- and temperature-induced degradation and consequently can influence their quality. Photosensitivity of therapeutic proteins continues to be examined, but the commonalities and trends of storage conditions and information about light and temperature sensitivity among currently licensed therapeutic proteins has not been previously surveyed. Using a comprehensive and relational database approach, we conducted a scientific survey of all licensed biotechnology-derived drug products with the goal of providing evidence-based information about recommended storage conditions of formulations sorted by light- and temperature-related attributes as described for each product at licensure. We report the prevalence of indications for light and temperature sensitivity in formulations categorized by their presentation type, number of doses, container type, dosage form and active molecule type. We also report the storage temperature range across formulations and diluents for reconstitution and dilution. Formulations with excipients that potentially facilitate light-induced and thermal degradation were also noted. The result of our analysis indicates that light and temperature sensitivity are prevalent across therapeutic protein formulations. However, when a formulation is reconstituted or diluted, both light and temperature sensitivity are less clear. In addition, light and temperature sensitivity are more well defined in liquid formulations than lyophilized powder formulations, and more well defined in products manufactured in autoinjectors, prefilled-syringes, and pens than products in vials. Overall, our report provides a data-driven summary of storage conditions among therapeutic protein formulations to support the development of future biologic drug products.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Transient Copper Exposure During Embryogenesis and Temperature Affect Developmental Rate, Survival, and Fin Regeneration in Japanese Medaka ( Oryzias latipes )

Combined environmental stressors that an organism experiences can have both immediate and lasting consequences. In this paper we exposed medaka (Oryzias latipes) embryos to sublethal copper sulfate (CuSO 4 ) (0, 10, and 100 ppb) in combination with different rearing temperatures (27, 30, and 33°C) to assess acute and latent effects on development, growth, and regenerative capacity. Embryos exposed to CuSO 4 and/or higher temperatures hatched significantly earlier. At 4 months post-exposure, fish exposed to low levels of CuSO 4 during development had higher survival, while fish exposed to both 100 ppb CuSO 4 and 33°C temperatures had significantly lower survival. Additionally, a sex-specific effect of embryonic CuSO 4 exposure was observed as female mass decreased with increasing copper dose. We also assessed caudal fin regenerative capabilities in both embryo-exposed fish at 4 months of age and adult medaka that were exposed to 0, 10, and 100 ppb CuSO 4 at room temperature during a 14- day trial. Whereas fin regeneration was unaffected by adult exposure to copper, fish transiently exposed during embryogenesis displayed an initial increase in fin growth rate and an increased incidence of abnormal fin morphology following regrowth. Collectively, these data suggest that developmental copper exposure has the potential to exert long lasting impacts to organismal growth, survival, and function.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

DOE OSTI2022

Transcriptional pathways linked to fetal and maternal hepatic dysfunction caused by gestational exposure to perfluorooctanoic acid (PFOA) or hexafluoropropylene oxide-dimer acid (HFPO-DA or GenX) in CD-1 mice

Per- and polyfluoroalkyl substances (PFAS) comprise a diverse class of chemicals used in industrial processes, consumer products, and fire-fighting foams which have become environmental pollutants of concern due to their persistence, ubiquity, and associations with adverse human health outcomes, including in pregnant persons and their offspring. Multiple PFAS are associated with adverse liver outcomes in adult humans and toxicological models, but effects on the developing liver are not fully described. Here we performed transcriptomic analyses in the mouse to investigate the molecular mechanisms of hepatic toxicity in the dam and its fetus after exposure to two different PFAS, perfluorooctanoic acid (PFOA) and its replacement, hexafluoropropylene oxide-dimer acid (HFPO-DA, known as GenX). Pregnant CD-1 mice were exposed via oral gavage from embryonic day (E) 1.5-17.5 to PFOA (0, 1, or 5 mg/kg-d) or GenX (0, 2, or 10 mg/kg-d). Maternal and fetal liver RNA was isolated (N = 5 per dose/group) and the transcriptome analyzed by Affymetrix Array. Differentially expressed genes (DEG) and differentially enriched pathways (DEP) were obtained. DEG patterns were similar in maternal liver for 5 mg/kg PFOA, 2 mg/kg GenX, and 10 mg/kg GenX (R2: 0.46-0.66). DEG patterns were similar across all 4 dose groups in fetal liver (R2: 0.59-0.81). There were more DEGs in fetal liver compared to maternal liver at the low doses for both PFOA (fetal = 69, maternal = 8) and GenX (fetal = 154, maternal = 93). Upregulated DEPs identified across all groups included Fatty Acid Metabolism, Peroxisome, Oxidative Phosphorylation, Adipogenesis, and Bile Acid Metabolism. Transcriptome-phenotype correlation analyses demonstrated > 1000 maternal liver DEGs were significantly correlated with maternal relative liver weight (R 2 >0.92). These findings show shared biological pathways of liver toxicity for PFOA and GenX in maternal and fetal livers in CD-1 mice. The limited overlap in specific DEGs between the dam and fetus suggests the developing liver responds differently than the adult liver to these chemical stressors. This work helps define mechanisms of hepatic toxicity of two structurally unique PFAS and may help predict latent consequences of developmental exposure.

54 ENVIRONMENTAL SCIENCES↗