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At least 361 records · Page 20

Quantitative Evaluation of Potassium Iodide Implementation Strategies for Emergency Preparedness and Response

This study evaluates the effectiveness of potassium iodide (KI) distribution strategies in mitigating exposure to radioiodine during severe nuclear power plant accidents. This analysis quantitatively compares various KI distribution methods (pre-distributed versus stockpiles), including scenarios with and without KI administration. The results indicate that differences in distribution strategies impact the projected thyroid dose by at least an order of magnitude. The results also indicate that the timing of KI administration is critical, as expected. For scenarios involving delayed releases of significant quantities of radionuclides, evacuation is the most effective protection strategy regardless of KI distribution method. For scenarios involving rapid releases, retrieving KI from stockpiles can have a detrimental effect. Pre-distributed KI is potentially the most effective approach when used as a supplement to evacuation and sheltering. However, these model results are based on idealized conditions for KI distribution and administration; the actual benefits of KI prophylaxis are likely to be less than estimated in this report due to many variables. The results highlight the importance of considering the cost and rigor of different distribution programs and public compliance with emergency instructions. This report includes suggested research to explore KI distribution plans for advanced reactors.

59 BASIC BIOLOGICAL SCIENCES↗

The radioracemization of amino acids by ionizing radiation - Geochemical and cosmochemical implications

The radiation-induced racemization of optically active amino acids by gamma radiation is investigated, and geochemical and cosmochemical implications of the reaction are discussed. Samples of solid or dissolved optically pure D and L amino acids were irradiated by Co-60 gamma radiation at a rate of 4 to 10 million rads/hr for time periods necessary to induce radiolysis of 50 to 70% of the sample. Gas chromatographic analysis of the products indicates that gamma radiation leads to the racemization of solid amino acids and aqueous solutions of their sodium but not hydrochloride salts, in proportion to the radiation dose received. Mechanisms for the radioracemization of solid amino acids and their sodium salts are discussed, and the absence of radioracemization in aqueous hydrochloride salts is accounted for. The effects of radioracemization on D/L amino acid ratios used in meteorite, geochronological and geothermal age determination are discussed, and implications of the observed radioracemization of isovaline for the determination of the primordial enantiomeric composition of the Murchison meteorite are considered.

Bonner, W. A.↗

Insights into Prismatic Loop Formation in Irradiated Fe–Cr Alloys from Hypothesis-Driven Active Learning and Causal Analysis

Neutron and electron irradiation experimental studies conducted on body-centered cubic Fe and Fe–Cr alloys have established two prismatic dislocation loop populations, which have Burgers vectors of either a/2$\langle$111$\rangle$ or a$\langle$100$\rangle$. Here, the loop formation depends on factors such as dose (D), dose rate (D rt ), temperature (T), chromium content (Cr%), and other alloying elements. Hence, it is important to understand how irradiation-induced dislocation loops evolve conditional upon the loop characteristics, such as loop density (DD), average loop size d̅, and irradiation parameters (D, D rt , T, and irradiation type), which is still an active area of research. To understand these complex structure–property relationships, machine learning (ML) is employed in a three-step approach. This includes imputing missing data with a k-nearest neighbor, generating functionalized features, and assessing feature importance with random forest classification and regression. Physics-based features are incorporated in a hypothesis-driven active learning scheme to overcome data unavailability challenges. Insights obtained from ML models (i) to categorize dislocation loop types, show the highest correlation with d̅; (ii) Log(DD), obtained through mathematical formulations involving D, Cr%, d̅, and T (e.g., Log(DD) ~ D + exp(-Cr%) + 1/d̅ and log(DD) ~ D + exp(-Cr%) + 1/T). Hypothesis-driven active learning is able to predict Log(DD) in which the experimental date is not known. Causal models verify cause–effect relationships for dislocation loop classification and irradiation factors in FeCr alloys.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Antimicrobial Materials for Advanced Microbial Control in Spacecraft Water Systems

Microbial detection, identification, and control are essential for the maintenance and preservation of spacecraft water systems. Requirements set by NASA put limitations on the energy, mass, materials, noise, cost, and crew time that can be devoted to microbial control. Efforts are being made to attain real-time detection and identification of microbial contamination in microgravity environments. Research for evaluating technologies for capability enhancement on-orbit is currently focused on the use of adenosine triphosphate (ATP) analysis for detection purposes and polymerase chain reaction (peR) for microbial identification. Additional research is being conducted on how to control for microbial contamination on a continual basis. Existing microbial control methods in spacecraft utilize iodine or ionic silver biocides, physical disinfection, and point-of-use sterilization filters. Although these methods are effective, they require re-dosing due to loss of efficacy, have low human toxicity thresholds, produce poor taste, and consume valuable mass and crew time. Thus, alternative methods for microbial control are needed. This project also explores ultraviolet light-emitting diodes (UV-LEDs), surface passivation methods for maintaining residual biocide levels, and several antimicrobial materials aimed at improving current microbial control techniques, as well as addressing other materials presently under analysis and future directions to be pursued.

Birmele, Michele↗

Calculation of Radiation Protection Quantities and Analysis of Astronaut Orientation Dependence

Health risk to astronauts due to exposure to ionizing radiation is a primary concern for exploration missions and may become the limiting factor for long duration missions. Methodologies for evaluating this risk in terms of radiation protection quantities such as dose, dose equivalent, gray equivalent, and effective dose are described. Environment models (galactic cosmic ray and solar particle event), vehicle/habitat geometry models, human geometry models, and transport codes are discussed and sample calculations for possible lunar and Mars missions are used as demonstrations. The dependence of astronaut health risk, in terms of dosimetric quantities, on astronaut orientation within a habitat is also examined. Previous work using a space station type module exposed to a proton spectrum modeling the October 1989 solar particle event showed that reorienting the astronaut within the module could change the calculated dose equivalent by a factor of two or more. Here the dose equivalent to various body tissues and the whole body effective dose due to both galactic cosmic rays and a solar particle event are calculated for a male astronaut in two different orientations, vertical and horizontal, in a representative lunar habitat. These calculations also show that the dose equivalent at some body locations resulting from a solar particle event can vary by a factor of two or more, but that the dose equivalent due to galactic cosmic rays has a much smaller (<15%) dependence on astronaut orientation.

Clowdsley, Martha S.↗

Infusing Statistical Thinking into the NASA Quesst Community Test Campaign

Statistical thinking permeates many important decisions as NASA plans its Quesst mission, which will culminate in a series of community overflights using the X-59 aircraft to demonstrate low-noise supersonic flight. Month-long longitudinal surveys will be deployed to assess human perception and annoyance to this new acoustic phenomenon. NASA works with a large contractor team to develop systems and methodologies to estimate noise doses, to test and field socio-acoustic surveys, and to study the relationship between the two quantities, dose and response, through appropriate choices of statistical models. This latter dose-response relationship will serve as an important tool as national and international noise regulators debate whether overland supersonic flights could be permitted once again within permissible noise limits. In this presentation we highlight several areas where statistical thinking has come into play, including issues of sampling, classification and data fusion, and analysis of longitudinal survey data that are subject to rare events and the consequences of measurement error. We note several operational constraints that shape the appeal or feasibility of some decisions on statistical approaches, and we identify several important remaining questions to be addressed.

Bayesian model↗

Discovery of highly potent and ALK2/ALK1 selective kinase inhibitors using DNA-encoded chemistry technology

Activin receptor type 1 (ACVR1; ALK2) and activin receptor like type 1 (ACVRL1; ALK1) are transforming growth factor beta family receptors that integrate extracellular signals of bone morphogenic proteins (BMPs) and activins into Mothers Against Decapentaplegic homolog 1/5 (SMAD1/SMAD5) signaling complexes. Several activating mutations in ALK2 are implicated in fibrodysplasia ossificans progressiva (FOP), diffuse intrinsic pontine gliomas, and ependymomas. The ALK2 R206H mutation is also present in a subset of endometrial tumors, melanomas, non-small lung cancers, and colorectal cancers, and ALK2 expression is elevated in pancreatic cancer. Using DNA-encoded chemistry technology, we screened 3.94 billion unique compounds from our diverse DNA-encoded chemical libraries (DECLs) against the kinase domain of ALK2. Off-DNA synthesis of DECL hits and biochemical validation revealed nanomolar potent ALK2 inhibitors. Further structure-activity relationship studies yielded center for drug discovery (CDD)-2789, a potent [NanoBRET (NB) cell IC50: 0.54 μM] and metabolically stable analog with good pharmacological profile. Crystal structures of ALK2 bound with CDD-2281, CDD-2282, or CDD-2789 show that these inhibitors bind the active site through Van der Waals interactions and solvent-mediated hydrogen bonds. CDD-2789 exhibits high selectivity toward ALK2/ALK1 in KINOMEscan analysis and NB K192 assay. In cell-based studies, ALK2 inhibitors effectively attenuated activin A and BMP-induced Phosphorylated SMAD1/5 activation in fibroblasts from individuals with FOP in a dose-dependent manner. Thus, CDD-2789 is a valuable tool compound for further investigation of the biological functions of ALK2 and ALK1 and the therapeutic potential of specific inhibition of ALK2.

Jimmidi, Ravikumar↗

Effects of high energy radiation on the mechanical properties of epoxy/graphite fiber reinforced composites

The epoxy resin system formed by tetraglycidyl 4,4'-diamino diphenyl methane (TGDDM) and 4,4'-diamino diphenyl sulfone (DDS) was characterized by dynamic mechanical analysis and differential scanning calorimetry. Dynamic mechanical properties of graphite fiber epoxy composite specimens formulated with two different adhesive systems (NARMCO 5208, NARMCO 5209) were determined. The specimens were exposed to varying dose levels of ionizing radiation (0.5 MeV electrons) with a maximum absorbed dose of 10,000 Mrads. Following irradiation, property measurements were made to assess the influence of radiation on the epoxy and composite specimens. The results established that ionizing radiation has a limited effect on the properties of epoxy and composite specimens.

Fornes, R. E.↗

Analysis of Ag/FEP Control Blanket Performance from Multiple Satellites

Published data reporting the change in solar absorptance as a function of time on orbit for certain satellites has been re-examined. The optical property change of metallized FEP as a function of total particulate radiation dose received by specific satellites has been estimated. Results tend to follow a common trend and a design curve has been constructed to estimate solar absorptance change as a function of radiation dose for metallized FEP at any altitude. Effects due to apparent contamination on several of the satellites are addressed and taken into account in determining property changes. Data from LDEF, ML-101, NavStar 1-5, NTS-2, the SCATHA experiment, and SOLRAD 11 are used as the basis of the design curve. A similar comparison is made between published atomic oxygen recession data from numerous Space Shuttle flights, a LEO experiment flown by Lockheed, and LDEF results. Variation of atomic oxygen recession rate of FEP as a function of exposure conditions is determined.

Pippin, H. G.↗

Changes in Plants Developed from Imbibed Seeds Irradiated by Simulated Solar Particle Events

One of the major concerns for long-term exploration missions beyond the Earth’s magnetosphere is radiation risk primarily from solar particle events (SPEs) and galactic cosmic rays (GCRs). With the goal of enabling manned Mars exploration, the production of fresh food during long duration space missions may provide nutritional supplementation and benefit astronauts’ behavioral health. However, the effects of space radiation on plants and plant propagules have not been sufficiently investigated and characterized. In this study, we evaluated the effect of simulated SPEs on imbibed seeds of mizuna mustard, ‘Outredgeous’ red romaine lettuce, and ‘Red Robin’ dwarf tomato. Seeds were exposed to various doses of simulated SPEs (0, 40, 80 cGy, and 200 cGy), either acutely or at a low dose rate (LDR only for 40 and 80 cGy doses), using the NASA Space Radiation Laboratory (NSRL) facility at Brookhaven National Lab (BNL). Simulated SPE exposure was achieved using sequential exposures to protons with a broad energy range at 50-150 MeV/n. Control and irradiated seeds were planted either onto 0.5% MS-based agar plates containing required nutrients for early seedling analysis, or in peat plugs/pots for 28 day (mizuna and lettuce) and 91 day (tomato) grow outs. All plants were maintained under space-vehicle relevant conditions at 3000 ppm CO2, 50% RH, and 23°C, and a 16/8 h photoperiod with 300 μmol·m(exp -2)·s(exp -1) photosynthetically active radiation. Plant/fruit morphometrics and edible fresh mass were measured. Additionally, nutrient analyses were performed on mizuna and tomato fruit. Seedlings from irradiated seeds (both 40 and 80 cGy) showed significant and dose dependent impacts on cotyledon development and root length. Interestingly, small, but significant changes in vitamin content were found in mizuna and tomato fruits grown from 80 cGy (LDR) irradiated seeds. In addition, 80 cGy (LDR) simulated SPEs significantly delayed tomato early seedling development and plant growth, and reduced the quantity of fruits produced from the surviving plants. (This study was supported by NASA Human Research Program.)

J. T. Richards↗

A polymer, random walk model for the size-distribution of large DNA fragments after high linear energy transfer radiation

DNA double-strand breaks (DSBs) produced by densely ionizing radiation are not located randomly in the genome: recent data indicate DSB clustering along chromosomes. Stochastic DSB clustering at large scales, from > 100 Mbp down to < 0.01 Mbp, is modeled using computer simulations and analytic equations. A random-walk, coarse-grained polymer model for chromatin is combined with a simple track structure model in Monte Carlo software called DNAbreak and is applied to data on alpha-particle irradiation of V-79 cells. The chromatin model neglects molecular details but systematically incorporates an increase in average spatial separation between two DNA loci as the number of base-pairs between the loci increases. Fragment-size distributions obtained using DNAbreak match data on large fragments about as well as distributions previously obtained with a less mechanistic approach. Dose-response relations, linear at small doses of high linear energy transfer (LET) radiation, are obtained. They are found to be non-linear when the dose becomes so large that there is a significant probability of overlapping or close juxtaposition, along one chromosome, for different DSB clusters from different tracks. The non-linearity is more evident for large fragments than for small. The DNAbreak results furnish an example of the RLC (randomly located clusters) analytic formalism, which generalizes the broken-stick fragment-size distribution of the random-breakage model that is often applied to low-LET data.

DNA/radiation effects↗

Variability in Galactic Cosmic Radiation- Induced DNA Damage Response in Inbred Mice Is Modulated by Genetics

In radiation biology, the ability to predict cancer risk associated with exposure to low doses of high-LET (Linear Energy Transfer) ionizing radiation remains a challenge. Epidemiological methods lack the sensitivity and power to provide detailed risk estimates for cancer and ignore individual sensitivity. We have hypothesized that DNA repair capacity is the primary factor differentiating peoples radiation sensitivity. We previously showed in immortalized human cell lines that characterizing the dose and time dependence of p53-binding protein 1 (53BP1) foci formation in the nucleus following X-rays exposure is sufficient to predict DNA repair response to any other LET in the same cell line. We now tested this hypothesis across a population of mice with different genetic background. Fibroblast cells were extracted and cultivated from 76 individual mice from 15 different strains and exposed to HZE (high (H) atomic number (Z) and energy (E) galactic cosmic ray particles) particles and X-rays. Individual radiation sensitivities were investigated by high throughput measurement of DNA repair kinetics that evaluated 53bp1 foci numbers as a surrogate for DNA double-strand breaks at various times post-irradiation. Instead of just counting foci which can be hard to distinguish for high-LET or high doses, we also took into account the track structure of high-LET particles to compute the remaining number of unrepaired tracks as a function of time post-irradiation. As expected, the percentage of unrepaired track over a 48 hours follow-up period increased with LET. In addition, repair rate was modulated by genetics, with animals from the same strain showing small variance while large rate differences were observed between strains. Radiation strain sensitivity ranking was estimated based on repair rates from exposure to each LET evaluated in this work, and ranking for high-LET correlated better with ranking from high dose of X-ray, not low dose. At the in-vivo level, drops in T-cells and B-cells number measured 24 hours after 0.1 Gy (Gray) X-ray exposure, correlated with slower DNA repair kinetic in fibroblast cells of the same strains of mice. At the genomic level, mouse genome wide association (GWA) analysis identified seven significant genetic loci on chromosomes 2, 3, 7, 10, 11, 13 and 19 with different significance depending on the LET. Interestingly, for the two highest LET, a common locus on Chromosome 10 was identified with high enrichment for DNA repair associated genes.Overall, this work suggests that repair kinetics of primary skin fibroblasts is a good surrogate marker for in-vivo radiation sensitivities in other tissues and that this response is modulated by genetics. Our study also confirms that DNA repair kinetics following high doses of X-ray can be used to predict radiation sensitivity to high-LET.

High-LET Radiation↗

Mortality of atomic bomb survivors predicted from laboratory animals

Exposure, pathology and mortality data for mice, dogs and humans were examined to determine whether accurate interspecies predictions of radiation-induced mortality could be achieved. The analyses revealed that (1) days of life lost per unit dose can be estimated for a species even without information on radiation effects in that species, and (2) accurate predictions of age-specific radiation-induced mortality in beagles and the atomic bomb survivors can be obtained from a dose-response model for comparably exposed mice. These findings illustrate the value of comparative mortality analyses and the relevance of animal data to the study of human health effects.

NASA Discipline Radiation Health↗

Stability of Radiation Induced Chromosome Damage in Human Peripheral Blood Lymphocytes

Chromosome damage in an individual's peripheral blood lymphocytes can be an indicator of radiation exposure and this data can be used to evaluate dose after accidental or occupational exposure. Evidence suggests that the yield of chromosome damage in lymphocytes is also a relevant biomarker of cancer risk in humans that reflects individual cancer susceptibility. It follows that biomonitoring studies can be used to uncover subjects who are particularly susceptible to radiation damage and therefore at higher risk of cancer. Translocations and other stable aberrations are commonly believed to persist in peripheral blood cells for many years after exposure, and it has been suggested that translocations can be used for assessing retrospective radiation doses or chronic exposures. However, recent investigations suggest that translocations might not always persist indefinitely. We measured chromosome aberrations in the blood lymphocytes of six astronauts before their respective missions of approximately 3 to 6 months onboard the international space station, and again at various intervals up to 5 years after flight. In samples collected a few days after return to earth, the yield of chromosome translocations had significantly increased compared with preflight values, and results indicate that biodosimetry estimates lie within the range expected from physical dosimetry. However, for five of the astronauts, follow up analysis revealed a temporal decline in translocations with half-lives ranging from 10 to 58 months. The yield of exchanges remained unchanged for the sixth astronaut during an observation period of 5 months post-flight. These results may indicate complications with the use of stable aberrations for retrospective dose reconstruction and could affect cancer risk predictions that are estimated from yields of chromosome damage obtained shortly after exposure.

Cucinotta, F. A.↗

Dose rate and repair effects on cell damage in earth orbit

Radiobiology experiments performed in space will encounter continuous exposures to the cosmic rays and fractionated exposures to trapped protons which accumulate to several hundred dose fractions in a few weeks. Using models of track structure and cellular kinetics combined with models of the radiation environment and radiation transport, we consider calculations of damage rates for cell cultures. Analysis of the role of repair mechanisms for space exposures for the endpoints of survival and transformation is emphasized.

Cucinotta, F. A.↗

Building a predictive model for polycyclic aromatic hydrocarbon dosimetry in organotypically cultured human bronchial epithelial cells using benzo[ a ]pyrene

The airway epithelium is a primary route of exposure for inhaled toxicants, and organotypic culture models represent an important advancement for toxicity testing compared to simple in vitro models that may lack metabolic capability and multicellular structure/communication associated with the bronchial epithelium in vivo. A quantitative understanding of chemical dosimetry is key for interpreting and extrapolating study results; however, dosimetry is understudied in organotypic models limiting ability to predict toxicity. We developed a dosimetry model for primary human bronchial epithelial cells (HBECs) cultured at the air-liquid interface (ALI) using benzo[a]pyrene (BAP), a representative polycyclic aromatic hydrocarbon. Dose and time course evaluation of metabolite formation and enzyme activity and expression were utilized to parameterize a cellular dosimetry model to improve the utility of ALI-HBECs for assessing chemical risk. Dosimetry analysis demonstrated absorption of BAP into cells and an increase in Phase 1 and 2 metabolites over time that correlated with regulation of metabolizing enzymes. BAP was cleared from cells by 48 h after exposure, and the primary metabolites generated in ALI-HBECs were BAP-3-phenol, BAP-4,5-dihydrodiol, BAP-7,8-dihydrodiol, BAP-9,10-dihydrodiol, BAP-7,8,9,10-tetrol, BAP-3-phenol-glucuronide, BAP-4,5-dihydrodiol-glucuronide, and BAP-9,10-dihydrodiol-glucuronide. The resulting dosimetry model described BAP and 7,8-dihydrodiol toxicokinetics in ALI-HBECs and suggested active excretion of 7,8-dihydrodiol. Overall, this study demonstrates metabolic competency of ALI-HBECs for BAP metabolism, demonstrates the usefulness of complex in vitro systems for human-relevant toxicity data, and exhibits how in silico models can be utilized for understanding the dosimetry of test compounds to aid in in vitro to human extrapolation of toxicity data for risk assessments.

Benzo[a]pyrene↗

Interaction of Molecular Hydrogen on α-Pu at 300 K: Nucleation of Hydrides and Pu-Catalyzed Carbides

An α-Pu sample was studied in its “as-received” and “sputtered” state by both X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectroscopy (ToF-SIMS). Analysis of the “as-received” surface indicated significant carbon and oxygen, with oxygen signal pertaining to plutonium dioxide (PuO 2 ) and sesquioxide (Pu 2 O 3 ). The “sputtered” clean metal surface was then dosed with hydrogen (H 2 ) gas at 300 K and found to nucleate hydride species (PuH x ). Interestingly, H 2 was observed to be critical for nucleation of carbides (Pu x C y ) by acting as a catalyst for Pu’s reaction with background gases. Because Pu metal has a high affinity for oxygen, reoxidation occurred under UHV, forming Pu x O y and disrupting both PuH x and Pu x C y growth. Observations from the experiments were modeled for the α-Pu(020) surface, illustrating the ability of H 2 to readily dissociate onto sputtered and speciated surfaces at 300 K. The projected density of states from these calculations were compared to experiments, showing good agreement between the Pu 5f, 6d, and 7s states and the H 1s, O 2p, and C 2p valence states. Overall, the above results indicated that the formed hydride layer is unstable at 300 K in UHV conditions.

36 MATERIALS SCIENCE↗

Retinoic acid stimulates interstitial collagenase messenger ribonucleic acid in osteosarcoma cells

The rat osteoblastic osteosarcoma cell line UMR 106-01 secretes interstitial collagenase in response to retinoic acid (RA). The present study demonstrates by Northern blot analysis that RA causes an increase in collagenase messenger RNA (mRNA) at 6 h, which is maximal at 24 h (20.5 times basal) and declines toward basal level by 72 h. This stimulation is dose dependent, with a maximal response at 5 x 10(-7) M RA. Nuclear run-on assays show a greater than 20-fold increase in the rate of collagenase mRNA transcription between 12-24 h after RA treatment. Cycloheximide blocks RA stimulation of collagenase mRNA, demonstrating the need for de novo protein synthesis. RA not only causes an increase in collagenase secretion, but is known to decrease collagen synthesis in UMR 106-01 cells. In this study, the increase in collagenase mRNA is accompanied by a concomitant decrease in the level of alpha 1(I) procollagen mRNA, which is maximal at 24 h (70% decrease), with a return to near-control levels by 72 h. Nuclear run-on assays demonstrated that the decrease in alpha 1 (I) procollagen expression does not have a statistically significant transcriptional component. RA did not statistically decrease the stability of alpha 1 (I) procollagen mRNA (calculated t1/2 = 8.06 +/- 0.30 and 9.01 +/- 0.62 h in the presence and absence of RA, respectively). However, transcription and stability together probably contribute to the major decrease in stable alpha 1 (I) procollagen mRNA observed. Cycloheximide treatment inhibits basal level alpha 1 (I) procollagen mRNA accumulation, demonstrating the need for on-going protein synthesis to maintain basal expression of this gene.

Non-NASA Center↗