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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 163 records · Page 9
All sourcesNASA NTRSDOE OSTI
DOE OSTI2024

Systemic immunological responses are dependent on sex and ovarian hormone presence following acute inhaled woodsmoke exposure

Background: Rural regions of the western United States have experienced a noticeable surge in both the frequency and severity of acute wildfire events, which brings significant challenges to both public safety and environmental conservation efforts, with impacts felt globally. Identifying factors contributing to immune dysfunction, including endocrinological phenotypes, is essential to understanding how hormones may influence toxicological susceptibility. Methods: This exploratory study utilized male and female C57BL/6 mice as in vivo models to investigate distinct responses to acute woodsmoke (WS) exposure with a focus on sex-based differences. In a second set of investigations, two groups were established within the female mouse cohort. In one group, mice experienced ovariectomy (OVX) to simulate an ovarian hormone-deficient state similar to surgical menopause, while the other group received Sham surgery as controls, to investigate the mechanistic role of ovarian hormone presence in driving immune dysregulation following acute WS exposure. Each experimental cohort followed a consecutive 2-day protocol with daily 4-h exposure intervals under two conditions: control HEPA-filtered air (FA) and acute WS to simulate an acute wildfire episode. Results: Metals analysis of WS particulate matter (PM) revealed significantly increased levels of 63 Cu, 182 W, 208 Pb, and 238 U, compared to filtered air (FA) controls, providing insights into the specific metal components most impacted by the changing dynamics of wildfire occurrences in the region. Male and female mice exhibited diverse patterns in lung mRNA cytokine expression following WS exposure, with males showing downregulation and females displaying upregulation, notably for IL-1β, TNF-α, CXCL-1, CCL-5, TGF-β, and IL-6. After acute WS exposure, there were notable differences in the responses of macrophages, neutrophils, and bronchoalveolar lavage (BAL) cytokines IL-10, IL-6, IL-1β, and TNF-α. Significant diverse alterations were observed in BAL cytokines, specifically IL-1β, IL-10, IL-6, and TNF-α, as well as in the populations of immune cells, such as macrophages and polymorphonuclear leukocytes, in both Sham and OVX mice, following acute WS exposure. These findings elucidated the profound influence of hormonal changes on inflammatory outcomes, delineating substantial sex-related differences in immune activation and revealing altered immune responses in OVX mice due to ovarian hormone deficiency. In addition, the flow cytometry analysis highlighted the complex interaction between OVX surgery, acute WS exposure, and their collective impact on immune cell populations within the hematopoietic bone marrow niche. Conclusions: In summary, both male and female mice, alongside females subjected to OVX and those who had sham surgery, exhibit significant variations in the expression of proinflammatory cytokines, chemokines, lung mRNA gene expression, and related functional networks linked to signaling pathways. These differences potentially act as mediators of sex-specific and hormonal influences in the systemic inflammatory response to acute WS exposure during a wildfire event. Understanding the regulatory roles of genes expressed differentially under environmental stressors holds considerable implications, aiding in identifying sex-specific therapeutic targets for addressing acute lung inflammation and injury.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Plutonium in Manhattan Project workers: Using autopsy data to evaluate organ content and dose estimates based on urine bioassay with implications for radiation epidemiology

Purpose Radiation dose estimates in epidemiology typically rely on intake predictions based on urine bioassay measurements. The purpose of this article is to compare the conventional dosimetric estimates for radiation epidemiology with the estimates based on additional post-mortem tissue radiochemical analysis results. Methods The comparison was performed on a unique group of 11 former Manhattan Project nuclear workers, who worked with plutonium in the 1940s, and voluntarily donated their bodies to the United States Transuranium and Uranium Registries. Results Post-mortem organ activities were predicted using different sets of urine data and compared to measured activities. Use of urinalysis data collected during the exposure periods overestimated the systemic (liver+skeleton) deposition of 239 Pu by 155±134%, while the average bias from using post-exposure urinalyses was –4±50%. Committed effective doses estimated using early urine data differed from the best estimate by, on average, 196±193%; inclusion of follow-up urine measurements in analyses decreased the mean bias to 0.6±36.3%. Cumulative absorbed doses for the liver, red marrow, bone surface, and brain were calculated for the actual commitment period. Conclusion On average, post-exposure urine bioassay results were in good agreement with post-mortem tissue analyses and were more reliable than results of urine bioassays collected during the exposure.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Dose estimates and their uncertainties for use in epidemiological studies of radiation-exposed populations in the Russian Southern Urals

Many residents of the Russian Southern Urals were exposed to radioactive environmental pollution created by the operations of the Mayak Production Association in the mid- 20 th century. There were two major releases: the discharge of about 1x10 17 Bq of liquid waste into the Techa River between 1949 and 1959; and the atmospheric release of 7.4 * 10 16 Bq as a result an explosion in the radioactive waste-storage facility in 1957. The releases into the Techa River resulted in the exposure of more than 30,000 people who lived in riverside villages between 1950 and 1961. The 1957 accident contaminated a larger area with the highest exposure levels in an area that is called the East Urals Radioactive Trace (EURT). Current epidemiologic studies of the exposed populations are based on dose estimates obtained using a Monte-Carlo dosimetry system (TRDS-2016MC) that provides multiple realizations of the annual doses for each cohort member. These dose realizations provide a central estimate of the individual dose and information on the uncertainty of these dose estimates. In addition, the correlation of individual annual doses over realizations provides important information on shared uncertainties that can be used to assess the impact of shared dose uncertainties on risk estimate uncertainty.This paper considers dose uncertainties in the TRDS-2016MC. Individual doses from external and internal radiation sources were reconstructed for 48,036 people based on environmental contamination patterns, residential histories, individual 90 Sr body-burden measurements and dietary intakes. Dietary intake of 90 Sr resulted in doses accumulated in active bone marrow (or simply, marrow) that were an order of magnitude greater than those in soft tissues. About 84% of the marrow dose and 50% of the stomach dose was associated with internal exposures. The lognormal distribution is well-fitted to the individual dose realizations, which, therefore, could be expressed and easily operated in terms of geometric mean (GM) and geometric standard deviation (GSD). Cohort average GM for marrow and stomach cumulative doses are 0.21 and 0.03 Gy, respectively. Cohort average dose uncertainties in terms of GSD are as follows: for marrow it is 2.93 (90%CI: 2.02–4.34); for stomach and the other non-calcified tissues it is 2.32 (90% CI: 1.78–2.9).

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2020

Radiobiological Studies Using Cs-137 Gamma or 320 kV X Rays

There are numerous self-shielded research irradiators used in various facilities throughout the United States. The irradiators employ radioactive sources containing either 137 Cs or 60 Co and the irradiators are used for a variety of radiobiological investigations involving cellular and/or animal models. A report from the National Academy of Sciences described security issues associated with particular radiation sources and the desire for their replacement with suitable X-ray irradiators. One possible replacement would be a 320 kV X-ray irradiator. The participants in this research successfully performed in vivo radiobiological studies involving mice exposed to filtered (HVL ≈ 4 mm Cu) 320 kV X rays. Two publications (one published and one submitted at the publishing of this report) documenting key findings are provided in Appendices A and B of this report. The 320 kV X rays were found suitable for in vivo (in mice) cell survival studies and are expected to be suitable for bone marrow transplantation studies using mice but this needs to be experimentally validated.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

Proteo-Genomic Analysis Identifies Two Major Sites of Vulnerability on Ebolavirus Glycoprotein for Neutralizing Antibodies in Convalescent Human Plasma

Three clinically relevant ebolaviruses – Ebola (EBOV), Bundibugyo (BDBV), and Sudan (SUDV) viruses, are responsible for severe disease and occasional deadly outbreaks in Africa. The largest Ebola virus disease (EVD) epidemic to date in 2013-2016 in West Africa highlighted the urgent need for countermeasures, leading to the development and FDA approval of the Ebola virus vaccine rVSV-ZEBOV (Ervebo ® ) in 2020 and two monoclonal antibody (mAb)-based therapeutics (Inmazeb ® [atoltivimab, maftivimab, and odesivimab-ebgn] and Ebanga ® (ansuvimab-zykl) in 2020. The humoral response plays an indispensable role in ebolavirus immunity, based on studies of mAbs isolated from the antibody genes in peripheral blood circulating ebolavirus-specific human memory B cells. However, antibodies in the body are not secreted by circulating memory B cells in the blood but rather principally by plasma cells in the bone marrow. Little is known about the protective polyclonal antibody responses in convalescent plasma. Here we exploited both single-cell antibody gene sequencing and proteomic sequencing approaches to assess the composition of the ebolavirus glycoprotein (GP)-reactive antibody repertoire in the plasma of an EVD survivor. We first identified 1,512 GP-specific mAb variable gene sequences from single cells in the memory B cell compartment. Using mass spectrometric analysis of the corresponding GP-specific plasma IgG, we found that only a portion of the large B cell antibody repertoire was represented in the plasma. Molecular and functional analysis of proteomics-identified mAbs revealed recognition of epitopes in three major antigenic sites - the GP head domain, the glycan cap, and the base region, with a high prevalence of neutralizing and protective mAb specificities that targeted the base and glycan cap regions on the GP. Polyclonal plasma antibodies from the survivor reacted broadly to EBOV, BDBV, and SUDV GP, while reactivity of the potently neutralizing mAbs we identified was limited mostly to the homologous EBOV GP. Together these results reveal a restricted diversity of neutralizing humoral response in which mAbs targeting two antigenic sites on GP – glycan cap and base – play a principal role in plasma-antibody-mediated protective immunity against EVD.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Protein Structure Inspired Discovery of a Novel Inducer of Anoikis in Human Melanoma

Drug discovery historically starts with an established function, either that of compounds or proteins. This can hamper discovery of novel therapeutics. As structure determines function, we hypothesized that unique 3D protein structures constitute primary data that can inform novel discovery. Using a computationally intensive physics-based analytical platform operating at supercomputing speeds, we probed a high-resolution protein X-ray crystallographic library developed by us. For each of the eight identified novel 3D structures, we analyzed binding of sixty million compounds. Top-ranking compounds were acquired and screened for efficacy against breast, prostate, colon, or lung cancer, and for toxicity on normal human bone marrow stem cells, both using eight-day colony formation assays. Effective and non-toxic compounds segregated to two pockets. One compound, Dxr2-017, exhibited selective anti-melanoma activity in the NCI-60 cell line screen. In eight-day assays, Dxr2-017 had an IC50 of 12 nM against melanoma cells, while concentrations over 2100-fold higher had minimal stem cell toxicity. Dxr2-017 induced anoikis, a unique form of programmed cell death in need of targeted therapeutics. Our findings demonstrate proof-of-concept that protein structures represent high-value primary data to support the discovery of novel acting therapeutics. This approach is widely applicable.

Oncology↗
NASA NTRS1972

Methods of space radiation dose analysis with applications to manned space systems

The full potential of state-of-the-art space radiation dose analysis for manned missions has not been exploited. Point doses have been overemphasized, and the critical dose to the bone marrow has been only crudely approximated, despite the existence of detailed man models and computer codes for dose integration in complex geometries. The method presented makes it practical to account for the geometrical detail of the astronaut as well as the vehicle. Discussed are the major assumptions involved and the concept of applying the results of detailed proton dose analysis to the real-time interpretation of on-board dosimetric measurements.

Langley, R. W.↗
NASA NTRS1972

Dosimetry for radiobiological studies of the human hematopoietic system

A system for estimating individual bone marrow doses in therapeutic radiation exposures of leukemia patients was studied. These measurements are used to make dose response correlations and to study the effect of dose protraction on peripheral blood cell levels. Three irradiators designed to produce a uniform field of high energy gamma radiation for total body exposures of large animals and man are also used for radiobiological studies.

Beck, W. L.↗
NASA NTRS1971

Inhaled ozone as a mutagen. II - Effect on the frequency of chromosome aberrations observed in irradiated Chinese hamsters.

Exposure-adjusted break frequencies for chromosome aberrations produced in Chinese hamster circulating blood lymphocytes were the quantitative indicator of damage from 5 hrs of exposure to X-radiation and/or to ozone. Radiation produced 5.51 x 0.0001 breaks/cell rad for cells withdrawn 2 weeks after exposure, a reasonable value when compared with data from in vivo exposure of human lymphocytes and Chinese hamster bone marrow cells. Animals exposed to the two agents simultaneously exhibited more than 70% of the total breaks anticipated assuming the expected equal contributions to be additive. Extending to humans, at presently permitted levels, exposure to ozone would be much more detrimental than exposure to radiati*n.

Zelac, R. E.↗
NASA NTRS1971

Erythropoietic radiosensitivity of the rat during altitude acclimatization.

The effect of a sublethal dose (300 R) of X-radiation upon the erythropoietic system of the rat, during 60-day acclimatization to moderate hypoxia (3,800 m altitude), was studied. Past work has shown that hypoxic animals are damaged less by radiation than animals irradiated in a normal environment; therefore, it was postulated that if, after acclimatization to hypoxia the bone marrow oxygen tension returns to sea-level values, these animals should suffer radiation damage equivalent to animals at sea level. The principal parameters followed were the rate of depletion of injected Fe-59 from the plasma of chronically catheterized rats, and its subsequent reappearance in the circulating erythrocytes. After 20 days of acclimatization, both parameters for altitude-irradiated animals returned to the values of animals irradiated at sea level, previously having reflected increased erythropoiesis. In altitude nonirradiated animals the parameters indicated erythropoietic stimulation persisting up to 45 days acclimatization. The protective effect of the hypoxia on the stem cells vanished during acclimatization, presumably as cellular oxygen tension rose.

Gaugl, J. F.↗
NASA NTRS1973

The Computerized Anatomical Man (CAM) model

A computerized anatomical man (CAM) model, representing the most detailed and anatomically correct geometrical model of the human body yet prepared, has been developed for use in analyzing radiation dose distribution in man. This model of a 50-percentile standing USAF man comprises some 1100 unique geometric surfaces and some 2450 solid regions. Internal body geometry such as organs, voids, bones, and bone marrow are explicitly modeled. A computer program called CAMERA has also been developed for performing analyses with the model. Such analyses include tracing rays through the CAM geometry, placing results on magnetic tape in various forms, collapsing areal density data from ray tracing information to areal density distributions, preparing cross section views, etc. Numerous computer drawn cross sections through the CAM model are presented.

Billings, M. P.↗
NASA NTRS1973

Blood volume and red cell life span (M113), part C

Prechamber, in-chamber, and postchamber blood samples taken from Skylab simulation crewmembers did not indicate significant shortening of the red cell life span during the mission. This does not suggest that the space simulation environment could not be associated with red cell enzyme changes. It does show that any changes in enzymes were not sufficiently great to significantly shorten red cell survival. There was no evidence of bone marrow erythropoetic suppression nor was there any evidence of increased red cell destruction.

Johnson, P. C., Jr.↗
NASA NTRS1974

Circadian rhythmometry of mammalian radiosensitivity

In the case of human bone marrow, the largest number of mitoses is seen in the evening in diurnally active men, mitotic activity being at a minimum in the morning. The opposite pattern is observed for nocturnal animals such as rats and mice on a regimen of light during the daytime alternating with darkness during the night hours. The entirety of these rhythms plays an important role in the organism's responses to environmental stimuli, including its resistance to potentially harmful agents. Conditions under which circadian rhythms can be observed and validated by inferential statistical means are discussed while emphasizing how artifacts of the laboratory environment can be shown to obscure circadian periodic variations in radiosensitivity.

Haus, E.↗
NASA NTRS1975

Effects of weightlessness on tissue proliferation

The repair of bone marrow stroma following mechanical injury was studied to obtain baseline data for a proposed space experiment regarding the effect of weightlessness on marrow stroma and other proliferating cell systems.

Crosby, W. H.↗
NASA NTRS1975

Electrophoresis of biological materials

The selection of biological products was studied for electrophoresis in space. Free flow electrophoresis, isoelectric focusing, and isotachophoresis are described. The candidates discussed include: immunoglobulins and gamma globulins; isolated islet of langerhans from pancreas; bone marrow; tumor cells; kidney cells, cryoprecipitate; and column separated cultures.

Source record↗