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At least 343 records · Page 19
All sourcesNASA NTRSDOE OSTI
NASA NTRS2017

Skin-Based DNA Repair Phenotype for Cancer Risk from GCR in Genetically Diverse Populations

Predicting cancer risk associated with cosmic radiation remains a mission-critical challenge for NASA radiation health scientists and mission planners. Epidemiological data are lacking and risk methods do not take individual radiation sensitivity into account. In our approach we hypothesize that genetic factors strongly influence risk of cancer from space radiation and that biomarkers reflecting DNA damage and cell death are ideal tools to predict risk and monitor potential health effects post-flight. At this workshop, we will be reporting the work we have done over the first 9 months of this proposal. Skin cells from 15 different strains of mice already characterized for radiation-induced cancer sensitivity (B6C3F; BALB/cByJ, C57BL/6J, CBA/CaJ, C3H/HeMsNrsf), and 10 strains from the DOE collaborative cross-mouse model were expanded from ear biopsy and cultivated until Passage 3. On average, 3 males and 3 females for each strain were expanded and frozen for further characterization at the NSRL beam line during the NSRL16C run for three LET (350 MeV/n Si, 350 MeV/n Ar and 600 MeV/n Fe) and two ion fluences (1 and 3 particles per cell). The mice work has established new metrics for the usage of Radiation Induced Foci as a marker for various aspect of DNA repair deficiencies. In year 2, we propose to continue characterization of the mouse lines with low LET to identify loci specific to high- versus low- LET and establish genetic linkage for the various DNA repair biomarkers. Correlation with cancer risk from each animals strain and gender will also be investigated. On the human side, we will start characterizing the DNA damage response induced ex-vivo in 200 human's blood donors for radiation sensitivity with a tentative 500 donors by the end of this project. All ex-vivo phenotypic data will be correlated to genetic characterization of each individual human donors using SNP arrays characterization as done for mice. Similarly, ex-vivo phenotypic features from mice will be associated to cancer risk, to identify which biomarkers correlate the most with cancer risk. Genetic traits across humans will also be associated to radiation phenotypic features as a function of age and gender.

radiation space biology↗
NASA NTRS2017

It's All Relative: A Validation of Radiation Quality Comparison Metrics

The difference between high-LET and low-LET radiation is quantified by a measure called relative biological effectiveness (RBE). RBE is defined as the ratio of the dose of a reference radiation to that of a test radiation to achieve the same effect level, and thus, is described either as an iso-effector dose-to-dose ratio. A single dose point is not sufficient to calculate an RBE value; therefore, studies with only one dose point usually calculate an effect-to-effect ratio. While not formally used in radiation protection, these iso-dose values may still be informative. Shuryak, et al 2017 investigated the use of an iso-dose metric termed "radiation effects ratio" (RER) and used both RBE and RER to estimate high-LET risks. To apply RBE or RER to risk prediction, the selected metric must be uniquely defined. That is, the calculated value must be consistent within a model given a constant set of constraints and assumptions, regardless of how effects are defined using statistical transformations from raw endpoint data. We first test the RBE and the RER to determine whether they are uniquely defined using transformations applied to raw data. Then, we test whether both metrics can predict heavy ion response data after simulated effect size scaling between human populations or when converting animal to human endpoints.

Chappell, Lori J.↗
NASA NTRS2010

Radiation Performance of Commercial SiGe HBT BiCMOS-High Speed Operational Amplifiers

We present results on heavy-ion and proton irradiations for commercial SiGe BiCMOS operational amplifiers: LTC6400-20 from Linear Technology and THS4304 from Texas Instruments. We found that the devices are susceptible to heavy-ion-induced SETs. The SET cross-sections increase with increasing operating frequency. The LTC6400 exhibits a LET(sub th) < 7.4 MeV·sq cm/mg for frequencies ranging from 10 to 1000 MHz. The THS4304 exhibits a LET(sub th) < 4.4 MeV·sq cm/mg at 200 MHz; the LET(sub th) decreases with increasing frequency. The significance of the SETs also increases with frequency. The SETs at 1000 MHz can erase several signal cycles. We al.so found that the LTC6400 is relatively robust against 198 and 54 MeV protons. We did not observe angular sensitivity from the proton irradiations.

Chen, Dakai↗
NASA NTRS2018

Potential Dietary Countermeasure Against Spaceflight-Induced Bone Loss

As humans venture further into space and beyond low Earth orbit, space radiation is one of the main challenges for astronauts' health. Radiation-induced bone loss is a potential health problem for long duration habitation in space. We showed that a dietary countermeasure prevents bone loss in mice exposed to total body irradiation (TBI). We used a range of ionizing radiation, gamma (137Cs), proton (1H), iron (56Fe), and a combination of sequential proton and iron beam (1H/56Fe/1H) to evaluate skeletal responses. These TBI cover a range of linear energy transfer (LET), from low-LET such as proton, to high-LET such as 56Fe (HZE: high Z- high energy) at doses between 1-2 Gy. The countermeasure diet, composed of 25% Dried Plum (DP) was effective at preventing radiation-induced cancellous bone loss in appendicular bone (tibia). Furthermore, exposing mice to HZE radiation, such as 56Fe (1Gy), impaired ex vivo growth of marrow-derived, bone-forming osteoblasts, which led to reduced mineralization capacity (-77%). In contrast, mice fed the DP diet did not display these deficits, showing the diet's capacity to protect marrow-derived osteoprogenitors. Dietary DP prevented the increase of bone resorbing osteoclast cells, inflammation and oxidative stress, while protecting the osteoprogenitors and mesenchymal stem cells, which few drugs against osteoporosis may achieve. Spaceflight is a combination of multiple factors including microgravity, in addition to space radiation. Therefore, we conducted additional studies to determine if the DP diet could prevent simulated spaceflight (simulated microgravity and radiation combined) bone loss. Mice were exposed to gamma (TBI, 137Cs, 2 Gy), simulated microgravity (using the hindlimb unloading system, HU) or TBI+HU. While we observed bone loss in mice fed the control diet (CD) due to both treatments (TBI=14%, HU=20%), and a worse effect with combined treatments (TBI+HU=25%), mice fed the DP diet did not sustain significant bone loss relative to untreated controls. The DP diet prevented microarchitectural decrements in both appendicular bone (tibia) and axial bone (vertebrae). In addition, the DP diet mitigated HU-induced deficits in osteoblastogenesis. Interestingly, lower doses of DP diet (5%, 10%) did not appear to prevent cancellous bone loss, which shows the importance of identifying the active component(s) of DP. Finally, we have preliminary data showing the potential of DP to prevent radiation-induced damage at a systematic level.. In summary, this novel dietary countermeasure is a promising candidate nutritional countermeasure for spaceflight-induced bone loss and tissue damage.

Countermeasure↗
NASA NTRSDate not supplied

Chimeric Mouse Models for Space Radiation Risk Investigations

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. For instance, mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, can be used for quantification of space radiation damage. A chimeric brain model, which was shown to perform superiorly in memory and cognitive tests, can also be a candidate for studying the CNS effects of radiation. It has also been reported that mice engrafted with human hematopoietic progenitor cells were exposed to X-rays and high-LET Si ions to investigate the radiation effects in the immune system. In a pilot study, we use PXB mice whose livers contain >90% human cells. These mice are exposed to gamma rays for investigations of DNA damage and transcriptomics changes in the humanized livers. Results obtained from PXB mice will be compared non-engrafted control animals from the same background strain that are exposed to identical conditions. The aim of the study is to determine whether chimeric mouse models are suitable for investigations of space radiation risks.

Honglu Wu↗
NASA NTRSDate not supplied

NASA’s Human Landing System: Enabling the Next Generation of Lunar Science

The Human Landing System (HLS) is the mode of transportation that will take astronauts to the lunar surface as part of NASA's Artemis exploration program. HLS also serves as a research platform both on the surface and in lunar orbit, enabling critical scientific investigations on and of the Moon. With support at NASA centers around the country, the HLS program, based at Marshall Space Flight Center in Huntsville, Alabama, is working closely with its commercial partners throughout the development process to design and build innovative and technically advanced lunar landers – new vehicles designed for the modern era of space travel – leveraging decades of human spaceflight experience and the speed of the commercial sector. In 2019, NASA asked U.S. industry for proposals to design and develop a human lander for the first human mission to the lunar surface under Artemis. Initial contracts were awarded to Blue Origin Federation, Dynetics, and SpaceX to advance their designs. Following the execution of the ten-month Base Period, NASA announced in April 2021 that the agency selected SpaceX to move forward with its human landing system [1] and land the first two astronauts on the lunar surface during the Artemis III mission. Following two protest periods, NASA awarded the contract, known as Option A, to SpaceX in July 2021 and resumed work in November 2021 (Fig. 1). In parallel, the HLS program has been preparing for the acquisition that will procure regular crewed transportation to the lunar surface following Artemis III. NASA released a request for information (RFI) in July 2021 asking U.S. industry for feedback to help inform the future solicitation, known as Lunar Exploration Transportation Services (LETS) [2]. Also in July 2021, NASA released the NextSTEP-2 Appendix N broad agency announcement soliciting new work from U.S. industry to mature their HLS designs and perform risk reduction activities in advance of the LETS procurement [3]. NASA selected Blue Origin Federation, Dynetics, Lockheed Martin, Northrop Grumman, and SpaceX to participate [4]. This work will also help better inform the LETS procurement and prepare industry to propose. NASA hopes to release a draft request for proposals (RFP) in Spring 2022.

R C Weber↗
NASA NTRSDate not supplied

Chimeric Mouse Models for Space Radiation Risk Investigations

Assessment of human health risks associated with space radiation exposure is based largely on the knowledge learned from studies in which animals, mostly rodents, are exposed to high-LET radiation on the ground. It has been recognized that translation of animal results to meaningful implications for human disease can be challenging, particularly for certain risk categories such as the high-LET radiation effects in the central nervous system (CNS). Considering limitations in utilizing non-human primates and clinical studies in humans, chimeric animals can potentially bridge the knowledge gap between rodents and humans. In a chimeric animal, a specific organ or a cell type is replaced with respective human cells that are functional. A number of chimeric mouse models have been developed in the medical research community to study human diseases, and some of the models can potentially be used for NASA applications. For instance, mice engrafted with human hepatocytes, which have been used in studies of genotoxicity from carcinogen exposures, can be used for quantification of space radiation damage. A chimeric brain model, which was shown to perform superiorly in memory and cognitive tests, can also be a candidate for studying the CNS effects of radiation. It has also been reported that mice engrafted with human hematopoietic progenitor cells were exposed to X-rays and high-LET Si ions to investigate the radiation effects in the immune system. In a pilot study, we use PXB mice whose livers contain >90% human cells. These mice are exposed to gamma rays for investigations of DNA damage and transcriptomics changes in the humanized livers. Results obtained from PXB mice will be compared non-engrafted control animals from the same background strain that are exposed to identical conditions. The aim of the study is to determine whether chimeric mouse models are suitable for investigations of space radiation risks.

Honglu Wu↗
NASA NTRSDate not supplied

Neurovascular Responses to Simulated Deep Space Radiation in a Human Organ-on-a-Chip Model

A major health risk for human deep space exploration is central nervous system (CNS) damage by galactic cosmic ray radiation. Simulated galactic cosmic rays or their components, especially the high-linear energy transfer (LET) particles such as 56Fe ions, have been shown to cause CNS damage, neuroinflammation and cognitive dysfunction in rodent models, but their effects on human CNS remain to be investigated. CNS damage from any insult, including ionizing radiation, is partially mediated by the blood-brain barrier (BBB), which regulates interactions between CNS and the rest of the body. The main cellular regulators of BBB permeability are astrocytes, which also modulate neuroinflammation. However, there have been few studies on BBB and astrocyte functions in regulating CNS responses, especially in human tissue analogs. Therefore, we utilized a high-throughput 3D organ-on-a-chip system, seeded with human induced pluripotent stem cell-derived astrocytes and brain endothelial cells, or brain endothelial cells alone, to study human neurovascular responses to simulated deep space radiation. We investigated the permeability and morphology of vascular structures formed by endothelial cells, as well as oxidative stress and secreted cytokines and chemokine levels over 1-7 days after irradiation with 0.25 – 0.5 Gy 5-ion simplified simulated galactic cosmic rays or 0.3 – 0.8 Gy high-LET 600 MeV/n 56Fe particles, and compared the outcomes to low-LET X-ray irradiation. We observed that simulated deep space radiation caused delayed astrocyte activation in a pattern resembling CNS responses to brain injury, caused oxidative stress and the production of inflammatory cytokines, and compromised BBB integrity by damaging tight junctions, thus increasing vascular permeability. Furthermore, our results indicate that astrocytes have a dual role in regulating radiation responses: they exacerbate blood-brain barrier permeability early after irradiation, followed by switching to a more protective scar-like phenotype by reducing oxidative stress and pro-inflammatory cytokine and chemokine secretion. In a follow-up study using the same platform, we investigated the dose-rate effects of ionizing radiation, by exposing our model to chronic, low dose-rate, gamma radiation. Our model was significantly improved by adding additional cell types composing the BBB, modelling immune cell infiltration into the brain, and studying the effect of an antioxidant, to measure more complex outcomes and model more closely the effect of deep space radiation on the human BBB. In summary, our results present a human neurovascular model for space radiation studies and potential future automated payload adaptation, and suggest astrocyte regulatory mechanisms as targets for countermeasures to mitigate human neurovascular impairments during deep space exploration.

Ionizing radiation↗
NASA NTRS2021

SEE Test Results for SAMA5D3

ARM processors power a class of high-performance, lower power system on a chip devices. In the absence of radiation effects, these devices are highly desirable for space use. The processor core architecture for ARM devices is licensed to provide computing on multiple hardware platforms. The A5 processor is in a unique pioneering space for providing detailed radiation response data to explore the baseline performance of these devices. These data can help set options for ARM processors and possibly impact design choices for the next generation of ARM fault tolerance capabilities. The SAMA5D3 was tested to establish general SEE performance for a relatively simple implementation of the ARM A5 core. This testing observed SRAM sensitivity starting at an LET of about 3 MeV-cm2/mg, with a saturated cross section of about 2x10-8cm2/bit, and this was determined by both active write and read of the caches, in addition to the use of a debugger to provide test results. Crash/SEFI data was collected using both Linux and bare metal C-code. The onset LET for crashes was about LET 1.5 MeV-cm2/mg, with saturated cross sections of about 2x10-5 cm2 for bare metal (low utilization), and 2x10-4cm2 for Linux (high utilization) tests.

Daniel, Andrew C.↗
NASA NTRS2020

The Potential Effects of Radiation on the Gut-Brain Axis

Humans may be exposed to different types of radiation in their lifetimes, typically in the form of low linear energy transfer (LET) radiation that is, for example, used as a treatment for cancer. In addition, astronauts may be exposed to high LET radiation in outer space. Here, we propose that alterations to the gastrointestinal (GI) microbiota may occur upon exposure to low or high LET radiation, and that these alterations may perturb important relationships that exist between the GI microbiota and human health. For example, the GI microbiota can communicate with the brain via various pathways and molecules, such as the enteric nervous system, the vagus nerve, microbial metabolites, and the immune system. This relationship has been termed the “gut-brain axis”. Alterations to the composition of the GI microbiome can lead to alterations in its functional metabolic output and means of communication, therefore potentially causing downstream cognitive effects. Consequently, studying how radiation can affect this important network of communication could lead to new and critical interventions, as well as prevention strategies. Herein, we review the evidence supporting a relationship between radiation exposure and disruption of the gut-brain axis as well as summarize strategies that may be used to counter the effects of radiation exposure on the GI microbiome.

Carli B. Jones↗
NASA NTRS1972

Response of mouse epidermal cells to single doses of heavy-particles

The survival of mouse epidermal cells to heavy-particles has been studied In Vivo by the Withers clone technique. Experiments with accelerated helium, lithium and carbon ions were performed. The survival curve for the helium ion irradiations used a modified Bragg curve method with a maximum tissue penetration of 465 microns, and indicated that the dose needed to reduce the original cell number to 1 surviving cell/square centimeters was 1525 rads with a D sub o of 95 rads. The LET at the basal cell layer was 28.6 keV per micron. Preliminary experiments with lithium and carbon used treatment doses of 1250 rads with LET's at the surface of the skin of 56 and 193 keV per micron respectively. Penetration depths in skin were 350 and 530 microns for the carbon and lithium ions whose Bragg curves were unmodified. Results indicate a maximum RBE for skin of about 2 using the skin cloning technique. An attempt has been made to relate the epidermal cell survival curve to mortality of the whole animal for helium ions.

Leith, J. T.↗
NASA NTRS1972

The general equilibria of a spinning satellite in a circular orbit.

Let a rigid satellite move in a circular orbit about a spherically symmetric central body, taking into account only the main term of the gravitational torque. We investigate and find all solutions of the following problem. Let the satellite be permitted to spin about an axis that is fixed in the orbit frame; the satellite need not be symmetric, the spin not uniform, and the spin axis not a principal axis of inertia. The complete discussion of this type of spin reveals that the cases found by Lagrange and by Pringle - and the well-known spin about a principal axis of inertia orthogonal to the orbit plane - are essentially the only ones possible.

Sperling, H. J.↗
NASA NTRS1974

Microdosimetry and the radiation danger of cosmic rays

The radiation danger of space flights is due primarily to intensive proton fluxes accompanying solar flares and heavy multiple charged ions in galactic cosmic radiation. Evaluation of the biological effect of these kinds of rays is based on calculations of tissue dose, taking into account the formation of secondary radiation in shielding and tissue. The essential role in such calculations is played by the dependence of the factor of quality on linear energy transfer (LET) of these charged particles. Recommendations concerning the dependence of the quality factor on LET are based on radiobiological experiments carried out on many biological systems using various kinds of rays, including heavy ions with energies in the 1-10 Mev/nucleon range. Justification of the results of these experiments, as well as their extrapolation to other energies, requires development of a model description of the radiation effect of charged particles on biological microstructures.

Gunter, K.↗
NASA NTRS1976

Nuclear emulsion measurements of the astronauts' radiation exposure on the Apollo-Soyuz mission

On the Apollo-Soyuz mission each astronaut carried one passive dosimeter containing nuclear photographic emulsions, plastic foils, TLD chips, and neutron-activation foils for recording radiation exposure. This report is limited to the presentation of data retrieved from nuclear emulsions. Protons, most of them trapped particles encountered in numerous passes through the South Atlantic Anomaly, contributed by far the largest share to the mission dose. Their linear energy transfer (LET) spectrum was established from track and grain counts in a G.5 emulsion which is used for medium and high energies, and from ender counts in a K.2 emulsion which is used for low energies. The total mission fluence of protons was found to be equivalent to a unidirectional beam of 448,500 square centimeters. The broad spectrum was broken down into small LET intervals, which allowed for the computation of absorbed doses and dose equivalents. The totals are 51 millirad and 74 millirem. Counts of disintegration stars in K.2 emulsion are incomplete at present. While a total of 467 stars were identified, counting their prong numbers is still in progress. It was concluded that the Apollo-Soyuz astronauts' radiation exposure as such did not contain anything out of the ordinary that would seem to require special attention.

Schaefer, H. J.↗
NASA NTRS1983

Special cases of friction and applications

Two techniques for reducing friction forces are presented. The techniques are applied to the generalized problem of reducing the friction between kinematic pairs which connect a moveable link to a frame. The basic principles are: (1) Let the moveable link be supported by two bearings where the relative velocities of the link with respect to each bearing are of opposite directions. Thus the resultant force (torque) of friction acting on the link due to the bearings is approximately zero. Then, additional perturbation of motion parallel to the main motion of the moveable link will require only a very small force; (2) Let the perturbation in motion be perpendicular to the main motion. Equations are developed which explain these two methods. The results are discussed in relation to friction in geared couplings, gyroscope gimbal bearings and a rotary conveyor system. Design examples are presented.

Litvin, F. L.↗
NASA NTRS1984

Special cases of friction and applications

Two techniques for reducing friction forces are presented. The techniques are applied to the generalized problem of reducing the friction between kinematic pairs which connect a moveable link to a frame. The basic principles are: (1) Let the moveable link be supported by two bearings where the relative velocities of the link with respect to each bearing are of opposite directions. Thus the resultant force (torque) of friction acting on the link due to the bearings is approximately zero. Then, additional perturbation of motion parallel to the main motion of the moveable link will require only a very small force; (2) Let the perturbation in motion be perpendicular to the main motion. Equations are developed which explain these two methods. The results are discussed in relation to friction in geared couplings, gyroscope gimbal bearings and a rotary conveyor system. Design examples are presented.

Litvin, F. L.↗
NASA NTRS1985

Radiation mapping on Spacelab 1: Experiment no. INS006

The first attempt at mapping the radiation environment inside Spacelab is described. Measurements were made by a set of passive radiation detectors distributed throughout the volume inside the Spacelab 1 module, in the access tunnel and outside on the pallet. Measurements of the low linear energy transfer (LET) component obtained from the TLD thermoluminescent detectors (TLD) ranged from 92 to 134 mrad, yielding an average low LET dose rate of 10.0 mrads/day inside the module. Because of the higher inclination orbit, substantial fluxes of highly ionizing (HZE particles) high charge and energy galactic cosmic rays were observed for the first time on an STS flight, yielding an overall average mission dose-equivalent of 295 mrem, or 29.5 mrem/day, which is about three times higher than that measured on previous STS missions. Little correlation is found between measured average dose rates or HZE fluences and the estimates shielding throughout the volume of the module.

Benton, E. V.↗