SEARCH · Engineering Papers

Results for “Dose Estimation”

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.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 271 records · Page 15

All sources NASA NTRS DOE OSTI

NASA NTRSDate not supplied

Shielding Considerations for CubeSat Structures During Solar Maximum

The purpose of this lessons learned is to communicate the utility of shielding in small spacecraft planning for the support of mission assurance and reliability. Numerous SmallSats have been flying in polar low earth orbit for scientific, communications, technology demonstrations, and imaging with academic, commercial, and government interests. Shielding has been part of mission assurance and reliability from the advent of long duration spacecraft missions. The Shields-1 CubeSat has been operating in polar low earth orbit since 16 December 2018 with atomic number (Z)-grade radiation shielding and demonstrates shielding effectiveness. Shields-1 has collected a representative example of solar minimum data in 2019 with 8 Teledyne dosimeters over varying shielding effectiveness. It serves as current experimental data and has been compared with NOVICE Shielding estimates using the AP8 –AE8 trapped radiation model with the Shields-1 CAD and generic CubeSat 3 unit (U) models. Using NOVICE model radiation analysis coding, the shielding effectiveness's, based on a generic CubeSat 3U structure with 4 electronic boards, were estimated for aluminum wall thicknesses ranging from 0.204 cmto4.44 cm (0.550 g/cm2–12.0 g/cm2) thick aluminum. For modeled polar orbiting spacecraft, solar maximum total ionizing dose (TID)increases by nearly a magnitude for thin-walled aluminum 0.550g/cm2-0.686 g/cm2(0.204 cm –0.254 cm) typical CubeSat structures. The shielding effectiveness by NOVICE Sigma estimates, which is a shielding sphere approximation around a detector, showed a linear relationship with wall thickness, which increased over the wall thickness by a ratio of 1.43 determined by linear regression analysis. Using NOVICE Adjoint Monte-Carlo Modeling of solar minimum and solar maximum with the inclusion of a worst-case solar particle event over a one year mission without geomagnetic shielding, the TID for minimum and maximum conditions for a generic 3U with a wall thickness of 0.254 cm is 158 RAD and 1540 RAD, respectively. The modeled total solar maximum TID is over estimated, because at low orbital latitudes a spacecraft will have shielding from Earth's magnetic field. However, TID will still be significant at high latitudes over the poles, where a spacecraft is exposed in a solar particle event. In contrast, to a thin walled generic 3U CubeSat, Shields-1 electronics enclosure has a shielding effectiveness of 21.3 g/cm2from NOVICE Sigma modeling and is expected to show reduced total ionizing dose increases during the present active Solar Cycle 25 period. Because solar particle events during solar maximum increase TID on electronic parts with thin-walled shielding in short periods of time, it is a mission assurance and reliability consideration on the spacecraft’s mission value versus adding shielding for risk reduction of premature spacecraft or instrument payload loss. Since the volumes of many instruments and system electronics have reduced with small spacecraft, shielding material costs and weight penalties have diminished. A small spacecraft project budget and schedule may limit traditional radiation-hardened part use and radiation testing requirements, where shielding can contribute to mission assurance and reliability with reduced costs.

Shields-1↗

NASA NTRS2001

Radiation transport modeling and assessment to better predict radiation exposure, dose, and toxicological effects to human organs on long duration space flights

NASA is very interested in improving its ability to monitor and forecast the radiation levels that pose a health risk to space-walking astronauts as they construct the International Space Station and astronauts that will participate in long-term and deep-space missions. Human exploratory missions to the moon and Mars within the next quarter century, will expose crews to transient radiation from solar particle events which include high-energy galactic cosmic rays and high-energy protons. Because the radiation levels in space are high and solar activity is presently unpredictable, adequate shielding is needed to minimize the deleterious health effects of exposure to radiation. Today, numerous models have been developed and used to predict radiation exposure. Such a model is the Space Environment Information Systems (SPENVIS) modeling program, developed by the Belgian Institute for Space Aeronautics. SPENVIS, which has been assessed to be an excellent tool in characterizing the radiation environment for microelectronics and investigating orbital debris, is being evaluated for its usefulness with determining the dose and dose-equivalent for human exposure. Thus far. the calculations for dose-depth relations under varying shielding conditions have been in agreement with calculations done using HZETRN and PDOSE, which are well-known and widely used models for characterizing the environments for human exploratory missions. There is disagreement when assessing the impact of secondary radiation particles since SPENVIS does a crude estimation of the secondary radiation particles when calculating LET versus Flux. SPENVIS was used to model dose-depth relations for the blood-forming organs. Radiation sickness and cancer are life-threatening consequences resulting from radiation exposure. In space. exposure to radiation generally includes all of the critical organs. Biological and toxicological impacts have been included for discussion along with alternative risk mitigation methods--shielding and anti-carcinogens. c 2001. Elsevier Science Ltd. All rights reserved.

STS-91 Shuttle Project↗

NASA NTRS1973

Effect of reactor coolant radioactivity upon configuration feasibility for a nuclear electric propulsion vehicle

A preliminary shielding analysis was carried out for a conceptual nuclear electric propulsion vehicle designed to transport payloads from low earth orbit to synchronous orbit. The vehicle employed a thermionic nuclear reactor operating at 1575 kilowatts and generated 120 kilowatts of electricity for a round-trip mission time of 2000 hours. Propulsion was via axially directed ion engines employing 3300 pounds of mercury as a propellant. The vehicle configuration permitted a reactor shadow shield geometry using LiH and the mercury propellant for shielding. However, much of the radioactive NaK reactor coolant was unshielded and in close proximity to the power conditioning electronics. An estimate of the radioactivity of the NaK coolant was made and its unshielded dose rate to the power conditioning equipment calculated. It was found that the activated NaK contributed about three-fourths of the gamma dose constraint. The NaK dose was considered a sufficiently high fraction of the allowable gamma dose to necessitate modifications in configuration.

Soffer, L.↗

NASA NTRS1986

Radiation environment and shielding for early manned Mars missions

The problem of shielding a crew during early manned Mars missions is discussed. Requirements for shielding are presented in the context of current astronaut exposure limits, natural ionizing radiation sources, and shielding inherent in a particular Mars vehicle configuration. An estimated range for shielding weight is presented based on the worst solar flare dose, mission duration, and inherent vehicle shielding.

Hall, Stephen B.↗

NASA NTRS2003

Body water handling in response to hypertonic-saline induced diuresis in fasting northern elephant seal pups (Mirounga angustirostris)

During natural fasting conditions in postweaned northern elephant seal (NES) (Mirounga angustirostris) pups, urinary water loss is minimized and percent total body water (TBW) is maintained constant. However, following infusion of hypertonic saline, glomerular filtration rate (GFR) and urine output increased in fasting pups. Therefore, we quantified the magnitude of the hypernatremia-induced diuresis relative to the animal's total body water (TBW) pool and the percentage of filtered water reabsorbed. Following a 24 h control period, naturally fasting NES pups (n=7) were infused (4 ml min(-1)) with hypertonic saline (16.7%) at a dose of 3 mmol NaCl kg(-1) body mass. Total body water was estimated prior to infusion by tritium dilution, GFR was estimated by standard creatinine clearance, and urine output (V) was measured for 24 h during the control and post infusion periods. Percentage of filtered water reabsorbed was calculated as (1-(V/GFR))x100. Twenty-four hours following the infusion, GFR (control: 69+/-12 ml min(-1) and post-infusion: 118+/-19 ml min(-1); mean+/-S.E.) increased 77+/-28% above control and the percentage of filtered water reabsorbed was decreased 0.4+/-0.1%. The increase in urine output (control: 218+/-47 ml d(-1) and post-infusion: 883+/-92 ml d(-1)) accounted for 1.7+/-0.2% of the pups' TBW. The hypernatremia-induced diuresis was accompanied by the loss of body water indicating the lack of water retention. Although the 77% increase in GFR was only associated with a 0.4% decrease in the percentage of filtered water reabsorbed, this decrease was significant enough to result in a 4-fold increase in urine output. Despite the observed diuresis, fasting NES pups appear to possess an efficient water recycling mechanism requiring only a small percentage of body water to excrete an excess salt load. This water recycling mechanism may allow pups to avoid negative perturbations in body water as they initiate feeding in a marine environment following the fast.

Non-NASA Center↗

NASA NTRS2006

Lunar Surface Reactor Shielding Study

Nuclear reactor system could provide power to support a long term human exploration to the moon. Such a system would require shielding to protect astronauts from its emitted radiations. Shielding studies have been performed for a Gas Cooled Reactor (GCR) system because it is considered to be the most suitable nuclear reactor system available for lunar exploration, based on its tolerance of oxidizing lunar regolith and its good conversion efficiency (Wright, 2003). The goals of the shielding studies were to provide optimal material shielding configuration that reduces the dose (rem) to the required level in order to protect astronauts, and to estimate the mass of regolith that would provide an equivalent protective effect if it were used as the shielding material. All calculations were performed using MCNPX code, a Monte Carlo transport code.

Monte Carlo N-Particle eXtended (MCNPX)↗

NASA NTRS2013

NASA Models of Space Radiation Induced Cancer, Circulatory Disease, and Central Nervous System Effects

The risks of late effects from galactic cosmic rays (GCR) and solar particle events (SPE) are potentially a limitation to long-term space travel. The late effects of highest concern have significant lethality including cancer, effects to the central nervous system (CNS), and circulatory diseases (CD). For cancer and CD the use of age and gender specific models with uncertainty assessments based on human epidemiology data for low LET radiation combined with relative biological effectiveness factors (RBEs) and dose- and dose-rate reduction effectiveness factors (DDREF) to extrapolate these results to space radiation exposures is considered the current "state-of-the-art". The revised NASA Space Risk Model (NSRM-2014) is based on recent radio-epidemiology data for cancer and CD, however a key feature of the NSRM-2014 is the formulation of particle fluence and track structure based radiation quality factors for solid cancer and leukemia risk estimates, which are distinct from the ICRP quality factors, and shown to lead to smaller uncertainties in risk estimates. Many persons exposed to radiation on earth as well as astronauts are life-time never-smokers, which is estimated to significantly modify radiation cancer and CD risk estimates. A key feature of the NASA radiation protection model is the classification of radiation workers by smoking history in setting dose limits. Possible qualitative differences between GCR and low LET radiation increase uncertainties and are not included in previous risk estimates. Two important qualitative differences are emerging from research studies. The first is the increased lethality of tumors observed in animal models compared to low LET radiation or background tumors. The second are Non- Targeted Effects (NTE), which include bystander effects and genomic instability, which has been observed in cell and animal models of cancer risks. NTE's could lead to significant changes in RBE and DDREF estimates for GCR particles, and the potential effectiveness of radiation mitigator's. The NSRM- 2014 approaches to model radiation quality dependent lethality and NTE's will be described. CNS effects include both early changes that may occur during long space missions and late effects such as Alzheimer's disease (AD). AD effects 50% of the population above age 80-yr, is a degenerative disease that worsens with time after initial onset leading to death, and has no known cure. AD is difficult to detect at early stages and the small number of low LET epidemiology studies undertaken have not identified an association with low dose radiation. However experimental studies in mice suggest GCR may lead to early onset AD. We discuss modeling approaches to consider mechanisms whereby radiation would lead to earlier onset of occurrence of AD. Biomarkers of AD include amyloid beta (A(Beta)) plaques, and neurofibrillary tangles (NFT) made up of aggregates of the hyperphosphorylated form of the micro-tubule associated, tau protein. Related markers include synaptic degeneration, dentritic spine loss, and neuronal cell loss through apoptosis. Radiation may affect these processes by causing oxidative stress, aberrant signaling following DNA damage, and chronic neuroinflammation. Cell types to be considered in multi-scale models are neurons, astrocytes, and microglia. We developed biochemical and cell kinetics models of DNA damage signaling related to glycogen synthase kinase-3(Beta) (GSK3(Beta)) and neuroinflammation, and considered multi-scale modeling approaches to develop computer simulations of cell interactions and their relationships to A(Beta) plaques and NFTs. Comparison of model results to experimental data for the age specific development of A(Beta) plaques in transgenic mice will be discussed.

Cucinotta, Francis A.↗

NASA NTRS1989

Cosmic-ray neutron albedo dose in low-earth orbits

An earth albedo neutron environmental model is proposed which provides a way to estimate neutron exposure in low-earth orbit. It is shown that, in the predominantly low inclination orbits (i=28.5 deg) used in the U.S. space program, the neutron exposures are relatively low (0.7 cSv/y). The neutron exposures are more significant for polar orbital missions and even high inclination missions, such as Skylab (i=57 deg).

Wilson, J. W.↗

NASA NTRSDate not supplied

Shielding Considerations for CubeSat Structures During Solar Maximum

The purpose of this lessons learned paper is to communicate the utility of shielding in small spacecraft planning for the support of mission assurance and reliability. Numerous SmallSats have been flying in polar low Earth orbit for science, communications, technology demonstrations, and imaging with academic, commercial, and government interests. Shielding has been part of mission assurance and reliability from the advent of long duration spacecraft missions. The Shields-1 CubeSat has been operating in polar low Earth orbit since 16 December 2018 with atomic number (Z)-grade radiation shielding and demonstrates shielding effectiveness. Shields-1 has collected a representative example of solar minimum data in 2019 with eight Teledyne µDosimeters over varying shielding effectivenesses. It serves as current experimental data and has been compared with NOVICE Shielding estimates using the AP8 – AE8 trapped radiation model with the Shields-1 CAD and generic CubeSat three unit (3U) models. Using NOVICE model radiation analysis coding, the shielding effectivenesses, based on a generic CubeSat 3U structure with four electronic boards, were estimated for aluminum wall thicknesses ranging from 0.204 cm to 4.44 cm (0.550 g/cm 2 to 12.0 g/cm 2 ). For modeled polar orbiting spacecraft, solar maximum total ionizing dose (TID) increases by nearly a magnitude for thin-walled aluminum 0.550-g/cm 2 - 0.686-g/cm 2 (0.204-cm – 0.254-cm) typical CubeSat structures. The shielding effectiveness estimated by NOVICE Sigma, which is a shielding sphere approximation around a detector, showed a linear relationship with wall thickness, which increased over the wall thickness by a ratio of 1.43 determined by linear regression analysis. Using NOVICE Adjoint Monte-Carlo Modeling of solar minimum and solar maximum with the inclusion of a worst-case solar particle event over a one-year mission without geomagnetic shielding, the TID for minimum and maximum conditions for a generic 3U with a wall thickness of 0.254 cm is 158 RAD and 1540 RAD, respectively. The modeled total solar maximum TID is over estimated, because at low orbital latitudes a spacecraft will have shielding from the Earth’s magnetic field. However, TID will still be significant at high latitudes over the poles, where a spacecraft is exposed in a solar particle event. In contrast to a thin-walled generic 3U CubeSat, the Shields-1 electronics enclosure has a shielding effectiveness of 21.3 g/cm 2 from NOVICE Sigma modeling and is expected to show reduced total ionizing dose increases during the present active Solar Cycle 25 period. Because solar particle events during solar maximum increase TID on electronic parts with thin-walled shielding in short periods of time, it is a mission assurance and reliability consideration on the mission value of the spacecraft versus adding shielding for risk reduction of premature spacecraft or instrument payload loss. Since the volumes of many instruments and system electronics have reduced with small spacecraft, shielding material costs and weight penalties have diminished. A small spacecraft project budget and schedule may limit traditional radiation-hardened part use and radiation testing requirements, where shielding can contribute to mission assurance and reliability with reduced costs.

Shields-1↗

NASA NTRS1990

Scoping estimates of the LDEF satellite induced radioactivity

The Long Duration Exposure Facility (LDEF) satellite was recovered after almost six years in space. It was well-instrumented with ionizing radiation dosimeters, including thermoluminescent dosimeters, plastic nuclear track detectors, and a variety of metal foil samples for measuring nuclear activation products. The extensive LDEF radiation measurements provide the type of radiation environments and effects data needed to evaluate and help resolve uncertainties in present radiation models and calculational methods. A calculational program was established to aid in LDEF data interpretation and to utilize LDEF data for assessing the accuracy of current models. A summary of the calculational approach is presented. The purpose of the reported calculations is to obtain a general indication of: (1) the importance of different space radiation sources (trapped, galactic, and albedo protons, and albedo neutrons); (2) the importance of secondary particles; and (3) the spatial dependence of the radiation environments and effects expected within the spacecraft. The calculational method uses the High Energy Transport Code (HETC) to estimate the importance of different sources and secondary particles in terms of fluence, absorbed dose in tissue and silicon, and induced radioactivity as a function of depth in aluminum.

Armstrong, Tony W.↗

NASA NTRS1991

Optimal sampling theory and population modelling - Application to determination of the influence of the microgravity environment on drug distribution and elimination

The optimal sampling theory is evaluated in applications to studies related to the distribution and elimination of several drugs (including ceftazidime, piperacillin, and ciprofloxacin), using the SAMPLE module of the ADAPT II package of programs developed by D'Argenio and Schumitzky (1979, 1988) and comparing the pharmacokinetic parameter values with results obtained by traditional ten-sample design. The impact of the use of optimal sampling was demonstrated in conjunction with NONMEM (Sheiner et al., 1977) approach, in which the population is taken as the unit of analysis, allowing even fragmentary patient data sets to contribute to population parameter estimates. It is shown that this technique is applicable in both the single-dose and the multiple-dose environments. The ability to study real patients made it possible to show that there was a bimodal distribution in ciprofloxacin nonrenal clearance.

Drusano, George L.↗

NASA NTRS1993

Time Course of the Response of Myofibrillar and Sarcoplasmic Protein Metabolism to Unweighting of the Soleus Muscle

Contributions of altered in vivo protein synthesis and degradation to unweighting atrophy of the soleus muscle in tail-suspended young female rats were analyzed daily for up to 6 days. Specific changes in myofibrillar and sarcoplasmic proteins were also evaluated to assess their contributions to the loss of total protein. Synthesis of myofibrillar and sarcoplasmic proteins was estimated by intramuscular (IM) injection and total protein by intraperitoneal (IP) injection of flooding doses of H-3-phenylaianine. Total protein loss was greatest during the first 3 days following suspension and was a consequence of the loss of myofibrillar rather than sarcoplasmic proteins. However, synthesis of total myofibrillar and sarcoplasmic proteins diminished in parallel beginning in the first 24 hours. Therefore sarcoplasmic proteins must be spared due to a decrease in their degradation. In contrast, myofibrillar protein degradation increased, thus explaining the elevated degradation of the total pool. Following 72 hours of suspension, protein synthesis remained low, but the rate of myofibrillar protein loss diminished, suggesting a slowing of degradation. These various results show acute loss of protein during unweighting atrophy is a consequence of decreased synthesis and increased degradation of myofibrillar proteins, and sarcoplasmic proteins are spared due to slower degradation, likely explaining the sparing of plasma membrane receptors. Based on other published data, we propose that the slowing of atrophy after the initial response may be attributed to an increased effect of insulin.

Munoz, Kathryn A.↗

NASA NTRS1994

An analysis of interplanetary space radiation exposure for various solar cycles

The radiation dose received by crew members in interplanetary space is influenced by the stage of the solar cycle. Using the recently developed models of the galactic cosmic radiation (GCR) environment and the energy-dependent radiation transport code, we have calculated the dose at 0 and 5 cm water depth; using a computerized anatomical man (CAM) model, we have calculated the skin, eye and blood-forming organ (BFO) doses as a function of aluminum shielding for various solar minima and maxima between 1954 and 1989. These results show that the equivalent dose is within about 15% of the mean for the various solar minima (maxima). The maximum variation between solar minimum and maximum equivalent dose is about a factor of three. We have extended these calculations for the 1976-1977 solar minimum to five practical shielding geometries: Apollo Command Module, the least and most heavily shielded locations in the U.S. space shuttle mid-deck, center of the proposed Space Station Freedom cluster and sleeping compartment of the Skylab. These calculations, using the quality factor of ICRP 60, show that the average CAM BFO equivalent dose is 0.46 Sv/year. Based on an approach that takes fragmentation into account, we estimate a calculation uncertainty of 15% if the uncertainty in the quality factor is neglected.

NASA Discipline Radiation Health↗

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 NTRSDate not supplied

Mitigating the Impacts of Measurement Error in the Quesst Mission Community Noise Study

Beginning in 2025, the NASA Quesst mission will conduct a series of community response tests involving flyovers of the X-59 aircraft at select localities across the United States. Several waves of a longitudinal survey will be administered over approximately one month of testing in order to capture perceptual responses to low-amplitude sonic booms, or “sonic thumps”. Simultaneously, noise exposure levels will be estimated by fusing model-based predictions with measurements taken from a sparse network of monitors in the region. As one of the aims of the study is to produce a dose-response curve, a regression model relating perceptual response to noise exposure levels, it is important to acknowledge the potential attenuation bias that results from measurement error in the estimated noise exposure levels. In this presentation we review and compare several methods for dealing with measurement error in generalized linear mixed models. The methods are demonstrated on simulated data and real data collected during past NASA risk reduction studies.

measurement error↗

NASA NTRS1996

Quantitative assessment of the cataractogenic potential of very low doses of neutrons

We report on the prevalence and relative biological effectiveness (RBE) for various stages of lens opacification in rats induced by very low doses (2 to 250 mGy) of medium-energy (440 keV) neutrons, compared to those for X rays. Neutron doses were delivered either in a single fraction or in four separate fractions and the irradiated animals were followed for over 100 weeks. At the highest observed dose (250 mGy) and at early observation times, there was evidence of an inverse dose-rate effect; i.e., a fractionated exposure was more potent than a single exposure. Neutron RBEs relative to X rays were estimated using a non-parametric technique. The results were only weakly dependent on time postirradiation. At 30 weeks, for example, 80% confidence intervals for the RBE of acutely delivered neutrons relative to X rays were 8-16 at 250 mGy, 10-20 at 50 mGy, 50-100 at 10 mGy and 250-500 at 2 mGy. The results are consistent with the estimated neutron RBEs in Japanese A-bomb survivors, though broad confidence bounds are present in the Japanese results. Our findings are also consistent with data reported earlier for cataractogenesis induced by heavy ions in rats, mice, and rabbits. We conclude from these results that, at very low doses (<10 mGy), the RBE for neutron-induced cataractogenesis is considerably larger than the RBE of 20 commonly used, and use of a significantly larger value for calculating equivalent dose would be prudent.

NASA Discipline Radiation Health↗

NASA NTRS2019

Predicting Cancer Risk from Ionizing Radiation

The ability to predict cancer risk associated with exposure to low doses of high-LET ionizing radiation (IR) remains a challenge. Epidemiological methods lack the sensitivity and power to provide detailed risk estimates for cancer and ignore individual variance in IR sensitivity. We have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. Our hypothesis was tested in 15 different mouse strains as well as in primary human immune cells. We first approached individual ionizing radiation sensitivity in a mouse model by culturing primary skin fibroblasts extracted from 76 mice of 15 different genetic backgrounds and exposing them to HZE particles and X-rays. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Our results is in agreement with a DNA repair model we previously postulated, where nearby DNA double strand breaks (DSB) in the nucleus are brought together for more efficient repair, leading to RIF clustering. Such mechanism was evidenced by a specific dose and LET dependence of RIF numbers. Briefly, RIF quantification after low-LET X-ray exposure showed an asymptotic saturation for doses between 1 Gy and 4 Gy 4 hours post-irradiation across all 15 strains. The clustering of DSB across all strains also led to more RIF/Gy for lower LET (X-ray and 350 MeV/n Ar) than for higher LET (600 MeV/n Fe) 4 hours post-exposure. Considering the fact that the number of DSB/Gy should be independent of LET, our data suggest there are more DSB in individual RIF as the LET increases. RIF numbers for 24 and 48 hours post-exposure led to the inverse trend, with more remaining RIF/Gy for higher LET (by 600 MeV/n Fe). This result suggests cells have more difficulty resolving RIF from higher LET as they the number DSB/RIF increases. Note that for most conditions, the variance of RIF/Gy was small within individual animals of the same strain and large between strains, suggesting a strong genetics component. Furthermore, we present our preliminary data from an ongoing study on human genetic associations with IR sensitivity. To address the human variability in responses to HZE particle irradiation in a maximally comprehensive manner, we are in the process of collecting and isolating primary blood mononuclear cells from 768 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. We will next complete the quantification of HZE particle-induced DNA and cellular damage in the remaining subjects and compare it to their responses to low-LET irradiation. Finally, we will perform GWAS analysis to identify human genomic associations with IR sensitivity and potential targets for biomarker development.

High-LET radiation↗

NASA NTRS2003

Perfectly Cold Crystals: What Happens When They Are X-rayed?

For many macromolecular crystals the cryo-preservation of these crystals during X-ray data collection is of crucial importance, particularly at synchrotron facilities where the crystals rapidly receive a high dose of radiation. A practical variable to ensure adequate preservation is the variation of the cryo-protectant present when the crystal is preserved. Our initial approach to study X-ray diffraction data quality as a function of cryo-protectant present when preserving a xylose isomerase crystal shows that the data quality can be tremendously improved by recipe adjustment. Guided by crystal mosaicity estimates, we optimized crystal growth conditions to obtain cryo-preserved xylose isomerase crystals that withstand a very high dose of X-rays, with only the smallest amount of radiation damage at ultra-high resolution (1.2Angstroms). The rate at which damage occurs allowed us to collect a series of complete data sets, which show how the data degradation proceeds over time. We are here presenting data for the xylose isomerase crystallization recipe improvement and our interpretation of the crystal degradation process during X-ray data collection.

vanderWoerd, Mark↗