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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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22 records · Page 2

Impaired Cytogenetic Damage Repair and Cell Cycle Regulation in Response to Ionizing Radiation in Human Fibroblast Cells with Individual Knock-down of 25 Genes

Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have demonstrated that genes with upregulated expression induced by IR may play important roles in DNA damage sensing, cell cycle checkpoint and chromosomal repair, the relationship between the regulation of gene expression by IR and its impact on cytogenetic responses to ionizing radiation has not been systematically studied. In our present study, the expression of 25 genes selected based on their transcriptional changes in response to IR or from their known DNA repair roles were individually knocked down by siRNA transfection in human fibroblast cells. Chromosome aberrations (CA) and micronuclei (MN) formation were measured as the cytogenetic endpoints. Our results showed that the yield of MN and/or CA formation were significantly increased by suppressed expression of 5 genes that included Ku70 in the DSB repair pathway; XPA in the NER pathway; RPA1 in the MMR pathway; RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes including MRE11A, RAD51 in the DSB pathway, and SESN1 and SUMO1 showed significant inhibition of cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, p21 and MLH1 expression resulted in both enhanced cell cycle progression and significantly higher yield of cytogenetic damage, indicating the involvement of these gene products in both cell cycle control and DNA damage repair. Of these 11 genes that affected the cytogenetic response, 9 were up-regulated in the cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulating the biological consequences after IR. Failure to express these IR-responsive genes, such as by gene mutation, could seriously change the outcome of the post IR scenario and lead to carcinogenesis.

Zhang, Ye↗

Modeling Respiratory Toxicity of Authentic Lunar Dust

The lunar expeditions of the Apollo operations from the 60 s and early 70 s have generated awareness about lunar dust exposures and their implication towards future lunar explorations. Critical analyses on the reports from the Apollo crew members suggest that lunar dust is a mild respiratory and ocular irritant. Currently, NASA s space toxicology group is functioning with the Lunar Airborne Dust Toxicity Assessment Group (LADTAG) and the National Institute for Occupational Safety and Health (NIOSH) to investigate and examine toxic effects to the respiratory system of rats in order to establish permissible exposure levels (PELs) for human exposure to lunar dust. In collaboration with the space toxicology group, LADTAG and NIOSH the goal of the present research is to analyze dose-response curves from rat exposures seven and twenty-eight days after intrapharyngeal instillations, and model the response using BenchMark Dose Software (BMDS) from the Environmental Protection Agency (EPA). Via this analysis, the relative toxicities of three types of Apollo 14 lunar dust samples and two control dust samples, titanium dioxide (TiO2) and quartz will be determined. This will be executed for several toxicity endpoints such as cell counts and biochemical markers in bronchoaveolar lavage fluid (BALF) harvested from the rats.

Santana, Patricia A.↗

The Importance of Contamination Knowledge - Insights into Mars Sample Return

The Astromaterials Acquisition and Curation Office at NASA Johnson Space Center (JSC), in Houston, TX (henceforth Curation Office) manages the curation of all past, present, and future extraterrestrial samples returned by NASA missions and shared collections from international partners, preserving their integrity for future scientific study while providing the samples to the international community in a fair and unbiased way. The Curation Office also curates all reference and witness materials for each mission (e.g., flight and non-flight hardware coupons; lubricants; non-flight, flight-like, and flown witness plates). These reference and witness materials provide the scientific community with the fundamental ability to reconstruct the contamination/alteration history of the sample collection through the course of the mission, with the overall goal of strengthening the scientific conclusions drawn from the study of returned materials. The information gained from characterizing the physical, biological, inorganic, and organic chemical properties of reference and witness materials is defined as the Contamination Knowledge (CK) of the sample collection. Unlike the data collected for Contamination Control (CC) and Planetary Protection (PP), CK is exclusively concerned with preserving reference and witness materials for study by future scientists upon sample return. Although CC and PP data collected for sample integrity and forward contamination purposes can be complementary to CK, they are two separate data sets with distinct objectives. A robust collection of samples for CK is necessary to allow the extraterrestrial material in a returned sample to be distinguished from terrestrial contamination. Traditionally CK is utilized by sample scientists in order to accomplish the mission’s scientific objectives, however this information can also be utilized by the Office of Planetary Protection to help evaluate the presence of any back contamination. Mars 2020, the first phase of a potential multipart Mars Sample Return (MSR) campaign, is expected to contribute to NASA’s Mars Exploration Program Science Goals by filling in knowledge gaps concerning: 1) the existence of past or present life on Mars, 2) the past and present climate of Mars, 3) the geology of Mars, and 4) hazards associated with human exploration of Mars. Although there is debate concerning which samples will best answer these questions, the necessity for proper sample blanks is well-understood. The CC and PP requirements, driven by the restricted Class V mission designation, are the most stringent of any sample return mission in recent history. The extremely low levels of allowable terrestrial contamination on the spacecraft and rover can complicate these analyses given the detection limits of current analytical instrumentation, especially in the case of biological contamination. By collecting and curating unanalyzed samples specifically for CK, future sample scientists will not be relegated to: 1) relying on data collected using possibly obsolete tools and techniques for return sample blanks, or 2) using remnants of extracted and/or cultured samples from ATLO (Assembly, Test, and Launch Operations), which could be incompatible with the desired experimental endpoints or state-of-the-art techniques available at the time of sample return.The addition of biological experimental endpoints to a sample return campaign’s objectives broadens the requisite range in preservation environments (e.g. inert ultra-pure nitrogen gaseous environment at 18 degrees Centigrade versus less than or equal to minus 80 degrees Centigrade) and types of CK samples. As a result, the Curation Office will also curate the following CK samples at less than or equal to minus 80 degrees Centigrade for the Mars 2020 mission: 1) unanalyzed swabs and wipes in sterile containers, 2) all recirculation filters from the clean rooms used for sample and caching subsystem assembly and all filters from the laminar flow benches used to assemble sample intimate hardware, and 3) witness plates collecting airborne contamination within the assembly clean rooms. It has been Curation Office policy since the Apollo missions to preserve as many pristine samples as possible for future scientific research. Although CK is required to be collected for all stages of the MSR campaign, the CK for the Mars 2020 mission is the most critical for understanding contamination in the returned samples given the intimacy between the Martian samples and the Mars 2020 flight hardware. This presentation highlights the importance of CK for sample return missions as well as the traditional and novel types of CK samples required for a successful MSR campaign.

Harrington, A. D.↗

Functional Task Tests in Partial Gravity During Parabolic Flight

BACKGROUND Understanding how critical mission tasks are performed in partial gravity such as on the moon or Mars is necessary to define effective and comprehensive countermeasure strategies for preserving crew performance during exploration missions. We studied the performance of tasks such as standing, walking, and jumping during the partial gravity phases of parabolic flight. We hypothesized that the acute effects of partial gravity on vestibular, proprioceptive, and sensorimotor functions would negatively impact performance. METHODS Twelve subjects were tested over three flights of 30 parabolas each, including 10 parabolas at 0.25g, 10 parabolas at 0.5g, and 10 parabolas at 0.75g. Subjects also performed tests in 1g between parabolas. During the sit-to-stand with obstacle walk task, subjects rose from a seated position and walked as quickly as possible straight ahead towards a cone (4 m distance), walked around the cone making a 180° left turn, returned, and sat in the chair. On the way to and from the cone, subjects stepped over a 30 cm high obstacle. For the recovery from fall task, subjects lay prone for the pull-up phase and initial 10 sec of the parabola. Then they were asked to rise as quickly as possible and maintain a quiet stance for 10 sec. The tandem rail balance task involved standing with both feet on a 4.5 cm wide rail. The time ended when subjects either stepped off the rail or grabbed on to support straps. The jump down task started with the subjects standing on a 30 cm high platform, then the subjects were instructed to step off the platform, land with both feet simultaneously, and settle in a quiet stance. The cone of stability task involved subjects leaning about the ankles as far as they could in the anterior, posterior, and lateral directions without unfolding their arms or taking a step. The center of pressure distance between endpoints was calculated. Data were collected using inertial measurement units (Opal V2, APDM, Portland, OR) worn on the head and trunk, heart rate monitors (RS800CX, Polar, Kempele, Finland), and a force plate (Bertec, Columbus, OH). RESULTS Gravity level had a significant effect on performance, with the greatest changes from 1g tending to be at the 0.25g level (Table 1). Lower gravity levels were associated with increased times to complete the sit-to-stand obstacle walk task and the recovery from fall task, decreased change in heart rate during the recovery from fall task, decreased rail balance times, and increased cone of stability distance in the anterior-posterior direction. Table 1. Functional task performance at different gravity levels during parabolic flight. Measure0.25g0.5g0.75g1gp-valueSit-to-stand with obstacle walk time (sec)9.8 ±1.4*7.2 ±0.76.9 ±0.8*7.4 ±0.9<0.001Recovery from fall time to settle (sec)5.3 ± 0.9*4.6 ± 0.84.2 ± 0.64.3 ± 0.70.002Recovery from fall change in heart rate (bpm)6.0 ± 7.3*11.2 ± 6.5*14.9 ± 4.915.9 ± 6.5<0.001Rail balance with eyes open time (sec)2.7 ±0.8*4.8 ±2.16.6 ±4.78.4 ±6.70.031Rail balance with eyes closed time (sec)1.6 ±0.4*2.1 ±0.42.4 ±0.62.6 ±0.8<0.001Jump down time to settle (sec)2.1 ± 0.41.9 ± 0.42.0 ± 0.31.8 ± 0.30.328Cone of stability –anterior-posterior (cm)20.8 ±2.7*18.8 ±2.218.6 ±1.717.9 ±2.00.039Cone of stability –lateral (cm)26.8 ±6.624.4 ±2.123.0 ±2.123.8 ±2.30.215p-value: one-way repeated measures analysis of variance; *Significant pairwise difference from 1g (p<0.05). DISCUSSION These data suggest that there is a dose-response relationship between gravity level and functional task performance. The largest changes in performance were expected at the lowest gravity level (0.25g) because subjects would no longer be able to use the gravitational reference for the perception of upright. Understanding the extent of performance deficits informs the risks and design of countermeasures for exploration spaceflight missions. ACKNOWLEDGEMENT This work is supported by NASA’s Human Research Program Human Health Countermeasures Element.

T R Macaulay↗