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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 37 records · Page 2

Crossroads Able "Gilda"

At 5:55 am local time on June 30, 1946, a B-29 bomber took to the air carrying a Fat Man bomb, christened Gilda. Named after a Rita Haworth movie character, Gilda was released over a target array of ninety-three ships, including the Japanese battleship Nagato, the German cruiser Prinz Eugen, and the United States aircraft carrier Independence, all of which carried varying amounts of munitions, fuel, and animals. Although Gilda missed its aiming point, the explosion sank five ships and severely damaged eight others. A large number of pigs, goats, and rats were exposed to lethal doses of ionizing radiation. Visually, Gilda was not that impressive, particularly to those expecting an apocalyptic event. As the New York Times reporter William Laurence recalled, “To some of the newspaper men aboard, keyed up to the point of expecting the observer ship to be blown out of the water, the spectacle, obscured somewhat by an intervening white cloud, was a disappointment. To me, who could distinguish between the natural cloud and the atomic cloud, the sight was awesome and spine chilling.”

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗

In Silico Prediction of the Toxicity of Nitroaromatic Compounds: Application of Ensemble Learning QSAR Approach

In this work, a dataset of more than 200 nitroaromatic compounds is used to develop Quantitative Structure–Activity Relationship (QSAR) models for the estimation of in vivo toxicity based on 50% lethal dose to rats (LD 50 ). An initial set of 4885 molecular descriptors was generated and applied to build Support Vector Regression (SVR) models. The best two SVR models, SVR_A and SVR_B, were selected to build an Ensemble Model by means of Multiple Linear Regression (MLR). The obtained Ensemble Model showed improved performance over the base SVR models in the training set (R 2 = 0.88), validation set (R 2 = 0.95), and true external test set (R 2 = 0.92). The models were also internally validated by 5-fold cross-validation and Y-scrambling experiments, showing that the models have high levels of goodness-of-fit, robustness and predictivity. The contribution of descriptors to the toxicity in the models was assessed using the Accumulated Local Effect (ALE) technique. The proposed approach provides an important tool to assess toxicity of nitroaromatic compounds, based on the ensemble QSAR model and the structural relationship to toxicity by analyzed contribution of the involved descriptors.

54 ENVIRONMENTAL SCIENCES↗

Ultrastructural pathogenesis of lesions produced by exposure to oxygen difluoride with correlative light microscopy

The lungs of rats exposed to OF2 were examined by light and electron microscopy. The exposures were for 30 to 60 minutes to an average of 4.5 ppm OF2, the minimal lethal dose. Animals were sacrificed after 30 (group 1) and 60 minutes (group 2) exposure and 1 (group 3) and 2 (group 4) hours following 60 minutes exposure. Mild gross changes were observed in groups 3 and 4, but no light microscopic lesions were found. Alterations were noted in all four groups using electron microscopy. These were mostly indicative of fluid change and consisted of blebbing of the endothelial and epithelial layers of the alveolocapillary wall and rarification of the cytoplasm of these cells. The lamellar bodies of the Type II cells showed an increasing and consistent loss of matrix structure and density. These fine structural changes increased in quantity and severity as time of exposure or post-exposure period increased. (Modified author abstract)

Harrison, G.↗

Radiation health for a Mars mission

Uncertainties in risk assessments for exposure of a Mars mission crew to space radiation place limitations on mission design and operation. Large shielding penalties are imposed in order to obtain acceptable safety margins. Galactic cosmic rays (GCR) and solar particle events (SPE) are the major concern. A warning system and 'safe-haven' are needed to protect the crew from large SPE which produce lethal doses. A model developed at NASA Johnson Space Center (JSC) to describe solar modulation of GCR intensities reduces that uncertainty to less than 10 percent. Radiation transport models used to design spacecraft shielding have large uncertainties in nuclear fragmentation cross sections for GCR which interact with spacecraft materials. Planned space measurements of linear energy transfer (LET) spectra behind various shielding thicknesses will reduce uncertainties in dose-versus-shielding thickness relationships to 5-10 percent. The largest remaining uncertainty is in biological effects of space radiation. Data on effects of energetic ions in human are nonexistent. Experimental research on effects in animals and cell is needed to allow extrapolation to the risk of carcinogenesis in humans.

Robbins, Donald E.↗

Natural Hazards of the Space Environment

Spacecraft in Low Earth Orbit (LEO) are subject to numerous environmental hazards. Here I'll briefly discuss three environment factors that pose acute threats to the survival of spacecraft systems and crew: atmospheric drag, impacts by meteoroids and orbital debris, and ionizing radiation. Atmospheric drag continuously opposes the orbital motion of a satellite, causing the orbit to decay. This decay will lead to reentry if not countered by reboost maneuvers. Orbital debris is a by-product of man's activities in space, and consists of objects ranging in size from miniscule paint chips to spent rocket stages and dead satellites. Ionizing radiation experienced in LEO has several components: geomagnetically trapped protons and electrons (Van Allen belts); energetic solar particles; galactic cosmic rays; and albedo neutrons. These particles can have several types of prompt harmful effects on equipment and crew, from single-event upsets, latchup, and burnout of electronics, to lethal doses to crew.All three types of prompt threat show some dependence on the solar activity cycle. Atmospheric drag mitigation and large debris avoidance require propulsive maneuvers. M/OD and ionizing radiation require some form of shielding for crew and sensitive equipment. Limiting exposure time is a mitigation technique for ionizing radiation and meteor streams.

Evans, Steven W.↗

Effects of the hindlimb-unloading model of spaceflight conditions on resistance of mice to infection with Klebsiella pneumoniae

BACKGROUND: It has been well documented in several studies that many immunologic parameters are altered in experimental animals and human subjects who have flown in space. However, it is not fully known whether these immunologic changes could result in increased susceptibility to infection. Hindlimb (antiorthostatic) unloading of rodents has been used successfully to simulate some of the effects of spaceflight on physiologic systems. OBJECTIVE: The objective of this study was to determine the effect of hindlimb unloading on the outcome of Klebsiella pneumoniae infection in mice. METHODS: Hindlimb-unloaded, hindlimb-restrained, and control mice were intraperitoneally infected with one 50% lethal dose of K pneumoniae 2 days after suspension. Mortality and bacterial load in several organs were compared among the groups. RESULTS: Unloaded mice showed significantly increased mortality and reduced mean time to death compared with that seen in the control groups. Kinetics of bacterial growth with smaller infective doses revealed that control mice were able to clear bacteria from the organs after 30 hours. In contrast, unloaded mice had continued bacterial growth at the same time point. CONCLUSION: The results of this study suggest that hindlimb unloading might enhance the dissemination of K pneumoniae, leading to increased mortality. The complex physiologic changes observed during hindlimb unloading, including stress, have a key role in the pathophysiology of this infection.

NASA Discipline Regulatory Physiology↗

Streptococcus pneumoniae PstS production is phosphate responsive and enhanced during growth in the murine peritoneal cavity

Differential display-PCR (DDPCR) was used to identify a Streptococcus pneumoniae gene with enhanced transcription during growth in the murine peritoneal cavity. Northern dot blot analysis and comparative densitometry confirmed a 1.8-fold increase in expression of the encoded sequence following murine peritoneal culture (MPC) versus laboratory culture or control culture (CC). Sequencing and basic local alignment search tool analysis identified the DDPCR fragment as pstS, the phosphate-binding protein of a high-affinity phosphate uptake system. PCR amplification of the complete pstS gene followed by restriction analysis and sequencing suggests a high level of conservation between strains and serotypes. Quantitative immunodot blotting using antiserum to recombinant PstS (rPstS) demonstrated an approximately twofold increase in PstS production during MPC from that during CCs, a finding consistent with the low levels of phosphate observed in the peritoneum. Moreover, immunodot blot and Northern analysis demonstrated phosphate-dependent production of PstS in six of seven strains examined. These results identify pstS expression as responsive to the MPC environment and extracellular phosphate concentrations. Presently, it remains unclear if phosphate concentrations in vivo contribute to the regulation of pstS. Finally, polyclonal antiserum to rPstS did not inhibit growth of the pneumococcus in vitro, suggesting that antibodies do not block phosphate uptake; moreover, vaccination of mice with rPstS did not protect against intraperitoneal challenge as assessed by the 50% lethal dose.

Non-NASA Center↗

Antiorthostatic suspension stimulates profiles of macrophage activation in mice

The antiorthostatic suspension model simulates certain physiological effects of spaceflight. We have previously reported BDF1 mice suspended by the tail in the antiorthostatic orientation for 4 days express high levels of resistance to virulent Listeria monocytogenesinfection. In the present study, we examined whether the increased resistance to this organism correlates with profiles of macrophage activation, given the role of the macrophage in killing this pathogen in vivo. We infected BDF1 mice with a lethal dose of virulent L. monocytogenes on day 4 of antiorthostatic suspension and 24 h later constructed profiles of macrophage activation. Viable listeria could not be detected in mice suspended in the antiorthostatic orientation 24 h after infection. Flow cytometric analysis revealed the numbers of granulocytes and mononuclear phagocytes in the spleen of infected mice were not significantly altered as a result of antiorthostatic suspension. Splenocytes from antiorthostatically suspended infected mice produced increased titers of IL-1. Serum levels of neopterin, a nucleotide metabolite secreted by activated macrophages, were enhanced in mice infected during antiorthostatic suspension, but not in antiorthostatically suspended naive mice. Splenic macrophages from mice infected on day 4 of suspension produced enhanced levels of lysozyme. In contrast to the results from antiorthostatically suspended infected mice, macrophages from antiorthostatically suspended uninfected mice did not express enhanced bactericidal activities. The collective results indicate that antiorthostatic suspension can stimulate profiles of macrophage activation which correlate with increased resistance to infection by certain classes of pathogenic bacteria.

Non-NASA Center↗

Forecasting the Impact of an 1859-calibre Superstorm on Satellite Resources

We have assembled a database of operational satellites in orbit as of 2004, and have developed a series of simple models to assess the economic impacts to this resource caused by various scenarios of superstorm events possible during the next sunspot cycle between 2010 and 2014. Despite the apparent robustness of our satellite assets against the kinds of storms we have encountered during the satellite era, our models suggest a potential economic loss exceeding $10(exp 11) for satellite replacement and lost profitability caused by a once a century single storm similar to the 1859 superstorm. From a combination of power system and attitude control system (the most vulnerable) failures, we estimate that 80 satellites (LEO, MEO, GEO) may be disabled as a consequence of a superstorm event. Additional consequences may include the failure of many of the GPS, GLONASS and Galileo satellite systems in MEO. Approximately 98 LEO satellites that normally would not have re-entered for many decades, may prematurely de-orbit in ca 2021 as a result of the temporarily increased atmospheric drag caused by the superstorm event occurring in 2012. The $10(exp 11) International Space Station may lose at least 15 kilometers of altitude, placing it in critical need for re-boosting by an amount that is potentially outside the range of typical Space Shuttle operations during the previous solar maximum in ca 2000, and at a time when NASA plans to decommission the Space Shuttle. Several LEO satellites will unexpectedly be placed on orbits that enter the ISS zone of avoidance, requiring some action by ground personnel and ISS astronauts to avoid close encounters. Radiation effects on astronauts have also been considered and could include a range of possibilities from acute radiation sickness for astronauts inside spacecraft, to near-lethal doses during EVAs. The specifics depends very sensitively on the spectral hardness of the accompanying SPE event. Currently, the ability to forecast extreme particle events and coronal mass ejections, or predict their fluences and geo-severity in the 24-hrs prior to the event, appears to be no better than 50/50. If the events of the 1859 superstorm serve as a guide, the scope of a contemporary superstorm will most certainly be an awesome event, but one that the vast majority of our other satellite resources may reasonably be expected to survive.

Odenwald, Sten↗

Full Mission Astronaut Radiation Exposure Assessments for Long Duration Lunar Surface Missions

Risk to astronauts due to ionizing radiation exposure is a primary concern for missions beyond Low Earth Orbit (LEO) and will drive mission architecture requirements, mission timelines, and operational practices. Both galactic cosmic ray (GCR) and solar particle event (SPE) environments pose a risk to astronauts for missions beyond LEO. The GCR environment, which is made up of protons and heavier ions covering a broad energy spectrum, is ever present but varies in intensity with the solar cycle, while SPEs are sporadic events, consisting primarily of protons moving outward through the solar system from the sun. The GCR environment is more penetrating and is more difficult to shield than SPE environments, but lacks the intensity to induce acute effects. Large SPEs are rare, but they could result in a lethal dose, if adequate shielding is not provided. For short missions, radiation risk is dominated by the possibility of a large SPE. Longer missions also require planning for large SPEs; adequate shielding must be provided and operational constraints must allow astronauts to move quickly to shielded locations. The dominant risk for longer missions, however, is GCR exposure, which accumulates over time and can lead to late effects such as cancer. SPE exposure, even low level SPE exposure received in heavily shielded locations, will increase this risk. In addition to GCR and SPE environments, the lunar neutron albedo resulting mainly from the interaction of GCRs with regolith will also contribute to astronaut risk. Full mission exposure assessments were performed for proposed long duration lunar surface mission scenarios. In order to accomplish these assessments, radiation shielding models were developed for a proposed lunar habitat and rover. End-to-End mission exposure assessments were performed by first calculating exposure rates for locations in the habitat, rover, and during extra-vehicular activities (EVA). Subsequently, total mission exposures were evaluated for proposed timelines. A number of computational tools and mathematical models, which have been incorporated into NASA's On-Line Tool for the Assessment of Radiation In Space (OLTARIS), were used for this study. These tools include GCR and SPE environment models, human body models, and the HZETRN space radiation transport code, which is used to calculate the transport of the charged particles and neutrons through shielding materials and human tissue. Mission exposure results, assessed in terms of effective dose, are presented for proposed timelines and recommendations are made for improved astronaut shielding and safer operational practice.

Adamczyk, Anne M.↗

Increased seizure susceptibility and other toxicity symptoms following acute sulforaphane treatment in mice

Activation of Nrf2 with sulforaphane has recently gained attention as a new therapeutic approach in the treatment of many diseases, including epilepsy. As a plant-derived compound, sulforaphane is considered to be safe and well-tolerated. It is widely consumed, also by patients suffering from seizure and taking antiepileptic drugs, but no toxicity profile of sulforaphane exists. Since many natural remedies and dietary supplements may increase seizure risk and potentially interact with antiepileptic drugs, the aim of our study was to investigate the acute effects of sulforaphane on seizure thresholds and activity of some first- and second-generation antiepileptic drugs in mice. In addition, some preliminary toxicity profile of sulforaphane in mice after intraperitoneal injection was evaluated. The LD{sub 50} value of sulforaphane in mice was estimated at 212.67 mg/kg, while the TD{sub 50} value – at 191.58 mg/kg. In seizure tests, sulforaphane at the highest dose tested (200 mg/kg) significantly decreased the thresholds for the onset of the first myoclonic twitch and generalized clonic seizure in the iv PTZ test as well as the threshold for the 6 Hz-induced psychomotor seizure. At doses of 10–200 mg/kg, sulforaphane did not affect the threshold for the iv PTZ-induced forelimb tonus or the threshold for maximal electroshock-induced hindlimb tonus. Interestingly, sulforaphane (at 100 mg/kg) potentiated the anticonvulsant efficacy of carbamazepine in the maximal electroshock seizure test. This interaction could have been pharmacokinetic in nature, as sulforaphane increased concentrations of carbamazepine in both serum and brain tissue. The toxicity study showed that high doses of sulforaphane produced marked sedation (at 150–300 mg/kg), hypothermia (at 150–300 mg/kg), impairment of motor coordination (at 200–300 mg/kg), decrease in skeletal muscle strength (at 250–300 mg/kg), and deaths (at 200–300 mg/kg). Moreover, blood analysis showed leucopenia in mice injected with sulforaphane at 200 mg/kg. In conclusion, since sulforaphane was proconvulsant at a toxic dose, the safety profile and the risk-to-benefit ratio of sulforaphane usage in epileptic patients should be further evaluated. - Highlights: • Sulforaphane, an Nrf2 activator, is proconvulsant at toxic doses in mice. • Sulforaphane at 100 mg/kg produces a pharmacokinetic interaction with carbamazepine. • Sulforaphane has an LD{sub 50} of 212.67 mg/kg in mice (after ip administration). • The risk-to-benefit ratio of sulforaphane needs further evaluation.

60 APPLIED LIFE SCIENCES↗

Lifelong cytomegalovirus and early‐LIFE irradiation synergistically potentiate age‐related defects in response to vaccination and infection

Abstract While whole‐body irradiation (WBI) can induce some hallmarks of immune aging, (re)activation of persistent microbial infection also occurs following WBI and may contribute to immune effects of WBI over the lifespan. To test this hypothesis in a model relevant to human immune aging, we examined separate and joint effects of lifelong latent murine cytomegalovirus (MCMV) and of early‐life WBI over the course of the lifespan. In late life, we then measured the response to a West Nile virus (WNV) live attenuated vaccine, and lethal WNV challenge subsequent to vaccination. We recently published that a single dose of non‐lethal WBI in youth, on its own, was not sufficient to accelerate aging of the murine immune system, despite widespread DNA damage and repopulation stress in hematopoietic cells. However, 4Gy sub‐lethal WBI caused manifest reactivation of MCMV. Following vaccination and challenge with WNV in the old age, MCMV‐infected animals experiencing 4Gy, but not lower, dose of sub‐lethal WBI in youth had reduced survival. By contrast, old irradiated mice lacking MCMV and MCMV‐infected, but not irradiated, mice were both protected to the same high level as the old non‐irradiated, uninfected controls. Analysis of the quality and quantity of anti‐WNV immunity showed that higher mortality in MCMV‐positive WBI mice correlated with increased levels of MCMV‐specific immune activation during WNV challenge. Moreover, we demonstrate that infection, including that by WNV, led to MCMV reactivation. Our data suggest that MCMV reactivation may be an important determinant of increased late‐life mortality following early‐life irradiation and late‐life acute infection.

59 BASIC BIOLOGICAL SCIENCES↗

A data-driven weighting scheme for multivariate phenotypic endpoints recapitulates zebrafish developmental cascades

Zebrafish have become a key alternative model for studying health effects of environmental stressors, partly due to their genetic similarity to humans, fast generation time, and the efficiency of generating high-dimensional systematic data. Studies aiming to characterize adverse health effects in zebrafish typically include several phenotypic measurements (endpoints). While there is a solid biomedical basis for capturing a comprehensive set of endpoints, making summary judgments regarding health effects requires thoughtful integration across endpoints. Here, we introduce a Bayesian method to quantify the informativeness of 17 distinct zebrafish endpoints as a data-driven weighting scheme for a multi-endpoint summary measure, called weighted Aggregate Entropy (wAggE). We implement wAggE using high-throughput screening (HTS) data from zebrafish exposed to five concentrations of all 1060 ToxCast chemicals. Our results show that our empirical weighting scheme provides better performance in terms of the Receiver Operating Characteristic (ROC) curve for identifying significant morphological effects and improves robustness over traditional curve-fitting approaches. From a biological perspective, our results suggest that developmental cascade effects triggered by chemical exposure can be recapitulated by analyzing the relationships among endpoints. Thus, wAggE offers a powerful approach for analysis of multivariate phenotypes that can reveal underlying etiological processes. - Highlights: • Introduced a data-driven weighting scheme for multiple phenotypic endpoints. • Weighted Aggregate Entropy (wAggE) implies differential importance of endpoints. • Endpoint relationships reveal developmental cascade effects triggered by exposure. • wAggE is generalizable to multi-endpoint data of different shapes and scales.

60 APPLIED LIFE SCIENCES↗

Mdr1a plays a crucial role in regulating the analgesic effect and toxicity of aconitine by altering its pharmacokinetic characteristics

Aconitine (AC) is the primary bioactive/toxic alkaloid in plants of the Aconitum species. Our previous study demonstrated that Mdr1 was involved in efflux of AC. However, the mechanism by which Mdr1 regulates the efficacy/toxicity of AC in vivo remains unclear. The present study aimed to determine the effects of Mdr1a on the efficacy/toxicity and pharmacokinetics of AC in wild-type and Mdr1a{sup −/−} FVB mice. After oral administration of AC, significantly higher analgesic effect was observed in Mdr1a{sup −/−} mice (49% to 105%) compared to wild-type mice (P < 0.05). The levels of s100-β protein and creatine kinase, which indicate cerebral and myocardial damage, respectively, were also significantly increased (P < 0.05) in Mdr1a{sup −/−} mice. Histopathological examination revealed that the Mdr1a{sup −/−} mice suffered from evident cerebral and myocardial damages, but the wild-type mice did not. These findings suggested that Mdr1a deficiency significantly promoted the analgesic effect of AC and exacerbated its toxicity. Pharmacokinetic experiments showed that T{sub 1/2} of AC in the Mdr1a{sup −/−} mice was significantly higher (from 87% to 300%) than that in wild-type mice (P < 0.05). The distribution of AC in the brain of Mdr1a{sup −/−} mice was 2- to 32-fold higher than that in the brains of wild-type mice (P < 0.05). Toxic reactions were more severe in Mdr1a{sup −/−} mice compared to wild-type mice. In conclusion, Mdr1a deficiency significantly enhanced the analgesic effect of AC and exacerbated its toxicity by upregulating its distribution to the brain and decreasing its plasma elimination rate. Thus, Mdr1a dysfunction may cause severe AC poisoning. - Highlights: • The efficacy and toxicity of aconitine were significantly enhanced in Mdr1a{sup −/−} mice. • The distribution of aconitine to the brain was remarkably increased in Mdr1a{sup −/−} mice. • The elimination rate of aconitine was significantly decreased in Mdr1a{sup −/−} mice.

60 APPLIED LIFE SCIENCES↗

Dysregulation of lung epithelial cell homeostasis and immunity contributes to Middle East respiratory syndrome coronavirus disease severity

Coronaviruses (CoV) emerge suddenly from animal reservoirs to cause novel diseases in new hosts. Discovered in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV) is endemic in camels in the Middle East and is continually causing local outbreaks and epidemics. While all three newly emerging human CoVs from the past 20 years (SARS-CoV, SARS-CoV-2, and MERS-CoV) cause respiratory disease, each CoV has unique host interactions that drive differential pathogeneses. To better understand the virus and host interactions driving lethal MERS-CoV infection, we performed a longitudinal multi-omics analysis of sublethal and lethal MERS-CoV infection in mice. Significant differences were observed in body weight loss, virus titers, and acute lung injury among lethal and sub-lethal virus doses. Virus-induced apoptosis of type I and II alveolar epithelial cells suggests that loss or dysregulation of these key cell populations was a major driver of severe disease. Omics analysis suggested differential pathogenesis was multi-factorial with clear differences among innate and adaptive immune pathways as well as those that regulate lung epithelial homeostasis. Infection of mice lacking functional T and B cells showed that adaptive immunity was important in controlling viral replication but also increased pathogenesis. In summary, we provide a high-resolution host response atlas for MERS-CoV infection and disease severity. Multi-omics studies of viral pathogenesis offer a unique opportunity to not only better understand the molecular mechanisms of disease but also to identify genes and pathways that can be exploited for therapeutic intervention all of which is important for our future pandemic preparedness.

MERS-CoV↗

Acute pulmonary pathology and sudden death in rats following the intravenous administration of the plasticizer, DI (2-ethylhexyl) phthalate, solubilized with Tween surfactants

Intravenous administration of 200-300 mg/kg of di(2-ethylhexyl)phthalate (DEHP) solubilized in aqueous solutions of several Tween surfactants caused respiratory distress in rats. There was a dose-dependent lethality with death generally occurring within 90 minutes after injection. The lungs from DEHP:Tween treated animals were enlarged, generally darkened, and in some cases showed hemorrhagic congestion. Neither the overt symptoms nor the morphologic alterations resulting from DEHP:Tween administration could be reproduced by intravenous administration of aqueous Tween solutions alone. The absence of pulmonary abnormalities following the intravenous administration of DEHP as an aqueous emulsion given either alone or even as soon as 2 minutes after pretreatment with Tween 80, suggests that the specific in vivo interaction between DEHP and Tween surfactants depends on the prior formation of water-soluble micelles of DEHP.

Schulz, C. O.↗