Engineering topics
Publications and source records attributed to James, John T..
The lunar surface is covered by a layer of fine, reactive dust. Very little is known regarding the toxicity of lunar dust on human physiology. This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and systemic immune parameters.
The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1‐2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose‐only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose‐dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.
The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1‐2% of very fine respirable dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust‐induced changes of the expression of fibrosis‐related genes, and to identify specific signaling pathways involved in lunar dustinduced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose‐only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 milligrams per cubic meters of lunar dust. Five rats per group were euthanized at 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The bronchoalveolar lavage fluid (BALF) was collected by lavaging with phosphate‐buffered saline (PBS). A zymosan‐induced luminolbased chemiluminescence assay was used to assess the activity of BAL cells. The lavaged lung tissue was snap frozen in LN2 and total RNA was isolated using the Qigen RNeasy kit. The expression of 84 fibrosisrelated genes were analyzed using the RT2 Profiler PCR Array technique. The expression of 18 genes of interest were further measured using real‐time PCR technique in all the samples. 10 out of 18 genes of interest showed persistently significant expression changes in the local lung tissue exposed to lunar dust, indicating a prolonged proinflammatory response. The expressions of several of these genes were dose‐ and time‐dependent and were significantly correlated with other pathological parameters. The potential signaling pathways and upstream regulators were further analyzed using IPA pathway analysis tool based on the gene expression data. The data presented in this study, for the first time, explore the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust‐induced toxicity in humans on earth.
Background: Due to millennia of meteorite impact with virtually no erosive effects, the surface of the Moon is covered by a layer of ultra‐fine, reactive Lunar dust. Very little is known regarding the toxicity of Lunar dust on human physiology. Given the size and electrostatic characteristics of Lunar dust, countermeasures to ensure non‐exposure of astronauts will be difficult. To ensure astronaut safety during any future prolonged Lunar missions, it is necessary to establish the effect of chronic pulmonary Lunar dust exposure on all physiological systems. Methods: This study assessed the toxicity of airborne lunar dust exposure in rats on pulmonary and system immune system parameters. Rats were exposed to 0, 20.8, or 60.8 mg/m3 of lunar dust (6h/d; 5d/wk) for up to 13 weeks. Sacrifices occurred after exposure durations of 1day, 7 days, 4 weeks and 13 weeks post‐exposure, when both blood and lung lavage fluid were collected for analysis. Lavage and blood assays included leukocyte distribution by flow cytometry, electron/fluorescent microscopy, and cytokine concentration. Cytokine production profiles following mitogenic stimulation were performed on whole blood only. Results: Untreated lavage fluid was comprised primarily of pulmonary macrophages. Lunar dust inhalation resulted in an influx of neutrophils and lymphocytes. Although the percentage of lymphocytes increased, the T cell CD4:CD8 ratio was unchanged. Cytokine analysis of the lavage fluid showed increased levels of IL‐1b and TNFa. These alterations generally persisted through the 13 week sampling. Blood analysis showed few systemic effects from the lunar dust inhalation. By week 4, the peripheral granulocyte percentage was elevated in the treated rats. Plasma cytokine levels were unchanged in all treated rats compared to controls. Peripheral blood analysis showed an increased granulocyte percentage and altered cytokine production profiles consisting of increased in IL‐1b and IL‐6, and decreased IL‐2 production. Conclusion: Lunar dust inhalation results in significant lung inflammation, and some systemic effects, that does not resolve through 13 weeks. Lunar dust may therefore represent a crew health risk during sortie or long‐duration Lunar missions.
The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.
The Moon's surface is covered by a layer of reactive dust, containing 1-2% of respirable fine dust (< 3 microns). The habitable area of any lunar landing vehicle would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents through inhalation to assess the health risk of dust exposures to humans and to identify the mechanisms and potential pathways involved in lunar dust-induced toxicity. Ccl3, Ccl12, Cxcl2, Cxcl5, Itgb8, Tnf, Ldhc, Clec4e, Bmp7, and Smad6, showed persistently significant expression changes in the lung tissue. The expression of several of these genes were dose- and time- dependent, and were significantly correlated with other pathological. Our previous data showed that no pathological changes were detected in low dose groups. However, several genes, primarily produced by lung epithelial, were significantly altered persistently in response to low-dose dust exposure. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity, contributing not only the risk assessment for future space exploration, but also understandings of the dust-induced toxicity to humans on earth.
The purpose of the study is to analyze the dynamics of global gene expression changes in the lung tissue of rats exposed to lunar dust particles. Multiple pathways and transcription factors were identified using the Ingenuity Pathway Analysis tool, showing the potential networks of these signaling regulations involved in lunar dust‐induced prolonged proflammatory response and toxicity. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity. This work contributes not only to the risk assessment for future space exploration, but also to the understanding of the dust‐induced toxicity to humans on earth.
The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to evaluate the toxicity of Apollo moon dust in rodents to assess the health risk of dust exposures to humans. One of the particular interests in the study is to evaluate dust-induced changes of the expression of fibrosis-related genes, and to identify specific signaling pathways involved in lunar dust-induced toxicity. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.1, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, 1 week, 1 month, and 3 months after the last inhalation exposure. The total RNAs were isolated from the blood or lung tissue after being lavaged, using the Qigen RNeasy kit. The Rat Fibrosis RT2 Profile PCR Array was used to profile the expression of 84 genes relevant to fibrosis. The genes with significant expression changes are identified and the gene expression data were further analyzed using IPA pathway analysis tool to determine the signaling pathways with significant changes.
The occupants of modern submarines and the International Space Station (ISS) have much in common as far as their air quality is concerned. Air is polluted by materials offgassing, use of utility compounds, leaks of systems chemicals, and anthropogenic sources. The primary anthropogenic compound of concern to submariners and astronauts has been carbon dioxide (CO2). NASA and the US Navy rely on the National Research Council Committee on Toxicology (NRC-COT) to help formulate exposure levels to CO2 that are thought to be safe for exposures of 3-6 months. NASA calls its limits Spacecraft Maximum Allowable Concentrations (SMACs). Years of experience aboard the ISS and a recent publication on deficits in decision making in ground-based subjects exposed briefly to 0.25% CO2 suggest that exposure levels that have been presumed acceptable to preserve health and performance need to be reevaluated. The current CO2 exposure limits for 3-6 months set by NASA and the UK Navy are 0.7%, and the limit for US submariners is 0.5%, although the NRC-COT recommended a 90-day level of 0.8% as safe a few years ago. NASA has set a 1000-day SMAC at 0.5% for exploration-class missions. Anecdotal experience with ISS operations approaching the current 180-day SMAC of 0.7% suggest that this limit is too high. Temporarily, NASA has limited exposures to 0.5% until further peer-reviewed data become available. In the meantime, a study published last year in the journal Environmental Health Perspectives (Satish U, et al. 2012) demonstrated that complexdecision- making performance is somewhat affected at 0.1% CO2 and becomes "dysfunctional" for at least half of the 9 indices of performance at concentrations approaching 0.25% CO2. The investigators used the Strategic Management Simulation (SMS) method of testing for decisionmaking ability, and the results were so surprising to the investigators that they declared that their findings need to be independently confirmed. NASA has responded to the findings on decision making by developing a study to either confirm or refute the published results. In addition, other neurocognitive tests that have been and will be used aboard the ISS will be part of the ground-based study. Further evaluations during the exposures will include ocular and cardiovascular effects of CO2 exposure. In addition, the 1- carbon genetics of the test subjects will be evaluated to determine if any individual subjects are unusually susceptible to CO2 exposure because of genetic factors. Our plan is to extend the published study from Satish by employing a wider series of CO2 exposures to include concentrations of 0.06, 0.12, 0.25, and 0.50%. We believe that our findings will be of keen interest to submariners and to those designing "tight" buildings.
A summary of the analytical results from 6 grab sample containers (GSCs) and 12 pairs of formaldehyde badges collected on ISS and returned aboard 29S or 31 S is shown in an accompanying table. The average recoveries of the 3 surrogate standards from the GSCs were as follows: C-l3-acetone, 128%; fluorobenzene, 114%; and chlorobenzene, 78%. Recoveries of two lab-control formaldehyde badges averaged 95%.
Brief exposures of Apollo Astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure ot lunar dust. Habitats for exploration, whether mobile of fixed must be designed to limit human exposure to lunar dust to safe levels. We have used a new technique we call Comparative Benchmark Dose Modeling to estimate safe exposure limits for lunar dust collected during the Apollo 14 mission.
On September 26 and September 28,2012 a chemist from the JSC Toxicology Group acquired samples of air in 500 m1 evacuated canisters from the sealed Space-Xl Dragon Module. One sample was also acquired from Space-X Facility near the module at the start of the test. Samples of the module air were taken in triplicate once the module had been sealed, and then taken again in triplicate 1.98 days later. Ofthe triplicate samples, the first served as a line purge, and the last two were analyzed. The results of 5 samples are reported.
There have been a cluster of anecdotal reports that ISS crews are experiencing adverse health effects from on orbit exposure to CO2 levels well below the current Spacecraft Maximum Allowable Concentration (SMAC), which is 5.3 mmHg for 180 days of exposure. Developing evidence that this standard should be reduced to protect crew health is not a simple process. Dr. John James' team looked at the reports of headaches by the crew during private medical conferences and matched these with CO2 levels around the time of these reports. They then compared these to CO2 levels when there were no reports of headache. Using benchmark dose modeling, they found that the risk of headache could be predicted in concentration ranges from 2 to 5 mmHg. However, the data are incomplete because there were insufficient data when crews were exposed to concentrations below 2 mmHg. James' team also asked whether neuro-cognitive effects could be identified with CO2 exposure levels and found that these could not be associated with CO2 levels. Finally, they addressed the question of resource use to meet various levels of CO2 control if the SMACs were lowered. They estimated that CO2 restrictions approaching 2 mmHg would require substantial increases in power use and up-mass resources. They are refining their data on CO2 and headaches, and are looking at potential interactions of intracranial pressure and CO2 levels in eliciting ocular effects.
The toxicological assessment of 17 GSCs returned aboard Soyuz 28 and 29 from the ISS is shown in Table 1. The average recoveries of the 3 surrogate standards from the GSCs were as follows: (C-13)-acetone, 110%; fluorobenzene, 107%; and chlorobenzene, 99%. Recoveries from formaldehyde badges, which were returned on 29S, averaged 101%.
The toxicological assessment of one sample collected on May 26, 2012 and returned to earth on May 31, 2012 was analyzed for pollutants that had offgassed into the Dragon capsule by the time of first entry operations performed by the ISS crew. The components identified in the first-entry sample and their contributions to the total T-value are shown.
NASA has been contemplating returning astronauts to the moon for long-duration habitation and research and using it as a stepping-stone to Mars. Other spacefaring nations are planning to send humans to the moon for the first time. The surface of the moon is covered by a layer of fine dust. Fine terrestrial dusts, if inhaled, are known to pose a health risk to humans. Some Apollo crews briefly exposed to moon dust that adhered to spacesuits and became airborne in the Lunar Module reported eye and throat irritation. The habitable area of any lunar landing vehicle or outpost would inevitably become contaminated with lunar dust. To assess the health risks of exposure of humans to airborne lunar dust, we evaluated the toxicity of Apollo 14 moon dust in animal lungs. Studies of the pulmonary toxicity of a dust are generally first done by intratracheal instillation (ITI) of aqueous suspensions of the test dust into the lungs of rodents. If a test dust is irritating or cytotoxic to the lungs, the alveolar macrophages, after phagocytizing the dust particles, will release cellular messengers to recruit white blood cells (WBCs) and to induce dilation of blood capillary walls to make them porous, allowing the WBCs to gain access to the alveolar space. The dilation of capillary walls also allows serum proteins and water entering the lung. Besides altering capillary integrity, a toxic dust can also directly kill the cells that come into contact with it or ingest it, after which the dead cells would release their contents, including lactate dehydrogenase (a common enzyme marker of cell death or tissue damage). In the treated animals, we lavaged the lungs 1 and 4 weeks after the dust instillation and measured the concentrations of these biomarkers of toxicity in the bronchioalveolar lavage fluids to determine the toxicity of the dust. To assess whether the inflammation and cellular injury observed in the biomarker study would lead to persistent or progressive histopathological changes, a similar study was conducted to microscopically examine rat lung tissue and the associated lymph nodes for lesions, including fibrosis, 1 or 3 months after the instillation. The results from this ITI study led us to select two concentrations (20 and 60 mg/cu m) for an inhalation study, in which rats were exposed to lunar dust 6 h daily for 4 weeks (5d/wk). Similar biochemical and histopathological assessments were carried out in these rats 1 day or 1, 4, or 13 weeks after the dust exposure. Rats exposed to lunar dust by ITI or inhalation showed effects indicating that the dust is moderately toxic. The data will be useful to establish safe exposure limits for astronauts working in a lunar habitat and also help engineers designing dust mitigation systems for lunar vehicles and habitats.
Between 7 April and 11 April 2012 a chemist from the JSC Toxicology Group acquired samples of air in 500 ml evacuated canisters from the sealed Dragon Module at the Space-X facility at KSC. Three samples were taken of facility air (two before the test and one after the test), and a total of 9 samples were taken from the sealed module in triplicate at the following times: 0 hours, 48 hours, and 96 hours. The module contained 470 kg, which was 100% of the mass to be launched. Analytical data contained in the Toxicology Group Report (attached) show that the ambient facility air was clean except for almost 9 milligrams per cubic meter of isopropanol (IPA) in the sample taken at the end of the test. Space-X must ensure that IPA is not introduced into the module before it is sealed for launch. Other minor contaminants in the ambient air included the following: perfluoro(2-methyl)pentane and hexamethylcyclotrisiloxane. The first-acquired samples of each triplicate from the module were not analyzed. Analyses of pairs of samples that were taken during the test show excellent agreement between the pairs and a linear increase in the T-values during the 4 days of the test (figure below). The rate of increase averaged 0.124 T units per day. If the time from last purge of the module on the ground to crew first entry on orbit is 10 days, then the T value at first entry should be less than 1.2 units, which is well below the criterion of 3.0 for consideration of additional protection of the crew from offgas products. The primary contributors were as follows: trimethylsilanol (0.057), fluorotrimethylsilane (0.047), acetaldehyde (0.004), hexamethylcyclopentasiloxane (0.003), and toluene (0.002).