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NASA NTRSDate not supplied

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Medicine and Pharmacogenomics for Human Deep Space Exploration

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expanding duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be even more essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to further tailor medications included in the spacecraft formulary and increased examination of appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of cutting-edge research and medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique factors and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. One example is the field of pharmacogenomics (PGX),the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on pharmaceutical choice and dosing to avoid adverse drug events and maximize pharmacological efficacy. The goal of this study was to evaluate which drugs in the current space pharmacy could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs onboard the International Space Station (ISS) was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both personal astronaut medications, including supplements and over the counter drugs (n=151) and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in 157 total drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure. Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent adverse events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost or technical and ranked from 1 (very low) to 5 (very high).A comprehensive assessment of commercially available PGX solutions is currently underway to evaluate specimen requirements, cost/benefit analysis (cost vs. number of alleles assessed), utility of variant analysis, relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments(LxC 5x5 table) indicated29medicationswere in the yellow or red zone driven predominantly by drug failure or safety concerns, with the remainder(n=128)of the medications in the green zone where risk is acceptable. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive pre-flight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve targeting drug efficacy and safety, and further open the door to countermeasure research exploring PGX-related allelic variants. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more cost effective and more efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing crew autonomy and providing tailored countermeasures

Alice R W Tang↗

NASA NTRSDate not supplied

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Health and Pharmacogenomics

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expand in duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to tailor medications for individual crewmembers and further examine appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique clinical and environmental history, genetic makeup, and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. A subset of this field is pharmacogenomics (PGX), the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on drug choice and dosing to avoid adverse events and maximize efficacy. The study goal was to identify which current space pharmacy drugs could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs on the ISS was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both astronauts’ personal medications, including supplements and over the counter drugs (n=151) contained in the ISS medical accessory kit (IMAK), and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in a total of 157 drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure (LxC). Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent ineffective treatment or impactful side effect events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost, or technical criteria and ranked from 1 (very low) to 5 (very high). An assessment of PGX reference laboratories is currently underway to evaluate sample requirements, benefit analysis (cost vs. utility of allele variant analysis), relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments (LxC 5x5 table) indicated 128 medications were in the green zone where risk is acceptable, with the remaining 29 of the medications in the yellow or red zone driven predominantly due to drug failure or safety concerns. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive preflight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve drug efficacy, and further open the door to countermeasure research. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more effective and efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing selection of the best treatment choice, and providing tailored countermeasures for individual crewmembers.

Pharmacogenomics↗

NASA NTRS2017

Fluid Shifts

Introduction. NASA's Human Research Program is focused on addressing health risks associated with long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but now more than 50 percent of ISS astronauts have experienced more profound, chronic changes with objective structural findings such as optic disc edema, globe flattening and choroidal folds. These structural and functional changes are referred to as the visual impairment and intracranial pressure (VIIP) syndrome. Development of VIIP symptoms may be related to elevated intracranial pressure (ICP) secondary to spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to determine if a relation exists with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as any VIIP-related effects of those shifts, are predicted by the crewmember's pre-flight status and responses to acute hemodynamic manipulations, specifically posture changes and lower body negative pressure. Methods. We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, and calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography; intraocular pressure; 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness; Doppler ultrasound of ophthalmic and retinal arteries and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, otoacoustic emissions). Pre- and post-flight, acute head-down tilt will induce cephalad fluid shifts, whereas lower body negative pressure will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome. Discussion. Ten subjects have consented to participate in this experiment, including the recent One-Year Mission crewmembers, who have recently completed R plus180 testing; all other subjects have completed pre-flight testing. Preliminary results from the One-Year Mission crewmembers will be presented, including measures of ocular structure and function, vascular dimensions, fluid distribution, and non-invasive estimates of intracranial pressure.

Stenger, M. B.↗

NASA NTRS2003

Age affects severity of venous gas emboli on decompression from 14.7 to 4.3 psia

INTRODUCTION: Variables that define who we are, such as age, weight and fitness level influence the risk of decompression sickness (DCS) and venous gas emboli (VGE) from diving and aviation decompressions. We focus on age since astronauts that perform space walks are approximately 10 yr older than our test subjects. Our null hypothesis is that age is not statistically associated with the VGE outcomes from decompression to 4.3 psia. METHODS: Our data are from 7 different NASA tests where 188 men and 50 women performed light exercise at 4.3 psia for planned exposures no less than 4 h. Prebreathe (PB) time on 100% oxygen ranged from 150-270 min, including ascent time, with exercise of different intensity and length being performed during the PB in four of the seven tests with 150 min of PB. Subjects were monitored for VGE in the pulmonary artery using a Doppler ultrasound bubble detector for a 4-min period every 12 min. There were six design variables; the presence or absence of lower body adynamia and five PB variables; plus five concomitant variables on physical characteristics: age, weight height, body mass index, and gender that were available for logistic regression (LR). We used LR models for the probability of DCS and VGE, and multinomial logit (ML) models for the probability of Spencer VGE Grades 0-IV at exposure times of 61, 95, 131, 183 min, and for the entire exposure. RESULTS: Age was significantly associated with VGE in both the LR and ML models, so we reject the null hypothesis. Lower body adynamia was significant for all responses. CONCLUSIONS: Our selection of tests produced a wide range of the explanatory variables, but only age, lower body adynamia, height, and total PB time was helpful in various combinations to model the probability of DCS and VGE.

Clinical Trial↗

NASA NTRS2008

Organizational Considerations for Implementing Systems Engineering and Integration in the Ares Projects Office

Systems Engineering and Integration (SE&I) is a critical discipline in developing new space systems. In 2005, NASA performed an internal study of 24 agency and Department of Defense (DoD) programs to evaluate methods of integrating SE&I practices and determine their effectiveness. The goal of the study was to determine the best SE&I implementation strategy for the Ares Projects Office. The study identified six SE&I organizational structures: 1. Lead systems integrator (LSI) with SE&I responsibility and government technical insight. 2a. Integration contractor with government SE&I responsibility (government insight). 2b. Integration contractor with government SE&I responsibility (government oversight). 3a. Prime contractor with SE&I responsibility (government insight). 3b. Prime contractor with SE&I responsibility (government oversight). 3c. Prime contractor with SE&I responsibility (government/industry partnership). 4a.Prime contractor with government SE&I responsibility (government insight). 4b. Prime contractor with government SE&I responsibility (government oversight). 4d.Prime contractors with total system performance responsibility (TSPR). 5. Prime contractor with government SE&I responsibility and integration products through a Federally Funded Research and Development Center (FFRDC). 6. Government/FFRDC in-house development with SE&I responsibility and function. The organizational structure used most often was number 4, using a prime contractor with government SE&I responsibility and government technical insight. However, data analyses did not establish a positive relationship between program development costs and specific SE&I organizational types, nor did it positively determine the relationship between successful programs or projects and their SE&I structure. The SE&I study reached the following conclusions: (1) Large, long-duration, technically complex programs or projects reach their technical goals, but rarely meet schedule or cost goals. NASA's recent successes have been smaller, short-duration development projects using heritage hardware/software, focused technology development, technical oversight and stable external factors. (2) Programs and projects have failed or been terminated due to lack of technical insight, relaxing of SE&I processes, and unstable external factors. (3) The study did not find a single, clear optimum SE&I organization type to fit all projects. However, while any organizational structure can be made to work, the fewer complexities in the program, the better the likelihood of success. (4) The most common successful SE&I organization structure type in the study was type 4b, where the government maintained integration responsibility, with the prime contractor providing SE&I products and the government providing technical oversight. This study was instrumental in helping the APO select organization structure 4, following the same SE&I and oversight process used during humanlund7s last voyages to the Moon.

Thomas, LeAnn↗

NASA NTRS2016

Fluid Shifts

NASA is focusing on long-duration missions on the International Space Station (ISS) and future exploration-class missions beyond low-Earth orbit. Visual acuity changes observed after short-duration missions were largely transient, but more than 50% of ISS astronauts experienced more profound, chronic changes with objective structural and functional findings such as papilledema and choroidal folds. Globe flattening, optic nerve sheath dilation, and optic nerve tortuosity also are apparent. This pattern is referred to as the visual impairment and intracranial pressure (VIIP) syndrome. VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) may be associated with the spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. The purpose of this study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight, and to correlate these findings with vision changes and other elements of the VIIP syndrome. We also seek to determine whether the magnitude of fluid shifts during spaceflight, as well as the VIIP-related effects of those shifts, is predicted by the crewmember's preflight conditions and responses to acute hemodynamic manipulations (such as head-down tilt). Lastly, we will evaluate the patterns of fluid distribution in ISS astronauts during acute reversal of fluid shifts through application of lower body negative pressure (LBNP) interventions to characterize and explain general and individual responses. METHODS: We will examine a variety of physiologic variables in 10 long-duration ISS crewmembers using the test conditions and timeline presented in the Figure below. Measures include: (1) fluid compartmentalization (total body water by D2O, extracellular fluid by NaBr, intracellular fluid by calculation, plasma volume by CO rebreathe, interstitial fluid by calculation); (2) forehead/eyelids, tibia, calcaneus tissue thickness (by ultrasound); (3) vascular dimensions by ultrasound (jugular veins, cerebral and carotid arteries, vertebral arteries and veins, portal vein); (4) vascular dynamics by MRI (head/neck blood flow, cerebrospinal fluid pulsatility); (5) ocular measures (optical coherence tomography, intraocular pressure, 2-dimensional ultrasound including optic nerve sheath diameter, globe flattening, and retina-choroid thickness, Doppler ultrasound of ophthalmic and retinal arteries, and veins); (6) cardiac variables by ultrasound (inferior vena cava, tricuspid flow and tissue Doppler, pulmonic valve, stroke volume, right heart dimensions and function, four-chamber views); and (7) ICP measures (tympanic membrane displacement, distortion-product otoacoustic emissions, and ICP calculated by MRI). On the ground, acute head-down tilt will induce cephalad fluid shifts, whereas LBNP will oppose these shifts. Controlled Mueller maneuvers will manipulate cardiovascular variables. Through interventions applied before, during, and after flight, we intend to fully evaluate the relationship between fluid shifts and the VIIP syndrome.

Stenger, M.↗

NASA NTRSDate not supplied

Flow Characterization of the NASA Langley Unitary Plan Wind Tunnel, Test Section 2: Computational Results

This is an abstract for an invited paper at the AIAA Aviation Conference, June 2021. The work described here is part of an effort of coordinated experiments in the Unitary Plan Wind Tunnel (UPWT) facility at the NASA Langley Research Center (LaRC) and matching CFD simulations. The primary goal of the work is to assess the productivity and true predictive accuracy of CFD, absent any guidance from experiment, in the high supersonic speed range as compared to experiments performed at the NASA LaRC’s UPWT facility. This report concerns CFD simulation of the primary flow-path in the empty wind tunnel, including the settling chamber, nozzle, test section, and some of the tunnel downstream of the test section. The Mach number in the test section ranges from M~2.4 to M~4.6, and the required area ratio variation is achieved by translation of a nozzle block which constricts the area of a loosely S-shaped throat. Flow past protuberances in the settling chamber and into this S-bend throat are predicted by CFD to generate streamwise vorticity that may, or may not, persist through the throat and into the test section as coherent vortices. Some flow conditions are notably unsteady at frequencies well below those of turbulence, due to unsteady separated flow ahead of the nozzle block. The bulk flow moves at velocities ranging from 'walking speed' in the settling chamber to M~4.6 in the test section. Heat transfer to the settling chamber walls and buoyancy are significant at high Mach number. Subtle variations in surface curvature in the nozzle generate Mach waves that propagate into the test section. CFD of the empty tunnel serves two purposes. Firstly, the full-tunnel simulations are used to provide upstream boundary conditions for CFD of vehicle aerodynamics which are generally performed in a domain confined to the wind tunnel test section; these companion studies are addressed in other papers. Secondly, it is a challenging test for CFD to resolve all of the empty tunnel flow phenomena relevant to flow in the test section. It requires a more complete definition of geometry than was originally anticipated. In addition, it requires good spatial and temporal accuracy, and turbulence modeling that performs well on specific phenomena such as corner flows. The boundary conditions and solution algorithms must perform well from incompressible to almost hypersonic speeds. The final state of the pre-test CFD was a product of an iterative self-improvement process. The initial simulations of the empty tunnel were deficient in many respects, but hints to those deficiencies were recognized in the solutions, and remedies were implemented. Possible further improvements will be studied in the post-test phase when comparisons with experimental data are possible. The CFD was performed by five separate collaborative teams using four different flow solvers: FUN3D, Overflow, Star-CCM+ and USM3D. The level of effort of these teams varied significantly, but each made important contributions to the goals of the work. A concerted effort to use uncertainty quantification methods (UQ) in CFD is also a goal of this work. To this end, variations in CFD results due to grid refinement, turbulence modeling, and boundary conditions have been characterized. Code-to-code variation is another means of assessing CFD uncertainty. All CFD solvers predict similarity among the primary flow features; these include the variation of Mach number due to changes in Reynolds number, and the bulk flow angularity due to tunnel-wall curvature. All CFD solvers also predict similar trends in secondary flows, such as the downwash in the side-wall boundary layers. Three of the high-spatial resolution simulations give similar predictions of a complex secondary flow phenomena, streamwise vortices generated in the S-bend throat that persist into the side-wall boundary layers of the test section. Two of the highest-resolution simulations, run with the same turbulence model in different CFD solvers, gave encouragingly similar predictions of a complex tertiary flow phenomenon, small transient "sprites" of upwash flows, resulting from vortices that presumably originate in the separated flow near the leading edge of the nozzle block. While the CFD was done in a "blind pre-test" mode, requests from the experimental team for CFD results pertaining to unsteadiness and total temperature variations in the test section resulted in CFD runs that included a cooled wall in settling chamber. This then led to a change in the standard practice for running the Overflow results, which would not have occurred without this "release" of this experimental information. CFD was also used to guide some measurements. The paper will focus on establishing the consensus among CFD results and understanding differences among those results. Initial findings from the efforts to characterize CFD uncertainty have been done and will be included in the paper.

Robert Edward Childs↗

NASA NTRS2025

Navigating Team Dynamics: Automated Detection of Micro-Behaviors Between Team Members Through Longitudinal Interaction Data

The success in future long term space exploration missions will depend on the cooperation, coordination, and mutual understanding among the crew members. Micro-behaviors are momentary, subtle linguistic and paralinguistic indicators of thinking and feeling toward another member of the team (Cortina et al., 2001; Smith & Griffiths, 2022) that can significantly impact team dynamics and influence the overall team performance (Paromita & Chaspari, 2024). Due to their interactive nature, micro-behaviors have a sender (i.e., the team member expressing the micro-behavior) and a target (the team member impacted by the micro-behavior). Detection of these behaviors can assist in avoiding possible conflict among crew members and promoting the overall team success. Our prior research focused on an initial proof of concept of machine learning (ML) models and natural language processing (NLP) techniques that were used for automatically detect micro-behaviors among crew members of the US National Aeronautics and Space Administration’s (NASA) Human Exploration Research Analog (HERA) Campaigns 4 and 5 missions (Paromita et al., 2023). Results underscored the importance of incorporating contextual information in the ML models in the form of sentiment analysis, type of task, and dyadic interaction among team members. Here, we expand the scope of our prior work in two ways. First, we assess ML/NLP methods on new behavioral annotations coded using an adapted version of Smith & Griffins (2022) theoretical framework in terms of Violation (i.e., presence of valenced behavior, uplifting/positive or discouraging/negative), Intensity (i.e., force of behavior in terms of how uplifting or discouraging is the behavior), and Intent (i.e., motive of the behavior in terms of whether it was deliberate or unintentional). Second, we expand the design of the ML model to preserve information about the role of each team member within the occurrence of the micro-behavior (in contrast to the previous model that only considered the sender and the target without determining the team member role). This allows to consider all team members' contributions in the conversation and model long-term dependencies in the dialogue. Our experiments for this study are conducted on data from 5 teams of the NASA HERA C4 (NASA grant NNX16AQ48G (PI: Bell)). Conversations were extracted from the 1.5 hour Team Interaction Battery (TIB) task that occurred 5 times in-mission per crew. This resulted in a total of 13,058 conversational turns (i.e., 17.8% uplifting, 3.3% discouraging, 75.76% neutral, 3.14% nulls). Our findings with the revised behavioral coding and ML/NLP models indicate a 43.66% macro F1-score (i.e., 38.29% precision (P), 50.8% recall (R)) for a dialog state-tracking model that includes information from the sender only, and a 40.9% F1-score (i.e., 38.7% P, 43.36% R) for the same model that includes information from both the sender and the target of the micro-behavior. These are significantly higher compared to simple random forest models that classify behaviors strictly based on speech content and do not consider iterative team dynamics, achieving a 36.07% F1-score (i.e., 39.04% R, 33.53% P). Our findings demonstrate potential ways to leverage large conversational datasets to better capture complex team dynamics. We will discuss future directions including proposed models that can incorporate additional mission days and tasks beyond the TIB for objectively quantifying team behavior at high temporal resolution in space exploration missions.

Projna Paromita↗

NASA NTRS1993

Ionospheric calibration for single frequency altimeter measurements

This report investigates the potential of using Global Positioning System (GPS) data and a model of the ionosphere to supply a measure of the sub-satellite Total Electron Current (TEC) of the required accuracy (10 TECU rms) for the purpose of calibrating single frequency radar altimeter measurements. Since climatological (monthly mean) models are known to be in error by as much as 50 percent, this work focused on the Parameterized Real-Time Ionospheric Specification Model (PRISM) which has the capability to improve model accuracy by ingesting (adjusting to) in situ ionospheric measurements. A set of globally distributed TEC measurements were generated using GPS data and were used as input to improve the accuracy of the PRISM model. The adjusted PRISM TEC values were compared to TOPEX dual frequency TEC measurements (which are considered truth) for a number of TOPEX sub-satellite tracks. The adjusted PRISM values generally compared to the TOPEX measurements within the 10 TECU accuracy requirements when the sub-satellite track passed within 300 to 400 km of the GPS TEC data or when the track passed through a night time ionosphere. However, when the sub-satellite points were greater than 300 to 400 km away from the GPS TEC data or when a local noon ionosphere was sampled, the adjusted PRISM values generally differed by greater than 10 TECU rms with data excursions from the TOPEX TEC measurements of as much as 40 TECU (an 8 cm path delay error at K band). Therefore, it can be concluded from this analysis that an unrealistically large number of GPS stations would be needed to predict sub-satellite TEC at the 10 TECU level in the day time ionosphere using a model such as PRISM. However, a technique currently being studied at the Jet Propulsion Laboratory (JPL) may provide a means of supplying adequate TEC data to meet the 10 TECU ionospheric correction accuracy when using a realistic number of ionospheric stations. This method involves using global GPS TEC data to estimate a global grid of vertical ionospheric TEC as a function of time (i.e. every one half hour) in a sun-fixed longitude frame. Working in a sun-fixed longitude frame, one is not limited by the spatial decorrelation distance of the ionosphere, but instead is limited more by the temporal correlations of the ionosphere in the sun-fixed frame which are a smaller effect. It is the opinion of the authors that using the global sun-fixed TEC grid data, in particular, ingesting it into PRISM, offers the best possibility of meeting the 10 TECU ionospheric correction accuracy requirement, and should be the subject of further study.

Schreiner, William S.↗

NASA NTRS2014

Investigation of HZETRN 2010 as a Tool for Single Event Effect Qualification of Avionics Systems

NASA's future missions are focused on deep space for human exploration that do not provide a simple emergency return to Earth. In addition, the deep space environment contains a constant background Galactic Cosmic Ray (GCR) radiation exposure, as well as periodic Solar Particle Events (SPEs) that can produce intense amounts of radiation in a short amount of time. Given these conditions, it is important that the avionics systems for deep space human missions are not susceptible to Single Event Effects (SEE) that can occur from radiation interactions with electronic components. The typical process to minimizing SEE effects is through using heritage hardware and extensive testing programs that are very costly. Previous work by Koontz, et al. [1] utilized an analysis-based method for investigating electronic component susceptibility. In their paper, FLUKA, a Monte Carlo transport code, was used to calculate SEE and single event upset (SEU) rates. This code was then validated against in-flight data. In addition, CREME-96, a deterministic code, was also compared with FLUKA and in-flight data. However, FLUKA has a long run-time (on the order of days), and CREME-96 has not been updated in several years. This paper will investigate the use of HZETRN 2010, a deterministic transport code developed at NASA Langley Research Center, as another tool that can be used to analyze SEE and SEU rates. The benefits to using HZETRN over FLUKA and CREME-96 are that it has a very fast run time (on the order of minutes) and has been shown to be of similar accuracy as other deterministic and Monte Carlo codes when considering dose [2, 3, 4]. The 2010 version of HZETRN has updated its treatment of secondary neutrons and thus has improved its accuracy over previous versions. In this paper, the Linear Energy Transfer (LET) spectra are of interest rather than the total ionizing dose. Therefore, the LET spectra output from HZETRN 2010 will be compared with the FLUKA and in-flight data to validate HZETRN 2010 as a computational tool for SEE qualification by analysis. Furthermore, extrapolation of these data to interplanetary environments at 1 AU will be investigated to determine whether HZETRN 2010 can be used successfully and confidently for deep space mission analyses.

Rojdev, Kristina↗

NASA NTRS1999

Principal Investigator-in-a-Box

Human performance in orbit is currently limited by several factors beyond the intrinsic awkwardness of motor control in weightlessness. Cognitive functioning can be affected by such factors as cumulative sleep loss, stress and the psychological effects of long-duration small-group isolation. When an astronaut operates a scientific experiment, the performance decrement associated with such factors can lead to lost or poor quality data and even the total loss of a scientific objective, at great cost to the sponsors and to the dismay of the Principal Investigator. In long-duration flights, as anticipated on the International Space Station and on any planetary exploration, the experimental model is further complicated by long delays between training and experiment, and the large number of experiments each crew member must perform. Although no documented studies have been published on the subject, astronauts report that an unusually large number of simple errors are made in space. Whether a result of the effects of microgravity, accumulated fatigue, stress or other factors, this pattern of increased error supports the need for a computerized decision-making aid for astronauts performing experiments. Artificial intelligence and expert systems might serve as powerful tools for assisting experiments in space. Those conducting space experiments typically need assistance exactly when the planned checklist does not apply. Expert systems, which use bits of human knowledge and human methods to respond appropriately to unusual situations, have a flexibility that is highly desirable in circumstances where an invariably predictable course of action/response does not exist. Frequently the human expert on the ground is unavailable, lacking the latest information, or not consulted by the astronaut conducting the experiment. In response to these issues, we have developed "Principal Investigator-in-a-Box," or [PI], to capture the reasoning process of the real expert, the Principal Investigator, and combine that with real-time data available in space in order to advise the astronaut about how to proceed in real time. [PI] advises the astronaut during the progress of an experiment in much the same way a real Principal Investigator might do while looking over the astronaut's shoulder. In its original application, [PI] mimicked several of the tasks of the Principal Investigator, including data quality monitoring, troubleshooting, prescheduling, protocol management and "interesting data" detection. The proposed research focuses on the efficacy of this technique as applied to the data quality monitoring and troubleshooting aspects of [PI].

Young, Laurence R.↗

NASA NTRS2011

A Data Mining Project to Identify Cardiovascular Related Factors That May Contribute to Changes in Visual Acuity Within the US Astronaut Corps

Many of the cardiovascular-related adaptations that occur in the microgravity environment are due, in part, to a well-characterized cephalad-fluid shift that is evidenced by facial edema and decreased lower limb circumference. It is believed that most of these alterations occur as a compensatory response necessary to maintain a "normal" blood pressure and cardiac output while in space. However, data from both flight and analog research suggest that in some instances these microgravity-induced alterations may contribute to cardiovascular-related pathologies. Most concerning is the potential relation between the vision disturbances experienced by some long duration crewmembers and changes in cerebral blood flow and intra-ocular pressure. The purpose of this project was to identify cardiovascular measures that may potentially distinguish individuals at risk for visual disturbances after long duration space flight. Toward this goal, we constructed a dataset from Medical Operation tilt/stand test evaluations pre- (days L-15-L-5) and immediate post-flight (day R+0) on 20 (3 females, 17 males). We restricted our evaluation to only crewmembers who participated in both shuttle and space station missions. Data analysis was performed using both descriptive and analytical methods (Stata 11.2, College Station, TX) and are presented as means +/- 95% CI. Crewmembers averaged 5207 (3447 - 8934) flight hours across both long (MIR-23 through Expedition16) and short (STS-27 through STS-101) duration missions between 1988 and 2008. The mean age of the crew at the time of their most recent shuttle flight was 41 (34-44) compared to 47 (40-54) years during their time on station. In order to focus our analysis (we did not have codes to separate out subjects by symptomotology) , we performed a visual inspection of each cardiovascular measures captured during testing and plotted them against stand time, pre- to post-flight, and between mission duration. It was found that pulse pressure most clearly differentiated the two mission types. Statistical analysis confirmed that pulse pressure was significantly higher before [45.6; (42.1 to 49.1)] and after [50.7; (46.9 to 54.6)] time on station compared with their most recent shuttle flight [31.6 (27.8 to 35.4), and 32.2 (28.3 to 36.0) respectively] even after correcting differences in age and cumulative number of mission hours. Without knowing the identity of which long duration crewmembers demonstrated visual changes, we were limited to examining whether certain crew regulate components of pulse pressure, systolic and diastolic blood pressure, differently due to microgravity exposure. To that end, we stratified crew into tertiles based on either their pre-flight measure of systolic or diastolic blood pressure. Those crew in the highest tertile for both systolic (lower tertile (n=8; 103-111), middle tertile (n=7; 113-121), and upper tertile (n=5; 125-136) and diastolic blood pressure (lower tertile (n=8; 58-64), middle tertile (n=7; 67-73), and upper tertile (n=5; 75-81) demonstrated less variability in pulse pressure between R+0 and L-10 (Figure 2). Interestingly, those crewmembers with the highest resting systolic blood pressure demonstrated either no change or in some instances an increase in total peripheral resistance, where those in the lower tertiles had lower values of total peripheral resistance compared to pre-flight levels. In this study, it was found that crewmembers in the highest tertile for both systolic and diastolic blood pressure demonstrated less variability in pulse pressure and that the decrease in variability was due in part to lower levels of compliance as indicated by similar or higher levels of total peripheral resistance after compared with before flight levels. Whether there is a relation between blood pressure regulation and total peripheral resistance in crew presenting with negative changes in visual acuity remains unknown.

Westby, Christian M.↗

NASA NTRS2010

The OMPS Limb Profiler Instrument: Two-Dimensional Retrieval Algorithm

The upcoming Ozone Mapper and Profiler Suite (OMPS), which will be launched on the NPOESS Preparatory Project (NPP) platform in early 2011, will continue monitoring the global distribution of the Earth's middle atmosphere ozone and aerosol. OMPS is composed of three instruments, namely the Total Column Mapper (heritage: TOMS, OMI), the Nadir Profiler (heritage: SBUV) and the Limb Profiler (heritage: SOLSE/LORE, OSIRIS, SCIAMACHY, SAGE III). The ultimate goal of the mission is to better understand and quantify the rate of stratospheric ozone recovery. The focus of the paper will be on the Limb Profiler (LP) instrument. The LP instrument will measure the Earth's limb radiance (which is due to the scattering of solar photons by air molecules, aerosol and Earth surface) in the ultra-violet (UV), visible and near infrared, from 285 to 1000 nm. The LP simultaneously images the whole vertical extent of the Earth's limb through three vertical slits, each covering a vertical tangent height range of 100 km and each horizontally spaced by 250 km in the cross-track direction. Measurements are made every 19 seconds along the orbit track, which corresponds to a distance of about 150km. Several data analysis tools are presently being constructed and tested to retrieve ozone and aerosol vertical distribution from limb radiance measurements. The primary NASA algorithm is based on earlier algorithms developed for the SOLSE/LORE and SAGE III limb scatter missions. All the existing retrieval algorithms rely on a spherical symmetry assumption for the atmosphere structure. While this assumption is reasonable in most of the stratosphere, it is no longer valid in regions of prime scientific interest, such as polar vortex and UTLS regions. The paper will describe a two-dimensional retrieval algorithm whereby the ozone distribution is simultaneously retrieved vertically and horizontally for a whole orbit. The retrieval code relies on (1) a forward 2D Radiative Transfer code (to model limb radiances within a non-uniform atmosphere and evaluate 2D analytical partial derivatives) and (2) an optimal estimator inversion routine. The algorithm uses the typically sparse nature of the kernel matrices as well as fast matrix inversion techniques to allow for fast inversion of limb data with efficient memory management (as was done for MIPAS data processing). While the method has so far only been developed in the context of Single Scatter, the paper will show how the CPU intensive Multiple Scatter modeling can be implemented using parallel CPU processing. Initial results will be presented in terms of retrieved ozone profiles and code performance.

Rault, Didier F.↗

NASA NTRSDate not supplied

On-Orbit Performance of the NOAA-21 Advanced Technology Microwave Sounder (ATMS)

The Advanced Technology Microwave Sounder (ATMS) instrument provides sounding measurements of Earth’s atmosphere to collect temperature and water vapor data for NOAA’s Joint Polar Satellite System (JPSS) program. ATMS is a total-power passive microwave radiometer with 22 channels spanning a frequency range from 22 to 183 GHz. A general description of the ATMS instrument is detailed in [1]. Three ATMS units are currently on-orbit. The Suomi National Polar-orbiting Partnership (SNPP) unit was launched in 2011 and the NOAA-20 (previously JPSS-1) unit was launch in 2017. Both SNPP and NOAA-20 ATMS units are currently operational and the data is used for numerical weather prediction (NWP) models. The NOAA-21 (formerly JPSS-2) ATMS unit was launched on November 10, 2022 from Vandenberg Space Force Base in California [2]. The ATMS instrument began generating radiance data on November 21, 2022. At the time of this abstract NOAA-21 ATMS is currently completing on-orbit commissioning and checkout activities; it is expected that the commissioning activities will be complete by the IGARSS 2023 conference. This paper will focus on the on-orbit performance of the NOAA-21 ATMS instrument based on measurements and activities from the commissioning period. Comparisons will be made to specifications and to expected performance based on pre-launch test activities. Pre-launch JPSS-2 (NOAA-21) ATMS performance is detailed in [4]. Additionally, the NOAA-21 performance will be compared to the on-orbit performance of the SNPP and NOAA-21 ATMS units. The post-launch performance of SNPP ATMS is detailed in [1][5][6][7]. The post-launch performance of NOAA-20 ATMS is detailed in [5][7][8]. On-orbit performance is evaluated through data collects from nominal mission operations as well as specific post-launch tests and spacecraft maneuvers. Nominal mission operations can be used to evaluate parameters such as instrument thermal stability, Noise Equivalent Delta Temperature (NEDT)/radiometric sensitivity, geolocation, inter-channel noise correlation, striping, and radiometric bias and stability. Shortly after instrument activation, the instrument thermal stability as measured from onboard temperature sensors is evaluated to demonstrate stable and steady-state behavior. Methods for computing NEDT are described in [9][10][11]. Passive geolocation measurements are performed using the coastline inflection point (CIP) method, described in [8][12]. The striping index, used as a metric to quantify striping, is the ratio of along-track variance to cross-track variance of the observed brightness temperature [4][8][14]. Inter-channel noise correlation has been previously reported for SNPP and NOAA-20 [1][8]. Dedicated post-launch tests and spacecraft maneuvers are utilized during the commissioning phase for further evaluation of on-orbit instrument performance. These activities provide information on the optimal space view selection, noise power spectral density (PSD), gain stability, scan bias, interference from onboard transmitters, reflector emissivity, active geolocation, and radiometric bias and stability detection methods. The optimal space view selection is used to determine which of ATMS space view sectors is preferred for minimizing contamination of the space view [1]. Point and stare testing is used to generate noise PSD and gain stability information, as described in [1][8]. Spacecraft roll and pitch maneuvers allow the ATMS to view different zones, including deep space, and the data can be used to provide information on scan biases and antenna sidelobe contamination [1][8]. The pitch maneuver can also be used to assess interference from onboard Ka-band transmitters and reflector emissivity [8]. Active geolocation is evaluated as a method for geolocation, described in [15].

Edward Kim↗

NASA NTRS2004

Physics of Galaxy Clusters and How it Affects Cosmological Tests

The main activities in 2004 were focused on completion of the new 400 square degrees ROSAT PSPC survey for distant galaxy clusters. We observed and reduced optical spectra for all X-ray candidates and now we have complete identification for a statistically complete sample of distant 283 clusters. The papers describing the cluster catalog and first science results are in preparation and will be submitted in early 2005. We also completed a project to measure temperature and density profiles at large radii using Chandra observations of a 11 well exposed low-redshift clusters. We were able to demonstrate that the density, temperature, and total mass profiles are self-similar at large radii. This analysis has led to significant improvements in determination of the cluster baryon fraction as well as cosmologically important scaling relations, such as Mtot-T. The paper describing these results is submitted to ApJ in November, 2004. We continued to study evolution of the cluster scaling relations at high redshifts using Chandra and XMM data. We developed code for image and spectral deconvolution of the XMM observations. This code was used to reconstruct the distribution of baryons and total mass from observations of distant clusters which suffer from the finite size of the XMM PSF. This study allowed us to derive a high-redshift relation between cluster temperature and mass and compare it with the local relation obtained. The paper describing the first results is submitted to the ApJ. However, the project is still on-going as more distant cluster observations enter XMh4 and Chandra public data archives. We continued our work on improving techniques for accurate measurements of the cluster mass function and obtaining cosmological constraints from such observations. We published (ApJ, 601, 610) a study in which we derived the baryon mass function for a complete sample of low-redshift clusters. These papers argued that it was an excellent proxy for the total mass function. The baryon mass function can be used to constrain the amplitude and slope of the density fluctuation power spectrum on cluster scales. This method does not use observational determinations of the total mass and thus bypasses major uncertainties in the traditional analyses based on the X-ray temperature function. We derived the measurements for the amplitude of density perturbations, sigma8 = 0.72 +/- 0.04 and the shape parameter Omega*h = 0.l3 +/- 0.07, in good agreement with a number of independent methods.

Oliversen, Ronald J.↗

NASA NTRS1998

A Synthesis of Fluid Dynamics and Quantum Chemistry for the Design of Nanoelectronics

In 1959, during a famous lecture entitled "There's Plenty of Room at the Bottom", Richard Feynman focused on the startling technical possibilities that would exist at the limit of miniaturization, that being atomically precise devices with dimensions in the nanometer range. A nanometer is both a convenient unit of length for medium to large sized molecules, and the root of the name of the new interdisciplinary field of "nanotechnology". Essentially, "nanoelectronics" denotes the goal of shrinking electronic devices, such as diodes and transistors, as well as integrated circuits of such devices that can perform logical operations, down to dimensions in the range of 100 nanometers. The thirty-year hiatus in the development of nanotechnology can figuratively be seen as a period of waiting for the bottom-up and atomically precise construction skills of synthetic chemistry to meet the top-down reductionist aspirations of device physics. The sub-nanometer domain of nineteenth-century classical chemistry has steadily grown, and state-of-the-art supramolecular chemistry can achieve atomic precision in non-repeating molecular assemblies of the size desired for nanotechnology. For nanoelectronics in particular, a basic understanding of the electron transport properties of molecules must also be developed. Quantum chemistry provides powerful computational methods that can accurately predict the properties of small to medium sized molecules on a desktop workstation, and those of large molecules if one has access to a supercomputer. Of the many properties of a molecule that quantum chemistry routinely predicts, the ability to carry a current is one that had not even been considered until recently. "Currently", there is a controversy over just how to define this key property. Reminiscent of the situation in high-Tc superconductivity, much of the difficulty arises from the different models that are used to simplify the complex electronic structure of real materials. A model-independent approach has been proposed, that sacrifices the plentiful molecular orbitals and Bloch functions of conventional approaches, for a single three-dimensional observable quantity, the electron momentum density Pi(sub rho). This quantity is simply the probability of any electron having momentum rho, multiplied by the total number of electrons in the system (the position of the electron is uncertain). We have explored the utility of this new approach in providing a fundamental understanding of the electron transport properties of molecules that have provi been nominated as candidates for components in the design of nanoelectronics; phenylene-ethynylene oligomers. Some of the molecular systems that have been studied are sketched below.

MacDougall, Preston J.↗

NASA NTRS1999

Carbon Fiber Reinforced/Silicon Carbide Turbine Blisk Testing in the SIMPLEX Turbopump

A program designed to implement a ceramic matrix composite integrally bladed disk (blisk) into rocket engine style turbomachinery has successfully completed testing. The Marshall Space Flight Center (MSFC) program, utilizing the MSFC turbomachinery design, analysis, and testing capabilities along with materials development capabilities from both Glenn Research Center (GRC) and MSFC, has tested two carbon fiber reinforced silicon carbide blisks in the Simplex Turbopump at MSFC's Test Stand 500. One blisk contained a polar woven fiber preform, while the second blisk tested utilized a quasi-isotropic preform. Vhile earlier papers have chronicled the program's design, material testing, and torque testing efforts, this paper focuses on the testing of the blisks in the Simplex turbopump. Emphasis will be placed on the actual condition of the blisks before and after the testing test program design methodology, and conclusions that can be drawn from the test data and blisk final conditions. The program performed three separate test series. The first series was needed to validate that the Simplex turbopump was correctly re-built following a major incident to the turbopump. The turbopump had two major differences from the original design. The most obvious difference was the sleeve required throughout the bore of the main housing. The second major difference was modifications to the pump diffuser to improve performance. Several areas were burnt during the incident and were either repaired by weld repair (pump inlet housing) or simply smoothed out (turbine nozzle discharge). The test series was designed to weed out any turbopump design and manufacturing flaws or fatigue issues prior to putting the C/SiC blisks into it. The second and third series were the C/SiC blisk test series. The primary goal of these series was to expose the blisks to as much fatigue causing dynamic stress as possible to examine the material's capability. Initially, the test plan was to put equal time on the two blisks, however, as the test series progressed, the funding allowed additional testing to occur. The additional test time was placed on the polar weave blisk. The total test time accrued on the polar blisk was 2550 seconds with 860 seconds near the turbopump design speed of 25,000 rpm. This testing included 6 tests / 775 seconds pumping liquid nitrogen and 7 tests / 1775 seconds pumping liquid oxygen. The drive gas for all of the tests was gaseous nitrogen due to the lack of hot gas source for the Simplex turbopump. The quasi-isotropic blisk was tested for XX total tests and XXXX seconds with X tests/XXXX seconds pumping liquid nitrogen and X tests/XXXX seconds pumping liquid \oxygen.During the test series, the blisks were inspected following each test. Inspections initially were viewed from the downstream side of the blisks only. Midway through the testing, a method of borescoping the leading edges of the blades was devised, and subsequently, both sides of the blades were inspected following each test. The leading and trailing edges of the polar blisk held up better than the quasi-isotropic blisk. This was a known possibility due to the varying fiber direction in the blades as the rectangular preform weave is cut in a circular pattern. The surprising fact about the testing was that there was no measurable performance loss due to the inaccuracies in the blade manufacturing in the C/SiC blisks, the surface roughness C/SiC of the blades, or the loss of the material in the polar blisk. A performance shift was seen in the quasi-isotropic blisk as portions of the leading and trailing edges were lost. After the testing was completed, detailed inspections of the blisks were performed. The largest surprise was the polar blisk had a obvious crack in a single blade that was located nearly midspan which was not detected in test. The crack ran completely through the blade circumferenciary and through the radial length of the blade. However, the crack does not appear to extend into the blisk hub. Although the cause of the crack is still under investigation, the material appears to be tolerant of this crack, and other hairline cracks discovered under higher magnification. This bodies well for eventual use of this material in actual flight turbopumps where monolithic fracture toughness issues limit its use.

Genge, Gary G.↗

NASA NTRS1994

Implementing Software Safety in the NASA Environment

Until recently, NASA did not consider allowing computers total control of flight systems. Human operators, via hardware, have constituted the ultimate safety control. In an attempt to reduce costs, NASA has come to rely more and more heavily on computers and software to control space missions. (For example. software is now planned to control most of the operational functions of the International Space Station.) Thus the need for systematic software safety programs has become crucial for mission success. Concurrent engineering principles dictate that safety should be designed into software up front, not tested into the software after the fact. 'Cost of Quality' studies have statistics and metrics to prove the value of building quality and safety into the development cycle. Unfortunately, most software engineers are not familiar with designing for safety, and most safety engineers are not software experts. Software written to specifications which have not been safety analyzed is a major source of computer related accidents. Safer software is achieved step by step throughout the system and software life cycle. It is a process that includes requirements definition, hazard analyses, formal software inspections, safety analyses, testing, and maintenance. The greatest emphasis is placed on clearly and completely defining system and software requirements, including safety and reliability requirements. Unfortunately, development and review of requirements are the weakest link in the process. While some of the more academic methods, e.g. mathematical models, may help bring about safer software, this paper proposes the use of currently approved software methodologies, and sound software and assurance practices to show how, to a large degree, safety can be designed into software from the start. NASA's approach today is to first conduct a preliminary system hazard analysis (PHA) during the concept and planning phase of a project. This determines the overall hazard potential of the system to be built. Shortly thereafter, as the system requirements are being defined, the second iteration of hazard analyses takes place, the systems hazard analysis (SHA). During the systems requirements phase, decisions are made as to what functions of the system will be the responsibility of software. This is the most critical time to affect the safety of the software. From this point, software safety analyses as well as software engineering practices are the main focus for assuring safe software. While many of the steps proposed in this paper seem like just sound engineering practices, they are the best technical and most cost effective means to assure safe software within a safe system.

Wetherholt, Martha S.↗