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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↗

Ambiguity resolution for satellite Doppler positioning systems

The implementation of satellite-based Doppler positioning systems frequently requires the recovery of transmitter position from a single pass of Doppler data. The least-squares approach to the problem yields conjugate solutions on either side of the satellite subtrack. It is important to develop a procedure for choosing the proper solution which is correct in a high percentage of cases. A test for ambiguity resolution which is the most powerful in the sense that it maximizes the probability of a correct decision is derived. When systematic error sources are properly included in the least-squares reduction process to yield an optimal solution the test reduces to choosing the solution which provides the smaller valuation of the least-squares loss function. When systematic error sources are ignored in the least-squares reduction, the most powerful test is a quadratic form comparison with the weighting matrix of the quadratic form obtained by computing the pseudoinverse of a reduced-rank square matrix. A formula for computing the power of the most powerful test is provided. Numerical examples are included in which the power of the test is computed for situations that are relevant to the design of a satellite-aided search and rescue system.

Argentiero, P.↗

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↗

Evaluating Algorithm Performance Metrics Tailored for Prognostics

Prognostics has taken a center stage in Condition Based Maintenance (CBM) where it is desired to estimate Remaining Useful Life (RUL) of the system so that remedial measures may be taken in advance to avoid catastrophic events or unwanted downtimes. Validation of such predictions is an important but difficult proposition and a lack of appropriate evaluation methods renders prognostics meaningless. Evaluation methods currently used in the research community are not standardized and in many cases do not sufficiently assess key performance aspects expected out of a prognostics algorithm. In this paper we introduce several new evaluation metrics tailored for prognostics and show that they can effectively evaluate various algorithms as compared to other conventional metrics. Specifically four algorithms namely; Relevance Vector Machine (RVM), Gaussian Process Regression (GPR), Artificial Neural Network (ANN), and Polynomial Regression (PR) are compared. These algorithms vary in complexity and their ability to manage uncertainty around predicted estimates. Results show that the new metrics rank these algorithms in different manner and depending on the requirements and constraints suitable metrics may be chosen. Beyond these results, these metrics offer ideas about how metrics suitable to prognostics may be designed so that the evaluation procedure can be standardized. 1

Saxena, Abhinav↗

Cleanroom Microbes Survive Drying, Vacuum, and Proton Irradiation

Introduction : The goal of planetary protection at NASA is to mitigate the risk of contaminating sensitive target bodies with biological life. While many cleaning procedures have been put in place to reduce bioburden on spacecraft, microbes are experts at evolving to survive harsh conditions. Specifically, the dry, low-nutrient environment of a cleanroom (commonly used for assembly of spacecraft) can represent an environment where extremophiles can survive. Methods : Scientists at NASA MSFC wished to gather a snapshot of the microbial population within a variety of cleanrooms on site. A study was undertaken to collect air, surface, and floor samples from clean-rooms and isolate unique morphologies. From this study, 95 isolates were collected and saved in a microbial library. About 86% of these were identified at least to a genus level. Following identification, 24 microbes were selected, based on a literature review, as potential extremophiles. These were grown in liquid cultures, diluted to a set optical density, washed with water, and then applied to a sterilized Kapton coupon. Droplets were allowed to dry overnight in a biosafety cabinet. Coupons were then installed in a pelletron and pumped down to high vacuum (~1E-6 Torr). Samples were then subjected 100 keV protons at a fluence of 2x10 15 p+/cm 2 up to 4x10 15 p+/cm 2 . Following exposure, samples were returned to the microbiology lab where they were pro-cessed by submerging in water, vortexing, and then plating either droplets or spread plates. Recovery data collected was qualitative with a ranking or +, minor, or – for growth. Some selected radiotolerant strains were sequenced using the Illumina sequencing platform. The resulting genomes were annotated with the Rapid Annotations using Subsystems Technology (RAST) server and analyzed for conserved and unique stress response relevant genomic signatures to identify clues related to specific tolerances. Results and Discussion : After five rounds of proton radiation, we narrowed our isolates to five, non-spore forming bacteria that demonstrated survival: Arthrobacter koreensis, Paenarthrobacter nitroguajacolicus, Mycetocola manganoxydans , and an Erwinia sp. Furthermore, we exposed these four microbes to 254 nm wavelength light at an intensity of 80 W/m 2 at a distance of ~18 cm for 10 minutes. Only A. koreensis demonstrated survival following UV exposure. Finally, we performed whole genome sequencing on the four strains to look for genetic markers of stress resistance. When we compared the genomes of the four strains, we found that genes coding for GGDEF and EAL domains with PAS/PAC sensors were only found in A. koreensis . These domains, modulated by PAS/PAC sensors, are hypothesized to facilitate survival under drying, desiccation, and proton irradiation. Drying and Desiccation : PAS domains sense hydration changes and modulate GGDEF and EAL domain activity to adjust c-di-GMP levels, enhancing resistance to desiccation. For instance, in Pseudomonas aeruginosa , the PAS domain of RbdA modulates activity under varying hydration conditions, affecting stress responses [1]. Proton Irradiation : Proton irradiation causes oxidative stress, leading to ROS generation. PAS domains detect this stress and modulate GGDEF and EAL domains to manage oxidative stress responses. In Shewanella , EAL domain proteins modulated by PAS sensors help bacteria adapt to extreme conditions [2]. These genes upregulate other stress response genes, protecting membrane function, protein stability, DNA repair, and antioxidant defenses. The modulation of c-di-GMP by PAS domains is crucial for bacterial adaptation to stress conditions, enabling dynamic physio-logical adjustments [3]. Understanding these mechanisms provides insights into bacterial stress responses and strategies for controlling bacterial growth [4]. Conclusions : These findings indicate that clean-rooms harbor extremophile microbes that may be able to survive conditions in deep space. Furthermore, while we identified certain stress-response genes that may be at least partly responsible for the phenotypes observed in this study, there are likely unidentified genes or characteristics about A. koreensis , and other bacteria, that may allow them to survive in harsh environments. Future studies will focus on identifying these unknown genes and characteristics, further elucidating the mechanisms of extremophile survival and potentially informing the development of new biotechnologies for space exploration and other extreme environments.

Chelsi Cassilly↗

Transcriptomics-based Machine Learning (ML) Analysis Predicts Space-Exposed Murine Livers

Limited sample sizes, high data dimensionality, and sensitivity to technical and biological variability of next generation sequencing (NGS), typically limits machine learning (ML) approaches in spaceflight studies that include radiation effects. However, pooling smaller studies while addressing intra- and inter-study variabilities allows for ML predictive modeling. Here, integration methods were applied to whole transcriptome shotgun sequencing (RNA-seq) data from six mouse liver GeneLab datasets (GLDS) (n ranging from 6 to 39 samples) from with a total of 81 spaceflight and ground-control samples to determine top features (i.e. genes) relevant to spaceflight including the effect of radiation exposure. RNASeq counts were normalized for each study, then merged and scaled across all datasets. Data dimensionality was reduced using a minimum redundancy maximum relevance (MRMR) methodology. Redundancy and relevance were computed using the Pearson correlation and F-statistic, respectively. The top 100 MRMR features were used to predict spaceflight vs. ground-control samples using Random Forest (RF), Support Vector Machine (SVM), and Linear Discriminant Analysis (LDA) classifiers with 5-fold cross validation (CV). Principal component analysis (PCA) on the complete feature set versus the MRMR features shows separation between spaceflight samples and ground controls (Figure 1A). The ML-based gene sets were compared against differential gene expression results obtained with DESeq2 from individual GLDS. Using all features or randomly sampled subsets at matching set sizes with MRMR, a maximum classifier accuracy of 69% on the test set over 5 folds. For all classifiers, CV training using at least the top 30 MRMR genes show minimum 89% accuracy and 0.95 AUC value on the test set over 5 folds (Figure 1B). Baseline set analysis on differentially expressed genes (DEGs) identified using padj ≤ 0.05 show 295 DEGs that overlap at least two studies and 13 DEGs that overlap three studies (Figure 1C). Set analysis between the top 100 MRMR features and the DEGs showed 47 genes that overlap at least one study and 24 genes that overlap two studies. Over-representation analysis showed overlapping biological processes related to fatty acid and lipid metabolism which may indicate these processes in the response to spaceflight stressors. MRMR feature selection for the selected ML methods improve performance relative to a classifier built on all features or randomly sampled subsets. Permutation feature importance within the decorrelated MRMR features showed concordance in feature ranking between ML methods. A challenge of applying ML methods across heterogeneous NGS data is accounting for signal:noise. Here, signal validation across studies was shown by intersecting sets between top MRMR genes and DEGs from DESeq2 analysis. Non-intersecting sets introduce opportunity to explore genes relevant to differentiating space flight exposed groups and implementing ML methods across existing NGS datasets may overcome sample size limitations.

Machine Learning↗

Transcriptomics-based Machine Learning Analysis Predicts Space-Exposed Murine Livers

Limited sample sizes, high data dimensionality, and sensitivity to technical and biological variability of next generation sequencing (NGS), typically limits machine learning (ML) approaches in spaceflight studies that include radiation effects. However, pooling smaller studies while addressing intra- and inter-study variabilities allows for ML predictive modeling. Here, integration methods were applied to whole transcriptome shotgun sequencing (RNA-seq) data from six mouse liver GeneLab datasets (GLDS) (n ranging from 6 to 39 samples) from with a total of 81 spaceflight and ground-control samples to determine top features (i.e. genes) relevant to spaceflight including the effect of radiation exposure. RNASeq counts were normalized for each study, then merged and scaled across all datasets. Data dimensionality was reduced using a minimum redundancy maximum relevance (MRMR) methodology. Redundancy and relevance were computed using the Pearson correlation and F-statistic, respectively. The top 100 MRMR features were used to predict spaceflight vs. ground-control samples using Random Forest (RF), Support Vector Machine (SVM), and Linear Discriminant Analysis (LDA) classifiers with 5-fold cross validation (CV). Principal component analysis (PCA) on the complete feature set versus the MRMR features shows separation between spaceflight samples and ground controls (Figure 1A). The ML-based gene sets were compared against differential gene expression results obtained with DESeq2 from individual GLDS. Using all features or randomly sampled subsets at matching set sizes with MRMR, a maximum classifier accuracy of 69% was shown on the test set over 5 folds. For all classifiers, CV training using at least the top 30 MRMR genes show minimum 89% accuracy and 0.95 AUC value on the test set over 5 folds (Figure 1B). Baseline set analysis on differentially expressed genes (DEGs) identified using padj ≤ 0.05 show 295 DEGs that overlap at least two studies and 13 DEGs that overlap three studies (Figure 1C). Set analysis between the top 100 MRMR features and the DEGs showed 47 genes that overlap at least one study and 24 genes that overlap two studies. Over-representation analysis showed overlapping biological processes related to fatty acid and lipid metabolism which may indicate these processes in the response to spaceflight stressors. MRMR feature selection for the selected ML methods improve performance relative to a classifier built on all features or randomly sampled subsets. Permutation feature importance within the decorrelated MRMR features showed concordance in feature ranking between ML methods. A challenge of applying ML methods across heterogeneous NGS data is accounting for signal:noise. Here, signal validation across studies was shown by intersecting sets between top MRMR genes and DEGs from DESeq2 analysis. Non-intersecting sets introduce opportunity to explore genes relevant to differentiating space flight exposed groups and implementing ML methods across existing NGS datasets may overcome sample size limitations.

Machine Learning↗

Transcriptomics-based Machine Learning Analysis Predicts Space-Exposed Murine Livers

Limited sample sizes, high data dimensionality, and sensitivity to technical and biological variability of next generation sequencing (NGS), typically limits machine learning (ML) approaches in spaceflight studies that include radiation effects. However, pooling smaller studies while addressing intra- and inter-study variabilities allows for ML predictive modeling. Here, integration methods were applied to whole transcriptome shotgun sequencing (RNA-seq) data from six mouse liver GeneLab datasets (GLDS) (n ranging from 6 to 39 samples) from with a total of 81 spaceflight and ground-control samples to determine top features (i.e. genes) relevant to spaceflight including the effect of radiation exposure. RNASeq counts were normalized for each study, then merged and scaled across all datasets. Data dimensionality was reduced using a minimum redundancy maximum relevance (MRMR) methodology. Redundancy and relevance were computed using the Pearson correlation and F-statistic, respectively. The top 100 MRMR features were used to predict spaceflight vs. ground-control samples using Random Forest (RF), Support Vector Machine (SVM), and Linear Discriminant Analysis (LDA) classifiers with 5-fold cross validation (CV). Principal component analysis (PCA) on the complete feature set versus the MRMR features shows separation between spaceflight samples and ground controls (Figure 1A). The ML-based gene sets were compared against differential gene expression results obtained with DESeq2 from individual GLDS. Using all features or randomly sampled subsets at matching set sizes with MRMR, a maximum classifier accuracy of 69% was shown on the test set over 5 folds. For all classifiers, CV training using at least the top 30 MRMR genes show minimum 89% accuracy and 0.95 AUC value on the test set over 5 folds (Figure 1B). Baseline set analysis on differentially expressed genes (DEGs) identified using padj ≤ 0.05 show 295 DEGs that overlap at least two studies and 13 DEGs that overlap three studies (Figure 1C). Set analysis between the top 100 MRMR features and the DEGs showed 47 genes that overlap at least one study and 24 genes that overlap two studies. Over-representation analysis showed overlapping biological processes related to fatty acid and lipid metabolism which may indicate these processes in the response to spaceflight stressors. MRMR feature selection for the selected ML methods improve performance relative to a classifier built on all features or randomly sampled subsets. Permutation feature importance within the decorrelated MRMR features showed concordance in feature ranking between ML methods. A challenge of applying ML methods across heterogeneous NGS data is accounting for signal:noise. Here, signal validation across studies was shown by intersecting sets between top MRMR genes and DEGs from DESeq2 analysis. Non-intersecting sets introduce opportunity to explore genes relevant to differentiating space flight exposed groups and implementing ML methods across existing NGS datasets may overcome sample size limitations.

Machine Learning↗

Development of Machine Learning-Derived Microbiological and Immune Signatures: Applications in Adaptive Risk Assessment of Infectious Disease During Spaceflight

Infectious diseases represent an urgent risk for spaceflight with consequences ranging from loss in crew performance to crew incapacitation or loss of life should an outbreak occur. The resident environmental microbiome on the International Space Station has been monitored through routine surveillance over almost twenty years, beginning with culture-based microbial detection which has advanced to molecular methods in recent years. This has created a wealth of data that we have begun mining to define the microbial ecology of the ISS. Summarized here is our analysis of data from the historical microbial population defined by culture-based monitoring from the past two decades, organized by their likelihood to cause disease into clinical categories. As expected, many residents of the normal microflora in environments where people work and live were detected. However, some known pathogens were also detected. As the spaceflight environment can predispose humans to infection, crew health records were used to source additional data for the set to uncover clinical relevance. Data mining was performed on crew health records to capture adverse health events that may be related to infectious disease. Machine learning, specifically Random Forest analysis, was used to analyze the microbial and crew health datasets. The symptom categories were not explained by the ranked bacteria, due to lack of sufficient data for some categories and due to poor ranking of the pathogens for others. Poor ranking of the bacteria could be due to the clinical symptoms being linked to other disease-causing factors, such as allergy or viral infection. These findings suggest a lack of relationship between bacteria detected on surfaces in the ISS and historical health events experienced by astronauts.

Kristyn Hoffman↗

On Noise Assessment for Blended Wing Body Aircraft

A system noise study is presented for the blended-wing-body (BWB) aircraft configured with advanced technologies that are projected to be available in the 2025 timeframe of the NASA N+2 definition. This system noise assessment shows that the noise levels of the baseline configuration, measured by the cumulative Effective Perceived Noise Level (EPNL), have a large margin of 34 dB to the aircraft noise regulation of Stage 4. This confirms the acoustic benefits of the BWB shielding of engine noise, as well as other projected noise reduction technologies, but the noise margins are less than previously published assessments and are short of meeting the NASA N+2 noise goal. In establishing the relevance of the acoustic assessment framework, the design of the BWB configuration, the technical approach of the noise analysis, the databases and prediction tools used in the assessment are first described and discussed. The predicted noise levels and the component decomposition are then analyzed to identify the ranking order of importance of various noise components, revealing the prominence of airframe noise, which holds up the levels at all three noise certification locations and renders engine noise reduction technologies less effective. When projected airframe component noise reduction is added to the HWB configuration, it is shown that the cumulative noise margin to Stage 4 can reach 41.6 dB, nearly at the NASA goal. These results are compared with a previous NASA assessment with a different study framework. The approaches that yield projections of such low noise levels are discussed including aggressive assumptions on future technologies, assumptions on flight profile management, engine installation, and component noise reduction technologies. It is shown that reliable predictions of component noise also play an important role in the system noise assessment. The comparisons and discussions illustrate the importance of practical feasibilities and constraints in aircraft system noise studies, which include aerodynamic performance, propulsion efficiency, flight profile limitation and many other factors. For a future aircraft concept to achieve the NASA N+2 noise goal it will require a range of fully successful noise reduction technology developments.

Guo, Yueping↗

Combustion of a polymer (PMMA) sphere in microgravity

Polymer combustion is a highly complicated process where chemical reactions may occur not only in the gas phase, but also in the condensed phase as well as at the solid-gas interphase. The chemistry depends strongly on the coupling between the condensed phase and gas phase phenomena. For some polymers, additional complications arise due to the formation of char layers. For others, the behavior of the condensed phase involves swelling, bubbling, melting, sputtering, and multi-stage combustion. Some of these features bear resemblance to the phenomena observed in coal particle combustion. In addition to its relevance to spacecraft fire safety, the combustion of polymeric materials is related to many applications including solid and hybrid rocket propulsion, and of recent interest, waste incineration . The burning rate is one of the most important parameters used to characterize the combustion of polymers. It has been used to rank the polymer flammability under the same experimental conditions and to evaluate various modes of inhibiting polymer flammability. The main objective of this work is to measure the burning rates of a polymeric material in low gravity. Because of inherent logistical difficulties involved in microgravity experiments, it is impossible to examine a wide spectrum of polymeric materials. It is desirable to investigate a polymer whose combustion is less complicated, and yet will lead to a better understanding of the burning characteristics of other more complicated materials. Therefore, a typical non-charring polymer is selected for use in this experimental study. PMMA (polymethylmethacrylate) has been chosen because its thermo-physical properties are well characterized. Although the combustion of PMMA has been extensively studied in 1G experiments, only a limited amount of work has been conducted in low gravity. A spherical sample geometry is chosen in this study because it is the simplest configuration in terms of the microgravity hardware design requirements. Furthermore, a burning PMMA sphere in microgravity represents a one-dimensional flame with overall combustion characteristics expected to be analogous to the combustion of a liquid fuel droplet, a field with many well-developed theories and models. However, differences can also be expected such as the flame-front standoff ratios and the condensed phase processes occurring during combustion.

Yang, Jiann C.↗

Continuing Development of a Collaborative Plan to Further Engage South Dakota in NASA's Earth Science Enterprise

An ongoing set of research planning activities have occurred in South Dakota as a consequence of the past two years of NASA-EPSCoR Preparation Grants. During this time a group of approximately 60 scientists, engineers, and university administrators in South Dakota have been directly involved as "theme team" members in a series of five all-day meetings to identify the research and technological priorities that are consistent both with NASA-ESE's interests and the State's expertise. Institutions represented within the group's membership include: South Dakota School of Mines & Technology, South Dakota State University, Augustana College, University of South Dakota, USGS EROS Data Center, Si ranks College, Santa Gleska University, Sisseton Wahpeton Community College, USGS Water Resources Division, US National Weather Service, and the SD Department of Environment & Natural Resources. Many of these organizations are also members and affiliates of the SD Space Grant Consortium. The evolving plan has been guided by the following desirable actions: 1. To establish new contacts and strengthen existing linkages with NASA Centers, relevant NASA researchers, and key personnel at the USGS EROS Data Center. 2. To promote participation from the State's major research institutions, State agencies, and relevant businesses in South Dakota that are interested in strengthening our scientific and technological enterprises. 3. To develop the State's scientific talent and infrastructure for enhanced competitiveness in research, development, and technology-based economic development. 4. To encourage greater participation by under represented groups, especially Native Americans, in scientific education and research. 5. To build greater public and political support in South Dakota for the overall science, engineering, and technology enterprise. 6. To communicate the benefits of current and future NASA programs to the progress and development of South Dakota, the Northern Great Plains Region, and the Nation.

Farwell, Sherry O.↗

The Ocean Colour Climate Change Initiative: III. A Round-Robin Comparison on In-Water Bio-Optical Algorithms

Satellite-derived remote-sensing reflectance (Rrs) can be used for mapping biogeochemically relevant variables, such as the chlorophyll concentration and the Inherent Optical Properties (IOPs) of the water, at global scale for use in climate-change studies. Prior to generating such products, suitable algorithms have to be selected that are appropriate for the purpose. Algorithm selection needs to account for both qualitative and quantitative requirements. In this paper we develop an objective methodology designed to rank the quantitative performance of a suite of bio-optical models. The objective classification is applied using the NASA bio-Optical Marine Algorithm Dataset (NOMAD). Using in situ Rrs as input to the models, the performance of eleven semianalytical models, as well as five empirical chlorophyll algorithms and an empirical diffuse attenuation coefficient algorithm, is ranked for spectrally-resolved IOPs, chlorophyll concentration and the diffuse attenuation coefficient at 489 nm. The sensitivity of the objective classification and the uncertainty in the ranking are tested using a Monte-Carlo approach (bootstrapping). Results indicate that the performance of the semi-analytical models varies depending on the product and wavelength of interest. For chlorophyll retrieval, empirical algorithms perform better than semi-analytical models, in general. The performance of these empirical models reflects either their immunity to scale errors or instrument noise in Rrs data, or simply that the data used for model parameterisation were not independent of NOMAD. Nonetheless, uncertainty in the classification suggests that the performance of some semi-analytical algorithms at retrieving chlorophyll is comparable with the empirical algorithms. For phytoplankton absorption at 443 nm, some semi-analytical models also perform with similar accuracy to an empirical model. We discuss the potential biases, limitations and uncertainty in the approach, as well as additional qualitative considerations for algorithm selection for climate-change studies. Our classification has the potential to be routinely implemented, such that the performance of emerging algorithms can be compared with existing algorithms as they become available. In the long-term, such an approach will further aid algorithm development for ocean-colour studies.

Phytoplankton↗

Satellite Broadcast of Graphical Weather Data Flight Tested

NASA Glenn Research Center at Lewis Field's aviation Weather Information Communications (WINCOMM) and NASA Langley Research Center's Aviation Weather Information (AWIN) programs collaborated in a flight test and evaluation of a worldwide weather data-link capability using satellites. This successful flight testing moves NASA closer to its goal of developing advanced communications and information technologies to enable high-quality and timely dissemination of aviation weather information to all relevant users on the aviation information network. Recognized as a major contributing factor in aviation accidents and incidents, weather contributes directly or indirectly to nearly 80 percent of fatal general aviation (small private aircraft) accidents. In 1997, the Aeronautics Safety Investment Strategy Team s weather team produced a prioritized list of investment areas under weather accident prevention. Weather data dissemination is the most critical and highest ranked priority on the list. NASA's Aviation Safety Program founded the Aviation Weather Information initiative to focus efforts on significantly reducing the number of weather-related aviation fatalities. Access to accurate and timely weather data could contribute to a major reduction of weather-related incidents and accidents. However, a cost-effective solution has eluded most general aviation pilots because of the high cost of onboard weather radar equipment. Rockwell Collins, through a contract with NASA and in cooperation with WorldSpace Corporation, successfully completed ground and flight testing of a receiver and antenna in Johannesburg, South Africa. This NASA/Rockwell Collins project is an evaluation of worldwide weather data-link capability using transmissions from the Satellite Digital Audio Radio Services (S DARS) AfriStar satellite. Owned and operated by WorldSpace, AfriStar is a geostationary satellite that broadcasts commercial digital audio services to stationary and mobile platforms. S DARS satellites are the most powerful communications satellites produced to date, allowing users to receive signals using simple, low-cost patch antennas instead of more expensive, beam-steered antenna arrays. Engineers connected an inexpensive, commercially available radio receiver to a laptop computer and an antenna designed and built by Rockwell Collins, enabling them to receive WorldSpace signals from the AfriStar satellite during flight tests. WorldSpace broadcast their composite color graphical weather data files, which were multiplexed with normal audio streams, to the flat patch antenna mounted on a single-engine aircraft. The aircraft was equipped with a modified commercial S-DARS receiver, a Global Positioning Satellite (GPS) receiver, and a laptop computer with color display. Continuous data reception occurred during normal aircraft maneuvers performed throughout takeoff, cruise, and landing operations. In addition, engineers monitored receiver power levels during steep turns and banks. In most instances, the receiver was able to maintain acceptable power levels during all phases of flight and to obtain weather data with little or with the successful completion of ground and flight testing of a receiver and antenna in Johannesburg, South Africa, the team has started to prepare for experiments using highspeed aircraft in areas of the world with limited access to timely weather data. NASA plans to provide a more advanced antenna design and consultation support. This successful test of real-time aviation-related weather data is a positive step toward solving communications-specific issues associated with the dissemination of weather data directly to the cockpit.

Mallasch, Paul G.↗

Experimentation for the Maturation of Deep Space Cryogenic Refueling Technologies

This report describes the results of the "Experimentation for the Maturation of Deep Space Cryogenic Refueling Technology" study. This study identifies cryogenic fluid management technologies that require low-gravity flight experiments bring technology readiness levels to 5 to 6; examines many possible flight experiment options; and develops near-term low-cost flight experiment concepts to mature the core technologies. A total of 25 white papers were prepared by members of the project team in the course of this study. The full text of each white paper is included and 89 relevant references are cited. The team reviewed the white papers that provided information on new or active concepts of experiments to pursue and assessed them on the basis of technical need, cost, return on investment, and flight platform. Based on on this assessment the "Centaur Test Bed for Cryogenic Fluid Management" was rated the highest. "Computational Opportunities for Cryogenics for Cryogenic and Low-g Fluid Systems" was ranked second, based on its high scores in state of the art and return on investment, even though scores in cost and time were second to last. "Flight Development Test Objective Approach for In-space Propulsion Elements" was ranked third.

Chato, David J.↗

Space and surface power for the space exploration initiative: Results from project outreach

The analysis and evaluations of the Space and Surface Power panel, one of eight panels created by RAND to screen and analyze submissions to the Space Exploration Initiative (SEI) Outreach Program, is documented. In addition to managing and evaluating the responses, or submissions, to this public outreach program, RAND conducted its own analysis and evaluation relevent to SEI mission concepts, systems, and technologies. The Power panel screened and analyzed submissions for which a substantial portion of the concepts involved power generation sources, transmission, distribution, thermal management, and handling of power (including conditioning, conversion, packaging, and enhancements in system components). A background discussion of the areas the Power panel covered and the issues the reviewers considered pertinent to the analysis of power submissions are presented. An overview of each of the highest-ranked submissions and then a discussion of these submissions is presented. The results of the analysis is presented.

Shipbaugh, C.↗

Comparison of Mixing Calculations for Reacting and Non-Reacting Flows in a Cylindrical Duct

A production 3-D elliptic flow code has been used to calculate non-reacting and reacting flow fields in an experimental mixing section relevant to a rich burn/quick mix/lean burn (RQL) combustion system. A number of test cases have been run to assess the effects of the variation in the number of orifices, mass flow ratio, and rich-zone equivalence ratio on the flow field and mixing rates. The calculated normalized temperature profiles for the non-reacting flow field agree qualitatively well with the normalized conserved variable isopleths for the reacting flow field indicating that non-reacting mixing experiments are appropriate for screening and ranking potential rapid mixing concepts. For a given set of jet momentum-flux ratio, mass flow ratio, and density ratio (J, MR, and DR), the reacting flow calculations show a reduced level of mixing compared to the non-reacting cases. In addition, the rich-zone equivalence ratio has noticeable effect on the mixing flow characteristics for reacting flows.

Oechsle, V. L.↗

Investigation of Fundamental Modeling and Thermal Performance Issues for a Metallic Thermal Protection System Design

A study was performed to develop an understanding of the key factors that govern the performance of metallic thermal protection systems for reusable launch vehicles. A current advanced metallic thermal protection system (TPS) concept was systematically analyzed to discover the most important factors governing the thermal performance of metallic TPS. A large number of relevant factors that influence the thermal analysis and thermal performance of metallic TPS were identified and quantified. Detailed finite element models were developed for predicting the thermal performance of design variations of the advanced metallic TPS concept mounted on a simple, unstiffened structure. The computational models were also used, in an automated iterative procedure, for sizing the metallic TPS to maintain the structure below a specified temperature limit. A statistical sensitivity analysis method, based on orthogonal matrix techniques used in robust design, was used to quantify and rank the relative importance of the various modeling and design factors considered in this study. Results of the study indicate that radiation, even in small gaps between panels, can reduce significantly the thermal performance of metallic TPS, so that gaps should be eliminated by design if possible. Thermal performance was also shown to be sensitive to several analytical assumptions that should be chosen carefully. One of the factors that was found to have the greatest effect on thermal performance is the heat capacity of the underlying structure. Therefore the structure and TPS should be designed concurrently.

Blosser, Max L.↗