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NASA NTRS2024

Risk of Bone Fracture due to Spaceflight-induced Changes to Bone

The Human Research Program (HRP) is taking a biomechanical approach to assessing subsequent fracture risk in active astronauts as a consequence of spaceflight exposure. Triennial testing of active and retired astronauts continues as Space Medicine monitors for a premature diagnosis of primary osteoporosis, which is associated with age-related bone loss and skeletal fragility. This updated 2023 Fracture Evidence Report has expanded the description of skeletal changes to capture the full effects of spaceflight on bone: • Recent analysis of fractures from health records of the full astronaut cohort, suggests an increased incidence rate of hip and spine fractures in astronauts following longer spaceflight duration flights compared to incident rates found in shorter duration flights. • Routine preflight-to-postflight surveillance by DXA (dual-energy x-ray absorptiometry) does not provide the full detection of loss and recovery in the long-duration (LD) astronaut nor the full recovery of hip trabecular bone. • The inclusion of hip quantitative computed tomography (QCT) in flight studies delineates effects of spaceflight, of countermeasures, and of post-flight recovery on cortical and trabecular bone parameters—some of which are verified predictors of hip fracture in the aged. • QCT detects and compares the distinct countermeasure effects of the pharmaceutical alendronate and of resistive exercise (on the Advanced Resistive Exercise Device, ARED) in specific cortical and trabecular bone sub-regions during spaceflight. • A published comparison of QCT-determined loss rates of hip trabecular bone in LD astronauts compared to terrestrial cohorts suggest that accelerated loss rates in trabecular volumetric BMD (vBMD) during spaceflight might be analogous to skeletal effects of accelerated loss rates in females due to menopause, potentially leading to disruptions in trabecular microarchitecture. • A dataset of finite element (FE) estimates of hip bone strength in aging terrestrial cohorts (spanning astronaut age-range) provides comparative context for changes in the FE of hip bone strength in LD astronauts, including comparison (force unit of newton) to percentiles (50th, 75th, and 100th) of sex-matched aged humans with hip fractures. • Risk of fracture, due to the mechanical overloading of bones, is being updated with IMPACT, the next-generation tool suite for probabilistic risk assessment (PRA) for exploration missions being created by the Exploration and Medical Capability Element (ExMC) at NASA. IMPACT is currently in development and will not be included in this 2024 update. The risk for fracture necessitates understanding the relationship between applied loads to bone and the biomechanical competence of bone. The Risk for Early Onset Osteoporosis focuses on the weakened condition of bone (including development of new technologies, measurements of novel skeletal attributes, translation of multiple measures to an index of bone fragility, and interpretations of data used to reflect a weakened bone), while the Risk for Fracture assesses factors that influence the probability an astronaut would encounter applied loads exceeding the biomechanical competence of bones, resulting in fracture. This Evidence Report combines the research gaps and tasks associated with both risks.

Fracture↗
NASA NTRSDate not supplied

Designing Experiments for SpinSat, A Novel Variable-Gravity-and-Radiation Platform for Deep-Space Science

Conducting experiments to measure the effects of deep-space radiation and reduced gravity on biological and physical systems remains challenging. The result is a substantial knowledge gap that poses risks to our ability to sustain life and conduct critical operations in deep space. The SpinSat spacecraft platform is designed to bridge such gaps by providing low-cost, reliable, and frequent access to deep space. A disk-shaped rotating satellite that can provide artificial gravity and exposure to space radiation simultaneously, SpinSat is designed to accommodate payloads in a CubeSat form factor (with at least 48 “U” volume), providing power, communications, and a benign thermal environment. It is orbit-agnostic, enabling access to a variety of radiation environments (Van Allen belts, deep space, cis-lunar); and can be equipped with shielding to mimic planetary radiation environments, for both short- and long-term experiments. Because of its versatility and prioritization of late loading for biological payloads, it is well suited to host a wide range of ranging from human tissues and organoids to microorganisms, plants, chemistry, and regolith. Here, we present examples of potential experiment concepts for SpinSat, and discuss the details of how experimental designs could interact with the platform. Potential SpinSat studies have diverse applications, including fundamental radiation biology and DNA repair; cancer biology and countermeasure development; space agriculture; bioproduction of nutrients and pharmaceuticals; understanding regolith dynamics in low gravity; prebiotic chemistry and panspermia. We will further highlight ideas for SpinSat-compatible experimental hardware, existing and in development, and experiment-relevant details on SpinSat capabilities including artificial gravity, potential radiation environments, data, and power. This presentation will aim to provide investigators with the high-level technical information necessary to inspire experiments for SpinSat. We also seek to stimulate conversation and to gain community input on accommodations needs to help guide the evolving design of this platform.

experiment design↗
NASA NTRSDate not supplied

Two-Phase Flow in Filters and Orifices: In preparation for Measurements on ISS Packed Bed Reactor Experiment-Water Recovery Series (PBRE-WRS)

Understanding the hydrodynamics of adiabatic two-phase flows in packed bed reactors offers numerous benefits. It enables the optimization of chemical reactions rates and products, crucial for pharmaceuticals and energy production industries. Additionally, this understanding aids in designing more efficient and compact reactors, reducing space and resource requirements. Insights gained from studying such flows in microgravity contribute to advancements of space technologies and the enhancement of our capabilities for undertaking future long duration safe, and sustainable space exploration missions. The Packed Bed Reactor Experiment-Water Recovery Series (PBRE-WRS) is a flight experiment planned for operation on the Microgravity Science Glove box (MSG) facility of the International Space Station (ISS). The objective of the experiment is to validate hydrodynamic models at a range of gas and liquid flow rates. The microgravity environment allows for measurement and observation of aspects of fluid dynamics that are unique when compared to observations made in full or partial gravity environments. The experiment consists of testing two-phase flow hydrodynamics in three different filters, four (4) orifices and one check valve test articles. The experiment utilizes the hardware of the previously flown PBRE and PBRE-2 with packed beds of different packings materials and sizes. The fluid system of the PBRE-WRS consists of a nitrogen gas delivery and water delivery subsystems. The gas delivery subsystem can accommodate two ranges of gas flow rates, just as for the water delivery system. The nitrogen gas loop is open whereas the water loop is closed. Gas is separated from the water using a gas-liquid phase separator which is located in the water delivery module. Preliminary results from ground testing show the pressure drop increasing at different rates with the liquid and gas flow rates in the Brine filter. In this work, a detailed system description is presented along with a summary of results from ground performance testing of different test sections in an end-to-end preflight testing campaign.

Packed Bed Reactor Experiment↗
NASA NTRS2024

Expanding Ketamine Application for Treatment of Acute Suicidality in Long-Duration Spaceflight

Introduction. The transition to exploration missions places a heightened risk on behavioral health in spaceflight. Although serious psychiatric emergencies during spaceflight have been rare, longer duration missions increase the possibility of emergence in latent mental health disorders due to genetic predisposition, increased autonomy, isolation, helplessness, loss of family member, or catastrophic events. Complicated grief and bereavement have the highest rate of suicidal ideation. Recently, ketamine has been used as an emergent intervention for acute suicidality, promoting its stability, ease of administration, favorable safety profile, and outcomes for reduction of suicidal intent. The goal of this study was to review current literature and collate the understanding of ketamine as a safe, effective pharmacological adjunct for acute suicidality in spaceflight. Methods. This literature review was conducted to collate data on ketamine use for acute suicidality and inform on stability, limitations and utilization of ketamine within extreme environments. Results. 122 publications were reviewed for relevance including 23 randomized-control trials for ketamine use in behavioral emergencies. Discussion. Ketamine is a diverse pharmaceutical with multiple advantageous indications, including acute suicidality, pain, and sedation. Terrestrial use of ketamine suggests a rapidly efficacious medication for reduction in acute suicidality. As behavioral stressors expand related to extended missions, contingencies for behavioral emergencies become increasingly important. Although this review is not intended to re-develop current International Space Station (ISS) protocols, it is the first to discuss the benefits of ketamine in spaceflight as a potential safe, effective multifaceted tool for future exploration missions and treatment for acute suicidal ideation.

Ketamine, Suicidality, Spaceflight↗
NASA NTRSDate not supplied

Harnessing Synthetic Communities and Microbial Recycling of Space Waste Streams for Biomanufacturing Applications

The long-term habitation of extraterrestrial environments such as the Moon or Mars presents significant challenges including supplying materials to sustain life. Off-world recycling of waste materials into biomanufacturer products may ameliorate this. Current literature highlights the need for efficient waste recycling systems to support the bioproduction of essential materials including foods, pharmaceuticals, and biomaterials. The study herein concerns itself with the investigation of three key aspects: 1) formulating an optimal wastewater media on which to grow recombinant microbes for bioproduction in space, 2) examining the potential for constructing stable and metabolically synergistic synthetic microbial communities for largescale and multi-tiered biomanufacturing, and 3) testing the efficacy of one such bioengineered enzyme, cutinase, on the degradation of PET plastics characteristic of those found in ISS waste as a model for recombinant recycling-based biomanufacturing of mission-critical substrates. Formulation of an optimal wastewater media involved growing several microorganisms on mixtures of synthetic planetary wastes representative of those found in space waste systems, combined with simple carbon sources derived from a physio-chemical CO conversion system to determine their growth potential. Potential synthetic microbial communities were conceptually designed, and their stability and metabolic synergism was evaluated within the context of co-cultures. Cutinase activity assays were utilized to determine the efficacy of bioengineered cutinase on PET plastic degradation. Findings will contribute to optimization of wastewater-based media formulations, data on stable synthetic microbial communities for bioproduction, and effective methods for measuring cutinase-based PET plastic degradation. These outcomes support the development of sustainable waste recycling systems for space habitation and aim to fill gaps in the current literature and proposing innovative solutions for waste recycling in space environments. By leveraging synthetic biology this study seeks to enhance the feasibility of long-term extraterrestrial habitation through sustainable resource management.

Bioprocessing↗
NASA NTRSDate not supplied

Developing a Genetic Variant Calling Pipeline for Quantifying the Complex Mutagenic Load Accumulated in BioNutrients-1 Production Pack Samples

Microorganisms hold great promise for on demand production of labile nutrients and pharmaceuticals as well recycling and in situ resource utilization. The utilization of microorganisms for such tasks on space missions is hindered by the limited data on how microbes respond to spaceflight. For example, the genetic stability of microorganisms, and the genomic engineered traits added to deliver desired functions, over long-term storage in the spacecraft environment is poorly understood. The BioNutrients-1 (BN-1) mission conducted a 5-year study of desiccated storage in Low Earth Orbit (LEO) to evaluate the suitability of eight synthetic biology chassis organisms for long-duration space missions. We are employing high-depth, whole genome sequencing (WGS) to determine the mutagenic load that accumulated during long-term storage. Mutation analysis pipelines are well established for homogenous culture grown from a single colony, but the mutational landscape of the BN-1 samples present a unique analysis challenge, as every cell in the BN-1 samples had a unique genetic journey of DNA damage and repair. Consequently, sequence variants are expected at low allele frequency within samples. To address this genetic complexity, we apply two distinct computational approaches to identify mutations in pre-existing WGS data collected from populations of Chlamydomonas reinhardtii that were exposed to UV mutagenesis and growth in LEO. For reference genome free mutation detection, we utilized DiscoSNP++, which is a de Bruijn graph approach. For reference genome-based mutation detection we utilize GATK for Microbes, which is a Bayesian probabilistic approach. We will benchmark these approaches against the mutations originally identified using CRISP, a method optimized for pooled samples. Ultimately, quantifying the mutation load imposed by storage or growth on the ISS will help identify chassis organisms with both high levels of genome stability and viability, which are desirable traits for implementation of bioproduction in long-duration missions.

SNP↗
NASA NTRSDate not supplied

Assessment of Quantum ML Applicability for Climate Actions: Comparison of the Variational Quantum Classifier and the Quantum Support Vector Classifier with Classical ML Models

Climate change refers to significant and long-term alterations in the Earth’s climate patterns, typically resulting from human activities that increase greenhouse gas emissions. Addressing climate change is not merely an option but a necessity, demanding creative solutions and efforts from individuals, researchers, communities, and governments. Despite the capabilities of machine learning (ML) with data-driven solutions promising to combat climate change-related problems, they face challenges stemming from traditional computational methods and prolonged training times, impeding their practical utility. Recent strides in quantum computing have permeated diverse domains, spanning from manufacturing engineering and pharmaceutical discovery to the latest frontier of detecting climate anomalies. With the potential to substantially reduce time and computational complexity, quantum computing shows promise in addressing climate change impacts. Its distinctive features will enable the concurrent exploration of expansive solution spaces, making it well-suited for analyzing extensive climate datasets, simulating intricate climate models, optimizing resource allocation, and discerning patterns in climate data for mitigation and adaptation endeavors. This study explores the potential of using Quantum machine learning (QML) techniques on climate and weather data obtained from NASA Giovannis. We used two QML algorithms, the Quantum Support Vector Classifier (QSVC) and the Variational Quantum Classifier (VQC) models, using the IBM Qiskit ML 0.7.2 ecosystem. We used an actual 127-Qubit IBM Quantum Computer (IBM 127-qubit Eagle) in this study. The methodology and results sections describe the experiences gained from applying and evaluating quantum ML results on climate and weather data obtained from NASA satellites as a novel practical application of quantum computing.

Earth Observational Data↗
NASA NTRSDate not supplied

Two-Phase Flow in Packed Beds, Filters and Orifices: Summary of Findings of the Packed Bed Reactor Experiment Onboard of the International Space Station

Understanding the hydrodynamics of adiabatic two-phase flows in packed bed reactors enables the optimization of chemical reaction rates and products that crucial in pharmaceuticals and energy production industries. Additionally, this understanding aids in designing more efficient and compact reactors and reducing space and resource requirements. Insights gained from studying and understanding such flows in microgravity contribute to advancements of space technologies and the enhancement of our capabilities for undertaking future long duration safe, and sustainable space exploration missions. The objective of the Packed Bed Reactor Experiment series (PBRE and PBRE-2) was to develop a fundamental understanding of the hydrodynamics of adiabatic two-phase flows through porous media in microgravity. This work provides a description of the PBRE fluid system and presents the highlights of the PBRE and PBRE-2 previously flown with different packings and operated onboard of the International Space Station Microgravity Science Glovebox (ISS-MSG). These highlights include flow patterns and two-phase pressure drop, and the impact of capillary effects on pressure drop at various gas and liquid flow rates. This work also presents preliminary results from the Packed Bed Reactor Experiment-Water Recovery Series (PBRE-WRS) recently flown with filters and orifices, which was also operated on the ISS-MSG. The objective of the experiment is to validate hydrodynamic models at a range of gas and liquid flow rates pertinent to the operation of these test articles. The microgravity environment allows for measurement and observation of aspects of fluid dynamics that are unique when compared to observations made in full or partial gravity environments.

ISS↗
NASA NTRS1986

An improved approach to the analysis of drug-protein binding by distance geometry

The calculation of side chain centers of coordinates and the subsequent generation of side chain-side chain and side chain-backbone distance matrices is suggested as an improved method for viewing interactions inside proteins and for the comparison of protein structures. The use of side chain distance matrices is demonstrated with free PTI, and the use of difference distance matrices for side chains is shown for free and trypsin-bound PTI as well as for the X-ray structures of trypsin complexes with PTI and with benzamidine. It is found that conformational variations are reflected in the side chain distance matrices much more than in the standard C-C distance representations.

NASA Discipline Exobiology↗
NASA NTRS1996

Interactions of anesthetics with the membrane-water interface

Although the potency of conventional anesthetics correlates with lipophilicity, an affinity to water also is essential. It was recently found that compounds with very low affinities to water do not produce anesthesia regardless of their lipophilicity. This finding implies that clinical anesthesia might arise because of interactions at molecular sites near the interface of neuronal membranes with the aqueous environment and, therefore, might require increased concentrations of anesthetic molecules at membrane interfaces. As an initial test of this hypothesis, we calculated in molecular dynamics simulations the free energy profiles for the transfer of anesthetic 1,1,2-trifluoroethane and nonanesthetic perfluoroethane across water-membrane and water-hexane interfaces. Consistent with the hypothesis, it was found that trifluoroethane, but not perfluoroethane, exhibits a free energy minimum and, therefore, increased concentrations at both interfaces. The transfer of trifluoroethane from water to the nonpolar hexane or interior of the membrane is accompanied by a considerable, solvent-induced shift in the conformational equilibrium around the C-C bond.

NASA Center ARC↗
NASA NTRS2000

Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

Controlled Clinical Trial↗
NASA NTRS1997

Quantification of urinary uric acid in the presence of thymol and thimerosal by high-performance liquid chromatography

A high-performance liquid chromatographic method was developed as an alternative to automated enzymatic analysis of uric acid in human urine preserved with thymol and/or thimerosal. Uric acid (tR = 10 min) and creatinine (tR = 5 min) were separated and quantified during isocratic elution (0.025 M acetate buffer, pH 4.5) from a mu Bondapak C18 column. The uric-acid peak was identified chemically by incubating urine samples with uricase. The thymol/thimerosal peak appeared at 31 min during the washing step and did not interfere with the analysis. We validated the high-performance liquid chromatographic method for linearity, precision and accuracy, and the results were found to be excellent.

NASA Discipline Regulatory Physiology↗