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NASA NTRS2015

Development of the NASA Digital Astronaut Project Muscle Model

This abstract describes development work performed on the NASA Digital Astronaut Project Muscle Model. Muscle atrophy is a known physiological response to exposure to a low gravity environment. The DAP muscle model computationally predicts the change in muscle structure and function vs. time in a reduced gravity environment. The spaceflight muscle model can then be used in biomechanical models of exercise countermeasures and spaceflight tasks to: 1) develop site specific bone loading input to the DAP bone adaptation model over the course of a mission; 2) predict astronaut performance of spaceflight tasks; 3) inform effectiveness of new exercise countermeasures concepts.

Mathematical Models↗
NASA NTRS2015

Omics Research on the International Space Station

The International Space Station (ISS) is an orbiting laboratory whose goals include advancing science and technology research. Completion of ISS assembly ushered a new era focused on utilization, encompassing multiple disciplines such as Biology and Biotechnology, Physical Sciences, Technology Development and Demonstration, Human Research, Earth and Space Sciences, and Educational Activities. The research complement planned for upcoming ISS Expeditions 45&46 includes several investigations in the new field of omics, which aims to collectively characterize sets of biomolecules (e.g., genomic, epigenomic, transcriptomic, proteomic, and metabolomic products) that translate into organismic structure and function. For example, Multi‐Omics is a JAXA investigation that analyzes human microbial metabolic cross‐talk in the space ecosystem by evaluating data from immune dysregulation biomarkers, metabolic profiles, and microbiota composition. The NASA OsteoOmics investigation studies gravitational regulation of osteoblast genomics and metabolism. Tissue Regeneration uses pan‐omics approaches with cells cultured in bioreactors to characterize factors involved in mammalian bone tissue regeneration in microgravity. Rodent Research‐3 includes an experiment that implements pan‐omics to evaluate therapeutically significant molecular circuits, markers, and biomaterials associated with microgravity wound healing and tissue regeneration in bone defective rodents. The JAXA Mouse Epigenetics investigation examines molecular alterations in organ specific gene expression patterns and epigenetic modifications, and analyzes murine germ cell development during long term spaceflight. Lastly, Twins Study ("Differential effects of homozygous twin astronauts associated with differences in exposure to spaceflight factors"), NASA's first foray into human omics research, applies integrated analyses to assess biomolecular responses to physical, physiological, and environmental stressors associated with spaceflight.

Love, John↗
NASA NTRS2016

Hindlimb Suspension (HLS) in Rodents for the Study of Intracranial Pressure, Molecular and Histologic Changes in the Eye, and CSF Production Regulation and Resorption: A Status Report of Two Studies

This status report corresponds to two studies tied to an animal experiment being executed at the University of California Davis (Charles Fuller's laboratory). The animal protocol uses the well-documented rat hindlimb suspension (HLS) model, to examine the relationship between cephalic fluid shifts and the regulation of intracranial (ICP) and intraocular (IOP) pressures as well as visual system structure and function. Long Evans rats are subjected to HLS durations of 7, 14, 28 and 90 days. Subgroups of the 90-day animals are studied for recovery periods of 7, 14, 28 or 90 days. All HLS subjects have age-matched cage controls. Various animal cohorts are planned for this study: young males, young females and old males. In addition to the live measures (ICP by telemetry, IOP and retinal parameters by optical coherence tomography) which are shared with the Fuller study, the specific outcomes for this study include: -Gene expression analysis of the retina -Histologic analysis - Analysis of the microvasculature of retina flat mounts by NASA's VESsel GENeration Analysis (VESGEN) Software. To date, the young male and female cohorts are being completed. Due to the need to keep technical variation to a minimum, the histologic and genomic analyses have been delayed until all samples from each cohort are available and can be processed in a single batch per cohort. The samples received so far correspond to young males sacrificed at 7,14, 28 and 90 days of HLS and at 90 days of recovery; and from young females sacrificed at 7, 14 and 28 of HLS. A complementary study titled: "A gene expression and histologic approach to the study of cerebrospinal fluid (CSF) production and outflow in hindlimb suspended rats" seeks to study the molecular components of CSF production and outflow modulation as a result of HLS, bringing a molecular and histologic approach to investigate genome wide expression changes in the arachnoid villi and choroid plexus of HLS rats compared to rats in normal posture.

Theriot, C. A.↗
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 NTRS2016

Proteomic Assessment of Fluid Shifts and Association with Visual Impairment and Intracranial Pressure in Twin Astronauts

BACKGROUND: Astronauts participating in long duration space missions are at an increased risk of physiological disruptions. The development of visual impairment and intracranial pressure (VIIP) syndrome is one of the leading health concerns for crew members on long-duration space missions; microgravity-induced fluid shifts and chronic elevated cabin CO2 may be contributing factors. By studying physiological and molecular changes in one identical twin during his 1-year ISS mission and his ground-based co-twin, this work extends a current NASA-funded investigation to assess space flight induced "Fluid Shifts" in association with the development of VIIP. This twin study uniquely integrates physiological and -omic signatures to further our understanding of the molecular mechanisms underlying space flight-induced VIIP. We are: (i) conducting longitudinal proteomic assessments of plasma to identify fluid regulation-related molecular pathways altered by long-term space flight; and (ii) integrating physiological and proteomic data with genomic data to understand the genomic mechanism by which these proteomic signatures are regulated. PURPOSE: We are exploring proteomic signatures and genomic mechanisms underlying space flight-induced VIIP symptoms with the future goal of developing early biomarkers to detect and monitor the progression of VIIP. This study is first to employ a male monozygous twin pair to systematically determine the impact of fluid distribution in microgravity, integrating a comprehensive set of structural and functional measures with proteomic, metabolomic and genomic data. This project has a broader impact on Earth-based clinical areas, such as traumatic brain injury-induced elevations of intracranial pressure, hydrocephalus, and glaucoma. HYPOTHESIS: We predict that the space-flown twin will experience a space flight-induced alteration in proteins and peptides related to fluid balance, fluid control and brain injury as compared to his pre-flight protein/peptide signatures. Conversely, the trajectory of these protein signatures will remain relatively constant in his ground based co-twin. METHODS: We are using proteomic and standard immunoelectrophoresis techniques to delineate the change in protein signatures throughout the course of a long duration space flight in relation to the development of VIIP. We are also applying a novel cell-based metaboloic organ system assay ("Organs on a Plate") to address how these circulating biomarkers affect physiological processes at the cellular and organ level which could result in VIIP symptoms. These molecular data will be correlated with physiological measures (eg. extra and intracellular fluid volume, vascular filling/flow patterns, MRI, and Optic Coherence Tomography. DISCUSSION: Pre- and in-flight data collection is in progress for the space-flown twin, and similar data have been obtained from the ground-based twin. Biosamples will be batch processed when received from ISS after the conclusion of the 1-year mission. Omic and Physiological measures from the twin astronauts will be compared to similar data being collected on twin subjects who participated in simulated microgravity study. bed rest study.

Rana, Brinda K.↗
NASA NTRS2015

Space Biophysics: Accomplishments, Trends, Challenges

Physics and biology are inextricably linked. All the chemical and biological processes of life are dutifully bound to follow the rules and laws of physics. In space, these physical laws seem to turn on their head and biological systems, from microbes to humans, adapt and evolve in myriad ways to cope with the changed physical influences of the space environment. Gravity is the most prominent change in space that influences biology. In microgravity, the physical processes of sedimentation, density-driven convective flow, influence of surface tension and fluid pressure profoundly influence biology at the molecular and cellular level as well as at the whole-body level. Gravity sensing mechanisms are altered, structural and functional components of biology (such as bone and muscle) are reduced and changes in the way fluids and gasses behave also drive the way microbial systems and biofilms grow as well as the way plants and animals adapt. The radiation environment also effects life in space. Solar particle events and high energy cosmic radiation can cause serious damage to DNA and other biomolecules. The results can cause mutation, cellular damage or death, leading to health consequences of acute radiation damage or long-term health consequences such as increased cancer risk. Space Biophysics is the study and utilization of physical changes in space that cause changes in biological systems. The unique physical environment in space has been used successfully to grow high-quality protein crystals and 3D tissue cultures that could not be grown in the presence of unidirectional gravitational acceleration here on Earth. All biological processes that change in space have their root in a biophysical alteration due to microgravity and/or the radiation environment of space. In order to fully-understand the risks to human health in space and to fully-understand how humans, plants, animals and microbes can safely and effectively travel and eventually live for long periods beyond the protective environment of Earth, the biophysical properties underlying these changes must be studied, characterized and understood. This lecture reviews the current state of NASA biophysics research accomplishments and identifies future trends and challenges for biophysics research on the International Space Station and beyond.

Space Biophysics: Accomplishments↗
NASA NTRS2016

Ab Initio Simulations of Temperature Dependent Phase Stability and Martensitic Transitions in NiTi

For NiTi based alloys, the shape memory effect is governed by a transition from a low-temperature martensite phase to a high-temperature austenite phase. Despite considerable experimental and computational work, basic questions regarding the stability of the phases and the martensitic phase transition remain unclear even for the simple case of binary, equiatomic NiTi. We perform ab initio molecular dynamics simulations to describe the temperature-dependent behavior of NiTi and resolve several of these outstanding issues. Structural correlation functions and finite temperature phonon spectra are evaluated to determine phase stability. In particular, we show that finite temperature, entropic effects stabilize the experimentally observed martensite (B19') and austenite (B2) phases while destabilizing the theoretically predicted (B33) phase. Free energy computations based on ab initio thermodynamic integration confirm these results and permit estimates of the transition temperature between the phases. In addition to the martensitic phase transition, we predict a new transition between the B33 and B19' phases. The role of defects in suppressing these phase transformations is discussed.

nickel titanium↗
NASA NTRS2017

Effects of Long Duration Spaceflight on Venous and Arterial Compliance: Bed Rest

The primary objective was to determine whether a high sodium diet during bed rest induced alterations in vascular compliance and was related to the incidence of VIIP. Ocular structural and functional measures and vascular ultrasound of the head and neck were acquired in bed rest subjects completing 10-14 days in 6deg head-down tilt.

Ribeiro, L. Christine↗
NASA NTRS2013

RadWorks Storm Shelter Design for Solar Particle Event Shielding

In order to enable long-duration human exploration beyond low-Earth orbit, the risks associated with exposure of astronaut crews to space radiation must be mitigated with practical and affordable solutions. The space radiation environment beyond the magnetosphere is primarily a combination of two types of radiation: galactic cosmic rays (GCR) and solar particle events (SPE). While mitigating GCR exposure remains an open issue, reducing astronaut exposure to SPEs is achievable through material shielding because they are made up primarily of medium-energy protons. In order to ensure astronaut safety for long durations beyond low-Earth orbit, SPE radiation exposure must be mitigated. However, the increasingly demanding spacecraft propulsive performance for these ambitious missions requires minimal mass and volume radiation shielding solutions which leverage available multi-functional habitat structures and logistics as much as possible. This paper describes the efforts of NASA's RadWorks Advanced Exploration Systems (AES) Project to design minimal mass SPE radiation shelter concepts leveraging available resources. Discussion items include a description of the shelter trade space, the prioritization process used to identify the four primary shelter concepts chosen for maturation, a summary of each concept's design features, a description of the radiation analysis process, and an assessment of the parasitic mass of each concept.

Simon, Matthew A.↗
NASA NTRS2017

Risk of Cardiac Rhythm Problems During Spaceflight

NASA has concerns regarding the incidence and clinical significance of cardiac arrhythmias that could occur during long-term exposure to the spaceflight environment, such as on the International Space Station (ISS) or during a prolonged (e.g., up to 3 years) sojourn to Mars or on the Moon. There have been some anecdotal reports and a few documented cases of cardiac arrhythmias in space, including one documented episode of non-sustained ventricular tachycardia. The potential catastrophic nature of a sudden cardiac death in the remote space environment has led to concerns from the early days of the space program that spaceflight might be arrhythmogenic. Indeed, there are known and well-defined changes in the cardiovascular system with spaceflight: a) plasma volume is reduced, b) left ventricular mass is decreased, and c) the autonomic nervous system adapts to the weightless environment. Combined, these physiologic adaptations suggest that changes in cardiac structure and neuro-humoral environment during spaceflight could alter electrical conduction, although the evidence supporting this contention consists mostly of minor changes in QT interval (the time between the start of the Q wave and the end of the T wave on an electrocardiogram tracing) in a small number of astronauts after long-duration spaceflight. Concurrent with efforts by NASA Medical Operations to refine and improve screening techniques relevant to arrhythmias and cardiovascular disease, as NASA enters the era of exploration-class missions it will be critical to determine with the highest degree of certainty whether spaceflight by itself alters cardiac structure and function sufficiently to increase the risk of arrhythmias.

Lee, Stuart M. C.↗
NASA NTRS2017

Vascular Patterning Analysis by VESGEN 2D/3D with Bioinformatics: Updates for Rodent Tissues

Fractally branching vascular systems are a complex physiological requirement shared by humans with all higher terrestrial life forms, including other vertebrates, insects, and higher land plants. Vascular trees, networks, and tree-network composites are therefore mapped and quantified by the VESsel GENeration Analysis (VESGEN) software according to weighted physiological vascular rules that include vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport depends upon a complex distributed system of highly regulated laminar flow. VESGEN has elucidated changes in vascular patterning resulting from inflammatory, developmental and other signaling pathways within numerous tissues of major model organisms important for Space Biology, especially for rodents. Important early stage regenerative opportunities have been identified by VESGEN vascular analysis for visual impairments in the human retina, and is currently being used for research into astronaut visual and ocular disorders associated with long duration missions. The VESGEN 2D software is a mature, automated, widely published capability for which beta testing and public release by NASA is planned for the upcoming year. Early-stage capabilities for VESGEN 3D analysis are under development for the rodent retina and intestine as prototype tissues. A prototype VESGEN 2D Bioinformatics software capability has also been developed to associate phenotypic changes in molecular expression with vascular structure and function. By new VESGEN bioinformatic innovations, expression patterns of the genetic, transcriptional, protein and other markers for regulatory molecules such as vascular endothelial growth factor (VEGF) and their receptors, often indicators of tissue oxygenation status, are co-localized with alterations in vascular pattern. Biomarkers are therefore mapped and quantified as information dimensions directly correlated with the spatial dimensions of a vascular pattern. Further important technology innovations by NASA include substantial image segmentation advances for more automated binary extraction of the grayscale vascular patterns, together with informative associated image quality assessments. Vascular mapping and quantification capabilities for the rodent retina and intestine are illustrated for VESGEN 2D, along with technology status reports on VESGEN 3D and Bioinformatic capabilities. Research partially supported by Ames Center Innovation Awards.

Parsons-Wingerter, P.↗
NASA NTRS2014

Deleterious Effects of Simulated Spaceflight on Bone and Microvasculature in Adult Mice

Long-term spaceflight leads to extensive changes in the musculoskeletal system attributable, in part, to unloading during microgravity exposure. Additionally, irradiation at doses similar to that of a solar flare or a round-trip sojourn to Mars may cause significant depletion of stem/progenitor cell pools throughout the body as well as inflammation associated with prompt skeletal-tissue degradation. Previously, we demonstrated that irradiation leads to rapid bone loss, which can be mitigated in the short term by injection of a potent antioxidant (-lipoic acid). Furthermore, simulated weightlessness in adult mice adversely affects skeletal responses to low linear energy transfer (LET) radiation (137Cs). Here, we hypothesized that simulated weightlessness exacerbates the adverse effects of simulated space radiation (including both protons and 56Fe ions) by adversely affecting skeletal structure and functions as well as associated vasculature. Furthermore, we hypothesized that an antioxidant cocktail, which has been shown to be protective in other tissues, mitigates space radiation induced bone loss.

Shirazi-Fard, Y.↗
NASA NTRS2016

Ab Initio Simulations of Phase Stability and Martensitic Transitions in NiTi

For NiTi based alloys, the shape memory effect is governed by a transition from a low-temperature martensite phase to a high-temperature austenite phase. Despite considerable experimental and computational work, basic questions regarding the stability of the phases and the martensitic phase transition remain unclear even for the simple case of binary, equiatomic NiTi. We perform ab initio molecular dynamics simulations to describe the temperature-dependent behavior of NiTi and resolve several of these outstanding issues. Structural correlation functions and finite temperature phonon spectra are evaluated to determine phase stability. We show that finite temperature, entropic effects stabilize the experimentally observed martensite (B19') and austenite (B2) phases while destabilizing the theoretically predicted (B33) phase. Free energy computations based on ab initio thermodynamic integration confirm these results and permit estimates of the transition temperature between the phases. In addition to the martensitic phase transition, we predict a new transition between the B33 and B19' phases. The role of defects in suppressing phase transformation temperatures is discussed.

Simulations↗
NASA NTRS2018

Discrete Assemblers Utilizing Conventional Motion Systems

An alternative to additive manufacturing is disclosed, introducing an end-to-end workflow in which discrete building blocks are reversibly joined to produce assemblies called digital materials. Described is the design of the bulk-material building blocks and the devices that are assembled from them. Detailed is the design and implementation of an automated assembler, which takes advantage of the digital material structure to avoid positioning errors within a large tolerance. To generate assembly sequences, a novel CAD/CAM workflow is described for designing, simulating, and assembling digital materials. The structures assembled using this process have been evaluated, showing that the joints perform well under varying conditions and that the assembled structures are functionally precise.

Langford, William Kai↗
NASA NTRS2019

New York City Panel on Climate Change 2019 Report Chapter 1: Introduction

While urban areas like New York City and its surrounding metropolitan region are key drivers of climate change through emissions of greenhouse gases, cities are also significantly impacted by climate shifts, both chronic changes and extreme events. These are already affecting the New York metropolitan region, including the five boroughs of New York City through higher temperatures, more intense precipitation, and higher sea levels, and will increasingly do so in the coming decades. The City of New York has embarked on a flexible adaptation pathway (i.e., strategies that can evolve through time as climate risk assessment, evaluation of adaptation strategies, and monitoring continues) to respond to climate change challenges. This entails significant programs to develop resilience in communities and critical infrastructure to observed and projected changes in temperature, precipitation, and sea level. The first NPCC Report laid out the risk management framing for the city and region via flexible adaptation pathways. The second New York City Panel on Climate Change Report (NPCC2) developed the “climate projections of record” that are currently being used by the City of New York in its resilience programs . The NPCC3 2019 Report co-generates new tools and methods for the next generation of climate risk assessments and implementation of region-wide resilience. Co-generation is an interactive process by which stakeholders and scientists work together to produce climate change information that is targeted to decision-making needs. These tools and methods can be used to observe, project, and map climate extremes; monitor risks and responses; and engage with communities to develop effective programs. They are especially important at “transformation points” in the adaptation process when large changes in the structure and function of physical, ecological, and social systems of the city and region are undertaken.

Rosenzweig, Cynthia↗
NASA NTRS2016

Spacecraft Vibration Testing: Benefits and Potential Issues

JPL has traditionally performed system level vibration testing of flight spacecraft. The benefits and potential issues of fully assembled flight spacecraft vibration testing are discussed herein. The following specific topics, which may be complementary to the special session on “Virtual Vibration Testing,” are discussed: spacecraft workmanship, functional and structural integrity testing to uncover workmanship problems, force- and moment-limited vibration testing, potential issues with structural frequency identification using base shake test data, and several failures related to vibration shaker testing. The information provided in this paper is complementary to the special session on “Virtual Shaker Testing,’ and attention is given to issues that virtual shaker testing may face.

Kolaini, Ali R.↗
NASA NTRS2019

Mice Exposed to Combined Chronic Low-Dose Irradiation and Modeled Microgravity Develop Long-Term Neurological Sequelae

Spaceflight poses many challenges for humans. Ground-based analogs typically focus on single parameters of spaceflight and their associated acute effects. This study assesses the long-term transcriptional effects following single and combination spaceflight analog conditions using the mouse model, simulated microgravity via hindlimb unloading (HLU) and/or low-dose irradiation (LDR) for 21-days, followed by 4 months of readaptation. Changes in gene expression and epigenetic modifications in whole brain samples during readaptation were analyzed by DESeq2 and reduced representation bisulfite sequencing (RRBS). The results showed minimal gene expression alterations at 4-months within single treatment conditions of HLU and LDR. Following combined HLU+LDR, gene ontology and methylation analyses showed multiple altered pathways involved in neurogenesis and neuroplasticity, regulation of neuropeptides and cellular signaling. In brief, neurological readaptation following combined chronic LDR and HLU is a dynamic process that impacts brain structure and function and may lead to late onset neurological sequelae

Overbey, Eliah G.↗