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NASA NTRS2018

Survey of Methods to Predict Controller Workload for Real-Time Monitoring of Airspace Safety

The Real Time Safety Monitoring (RTSM) approach allows for assessment and prediction of the safety margin in the National Airspace System (NAS) to help preempt incidents and accidents, rather than having to reactively mitigate them. In RTSM, the NAS is modeled using state variables, and safety metrics are defined in terms of these state variables. The safety metrics have been classified as weather-related, airspace-related, and human-related. Many of the formulated human-related safety metrics need an estimate of the controller workload for their computation. However, this computation is not trivial. Hence, in this report, we perform a literature survey to identify the different factors that enable the computation of controller workload and categorize these factors. Next, we describe studies undertaken to determine a minimal set of factors that pro- vide a correct assessment of controller workload. Lastly, we survey approaches for evaluating how well the selected factors correlate with the controllers' subjective assessment of their workload. Based on this survey, we present factors beneficial to computing and predicting controller workload in real time, and discuss the status of data sources necessary for these computations.

National Airspace System↗

NASA NTRS2018

Supply Chain Research and Analysis for Space Systems

The implementation of NASA GSFC's portfolio of mission projects relies upon inter-connected, multi-tiered supply chains of organizations operating under direct and indirect contracts and other agreements throughout the U.S. and around the world. These supply chains are subject to an inter-related array of technical/production, business, market and security risks that are amplified by the ongoing globalization of industry and technology and which can disrupt or threaten the production and delivery of products and services when needed and in conformance with requirements. In recognition of such risks and associated challenges, GSFC's SMA directorate launched an innovative Supply Chain Research and Analysis capability three years ago to gain greater insight into the operating environment, performance, capabilities and viability of current and prospective suppliers for GSFC projects and proposals. The capability uses business intelligence techniques and primarily open source information resources as part of a cost-effective, non-intrusive methodology to produce several types of research and analysis reports. The reports are based on a holistic analytical framework encompassing key technical/production, business enterprise management, market and security factors, and feature in-depth information, summary information profiles, SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis, and candidate risk concerns in order to pro-actively support SMA and project management needs. The SRA capability, which is designed to complement and support ongoing SMA/project management activities and practices, has produced over 105 reports since its start-up in early 2015.This presentation addresses the approach, methodology and performance of the Supply Chain Research and Analysiscapability and its value in assuring the success of NASA mission projects. In doing so, the presentation provides lessons-learned, best practices, case examples and address how it fits into the development of an enterprise-level Supply Chain Risk Management capability.

supply chain risk management↗

NASA NTRS2016

Gene Expression and Structural Skeletal Responses to Long-Duration Simulated Microgravity in Rats

Spaceflight has deleterious effects on skeletal structure and function, specifically causingprofound loss in bone mass, density, and strength, as well as changes in expression levels of genes related to oxidative stress [Hyeon et al., Smith et al.]. It is known that bone resorption remains elevated after spaceflight and that bone density and strength fail to recover completely even years following spaceflight [Smith et al., Carpenter et al.]. However, our current understanding of the signaling pathways and molecular mechanisms that control bone loss and that link oxidative stress, bone resorption, and mechanical unloading of skeletal tissue is incomplete. Here, we aim to examine skeletal responses to simulated long-duration spaceflight on bone loss using the ground-based hindlimb unloading (HU) model in adult (9 months old) male rats. We hypothesized that simulated microgravity leads to the temporal regulation of oxidative-defense genes and pro-osteoclastogenic factors, showing progression and eventual plateau during long-term unloading, and that transient changes at early timepoints in these pathways precede skeletal adaptations to long-duration unloading. We will identify oxidativestress and bone resorption-related changes using global gene expression analysis (Affymetrix arrays) for both acute (within 14 days) and long-term timepoints (90 days). We will also use quantitative PCR to examine changes in expression of genes related to oxidative metabolism (e.g. Nrf2, SOD-1), bone turnover (resorption and formation markers, e.g. TRAP, osteocalcin respectively, SOST), and osteoclastogenesis (e.g. RANKL, OPG) at both early and late timepoints. We will then use detailed microarchitectural and structural analysis through microcomputed tomography to relate gene expression changes with structural changes in bone, expecting that plateaus in gene expression correlate with long-term changes in bone microarchitecture.

Rael, Victoria E.↗

NASA NTRS2018

An Overview of the Layered and Extensible Aircraft Performance System (LEAPS) Development

The Layered and Extensible Aircraft Performance System (LEAPS) is a new sizing and synthesis tool being developed within the Aeronautics Systems Analysis Branch (ASAB) at NASA Langley Research Center. It is a modular, multidisciplinary, multi- fidelity sizing and synthesis tool for modeling advanced aircraft concepts and architectures such as electric/hybrid-electric propulsion, unconventional propulsion airframe integration, and non-traditional mission trajectories. The development of LEAPS is motivated by the lack of existing tools that meet the needs of ASAB. The Flight Optimization System (FLOPS) has been the primary sizing and synthesis tool of ASAB for three decades. However, FLOPS has a number of limitations that make it dicult to use for unconventional aircraft designs. Three high-level goals have been adopted to guide the LEAPS development pro- cess. LEAPS is being developed in Python with an architecture built to enable a exible and extensible analysis capability using the concept of an aircraft object that combines data and analysis models. Five challenge problems for LEAPS have been identi ed to measure progress: analysis of a conventional tube-and-wing aircraft using legacy methods, coupled aeroelastic analysis for weight estimation of a conventional tube-and-wing aircraft, analysis of an advanced hybrid-electric concept, analysis of the X-57 Maxwell distributed electric propulsion aircraft, and optimization of the trajectory of a supersonic vehicle to minimize sonic boom. LEAPS will be a publicly available capability of exceptional quality with modularity and extensibility that makes it a robust tool for design and analysis of current and future unconventional aircraft concepts.

Welstead, Jason R.↗

NASA NTRS2019

Rapid Development of the Seeker Free-Flying Inspector Guidance, Navigation, and Control System

Seeker is an automated extravehicular free-flying inspector CubeSat designed and built in-house at the Johnson Space Center (JSC). As a Class 1E project funded by the International Space Station (ISS) Program, Seeker had a streamlined process to flight certification, but the vehicle had to be designed, developed, tested, and delivered within approximately one year after authority to pro-ceed (ATP) and within a $1.8 million budget. These constraints necessitated an expedited Guidance, Navigation, and Control (GNC) development schedule, development began with a navigation sensor trade study using Linear Covariance (LinCov) analysis and a rapid sensor downselection process, resulting in the use of commercial off-the-shelf (COTS) sensors which could be procured quickly and subjected to in-house environmental testing to qualify them for flight. A neural network was used to enable a COTS camera to provide bearing measurements for visual navigation. The GNC flight software (FSW) algorithms utilized lean development practices and leveraged the Core Flight Software (CFS) architecture to rapidly develop the GNC system, tune the system parameters, and verify performance in simulation. This pace was anchored by several Hardware-Software Integration (HSI) milestones, which forced the Seeker GNC team to develop the interfaces both between hardware and software and between the GNC domains early in the project and to enable a timely delivery.

Sullivan, Jacob↗

NASA NTRS2018

Constraining the Thickness of Polar Ice Deposits on Mercury Using the Mercury Laser Altimeter and Small Craters in Permanently Shadowed Regions

Radar-bright deposits at the poles of Mercury are located in permanently shadowed regions, which pro- vide thermally stable environments for hosting and retaining water ice on the surface or in the near sub- surface for geologic timescales. While the areal distribution of these radar-bright deposits is well characterized, their thickness, and thus their total mass and volume, remain poorly constrained. Here we derive thickness estimates for selected water-ice deposits using small, simple craters visible within the permanently shadowed, radar-bright deposits. We examine two endmember scenarios: in Case I, these craters predate the emplacement of the ice, and in Case II, these craters postdate the emplacement of the ice. In Case I, we find the difference between estimated depths of the original unfilled craters and the measured depths of the craters to find the estimated infill of material. The average estimated infilled material for 9 craters assumed to be overlain with water ice is ∼41 +30 −14 m, where 1 −σ standard error of the mean is reported as uncertainty. Reported uncertainties are for statistical errors only. Additional systematic uncertainty may stem from georeferencing the images and topographic datasets, from the radial accuracy of the altimeter measurements, or from assumptions in our models including (1) ice is flat in the bowl- shaped crater and (2) there is negligible ice at the crater rims. In Case II, we derive crater excavation depths to investigate the thickness of the ice layer that may have been penetrated by the impact. While the absence of excavated regolith associated with the small craters observed suggests that impacts generally do not penetrate through the ice deposit, the spatial resolution and complex illumination geometry of images may limit the observations. Therefore, it is not possible to conclude whether the small craters in this study penetrate through the ice deposit, and thus Case II does not provide a constraint on the ice thickness. For Mercury’s polar deposits, we argue that Case I of the small craters predating the emplacement of the ice deposits is more likely, given other geologic evidence that suggests that these ice deposits are relatively young. Using the ice thickness estimates from Case I to calculate the total amount of water ice currently contained in Mercury’s polar deposits results in a value of ∼10 14 –10 15 kg. This is equivalent to ∼100–1000 km 3 ice in volume. This volume of water ice is consistent with delivery via micrometeorite bombardment, Jupiter-family comets, or potentially a single impactor.

Deutsch, Ariel N.↗

NASA NTRS2016

Sex-specific Effects of Unpredictable Variable Prenatal Stress: Implications for Mammalian Developmental Programming During Spaceflight

During initial exposure and adaptation to the microgravity environment, adult mammals exhibit elevated stress, mediated by the Hypothalamic-Pituitary-Adrenal (HPA) axis. In our previous studies of pregnant rats exposed to 2-g hypergravity via continuous centrifugation, we reported changes in neuroendocrine profiles including decreased corticosterone and a concomitant increase in body mass and leptin in adult male offspring. Prenatally stressed adult offspring have been shown to exhibit an elevated stress response in adulthood, therefore we hypothesized that these changes resulted from stress exposure during fetal development. Future studies examining reproduction, gestation, and development on-orbit need to consider the unique stressors of vehicle launch, the space environment, and landing on the development of the HPA axis in animals born and raised in microgravity. In this study, we utilize Unpredictable Variable Prenatal Stress (UVPS) to simulate the stressors of spaceflight by exposing dams to three different stressors: (1) White Noise, (2) Strobe Light, and (3) Tube Restraint. Stressors were applied from Gestational Day 0 (G0), following an unpredictable schedule (morning [0600-1200hrs]; afternoon [1200-1800hrs]; evening [1800-2400hrs] in 15, 30, or 60 minute durations alongside non-stressed (NS) control dams. Following parturition, pups were fostered to non-manipulated, newly parturient dams to control for differential maternal care. On postnatal day 90 (P90), we harvested the hypothalamus, pituitary, and adrenal glands, and analyzed mRNA expression of the following genes via RT-qPCR: 1) melanocortin-2 receptor (MC2R), POMC, corticotropin-releasing hormone (CRH) in the pituitary; 2) glucocorticoid receptor (NR3C1), pro-opiomelanocortin (POMC), corticotropin-releasing hormone (CRH), brain-derived neurotropic factor (BDNF), in the hypothalamus; and 3) MC2R, tyrosine hydroxylase (TH), steroidogenic acute regulatory protein (STAR), cytochrome P450scc enzyme (CYP) in the adrenal. The identification of sex-specific fetal programming effects on adult stress response is a key step in determining potential animal behavior on-orbit, and will guide future multi-generational studies in microgravity.

prenatal stress↗

NASA NTRS2019

Status of the Post Flight MMOD Inspection Campaign for the SpaceX Cargo Dragon

The SpaceX Cargo Dragon has been flying supply missions for NASA to the International Space Station (ISS) since 2012. At the time of this writing, SpaceX has completed 14 missions to ISS with each returning to Earth via water landing. After each mission, a team from the NASA Johnson Space Center performs an inspection of the exterior surfaces of the Cargo Dragon spacecraft for hypervelocity impact damage features. Data from these inspections are collected into a database that includes impact feature dimensions as well as the location on the vehicle. Additional details on the type and size of particle that produced the damage site are pro-vided when sampling data and definitive spectroscopic analysis results are available. Observation data can be compared with impact estimates from risk assessment codes as a check on the micro-meteoroid and orbital debris (MMOD) environment predictions.

Hyde, James L.↗

NASA NTRS2019

Overexpression of Catalase in Mitochondria Mitigates the Effects of Simulated Microgravity and Social Isolation on Cytokine Expression in Mouse Hippocampus

Space flight missions are becoming longer and more common and evidence points to the physiological toll the missions have on the human body. Aging, sedentary lifestyle, and spaceflight have similar degenerative effects on almost every part of our body; both exposure to the space environment and aging result in cardiovascular deconditioning, bone loss, muscle atrophy, brain changes, and immune response impairment. We hypothesize that exposure to the space environment generates excessive Reactive Oxygen Species (ROS), which results in neuroinflammation and aging-like degenerative symptoms in the brain. We used the hindlimb unloading (HU) model to mimic microgravity with either paired or single housed animals (social isolation). Responses to 30d (30 days) of HU were compared in wildtype or transgenic MCAT (Mitochondrial-targeted CATalase) mice, in which mitochondrial ROS is quenched by over-expression of human catalase. Expression of 4-Hydroxynonenal (4HNE) and Park7 (redox-sensitive chaperone and sensor of oxidative stress) were measured by ELISA (Enzyme-Linked ImmunoSorbent Assay), a protein array quantified from the hippocampal cytokines and 8-hydroxy-2'-deoxyguanosine in serum was measured by ELISA to assess oxidative DNA damage. Preliminary analysis of cage behavior patterns from video collected at the end of the study showed that MCAT HU mice (socially housed) were more active and conducted more exploratory activities compared to NL (Normally Loaded). Our biochemical results showed simulated microgravity and/or social isolation caused changes in levels of cytokines related to immune responses. Two-way ANOVA (Analysis of Variance) revealed significant interaction effects of HU and genotype in expression levels of five cytokines (out of 35) in socially-housed animals. Elevation of these generally pro-inflammatory cytokines by HU in WT (Wild Type) mice was mitigated in MCAT mice, suggesting a role for mitochondrial ROS signaling in inflammatory CNS (Central Nervous System) responses to microgravity. Interestingly, some of these cytokines in the hippocampus displayed strong correlations to the 4HNE levels. We also found substantive cytokine responses to social isolation in the hippocampus; housing and genotype interaction effects were significant (by 2-Factor ANOVA) for 15 cytokines, most of which were mitigated in MCAT mice.Taken together, our results showed that both simulated microgravity and social isolation influenced cytokine levels in the hippocampus and MCAT mice were at least partially protected from these changes. These findings implicate a potentially important role for mitochondrial ROS in CNS responses to the challenges posed by long duration spaceflight.

MCAT↗

NASA NTRS2016

Conceive, Believe and Achieve; A Path to Miniaturization, COTS Infusion, and Size Weight and Power Realization for Flight

JPL along with other aerospace agencies such as the US Air Force Space Pro-grams and a packaging technology innovator, i3 Electronics, Inc., are evaluating the use of state-of-the-art (SOA) commercial off-the-shelf (COTS) and alternative packaging technologies for future high performance and high reliability space applications. Utilization of SOA COTS technologies have resulted in large scale reduction in electronics volume, weight, power, cost and schedule with outstanding electrical performance and high reliability. We will share JPL’s joint design, architectural approach, alternative substrate materials selection, associated processes, and mission assurance role in identifying reliability and qualification risks, as part of the three year Heterogeneous Packaging/Device Integration effort under the guidance and leadership of JPL’s Mission Assurance Directorate.

Hunter, Don J.↗

NASA NTRS2019

Mars Phoenix EDL Trajectory and Atmosphere Reconstruction Using NewSTEP

This document describes the trajectory and atmosphere reconstruction of the Mars Phoenix Entry, Descent, and Landing using the New Statistical Trajectory Estimation Program. The approach utilizes a Kalman filter to blend inertial measurement unit data with initial conditions and radar altimetry to obtain the inertial trajectory of the entry vehicle. The nominal aerodynamic database is then used in combination with the sensed accelerations to obtain estimates of the atmosphere-relative state. The reconstructed atmosphere pro le is then blended with pre-flight models to construct an estimate of the as-flown atmosphere.

Karlgaard, Christopher D.↗

NASA NTRS2019

Implementing CubeSat Avionics Components to Full-Scale Capsule Return Missions

Returning samples from Low Earth Orbit (LEO) is no simple task. Whether the samples are scientific experiments or surveillance footage, engineers must overcome many challenges to achieve mission success. In August of 1960 the first payload recovered from LEO, the Corona capsule, carried “more photographic coverage of the Soviet Union than all previous U-2 missions”. The Corona program proved that re-turning surveillance footage from LEO is possible, the program is still referenced today when designing new sample return missions. Although there are many crucial subsystems that make up a sample return capsule, the avionics subsystem demands the most attention. This paper will discuss how current CubeSat avionics components can be applied to large sample return missions. One advantage of using CubeSat avionics components is that they can fit into a 1.5 U (10x10x15 cm) compartment, leaving more room for the payload. This paper is broken down as follows. First, the reader is introduced to the history of sample return projects. The major design strengths of previous projects are analyzed and applied to the current capsule design. Next, the typical trajectory of a capsule is presented along with mission requirements and operations. During the re-entry phase, the avionics subsystem is responsible for commanding the deployment of the parachute, back shell, and the heat shield. Next, the power subsystem is discussed in detail including a trade study on batteries and voltage regulators. Next, the interface between the Ground Support Equipment (GSE) and the avionics components is discussed. It is important that the capsule is able to provide avionics system state of health to ensure proper functionality before the capsule is launched. Next, an in-depth analysis of current TechEdSat avionics components, with proven flight history, are presented. The various avionics components including the radios, GPS, IMU, temperature sensors, altitude sensors, and ejectors are discussed. The application of cur-rent avionics components to a sample return projects are analyzed. After, the wiring diagram is presented along with a discussion of the design. Next, a summary of how the avionics components are tested and validated is pro-vided. Finally, this article will present current sample return missions TechEdSat avionics components are being applied to. CubeSat Avionics can be applied to almost all sample return missions due to their compact configuration and proven space flight heritage. The TechEdSat team is currently making great progress in returning samples from the International Space Station (ISS) and is excited to present how their avionics components can be applied to a full-scale sample return mission.

Hughes, Z. M.↗

NASA NTRS2018

Wall-Modeled Lattice Boltzmann and Navier-Stokes Approaches for Separated Flows

Lattice Boltzmann (LB) and hybrid Reynolds-averaged Navier-Stokes/large eddy simulation (RANS/LES) methods within the Launch Ascent and Vehicle Aerodynamics (LAVA) solver framework are applied to NASA's Revolutionary Computational Aerosciences (RCA) standard test cases for separated flows. A detailed comparison between the performance and accuracy of the two emerging numerical methodologies for turbulence resolving simulations, i.e. the LB and hybrid RANS/LES methods will be presented. This contribution addresses the RCA technical challenge to identify and down-select critical turbulence, transition, and numerical method technologies for 40% reduction in predictive error for standard turbulence separated flow test cases. Results for the 2D NASA wall-mounted hump and the axisymmetric transonic bump including time-averaged pressure coefficient, skin friction, and velocity pro les, as well as resolved and modeled Reynolds stresses for both numerical approaches will be presented and differences between LB and hybrid RANS/LES will be discussed.

Lattice Boltzmann↗

NASA NTRS2019

Implementation Recommendations and Usage Boundaries for the Two-Dimensional Probability of Collision Calculation

The two-dimensional (2D) probability of collision (𝑃𝑐) estimation method relies on several assumptions that must be satisfied for accurate results. Monte Carlo analysis of ~44,000 conjunctions indicates that 2D-𝑃(sub 𝑐) pro-vides accurate estimates for most typical conjunctions, but occasionally underestimates 𝑃(sub 𝑐) significantly, indicating an assumption violation. A test to detect large-amplitude underestimation inaccuracies can be based on how much “offset-from-TCA” 2D-𝑃(sub 𝑐) values vary during a well-defined time interval bracketing closest approach. The test successfully detects all large-amplitude 2D-𝑃(sub 𝑐) underestimations found to date, but with a high false-alarm rate. The analysis also provides implementation recommendations and usage boundaries for the 2D-𝑃(sub 𝑐) method.

Hall, Doyle T.↗

NASA NTRS2019

Implementation Recommendations and Usage Boundaries for the Two-Dimensional Probability of Collision Calculation

Hall, Doyle T.↗

NASA NTRS2019

An Approach for Uncertainty Quantification and Management of Unmanned Aerial Vehicle Health

The increasing interest in low-altitude unmanned aerial vehicle (UAV) operations is bringing along safety concerns. Performance of small, low-cost UAVs drastically changes with type, size and controller of the vehicle. Their reliability is lower when compared to reliability of commercial aircrafts, and the availability of on-board sensors for health and state awareness is extremely limited due to their size and propulsion capabilities. Uncertainty plays a dominant role in such a scenario, where a variety of UAVs of different size, propulsion systems, dynamic performance and reliability enters the low-altitude airspace. Unexpected failures could have dangerous consequences for both equipment and humans within that same airspace. As a result, a number of research works and methodologies are being proposed in the area of UAV dynamic modeling, health and safety monitoring, but uncertainty quantification is rarely addressed. Thus, this paper pro- poses a perspective towards uncertainty quantification for autonomous systems, giving special emphasis to a UAV health monitoring application. A formal approach to classify uncertainty is presented; it is utilized to identify the uncertainty sources in UAVs health and operations, and then map uncertainty within a predictive process. To show the application of the methodology proposed here, the design of a model-based powertrain health monitoring algorithm for small-size UAVs is used as case study. The example illustrates how the uncertainty quantification approach can help the modeling strategy, as well as the assessment of diagnostic and prognostic performance.

Health Monitoring↗

NASA NTRS2019

NASA Station Explorer for X-Ray Timing and Navigation Technology (SEXTANT) Mission Operations Architecture

"The Station Explorer for X-Ray Timing and Navigation (SEXTANT) mission is a technology demonstrationenhancement to the Neutron Star Interior Composition Explorer (NICER) mission, a NASA AstrophysicsExplorer Mission of Opportunity to the International Space Station (ISS) that was launched in June of 2017.The NICER instrument is a precision pointing X-ray telescope that provides measurements of neutron stars,which the SEXTANT mission uses to perform autonomous onboard X-ray Pulsar Navigation (XNAV) by usingmilli-second pulsars (MSPs), a category of neutron stars, as timing sources for navigation. By comparing thedetected time of arrival of X-ray photons to a reference of expected pulsar lightcurve timing models, one caninfer a range and range rate measurement based on light time delay. Since both timing and orientationinformation comes from a celestial source, this technology could provide a GPS-like navigation capabilityavailable throughout our Solar System and beyond. Applications that XNAV can support include outer planetand interstellar missions, manned missions, libration orbit missions, and current infrastructure such as the DeepSpace Network (DSN). The SEXTANT team successfully completed a rst demonstration of in-space andautonomous XNAV in November 2017. NICER and SEXTANT have separate teams, with NICER being theprimary team with its own science objectives. Operational modes for both missions must have concurrent andindependent components as well as an integrated ground system. Within this joint mission pro le, SEXTANToperations requires an infrastructure and cadence that is exible to handle concurrent science operations fromthe NICER team, independent autonomous navigation demonstrations, and events within the extensive ISSoperations environment. This paper rst details the infrastructure implemented and its concept of operations.It then describes the operations for the SEXTANT demonstration and lessons learned."

Yu, Wayne H.↗

NASA NTRS2019

Simulated Weightlessness Alters Cardiomyocyte Structure and Transcriptional Regulation of Mediators Related to Immunity and Cardiovascular Disease

Spaceflight and the ensuing fluid shifts, together with an overall reduction in physical activity, lead to acute and latent effects on the cardiovascular system. This current study makes use of the rodent hindlimb unloading (HU) model to determine how factors such as sex, age, and duration of exposure impact cardiac responses to weightlessness. We hypothesize that extended exposure to simulated weightlessness and the ensuing recovery alters cardiac structure and expression of select genes, including those involved in redox signaling which together, negatively impact long-term cardiac tissue health. To begin to test this hypothesis, male and female rats underwent HU at various durations up to 90 days, with a subset reambulated after 90 days of HU. Physiological stress or contractility changes lead to alterations in ventricular cardiomyocyte size and ventricular wall thickness to adapt to greater functional demand and mitigate mechanical stress to ventricular tissue; under certain conditions, these changes also may mark progression to cardiac failure. Hence, left ventricular cardiomyocyte size (cardiomyocyte cross sectional area, CSA) was quantified to determine if HU leads to structural adaptation responses in cardiac tissue and if age and sex had any impact on this outcome. Cardiomyocyte CSA of older males (9 months) were altered by HU in a time-dependent manner, where HU led to decreases in CSA at 14 days and increases at 90 days. In contrast, younger males (3 months) did not show any changes at day 14 of HU. CSA of females (3 months) was increased in response to short-term HU (14 days) suggesting sex-dependence of structural changes. In older HU males, cardiomyocyte CSA was comparable to controls after 90 days of re-ambulation. Levels of the DNA oxidative damage marker, 8-hydroxydeoxyguanosine (8-OHdG) were greater in left ventricular tissue of females that underwent HU compared to sex-matched controls, while there were no such differences in older or younger males. To gain insight into the signals that drive cardiac adaptations to HU, global transcriptomic analysis (RNAseq) was performed on left ventricular tissue of older males that underwent 14 days of HU. Short-term simulated weightlessness led to differential expression of genes involved in immune and pro-inflammatory signaling. A subset of these genes play a role in autoimmune and cardiovascular disease and are targets of current drugs used to treat bradycardia, hypertension, atherosclerosis and rheumatoid arthritis, amongst others. Oxidative damage/redox signaling pathways were not enriched at the timepoint tested in older males. Since young females displayed greater oxidative damage to DNA, activation of oxidative stress responses at earlier or later time points cannot be ruled out. In summary, simulated weightlessness in adult rats caused changes in cardiomyocyte structure in a sex and age-dependent manner, and the transcriptional regulation of key mediators of immunity and cardiovascular disease, meriting further study to define cardiac risks for interplanetary travel of human crew. Our findings also confirm the value of the rat HU model for cardiac health and countermeasure research.

Tahimic, Candice↗