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NASA NTRS2017

The Effects of CDKN1a/p21 on Oxidative Stress and Mitochondrial Function During Long Duration Spaceflight

Spaceflight factors, such as microgravity and space radiation, are known to put astronauts at risk for negative effects to their tissue regeneration and degenerative conditions. On our previous spaceflight research, we found that long duration spaceflight produced increased oxidative stress and activation of the inflammatory response as a major contributor to physiological changes, including alterations to the cardiovascular and musculoskeletal systems, metabolism, and the liver. Proliferation, apoptosis, and ion-channel remodeling of vascular smooth muscle cells, as well as endothelial inflammation, and nitric oxide synthase-nitric oxide system regulation have been shown by spaceflight and simulated spaceflight projects. CDKN1ap21 is a regulatory gene for tissue regeneration and also plays an important role in upregulating oxidative stress caused by radiation. In further research, we have also determined CDKN1ap21 to be overexpressed during spaceflight. When knocked out in mice, however, it protects against unloading-induced changes to the morphology and physiology of carotid arteries. In this proposal, we seek to test a potential dietary countermeasure to down-regulate CDKN1ap21 in the mice and protect against oxidative stress in the rodents. Specifically, we will expose both Wildtype and CDKN1ap21-null mice to hydrogen peroxide to induce oxidative stress and observe the molecular mechanisms in which a dietary supplement protects vascular smooth muscle cells against the consequences of the apoptotic environment within Wildtype mice versus the, hypothetically, sound physiology of CDKN1ap21-null mice. The successful completion of this experiment will conclusively determine accuracy of a dietary supplement as a CDKN1ap21 suppressor. This will provide a new perspective on the problem of increased oxidative stress developing into cardiovascular disease as a result of long-term space flight. This research will address the Human Research Plan Roadmaps Risk of Cardiac Rhythm Problems including CV-8, the Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure including Degen-6 and Degen-7, and the Risk of Adverse Health Event from Radiation Exposure including IM-8. Additionally, this research will address Space Biology Research Plans questions SBP CMB-1, SBP CMB-3, and SB AN-2.

Oxidative Stress↗

NASA NTRS1992

Reducing the complexity of software systems - A strategic software perspective

The results of a combined management and technical initiative aimed at reducing the size and complexity associated with developing operations planning, scheduling, and resource management software systems are presented. The initiative has produced operations concepts, functional requirements, system architectures, a comprehensive lexicon, and software tools to revolutionize the traditional software technology and development practices for planning, scheduling, and resource management systems used in space operations control centers. Examples of technology and practices to reduce complexity include a method for projecting design consequences from an operations concept, a universal architecture for heuristic algorithms, an object-oriented framework for describing large classes of problems that parametrically adapt to all domain peculiarities, the identification of general approaches which respond to changes with minimum impact on systems implementations, and a management structure for prototyping to minimize the risks of ill-conceived designs.

Hornstein, Rhoda S.↗

NASA NTRS1994

Flight Testing of Hypersonic Airbreathing Propulsion for Developing Computational Design Technology

The objective of this paper is to present and discuss a scenario and the requirements for flight testing of hypersonic airbreathing propulsion leading to the development of computational design technology. Flight Testing for this development is a significant part of a triad/synergistic, design approach which integrates computations, flight testing, and ground testing. These three complementary, design developmental tools have various capabilities and limitations. An incremental approach is necessary to use and to develop these tools effectively and efficiently. This computational technology must be developed keeping in focus the aerospace plane that is to be developed. The criteria for selecting the right plane are presented and consequently, the appropriate flight tests are identified. Two conceptual, flight-test systems are suggested considering the following: (1) the relevant, lessons learned from previous and current United States hypersonic programs, from the Apollo program, from the Space Shuttle program, and from the space station program; (2) the current need for a low risk, affordable access to space; and (3) the design challenge for hypersonic airbreathing propulsion testing. How these systems may be used for developing the computational design technology is described. The requirements for conducting propulsion- design computations, sources of uncertainties in these computations, and a guide for establishing the credibility of these computations are also presented.

Mehta, Unmeel B.↗

NASA NTRS2009

Microdosimeter Instrument (MIDN-II) for Personnel Dosimetry

This group of collaborators has been funded, by the National Space Biomedical Research Institute (NSBRI) and the U. S. National Aeronautics and Space Administration (NASA) as of February, 2009 to develop a prototypic dosimeter/microdosimeter instrument that measures in real time the radiation risk to personnel in a time varying radiation field of possibly unknown composition. The microdosimetric detectors will be solid-state devices more compact, more rugged than conventional microdosimetric proportional counters used previously in space and will consume less power. The proposed detector will be based on the heritage of the MIDN-MidSTAR microdosimeter launched on the MidSTAR spacecraft on March, 2007, the only solid-state microdosimeter ever flown in space. The system will be suitable for measurements in spacesuits, spacecrafts, remote rovers, or other dynamic or static environments. Measurements as a function of time will not only provide the instantaneous and average absorbed physical dose but also corresponding microdosimetric spectra, dose rates, the dose equivalents, and the dose equivalent rates. Values of the dose equivalents are used to establish relative risks for humans exposed to radiation and to determine regulatory limits. Because these parameters will be available to the astronauts and mission control in real time, these systems can be used not only to quantify exposures and limits, but also to allow appropriate actions to be taken to reduce radiation exposures and their consequences. Earlier prototypes have been used successfully to characterize beams of energetic protons and heavier ions including carbon, oxygen, silicon, titanium, and iron at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. The initial design will be presented and discussed and spectra will be presented.

Pisacane, V. L.↗

NASA NTRSDate not supplied

Teams in Space: Knowledge Gained, but More to Explore

NASA’s Human Research Program oversees the Team Risk (i.e., Risk of Performance and Behavioral Health Decrements due to Inadequate Cooperation, Coordination, Communication and Psychosocial Adaptation within a Team). Research in this area informs all aspects of an astronaut’s career, from hiring to training to mission support, and works to address new challenges related to lunar and Mars missions. NASA’s astronaut selection process creates an astronaut corps of highly qualified, team-oriented individuals, which allows mission planners much flexibility in composing small crews for specific missions. These crews are further developed and supported through extensive training, including team skills training, and countermeasures available to the crew throughout the mission. However, in the high consequence environment of long-duration missions, team composition is complex and is not a one-time concern to be addressed pre-mission. Team factors such as team cohesion, dyadic relationships, and shared team cognition are likely to change dynamically in response to each interaction and event experienced by the individuals and the team as a whole. Thus, monitoring and optimizing team composition at a more micro level (e.g., per task) is one way to support team functioning and performance. Spaceflight teams research also includes the multi-team system of Mission Control and coordination between space-to-ground, adding another avenue in which risk might be introduced, particularly under exploration missions that experience significant communication delays. Spaceflight teams research has recently experienced a concentrated flurry of analog research over the past decade, shedding light on the many unique challenges and potential solutions to mitigate the team risk in long-duration exploration missions. However, questions still remain about how to, for example, create unobtrusive operational measures and how to advance interdisciplinary teams research and countermeasure development. We present an overview of the challenges facing teams in space, our current knowledge, and the next steps for research and spaceflight operations.

Lauren Blackwell Landon↗

NASA NTRS1990

Radiation biology of HZE particles

The biological effects of heavy charged particle (HZE) radiation are of particular interest to travellers and planners for long duration space flights where exposure levels represent a potential health hazard. The unique feature of HZE radiation is the structured pattern of its energy deposition in targets which may be related to charge, velocity, or rate of energy loss. There are many consequences of this feature to biological endpoints when compared to effects of ionizing photons. Dose vs response and dose rate kinetics are modified, DNA and cellular repair systems are altered in their abilities to cope with damage and, the qualitative features of damage are unique for different ions. These features must be incorporated into any risk assessment system for radiation health management. HZE induced mutation, cell inactivation and altered organogenesis will be discussed emphasizing studies with the nematode Caenorhabditis elegans and cultured cells. Observations from radiobiology experiments in space will also be reviewed along with plans for future space-based studies.

Nelson, Gregory A.↗

NASA NTRS2014

Astronaut Bone Medical Standards Derived from Finite Element (FE) Models of QCT Scans from Population Studies

This work was accomplished in support of the Finite Element [FE] Strength Task Group, NASA Johnson Space Center [JSC], Houston, TX. This group was charged with the task of developing rules for using finite-element [FE] bone-strength measures to construct operating bands for bone health that are relevant to astronauts following exposure to spaceflight. FE modeling is a computational tool used by engineers to estimate the failure loads of complex structures. Recently, some engineers have used this tool to characterize the failure loads of the hip in population studies that also monitored fracture outcomes. A Directed Research Task was authorized in July, 2012 to investigate FE data from these population studies to derive these proposed standards of bone health as a function of age and gender. The proposed standards make use of an FE-based index that integrates multiple contributors to bone strength, an expanded evaluation that is critical after an astronaut is exposed to spaceflight. The current index of bone health used by NASA is the measurement of areal BMD. There was a concern voiced by a research and clinical advisory panel that the sole use of areal BMD would be insufficient to fully evaluate the effects of spaceflight on the hip. Hence, NASA may not have a full understanding of fracture risk, both during and after a mission, and may be poorly estimating in-flight countermeasure efficacy. The FE Strength Task Group - composed of principal investigators of the aforementioned population studies and of FE modelers -donated some of its population QCT data to estimate of hip bone strength by FE modeling for this specific purpose. Consequently, Human Health Countermeasures [HHC] has compiled a dataset of FE hip strengths, generated by a single FE modeling approach, from human subjects (approx.1060) with ages covering the age range of the astronauts. The dataset has been analyzed to generate a set of FE strength cutoffs for the following scenarios: a) Qualify an applicant for astronaut candidacy, b) Qualify an astronaut for a long-duration (LD) mission, c) Qualify a veteran LD astronaut for a second LD mission, and d) Establish a non-permissible, minimum hip strength following a given mission architecture. This abstract will present the FE-based standards accepted by the FE Strength Task Group for its recommendation to HHC in January 2015.

Sibonga, J. D.↗

NASA NTRS2015

Can Simulation Credibility Be Improved Using Sensitivity Analysis to Understand Input Data Effects on Model Outcome?

Model and simulation (MS) credibility is defined as, the quality to elicit belief or trust in MS results. NASA-STD-7009 [1] delineates eight components (Verification, Validation, Input Pedigree, Results Uncertainty, Results Robustness, Use History, MS Management, People Qualifications) that address quantifying model credibility, and provides guidance to the model developers, analysts, and end users for assessing the MS credibility. Of the eight characteristics, input pedigree, or the quality of the data used to develop model input parameters, governing functions, or initial conditions, can vary significantly. These data quality differences have varying consequences across the range of MS application. NASA-STD-7009 requires that the lowest input data quality be used to represent the entire set of input data when scoring the input pedigree credibility of the model. This requirement provides a conservative assessment of model inputs, and maximizes the communication of the potential level of risk of using model outputs. Unfortunately, in practice, this may result in overly pessimistic communication of the MS output, undermining the credibility of simulation predictions to decision makers. This presentation proposes an alternative assessment mechanism, utilizing results parameter robustness, also known as model input sensitivity, to improve the credibility scoring process for specific simulations.

Credibility↗

NASA NTRSDate not supplied

Synthetic Failure Mode Generation for Resilience Analysis and Failure Mechanism Discovery

Traditional risk-based design processes seek to mitigate operational hazards by manually identifying possible faults and corresponding mitigation strategies—a tedious process which critically relies on the designer’s limited knowledge. Resilience-based design, on the other hand, seeks to embody generic hazard-mitigating properties in the system to mitigate unknown hazards, often by modelling the system's response to potential hazardous events. This work adapts this approach to the traditional risk-based design process to synthetically generate hazardous modes, by representing them as a unique combination of internal component health-states which can then be injected and simulated in a model of the system failure dynamics. The design process may then reduce the risk of unknown internal hazards by iteratively mitigating the effects of these modes. The performance of this approach is evaluated in a model of an autonomous rover, where cluster analysis shows that elaborating the space of synthetic faults in the drive system using this approach uncovers a wider range of possible hazardous trajectories and failure consequences within each trajectory. However, this increase in hazard information comes at a high computational expense, highlighting the need for advanced, efficient methods to search and sample the hazard space.

Simulation↗

NASA NTRSDate not supplied

Synthetic Failure Mode Generation for Resilience Analysis and Failure Mechanism Discovery

Simulation↗

NASA NTRS2004

Results from an Investigation into Extra-Vehicular Activity (EVA) Training Related Shoulder Injuries

The number and complexity of extravehicular activities (EVAs) required for the completion and maintenance of the International Space Station (ISS) is unprecedented. The training required to successfully complete this magnitude of space walks presents a real risk of overuse musculoskeletal injuries to the EVA crew population. There was mounting evidence raised by crewmembers, trainers, and physicians at the Johnson Space Center (JSC) between 1999 and 2002 that suggested a link between training in the Neutral - Buoyancy Lab (NBL) and the several reported cases of shoulder injuries. The short- and long-term health consequences of shoulder injury to astronauts in training as well as the potential mission impact associated with surgical intervention to assigned EVA crew point to this as a critical problem that must be mitigated. Thus, a multi-directorate tiger team was formed in December of 2002 led by the EVA Office and Astronaut Office at the JSC. The primary objectives of this Tiger Team were to evaluate the prevalence of these injuries and substantiate the relationship to training in the NBL with the crew person operating in the EVA Mobility Unit (EMU). Between December 2002 and June of 2003 the team collected data, surveyed crewmembers, consulted with a variety of physicians, and performed tests. The results of this effort were combined with the vast knowledge and experience of the Tiger Team members to formulate several findings and over fifty recommendations. This paper summarizes those findings and recommendations as well as the process by which these were determined. The Tiger Team concluded that training in the NBL was directly linked to several major and minor shoulder injuries that had occurred. With the assistance of JSC flight surgeons, outside consultants, and the lead crewmember/physician on the team, the mechanisms of injury were determined. These mechanisms were then linked to specific aspects of the hardware design, operational techniques, and the training environment. During the 1999 to 2003 time frame many variables converged to make it impossible to determine with any accuracy which one or two root causes were primarily involved. Therefore a broad range of recommendations was established to prevent future injury to crewmembers training in the NBL in the near term. Many of these recommendations are lessons learned that are essentially timeless and therefore should be passed on to future EVA endeavors to ensure that hardware designs and operational techniques utilized in the future consider the demands of training on the human body here on earth.

Johnson, Brian J.↗

NASA NTRS2008

RT-MATRIX: Measuring Total Organic Carbon by Photocatalytic Oxidation of Volatile Organic Compounds

Volatile organic compounds (VOCs) inevitably accumulate in enclosed habitats such as the International Space Station and the Crew Exploration Vehicle (CEV) as a result of human metabolism, material off-gassing, and leaking equipment. Some VOCs can negatively affect the quality of the crew's life, health, and performance; and consequently, the success of the mission. Air quality must be closely monitored to ensure a safe living and working environment. Currently, there is no reliable air quality monitoring system that meets NASA's stringent requirements for power, mass, volume, or performance. The ultimate objective of the project -- the development of a Real-Time, Miniaturized, Autonomous Total Risk Indicator System (RT.MATRIX).is to provide a portable, dual-function sensing system that simultaneously determines total organic carbon (TOC) and individual contaminants in air streams.

Source record↗

NASA NTRS2011

Lessons Learned from the Space Shuttle Engine Hydrogen Flow Control Valve Poppet Breakage

The Main Propulsion System (MPS) uses three Flow Control Valves (FCV) to modulate the flow of pressurant hydrogen gas from the Space Shuttle Main Engines (SSME) to the hydrogen External Tank (ET). This maintains pressure in the ullage volume as the liquid level drops, preserving ET structural integrity and assuring the engines receive a sufficient amount of head pressure. On Space Transportation System (STS)-126 (2009), with only a handful of International Space Station (ISS) assembly flights from the end of the Shuttle program, a portion of a single FCV?s poppet head broke off at about a minute and a half after liftoff. The risk of the poppet head failure is that the increased flow area through the FCV could result in excessive gaseous hydrogen flow back to the external tank, which could result in overboard venting of hydrogen ullage pressure. If the hydrogen venting were to occur in first stage (i.e., lower atmosphere), a flammability hazard exists that could lead to catastrophic loss of crew and vehicle. Other failure risks included particle impact damage to MPS downstream hardware. Although the FCV design had been plagued by contamination-related sluggish valve response problems prior to a redesign at STS-80 (1996), contamination was ruled out as the cause of the STS-126 failure. Employing a combination of enhanced hardware inspection and a better understanding of the consequences of a poppet failure, safe flight rationale for subsequent flights (STS-119 and later) was achieved. This paper deals with the technical lessons learned during the investigation and mitigation of this problem at a time when assembly flights were each in the critical path to Space Station success.

Martinez, Hugo E.↗

NASA NTRS2018

Reliability Analysis in the Presence of Aleatory Uncertainty

This paper proposes a method for modeling a system’s response using data. In contrast to approaches that identify a limit state function, we focus on the case in which not all uncertain parameters affecting the response are observable and the measured response is corrupted by noise. To this end, the system response is not characterized by a limit state function but instead by a Random Predictor Model (RPM) having a nonparametric structure. Consequently, the resulting failure probability is not a scalar but a random variable. This variable accounts for the aleatory contributions of the model-form uncertainty and the measurement noise into the response. Furthermore, we propose a framework that enables trading off the predicted range of failure probabilities resulting from such an analysis with a measure of risk. In this context, risk is the percentage of all predicted outcomes the analyst is willing to ignore. The reliability analysis of an aeroelastic structure subject to flutter is used to illustrate the ideas proposed.

Crespo, L. G.↗

NASA NTRS2016

Acute Effects of Simulated Space Radiation and Micro-Gravity on Cancellous Bone Loss in Mice Tibiae

Space radiation and micro-gravity are the two major obstacles impeding human exploration of Mars and beyond. Long-duration space flights expose astronauts to high doses of high linear energy transfer (LET) radiation as well as prolonged periods of skeletal disuse due to weightlessness. One important consequence of both radiation exposure and micro-gravity is acute bone loss. However, biological responses to different radiation types and combined radiation and micro-gravity environments remain unknown. Thus, the purpose of this study is to compare the acute effects of different radiation species and simulated weightlessness on bone degeneration for the purpose of developing accurate risk assessments of prolonged space flight. Mouse models were used to simulate space flight-relevant doses of different radiation types as well as weightlessness via hind-limb unloading. Three groups of mice (n 9) were irradiated with 1 Gy (Gray) H+, 1 Gy 56Fe, and 1 Gy combined H+ and 56Fe (dual ion) respectively and compared to sham irradiated (n 9) and 2 Gy 56Fe irradiated positive controls (n 6). Two groups of mice (n 9) were hind-limb unloaded for three days and then either sham irradiated or dual ion irradiated respectively, followed by subsequent hind-limb unloading for 11 days. Cancellous tissue from tibiae metaphyses were harvested 11 days post-irradiation for ex vivo micro-computed tomography analysis. Microarchitecture parameters including bone volume to total volume ratio (BVTV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular spacing (Tb.S), and connectivity density (Conn.D) will be quantified using a novel automated segmentation procedure developed in our lab. The anticipated results will be instrumental in developing counter-measures against micro-gravity and radiation-induced bone loss. Moreover, possible synergistic effects may provide insight into underlying mechanisms mediating biological response.

Micro-Gravity↗

NASA NTRSDate not supplied

NASA CARA Tools

The NASA Conjunction Assessment Risk Analysis (CARA) team has created and posted to GitHub a set of MATLAB software tools for collision assessment (CA) analysis. The software is provided to the public under a NASA Open-Source Software Agreement and is maintained/updated by the CARA Analysis team. Capabilities provided within the toolset include algorithms in assessing probability of collision (Pc), collision consequence, covariance realism, Orbit Determination (OD) quality assessment, and single covariance max Pc. Additionally, a set of utilities are provided for astrodynamics topics closely related to CA, such as: Conjunction Data Message (CDM) parsing, covariance transformations, coordinate system transformations, etc. The repository is regularly updated on a monthly basis and new functionality will be added as algorithms are approved for public release. This presentation will provide a brief introduction to the toolset, highlight some of the key components which can be used in operations, and will present information on algorithms that are in the release pipeline and can be expected soon. This software will enable operators to independently perform CA calculations using the same core algorithms that CARA uses in operations.

L. Baars↗

NASA NTRSDate not supplied

NASA CARA Tools

Luis Baars↗

NASA NTRS2011

The Near Earth Asteroid Medical Conditions List

Purpose: The Exploration Medical Capability (ExMC) element is one of six elements within NASA s Human Research Program (HRP) and is responsible for addressing the risk of "the inability to adequately recognize or treat an ill or injured crewmember" for exploration-class missions. The Near Earth Asteroid (NEA) Medical Conditions List, constructed by ExMC, is the first step in addressing the above-mentioned risk for the 13-month long NEA mission. The NEA mission is being designed by NASA's Human Space Flight Architecture Team (HAT). The purpose of the conditions list is to serve as an evidence-based foundation for determining which medical conditions could affect a crewmember during the NEA mission, which of those conditions would be of concern and require treatment, and for which conditions a gap in knowledge or technology development exists. This information is used to focus research efforts and technology development to ensure that the appropriate medical capabilities are available for exploration-class missions. Scope and Approach: The NEA Medical Conditions List is part of a broader Space Medicine Exploration Medical Conditions List (SMEMCL), which incorporates various exploration-class design reference missions (DRMs). The conditions list contains 85 medical conditions which could occur during space flight and which are derived from several sources: Long-Term Surveillance of Astronaut Health (LSAH) in-flight occurrence data, The Space Shuttle (STS) Medical Checklist, The International Space Station (ISS) Medical Checklist, and subject matter expert opinion. Each medical condition listed has been assigned a clinical priority and a clinical priority rationale based on incidence, consequence, and mitigation capability. Implementation: The conditions list is a "living document" and as such, new conditions can be added to the list, and the priority of conditions on the list can be adjusted as the DRM changes, and as screening, diagnosis, or treatment capabilities change. The NEA medical conditions list was used recently as the basis for identifying gaps in in-flight medical evaluation (screening) capabilities. Learning Objectives: The audience will become familiar with the approach taken by NASA's Exploration Medical Capability element in addressing the risk of inability to recognize and treat medical conditions in the setting of a Near Earth Asteroid mission. Which one of the following statements is incorrect? a) The Near Earth Asteroid (NEA) medical conditions list includes 85 medical conditions which could occur during space flight. b) Each condition on the NEA medical conditions list has been assigned a clinical priority and a clinical priority rationale. c) The NEA medical conditions list targets a mission to Mars. d) The NEA medical conditions list should be viewed as a "living document" where new conditions can be added and clinical priorities adjusted to address changes in the design reference mission or medical capabilities. The incorrect answer is c). The NEA medical conditions list targets a mission to a Near Earth Asteroid.

Barr, Yael R.↗