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Current Concepts and Future Directions of CELSS

Bioregenerative life support systems for use in space were studied. Concepts of such systems include the use of higher plants and/or microalgae as sources of food, potable water and oxygen, and as sinks for carbon dioxide and metabolic wastes. Recycling of materials within the system will require processing of food organism and crew wastes using microbiological and/or physical chemical techniques. The dynamics of material flow within the system will require monitoring, control, stabilization and maintenance imposed by computers. Studies included higher plant and algal physiology, environmental responses, and control; flight experiments for testing responses of organisms to weightlessness and increased radiation levels; and development of ground based facilities for the study of recycling within a bioregenerative life support system.

Macelroy, R. D.↗

Musculoskeletal Modeling Component of the NASA Digital Astronaut Project

The NASA Digital Astronaut Project s (DAP) objective is to provide computational tools that support research of the physiological response to low gravity environments and analyses of how changes cause health and safety risks to the astronauts and to the success of the mission. The spaceflight risk associated with muscle atrophy is impaired performance due to reduced muscle mass, strength and endurance. Risks of early onset of osteoporosis and bone fracture are among the spaceflight risks associated with loss of bone mineral density. METHODS: Tools under development include a neuromuscular model, a biomechanical model and a bone remodeling model. The neuromuscular model will include models of neuromuscular drive, muscle atrophy, fiber morphology and metabolic processes as a function of time in space. Human movement will be modeled with the biomechanical model, using muscle and bone model parameters at various states. The bone remodeling model will allow analysis of bone turnover, loss and adaptation. A comprehensive trade study was completed to identify the current state of the art in musculoskeletal modeling. The DAP musculoskeletal models will be developed using a combination of existing commercial software and academic research codes identified in the study, which will be modified for use in human spaceflight research. These individual models are highly dependent upon each other and will be integrated together once they reach sufficient levels of maturity. ANALYSES: The analyses performed with these models will include comparison of different countermeasure exercises for optimizing effectiveness and comparison of task requirements and the state of strength and endurance of a crew member at a particular time in a mission. DISCUSSION: The DAP musculoskeletal model has the potential to complement research conducted on spaceflight induced changes to the musculoskeletal system. It can help with hypothesis formation, identification of causative mechanisms and supplementing small data samples.

Lewandowski, B. E.↗

Expanding Biological Repository Data Available for Sharing and Knowledge Discovery

Biology has developed next-generation data science and alternative analytical approaches with methodologies which require principal investigator (PI) experimental assay data be re-used. This new approach involves mining multiple datasets at once from various hierarchical organizations of biological complexity, while concurrently evaluating how experimental factors affect endpoints of standard assays. The purpose of the NASA Ames Life Sciences Data Archive (ALSDA) is to collect, curate, and make findable, accessible, interoperable, and reusable (FAIR) all non-human space-relevant biological data. These data include mission metadata, subject metadata, assay metadata (parameters), raw and processed assay data, assay imagery, and subject-experienced telemetry (radiation, temperature, humidity, acoustics, vibrations). ALSDA has transformed to bring current biological repository data and all future collected data into this new scientific data mining reality. It has integrated into the ‘NASA Open Science’ group of projects to facilitate a suite of new tools and workflows to improve data accessibility and reusability by implementing data management plans, automating data submission agreements, and adopting the single-point-of-entry data submission portal, originally developed by NASA GeneLab. These systems required ALSDA to develop science assay configurations for the submission portal, capturing essential assay parameters according to established norms in each sub-field within biology. The submission portal expedites data collection by enhancing ease of PI data submission, providing a user interface and specificity for which data is to be submitted. ALSDA datasets are curated to maintain rich metadata, accuracy of datasets, data transparency, provenance, and additionally ensure data are machine-readable (e.g., R and Python languages). ALSDA integration with GeneLab and its analysis portals enable higher-order physiological-level datasets be mined in conjunction with -omics datasets. As ALSDA physiological-level datasets are published (micro-computed tomography, histology, intraocular pressure, hormonal assays, immunostaining, ultrasonography), the merging of hierarchical organizations of biological complexity from spaceflight will enable new knowledge discovery approaches.

Ryan T Scott↗

Credibility Assessment and Evaluation of the Astronaut Musculoskeletal Boot/Ankle Injury Scenario Using Open SIM(TM) Computational Modeling

The musculoskeletal system of astronauts is subject to physiological changes, potentially leading to injuries due to the exposure to different gravitational environments experienced during spaceflight. These injuries can occur while an astronaut is performing an extravehicular activity (EVA) in space, on lunar or planetary surfaces or while wearing a spacesuit during terrestrial training for an EVA. One area of concern are injuries occurring at the feet and ankles due to a poor fit of the spacesuit boot. These injuries can occur if the boot does not support the ankle sufficiently and the astronaut steps awkwardly, twisting the ankle or foot, during an EVA. The OpenSimTM software can assess EVA induced musculoskeletal injuries for muscle strains, ligament injuries and joint injuries. A modeling and simulation credibility assessment of the OpenSim musculoskeletal modeling and simulation procedures, applied to the boot/ankle injury scenario injury mechanisms that may occur while carrying out tasks in these environments, is performed. These modeling and simulation credibility assessments give information on the credibility of the model’s use in simulating foot/ankle related injury mechanisms.

C A Gallo↗

A continuous physiological data collector

COP-DAC system utilizes oxygen and carbon dioxide analyzers, gas-flow meter, gas breathe-through system, analog computer, and data storage system to provide actual rather than average measurements of physiological and metabolic functions.

Bush, J. C.↗

Development of techniques for measuring pilot workload

An objective method of assessing information workload based on physiological measurements was developed. Information workload, or reserve capacity, was measured using a visual discrimination secondary task and subjective rating of task difficulty. The primary task was two axis (pitch and roll) tracking, and the independent variables in this study were aircraft pitch dynamics and wind gust disturbances. The study was structured to provide: (1) a sensitive, nonloading measure of reserve capacity, and (2) an unencumbering reliable measurement of the psychophysiological state. From these, a measured workload index (MWI) and physiological workload index (PWI) were extracted. An important measure of the success of this study was the degree to which the MWI and PWI agreed across the 243 randomly-presented, four-minute trials (9 subjects X 9 tasks X 3 replications). The electrophysiological data collected included vectorcardiogaram, respiration, electromyogram, skin impedance, and electroencephalogram. Special computer programs were created for the analysis of each physiological variable. The digital data base then consisted of 82 physiological features for each of the 243 trials. A prediction of workload based on physiological observations was formulated as a simultaneous least-squares prediction problem. A best subset of 10 features was chosen to predict the three measures of reserve capacity. The cannonical correlation coefficient was .754 with a chi squared value of 91.3 which allows rejection of the null hypothesis with p of .995.

Spyker, D. A.↗

Simulations of light effects on the human circadian pacemaker: implications for assessment of intrinsic period

The sensitivity of the human circadian system to light has been the subject of considerable debate. Using computer simulations of a recent quantitative model for the effects of light on the human circadian system, we investigated these effects of light during different experimental protocols. The results of the simulations indicate that the nonuniform distribution over the circadian cycle of exposure to ordinary room light seen in classical free-run studies, in which subjects select their exposure to light and darkness, can result in an observed period of approximately 25 h, even when the intrinsic period of the subject's endogenous circadian pacemaker is much closer to 24 h. Other simulation results suggest that accurate assessment of the true intrinsic period of the human circadian pacemaker requires low ambient light intensities (approximately 10-15 lx) during scheduled wake episodes, desynchrony of the imposed light-dark cycle from the endogenous circadian oscillator, and a study length of at least 20 days. Although these simulations await further experimental substantiation, they highlight the sensitivity to light of the human circadian system and the potential confounding influence of light on the assessment of the intrinsic period of the circadian pacemaker.

Non-NASA Center↗

Structural organization of the spongy mesophyll

Summary Many plant leaves have two layers of photosynthetic tissue: the palisade and spongy mesophyll. Whereas palisade mesophyll consists of tightly packed columnar cells, the structure of spongy mesophyll is not well characterized and often treated as a random assemblage of irregularly shaped cells. Using micro‐computed tomography imaging, topological analysis, and a comparative physiological framework, we examined the structure of the spongy mesophyll in 40 species from 30 genera with laminar leaves and reticulate venation. A spectrum of spongy mesophyll diversity encompassed two dominant phenotypes: first, an ordered, honeycomblike tissue structure that emerged from the spatial coordination of multilobed cells, conforming to the physical principles of Euler’s law; and second, a less‐ordered, isotropic network of cells. Phenotypic variation was associated with transitions in cell size, cell packing density, mesophyll surface‐area‐to‐volume ratio, vein density, and maximum photosynthetic rate. These results show that simple principles may govern the organization and scaling of the spongy mesophyll in many plants and demonstrate the presence of structural patterns associated with leaf function. This improved understanding of mesophyll anatomy provides new opportunities for spatially explicit analyses of leaf development, physiology, and biomechanics.

3D↗

Prognostic significance of electrical alternans versus signal averaged electrocardiography in predicting the outcome of electrophysiological testing and arrhythmia-free survival

OBJECTIVE: To investigate the accuracy of signal averaged electrocardiography (SAECG) and measurement of microvolt level T wave alternans as predictors of susceptibility to ventricular arrhythmias. DESIGN: Analysis of new data from a previously published prospective investigation. SETTING: Electrophysiology laboratory of a major referral hospital. PATIENTS AND INTERVENTIONS: 43 patients, not on class I or class III antiarrhythmic drug treatment, undergoing invasive electrophysiological testing had SAECG and T wave alternans measurements. The SAECG was considered positive in the presence of one (SAECG-I) or two (SAECG-II) of three standard criteria. T wave alternans was considered positive if the alternans ratio exceeded 3.0. MAIN OUTCOME MEASURES: Inducibility of sustained ventricular tachycardia or fibrillation during electrophysiological testing, and 20 month arrhythmia-free survival. RESULTS: The accuracy of T wave alternans in predicting the outcome of electrophysiological testing was 84% (p < 0.0001). Neither SAECG-I (accuracy 60%; p < 0.29) nor SAECG-II (accuracy 71%; p < 0.10) was a statistically significant predictor of electrophysiological testing. SAECG, T wave alternans, electrophysiological testing, and follow up data were available in 36 patients while not on class I or III antiarrhythmic agents. The accuracy of T wave alternans in predicting the outcome of arrhythmia-free survival was 86% (p < 0.030). Neither SAECG-I (accuracy 65%; p < 0.21) nor SAECG-II (accuracy 71%; p < 0.48) was a statistically significant predictor of arrhythmia-free survival. CONCLUSIONS: T wave alternans was a highly significant predictor of the outcome of electrophysiological testing and arrhythmia-free survival, while SAECG was not a statistically significant predictor. Although these results need to be confirmed in prospective clinical studies, they suggest that T wave alternans may serve as a non-invasive probe for screening high risk populations for malignant ventricular arrhythmias.

Non-NASA Center↗

Digital Astronaut Project Biomechanical Models: Biomechanical Modeling of Squat, Single-Leg Squat and Heel Raise Exercises on the Hybrid Ultimate Lifting Kit (HULK)

The NASA Digital Astronaut Project (DAP) implements well-vetted computational models to predict and assess spaceflight health and performance risks, and to enhance countermeasure development. The DAP Musculoskeletal Modeling effort is developing computational models to inform exercise countermeasure development and to predict physical performance capabilities after a length of time in space. For example, integrated exercise device-biomechanical models can determine localized loading, which will be used as input to muscle and bone adaptation models to estimate the effectiveness of the exercise countermeasure. In addition, simulations of mission tasks can be used to estimate the astronaut's ability to perform the task after exposure to microgravity and after using various exercise countermeasures. The software package OpenSim (Stanford University, Palo Alto, CA) (Ref. 1) is being used to create the DAP biomechanical models and its built-in muscle model is the starting point for the DAP muscle model. During Exploration missions, such as those to asteroids and Mars, astronauts will be exposed to reduced gravity for extended periods. Therefore, the crew must have access to exercise countermeasures that can maintain their musculoskeletal and aerobic health. Exploration vehicles may have very limited volume and power available to accommodate such capabilities, even more so than the International Space Station (ISS). The exercise devices flown on Exploration missions must be designed to provide sufficient load during the performance of various resistance and aerobic/anaerobic exercises while meeting potential additional requirements of limited mass, volume and power. Given that it is not practical to manufacture and test (ground, analog and/or flight) all candidate devices, nor is it always possible to obtain data such as localized muscle and bone loading empirically, computational modeling can estimate the localized loading during various exercise modalities performed on a given device to help formulate exercise prescriptions and other operational considerations. With this in mind, NASA's Digital Astronaut Project (DAP) is supporting the Advanced Exercise Concepts (AEC) Project, Exercise Physiology and Countermeasures (ExPC) laboratory and NSBRI-funded researchers by developing and implementing well-validated computational models of exercises with advanced exercise device concepts. This report focuses specifically on lower-body resistance exercises performed with the Hybrid Ultimate Lifting Kit (HULK) device as a deliverable to the AEC Project.

health↗

Macular Bioaccelerometers on Earth and in Space

Space flight offers the opportunity to study linear bioaccelerometers (vestibular maculas) in the virtual absence of a primary stimulus, gravitational acceleration. Macular research in space is particularly important to NASA because the bioaccelerometers are proving to be weighted neural networks in which information is distributed for parallel processing. Neural networks are plastic and highly adaptive to new environments. Combined morphological-physiological studies of maculas fixed in space and following flight should reveal macular adaptive responses to microgravity, and their time-course. Ground-based research, already begun, using computer-assisted, 3-dimensional reconstruction of macular terminal fields will lead to development of computer models of functioning maculas. This research should continue in conjunction with physiological studies, including work with multichannel electrodes. The results of such a combined effort could usher in a new era in understanding vestibular function on Earth and in space. They can also provide a rational basis for counter-measures to space motion sickness, which may prove troublesome as space voyager encounter new gravitational fields on planets, or must re-adapt to 1 g upon return to earth.

Ross, M. D.↗

Macular bioaccelerometers on earth and in space

Spaceflight offers the unique opportunity to study linear bioaccelerometers (vestibular maculas) in the virtual absence of a primary stimulus, gravitational acceleration. Combined morphological-physiological studies of maculas fixed in space and following flight should reveal macular adaptive responses to microgravity, and their time-course. Ground-based research, already begun, using computer-assisted, three-dimensional reconstructions of macular terminal fields will lead to development of computer models of functioning maculas. This research should continue in conjunction with physiological studies, including work with multichannel electrodes.

Ross, M. D.↗

New Computer Simulations of Macular Neural Functioning

We use high performance graphics workstations and supercomputers to study the functional significance of the three-dimensional (3-D) organization of gravity sensors. These sensors have a prototypic architecture foreshadowing more complex systems. Scaled-down simulations run on a Silicon Graphics workstation and scaled-up, 3-D versions run on a Cray Y-MP supercomputer. A semi-automated method of reconstruction of neural tissue from serial sections studied in a transmission electron microscope has been developed to eliminate tedious conventional photography. The reconstructions use a mesh as a step in generating a neural surface for visualization. Two meshes are required to model calyx surfaces. The meshes are connected and the resulting prisms represent the cytoplasm and the bounding membranes. A finite volume analysis method is employed to simulate voltage changes along the calyx in response to synapse activation on the calyx or on calyceal processes. The finite volume method insures that charge is conserved at the calyx-process junction. These and other models indicate that efferent processes act as voltage followers, and that the morphology of some afferent processes affects their functioning. In a final application, morphological information is symbolically represented in three dimensions in a computer. The possible functioning of the connectivities is tested using mathematical interpretations of physiological parameters taken from the literature. Symbolic, 3-D simulations are in progress to probe the functional significance of the connectivities. This research is expected to advance computer-based studies of macular functioning and of synaptic plasticity.

Ross, Muriel D.↗

Acquisition and analysis of primate physiologic data for the Space Shuttle

This paper describes the design and prototypes of the Physiologic Acquisition and Telemetry System (PATS), which is a multichannel system, designed for large primates, for the data acquisition, telemetry, storage, and analysis of physiological data. PATS is expected to acquire data from units implanted in the abdominal cavities of rhesus monkeys that will be flown aboard the Spacelab. The system will telemeter both stored and real-time internal physiologic measurements to an external Flight Support Station (FSS) computer system. The implanted Data Acquition and Telemetry Subsystem subunit will be externally activated, controlled and reprogrammed from the FSS.

Eberhart, Russell C.↗

Monitoring Outpatient Care

Each year, health care costs for managing chronically ill patients increase as the life expectancy of Americans continues to grow. To handle this situation, many hospitals, doctors practices, and home care providers are turning to disease management, a system of coordinated health care interventions and communications, to improve outpatient care. By participating in daily monitoring programs, patients with congestive heart failure, chronic obstructive pulmonary disease, diabetes, and other chronic conditions requiring significant self-care are facing fewer emergency situations and hospitalizations. Cybernet Medical, a division of Ann Arbor, Michigan-based Cybernet Systems Corporation, is using the latest communications technology to augment the ways health care professionals monitor and assess patients with chronic diseases, while at the same time simplifying the patients interaction with technology. Cybernet s newest commercial product for this purpose evolved from research funded by NASA, the National Institute of Mental Health, and the Advanced Research Projects Agency. The research focused on the physiological assessment of astronauts and soldiers, human performance evaluation, and human-computer interaction. Cybernet Medical's MedStar Disease Management Data Collection System is an affordable, widely deployable solution for improving in-home-patient chronic disease management. The system's battery-powered and portable interface device collects physiological data from off-the-shelf instruments.

Source record↗

HRP's Healthcare Spin-Offs Through Computational Modeling and Simulation Practice Methodologies

Spaceflight missions expose astronauts to novel operational and environmental conditions that pose health risks that are currently not well understood, and perhaps unanticipated. Furthermore, given the limited number of humans that have flown in long duration missions and beyond low Earth-orbit, the amount of research and clinical data necessary to predict and mitigate these health and performance risks are limited. Consequently, NASA's Human Research Program (HRP) conducts research and develops advanced methods and tools to predict, assess, and mitigate potential hazards to the health of astronauts. In this light, NASA has explored the possibility of leveraging computational modeling since the 1970s as a means to elucidate the physiologic risks of spaceflight and develop countermeasures. Since that time, substantial progress has been realized in this arena through a number of HRP funded activates such as the Digital Astronaut Project (DAP) and the Integrated Medical Model (IMM). Much of this success can be attributed to HRP's endeavor to establish rigorous verification, validation, and credibility (VV&C) processes that ensure computational models and simulations (M&S) are sufficiently credible to address issues within their intended scope. This presentation summarizes HRP's activities in credibility of modeling and simulation, in particular through its outreach to the community of modeling and simulation practitioners. METHODS: The HRP requires all M&S that can have moderate to high impact on crew health or mission success must be vetted in accordance to NASA Standard for Models and Simulations, NASA-STD-7009 (7009) [5]. As this standard mostly focuses on engineering systems, the IMM and DAP have invested substantial efforts to adapt the processes established in this standard for their application to biological M&S, which is more prevalent in human health and performance (HHP) and space biomedical research and operations [6,7]. These methods have also generated substantial interest by the broader medical community though institutions like the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) to develop similar standards and guidelines applicable to the larger medical operations and research community. DISCUSSION: Similar to NASA, many leading government agencies, health institutions and medical product developers around the world are recognizing the potential of computational M&S to support clinical research and decision making. In this light, substantial investments are being made in computational medicine and notable discoveries are being realized [8]. However, there is a lack of broadly applicable practice guidance for the development and implementation of M&S in clinical care and research in a manner that instills confidence among medical practitioners and biological researchers [9,10]. In this presentation, we will give an overview on how HRP is working with the NIH's Interagency Modeling and Analysis Group (IMAG), the FDA and the American Society of Mechanical Engineers (ASME) to leverage NASA's biomedical VV&C processes to establish a new regulatory standard for Verification and Validation in Computational Modeling of Medical Devices, and Guidelines for Credible Practice of Computational Modeling and Simulation in Healthcare.

Mulugeta, Lealem↗

A metabolic modeling platform for the computation of microbial ecosystems in time and space (COMETS)

Genome-scale stoichiometric modeling of metabolism has become a standard systems biology tool for modeling cellular physiology and growth. Extensions of this approach are emerging as a valuable avenue for predicting, understanding and designing microbial communities. Computation of microbial ecosystems in time and space (COMETS) extends dynamic flux balance analysis to generate simulations of multiple microbial species in molecularly complex and spatially structured environments. Here we describe how to best use and apply the most recent version of COMETS, which incorporates a more accurate biophysical model of microbial biomass expansion upon growth, evolutionary dynamics and extracellular enzyme activity modules. In addition to a command-line option, COMETS includes user-friendly Python and MATLAB interfaces compatible with the well-established COBRA models and methods, as well as comprehensive documentation and tutorials. Overall, this protocol provides a detailed guideline for installing, testing and applying COMETS to different scenarios, generating simulations that take from a few minutes to several days to run, with broad applicability to microbial communities across biomes and scales.

59 BASIC BIOLOGICAL SCIENCES↗