SEARCH · Search NASA

Results for “Humans”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12

All sources NASA NTRS DOE OSTI

NASA NTRSDate not supplied

Identifying Human Errors and Error Mechanisms From Accident Reports Using Large Language Models

Emerging operational concepts for aviation hinge on novel paradigms for human machine interaction. Critical to their safe operation is early consideration of human error into the design process. Existing methods for consideration of human error require significant expert input, which is challenging both in early design and in novel systems for which there is little existing safety expertise. In this research, we propose a methodology for identifying human error, error producing factors, and mechanisms in early design from historical incident reports. Additionally, we hypothesize that cross-domain sharing of lessons learned can aid with early design human considerations in circumstances where data is not relevant or incomplete. This is addressed by identifying causes of human error in aviation and railway domains through applying state-of-the art natural language processing techniques to historical incident reports. Using this method, it is possible to extract extensive reports on human error from past incidents. Using the proposed approach, we identify nine human errors from railway reports and fourteen from aviation reports, with three errors common to both domains. There is at least one error producing conditions for each human error while a majority of the errors have more than one error mechanism. We also found that a majority of the human errors, error producing factors, and error mechanisms (even if they are not common between the domains) can be used to inform safe operations across domains as long as the errors are not domain specific and are interpreted and contextualized using engineering judgement.

Human Errors↗

DOE OSTI2025

Implications of Safety and Operational Features of Small, Advanced Reactors for the Evaluation of Important Human Actions

The design and operational characteristics of non-light water reactors are likely to change the role of human actions in safety function management and the types of human actions that are deemed important. The objectives of this report are to: • Identify the implications of small, advanced reactor design characteristics on human performance and the changing role of human actions in the management of safety functions. • Identify the methods that may be used to identify important human actions. • Identify how HFE safety reviewers can help ensure that the methods adequately model human actions to identify those that are important to safety. We identified the implications of small, advanced reactor characteristics on the role of personnel in safety function management. Then we addressed how designers can identify which human actions are important to safety using both probabilistic risk assessment (PRA) and deterministic analyses. PRA identifies important human actions using risk-importance criteria. Deterministically identified important human actions include those identified by analyses of situations such as transients and accidents and defense in depth. In all cases, the acceptability of the analyses is dependent on the modeling, quantification, and criterion selection to determine which human actions are important. How well the designers address these processes determines the acceptability of their methodology.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

NASA NTRS2017

What Machines Need to Learn to Support Human Problem-Solving

In the development of intelligent systems that interact with humans, there is often confusion between how the system functions with respect to the humans it interacts with and how it interfaces with those humans. The former is a much deeper challenge than the latter it requires a system-level understanding of evolving human roles as well as an understanding of what humans need to know (and when) in order to perform their tasks. This talk will focus on some of the challenges in getting this right as well as on the type of research and development that results in successful human-autonomy teaming. Brief Bio: Dr. Alonso Vera is Chief of the Human Systems Integration Division at NASA Ames Research Center. His expertise is in human-computer interaction, information systems, artificial intelligence, and computational human performance modeling. He has led the design, development and deployment of mission software systems across NASA robotic and human space flight missions, including Mars Exploration Rovers, Phoenix Mars Lander, ISS, Constellation, and Exploration Systems. Dr. Vera received a Bachelor of Science with First Class Honors from McGill University in 1985 and a Ph.D. from Cornell University in 1991. He went on to a Post-Doctoral Fellowship in the School of Computer Science at Carnegie Mellon University from 1990-93.

intelligent systems↗

NASA NTRSDate not supplied

Logistics Rates and Assumptions for Future Human Spaceflight Missions Beyond LEO

As NASA prepares for future human spaceflight missions with extended crew duration in destinations beyond low Earth orbit (LEO), the Agency has focused itself on understanding the drivers to sustainably support human life beyond Earth’s atmosphere. Future missions to deep space, the lunar surface, and eventually the Martian surface pose new challenges in ensuring the crew is sufficiently supplied with all necessary materials. To mitigate the risk of not delivering sufficient consumables and logistics for human spaceflight missions, NASA has examined past human space mission data and developed metabolic modeling to determine estimates for the crew consumption rates of fluids, solid consumables, and additional equipment needed. This paper is a compilation of guidelines, rates, and assumptions necessary to evaluate the logistics needs for future human exploration conceptual missions beyond LEO, providing a starting point and resource of information regarding usage rates and overall logistics supply planning for crewed exploration missions. Logistics represent all equipment and supplies not installed as part of the vehicle that are needed to support mission activities. Logistics can be further divided into specific categories, including consumables, maintenance items, spares, utilization, outfitting, as well as any packaging required. This paper will also provide use case examples of logistics needs to support human missions in deep space, including a conceptual lunar surface mission. The paper provides information necessary to calculate the mass and volume of known logistics for conceptual future human exploration missions beyond LEO. The assumptions in the paper are updated versions of previous assumptions made by the Agency and were derived from a number of sources, including International Space Station (ISS) historical usage and resupply rates, the Life Support Baseline Values and Assumptions Document (BVAD) 2022, Human Integration Design Handbook (HIDH) 2014, and data gathered from NASA human spaceflight programs and projects. The primary goal of the paper is to establish a set of consistent reference rates that multiple teams and groups can utilize to conduct logistics analysis and compare cases. This methodology is for initial estimates of conceptual human missions and does not take the place of detailed analysis for programs, nor does it provide requirements for programs.

Human Spaceflight↗

NASA NTRSDate not supplied

Logistics Rates and Assumptions for Future Human Spaceflight Missions Beyond LEO

Human Spaceflight↗

NASA NTRS2002

On the nature and evolution of the neural bases of human language

The traditional theory equating the brain bases of language with Broca's and Wernicke's neocortical areas is wrong. Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, and comprehending the meaning of sentences. When we hear or read a word, neural structures involved in the perception or real-world associations of the word are activated as well as posterior cortical regions adjacent to Wernicke's area. Many areas of the neocortex and subcortical structures support the cortical-striatal-cortical circuits that confer complex syntactic ability, speech production, and a large vocabulary. However, many of these structures also form part of the neural circuits regulating other aspects of behavior. For example, the basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human linguistic ability and abstract reasoning. The cerebellum, traditionally associated with motor control, is active in motor learning. The basal ganglia are also key elements in reward-based learning. Data from studies of Broca's aphasia, Parkinson's disease, hypoxia, focal brain damage, and a genetically transmitted brain anomaly (the putative "language gene," family KE), and from comparative studies of the brains and behavior of other species, demonstrate that the basal ganglia sequence the discrete elements that constitute a complete motor act, syntactic process, or thought process. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. As Dobzansky put it, "Nothing in biology makes sense except in the light of evolution" (cited in Mayr, 1982). That applies with as much force to the human brain and the neural bases of language as it does to the human foot or jaw. The converse follows: the mark of evolution on the brains of human beings and other species provides insight into the evolution of the brain bases of human language. The neural substrate that regulated motor control in the common ancestor of apes and humans most likely was modified to enhance cognitive and linguistic ability. Speech communication played a central role in this process. However, the process that ultimately resulted in the human brain may have started when our earliest hominid ancestors began to walk.

Review, Tutorial↗

DOE OSTI2025

Sulfoquinovose is exclusively metabolized by the gut microbiota and degraded differently in mice and humans

Abstract Background Sulfoquinovose (SQ) is a green-diet-derived sulfonated glucose and a selective substrate for a limited number of human gut bacteria. Complete anaerobic SQ degradation via interspecies metabolite transfer to sulfonate-respiring bacteria produces hydrogen sulfide, which has dose- and context-dependent health effects. Here, we studied potential SQ degradation by the mammalian host and the impact of SQ supplementation on human and murine gut microbiota diversity and metabolism. Results 13 CO 2 breath tests with germ-free C57BL/6 mice gavaged with 13 C-SQ were negative. Also, SQ was not degraded by human intestinal cells in vitro, indicating that SQ is not directly metabolized by mice and humans. Addition of increasing SQ concentrations to human fecal microcosms revealed dose-dependent responses of the microbiota and corroborated the relevance ofAgathobacter rectalisandBilophila wadsworthiain cooperative degradation of SQ to hydrogen sulfide via interspecies transfer of 2,3-dihydroxy-1-propanesulfonate (DHPS). Similar to the human gut microbiome, the genetic capacity for SQ or DHPS degradation is sparsely distributed among bacterial species in the gut of conventional laboratory mice.Escherichia coliandEnterocloster clostridioformiswere identified as primary SQ degraders in the mouse gut. SQ and DHPS supplementation experiments with conventional laboratory mice and their intestinal contents showed that SQ was incompletely catabolized to DHPS. Although someE. clostridioformisgenomes encode an extended sulfoglycolytic pathway for both SQ and DHPS fermentation, SQ was only degraded to DHPS by a mouse-derivedE. clostridioformisstrain. Conclusions Our findings suggest that SQ is solely a nutrient for the gut microbiota and not for mice and humans, emphasizing its potential as a prebiotic. SQ degradation by the microbiota of conventional laboratory mice differs from the human gut microbiota by absence of DHPS degradation activity. Hence, the microbiota of conventional laboratory mice does not fully represent the SQ metabolism in humans, indicating the need for alternative model systems to assess the impact of SQ on human health. This study advances our understanding of how individual dietary compounds shape the microbial community structure and metabolism in the gut and thereby potentially influence host health.

Microbiology↗

NASA NTRS1993

Cognitive engineering models: A prerequisite to the design of human-computer interaction in complex dynamic systems

This chapter examines a class of human-computer interaction applications, specifically the design of human-computer interaction for the operators of complex systems. Such systems include space systems (e.g., manned systems such as the Shuttle or space station, and unmanned systems such as NASA scientific satellites), aviation systems (e.g., the flight deck of 'glass cockpit' airplanes or air traffic control) and industrial systems (e.g., power plants, telephone networks, and sophisticated, e.g., 'lights out,' manufacturing facilities). The main body of human-computer interaction (HCI) research complements but does not directly address the primary issues involved in human-computer interaction design for operators of complex systems. Interfaces to complex systems are somewhat special. The 'user' in such systems - i.e., the human operator responsible for safe and effective system operation - is highly skilled, someone who in human-machine systems engineering is sometimes characterized as 'well trained, well motivated'. The 'job' or task context is paramount and, thus, human-computer interaction is subordinate to human job interaction. The design of human interaction with complex systems, i.e., the design of human job interaction, is sometimes called cognitive engineering.

Mitchell, Christine M.↗

NASA NTRS1999

Human Modeling Evaluations in Microgravity Workstation and Restraint Development

The International Space Station (ISS) will provide long-term missions which will enable the astronauts to live and work, as well as, conduct research in a microgravity environment. The dominant factor in space affecting the crew is "weightlessness" which creates a challenge for establishing workstation microgravity design requirements. The crewmembers will work at various workstations such as Human Research Facility (HRF), Microgravity Sciences Glovebox (MSG) and Life Sciences Glovebox (LSG). Since the crew will spend considerable amount of time at these workstations, it is critical that ergonomic design requirements are integral part of design and development effort. In order to achieve this goal, the Space Human Factors Laboratory in the Johnson Space Center Flight Crew Support Division has been tasked to conduct integrated evaluations of workstations and associated crew restraints. Thus, a two-phase approach was used: 1) ground and microgravity evaluations of the physical dimensions and layout of the workstation components, and 2) human modeling analyses of the user interface. Computer-based human modeling evaluations were an important part of the approach throughout the design and development process. Human modeling during the conceptual design phase included crew reach and accessibility of individual equipment, as well as, crew restraint needs. During later design phases, human modeling has been used in conjunction with ground reviews and microgravity evaluations of the mock-ups in order to verify the human factors requirements. (Specific examples will be discussed.) This two-phase approach was the most efficient method to determine ergonomic design characteristics for workstations and restraints. The real-time evaluations provided a hands-on implementation in a microgravity environment. On the other hand, only a limited number of participants could be tested. The human modeling evaluations provided a more detailed analysis of the setup. The issues identified during the real-time testing were investigated in the human modeling analyses. In some cases, the opposite was true where preliminary human modeling analyses provided the design engineers with critical issues that needed to be addressed further. This extensive approach provided an effective means to fully address ergonomic design considerations and accurately identify critical issues.

Whitmore, Mihriban↗

NASA NTRS2002

Human Factors Directions for Civil Aviation

Despite considerable progress in understanding human capabilities and limitations, incorporating human factors into aircraft design, operation, and certification, and the emergence of new technologies designed to reduce workload and enhance human performance in the system, most aviation accidents still involve human errors. Such errors occur as a direct or indirect result of untimely, inappropriate, or erroneous actions (or inactions) by apparently well-trained and experienced pilots, controllers, and maintainers. The field of human factors has solved many of the more tractable problems related to simple ergonomics, cockpit layout, symbology, and so on. We have learned much about the relationships between people and machines, but know less about how to form successful partnerships between humans and the information technologies that are beginning to play a central role in aviation. Significant changes envisioned in the structure of the airspace, pilots and controllers' roles and responsibilities, and air/ground technologies will require a similarly significant investment in human factors during the next few decades to ensure the effective integration of pilots, controllers, dispatchers, and maintainers into the new system. Many of the topics that will be addressed are not new because progress in crucial areas, such as eliminating human error, has been slow. A multidisciplinary approach that capitalizes upon human studies and new classes of information, computational models, intelligent analytical tools, and close collaborations with organizations that build, operate, and regulate aviation technology will ensure that the field of human factors meets the challenge.

Hart, Sandra G.↗

NASA NTRS2005

Future Visions for Scientific Human Exploration

Today, humans explore deep-space locations such as Mars, asteroids, and beyond, vicariously here on Earth, with noteworthy success. However, to achieve the revolutionary breakthroughs that have punctuated the history of science since the dawn of the Space Age has always required humans as "the discoverers," as Daniel Boorstin contends in this book of the same name. During Apollo 17, human explorers on the lunar surface discovered the "genesis rock," orange glass, and humans in space revamped the optically crippled Hubble Space Telescope to enable some of the greatest astronomical discoveries of all time. Science-driven human exploration is about developing the opportunities for such events, perhaps associated with challenging problems such as whether we can identify life beyond Earth within the universe. At issue, however, is how to safely insert humans and the spaceflight systems required to allow humans to operate as they do best in the hostile environment of deep space. The first issue is minimizing the problems associated with human adaptation to the most challenging aspects of deep space space radiation and microgravity (or non-Earth gravity). One solution path is to develop technologies that allow for minimization of the exposure time of people to deep space, as was accomplished in Apollo. For a mission to the planet Mars, this might entail new technological solutions for in-space propulsion that would make possible time-minimized transfers to and from Mars. The problem of rapid, reliable in-space transportation is challenged by the celestial mechanics of moving in space and the so-called "rocket equation." To travel to Mars from Earth in less than the time fuel-minimizing trajectories allow (i.e., Hohmann transfers) requires an exponential increase in the amount of fuel. Thus, month-long transits would require a mass of fuel as large as the dry mass of the ISS, assuming the existence of continuous acceleration engines. This raises the largest technological stumbling block to moving humans on site as deep-space explorers, delivering the masses required for human spaceflight systems to LEO or other Earth orbital vantage points using the existing or projected fleet of Earth-to-orbit (ETO) launch vehicles. Without a return to Saturn V-class boosters or an alternate path, one cannot imagine emplacing the masses that would be required for any deep-space voyage without a prohibitive number of Shuttle-class launches. One futurist solution might involve mass launch systems that could be used to move the consumables, including fuel, water, food, and building materials, to LEO in pieces rather than launching integrated systems. This approach would necessitate the development of robotic assembly and fuel-storage systems in Earth orbit, but could provide for a natural separation of low-value cargo (e.g., fuel, water).

Garvin, James↗

NASA NTRS2007

NASA-STD 3001 and the Human Integration Design Handbook (HIDH): Evolution of NASA-STD-3000

The Habitability & Environmental Factors and Space Medicine Divisions have developed the Space Flight Human System Standard (SFHSS) (NASA-STD-3001) to replace NASA-STD-3000 as a new NASA standard for all human spaceflight programs. The SFHSS is composed of 2 volumes. Volume 1, Crew Health, contains medical levels of care, permissible exposure limits, and fitness for duty criteria, and permissible outcome limits as a means of defining successful operating criteria for the human system. Volume 2, Habitability and Environmental Health, contains environmental, habitability and human factors standards. Development of the Human Integration Design Handbook (HIDH), a companion to the standard, is currently under construction and entails the update and revision of NASA-STD-3000 data. This new handbook will, in the fashion of NASA STD-3000, assist engineers and designers in appropriately applying habitability, environmental and human factors principles to spacecraft design. Organized in a chapter-module-element structure, the HIDH will provide the guidance for the development of requirements, design considerations, lessons learned, example solutions, background research, and assist in the identification of gaps and research needs in the disciplines. Subject matter experts have been and continue to be solicited to participate in the update of the chapters. The purpose is to build the HIDH with the best and latest data, and provide a broad representation from experts in industry, academia, the military and the space program. The handbook and the two standards volumes work together in a unique way to achieve the required level of human-system interface. All new NASA programs will be required to meet Volumes 1 and 2. Volume 2 presents human interface goals in broad, non-verifiable standards. Volume 2 also requires that each new development program prepare a set of program-specific human factors requirements. These program-specific human and environmental factors requirements must be verifiable and tailored to assure the new system meets the Volume 2 standards. Programs will use the HIDH to write their verifiable program-specific requirements.

Pickett, Lynn↗

NASA NTRS2007

Human Error: A Concept Analysis

Human error is the subject of research in almost every industry and profession of our times. This term is part of our daily language and intuitively understood by most people however, it would be premature to assume that everyone's understanding of human error s the same. For example, human error is used to describe the outcome or consequence of human action, the causal factor of an accident, deliberate violations,a nd the actual action taken by a human being. As a result, researchers rarely agree on the either a specific definition or how to prevent human error. The purpose of this article is to explore the specific concept of human error using Concept Analysis as described by Walker and Avant (1995). The concept of human error is examined as currently used in the literature of a variety of industries and professions. Defining attributes and examples of model, borderline, and contrary cases are described. The antecedents and consequences of human error are also discussed and a definition of human error is offered.

Hansen, Frederick D.↗

NASA NTRS2009

Human Systems Integration (HSI) Case Studies from the NASA Constellation Program

The National Aeronautics and Space Administration (NASA) Constellation Program is responsible for planning and implementing those programs necessary to send human explorers back to the moon, onward to Mars and other destinations in the solar system, and to support missions to the International Space Station. The Constellation Program has the technical management responsibility for all Constellation Projects, including both human rated and non-human rated vehicles such as the Crew Exploration Vehicle, EVA Systems, the Lunar Lander, Lunar Surface Systems, and the Ares I and Ares V rockets. With NASA s new Vision for Space Exploration to send humans beyond Earth orbit, it is critical to consider the human as a system that demands early and continuous user involvement, inclusion in trade offs and analyses, and an iterative "prototype/test/ redesign" process. Personnel at the NASA Johnson Space Center are involved in the Constellation Program at both the Program and Project levels as human system integrators. They ensure that the human is considered as a system, equal to hardware and software vehicle systems. Systems to deliver and support extended human habitation on the moon are extremely complex and unique, presenting new opportunities to employ Human Systems Integration, or HSI practices in the Constellation Program. The purpose of the paper is to show examples of where human systems integration work is successfully employed in the Constellation Program and related Projects, such as in the areas of habitation and early requirements and design concepts.

Baggerman, Susan↗

NASA NTRS2011

Development of Methodologies, Metrics, and Tools for Investigating Human-Robot Interaction in Space Robotics

Human-robot systems are expected to have a central role in future space exploration missions that extend beyond low-earth orbit [1]. As part of a directed research project funded by NASA s Human Research Program (HRP), researchers at the Johnson Space Center have started to use a variety of techniques, including literature reviews, case studies, knowledge capture, field studies, and experiments to understand critical human-robot interaction (HRI) variables for current and future systems. Activities accomplished to date include observations of the International Space Station s Special Purpose Dexterous Manipulator (SPDM), Robonaut, and Space Exploration Vehicle (SEV), as well as interviews with robotics trainers, robot operators, and developers of gesture interfaces. A survey of methods and metrics used in HRI was completed to identify those most applicable to space robotics. These methods and metrics included techniques and tools associated with task performance, the quantification of human-robot interactions and communication, usability, human workload, and situation awareness. The need for more research in areas such as natural interfaces, compensations for loss of signal and poor video quality, psycho-physiological feedback, and common HRI testbeds were identified. The initial findings from these activities and planned future research are discussed. Human-robot systems are expected to have a central role in future space exploration missions that extend beyond low-earth orbit [1]. As part of a directed research project funded by NASA s Human Research Program (HRP), researchers at the Johnson Space Center have started to use a variety of techniques, including literature reviews, case studies, knowledge capture, field studies, and experiments to understand critical human-robot interaction (HRI) variables for current and future systems. Activities accomplished to date include observations of the International Space Station s Special Purpose Dexterous Manipulator (SPDM), Robonaut, and Space Exploration Vehicle (SEV), as well as interviews with robotics trainers, robot operators, and developers of gesture interfaces. A survey of methods and metrics used in HRI was completed to identify those most applicable to space robotics. These methods and metrics included techniques and tools associated with task performance, the quantification of human-robot interactions and communication, usability, human workload, and situation awareness. The need for more research in areas such as natural interfaces, compensations for loss of signal and poor video quality, psycho-physiological feedback, and common HRI testbeds were identified. The initial findings from these activities and planned future research are discussed.

Ezer, Neta↗

NASA NTRS2012

Human Missions to Near-Earth Asteroids: An Update on NASA's Current Status and Proposed Activities for Small Body Exploration

Introduction: Over the past several years, much attention has been focused on the human exploration of near-Earth asteroids (NEAs). Two independent NASA studies examined the feasibility of sending piloted missions to NEAs, and in 2009, the Augustine Commission identified NEAs as high profile destinations for human exploration missions beyond the Earth-Moon system as part of the Flexible Path. More recently the current U.S. presidential administration directed NASA to include NEAs as destinations for future human exploration with the goal of sending astronauts to a NEA in the mid to late 2020s. This directive became part of the official National Space Policy of the United States of America as of June 28, 2010. Dynamical Assessment: The current near-term NASA human spaceflight capability is in the process of being defined while the Multi-Purpose Crew Vehicle (MPCV) and Space Launch System (SLS) are still in development. Hence, those NEAs in more accessible heliocentric orbits relative to a minimal interplanetary exploration capability will be considered for the first missions. If total mission durations for the first voyages to NEAs are to be kept to less than one year, with minimal velocity changes, then NEA rendezvous missions ideally will take place within 0.1 AU of Earth (approx about 5 million km or 37 lunar distances). Human Exploration Considerations: These missions would be the first human expeditions to inter-planetary bodies beyond the Earth-Moon system and would prove useful for testing technologies required for human missions to Mars, Phobos and Deimos, and other Solar System destinations. Missions to NEAs would undoubtedly provide a great deal of technical and engineering data on spacecraft operations for future human space exploration while conducting detailed scientific investigations of these primitive objects. Current analyses of operational concepts suggest that stay times of 15 to 30 days may be possible at these destinations. In addition, the resulting scientific investigations would refine designs for future extraterrestrial In Situ Resource Utilization (ISRU), and assist in the development of hazard mitigation techniques for planetary defense. Conclusions: The scientific and hazard mitigation benefits, along with the programmatic and operational benefits of a human venture beyond the Earth-Moon system, make a piloted mission to a NEA using NASA's proposed human exploration systems a compelling endeavor

Abell, P. A.↗

NASA NTRS2012

Paramyxovirus Infection Mimics In Vivo Cellular Dynamics in Three-Demensional Human Bronchio-Epithelial Tissue-Like Assemblies

Respiratory syncytial virus and parainfluenza virus cause severe respiratory disease, especially in infants, children and the elderly. An in vitro model that accurately mimics infection of the human respiratory epithelium (HRE) would facilitate vaccine development greatly. Monolayer cultures traditionally used to study these viruses do not accurately and precisely differentiate the replication efficiencies of wild type and attenuated viruses. Therefore, we engineered novel three-dimensional (3D) tissue-like assemblies (TLAs) of human broncho-epithelial (HBE) cells to produce a more physiologically relevant in vitro model of the HRE. TLAs resemble HRE structurally and by expression of differentiated epithelial cell markers. Most significantly, wild type viruses exhibited a clear growth advantage over attenuated strains in TLAs unlike monolayer cultures. In addition, the TLAs responded to virus infection by secreting pro-inflammatory mediators similar to the respiratory epithelia of infected children. These characteristics make the TLA model a valuable platform technology to develop and evaluate live, attenuated respiratory virus vaccine candidates for human use. Respiratory virus diseases, the most frequent and least preventable of all infectious diseases, range in severity from the common cold to severe bronchiolitis and pneumonia . Two paramyxoviruses, respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3), are responsible for a majority of the most severe respiratory diseases of infants and young children. RSV causes 70% of all bronchiolitis cases and is a major cause of morbidity and mortality worldwide, especially in infants. PIV3 causes 10-15% of bronchiolitis and pneumonia during infancy, second only to RSV, and 40% of croup in infants To date, licensed vaccines are not available to prevent these respiratory diseases. At present, traditional monkey kidney (Vero and LLC-MK2) and human (HEp-2) tissue culture cells and small animal models (mouse, cotton rat, guinea pig, ferret, and hamster) fail to accurately imitate viral replication and human disease states (8). Lacking an authentic model has impeded the development and evaluation of live, attenuated vaccine candidates. Development of a physiologically relevant in vitro tissue culture model that reproduces characteristics of the HRE, the primary target of RSV and PIV3, would aid in predicting clinical attenuation and safety of vaccine candidates. Successful tissue engineering of a 3D human intestinal model using novel NASA technology inspired the development of a tri-culture 3D model for the HRE. Sequential layering of primary mesenchymal cells (comprised of normal human fibroblasts and endothelial cells) followed by BEAS-2B epithelial cells derived from human bronchi and tracheae were recapitulated on Cultisphere and/or cytodex3 microcarriers in cylindrical vessels that rotate horizontally creating an organized epithelial structure. Horizontal rotation randomizes the gravity vector modeling aspects of microgravity. Mesenchymal and epithelial cells grown under these conditions reproduce the structural organization, multi-cellular complexity, and differentiation state of the HRE. The opportunity to study respiratory viruses in a nasal epithelium model is invaluable because the most promising respiratory virus vaccine candidates are live attenuated viruses for intranasal administration. Here we characterize the interactions of respiratory viruses and epithelial cells grown under modeled microgravity in comparison to gravity-ladened monolayers. 3D HBE TLAs and traditional monolayers (2D) are infected at 35 C, the upper temperature of the upper HRE, to simulate in vivo infection conditions. Growth kinetics of wild type (wt) RSV and PIV3 viruses were compared in 2D and 3D cells to that of strains attenuated in humans or rhesus macaques. This novel 3D HBE model also offers an opportunity to study whether the epithelial cell function, especially in host defenses recapitulated by mimicking the structural organization of the HRE. In vivo, airway epithelial cells play a significant and dynamic role in host defense by blocking paracellular permeability and modulating airway function through cellular interactions or tight junctions. As regulators of the innate immune response, epithelial cells constitutively express cytokines, chemokines, and colony stimulating factors including RANTES, IL-8, IL-6, GM-CSF, and G-CSF for proactive host defense. In response to viral infection, epithelial cells induce potent immuno-modulatory and pro-inflammatory cytokines that recruit phagocytic and inflammatory cells to clear the virus and enhance protection. Although disease pathogenesis is classically attributed to the cytopathic effects of the pathogen, severe disease states associated with RSV and PIV3 are attributed to the inflammatory response, especially in infants. RSV is a potent inducer of cytokines and pro-inflammatory mediators in epithelial cells in vivo. A differentiated human epithelial model independent of the complete functional immune system will help elucidate the role of epithelial cells in respiratory disease. We reported here, virus and host cell interactions in 3D HBE TLAs are similar to that in vivo. Because the epithelial cell organization of the TLAs impacts not only the expression of airway epithelial characteristics, but also cellular communication, the TLAs represent a more physiologically relevant model of the HRE than BEAS-2B or other non-tumour monolayer models of respiratory disease. As a result, wild type respiratory viruses have a clear growth advantage over attenuated viruses in TLAs unlike traditional monolayers. In addition, the TLAs respond to wild type virus infection by secreting pro-inflammatory mediators characteristic of infected HRE. TLAs expressing microbial defense mechanisms provide an excellent model to study the interactions of respiratory pathogens with their host and to identify the innate immunity mediators. Therefore, 3D HBE TLAs offer advantages for the study of respiratory viruses and the development of viral vaccine candidates.

Deatly, Anne M.↗

NASA NTRS2013

Future Challenges in Managing Human Health and Performance Risks for Space Flight

The global economy forces many nations to consider their national investments and make difficult decisions regarding their investment in future exploration. To enable safe, reliable, and productive human space exploration, we must pool global resources to understand and mitigate human health & performance risks prior to embarking on human exploration of deep space destinations. Consensus on the largest risks to humans during exploration is required to develop an integrated approach to mitigating risks. International collaboration in human space flight research will focus research on characterizing the effects of spaceflight on humans and the development of countermeasures or systems. Sharing existing data internationally will facilitate high quality research and sufficient power to make sound recommendations. Efficient utilization of ISS and unique ground-based analog facilities allows greater progress. Finally, a means to share results of human research in time to influence decisions for follow-on research, system design, new countermeasures and medical practices should be developed. Although formidable barriers to overcome, International working groups are working to define the risks, establish international research opportunities, share data among partners, share flight hardware and unique analog facilities, and establish forums for timely exchange of results. Representatives from the ISS partnership research and medical communities developed a list of the top ten human health & performance risks and their impact on exploration missions. They also drafted a multilateral data sharing plan to establish guidelines and principles for sharing human spaceflight data. Other working groups are also developing methods to promote international research solicitations. Collaborative use of analog facilities and shared development of space flight research and medical hardware continues. Establishing a forum for exchange of results between researchers, aerospace physicians and program managers takes careful consideration of researcher concerns and decision maker needs. Active participation by researchers in the development of this forum is essential, and the benefit can be tremendous. The ability to rapidly respond to research results without compromising publication rights and intellectual property will facilitate timely reduction in human health and performance risks in support of international exploration missions.

Corbin, Barbara J.↗