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Novel brain-expressed noncoding RNA, HSTR1, identified at a human-specific variable number tandem repeat locus with a human accelerated region

Highlights: • A novel noncoding RNA gene HSTR1 is expressed in human brain and testis. • The evolutionary accelerated region showed enhanced promoter activity in human. • The variable number tandem repeat in HSTR1 is associated with its RNA stability. The evolutionary conserved genomic sequences that have acquired significantly increased number of nucleotide substitutions specifically in the human lineage, called human accelerated regions (HARs), have been identified as candidate genomic regions that have contributed to the evolution of human-specific traits. A number of HARs were indeed shown to have novel enhancer activity and be associated with human-specific brain development and with cognition and social behavior. It is therefore of great importance to investigate the details of genomic function of each HAR to understand the roles of HARs as critical contributors to the genetic basis of human evolution. In this study, we identified a previously unannotated brain-expressed noncoding RNA gene, HSTR1, at a human-specific tandem repeat locus. Notably, the 5′ flanking sequence of HSTR1 showed the signature of HARs and the dramatic human-specific enhancement of promoter activity, providing the evidence of positive selection to increase the expression level of HSTR1 during human evolution. We also revealed that the tandem repeat number in HSTR1 was highly variable among individual alleles and affected the stability of HSTR1 RNA, suggesting variation in the activity of HSTR1 between human individuals. Our work thus provides a novel candidate gene that potentially contributed to the evolution of the human brain. It may also underpin some of the variation between human brains.

60 APPLIED LIFE SCIENCES↗

E3SM‐GCAM: A Synchronously Coupled Human Component in the E3SM Earth System Model Enables Novel Human‐Earth Feedback Research

Abstract Modeling human‐environment feedbacks is critical for assessing the effectiveness of climate change mitigation and adaptation strategies under a changing climate. The Energy Exascale Earth System Model (E3SM) now includes a human component, with the Global Change Analysis Model (GCAM) at its core, that is synchronously coupled with the land and atmosphere components through the E3SM coupling software. Terrestrial productivity is passed from E3SM to GCAM to make climate‐responsive land use and CO 2 emission projections for the next 5‐year period, which are interpolated and passed to E3SM annually. Key variables affected by the incorporation of these feedbacks include land use/cover change, crop prices, terrestrial carbon, local surface temperature, and climate extremes. Regional differences are more pronounced than global differences because the effects are driven primarily by differences in land use. This novel system enables a new type of scenario development and provides a powerful modeling framework that facilitates the addition of other feedbacks between these models. This system has the potential to explore how human responses to climate change impacts in a variety of sectors, including heating/cooling energy demand, water management, and energy production, may alter emissions trajectories and Earth system changes. Plain Language Summary Earth system models help us understand how humans are changing the climate. Currently, these models do not include human systems, so predetermined greenhouse gas, aerosol, and land use change data are input to these models. These data do not reflect human responses to changes projected by Earth system models. We have added a human component to an Earth system model to represent human responses to environmental change and calculate corresponding greenhouse gas and land use change data instead of using predetermined data. Including this human component changes projections of land use, land carbon storage, and regional climate. Key Points We have incorporated a novel, advanceable human component in an Earth system model to simulate human‐Earth feedbacks Including terrestrial productivity feedbacks from the Earth to the human systems affects land change, crop prices, carbon, and climate Regional effects of including terrestrial productivity feedbacks are greater than global effects because land change is the main driver

E3SM↗

Human Microdosing with Carcinogenic Polycyclic Aromatic Hydrocarbons: In Vivo Pharmacokinetics of Dibenzo[ def,p ]chrysene and Metabolites by UPLC Accelerator Mass Spectrometry

Metabolism is a key health risk factor following exposures to pro-carcinogenic polycyclic aromatic hydrocarbons (PAHs) such as dibenzo[def,p]chrysene (DBC), an IARC classified 2A probable human carcinogen. Human exposure to PAHs occurs primarily from the diet in non-smokers. However, little data is available on the metabolism and pharmacokinetics in humans of high molecular weight PAHs (≥4 aromatic rings), including DBC. We previously determined the pharmacokinetics of DBC in human volunteers orally administered a micro-dose (29 ng; 5 nCi) of [14C]-DBC by accelerator mass spectrometry (AMS) analysis of total [14C] in plasma and urine. In the current study, we utilized a novel “moving wire” interface between ultra-performance liquid chromatography (UPLC) and AMS to detect and quantify parent DBC and its major metabolites. The major [14C] product identified in plasma was unmetabolized [14C]-DBC itself, (Cmax= 18.5 ± 15.9 fg/mL, Tmax= 2.1 ± 1.0 h), whereas the major metabolite was identified as [14C]-(+/-)-DBC-11,12-diol (Cmax= 2.5 ± 1.3 fg/mL, Tmax= 1.8 h). Several minor species of [14C]-DBC metabolites were also detected for which no reference standards were available. Free and conjugated metabolites were detected in urine with [14C]-(+/-)-DBC-11,12,13,14-tetraol isomers identified as the major metabolites, 56.3% of which were conjugated (Cmax= 35.8 ± 23.0 pg/pool, Tmax= 6-12 h pool). [14C]-DBC-11,12-diol, of which 97.5% was conjugated, was also identified in urine (Cmax= 29.4 ± 11.6 pg/pool, Tmax= 6-12 h pool). Parent [14C]-DBC was not detected in urine. This is the first dataset to assess metabolite profiles and associated pharmacokinetics of a carcinogenic PAH in human volunteers at an environmentally relevant dose, providing the data necessary for translation of high dose animal models to humans for translation of environmental health risk assessment.

Madeen, Erin P.↗

Human Factors, Habitability and Environmental Health and the Human Integration Design Handbook

For decades, Space Life Sciences and NASA as an Agency have considered NASA-STD-3000, Man-Systems Integration Standards, a significant contribution to human spaceflight programs and to human-systems integration in general. The document has been referenced in numerous design standards both within NASA and by organizations throughout the world. With research program and project results being realized, advances in technology and new information in a variety of topic areas now available, the time arrived to update this extensive suite of requirements and design information. During the past several years, a multi-NASA center effort has been underway to write the update to NASA-STD-3000 with standards and design guidance that would be applicable to all future human spaceflight programs. NASA-STD-3001 - Volumes 1 and 2 - and the Human Integration Design Handbook (HIDH) were created. Volume 1, Crew Health, establishes NASA s spaceflight crew health standards for the pre-flight, in-flight, and post-flight phases of human spaceflight. Volume 2, Human Factors, Habitability and Environmental Health, focuses on the requirements of human-system integration and how the human crew interacts with other systems, and how the human and the system function together to accomplish the tasks for mission success. The HIDH is a compendium of human spaceflight history and knowledge, and provides useful background information and research findings. And as the HIDH is a stand-alone companion to the Standards, the maintenance of the document has been streamlined. This unique and flexible approach ensures that the content is current and addresses the fundamental advances of human performance and human capabilities and constraints research. Current work focuses on the development of new sections of Volume 2 and collecting updates to the HIDH. The new sections in development expand the scope of the standard and address mission operations and support operations. This effort is again collaboration with representatives from the Johnson Space Center Missions Operations and Space Life Sciences Directorates and the Engineering Directorate from Kennedy Space Center as well as discipline experts from across the Agency.

Houbec, Keith↗

Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

bacillus anthracis↗

Characteristics of human-climate feedbacks differ at different radiative forcing levels

The human and Earth systems are intricately linked: climate influences agricultural production, renewable energy potential, and water availability, for example, while anthropogenic emissions from industry and land use change alter temperature and precipitation. Such feedbacks have the potential to significantly alter future climate change. These feedbacks may also exert significant changes on 21st-century energy, agriculture, land use and carbon cycle projections, but little is known about their possible magnitudes, or about regional and sector dynamics under different forcing scenarios. Here we use an integrated Earth System Model (ESM) featuring bidirectional information exchange between an economically-oriented integrated assessment model and the ESM to examine how human-natural feedbacks operate under high and medium radiative forcing (RF) scenarios. Specifically, we examine the effect of changing land productivity on human systems, and the effect of changing land use/land cover and CO2 emissions on the Earth system. We find that the effect of coupling differs across radiative forcing levels and across regions, due to differences in the climate signal, human responses to those signals, and regional characteristics. In particular, we find reductions in cropland area due to feedbacks in both the medium and high RF scenarios. In the medium RF scenario, these reductions result in increased area for bioenergy and afforestation and reduced energy system CO2 emissions, as the carbon price in this scenario incentivizes low carbon energy sources and terrestrial carbon storage; these incentives are absent in the high RF scenario. These differences are key to understanding the possible future evolution pathways of the integrated Earth system in response to 21st century climate change. Additional models and hypothesis testing are needed to determine exactly when and how bidirectional feedbacks between human and Earth systems should be considered in future assessments.

Calvin, Katherine V.↗

In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes

Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase I metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14 µM), and higher intrinsic clearance at lower substrate concentrations (<0.07 µM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.

59 BASIC BIOLOGICAL SCIENCES↗

Investigating the Partitioning of Inorganic Elements Consumed by Humans between the Various Fractions of Human Wastes: An Alternative Approach

The elemental composition of food consumed by astronauts is well defined. The major elements carbon, hydrogen, oxygen, nitrogen and sulfur are taken up in large amounts and these are often associated with the organic fraction (carbohydrates, proteins, fats etc) of human tissue. On the other hand, a number of the elements are located in the extracellular fluids and can be accounted for in the liquid and solid waste fraction of humans. These elements fall into three major categories - cationic macroelements (e.g. Ca, K, Na, Mg and Si), anionic macroelements (e.g. P, S and Cl and 17 essential microelements, (e.g. Fe, Mn, Cr, Co, Cu, Zn, Se and Sr). When provided in the recommended concentrations to an adult healthy human, these elements should not normally accumulate in humans and will eventually be excreted in the different human wastes. Knowledge of the partitioning of these elements between the different human waste fractions is important in understanding (a) developing waste separation technologies, (b) decision-making on how these elements can be recovered for reuse in space habitats, and (c) to developing the processors for waste management. Though considerable literature exists on these elements, there is a lack of understanding and often conflicting data. Two major reasons for these problems include the lack of controlled experimental protocols and the inherently large variations between human subjects (Parker and Gallagher, 1988). We have used the existing knowledge of human nutrition and waste from the available literature and NASA documentation to build towards a consensus to typify and chemically characterize the various human wastes. It is our belief, that this could be a building block towards integrating a human life support and waste processing in a closed system.

Wignarajah, Kanapathipillai↗

Partitioning of Inorganic Elements Consumed by Humans Between the Various Fractions of Human Wastes: A Review and Analysis of Existing Literature

The nutritional requirements of humans and astronauts are well defined and show consistency, but the same cannot be said of human wastes. Nutrients taken up by humans can be considered to fall into two major categories - organic and inorganic fractions. Carbon, hydrogen, oxygen, nitrogen and sulfur are elements that are associated with the organic fraction. These elements are taken up in large amounts by humans and when metabolized released in wastes often in gaseous forms or as water. On the other hand, a large number of the elements are simply exchanged and can be accounted for in the liquid and solid wastes of humans. These elements fall into three major categories - cationic macroelements (e.g. Ca, K, Na, Mg and Si), anionic macroelements (e.g P, S and Cl), 17 essential microelements, (e.g. Fe, Mn, Cr, Co, Cu, Zn, Se and Sr). When provided in the recommended concentrations to an adult human, these elements should not normally accumulate in humans, but will be excreted in the different human wastes. Knowledge of the partitioning of these elements between the different human waste fractions is fundamental to understanding (a) how these elements can be recovered for reuse in space habitats, and (b) to developing the processors for waste management. The current literature is exhaustive but sometimes also conflicting. We have used the existing knowledge of nutrition and waste from medical literature and NASA documentation to develop a consensus to typify and chemically characterize the various human wastes. The partitioning of these elements has been developed into a functional model.

Wignarajah, K.↗

Human Factors Interface with Systems Engineering for NASA Human Spaceflights

This paper summarizes the past and present successes of the Habitability and Human Factors Branch (HHFB) at NASA Johnson Space Center s Space Life Sciences Directorate (SLSD) in including the Human-As-A-System (HAAS) model in many NASA programs and what steps to be taken to integrate the Human-Centered Design Philosophy (HCDP) into NASA s Systems Engineering (SE) process. The HAAS model stresses systems are ultimately designed for the humans; the humans should therefore be considered as a system within the systems. Therefore, the model places strong emphasis on human factors engineering. Since 1987, the HHFB has been engaging with many major NASA programs with much success. The HHFB helped create the NASA Standard 3000 (a human factors engineering practice guide) and the Human Systems Integration Requirements document. These efforts resulted in the HAAS model being included in many NASA programs. As an example, the HAAS model has been successfully introduced into the programmatic and systems engineering structures of the International Space Station Program (ISSP). Success in the ISSP caused other NASA programs to recognize the importance of the HAAS concept. Also due to this success, the HHFB helped update NASA s Systems Engineering Handbook in December 2007 to include HAAS as a recommended practice. Nonetheless, the HAAS model has yet to become an integral part of the NASA SE process. Besides continuing in integrating HAAS into current and future NASA programs, the HHFB will investigate incorporating the Human-Centered Design Philosophy (HCDP) into the NASA SE Handbook. The HCDP goes further than the HAAS model by emphasizing a holistic and iterative human-centered systems design concept.

Wong, Douglas T.↗

Human Thermal Model Evaluation Using the JSC Human Thermal Database

The human thermal database developed at the Johnson Space Center (JSC) is used to evaluate a set of widely used human thermal models. This database will facilitate a more accurate evaluation of human thermoregulatory response using in a variety of situations, including those situations that might otherwise prove too dangerous for actual testing--such as extreme hot or cold splashdown conditions. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models. Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality.

Cognata, T.↗

NASA's Human Research Program: Evolving Collaborations to Enable the Future of Human Spaceflight

Since its formation in 2007, the NASA Human Research Program’s (HRP) mission has been to protect the health and performance of astronauts as they explore beyond low Earth orbit. The HRP helps enable exploration spaceflight through a focused program of research that leads to the development and delivery of solutions to protect human health and performance during and after these missions. This research is conducted primarily in ground analogs of the spaceflight environment and on the International Space Station (ISS). Over the last 3 years, NASA has undergone transformative changes with the flight of Artemis I, the formation of the Commercial Low Earth Orbit Destinations Program, commercial flights to the ISS, and collaboration with new international partners participating in human spaceflight. The HRP has embraced these new opportunities and is collaborating on all these fronts to collect biomedical research data. Artemis I marked the arrival of NASA’s new human spaceflight exploration missions. NASA established the Moon to Mars Program Office to design a roadmap for the exploration of the lunar surface and the journey beyond to Mars. The HRP has a critical role in conducting research and delivering technologies that will lead to solutions that protect human health and performance, and is working closely with the Moon to Mars Office to ensure these deliverables are ready in time to support their strategy. The HRP is also developing the partnership strategies required to support these deliverables. Commercial space flights, both free flyer and suborbital missions and private astronaut missions to the ISS, are providing broader opportunities and more subjects to characterize spaceflight-induced changes to the human system and to test countermeasures. To better use these opportunities to achieve its mission, the HRP has been working to understand the commercial spaceflight companies’ needs and then partnering with them on aspects of mutual interest. In addition, the HRP continues to engage in long-standing relationships with its international partners through the International Space Life Sciences Working Group and other joint international groups. The HRP is interested in sharing its knowledge and collaborating on projects of mutual interest with new countries that are developing capabilities for human spaceflight. The next 10 years will shape how humanity partners on exploration missions to Mars, and the HRP is committed to enabling and developing collaborative strategies with commercial and international partners to keep humans safe and productive as they explore longer and further into space.

Human research↗

Recent trends in digital human modeling and the concurrent issues that face human modeling approach

Tremendous strides have been made in the recent years to digitally represent human beings in computer simulation models ranging from assembly plant maintenance operations to occupants getting in and out of vehicles to action movie scenarios. While some of these tools are being actively pursued by the engineering communities, there is still a lot of work that remains to be done for the newly planned planetary exploration missions. For example, certain unique and several common challenges are seen in developing computer generated suited human models for designing the next generation space vehicle. The purpose of this presentation is to discuss NASA s potential needs for better human models and to show also many of the inherent yet not too obvious pitfalls that still are left unresolved in this new arena of digital human modeling. As part of NASA s Habitability and Human Factors Branch, the Anthropometry and Biomechanics Facility has been engaged in studying the various facets of computer generated human physical performance models; for instance, it has been engaged in utilizing three-dimensional laser scan data along with three dimensional video based motion and reach data to gather suited anthropometric and shape and size information that are not available yet in the form of computer mannequins. Our goal is to bring in new approaches to deal with heavily clothed humans (such as, suited astronauts) and to overcome the current limitations of wrongly identifying humans (either real or virtual) as univariate percentiles. We are looking at whole-body posture based anthropometric models as a means to identify humans of significantly different shapes and sizes to arrive at mathematically sound computer models for analytical purposes.

Rajulu, Sudhakar↗

An International Strategy for Human Exploration of the Moon: The International Space Exploration Coordination Group (ISECG) Reference Architecture for Human Lunar Exploration

The International Space Exploration Coordination Group (ISECG) was established in response to The Global Exploration Strategy: The Framework for Coordination developed by fourteen space agencies and released in May 2007. Several ISECG participating space agencies have been studying concepts for human exploration of the moon that allow individual and collective goals and objectives to be met. This 18 month study activity culminated with the development of the ISECG Reference Architecture for Human Lunar Exploration. The reference architecture is a series of elements delivered over time in a flexible and evolvable campaign. This paper will describe the reference architecture and how it will inform near-term and long-term programmatic planning within interested agencies. The reference architecture is intended to serve as a global point of departure conceptual architecture that enables individual agency investments in technology development and demonstration, International Space Station research and technology demonstration, terrestrial analog studies, and robotic precursor missions to contribute towards the eventual implementation of a human lunar exploration scenario which reflects the concepts and priorities established to date. It also serves to create opportunities for partnerships that will support evolution of this concept and its eventual realization. The ISECG Reference Architecture for Human Lunar Exploration (commonly referred to as the lunar gPoD) reflects the agency commitments to finding an effective balance between conducting important scientific investigations of and from the moon, as well as demonstrating and mastering the technologies and capabilities to send humans farther into the Solar System. The lunar gPoD begins with a robust robotic precursor phase that demonstrates technologies and capabilities considered important for the success of the campaign. Robotic missions will inform the human missions and buy down risks. Human exploration will start with a thorough scientific investigation of the polar region while allowing the ability to demonstrate and validate the systems needed to take humans on more ambitious lunar exploration excursions. The ISECG Reference Architecture for Human Lunar Exploration serves as a model for future cooperation and is documented in a summary report and a comprehensive document that also describes the collaborative international process that led to its development. ISECG plans to continue with architecture studies such as this to examine an open transportation architecture and other destinations, with expanded participation from ISECG agencies, as it works to inform international partnerships and advance the Global Exploration Strategy.

Laurini, Kathleen C.↗

Human Thermal Model Evaluation Using the JSC Human Thermal Database

Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested space environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality. The human thermal database developed at the Johnson Space Center (JSC) is intended to evaluate a set of widely used human thermal models. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models.

Bue, Grant↗

NASA-STD-3001, Space Flight Human-System Standard and the Human Integration Design Handbook

NASA-STD-3001 Space Flight Human-System Standard Volume 1, Crew Health, Volume 2, Human Factors, Habitability and Environmental Health, and the Human Integration Design Handbook (HIDH) have replaced the Man-Systems Integration Standards (MSIS), NASA-STD-3000. For decades, NASA-STD-3000 was a significant contribution to human spaceflight programs and to human-systems integration. However, with research program and project results being realized, advances in technology, and the availability of new information in a variety of topic areas, the time had arrived to update this extensive suite of standards and design information. NASA-STD-3001, Volume 2 contains the Agency level standards from the human and environmental factors disciplines that ensure human spaceflight operations are performed safely, efficiently, and effectively. The HIDH is organized in the same sequence and serves as the companion document to NASA-STD-3001, Volume 2, providing a compendium of human spaceflight history and knowledge. The HIDH is intended to aid interpretation of NASA-STD-3001, Volume 2 standards and to provide guidance for requirement writers and vehicle and habitat designers. Keywords Human Factors, Standards, Environmental Factors, NASA

Whitmore, Mihriban↗

And the Human Saves the Day or Maybe They Ruin It, The Importance of Humans in the Loop

Flying a mission in space requires a massive commitment of resources, and without the talent and commitment of the people involved in this effort we would never leave the atmosphere of Earth as safely as we have. When we use the phrase "humans in the loop", it could apply to almost any endeavor since everything starts with humans developing a concept, completing the design process, building or implementing a product and using the product to achieve a goal or purpose. Narrowing the focus to spaceflight, there are a variety of individuals involved throughout the preparations for flight and the flight itself. All of the humans involved add value and support for program success. The paper discusses the concepts of human involvement in technological programs, how a Probabilistic Risk Assessment (PRA) accounts for the human in the loop for potential missions using a technique called Human Reliability Analysis (HRA) and the tradeoffs between having a human in the loop or not. Human actions can increase or decrease the overall risk via initiating events or mitigating them, thus removing the human from the loop doesn't always lowers the risk.

DeMott, Diana L.↗

Implementation of Human System Integration Workshop at NASA for Human Spaceflight

The human is a key element in the complex system of systems underlying space exploration missions. As a critical system, its operating bands and requirements need to be characterized and integrated with other systems. Optimal integration of the human system with hardware and software elements has an impact on multiple aspects of mission execution, including human health and performance, risk mitigation, effective design and functionality, enhanced safety, and reduced lifecycle costs. The field of Human Systems Integration (HSI) represents an interdisciplinary and comprehensive cross-cutting approach encompassing technical and management processes for integrating human as a system consideration and objective within and across all other system components and multiple domains. In addition to human activities, HSI covers training, operations and support dimensions. Moreover, HSI is an essential enabler to systems engineering practice, emphasizing human system aspects toward optimizing fully integrated system of systems performance while systematically infusing the needs of all users during the earliest stages of development. Consistent with the National Space Exploration Campaign, NASA is developing the Gateway, a lunar orbiting platform that will serve as astronaut habitat, support transit to deep space, validate new technologies and systems, and function as a science laboratory and communications hub, among other uses. It is an essential element of a phase that will extend human exploration into deep space through evolvable infrastructure and advanced technology, supporting assembly and logistics of other exploration architecture elements. In an effort to explore the current status and forward plan of HSI implementation in the mission (system of systems) lifecycle, the HSI Employee Resource Group conducted an HSI workshop using the Gateway Program as a case study. It revealed how different organizations at the Johnson Space Center incorporate HSI in their processes in preparation for the development and operation of the Gateway. The workshop focused on HSI methodology for implementation of the six NASA HSI domains: Human Factors Engineering, Operations Resources, Habitability and Environment, Maintainability and Supportability, Safety, and Training. Results from the workshop are reported on this paper, as well as some historical background of HSI at NASA, and the success in using an Employee Resource Group to promote technical knowledge. The authors hope that this information can be used to disseminate best practices for translational applications to other space exploration systems.

Silva-Martinez, Jackelynne↗