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Upregulation of miR-199 attenuates TNF-α-induced Human nucleus pulposus cell apoptosis by downregulating MAP3K5

MicroRNA-199 has been reported to play a potential role in the apoptosis of Human nucleus pulposus cells. However, the effect of miR-199 in regulating Human nucleus pulposus cell injury induced by TNF-α has not been previously illustrated. This study searched to probe the effect and the molecular mechanism of miR-199 on Human nucleus pulposus cell injury induced by TNF-α. Using the TNF-α model of Human nucleus pulposus cell in vitro, we found that miR-199 was extremely decreased in Human nucleus pulposus cells after TNF-α treatment. Knockdown the expression of miR-199 by recombinant adeno-associated viral vector infection markedly promoted the apoptosis of Human nucleus pulposus cells induced by TNF-α treatment, whereas miR-199 overexpression significantly decreased Human nucleus pulposus cell apoptosis. Both Dual-luciferase reporter and western blot assay proved that MAP3K5 was a direct target gene of miR-199, and miR-199 inhibited the expression of MAP3K5 via binding to its 3′-UTR. Furthermore, we proved that overexpression of miR-199 could inhibit the expression of MAP3K5 at the transcription and translation levels, whereas the inhibition of miR-199 could upregulate the expression of MAP3K5. Moreover, MAP3K5 was highly expressed in TNF-α treated Human nucleus pulposus cells and the apoptosis rate induced by TNF-α was associated with the increase in MAP3K5 expression. Importantly, knockdown the expression of MAP3K5 apparently abrogated the inhibitory effect of miR-199 mimics on TNF-α induced Human nucleus pulposus cell apoptosis. In conclusion, these results indicate that upregulation of miR-199 could inhibit Human nucleus pulposus cells injury through downregulation of MAP3K5 expression, providing an important molecular target mechanism for Human nucleus pulposus cells injury.

60 APPLIED LIFE SCIENCES↗

Integrated Human-Robotic Missions to the Moon and Mars: Mission Operations Design Implications

For most of the history of space exploration, human and robotic programs have been independent, and have responded to distinct requirements. The NASA Vision for Space Exploration calls for the return of humans to the Moon, and the eventual human exploration of Mars; the complexity of this range of missions will require an unprecedented use of automation and robotics in support of human crews. The challenges of human Mars missions, including roundtrip communications time delays of 6 to 40 minutes, interplanetary transit times of many months, and the need to manage lifecycle costs, will require the evolution of a new mission operations paradigm far less dependent on real-time monitoring and response by an Earthbound operations team. Robotic systems and automation will augment human capability, increase human safety by providing means to perform many tasks without requiring immediate human presence, and enable the transfer of traditional mission control tasks from the ground to crews. Developing and validating the new paradigm and its associated infrastructure may place requirements on operations design for nearer-term lunar missions. The authors, representing both the human and robotic mission operations communities, assess human lunar and Mars mission challenges, and consider how human-robot operations may be integrated to enable efficient joint operations, with the eventual emergence of a unified exploration operations culture.

human robotic missions↗

Identifying human failure events (HFEs) for external hazard probabilistic risk assessment

In recent years, several advancements in nuclear power plant (NPP) probabilistic risk assessment (PRA) have been driven by increased understanding of external hazards, plant response, and uncertainties. However, major sources of uncertainty associated with external hazard PRA remain. One important source is how risk-significant human actions that are carried out to enable plant response and recovery from natural hazards cause the close coupling of physical impacts on plants and overall plant risk during these hazard events. This makes human reliability and human-plant interactions important elements to consider in resolving PRA gaps in external hazards. One of the challenges in considering human response in external hazard probabilistic risk assessment (XHPRA) is that most existing human reliability analysis (HRA) models were not developed for assessing actions outside the control room (termed ex-control room actions) and hazard response. To support this new scope, HRA models will need to be developed or modified to support identification of human activities, causal factors, and uncertainties inherent in external hazard response, thereby providing insights regarding event timing and physical event conditions as they relate to human performance. In this study, there are two main objectives: (1) evaluate the applicability of an existing cognitive-based HRA method, Phoenix, to ex-control room actions, and (2) identify sources of uncertainty to be characterized or reduced in order to make this method suitable for XHPRA. The first step of such work is performed by assessing the suitability of existing HRA methods to support identifying human failure events (HFEs) for human response to flooding hazards. These HFEs are human actions or inactions that are involved in human responses to flooding hazards and could contribute to the loss of a critical function for the plant in the scenario being examined. Here, in this work, decomposition analyses using the cognitive-based Phoenix HRA model are used to identify HFEs. The Phoenix method was found to be suitable for analyzing ex-control room actions as well as identifying specific HFEs and underlying crew failure modes (CFMs). However, the method's suitability for use in ex-control room actions would benefit from expanding the available CFMs to accommodate a larger variety of physical and communication tasks.

42 ENGINEERING↗

Estimation of tetrabromobisphenol A (TBBPA) percutaneous uptake in humans using the parallelogram method

Tetrabromobisphenol A (TBBPA) is currently the world's highest production volume brominated flame retardant. Humans are frequently exposed to TBBPA by the dermal route. In the present study, a parallelogram approach was used to make predictions of internal dose in exposed humans. Human and rat skin samples received 100 nmol of TBBPA/cm{sup 2} skin and absorption and penetrance were determined using a flow-through in vitro system. TBBPA-derived [{sup 14}C]-radioactivity was determined at 6 h intervals in the media and at 24 h post-dosing in the skin. The human skin and media contained an average of 3.4% and 0.2% of the total dose at the terminal time point, respectively, while the rat skin and media contained 9.3% and 3.5%, respectively. In the intact rat, 14% of a dermally-administered dose of ~ 100 nmol/cm{sup 2} remained in the skin at the dosing site, with an additional 8% reaching systemic circulation by 24 h post-dosing. Relative absorption and penetrance were less (10% total) at 24 h following dermal administration of a ten-fold higher dose (~ 1000 nmol/cm{sup 2}) to rats. However, by 72 h, 70% of this dose was either absorbed into the dosing-site skin or had reached systemic circulation. It is clear from these results that TBBPA can be absorbed by the skin and dermal contact with TBBPA may represent a small but important route of exposure. Together, these in vitro data in human and rat skin and in vivo data from rats may be used to predict TBBPA absorption in humans following dermal exposure. Based on this parallelogram calculation, up to 6% of dermally applied TBBPA may be bioavailable to humans exposed to TBBPA. - Highlights: • Tetrabromobisphenol A is the brominated flame retardant with highest global production volumes. • Humans are frequently exposed to TBBPA by the dermal route, especially via contaminated dust. • Human and rat skin data were integrated using a parallelogram method to predict human absorption. • TBBPA was dermally absorbed and skin contact may represent a small but important route of exposure. • Up to 6% of dermally applied TBBPA may be bioavailable to humans exposed to TBBPA.

60 APPLIED LIFE SCIENCES↗

Estimation of human percutaneous bioavailability for two novel brominated flame retardants, 2-ethylhexyl 2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl) tetrabromophthalate (BEH-TEBP)

2-Ethylhexyl-2,3,4,5-tetrabromobenzoate (EH-TBB) and bis(2-ethylhexyl)tetrabromophthalate (BEH-TEBP) are novel brominated flame retardants used in consumer products. A parallelogram approach was used to predict human dermal absorption and flux for EH-TBB and BEH-TEBP. [{sup 14}C]-EH-TBB or [{sup 14}C]-BEH-TEBP was applied to human or rat skin at 100 nmol/cm{sup 2} using a flow-through system. Intact rats received analogous dermal doses. Treated skin was washed and tape-stripped to remove “unabsorbed” [{sup 14}C]-radioactivity after continuous exposure (24 h). “Absorbed” was quantified using dermally retained [{sup 14}C]-radioactivity; “penetrated” was calculated based on [{sup 14}C]-radioactivity in media (in vitro) or excreta + tissues (in vivo). Human skin absorbed EH-TBB (24 ± 1%) while 0.2 ± 0.1% penetrated skin. Rat skin absorbed more (51 ± 10%) and was more permeable (2 ± 0.5%) to EH-TBB in vitro; maximal EH-TBB flux was 11 ± 7 and 102 ± 24 pmol-eq/cm{sup 2}/h for human and rat skin, respectively. In vivo, 27 ± 5% was absorbed and 13% reached systemic circulation after 24 h (maximum flux was 464 ± 65 pmol-eq/cm{sup 2}/h). BEH-TEBP in vitro penetrance was minimal (< 0.01%) for rat or human skin. BEH-TEBP absorption was 12 ± 11% for human skin and 41 ± 3% for rat skin. In vivo, total absorption was 27 ± 9%; 1.2% reached systemic circulation. In vitro maximal BEH-TEBP flux was 0.3 ± 0.2 and 1 ± 0.3 pmol-eq/cm{sup 2}/h for human and rat skin; in vivo maximum flux for rat skin was 16 ± 7 pmol-eq/cm{sup 2}/h. EH-TBB was metabolized in rat and human skin to tetrabromobenzoic acid. BEH-TEBP-derived [{sup 14}C]-radioactivity in the perfusion media could not be characterized. < 1% of the dose of EH-TBB and BEH-TEHP is estimated to reach the systemic circulation following human dermal exposure under the conditions tested. Chemical compounds studied in this article: 2-Ethylhexyl 2,3,4,5-tetrabromobenzoate (PubChem CID: 71316600; CAS No. 183658-27-7 FW: 549.92 g/mol logP{sub est}: 7.73–8.75 (12)) Abdallah et al., 2015a. Other published abbreviations for 2-ethylhexyl-2,3,4,5-tetrabromobenzoate are TBB EHTeBB or EHTBB Abdallah and Harrad, 2011. bis(2-ethylhexyl) tetrabromophthalate (PubChem CID: 117291; CAS No. 26040-51-7 FW: 706.14 g/mol logP{sub est}: 9.48-11.95 (12)). Other published abbreviations for bis(2-ethylhexyl)tetrabromophthalate are TeBrDEPH TBPH or BEHTBP. - Highlights: • Human skin maximal flux was 11 ± 7 (EH-TBB) & 0.3 ± 0.2 (BEH-TEBP) pmol-eq/cm{sup 2}/h. • Predicted systemic bioavailability was < 1% for either chemical after 24 h. • Skin retained EH-TBB & BEH-TEBP after 24 h dermal exposure. • EH-TBB was hydrolyzed to tetrabromobenzoic acid; BEH-TEBP was not metabolized. • Skin contact is an important route of human exposure to EH-TBB & BEH-TEBP.

60 APPLIED LIFE SCIENCES↗

Swine acute diarrhea syndrome coronavirus replication in primary human cells reveals potential susceptibility to infection

Zoonotic coronaviruses represent an ongoing threat, yet the myriads of circulating animal viruses complicate the identification of higher-risk isolates that threaten human health. Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered, highly pathogenic virus that likely evolved from closely related HKU2 bat coronaviruses, circulating in Rhinolophus spp. bats in China and elsewhere. As coronaviruses cause severe economic losses in the pork industry and swine are key intermediate hosts of human disease outbreaks, we synthetically resurrected a recombinant virus (rSADS-CoV) as well as a derivative encoding tomato red fluorescent protein (tRFP) in place of ORF3. rSADS-CoV replicated efficiently in a variety of continuous animal and primate cell lines, including human liver and rectal carcinoma cell lines. Of concern, rSADS-CoV also replicated efficiently in several different primary human lung cell types, as well as primary human intestinal cells. rSADS-CoV did not use human coronavirus ACE-2, DPP4, or CD13 receptors for docking and entry. Contemporary human donor sera neutralized the group I human coronavirus NL63, but not rSADS-CoV, suggesting limited human group I coronavirus cross protective herd immunity. Importantly, remdesivir, a broad-spectrum nucleoside analog that is effective against other group 1 and 2 coronaviruses, efficiently blocked rSADS-CoV replication in vitro. rSADS-CoV demonstrated little, if any, replicative capacity in either immune-competent or immunodeficient mice, indicating a critical need for improved animal models. Efficient growth in primary human lung and intestinal cells implicate SADS-CoV as a potential higher-risk emerging coronavirus pathogen that could negatively impact the global economy and human health.

59 BASIC BIOLOGICAL SCIENCES↗

“One Table to Rule Them All”: How a Single Table can Enable Extensive Insights, Analytics and Assessment on Human Mobility Data

While much research has been conducted in Human Mobility Science, most studies on the analytics/insights part generally focus on one of the following: processing and analytics on human stop-trip behavior, design of individual mobility metrics (often in silos), calculation and characterization of only a handful (typically 5-6) of human mobility metrics on geospatial-temporal human mobility data of interest. Although human mobility research offers a vast and diverse array of available metrics, most individual studies typically compute only a small subset of five or six metrics at a time when analyzing trajectory datasets of human mobility across different areas of interest. This paper is motivated by the critical need to repeatedly compute an extensive array of human mobility metrics across several trajectory datasets and perform individual metric-level benchmarking to establish a new, standardized Test and Evaluation (T&E) suite for the field of Human Mobility Science. We first present our findings on the minimal yet sufficient pre-processing required to reliably and efficiently compute a wide range of human mobility metrics. The key findings are specifically related to the proposed Composite Stop Locations table, which serves as a core pre-processing data layer. Subsequently, we present a case study demonstrating how the Composite Stop Locations table facilitates computation of at least 14 distinct human mobility metrics (unlike 5-6 different set of metrics used for studies in the literature) using the popular and open-source OpenPFLOW dataset. Finally, we have also presented an example of our benchmarking methodology to evaluate the quality and performance of the trajectory dataset of interest, assessed across multiple human mobility metrics.

De, Debraj [ORNL] (ORCID:0000000233630020)↗

Robotic and Human-Tended Collaborative Drilling Automation for Subsurface Exploration

Future in-situ lunar/martian resource utilization and characterization, as well as the scientific search for life on Mars, will require access to the subsurface and hence drilling. Drilling on Earth is hard - an art form more than an engineering discipline. Human operators listen and feel drill string vibrations coming from kilometers underground. Abundant mass and energy make it possible for terrestrial drilling to employ brute-force approaches to failure recovery and system performance issues. Space drilling will require intelligent and autonomous systems for robotic exploration and to support human exploration. Eventual in-situ resource utilization will require deep drilling with probable human-tended operation of large-bore drills, but initial lunar subsurface exploration and near-term ISRU will be accomplished with lightweight, rover-deployable or standalone drills capable of penetrating a few tens of meters in depth. These lightweight exploration drills have a direct counterpart in terrestrial prospecting and ore-body location, and will be designed to operate either human-tended or automated. NASA and industry now are acquiring experience in developing and building low-mass automated planetary prototype drills to design and build a pre-flight lunar prototype targeted for 2011-12 flight opportunities. A successful system will include development of drilling hardware, and automated control software to operate it safely and effectively. This includes control of the drilling hardware, state estimation of both the hardware and the lithography being drilled and state of the hole, and potentially planning and scheduling software suitable for uncertain situations such as drilling. Given that Humans on the Moon or Mars are unlikely to be able to spend protracted EVA periods at a drill site, both human-tended and robotic access to planetary subsurfaces will require some degree of standalone, autonomous drilling capability. Human-robotic coordination will be important, either between a robotic drill and humans on Earth, or a human-tended drill and its visiting crew. The Mars Analog Rio Tinto Experiment (MARTE) is a current project that studies and simulates the remote science operations between an automated drill in Spain and a distant, distributed human science team. The Drilling Automation for Mars Exploration (DAME) project, by contrast: is developing and testing standalone automation at a lunar/martian impact crater analog site in Arctic Canada. The drill hardware in both projects is a hardened, evolved version of the Advanced Deep Drill (ADD) developed by Honeybee Robotics for the Mars Subsurface Program. The current ADD is capable of 20m, and the DAME project is developing diagnostic and executive software for hands-off surface operations of the evolved version of this drill. The current drill automation architecture being developed by NASA and tested in 2004-06 at analog sites in the Arctic and Spain will add downhole diagnosis of different strata, bit wear detection, and dynamic replanning capabilities when unexpected failures or drilling conditions are discovered in conjunction with simulated mission operations and remote science planning. The most important determinant of future 1unar and martian drilling automation and staffing requirements will be the actual performance of automated prototype drilling hardware systems in field trials in simulated mission operations. It is difficult to accurately predict the level of automation and human interaction that will be needed for a lunar-deployed drill without first having extensive experience with the robotic control of prototype drill systems under realistic analog field conditions. Drill-specific failure modes and software design flaws will become most apparent at this stage. DAME will develop and test drill automation software and hardware under stressful operating conditions during several planned field campaigns. Initial results from summer 2004 tests show seven identifi distinct failure modes of the drill: cuttings-removal issues with low-power drilling into permafrost, and successful steps at executive control and initial automation.

Glass, Brian↗

Pushing Human Frontiers

With human colonization of Mars, I think you will see a higher standard of civilization, just as America set a higher standard of civilization which then promulgated back into Europe. I think that if you want to maximize human potential, you need a higher standard of civilization, and that becomes an example that benefits everyone. Without an open frontier, closed world ideologies, such as the Malthus Theory, tend to come to the forefront. It is that there are limited resources; therefore, we are all in deadly competition with each other for the limited pot. The result is tyrannical and potentially genocidal regimes, and we've already seen this in the twentieth century. There s no truth in the Malthus Theory, because human beings are the creators of their resources. With every mouth comes a pair of hands and a brain. But if it seems to be true, you have a vector in this direction, and it is extremely unfortunate. It is only in a universe of infinite resources that all humans can be brothers and sisters. The fundamental question which affects humanity s sense of itself is whether the world is changeable or fixed. Are we the makers of our world or just its inhabitants? Some people have a view that they re living at the end of history within a world that s already defined, and there is no fundamental purpose to human life because there is nothing humans can do that matters. On the other hand, if humans understand their own role as the creators of their world, that s a much more healthy point of view. It raises the dignity of humans. Indeed, if we do establish a new branch of human civilization on Mars that grows in time and potency to the point where it cannot really settle Mars, but transforms Mars, and brings life to Mars, we will prove to everyone and for all time the precious and positive nature of the human species and every member of it.

Zubrin, Robert↗

Sensing Super-Position: Human Sensing Beyond the Visual Spectrum

The coming decade of fast, cheap and miniaturized electronics and sensory devices opens new pathways for the development of sophisticated equipment to overcome limitations of the human senses. This paper addresses the technical feasibility of augmenting human vision through Sensing Super-position by mixing natural Human sensing. The current implementation of the device translates visual and other passive or active sensory instruments into sounds, which become relevant when the visual resolution is insufficient for very difficult and particular sensing tasks. A successful Sensing Super-position meets many human and pilot vehicle system requirements. The system can be further developed into cheap, portable, and low power taking into account the limited capabilities of the human user as well as the typical characteristics of his dynamic environment. The system operates in real time, giving the desired information for the particular augmented sensing tasks. The Sensing Super-position device increases the image resolution perception and is obtained via an auditory representation as well as the visual representation. Auditory mapping is performed to distribute an image in time. The three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. This paper details the approach of developing Sensing Super-position systems as a way to augment the human vision system by exploiting the capabilities of Lie human hearing system as an additional neural input. The human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns. The known capabilities of the human hearing system to learn and understand complicated auditory patterns provided the basic motivation for developing an image-to-sound mapping system. The human brain is superior to most existing computer systems in rapidly extracting relevant information from blurred, noisy, and redundant images. From a theoretical viewpoint, this means that the available bandwidth is not exploited in an optimal way. While image-processing techniques can manipulate, condense and focus the information (e.g., Fourier Transforms), keeping the mapping as direct and simple as possible might also reduce the risk of accidentally filtering out important clues. After all, especially a perfect non-redundant sound representation is prone to loss of relevant information in the non-perfect human hearing system. Also, a complicated non-redundant image-to-sound mapping may well be far more difficult to learn and comprehend than a straightforward mapping, while the mapping system would increase in complexity and cost. This work will demonstrate some basic information processing for optimal information capture for headmounted systems.

Maluf, David A.↗

Integrated Human-Robotic Missions to the Moon and Mars: Mission Operations Design Implications

For most of the history of space exploration, human and robotic programs have been independent, and have responded to distinct requirements. The NASA Vision for Space Exploration calls for the return of humans to the Moon, and the eventual human exploration of Mars; the complexity of this range of missions will require an unprecedented use of automation and robotics in support of human crews. The challenges of human Mars missions, including roundtrip communications time delays of 6 to 40 minutes, interplanetary transit times of many months, and the need to manage lifecycle costs, will require the evolution of a new mission operations paradigm far less dependent on real-time monitoring and response by an Earthbound operations team. Robotic systems and automation will augment human capability, increase human safety by providing means to perform many tasks without requiring immediate human presence, and enable the transfer of traditional mission control tasks from the ground to crews. Developing and validating the new paradigm and its associated infrastructure may place requirements on operations design for nearer-term lunar missions. The authors, representing both the human and robotic mission operations communities, assess human lunar and Mars mission challenges, and consider how human-robot operations may be integrated to enable efficient joint operations, with the eventual emergence of a unified exploration operations culture.

Korth, David↗

A Human View Model for Socio-Technical Interactions

The Human View was developed as an additional architectural viewpoint to focus on the human part of a system. The Human View can be used to collect and organize data in order to understand how human operators interact and impact the other elements of a system. This framework can also be used to develop a model to describe how humans interact with each other in network enabled systems. These socio-technical interactions form the foundation of the emerging area of Human Interoperability. Human Interoperability strives to understand the relationships required between human operators that impact collaboration across networked environments, including the effect of belonging to different organizations. By applying organizational relationship concepts from network theory to the Human View elements, and aligning these relationships with a model developed to identify layers of coalition interoperability, the conditions for different levels for Human Interoperability for network enabled systems can be identified. These requirements can then be captured in the Human View products to improve the overall network enabled system.

Handley, Holly A.↗

Human Exploration of Near-Earth Asteroids and Sample Collection Considerations

In 2009 the Augustine Commission identified near-Earth asteroids (NEAs) as high profile destinations for human exploration missions beyond the Earth-Moon system as part of the Flexible Path. Subsequently, the U.S. presidential administration directed NASA on April 15, 2010 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. Human Exploration Considerations: These missions would be the first human expeditions to interplanetary 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 in-depth scientific examinations of these primitive objects. However, prior to sending human explorers to NEAs, robotic investigations of these bodies would be required in order to maximize operational efficiency and reduce mission risk. These precursor missions to NEAs would fill crucial strategic knowledge gaps concerning their physical characteristics that are relevant for human exploration of these relatively unknown destinations. Sample Science Benefits: Information obtained from a human investigation of a NEA, together with ground-based observations and prior spacecraft investigations of asteroids and comets, will also provide a real measure of ground truth to data obtained from terrestrial meteorite collections. Major advances in the areas of geochemistry, impact history, thermal history, isotope analyses, mineralogy, space weathering, formation ages, thermal inertias, volatile content, source regions, solar system formation, etc. can be expected from human NEA missions. Samples directly returned from a primitive body would lead to the same kind of breakthroughs for understanding NEAs that the Apollo samples provided for understanding the Earth-Moon system and its formation history. International Participation: In addition, robotic precursor and human exploration missions to NEAs would allow the NASA and its international partners to gain operational experience in performing complex tasks (e.g., sample collection, deployment of payloads, retrieval of payloads, etc.) with crew, robots, and spacecraft under microgravity conditions at or near the surface of a small body. This would provide an important synergy between the worldwide Science and Exploration communities, which will be crucial for development of future international deep space exploration architectures and has potential benefits for future exploration of other destinations beyond low-Earth orbit.

Abell, Paul↗

Human Reliability and the Cost of Doing Business

Most businesses recognize that people will make mistakes and assume errors are just part of the cost of doing business, but does it need to be? Companies with high risk, or major consequences, should consider the effect of human error. In a variety of industries, Human Errors have caused costly failures and workplace injuries. These have included: airline mishaps, medical malpractice, administration of medication and major oil spills have all been blamed on human error. A technique to mitigate or even eliminate some of these costly human errors is the use of Human Reliability Analysis (HRA). Various methodologies are available to perform Human Reliability Assessments that range from identifying the most likely areas for concern to detailed assessments with human error failure probabilities calculated. Which methodology to use would be based on a variety of factors that would include: 1) how people react and act in different industries, and differing expectations based on industries standards, 2) factors that influence how the human errors could occur such as tasks, tools, environment, workplace, support, training and procedure, 3) type and availability of data and 4) how the industry views risk & reliability influences ( types of emergencies, contingencies and routine tasks versus cost based concerns). The Human Reliability Assessments should be the first step to reduce, mitigate or eliminate the costly mistakes or catastrophic failures. Using Human Reliability techniques to identify and classify human error risks allows a company more opportunities to mitigate or eliminate these risks and prevent costly failures.

DeMott, Diana↗

Robotic Reconnaissance Missions to Small Bodies and Their Potential Contributions to Human Exploration

Introduction: Robotic reconnaissance missions to small bodies will directly address aspects of NASA's Asteroid Initiative and will contribute to future human exploration. The NASA Asteroid Initiative is comprised of two major components: the Grand Challenge and the Asteroid Mission. The first component, the Grand Challenge, focuses on protecting Earth's population from asteroid impacts by detecting potentially hazardous objects with enough warning time to either prevent them from impacting the planet, or to implement civil defense procedures. The Asteroid Mission involves sending astronauts to study and sample a near- Earth asteroid (NEA) prior to conducting exploration missions of the Martian system, which includes Phobos and Deimos. The science and technical data obtained from robotic precursor missions that investigate the surface and interior physical characteristics of an object will help identify the pertinent physical properties that will maximize operational efficiency and reduce mission risk for both robotic assets and crew operating in close proximity to, or at the surface of, a small body. These data will help fill crucial strategic knowledge gaps (SKGs) concerning asteroid physical characteristics that are relevant for human exploration considerations at similar small body destinations. Small Body Strategic Knowledge Gaps: For the past several years NASA has been interested in identifying the key SKGs related to future human destinations. These SKGs highlight the various unknowns and/or data gaps of targets that the science and engineering communities would like to have filled in prior to committing crews to explore the Solar System. An action team from the Small Bodies Assessment Group (SBAG) was formed specifically to identify the small body SKGs under the direction of the Human Exploration and Operations Missions Directorate (HEOMD), given NASA's recent interest in NEAs and the Martian moons as potential human destinations [1]. The action team organized the SKGs into four broad themes: 1) Identify human mission targets; 2) Understand how to work on and interact with the small body surface; 3) Understand the small body environment and its potential risk/benefit to crew, systems, and operational assets; and 4) Understand the small body resource potential. Each of these themes were then further subdivided into categories to address specific SKG issues. Robotic Precursor Contributions to SKGs: Robotic reconnaissance missions should be able to address specific aspects related to SKG themes 1 through 4. Theme 1 deals with the identification of human mission targets within the NEA population. The current guideline indicates that human missions to fastspinning, tumbling, or binary asteroids may be too risky to conduct successfully from an operational perspective. However, no spacecraft mission has been to any of these types of NEAs before. Theme 2 addresses the concerns about interacting on the small body surface under microgravity conditions, and how the surface and/or sub-surface properties affect or restrict the interaction for human exploration. The combination of remote sensing instruments and in situ payloads will provide good insight into the asteroid's surface and subsurface properties. SKG theme 3 deals with the environment in and around the small body that may present a nuisance or hazard to any assets operating in close proximity. Impact and surface experiments will help address issues related to particle size, particle longevity, internal structure, and the near-surface mechanical stability of the asteroid. Understanding or constraining these physical characteristics are important for mission planning. Theme 4 addresses the resource potential of the small body. This is a particularly important aspect of human exploration since the identification and utilization of resources is a key aspect for deep space mission architectures to the Martian system (i.e., Phobos and Deimos). Conclusions: Robotic reconnaissance of small bodies can provide a wealth of information relevant to the science and planetary defense of NEAs. However, such missions to investigate NEAs can also provide key insights into small body strategic knowledge gaps and contribute to the overall success for human exploration missions to asteroids.

Abell, P. A.↗

Human Mars Landing Site and Impacts on Mars Surface Operations

NASA has begun a process to identify and discuss candidate locations where humans could land, live and work on the Martian surface. These locations are referred to as Exploration Zones (EZs). Given current mission concepts, an EZ is a collection of Regions of Interest (ROIs) that are located within approximately 100 kilometers of a centralized landing site. ROIs are areas that are relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. The EZ also contains a landing site and a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. These candidate EZs will be used by NASA as part of a multi‐year process of determining where and how humans could explore Mars. In the near term this process includes: (a) identifying locations that would maximize the potential science return from future human exploration missions, (b) identifying locations with the potential for resources required to support humans, (c) developing concepts and engineering systems needed by future human crews to conduct operations within an EZ, and (d) identifying key characteristics of the proposed candidate EZs that cannot be evaluated using existing data sets, thus helping to define precursor measurements needed in advance of human missions. Existing and future robotic spacecraft will be tasked to gather data from specific Mars surface sites within the representative EZs to support these NASA activities. The proposed paper will describe NASA's initial steps for identifying and evaluating candidate EZs and ROIs. This includes plans for the "First Landing Site/Exploration Zone Workshop for Human Missions to the Surface of Mars" to be held in October 2015 at which proposals for EZs and ROIs will be presented and discussed. It will also include a discussion of how these considerations are (or will be) taken into account as future robotic Mars missions are defined and developed. One or more representative EZs, drawn from similar previous studies involving Mars sites, will be used in the proposed paper to illustrate the process NASA envisions for gathering additional data from robotic precursor missions to assist in making a final selection of an EZ for human crews as well as the steps likely to occur during the buildup of a habitation site. Examples of the systems and operations likely to be used by human crews, assisted by robotic vehicles, to explore the scientific ROIs as well as developing the resource ROIs within the example EZs will be discussed.

Bussey, Ben↗

Cislunar Near Rectilinear Halo Orbit for Human Space Exploration

In order to conduct sustained human exploration beyond Low Earth Orbit (LEO), spacecraft systems are designed to operate in a series of missions of increasing complexity. Regardless of the destination, Moon, Mars, asteroids or beyond, there is a substantial set of common objectives that must be met. Many orbit characterization studies have endeavored to evaluate the potential locations in cislunar space that are favorable for meeting common human exploration objectives in a stepwise approach. Multiple studies, by both NASA and other international space agencies, have indicated that Earth-­‐moon libration point orbits are attractive candidates for staging operations in the proving ground and beyond. In particular, the Near Rectilinear Orbit (NRO) has been demonstrated to meet multi-­‐mission and multi-­‐destination architectural constraints. However, a human mission to a selected NRO presents a variety of new challenges for mission planning. While a growing number of robotic missions have completed successful operations to various specific libration point orbits, human missions have never been conducted to orbits of this class. Human missions have unique challenges that differ significantly from robotic missions, including a lower tolerance for mission risk and additional operational constraints that are associated only with human spacecraft. In addition, neither robotic nor human missions have been operated in the NRO regime specifically, and NROs exhibit dynamical characteristics that can differ significantly as compared to other halo orbits. Finally, multi-­‐body orbits, such as libration point orbits, are identified to exist in a simplified orbit model known as the Circular Restricted Three Body Problem (CRTBP) and must then be re-­‐solved in the full ephemeris model. As a result, the behavior of multi-­‐body orbits cannot be effectively characterized within the classical two-­‐body orbit dynamics framework more familiar to the human spaceflight community. In fact, a given NRO is not identified by a set of Keplerian orbit parameters, and a valid epoch specific state vector must be first obtained from a multi-body dynamical model. In this paper, the significant performance and operational challenges of conducting human missions to the NRO are evaluated. First, a systematic process for generating full ephemeris based ballistic NROs of various families is outlined to demonstrate the relative ease in which a multi-­‐revolution orbit can be found for any epoch and for various orbit geometries. In the Earth-­‐Moon system, NROs, which are halo orbits with close passage over a lunar pole, can exist with respect to libration point 1 (L1) or libration point 2 (L2) and are either from a North or South family orbit class with respect to the ecliptic. Second, the ability to maintain the orbit over the lifetime of a habitat mission by applying a reliable station-keeping strategy is investigated. The NRO, while similar to the quasi-­‐halo orbits that the Artemis mission flew, requires an updated station keeping strategy. This is due to several dynamical differences such as the increased relative stability of the NRO compared to other halo orbits and the close passage over the lunar surface as shown in Figure 1. Multiple station-keeping strategies are being investigated to ensure a human spacecraft remains on a predictable path. As the NRO is not described in simple two-­‐body parameters, analysis must determine the best strategy for targeting a reference NRO as well as how closely a future state should be constrained. In addition, costs will be minimized by determining maneuver directionality based on an identified pattern in the optimal station-keeping solutions or an analytically derived relationship. The candidate station-keeping algorithm must be stable and robust to environmental and vehicle uncertainties as well to navigation estimation and flight control execution errors. To that end, navigation accuracies, the impact on the station-keeping execution errors as well as other vehicle uncertainties need to be assessed. Starting with Orion, current navigation accuracies are evaluated and then navigation requirements are derived assuming a desired station-keeping propellant budget. Third, the performance requirements to and from the NRO are evaluated. Important parameters for developing expected propellant costs include epoch of operation, size and type of NRO, Earth departure and return constraints, as well as abort or early-­‐return capability. Finally, rendezvous and proximity operations are vital aspects of multi-­‐mission human exploration endeavors. The ability to conduct rendezvous and the associated propellant costs are assessed as well as the impacts of various profile assumptions including the location within the NRO the rendezvous is performed. The results of these studies will influence plans for international cooperation on both nearer term proving ground missions and beyond.

Whitley, Ryan↗

Inserting New Technologies into Human-Computer Interfaces for Future Lunar and Mars Missions

Plans call for human cislunar operations and lunar surface access, to prepare for eventual Mars missions. NASA will also develop new opportunities in lunar orbit that provide the foundation and act as a gateway for human exploration deeper into the solar system. Current human spaceflight is complex and requires as many as fifty people to support the International Space Station (ISS) Mission Control Center (MCC) in Houston, Texas. These flight controllers in the front and back rooms of the MCC, serve as an extra pair of eyes overseeing the numerous station systems. Deep space missions - to the moon, Mars, and beyond - will be more complex and place challenging mission constraints on the crew. As the round-trip communication delays increase in deep space exploration, more on-board systems autonomy and functionality will be needed to maintain and control the vehicle. These mission constraints will change the Earth-based ground control approach and will demand efficient and effective human-computer interfaces (HCI) to control a highly complex vehicle or habitat system. All of this necessitates a different approach to designing and developing spacecraft and habitats. In the beginning of new human spaceflight programs, focus is typically on launch vehicle and uncrewed spacecraft design and development. The reasoning behind this focus to enable flight testing of an integrated launch vehicle and spacecraft system to ensure it will be safe enough to allow humans on board. This is an essential process for new spacecraft, however, the practical effect is a lack of funding for the spacecraft’s human interfaces development. It can be many years before the human interface development begins, putting it late in the spacecraft lifecycle, when almost all other spacecraft systems and subsystems are already in place. This forces the usage of existing and proven technologies for the HCI interfaces. We posit that putting the human first in a spacecraft design process will yield a more effective spacecraft for exploration and long duration missions. NASA Human Research Program (HRP) has identified inadequate HCI as a risk for future missions. New tools and procedures to aid the crew in operating a complex spacecraft will be required. This paper discusses ongoing activities in the development of the next generation HCI components and systems, and a new approach toward human interfaces for spacecraft.

Salazar, George A.↗