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At least 145 records · Page 8

Human Space Exploration and Human Space Flight: Latency and the Cognitive Scale of the Universe

The role of telerobotics in space exploration as placing human cognition on other worlds is limited almost entirely by the speed of light, and the consequent communications latency that results from large distances. This latency is the time delay between the human brain at one end, and the telerobotic effector and sensor at the other end. While telerobotics and virtual presence is a technology that is rapidly becoming more sophisticated, with strong commercial interest on the Earth, this time delay, along with the neurological timescale of a human being, quantitatively defines the cognitive horizon for any locale in space. That is, how distant can an operator be from a robot and not be significantly impacted by latency? We explore that cognitive timescale of the universe, and consider the implications for telerobotics, human space flight, and participation by larger numbers of people in space exploration. We conclude that, with advanced telepresence, sophisticated robots could be operated with high cognition throughout a lunar hemisphere by astronauts within a station at an Earth-Moon Ll or L2 venue. Likewise, complex telerobotic servicing of satellites in geosynchronous orbit can be carried out from suitable terrestrial stations.

Lester, Dan↗

Humans vs Hardware: The Unique World of NASA Human System Risk Assessment

Understanding spaceflight risks to crew health and performance is a crucial aspect of preparing for exploration missions in the future. The research activities of the Human Research Program (HRP) provide substantial evidence to support most risk reduction work. The Human System Risk Board (HSRB), acting on behalf of the Office of Chief Health and Medical Officer (OCHMO), assesses these risks and assigns likelihood and consequence ratings to track progress. Unfortunately, many traditional approaches in risk assessment such as those used in the engineering aspects of spaceflight are difficult to apply to human system risks. This presentation discusses the unique aspects of risk assessment from the human system risk perspective and how these limitations are accommodated and addressed in order to ensure that reasonable inputs are provided to support the OCHMO's overall risk posture for manned exploration missions.

Anton, W.↗

NASA’s Identified Risks of Adverse Outcomes Due to Inadequate Human Systems Integration Architecture in Human Spaceflight

The NASA Human System Risk Board (HSRB) has the overall responsibility for tracking the evolution of the top ~30 human system risks that it has identified to be associated with human spaceflight. As part of this process, the Board is charged with maintaining a consistent, integrated process to mitigate those risks, and developing evidence-based risk posture recommendations. One of the identified risks is due to inadequate human systems integration architecture (HSIA) and a driving factor of this risk is that given decreasing real-time ground support for execution of complex operations during future exploration missions, there is a possibility of adverse performance outcomes including that crew are unable to adequately respond to unanticipated critical malfunctions or detect safety critical procedural errors. The HSRB uses Directed Acyclic Graphs (DAGs) as a communication tool for describing how astronaut exposure to spaceflight hazards leads to meaningful mission-level health and performance outcomes and as the basis for understanding intermediate causal relationships between risk contributing factors and countermeasures that link hazards to outcomes. The HSIA risk DAG will be presented and described. Historically, critical malfunctions requiring Crew/MCC management occurred at a rate of 1.7 times per year for ISS averaged over the lifetime and 3-4 times per year in the burn in phase for the vehicle. These averages do not include EVA data, which greatly increases the incident rate. Prior experience from the Apollo program showed 10/11 crewed missions experienced significant anomalies where crew relied heavily on MCC expertise in real-time. These failure patterns are in line with those observed in other complex engineered systems (e.g., oil rigs, launch systems, commercial aviation, etc.) It is likely that general malfunction and error rates are > 10% for short duration missions (<30 days), based on past and current spaceflight operations data. Likelihood of adverse outcomes has the potential to increase as crew conduct work with new, complex systems and with less ground support. For Low Earth Orbit missions and Lunar missions less than 30 days, assuming minimal comm delays, disruptions and bandwidth limitations, malfunctions and errors can affect mission objectives and crew health but may be mitigated by ground support. For Lunar missions greater than 30 days and any potential Mars mission malfunctions and errors can have Loss of Crew and Loss of Mission consequences due to reduced ground support (communication delays, constraints and blackouts) for more complex operations, as well as reduced resupply and evacuation options.

Daniel M Buckland↗

Human Contribution to Safety: Human Performance is Not Just About Error

- When the only data that are available are about human failure, then data-driven designs only consider that humans fail. - Designs intended to "protect" the system from "error-prone" humans can design-out the capability for humans to effectively intervene/adapt, which is a far more common behavior.

Jon Holbrook↗

Humans to Mars, but How Many? Using Imprint Human Performance Models to Inform Crew Size

HUMANS TO MARS, BUT HOW MANY? USING IMPRINT HUMAN PERFORMANCE MODELS TO INFORM CREW SIZE Missions to Mars will differ from previous human spaceflight missions in that the onboard crew of astronauts will be required to operate in an Earth-independent manner due to long communication delays. Without a systematic, repeatable process to determine the number and composition of crew necessary to successfully accomplish these missions, NASA increases the risk that crew sizes may be too small to meet primary mission objectives under nominal conditions and, more consequentially, that crewmembers may not have the expertise needed to successfully respond to unforeseen failures without the real-time expertise of the Mission Control Central (MCC) team NASA currently relies upon. The NASA Engineering and Safety Center (NESC) is developing a methodology for assessing the trade space of factors that affect the number of crew for future missions. This methodology includes the consideration of results from three human performance models developed using the Improved Performance Research and Integration Tool (IMPRINT) modeling platform as well as a custom-built model on expertise trained within the crew. The custom-built crew expertise model results will be presented in the training sub-tag. Here we present results of the three IMPRINT models. Two of these models were built using IMPRINT’s Operations Model capability, with detailed task networks for specific systems and scenarios allowing for a comprehensive mental workload analysis on certain crew positions. The third model was built using IMPRINT’s Force Model capability, allowing for a higher-level manpower analysis based on crew engagement in activities performed over a longer Mars transit scenario, and how those activities may be impacted by unplanned events and new tasking unique to the Mars mission. Differences between the models will be presented, as well as examples of model results and a discussion of how those results may inform future Mars mission manpower requirements, system design, and operating procedures.

Donna L Dempsey↗

SIMULATED HUMAN ERROR PROBABILITY AND ITS APPLICATION TO DYNAMIC HUMAN FAILURE EVENTS

Abstract Objectives: Human reliability analysis (HRA) methods typically analyze human failure events (HFEs) at the overall task level. For dynamic HRA, it is important to model human activities at the subtask level. There exists a disconnect between dynamic subtask level and static task level that presents issues when modeling dynamic scenarios. For example, the SPAR-H method is typically used to calculate the human error probability (HEP) at the task level. As demonstrated in this paper, quantification in SPAR-H does not translate to the subtask level. Methods: Two different discrete distributions were generated for each SPAR-H Performance Shaping Factor (PSF) to define the frequency of PSF levels. The first distribution was a uniform, or uninformed distribution that assumed the frequency of each PSF level was equally likely. The second non-continuous distribution took the frequency of PSF level as identified from an assessment of the HERA database. These two different approaches were created to identify the resulting distribution of the HEP. The resulting HEP that appears closer to the known distribution, a log-normal centered on 1E-3, is the more desirable. Each approach then has median, average and maximum HFE calculations applied. To calculate these three values, three events, A, B and C are generated from the PSF level frequencies comprised of subtasks. The median HFE selects the median PSF level from each PSF and calculates HEP. The average HFE takes the mean PSF level, and the maximum takes the maximum PSF level. The same data set of subtask HEPs yields starkly different HEPs when aggregated to the HFE level in SPAR-H. Results: Assuming that each PSF level in each HFE is equally likely creates an unrealistic distribution of the HEP that is centered at 1. Next the observed frequency of PSF levels was applied with the resulting HEP behaving log-normally with a majority of the values under 2.5% HEP. The median, average and maximum HFE calculations did yield different answers for the HFE. The HFE maximum grossly over estimates the HFE, while the HFE distribution occurs less than HFE median, and greater than HFE average. Conclusions: Dynamic task modeling can be perused through the framework of SPAR-H. Identification of distributions associated with each PSF needs to be defined, and may change depending upon the scenario. However it is very unlikely that each PSF level is equally likely as the resulting HEP distribution is strongly centered at 100%, which is unrealistic. Other distributions may need to be identified for PSFs, to facilitate the transition to dynamic task modeling. Additionally discrete distributions need to be exchanged for continuous so that simulations for the HFE can further advance. This paper provides a method to explore dynamic subtask to task translation and provides examples of the process using the SPAR-H method.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Human Reliability Analysis for Digital Human-Machine Interfaces

This paper addresses the fact that existing human reliability analysis (HRA) methods do not provide guidance on digital human-machine interfaces (HMIs). Digital HMIs are becoming ubiquitous in nuclear power operations, whether through control room modernization or new-build control rooms. Legacy analog technologies like instrumentation and control (I&C) systems are costly to support, and vendors no longer develop or support analog technology, which is considered technologically obsolete. Yet, despite the inevitability of digital HMI, no current HRA method provides guidance on how to treat human reliability considerations for digital technologies.

99 GENERAL AND MISCELLANEOUS↗

The gene expression profile of non-cultured, highly purified human adipose tissue pericytes: Transcriptomic evidence that pericytes are stem cells in human adipose tissue

Pericytes (PCs) are a subset of perivascular cells that can give rise to mesenchymal stromal cells (MSCs) when culture-expanded, and are postulated to give rise to MSC-like cells during tissue repair in vivo. PCs have been suggested to behave as stem cells (SCs) in situ in animal models, although evidence for this role in humans is lacking. Here, we analyzed the transcriptomes of highly purified, non-cultured adipose tissue (AT)-derived PCs (ATPCs) to detect gene expression changes that occur as they acquire MSC characteristics in vitro, and evaluated the hypothesis that human ATPCs exhibit a gene expression profile compatible with an AT SC phenotype. The results showed ATPCs are non-proliferative and express genes characteristic not only of PCs, but also of AT stem/progenitor cells. Additional analyses defined a gene expression signature for ATPCs, and revealed putative novel ATPC markers. Almost all AT stem/progenitor cell genes differentially expressed by ATPCs were not expressed by ATMSCs or culture-expanded ATPCs. Genes expressed by ATMSCs but not by ATPCs were also identified. These findings strengthen the hypothesis that PCs are SCs in vascularized tissues, highlight gene expression changes they undergo as they assume an MSC phenotype, and provide new insights into PC biology. - Highlights: • Non-cultured adipose tissue-derived human pericytes (ncATPCs) exhibit a distinctive gene expression signature. • ncATPCs express key adipose tissue stem cell genes previously described in vivo in mice. • ncATPCs express message for anti-proliferative and antiangiogenic molecules. • Most ncATPC-specific transcripts are absent in culture-expanded pericytes or ATMSCs • Gene expression changes ncATPCs undergo as they acquire a cultured ATMSC phenotype are pointed out.

60 APPLIED LIFE SCIENCES↗

Human Research Program: Human Factors and Behavioral Performance

This discussion provides an overview of the Human Research Program (HRP), the Human Factors and Behavioral Performance Element (HFBP), and outlines currently documented research using AR/VR or Hybrid Reality to maintain or improve human behavior for long duration exploration mission environments. Different analog environments are also discussed in this presentation (ISS and HERA).

Human Research Program↗

Human Research Program: Human Factors and Behavioral Performance Research to Enable Artemis

This discussion provides an overview of the human research program (HRP), the Human Factors and Behavioral Performance Element (HFBP), and outlines currently documented research using AR/VR or Hybrid Reality to maintain or improve human behavior for long duration exploration mission environments. Different analog environments are also discussed in this presentation (ISS and HERA).

Human Research Program↗

Human papillomavirus types detected in skin warts and cancer differ in their transforming properties but commonly counteract UVB induced protective responses in human keratinocytes

In the present study, E6E7 and E6 proteins of human papillomaviruses (HPVs) associated with skin warts and cancer were compared for their transforming and carcinogenic abilities in primary human keratinocytes (PHKs). We show that E6E7 of cancer associated beta HPV types, notably 49 and 24, were able to extend the life span and enhance the clonogenic efficiency of PHKs when maintained in serum free/low calcium medium. Activities of the beta HPV E6E7 were lower than those of HPV16 E6E7. In contrast, E6 proteins from HPV types detected in skin warts or cancer, notably 10, 49 and 38, attenuated UVB induced protective responses in PHKs including cell death, proliferation arrest and accumulation of the proapoptotic proteins, p53, bax or bak. Together, this investigation revealed functional differences and commonalities between HPVs associated with skin warts and cancer, and allowed the identification of specific properties of beta HPVs supporting their involvement in skin carcinogenesis. - Highlights: • Primary keratinocytes were used to evaluate transforming and carcinogenic abilities of cutaneous HPVs. • E6E7 of cancer associated β HPV types transform primary human keratinocytes. • E6 proteins of cancer and wart associated HPVs inhibit UVB induced cell death. • E6s of cancer and wart associated HPVs attenuate UVB induced proliferation arrest. • E6s of cancer and wart associated HPVs attenuate UVB induced apoptosis signaling.

60 APPLIED LIFE SCIENCES↗

Development of a human live attenuated West Nile infectious DNA vaccine: Identification of a minimal mutation set conferring the attenuation level acceptable for a human vaccine

ABSTRACT: For the development of a human West Nile (WN) infectious DNA (iDNA) vaccine, we created highly attenuated chimeric virus W1806 with the serological identity of highly virulent WN-NY99. Earlier, we attempted to utilize mutations found in the E protein of the SA14-14-2 vaccine to bring safety of W1806 to the level acceptable for human use (). Here, we analyzed effects of the SA14-14-2 changes on growth properties and neurovirulence of W1806. A set including the E138K, K279M, K439R and G447D changes was identified as the perspective subset for satisfying the target safety profile without compromising immunogenicity of the vaccine candidate. The genetic stability of the attenuated phenotype was found to be unsatisfactory being dependent on a subset of attenuating changes incorporated in W1806. Elucidation of underlying mechanisms influencing selection of pathways for restoration of the envelope protein functionality will facilitate resolution of the emerged genetic stability issue. - Highlights: •Effect of mutations in E on properties of WN1806 is determined. •A subset of attenuating mutations suitable for a human vaccine is defined. •Mechanism of attenuation is proposed and illustrated. •Underlying mechanisms of neurovirulence reversion are suggested.

60 APPLIED LIFE SCIENCES↗

The human body at cellular resolution: the NIH Human Biomolecular Atlas Program

Transformative technologies are enabling the construction of three dimensional (3D) maps of tissues with unprecedented spatial and molecular resolution. Over the next seven years, the NIH Common Fund Human Biomolecular Atlas Program (HuBMAP) aims to develop a widely accessible framework for comprehensively mapping the human body at single-cell resolution by supporting technology development, data acquisition, and detailed spatial mapping. HuBMAP will integrate its efforts with other funding agencies, programs, and the biomedical research community at large towards the shared vision of a comprehensive, accessible 3D molecular and cellular atlas of the human body, in health and various disease settings.

59 BASIC BIOLOGICAL SCIENCES↗

Structure of the human MLH1 N-terminus: implications for predisposition to Lynch syndrome

Mismatch repair prevents the accumulation of erroneous insertions/deletions and non-Watson–Crick base pairs in the genome. Pathogenic mutations in the MLH1 gene are associated with a predisposition to Lynch and Turcot's syndromes. Although genetic testing for these mutations is available, robust classification of variants requires strong clinical and functional support. Here, the first structure of the N-terminus of human MLH1, determined by X-ray crystallography, is described. Lastly, the structure shares a high degree of similarity with previously determined prokaryotic MLH1 homologs; however, this structure affords a more accurate platform for the classification of MLH1 variants.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Structure of the lutein-binding domain of human StARD3 at 1.74 Å resolution and model of a complex with lutein

A crystal structure of the lutein-binding domain of human StARD3 (StAR-related lipid-transfer protein 3; also known as MLN64) has been refined to 1.74 Å resolution. A previous structure of the same protein determined to 2.2 Å resolution highlighted homology with StARD1 and shared cholesterol-binding character. StARD3 has since been recognized as a carotenoid-binding protein in the primate retina, where its biochemical function of binding lutein with specificity appears to be well suited to recruit this photoprotective molecule. The current and previous structures correspond closely to each other (r.m.s.d. of 0.25 Å), especially in terms of the helix-grip fold constructed around a solvent-filled cavity. Regions of interest were defined with alternate conformations in the current higher-resolution structure, including Arg351 found within the cavity and Ω1, a loop of four residues found just outside the cavity entrance. Models of the complex with lutein generated by rigid-body docking indicate that one of the ionone rings must protrude outside the cavity, and this insight has implications for molecular interactions with transport proteins and enzymes that act on lutein. Interestingly, models with the ϵ-ionone ring characteristic of lutein pointing towards the bottom of the cavity were associated with fewer steric clashes, suggesting that steric complementarity and ligand asymmetry may play a role in discriminating lutein from the other ocular carotenoids zeaxanthin and meso -zeaxanthin, which only have β-ionone rings.

Biochemistry & Molecular Biology↗