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At least 127 records · Page 7

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 ↗

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↗

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 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↗

Human V H 1-69 Gene-Encoded Human Monoclonal Antibodies against Staphylococcus aureus IsdB Use at Least Three Distinct Modes of Binding To Inhibit Bacterial Growth and Pathogenesis

Staphylococcus aureus is an important human pathogen that infects nearly every human tissue. Like most organisms, the acquisition of nutrient iron is necessary for its survival. One route by which it obtains this metal is through the iron-regulated surface determinant (Isd) system that scavenges iron from the hemoglobin of the host. We show that the heavy chain variable region IGHV1-69 gene commonly encodes human monoclonal antibodies (mAbs) targeting IsdB-NEAT2. Remarkably, these antibodies bind to multiple antigenic sites. One class of IGHV1-69-encoded mAbs blocks S. aureus heme acquisition by binding to the heme-binding site of NEAT2, while two additional classes reduce the bacterial burden in vivo by an alternative Fc receptor-mediated mechanism. We further identified clonal lineages of IGHV1-69-encoded mAbs using donor samples, showing that each lineage diversifies during infection by somatic hypermutation. These studies reveal that IGHV1-69-encoded antibodies contribute to a protective immune response, furthering our understanding of the correlates of protection against S. aureus infection.

59 BASIC BIOLOGICAL SCIENCES↗

Human exploration and settlement of Mars - The roles of humans and robots

The scientific objectives and strategies for human settlement on Mars are examined in the context of the Space Exploration Initiative (SEI). An integrated strategy for humans and robots in the exploration and settlement of Mars is examined. Such an effort would feature robotic, telerobotic, and human-supervised robotic phases.

Duke, Michael B.↗

Technology Development for Human Exploration Beyond LEO in the New Millennium IAA-13-3 Strategies and Plans for Human Mars Missions

As we look forward into the new millennium, the extension of human presence beyond Low-Earth Orbit (LEO) looms large in the plans of NASA. The Agency's Strategic Plan specifically calls out the need to identify and develop technologies for 100 and 1000-day class missions beyond LEO. To meet the challenge of these extended duration missions, it is important that we learn how to utilize the indigenous resources available to us on extraterrestrial bodies. This concept, known as In-Situ Resource Utilization (ISRU) can greatly reduce the launch mass & cost of human missions while reducing the risk. These technologies may also pave the way for the commercial development of space. While no specific target beyond LEO is identified in NASA's Strategic Plan, mission architecture studies have been on-going for the Moon, Mars, Near-Earth Asteroids and Earth/Moon & Earth/Sun Libration Points. As a result of these studies, the NASA Office of Space Flight (Code M) through the Johnson and Kennedy Space Centers, is leading the effort to develop ISRU technologies and systems to meet the current and future needs of human missions beyond LEO and on to Mars. This effort also receives support from the NASA Office of Biological and Physical Research (Code U), the Office of Space Science (Code S), and the Office of Aerospace Technology (Code R). This paper will present unique developments in the area of fuel and oxidizer production, breathing air production, water production, C02 collection, separation of atmospheric gases, and gas liquefaction and storage. A technology overview will be provided for each topic along with the results achieved to date, future development plans, and the mission architectures that these technologies support.

Larson, William E.↗