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At least 721 records · Page 40

Human Factors in Training - Space Flight Resource Management Training

Accidents and incidents show that high workload-induced stress and poor teamwork skills lead to performance decrements and errors. Research on teamwork shows that effective teams are able to adapt to stressful situations, and to reduce workload by using successful strategies for communication and decision making, and through dynamic redistribution of tasks among team members. Furthermore, superior teams are able to recognize signs and symptoms of workload-induced stress early, and to adapt their coordination and communication strategies to the high workload, or stress conditions. Mission Control Center (MCC) teams often face demanding situations in which they must operate as an effective team to solve problems with crew and vehicle during onorbit operations. To be successful as a team, flight controllers (FCers) must learn effective teamwork strategies. Such strategies are the focus of Space Flight Resource Management (SFRM) training. SFRM training in MOD has been structured to include some classroom presentations of basic concepts and case studies, with the assumption that skill development happens in mission simulation. Integrated mission simulations do provide excellent opportunities for FCers to practice teamwork, but also require extensive technical knowledge of vehicle systems, mission operations, and crew actions. Such technical knowledge requires lengthy training. When SFRM training is relegated to integrated simulations, FCers can only practice SFRM after they have already mastered the technical knowledge necessary for these simulations. Given the centrality of teamwork to the success of MCC, holding SFRM training till late in the flow is inefficient. But to be able to train SFRM earlier in the flow, the training cannot rely on extensive mission-specific technical knowledge. Hence, the need for a generic SFRM training framework that would allow FCers to develop basic teamwork skills which are mission relevant, but without the required mission knowledge. Work on SFRM training has been conducted in collaboration with the Expedition Vehicle Division at the Mission Operations Directorate (MOD) and with United Space Alliance (USA) which provides training to Flight Controllers. The space flight resource management training work is part of the Human Factors in Training Directed Research Project (DRP) of the Space Human Factors Engineering (SHFE) Project under the Space Human Factors and Habitability (SHFH) Element of the Human Research Program (HRP). Human factors researchers at the Ames Research Center have been investigating team work and distributed decision making processes to develop a generic SFRM training framework for flight controllers. The work proposed for FY10 continues to build on this strong collaboration with MOD and the USA Training Group as well as previous research in relevant domains such as aviation. In FY10, the work focuses on documenting and analyzing problem solving strategies and decision making processes used in MCC by experienced FCers.

Bryne, Vicky↗

Maximally Expressive Task Modeling

Planning and scheduling systems organize "tasks" into a timeline or schedule. The tasks are defined within the scheduling system in logical containers called models. The dictionary might define a model of this type as "a system of things and relations satisfying a set of rules that, when applied to the things and relations, produce certainty about the tasks that are being modeled." One challenging domain for a planning and scheduling system is the operation of on-board experiment activities for the Space Station. The equipment used in these experiments is some of the most complex hardware ever developed by mankind, the information sought by these experiments is at the cutting edge of scientific endeavor, and the procedures for executing the experiments are intricate and exacting. Scheduling is made more difficult by a scarcity of space station resources. The models to be fed into the scheduler must describe both the complexity of the experiments and procedures (to ensure a valid schedule) and the flexibilities of the procedures and the equipment (to effectively utilize available resources). Clearly, scheduling space station experiment operations calls for a "maximally expressive" modeling schema. Modeling even the simplest of activities cannot be automated; no sensor can be attached to a piece of equipment that can discern how to use that piece of equipment; no camera can quantify how to operate a piece of equipment. Modeling is a human enterprise-both an art and a science. The modeling schema should allow the models to flow from the keyboard of the user as easily as works of literature flowed from the pen of Shakespeare. The Ground Systems Department at the Marshall Space Flight Center has embarked on an effort to develop a new scheduling engine that is highlighted by a maximally expressive modeling schema. This schema, presented in this paper, is a synergy of technological advances and domain-specific innovations.

Japp, John↗

Structure of saguaro cactus virus 3′ translational enhancer mimics 5′ cap for eIF4E binding

The genomes of several plant viruses contain RNA structures at their 3' ends called cap-independent translation enhancers (CITEs) that bind the host protein factors such as mRNA 5' cap-binding protein eIF4E for promoting cap-independent genome translation. However, the structural basis of such 5' cap-binding protein recognition by the uncapped RNA remains largely unknown. Here, we have determined the crystal structure of a 3' CITE, panicum mosaic virus-like translation enhancer (PTE) from the saguaro cactus virus (SCV), using a Fab crystallization chaperone. The PTE RNA folds into a three-way junction architecture with a pseudoknot between the purine-rich R domain and pyrimidine-rich Y domain, which organizes the overall structure to protrude out a specific guanine nucleotide, G18, from the R domain that comprises a major interaction site for the eIF4E binding. The superimposable crystal structures of the wild-type, G18A, G18C, and G18U mutants suggest that the PTE scaffold is preorganized with the flipped-out G18 ready to dock into the eIF4E 5' cap-binding pocket. The binding studies with wheat and human eIF4Es using gel electrophoresis and isothermal titration calorimetry, and molecular docking computation for the PTE–eIF4E complex demonstrated that the PTE structure essentially mimics the mRNA 5' cap for eIF4E binding. Such 5' cap mimicry by the uncapped and structured viral RNA highlights how viruses can exploit RNA structures to mimic the host protein-binding partners and bypass the canonical mechanisms for their genome translation, providing opportunities for a better understanding of virus-host interactions and non-canonical translation mechanisms found in many pathogenic RNA viruses.

3' cap-independent translation enhancers↗

EfgA is a conserved formaldehyde sensor that leads to bacterial growth arrest in response to elevated formaldehyde

Normal cellular processes give rise to toxic metabolites that cells must mitigate. Formaldehyde is a universal stressor and potent metabolic toxin that is generated in organisms from bacteria to humans. Methylotrophic bacteria such as Methylorubrum extorquens face an acute challenge due to their production of formaldehyde as an obligate central intermediate of single-carbon metabolism. Mechanisms to sense and respond to formaldehyde were speculated to exist in methylotrophs for decades but had never been discovered. Here, we identify a member of the DUF336 domain family, named efgA for enhanced formaldehyde growth, that plays an important role in endogenous formaldehyde stress response in M . extorquens PA1 and is found almost exclusively in methylotrophic taxa. Our experimental analyses reveal that EfgA is a formaldehyde sensor that rapidly arrests growth in response to elevated levels of formaldehyde. Heterologous expression of EfgA in Escherichia coli increases formaldehyde resistance, indicating that its interaction partners are widespread and conserved. EfgA represents the first example of a formaldehyde stress response system that does not involve enzymatic detoxification. Thus, EfgA comprises a unique stress response mechanism in bacteria, whereby a single protein directly senses elevated levels of a toxic intracellular metabolite and safeguards cells from potential damage.

59 BASIC BIOLOGICAL SCIENCES↗

Structure of the EphB6 receptor ectodomain

Eph receptors are the largest group amongst the receptor tyrosine kinases and are divided into two subgroups, A and B, based on ligand binding specificities and sequence conservation. Through ligand-induced and ligand-independent activities, Ephs play central roles in diverse biological processes, including embryo development, regulation of neuronal signaling, immune responses, vasculogenesis, as well as tumor initiation, progression, and metastasis. The Eph extracellular regions (ECDs) are constituted of multiple domains, and previous structural studies of the A class receptors revealed how they interact with ephrin ligands and simultaneously mediate Eph-Eph clustering necessary for biological activity. Specifically, EphA structures highlighted a model, where clustering of ligand-bound receptors relies on two distinct receptor/receptor interfaces. Interestingly, most unliganded A class receptors also form an additional, third interface, between the ligand binding domain (LBD) and the fibronectin III domain (FN3) of neighboring molecules. Structures of B-class Eph ECDs, on the other hand, have never been reported. To further our understanding of Eph receptor function, we crystallized the EphB6-ECD and determined its three-dimensional structure using X-ray crystallography. EphB6 has important functions in both normal physiology and human malignancies and is especially interesting because this atypical receptor innately lacks kinase activity and our understanding of the mechanism of action is still incomplete. Our structural data reveals the overall EphB6-ECD architecture and shows EphB6-LBD/FN3 interactions similar to those observed for the unliganded A class receptors, suggesting that these unusual interactions are of general importance to the Eph group. We also observe unique structural features, which likely reflect the atypical signaling properties of EphB6, namely the need of co-receptor(s) for this kinase-inactive Eph. These findings provide new valuable information on the structural organization and mechanism of action of the B-class Ephs, and specifically EphB6, which in the future will assist in identifying clinically relevant targets for cancer therapy.

59 BASIC BIOLOGICAL SCIENCES↗

Comparison of display enhancement with intelligent decision-aiding

Currently, two main approaches exist for improving the human-machine interface component of a system in order to improve overall system performance, display enhancement and intelligent decision aiding. Each of these two approaches has its own set of advantages and disadvantages, as well as introduce its own set of additional performance problems. These characteristics should help identify which types of problem situations and domains are better aided by which type of strategy. The characteristic issues are described of these two decision aiding strategies. Then differences in expert and novice decision making are described in order to help determine whether a particular strategy may be better for a particular type of user. Finally, research is outlined to compare and contrast the two technologies, as well as to examine the interaction effects introduced by the different skill levels and the different methods for training operators.

Kirlik, Alex↗

Experiments with Test Case Generation and Runtime Analysis

Software testing is typically an ad hoc process where human testers manually write many test inputs and expected test results, perhaps automating their execution in a regression suite. This process is cumbersome and costly. This paper reports preliminary results on an approach to further automate this process. The approach consists of combining automated test case generation based on systematically exploring the program's input domain, with runtime analysis, where execution traces are monitored and verified against temporal logic specifications, or analyzed using advanced algorithms for detecting concurrency errors such as data races and deadlocks. The approach suggests to generate specifications dynamically per input instance rather than statically once-and-for-all. The paper describes experiments with variants of this approach in the context of two examples, a planetary rover controller and a space craft fault protection system.

Artho, Cyrille↗

Speech Acquisition and Automatic Speech Recognition for Integrated Spacesuit Audio Systems

A voice-command human-machine interface system has been developed for spacesuit extravehicular activity (EVA) missions. A multichannel acoustic signal processing method has been created for distant speech acquisition in noisy and reverberant environments. This technology reduces noise by exploiting differences in the statistical nature of signal (i.e., speech) and noise that exists in the spatial and temporal domains. As a result, the automatic speech recognition (ASR) accuracy can be improved to the level at which crewmembers would find the speech interface useful. The developed speech human/machine interface will enable both crewmember usability and operational efficiency. It can enjoy a fast rate of data/text entry, small overall size, and can be lightweight. In addition, this design will free the hands and eyes of a suited crewmember. The system components and steps include beam forming/multi-channel noise reduction, single-channel noise reduction, speech feature extraction, feature transformation and normalization, feature compression, model adaption, ASR HMM (Hidden Markov Model) training, and ASR decoding. A state-of-the-art phoneme recognizer can obtain an accuracy rate of 65 percent when the training and testing data are free of noise. When it is used in spacesuits, the rate drops to about 33 percent. With the developed microphone array speech-processing technologies, the performance is improved and the phoneme recognition accuracy rate rises to 44 percent. The recognizer can be further improved by combining the microphone array and HMM model adaptation techniques and using speech samples collected from inside spacesuits. In addition, arithmetic complexity models for the major HMMbased ASR components were developed. They can help real-time ASR system designers select proper tasks when in the face of constraints in computational resources.

Huang, Yiteng↗

An Unobtrusive System to Measure, Assess, and Predict Cognitive Workload in Real-World Environments

Across many careers, individuals face alternating periods of high and low attention and cognitive workload, which can result in impaired cognitive functioning and can be detrimental to job performance. For example, some professions (e.g., fire fighters, emergency medical personnel, doctors and nurses working in an emergency room, pilots) require long periods of low workload (boredom), followed by sudden, high-tempo operations during which they may be required to respond to an emergency and perform at peak cognitive levels. Conversely, other professions (e.g., air traffic controllers, market investors in financial industries, analysts) require long periods of high workload and multitasking during which the addition of just one more task results in cognitive overload resulting in mistakes. An unobtrusive system to measure, assess, and predict cognitive workload could warn individuals, their teammates, or their supervisors when steps should be taken to augment cognitive readiness. In this talk I will describe an approach to this problem that we have found to be successful across work domains including: (1) a suite of unobtrusive, field-ready neurophysiological, physiological, and behavioral sensors that are chosen to best suit the target environment; (2) custom algorithms and statistical techniques to process and time-align raw data originating from the sensor suite; (3) probabilistic and statistical models designed to interpret the data into the human state of interest (e.g., cognitive workload, attention, fatigue); (4) and machine-learning techniques to predict upcoming performance based on the current pattern of events, and (5) display of each piece of information depending on the needs of the target user who may or may not want to drill down into the functioning of the system to determine how conclusions about human state and performance are determined. I will then focus in on our experimental results from our custom functional near-infrared spectroscopy sensor, designed to operate in real-world environments to be worn comfortably (e.g., positioned into a baseball cap or a surgeons cap) to measure changes in brain blood oxygenation without adding burden to the individual being assessed.

workload collection↗

Workload Considerations in Urban Air Mobility

Urban air mobility (UAM) is receiving increased attention in aviation as a system for passenger and cargo-carrying new entrants in urban airspace. In order to develop a safe and efficient system, numerous possible concepts of operation for UAM are being explored throughout industry and research domains, the features and assumptions of which may differ according to near, medium and far term operations. Much of the current research into the development of UAM has dominantly focused on technological and engineering capabilities, such as vehicle development. Although these areas of research are essential to furthering UAM, research into the role of the human operator in UAM is limited. The research described in this paper aims to begin to address this gap by investigating the capabilities and implications of human operators as traffic managers in the UAM system, focusing on near-term UAM operations. A human in the loop air traffic control simulation was used to investigate the effect of UAM traffic density, airspace routes and communication procedures on subjective workload and efficiency-related task performance. Findings indicate that medium and high-density operations were associated with high workload. A reduction in verbal communications through a letter of agreement, and optimized routes, were associated with reduced workload and increased performance efficiency. However, even with these adjustments, reported workload remained high, particularly during the high-density scenario. Future research should focus on the human operator roles and responsibilities, and the amount of involvement, in UAM system management. Particular focus should be directed on the impact of reduced human operator involvement and increased automation, on the safety and efficiency of UAM operations and the integration of UAM with traditional air traffic management.

Edwards, Tamsyn↗

Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition

Presequence protease (PreP), a 117kDa mitochondrial M16C metalloprotease vital for mitochondrial proteostasis, degrades presequence peptides cleaved off from nuclear-encoded proteins and other aggregation-prone peptides, such as amyloid β (Aβ). PreP structures have only been determined in a closed conformation; thus, the mechanisms of substrate binding and selectivity remain elusive. Here, we leverage advanced vitrification techniques to overcome the preferential denaturation of one of two ~55 kDa homologous domains of PreP caused by air-water interface adsorption. Thereby, we elucidate cryoEM structures of three apo-PreP open states along with Aβ- and citrate synthase presequence-bound PreP at 3.3–4.6 Å resolution. Together with integrative biophysical and pharmacological approaches, these structures reveal the key stages of the PreP catalytic cycle and how the binding of substrates or PreP inhibitor drives a rigid body motion of the protein for substrate binding and catalysis. Together, our studies provide key mechanistic insights into M16C metalloproteases for future therapeutic innovations.

59 BASIC BIOLOGICAL SCIENCES↗

Performance Data Report: Space Medicine Division, Human Research Program, Behavioural Health and Performance Research Element

This report is the result of a collaborative effort between NASA?s Behavioral Health & Performance (BHP) Research and Operations Group to investigate and determine the availability of data pertaining to behavioral performance (and other pertinent variables) that have been collected by the laboratories at NASA?s Johnson Space Center. BHP?s Operations and Research groups collaborated to systematically identify what types of performance data are needed in relevant BHP performance domains and also to conduct structured interviews with NASA personnel to identify which data do or do not exist currently (and for instances where such data exist, to evaluate the type, quality, accessibility, and confidentiality of those data). The authors defined outcome categories of performance that encapsulate BHP performance domains, mapped BHP Research Risks and Gaps onto those performance outcome categories, and identified and prioritized indicators for each outcome category. The team identified key points of contact (subject matter experts [SMEs]) as potential interviewees, created a template for structured interview questions about sources and accessibility of performance data, and coordinated and conducted structured interviews with the SMEs. The methodology, results, and implications of this effort, as well as forward work needed, are discussed in this report.

Shea, Camille↗

Classification and evolution of EF-hand proteins

Forty-five distinct subfamilies of EF-hand proteins have been identified. They contain from two to eight EF-hands that are recognizable by amino acid sequence as being statistically similar to other EF-hand domains. All proteins within one subfamily are congruent to one another, i.e. the dendrogram computed from one of the EF-hand domains is similar, within statistical error, to the dendrogram computed from another(s) domain. Thirteen subfamilies--including Calmodulin, Troponin C, Essential light chain, Regulatory light chain--referred to collectively as CTER, are congruent with one another. They appear to have evolved from a single ur-domain by two cycles of gene duplication and fusion. The subfamilies of CTER subsequently evolved by gene duplications and speciations. The remaining 32 subfamilies do not show such general patterns of congruence; however, some--such as S100, intestinal calcium binding protein (calbindin 9 kd), and trichohylin--do not form congruent clusters of subfamilies. Nearly all of the domains 1, 3, 5, and 7 are most similar to other ODD domains. Correspondingly the EVEN numbered domains of all 45 subfamilies most closely resemble EVEN domains of other subfamilies. Many sequence and chemical characteristics do not show systemic trends by subfamily or species of host organisms; such homoplasy is widespread. Eighteen of the subfamilies are heterochimeric; in addition to multiple EF-hands they contain domains of other evolutionary origins.

Non-NASA Center↗

A New Control Paradigm: Multiple Aircraft Controlled by Multiple Operators

Remotely piloted aircraft systems (RPAS) are becoming more and more prevalent in the aerospace operations. This is true in a number of diverse domains; urban air mobility, medical product delivery, infrastructure inspection, high altitude pseudo-satellites, search and rescue, auto cargo and several other applications. One aspect that all of these share in common is the need for scalability to be viable and continue to grow. The Association of Uncrewed Vehicle Systems International (AUVSI) develops an annual economic report. They project that in the first three years of integration more than 70,000 jobs will be created in the US alone, with an economic impact of more than $13.6 billion. This benefit will grow through 2025 when we foresee more than 100,000 jobs created and economic impact of $82 billion. For many of these domains to reach these levels and have the scalability needed, they will require a remote pilot to control multiple aircraft (1:N) or the extension of that, multiple pilots controlling multiple aircraft (m:N). This is a new control paradigm that raises multiple issues in various areas. The issues include regulatory, technical, safety, community acceptance and Human Factors. Human factors issues include displays, pilot workload, pilot situation awareness just to name a few. This panel brings together researchers, developers and operators that have been working in the area of m:N. They will discuss the need, the issues and some potential solutions.

multi-vehicle control↗

Ensemble learning-iterative training machine learning for uncertainty quantification and automated experiment in atom-resolved microscopy

Deep learning has emerged as a technique of choice for rapid feature extraction across imaging disciplines, allowing rapid conversion of the data streams to spatial or spatiotemporal arrays of features of interest. However, applications of deep learning in experimental domains are often limited by the out-of-distribution drift between the experiments, where the network trained for one set of imaging conditions becomes sub-optimal for different ones. This limitation is particularly stringent in the quest to have an automated experiment setting, where retraining or transfer learning becomes impractical due to the need for human intervention and associated latencies. Here we explore the reproducibility of deep learning for feature extraction in atom-resolved electron microscopy and introduce workflows based on ensemble learning and iterative training to greatly improve feature detection. This approach allows incorporating uncertainty quantification into the deep learning analysis and also enables rapid automated experimental workflows where retraining of the network to compensate for out-of-distribution drift due to subtle change in imaging conditions is substituted for human operator or programmatic selection of networks from the ensemble. This methodology can be further applied to machine learning workflows in other imaging areas including optical and chemical imaging.

36 MATERIALS SCIENCE↗

Structure of a paramyxovirus polymerase complex reveals a unique methyltransferase-CTD conformation

Paramyxoviruses are enveloped, nonsegmented, negative-strand RNA viruses that cause a wide spectrum of human and animal diseases. The viral genome, packaged by the nucleoprotein (N), serves as a template for the polymerase complex, composed of the large protein (L) and the homo-tetrameric phosphoprotein (P). The ~250-kDa L possesses all enzymatic activities necessary for its function but requires P in vivo. Structural information is available for individual P domains from different paramyxoviruses, but how P interacts with L and how that affects the activity of L is largely unknown due to the lack of high-resolution structures of this complex in this viral family. In this study we determined the structure of the L–P complex from parainfluenza virus 5 (PIV5) at 4.3-Å resolution using cryoelectron microscopy, as well as the oligomerization domain (OD) of P at 1.4-Å resolution using X-ray crystallography. P-OD associates with the RNA-dependent RNA polymerase domain of L and protrudes away from it, while the X domain of one chain of P is bound near the L nucleotide entry site. The methyltransferase (MTase) domain and the C-terminal domain (CTD) of L adopt a unique conformation, positioning the MTase active site immediately above the poly-ribonucleotidyltransferase domain and near the likely exit site for the product RNA 5' end. Our study reveals a potential mechanism that mononegavirus polymerases may employ to switch between transcription and genome replication. This knowledge will assist in the design and development of antivirals against paramyxoviruses.

59 BASIC BIOLOGICAL SCIENCES↗

Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression

Synthetic biology tools for regulating gene expression have many useful biotechnology and therapeutic applications. Most tools developed for this purpose control gene expression at the level of transcription, and relatively few methods are available for regulating gene expression at the translational level. Here, we design and engineer split orthogonal aminoacyl-tRNA synthetases (o-aaRS) as unique tools to control gene translation in bacteria and mammalian cells. Using chemically induced dimerization domains, we developed split o-aaRSs that mediate gene expression by conditionally suppressing stop codons in the presence of the small molecules rapamycin and abscisic acid. Furthermore, by activating o-aaRSs, these molecular switches induce stop codon suppression, and in their absence stop codon suppression is turned off. We demonstrate, in Escherichia coli and in human cells, that split o-aaRSs function as genetically encoded AND gates where stop codon suppression is controlled by two distinct molecular inputs. In addition, we show that split o-aaRSs can be used as versatile biosensors to detect therapeutically relevant protein–protein interactions, including those involved in cancer, and those that mediate severe acute respiratory syndrome-coronavirus-2 infection.

59 BASIC BIOLOGICAL SCIENCES↗

Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention

The receptor tyrosine kinase KIT and its ligand stem cell factor (SCF) are required for the development of hematopoietic stem cells, germ cells, and other cells. A variety of human cancers, such as acute myeloid leukemia, gastrointestinal stromal tumor, and mast cell leukemia, are driven by somatic gain-of-function KIT mutations. Here, we report cryo electron microscopy (cryo-EM) structural analyses of full-length wild-type and two oncogenic KIT mutants, which show that the overall symmetric arrangement of the extracellular domain of ligand-occupied KIT dimers contains asymmetric D5 homotypic contacts juxtaposing the plasma membrane. Mutational analysis of KIT reveals in D5 region an “Achilles heel” for therapeutic intervention. A ligand-sensitized oncogenic KIT mutant exhibits a more comprehensive and stable D5 asymmetric conformation. A constitutively active ligand-independent oncogenic KIT mutant adopts a V-shaped conformation solely held by D5-mediated contacts. Binding of SCF to this mutant fully restores the conformation of wild-type KIT dimers, including the formation of salt bridges responsible for D4 homotypic contacts and other hallmarks of SCF-induced KIT dimerization. These experiments reveal an unexpected structural plasticity of oncogenic KIT mutants and a therapeutic target in D5.

60 APPLIED LIFE SCIENCES↗