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At least 163 records · Page 9

All sources NASA NTRS DOE OSTI

DOE OSTI2016

Structural basis for nonneutralizing antibody competition at antigenic site II of the respiratory syncytial virus fusion protein

Palivizumab was the first antiviral monoclonal antibody (mAb) approved for therapeutic use in humans, and remains a prophylactic treatment for infants at risk for severe disease because of respiratory syncytial virus (RSV). Palivizumab is an engineered humanized version of a murine mAb targeting antigenic site II of the RSV fusion (F) protein, a key target in vaccine development. There are limited reported naturally occurring human mAbs to site II; therefore, the structural basis for human antibody recognition of this major antigenic site is poorly understood. Here, we describe a nonneutralizing class of site II-specific mAbs that competed for binding with palivizumab to postfusion RSV F protein. We also describe two classes of site II-specific neutralizing mAbs, one of which escaped competition with nonneutralizing mAbs. Here, an X-ray crystal structure of the neutralizing mAb 14N4 in complex with F protein showed that the binding angle at which human neutralizing mAbs interact with antigenic site II determines whether or not nonneutralizing antibodies compete with their binding. Fine-mapping studies determined that nonneutralizing mAbs that interfere with binding of neutralizing mAbs recognize site II with a pose that facilitates binding to an epitope containing F surface residues on a neighboring protomer. Neutralizing antibodies, like motavizumab and a new mAb designated 3J20 that escape interference by the inhibiting mAbs, avoid such contact by binding at an angle that is shifted away from the nonneutralizing site. Furthermore, binding to rationally and computationally designed site II helix–loop–helix epitope-scaffold vaccines distinguished neutralizing from nonneutralizing site II antibodies.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1990

National plan to enhance aviation safety through human factors improvements

The purpose of this section of the plan is to establish a development and implementation strategy plan for improving safety and efficiency in the Air Traffic Control (ATC) system. These improvements will be achieved through the proper applications of human factors considerations to the present and future systems. The program will have four basic goals: (1) prepare for the future system through proper hiring and training; (2) develop a controller work station team concept (managing human errors); (3) understand and address the human factors implications of negative system results; and (4) define the proper division of responsibilities and interactions between the human and the machine in ATC systems. This plan addresses six program elements which together address the overall purpose. The six program elements are: (1) determine principles of human-centered automation that will enhance aviation safety and the efficiency of the air traffic controller; (2) provide new and/or enhanced methods and techniques to measure, assess, and improve human performance in the ATC environment; (3) determine system needs and methods for information transfer between and within controller teams and between controller teams and the cockpit; (4) determine how new controller work station technology can optimally be applied and integrated to enhance safety and efficiency; (5) assess training needs and develop improved techniques and strategies for selection, training, and evaluation of controllers; and (6) develop standards, methods, and procedures for the certification and validation of human engineering in the design, testing, and implementation of any hardware or software system element which affects information flow to or from the human.

Foushee, Clay↗

NASA NTRSDate not supplied

Discovering Digital Engineering Needs Through Human-Centered Approaches

Digital engineering has the power to transform organizations in profound ways, but digitizing legacy workflows and infusing new technologies into existing practices may not yield the intended results or address the underlying problems or bottlenecks. This paper describes the human-centered approaches used to understand stakeholder challenges and identify digital engineering needs during the design-build-test portion of the systems development lifecycle. Through a series of interactive stakeholder workshops and need-finding activities, key stakeholder needs were identified to help guide the integration of digital engineering technologies. The overarching need was for downstream system development steps to be considered further upstream in the project lifecycle in a manner that allows for proactive and interactive co-constructive idea exploration, problem resolution, and requirements considerations in a collective engagement with engineers and technicians from multiple disciplines to increase efficiency and reduce risks while offering opportunities to improve the final engineered system. Supporting this need was a wide-ranging desire from stakeholders for digital and non-digital support structures for efficient rapid iteration during system development. This work yielded several improvements for system development processes and for digital engineering infusion.

Design Science↗

NASA NTRS1986

Intelligent user interface concept for space station

The space station computing system must interface with a wide variety of users, from highly skilled operations personnel to payload specialists from all over the world. The interface must accommodate a wide variety of operations from the space platform, ground control centers and from remote sites. As a result, there is a need for a robust, highly configurable and portable user interface that can accommodate the various space station missions. The concept of an intelligent user interface executive, written in Ada, that would support a number of advanced human interaction techniques, such as windowing, icons, color graphics, animation, and natural language processing is presented. The user interface would provide intelligent interaction by understanding the various user roles, the operations and mission, the current state of the environment and the current working context of the users. In addition, the intelligent user interface executive must be supported by a set of tools that would allow the executive to be easily configured and to allow rapid prototyping of proposed user dialogs. This capability would allow human engineering specialists acting in the role of dialog authors to define and validate various user scenarios. The set of tools required to support development of this intelligent human interface capability is discussed and the prototyping and validation efforts required for development of the Space Station's user interface are outlined.

Comer, Edward↗

DOE OSTI2024

Graph-Based Modeling for the Detection and Tracking of Sarin-Surrogate-Induced Neurotoxicity Using a Human-Relevant, In-Vitro Brain Model

Organophosphorus (OP) nerve agents are a chemical threat to the United States, to the civilian population (e.g., pesticides) and historically weaponized (e.g., sarin) as chemical warfare agents. The unprecedented, accelerated process from “bench-to-bedside” during the SARSCov2 pandemic has made it clear that technology and tools need to be readily available for immediate response. Advances in human organ tissue mimetic systems are a promising technology to evaluate the human-relevant response in vitro for basic and applied research and drug screening. In particular, current brain microphysiological systems (MPS) have the capability to monitor and detect changes in engineered human neural circuit activity. However, current data analytics approaches for these systems lack the granularity to functionally detect and distinguish the different mechanisms that occur in the brain following neurotoxicity, injury, and disease. The goal of this project was to advance the computational analytical capabilities of the brain MPS to detect functional changes in neural circuit structure at different stages of Sarin surrogate-induced neurotoxicity. We developed graph-based models to (1) identify the composition of the neural circuit structure; (2) detect and monitor how this structure changes following sarin-induced neurotoxicity; and (3) evaluate the analytical pipeline using known/promising oxime reactivators. Through experiments on the bMPS where in vitro neuronal cultures were exposed to a sarin surrogate, we demonstrated the capabilities of our computational pipeline to identify different responses in the functional networks of brain cells exposed to low and high concentrations of the nerve agent. We identified a biphasic response of human neural network activity following exposure to a sarin-surrogate that had not been reported in the literature before. The graph-based models and software developed in this project can be used for future studies that leverage the brain MPS technology, such as treatment efficacy assessment.

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS1981

NASA's Role in Aeronautics: A Workshop. Volume 1: Summary

The state of the U.S. aeronautic industry and progressive changes in national priorities as reflected in federal unified budget outlays are reviewed as well as the contribution of NACA and the character and substance of U.S. aeronautical research under NASA. Eight possible roles for the future defined by NASA are examined and the extent to which the agency should carry out these activities is considered. The roles include: (1) national facilities expertise; (2) flight sciences research; (3) generic technology evolution; (4) vehicle class evolution; (5) technology demonstration; (6) prototype development; (7) technology validation; and (8) operations feasibility; How NASA's roles varies in the areas of military aviation, general aviation, transport aircraft aeronautics, rotorcraft aeronautics, engineering education, information dissemination, and cooperation with other organizations and agencies is discussed with regard to research in aerodynamics; structures and materials; propulsion; electronics and avionics; vehicle operations; and human engineering.

Source record↗

NASA NTRSDate not supplied

Discovering Digital Engineering Needs Through Human-Centered Approaches

Human-centered Design↗

NASA NTRS2009

Results and Lessons Learned from Performance Testing of Humans in Spacesuits in Simulated Reduced Gravity

NASA's Constellation Program has plans to return to the Moon within the next 10 years. Although reaching the Moon during the Apollo Program was a remarkable human engineering achievement, fewer than 20 extravehicular activities (EVAs) were performed. Current projections indicate that the next lunar exploration program will require thousands of EVAs, which will require spacesuits that are better optimized for human performance. Limited mobility and dexterity, and the position of the center of gravity (CG) are a few of many features of the Apollo suit that required significant crew compensation to accomplish the objectives. Development of a new EVA suit system will ideally result in performance close to or better than that in shirtsleeves at 1 G, i.e., in "a suit that is a pleasure to work in, one that you would want to go out and explore in on your day off." Unlike the Shuttle program, in which only a fraction of the crew perform EVA, the Constellation program will require that all crewmembers be able to perform EVA. As a result, suits must be built to accommodate and optimize performance for a larger range of crew anthropometry, strength, and endurance. To address these concerns, NASA has begun a series of tests to better understand the factors affecting human performance and how to utilize various lunar gravity simulation environments available for testing.

Chappell, Steven P.↗

NASA NTRS2007

Integrating Human Factors into Crew Exploration Vehicle (CEV) Design

The purpose of this design process is to apply Human Engineering (HE) requirements and guidelines to hardware/software and to provide HE design, analysis and evaluation of crew interfaces. The topics include: 1) Background/Purpose; 2) HE Activities; 3) CASE STUDY: Net Habitable Volume (NHV) Study; 4) CASE STUDY: Human Modeling Approach; 5) CASE STUDY: Human Modeling Results; 6) CASE STUDY: Human Modeling Conclusions; 7) CASE STUDY: Human-in-the-Loop Evaluation Approach; 8) CASE STUDY: Unsuited Evaluation Results; 9) CASE STUDY: Suited Evaluation Results; 10) CASE STUDY: Human-in-the-Loop Evaluation Conclusions; 11) Near-Term Plan; and 12) In Conclusion

Mihriban Whitmore↗

NASA NTRS1988

Pilot factors guidelines for the operational inspection of navigation systems

A computerized human engineered inspection technique is developed for use by FAA inspectors in evaluating the pilot factors aspects of aircraft navigation systems. The short title for this project is Nav Handbook. A menu-driven checklist, computer program and data base (Human Factors Design Criteria) were developed and merged to form a self-contained, portable, human factors inspection checklist tool for use in a laboratory or field setting. The automated checklist is tailored for general aviation navigation systems and can be expanded for use with other aircraft systems, transports or military aircraft. The Nav Handbook inspection concept was demonstrated using a lap-top computer and an Omega/VLF CDU. The program generates standardized inspection reports. Automated checklists for LORAN/C and R NAV were also developed. A Nav Handbook User's Guide is included.

Sadler, J. F.↗

NASA NTRS1988

Man-systems requirements for the control of teleoperators in space

The microgravity of the space environment has profound effects on humans and, consequently, on the design requirements for subsystems and components with which humans interact. There are changes in the anthropometry, vision, the perception of orientation, posture, and the ways in which we exert energy. The design requirements for proper human engineering must reflect each of the changes that results, and this is especially true in the exercise of control over remote and teleoperated systems where the operator is removed from any direct sense of control. The National Aeronautics and Space Administration has recently completed the first NASA-wide human factors standard for microgravity. The Man-Systems Integration Standard, NASA-STD-3000, contains considerable information on the appropriate design criteria for microgravity, and there is information that is useful in the design for teleoperated systems. There is not, however, a dedicated collection of data which pertains directly to the special cases of remote and robotic operations. The design considerations for human-system interaction in the control of remote systems in space are discussed, with brief details on the information to be found in the NASA-STD-3000, and arguments for a dedicated section within the Standard which deals with robotic, teleoperated and remote systems and the design requirements for effective human control of these systems in the space environment, and from the space environment.

Shields, Nicholas L., Jr.↗

DOE OSTI2019

Using a coupled agent-based modeling approach to analyze the role of risk perception in water management decisions

Abstract. Managing water resources in a complex adaptive natural–human system is a challenge due to the difficulty of modeling human behavior under uncertain risk perception. The interaction between human-engineered systems and natural processes needs to be modeled explicitly with an approach that can quantify the influence of incomplete/ambiguous information on decision-making processes. In this study, we two-way coupled an agent-based model (ABM) with a river-routing and reservoir management model (RiverWare) to address this challenge. The human decision-making processes is described in the ABM using Bayesian inference (BI) mapping joined with a cost–loss (CL) model (BC-ABM). Incorporating BI mapping into an ABM allows an agent's psychological thinking process to be specified by a cognitive map between decisions and relevant preceding factors that could affect decision-making. A risk perception parameter is used in the BI mapping to represent an agent's belief on the preceding factors. Integration of the CL model addresses an agent's behavior caused by changing socioeconomic conditions. We use the San Juan River basin in New Mexico, USA, to demonstrate the utility of this method. The calibrated BC-ABM–RiverWare model is shown to capture the dynamics of historical irrigated area and streamflow changes. The results suggest that the proposed BC-ABM framework provides an improved representation of human decision-making processes compared to conventional rule-based ABMs that do not take risk perception into account. Future studies will focus on modifying the BI mapping to consider direct agents' interactions, up-front cost of agent's decision, and upscaling the watershed ABM to the regional scale.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗

NASA NTRS2022

Design Thinking, Lean Startup, and High-Technology Marketing for Human-Centered Systems Engineering

The use of design thinking, lean startup, and high-technology marketing in systems engineering are presented as a case study. All were used and evaluated for their potential to improve systems engineering processes and design, address the challenges of culture change, increase the adoption rate of new technology, and engage with potential users and sponsors more effectively. Multiple examples of training and use on a model-based systems engineering initiative at a large government agency showcase how these approaches were tailored and used successfully for significant benefits such as enhanced collaboration and better problem definition and design solutions. Challenges remain for use by quiet thinkers and with virtual teams. These new ways of thinking are well aligned with creating and using new technologies and are suitable for situations involving innovation, uncertainty, and change within organizations. This case study intends to familiarize systems engineers with the application of these human-centered approaches, to interest systems engineers in incorporating these approaches into their work processes ,and to inspire the systems engineering research community to investigate further.

Karen J. Weiland↗

NASA NTRS2007

Integrating Human Factors into Crew Exploration Vehicle Design

With NASA's new Vision for Exploration to send humans beyond Earth orbit, it is critical to consider the human as a system that demands early and continuous user involvement, and an iterative prototype/test/redesign process. Addressing human-system interface issues early on can be very cost effective even cost reducing when performed early in the design and development cycle. To achieve this goal within Crew Exploration Vehicle (CEV) Project Office, human engineering (HE) team is formed. Key tasks are to apply HE requirements and guidelines to hardware/software, and provide HE design, analysis and evaluation of crew interfaces. Initial activities included many practice-orientated evaluations using low-fidelity CEV mock-ups. What follows is a description of such evaluations that focused on a HE requirement regarding Net Habitable Volume (NHV). NHV is defined as the total remaining pressurized volume available to on-orbit crew after accounting for the loss of volume due to deployed hardware and structural inefficiencies which decrease functional volume. The goal of the NHV evaluations was to develop requirements providing sufficient CEV NHV for crewmembers to live and perform tasks in support of mission goals. Efforts included development of a standard NHV calculation method using computer models and physical mockups, and crew/ stakeholder evaluations. Nine stakeholders and ten crewmembers participated in the unsuited evaluations. Six crewmembers also participated in a suited evaluation. The mock-up was outfitted with volumetric representation of sub-systems such as seats, and stowage bags. Thirteen scenarios were developed to represent mission/crew tasks and considered to be primary volume drivers (e.g., suit donning) for the CEV. Unsuited evaluations included a structured walkthrough of these tasks. Suited evaluations included timed donning of the existing launch and entry suit to simulate a contingency scenario followed by doffing/ stowing of the suits. All mockup evaluations were videotaped. Structured questionnaires were used to document user interface issues and volume impacts of layout configuration. Computer model and physical measures of the NHV agreed within 1 percent. This included measurement of the gross habitable volume, subtraction of intrusive volumes, and other non-habitable spaces. Calculation method developed was validated as a standard means of measuring NHV, and was recommended as a verification method for the NHV requirements. Evaluations confirmed that there was adequate volume for unsuited scenarios and suit donning/ doffing activity. Seats, suit design stowage and waste hygiene system noted to be critical volume drivers. The low-fidelity mock-up evaluations along with human modeling analysis generated discussions that will lead to high-level systems requirements and human-centered design decisions. This approach allowed HE requirements and operational concepts to evolve in parallel with engineering system concepts and design requirements. As the CEV design matures, these evaluations will continue and help with design decisions, and assessment, verification and validation of HE requirements.

Whitmore, Mihriban↗

DOE OSTI2018

Crystallographic and kinetic analyses of human IPMK reveal disordered domains modulate ATP binding and kinase activity

Inositol polyphosphate multikinase (IPMK) is a member of the IPK-superfamily of kinases, catalyzing phosphorylation of several soluble inositols and the signaling phospholipid PI(4,5)P 2 (PIP 2 ). IPMK also has critical non-catalytic roles in p53, mTOR/Raptor, TRAF6 and AMPK signaling mediated partly by two disordered domains. Although IPMK non-catalytic functions are well established, it is less clear if the disordered domains are important for IPMK kinase activity or ATP binding. Here, kinetic and structural analyses of an engineered human IPMK lacking all disordered domains (ΔIPMK) are presented. Although the K M for PIP 2 is identical between ΔIPMK and wild type, ΔIPMK has a 1.8-fold increase in k cat for PIP 2 , indicating the native IPMK disordered domains decrease IPMK activity in vitro . The 2.5 Å crystal structure of ΔIPMK is reported, confirming the conserved ATP-grasp fold. A comparison with other IPK-superfamily structures revealed a putative “ATP-clamp” in the disordered N-terminus, we predicted would stabilize ATP binding. Consistent with this observation, removal of the ATP clamp sequence increases the K M for ATP 4.9-fold, indicating the N-terminus enhances ATP binding to IPMK. Together, these structural and kinetic studies suggest in addition to mediating protein-protein interactions, the disordered domains of IPMK impart modulatory capacity to IPMK kinase activity through multiple kinetic mechanisms.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Multi-Objective Optimization of Uranium Target Assembly–3: A Comparison of Genetic and Traditional Methods

Commonly produced as a byproduct of uranium fission, 99 Mo is a key medical isotope that is in high demand in the United States. An international goal is to switch from medical isotope production technologies that require highly enriched uranium to medical isotope production technologies that require only low-enriched uranium. Niowave Inc. is contributing to this goal by developing an accelerator-driven subcritical assembly called the Uranium Target Assembly (UTA). This work compares the performance of Dakota’s Multi-Objective Genetic Algorithm (MOGA) against traditional sensitivity analysis in the neutronic optimization of the UTA-3 system. The design objectives are k-eigenvalue (k eff ) and natural uranium fission power, which are directly correlated with the amount of 99 Mo produced. Dakota:MOGA did not perform as well as human engineering ingenuity in optimization studies with high numbers of input parameters, such as fuel rod type selection and fuel rod placement. However, Dakota:MOGA did outperform traditional sensitivity analysis in optimization studies with fewer than 20 parameters and revealed the degree to which each parameter influences the optimal design space for k eff and natural uranium fission power (to a lesser extent). As the design model became more complex in the final stage of design, the computational resources required to calculate the design objective values in the Monte Carlo N-Particle transport code from selected input parameter combinations limited Dakota:MOGA’s performance, and, unfortunately, human intervention was required to discern the optimal design space. In conclusion, future work will attempt to reduce computational resource constraints by incorporating areduced-order neutronics model into the optimization cycle.

Accelerator-driven systems↗

DOE OSTI2022

Asteroids for μ Hz gravitational-wave detection

A major challenge for gravitational-wave (GW) detection in the μHz band is engineering a test mass (TM) with sufficiently low acceleration noise. We propose a GW detection concept using asteroids located in the inner Solar System as TMs. Our main purpose is to evaluate the acceleration noise of asteroids in the μHz band. We show that a wide variety of environmental perturbations are small enough to enable an appropriate class of ~10 km-diameter asteroids to be employed as TMs. This would allow a sensitive GW detector in the band (few) × 10 -7 Hz ≲ fGW ≲ (few) × 10 -5 Hz, reaching strain hc ~ 10 -19 around f GW ~10 μHz, sufficient to detect a wide variety of sources. To exploit these asteroid TMs, human-engineered base stations could be deployed on multiple asteroids, each equipped with an electromagnetic transmitter/receiver to permit measurement of variations in the distance between them. We discuss a potential conceptual design with two base stations, each with a space-qualified optical atomic clock measuring the round-trip electromagnetic pulse travel time via laser ranging. Trade space exists to optimize multiple aspects of this mission: for example, using a radio-ranging or interferometric link system instead of laser ranging. This motivates future dedicated technical design study. This mission concept holds exceptional promise for accessing this GW frequency band.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

DOE OSTI2017

Engineered antibody CH2 domains binding to nucleolin: Isolation, characterization and improvement of aggregation

Smaller recombinant antibody fragments are now emerging as alternatives of conventional antibodies. Especially, immunoglobulin (Ig) constant CH2 domain and engineered CH2 with improved stability are promising as scaffolds for selection of specific binders to various antigens. We constructed a yeast display library based on an engineered human IgG1 CH2 scaffold with diversified loop regions. A group of CH2 binders were isolated from this yeast display library by panning against nucleolin, which is a tumor-associated antigen involved in cell proliferation, tumor cell growth and angiogenesis. Out of 20 mutants, we selected 3 clones exhibiting relatively high affinities to nucleolin on yeasts. However, recombinant CH2 mutants aggregated when they were expressed. To find the mechanism of the aggregation, we employed computational prediction approaches through structural homology models of CH2 binders. The analysis of potential aggregation prone regions (APRs) and solvent accessible surface areas (ASAs) indicated two hydrophobic residues, Val{sub 264} and Leu{sub 309}, in the β-sheet, in which replacement of both charged residues led to significant decrease of the protein aggregation. The newly identified CH2 binders could be improved to use as candidate therapeutics or research reagents in the future. - Highlights: • Novel engineered CH2 domains to nucleolin were identified from the yeast display CH2-based library. • Aggregation prone regions (APRs) were predicted through structural homology models CH2 domains. • The replacement of two hydrophobic residues in APRs significantly led to decrease of the CH2 aggregation.

60 APPLIED LIFE SCIENCES↗