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NASA NTRS2020

Enabling Space Exploration Medical System Development Using a Tool Ecosystem

The NASA Human Research Program's (HRP) Exploration Medical Capability (ExMC) Element is utilizing a Model Based Systems Engineering (MBSE) approach to enhance the development of systems engineering products that will be used to advance medical system designs for exploration missions beyond Low Earth Orbit. In support of future missions, the team is capturing content such as system behaviors, functional decompositions, architecture, system requirements and interfaces, and recommendations for clinical capabilities and resources in Systems Modeling Language (SysML) models. As these products mature, SysML models provide a way for ExMC to capture relationships among the various products, which includes supporting more integrated and multi-faceted views of future medical systems. In addition to using SysML models, HRP and ExMC are developing supplementary tools to support two key functions: 1) prioritizing current and future research activities for exploration missions in an objective manner; and 2) enabling risk-informed and evidence-based trade space analysis for future space vehicles, missions, and systems. This paper will discuss the long-term HRP and ExMC vision for the larger ecosystem of tools, which include dynamic Probabilistic Risk Assessment (PRA) capabilities, additional SysML models, a database of system component options, and data visualizations. It also includes a review of an initial Pilot Project focused on enabling medical system trade studies utilizing data that is coordinated across tools for consistent outputs (e.g., mission risk metrics that are associated with medical system mass values and medical conditions addressed). This first Pilot Project demonstrated successful operating procedures and integration across tools. Finally, the paper will also cover a second Pilot Project that utilizes tool enhancements such as medical system optimization capabilities, post-processing, and visualization of generated data for subject matter expert review, and increased integration amongst the tools themselves.

Amador, Jennifer R.↗

DOE OSTI2015

Risk considerations for WIPP passive institutional controls - 15173

The regulatory assurance measures for the Waste Isolation Pilot Plant (WIPP) include such things as active and passive institutional controls, monitoring, waste retrieval/removal capabilities and engineered barriers. Passive Institutional Controls (PICs) are an assurance measure intended to reduce the likelihood of humans unintentionally intruding the WIPP geologic radioactive waste disposal system for thousands of years after it is closed. The waste repository is designed such that it should not pose a significant risk to future populations if it is left undisturbed. The design has also been demonstrated through a performance assessment (PA) analysis to not pose a significant risk to future generations even if it is intruded upon by an inadvertent drilling intrusion [1, Appendix PA]. Through PA, it has been determined that the overall risk of the disposal system to people and the environment is small. The intent of the regulatory Assurance Requirements and PICs is to provide additional confidence that the repository will perform as expected after closure. However, the actual implementation of the proposed PICs design may pose a greater risk to the current population than they would potentially reduce for future generations. Specifically, the risks due to industrial accidents, construction and transportation risks incurred during the fabrication and construction of the permanent markers system may be greater than the overall reduction in risk to future generations due to the existence of the permanent markers. If this were true, implementation of the current PICs design may be counter to the intention of the regulatory requirement to include such assurance measures. As such, provisions for assurance measures used in geologic radioactive waste disposal facilities, such as PICs, should consider risk impacts. A provision of any disposal program's Regulatory Assurance Requirements should address the impacts of the known risks from all the components of the assurance-related systems. The initial WIPP PICs design was developed as part of the regulatory certification process in 1996 with the intent of being revised when the WIPP closes several decades from now [2, Appendix PIC]. The revised design that will be developed at closure should address the design's potential reduction to long-term risks from the repository and the risks due to the implementation of the final design. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

DOE OSTI2015

Silica bioreplication preserves three-dimensional spheroid structures of human pluripotent stem cells and HepG2 cells

Three-dimensional (3D) cell cultures produce more in vivo-like multicellular structures such as spheroids that cannot be obtained in two-dimensional (2D) cell cultures. Thus, they are increasingly employed as models for cancer and drug research, as well as tissue engineering. It has proven challenging to stabilize spheroid architectures for detailed morphological examination. Here we overcome this issue using a silica bioreplication (SBR) process employed on spheroids formed from human pluripotent stem cells (hPSCs) and hepatocellular carcinoma HepG2 cells cultured in the nanofibrillar cellulose (NFC) hydrogel. The cells in the spheroids are more round and tightly interacting with each other than those in 2D cultures, and they develop microvilli-like structures on the cell membranes as seen in 2D cultures. Furthermore, SBR preserves extracellular matrix-like materials and cellular proteins. In conclusion, these findings provide the first evidence of intact hPSC spheroid architectures and similar fine structures to 2D-cultured cells, providing a pathway to enable our understanding of morphogenesis in 3D cultures.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2025

Data for "RT-EZ: A Golden Gate Assembly Toolkit for Streamlined Genetic Engineering of Rhodotorula toruloides"

For economic and sustainable biomanufacturing, the oleaginous yeast Rhodotorula toruloides has emerged as a promising platform for producing biofuels, pharmaceuticals, and other valuable chemicals. However, genetic manipulation of R. toruloides has been limited by its high GC content and the lack of a replicating plasmid, necessitating gene integration into the genome of the yeast. To address these challenges, we developed the RT-EZ ( R. toruloides Efficient Zipper) toolkit, a versatile tool based on Golden Gate assembly, designed to streamline R. toruloides engineering with improved efficiency and flexibility. The RT-EZ toolkit simplifies vector construction by incorporating new features such as bidirectional promoters and 2A peptides, color-based screening using RFP, and sequences optimized for both Agrobacterium tumefaciens-mediated transformation (ATMT) and easy linearization, enabling straightforward selection and transformation. Notably, the RT-EZ kit can be used to construct an expression cassette with four different genes in one assembly reaction, significantly improving vector construction speed and efficiency. The utility of the RT-EZ toolkit was demonstrated through the successful synthesis of arachidonic acid in R. toruloides by coexpressing fatty acid elongases and desaturases. This result underscores the potential of the RT-EZ toolkit to advance synthetic biology in R. toruloides , providing a streamlined method for addressing genetic engineering challenges in the yeast.

gene editing↗

DOE OSTI2018

UNC-5 netrin receptor B mediates osteogenic differentiation by modulating bone morphogenetic protein signaling in human adipose-derived stem cells

Highlights: • UNC5B facilitates osteogenic differentiation of human adipose-derived stem cells. • It does so by modulation bone morphogenetic protein signaling. • UNC5B may be useful for bone tissue engineering and therapy for bone defects. UNC-5 netrin receptor B (UNC5B) is a dependence receptor of netrin-1 that plays an essential role in mediating angiogenesis and tumorigenesis. Despite its significant roles, there is limited knowledge about the role played by UNC5B in osteogenesis. In the present study, we first demonstrated that UNC5B was required for osteogenic differentiation of human adipose-derived stem cells (hASCs), both in vitro and in vivo. We also found that mechanistically, UNC5B promotes osteogenic differentiation by activating bone morphogenetic protein signaling. These findings point to a new important function of UNC5B and provide a potential basis for hASCs-mediated bone regeneration.

60 APPLIED LIFE SCIENCES↗

NASA NTRS2000

Information Power Grid: Distributed High-Performance Computing and Large-Scale Data Management for Science and Engineering

The term "Grid" refers to distributed, high performance computing and data handling infrastructure that incorporates geographically and organizationally dispersed, heterogeneous resources that are persistent and supported. The vision for NASN's Information Power Grid - a computing and data Grid - is that it will provide significant new capabilities to scientists and engineers by facilitating routine construction of information based problem solving environments / frameworks that will knit together widely distributed computing, data, instrument, and human resources into just-in-time systems that can address complex and large-scale computing and data analysis problems. IPG development and deployment is addressing requirements obtained by analyzing a number of different application areas, in particular from the NASA Aero-Space Technology Enterprise. This analysis has focussed primarily on two types of users: The scientist / design engineer whose primary interest is problem solving (e.g., determining wing aerodynamic characteristics in many different operating environments), and whose primary interface to IPG will be through various sorts of problem solving frameworks. The second type of user if the tool designer: The computational scientists who convert physics and mathematics into code that can simulate the physical world. These are the two primary users of IPG, and they have rather different requirements. This paper describes the current state of IPG (the operational testbed), the set of capabilities being put into place for the operational prototype IPG, as well as some of the longer term R&D tasks.

Johnston, William E.↗

NASA NTRS1992

Engineering verification of the biomass production chamber

The requirements for life support systems, both biological and physical-chemical, for long-term human attended space missions are under serious study throughout NASA. The KSC 'breadboard' project has focused on biomass production using higher plants for atmospheric regeneration and food production in a special biomass production chamber. This chamber is designed to provide information on food crop growth rate, contaminants in the chamber that alter plant growth requirements for atmospheric regeneration, carbon dioxide consumption, oxygen production, and water utilization. The shape and size, mass, and energy requirements in relation to the overall integrity of the biomass production chamber are under constant study.

Prince, R. P.↗

NASA NTRS1990

The cleanroom case study in the Software Engineering Laboratory: Project description and early analysis

This case study analyzes the application of the cleanroom software development methodology to the development of production software at the NASA/Goddard Space Flight Center. The cleanroom methodology emphasizes human discipline in program verification to produce reliable software products that are right the first time. Preliminary analysis of the cleanroom case study shows that the method can be applied successfully in the FDD environment and may increase staff productivity and product quality. Compared to typical Software Engineering Laboratory (SEL) activities, there is evidence of lower failure rates, a more complete and consistent set of inline code documentation, a different distribution of phase effort activity, and a different growth profile in terms of lines of code developed. The major goals of the study were to: (1) assess the process used in the SEL cleanroom model with respect to team structure, team activities, and effort distribution; (2) analyze the products of the SEL cleanroom model and determine the impact on measures of interest, including reliability, productivity, overall life-cycle cost, and software quality; and (3) analyze the residual products in the application of the SEL cleanroom model, such as fault distribution, error characteristics, system growth, and computer usage.

Green, Scott↗

NASA NTRS2011

Modeling Constellation Virtual Missions Using the Vdot(Trademark) Process Management Tool

The authors have identified a software tool suite that will support NASA's Virtual Mission (VM) effort. This is accomplished by transforming a spreadsheet database of mission events, task inputs and outputs, timelines, and organizations into process visualization tools and a Vdot process management model that includes embedded analysis software as well as requirements and information related to data manipulation and transfer. This paper describes the progress to date, and the application of the Virtual Mission to not only Constellation but to other architectures, and the pertinence to other aerospace applications. Vdot s intuitive visual interface brings VMs to life by turning static, paper-based processes into active, electronic processes that can be deployed, executed, managed, verified, and continuously improved. A VM can be executed using a computer-based, human-in-the-loop, real-time format, under the direction and control of the NASA VM Manager. Engineers in the various disciplines will not have to be Vdot-proficient but rather can fill out on-line, Excel-type databases with the mission information discussed above. The author s tool suite converts this database into several process visualization tools for review and into Microsoft Project, which can be imported directly into Vdot. Many tools can be embedded directly into Vdot, and when the necessary data/information is received from a preceding task, the analysis can be initiated automatically. Other NASA analysis tools are too complex for this process but Vdot automatically notifies the tool user that the data has been received and analysis can begin. The VM can be simulated from end-to-end using the author s tool suite. The planned approach for the Vdot-based process simulation is to generate the process model from a database; other advantages of this semi-automated approach are the participants can be geographically remote and after refining the process models via the human-in-the-loop simulation, the system can evolve into a process management server for the actual process.

Hardy, Roger↗

DOE OSTI2022

Cryo-EM, Protein Engineering, and Simulation Enable the Development of Peptide Therapeutics against Acute Myeloid Leukemia

Cryogenic electron microscopy (cryo-EM) has emerged as a viable structural tool for molecular therapeutics development against human diseases. However, it remains a challenge to determine structures of proteins that are flexible and smaller than 30 kDa. The 11 kDa KIX domain of CREB-binding protein (CBP), a potential therapeutic target for acute myeloid leukemia and other cancers, is a protein which has defied structure-based inhibitor design. Here, we develop an experimental approach to overcome the size limitation by engineering a protein double-shell to sandwich the KIX domain between apoferritin as the inner shell and maltose-binding protein as the outer shell. To assist homogeneous orientations of the target, disulfide bonds are introduced at the target–apoferritin interface, resulting in a cryo-EM structure at 2.6 Å resolution. We used molecular dynamics simulations to design peptides that block the interaction of the KIX domain of CBP with the intrinsically disordered pKID domain of CREB. The double-shell design allows for fluorescence polarization assays confirming the binding between the KIX domain in the double-shell and these interacting peptides. Further cryo-EM analysis reveals a helix–helix interaction between a single KIX helix and the best peptide, providing a possible strategy for developments of next-generation inhibitors.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

NASA NTRS2012

Propulsion Progress for NASA's Space Launch System

Leaders from NASA's Space Launch System (SLS) will participate in a panel discussing the progress made on the program's propulsion systems. The SLS will be the nation's next human-rated heavy-lift vehicle for new missions beyond Earth's orbit. With a first launch slated for 2017, the SLS Program is turning plans into progress, with the initial rocket being built in the U.S.A. today, engaging the aerospace workforce and infrastructure. Starting with an overview of the SLS mission and programmatic status, the discussion will then delve into progress on each of the primary SLS propulsion elements, including the boosters, core stage engines, upper stage engines, and stage hardware. Included will be a discussion of the 5-segment solid rocket motors (ATK), which are derived from Space Shuttle and Ares developments, as well as the RS-25 core stage engines from the Space Shuttle inventory and the J- 2X upper stage engine now in testing (Pratt and Whitney Rocketdyne). The panel will respond to audience questions about this important national capability for human and scientific space exploration missions.

May, Todd A.↗

NASA NTRS2005

Return to Flight Resource Reel 1 of 2

A video presentation detailing the tests performed on the Space Shuttle Discovery in preparation for its return to flight is shown. The tests include: 1) Reinforced Carbon-Carbon (RCC) Impact Test Article; 2) RCC Foam Impact Testing; 3) Thermal Protection System (TPS) Ice Impact Testing featuring Justin Kerr, Project Engineer; 4) Wing Leading Edge Wireless Sensors featuring Karl Kiefer, President and CEO of Invocon, and Kevin Champaigne of Invocon; 5) TPS Repair Testing KC-135 Zero-G Environment featuring Soichi Noguchi, Mission Specialist; 6) TPS Extravehicular Activity Tool Demonstration; 7) TPS Repair Testing Vacuum Glove box; 8) TPS Repair Testing Human Thermal Vacuum Chamber; 9) TPS Reentry Testing Atmospheric Reentry Materials and Structures Evaluation Facility; 10) TPS Alternative Repair Concept; 11) Lora Bailey Lead Engineer for EVA Tools; 12) Reinforced Carbon-Carbon ATK Thiokol Plug Repair Animation; 13) 3-Percent Model Build-Up; and 14) Wind Tunnel Testing RCC Aging Research Ballistic Testing.

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DOE OSTI2023

CASTLE: Conflict Analysis Strategy Testing Laboratory Environment v.1.0.0

SAND2024-01743O The Conflict Analysis Strategy Testing Laboratory Environment (CASTLE) is a software framework that enables and simplifies building a novel, turn-based strategy game in which it can define its own rules, maps, pieces, and interactions. The software is for novice to experienced programmers with some knowledge of Unity3D, a tool used in game production. CASTLE includes a library of common game mechanics used for strategic wargames and traditional board games, such as cards, tokens, dice, and grid maps. It follows design principles popularized by the video game industry and uses singletons for managing portions of the code. CASTLE builds on Unity's component-based design and can respond to engine events during execution. Among the numerous user-friendly features: Build games quickly and cost-effectively Network in real-time and apply data to new games developed on the framework Host multiple participants online Connect rule- or machine learning-based agents to a CASTLE game to serve as opponents or to simulate games Collect data collection from players and in-game behaviors Create a survey to gather demographics or opinions from players Store data locally or save it to an external database through Representational State Transfer (REST) functions CASTLE, which was prototyped using Microsoft Azure, is also designed for easily distributing online games using popular cloud services. The multiplayer functionality includes an agent interface, allowing developers to construct AI players that can substitute for humans in any of the games. Sandia National Laboratories is a multimission laboratory managed and operated by National Technology & Engineering Solutions of Sandia, LLC, a wholly owned subsidiary of Honeywell International Inc., for the U.S. Department of Energy’s National Nuclear Security Administration under contract DE-NA0003525.

Fabian, Nathan↗

NASA NTRS2017

NASA Collaborative Design Processes

This is Block 1, the first evolution of the world's most powerful and versatile rocket, the Space Launch System, built to return humans to the area around the moon. Eventually, larger and even more powerful and capable configurations will take astronauts and cargo to Mars. On the sides of the rocket are the twin solid rocket boosters that provide more than 75 percent during liftoff and burn for about two minutes, after which they are jettisoned, lightening the load for the rest of the space flight. Four RS-25 main engines provide thrust for the first stage of the rocket. These are the world's most reliable rocket engines. The core stage is the main body of the rocket and houses the fuel for the RS-25 engines, liquid hydrogen and liquid oxygen, and the avionics, or "brain" of the rocket. The core stage is all new and being manufactured at NASA's "rocket factory," Michoud Assembly Facility near New Orleans. The Launch Vehicle Stage Adapter, or LVSA, connects the core stage to the Interim Cryogenic Propulsion Stage. The Interim Cryogenic Propulsion Stage, or ICPS, uses one RL-10 rocket engine and will propel the Orion spacecraft on its deep-space journey after first-stage separation. Finally, the Orion human-rated spacecraft sits atop the massive Saturn V-sized launch vehicle. Managed out of Johnson Space Center in Houston, Orion is the first spacecraft in history capable of taking humans to multiple destinations within deep space. 2) Each element of the SLS utilizes collaborative design processes to achieve the incredible goal of sending human into deep space. Early phases are focused on feasibility and requirements development. Later phases are focused on detailed design, testing, and operations. There are 4 basic phases typically found in each phase of development.

Jones, Davey↗

DOE OSTI2024

Improving the User Interface of the DeepLynx Data Warehouse

DeepLynx is an open-source ontology-based data warehouse created by INL to support the creation and life cycle of digital engineering projects, with a particular emphasis on digital twins [1]. Digital twins are systems that represent physical assets and process in a real-time digital environment [1]. Most well-known commercial data warehouses use Graphical User Interfaces (GUIs) for users to interact with their systems [3]. Limited publications have addressed the design of these interfaces and understanding of their target users. The current users and development team acknowledge the need to improve the current UI, not just for aesthetics but to improve functionality and workflow of DeepLynx. Traditional data warehouse users are developers, data scientists and business analysts [2]. DeepLynx users have a vast range of experience using data warehouses, and diverse roles, including engineers, scientists and management positions. Because there is a broader audience of target users for DeepLynx than a typical data warehouse, it is essential that DeepLynx has a useable and intuitive user interface. To achieve this the team performed human-computer interaction methods, including a Heuristic Evaluation of current UI using Neilsen’s Usability Heuristic, create personas based on current users by designing a user survey, data analysis and develop of personas. Followed by a redesign of the UI following using Neilsen’s Usability Heuristic and Norman’s Principles of Interactive Design in industry standard software Figma. Lastly a Heuristic Evaluation of new UI design, using Neilsen’s Usability Heuristic and User testing of redesign UI and have a group of users complete a Thinking Aloud Test of the new UI. Preliminary results of the Heuristic Evaluation of current UI arise issue with Consistency and Standards, Visibility of System Status, Match System and Real World and Recognition Rather than Recall. These issues were addressed in the proposed redesign by applying Neilsen’s Usability Heuristic and Norman’s Principles of Interactive Design. Next steps include formalized list of lessons learned and design implications for future publications.

97 MATHEMATICS AND COMPUTING↗

NASA NTRSDate not supplied

Integrated Systems and Operational Autonomy for Gateway

The Lunar Gateway space station will be operated with less human oversight and control than any human spacecraft thus far. An autonomous software control architecture has been developed to allow the spacecraft to maintain safe operations of the vehicle during times of no human involvement. The development of these autonomous control functionalities has been both technical and process driven. Given that the Gateway will be built modularly with contributions from all over the world, the systems engineering processes had to be shaped to fit with the contractual and political realities of the construction of the international lunar habitat. This paper will describe these challenges and contributions to the development of human spacecraft for sustainable deep space missions.

J M Badger↗

NASA NTRS1989

A Boltzmann machine for the organization of intelligent machines

In the present technological society, there is a major need to build machines that would execute intelligent tasks operating in uncertain environments with minimum interaction with a human operator. Although some designers have built smart robots, utilizing heuristic ideas, there is no systematic approach to design such machines in an engineering manner. Recently, cross-disciplinary research from the fields of computers, systems AI and information theory has served to set the foundations of the emerging area of the design of intelligent machines. Since 1977 Saridis has been developing an approach, defined as Hierarchical Intelligent Control, designed to organize, coordinate and execute anthropomorphic tasks by a machine with minimum interaction with a human operator. This approach utilizes analytical (probabilistic) models to describe and control the various functions of the intelligent machine structured by the intuitively defined principle of Increasing Precision with Decreasing Intelligence (IPDI) (Saridis 1979). This principle, even though resembles the managerial structure of organizational systems (Levis 1988), has been derived on an analytic basis by Saridis (1988). The purpose is to derive analytically a Boltzmann machine suitable for optimal connection of nodes in a neural net (Fahlman, Hinton, Sejnowski, 1985). Then this machine will serve to search for the optimal design of the organization level of an intelligent machine. In order to accomplish this, some mathematical theory of the intelligent machines will be first outlined. Then some definitions of the variables associated with the principle, like machine intelligence, machine knowledge, and precision will be made (Saridis, Valavanis 1988). Then a procedure to establish the Boltzmann machine on an analytic basis will be presented and illustrated by an example in designing the organization level of an Intelligent Machine. A new search technique, the Modified Genetic Algorithm, is presented and proved to converge to the minimum of a cost function. Finally, simulations will show the effectiveness of a variety of search techniques for the intelligent machine.

Moed, Michael C.↗

NASA NTRS2010

2010 NASA Exploration Systems Mission Directorate: Lunabotics Mining Competition Systems Engineering Paper

A fast growing approach in determining the best design concept for a problem is to hold a competition in which the rules are based on requirements similar to the actual problem. By going public with such competitions, sponsoring entities receive some of the most innovative engineering solutions in a fraction of the time and cost it would have taken to develop such concepts internally. Space exploration is a large benefactor of such design competitions as seen by the results of X-Prize Foundation and NASA lunar excavation competitions [1]. The results of NASA's past lunar excavator challenges has led to the need for an effective means of collecting lunar regolith in the absence of human beings. The 2010 Exploration Systems Mission Directorate (ESMD) Lunar Excavation Challenge was created "to engage and retain students in science, technology, engineering, and mathematics, or STEM, in a competitive environment that may result in innovative ideas and solutions, which could be applied to actual lunar excavation for NASA." [2]. The ESMD Challenge calls for "teams to use telerobotics or autonomous operations to excavate at least 10kg of lunar regolith simulant in a 15 minute time limit" [2]. The Systems Engineering approach was used in accordance with Auburn University's mechanical engineering senior design course (MECH 4240-50) to develop a telerobotic lunar excavator, seen in Fig. 1, that fulfilled requirements imposed by the NASA ESMD Competition Rules. The goal of the senior design project was to have a validated lunar excavator that would be used in the NASA ESMD lunar excavation challenge.

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