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Oversimplification of Systems Engineering Goals, Processes, and Criteria in NASA Space Life Support

This paper investigates the oversimplification of the inherently complex systems engineering process in space life support. The standard systems engineering process steps are described. The International Space Station (ISS) life support system is explained with its goals and performance criteria. Although it is not usually emphasized, the essential function of developing a hierarchy of systems and subsystems is to simplify the design process. The System Complexity Metric (SCM) shows how this di-vide-and-conquer approach also reduces the system complexity. The complete systems engineering process has many detailed steps. It is often simplified because of the effort required and the human limitations on working memory and decision span. Systems analysis demands slow, logical, and fo-cused thinking but is often bypassed in favor of quick, intuitive, subconscious “gut feel.” A study of 100 system designs found examples of 12 specific mental mistakes, such as ignoring stakeholder needs, and these mistakes are essentially oversimplifications of the systems engineering process. An analysis of space life support goals, options, criteria, and processes found 11 examples of oversimplifications in systems engineering, such as neglecting safety and cost. All these 11 oversimplifications could be traced to one or more of the 12 previously identified mental mistakes or other well-known ones, such as ig-noring sunk costs. Oversimplification of the systems engineering process is rarely noticed but is a common and harmful problem. A study of failures in 50 different space systems found that problems in systems engineering caused failures and often led to errors in design, development, and test that further contributed to failure. It seems that more diligent systems engineering could prevent many project problems and failures, but projects seem to be more guided by “gut feel” based on tradition, authority, and consensus than on the logical, rational systems engineering approach.

Simplified systems engineering↗

RELAP-7 Pressurizer Component Development Updates

RELAP-7 is a nuclear systems safety analysis code being developed at the Idaho National Laboratory (INL). RELAP-7 development began in 2011 to support the Risk Informed Safety Margins Characterization (RISMC) Pathway of the Light Water Reactor Sustainability (LWRS) program. The overall design goal of RELAP-7 is to take advantage of the previous thirty years of advancements in computer architecture, software design, numerical methods, and physical models in order to provide capabilities needed for the RISMC methodology and to support nuclear power safety analysis. The code is being developed based on Idaho National Laboratory’s modern scientific software development framework – MOOSE (the Multi-Physics Object-Oriented Simulation Environment). The initial development goal of the RELAP-7 approach focused primarily on the development of an implicit algorithm capable of strong (nonlinear) coupling of the dependent hydrodynamic variables contained in the 1-D/2-D flow models with the various 0-D system reactor components that compose various boiling water reactor (BWR) and pressurized water reactor nuclear power plants (NPPs). As part of the efforts to expand the capability for PWR simulation, an equilibrium single-region pressurizer model has been implemented in RELAP-7. The pressurizer component can simulate pressure and water level change through insurge, spray, and heating processes. Two simple tests – one for insurge process and another for outsurge process – have been reported to demonstrate and verify the functions of the pressurizer model. The typical single-phase PWR system model presented in the first RELAP-7 milestone report has been updated, as part of system level test for the new pressurizer model. The updated PWR system model with the pressurizer component can be used for more realistic transient simulations. The addition of the equilibrium single-region pressurizer model represents the first step of developing a suite of pressurizer models with different levels of fidelities. Non-equilibrium two-region two-zone model and non-equilibrium five-region three zone model will be implemented in the near future. Cross comparison and validation will be pursued when higher fidelity pressurizer models are completed.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

Optimization Studies of Radiation Shielding for PIP-II Project at Fermilab

The Proton Improvement Plan-II (PIP-II) at Fermilab represents a significant advancement in the quest to answer some of the most profound questions about our universe using the world's most intense high-energy neutrino beam. The project requires the construction of a new addition to the Fermilab accelerator complex – an 800-MeV high-intensity superconducting linear accelerator. Ensuring the safety and regulatory compliance of this ambitious project is paramount, necessitating thorough dose rate assessments under both normal operational and accidental scenarios to align with the Fermilab Radiological Control Manual (FRCM) standards. Our approach included a shielding optimization used for the simulations with the Monte Carlo code MARS [1,2,3] to incorporate new magnet and collimator designs, essential for reflecting the current state of PIP-II infrastructure. The implementation of high-resolution detector planes, despite their computational demands, enabled us to gather detailed radiation field data crucial for optimizing shielding configurations. To overcome the significant computational demands, we developed a branching code that drastically reduced simulation runtimes while maintaining statistical integrity. This was achieved through geometry splitting and the application of Russian Roulette techniques, tailored to prioritize regions of interest based on predefined importances and weight limits.

43 PARTICLE ACCELERATORS↗

Optimization Studies of Radiation Shielding for PIP-II Project at Fermilab

The Proton Improvement Plan-II (PIP-II) at Fermilab represents a significant advancement in the quest to answer some of the most profound questions about our universe using the world's most intense high-energy neutrino beam. The project requires the construction of a new addition to the Fermilab accelerator complex – an 800-MeV high-intensity superconducting linear accelerator. Ensuring the safety and regulatory compliance of this ambitious project is paramount, necessitating thorough dose rate assessments under both normal operational and accidental scenarios to align with the Fermilab Radiological Control Manual (FRCM) standards. Our approach included a shielding optimization used for the simulations with the Monte Carlo code MARS [1,2,3] to incorporate new magnet and collimator designs, essential for reflecting the current state of PIP-II infrastructure. The implementation of high-resolution detector planes, despite their computational demands, enabled us to gather detailed radiation field data crucial for optimizing shielding configurations. To overcome the significant computational demands, we developed a branching code that drastically reduced simulation runtimes while maintaining statistical integrity. This was achieved through geometry splitting and the application of Russian Roulette techniques, tailored to prioritize regions of interest based on predefined importances and weight limits.

Makovec, Alajos↗

Risk Trade-Space Analysis for Safe Human Expeditions to Mars

We assessed the integrated safety, health, and performance risk to crews on long-duration missions, specifically to Mars. Using a systems approach rather than one focused on individual countermeasures, we examined the trade space around several such risks to identify high-potential risk mitigation strategies and characterize aspects of Mars mission architectures that could lower aggregated risk. Current Mars Design Reference missions would require durations well over two years and would increase crew exposure to radiation and microgravity well beyond ISS levels, likely resulting in significantly reduced performance beyond our current capability to mitigate that could jeopardize mission success. A “fast Mars transit” round-trip mission concept was studied using an innovative flight dynamics approach to quantify the minimum total mission energy required for a Mars transit with total mission duration less than 400 days. This approach holds promise for sending humans to Mars and returning them safely with acceptable, potentially mitigatable, exposure to microgravity and radiation using current or near-term technologies. The fast transit concept would also result in fewer time-driven vehicle failures and enable sustainable deployment of humans and infrastructure to Mars on a regular cadence, allowing steady exploration and colonization of Mars. Finally, we conclude that reliance on the Low Earth Orbit (LEO) mission operations paradigm – i.e., one of near-complete real-time dependence on experts at Mission Control to manage the combined state of the mission, vehicle, and crew – is high risk given the communication delays and limited resupply of any Mars mission, and this risk is not eliminated by the shorter missions durations of fast transit scenarios. Based on historical trends, it is highly likely that the crew will face a high-consequence problem of uncertain origin during Mars transit when ground support will be greatly reduced. While it may be possible to reduce anomaly rates through improved reliability analysis and testing, and to reduce anomaly impacts through added robustness, such mitigations address only known failure modes and known uncertainties. Therefore, a radical shift in the Human-Systems Integration Architecture (HSIA) that defines the operational paradigm, systems design, and human-systems interactions is required to improve the risk posture to an acceptable level regardless of mission duration.

Mars↗

Space Suit Portable Life Support System Oxygen Regulator History, Development, & Testing Results

An oxygen regulator has been in development for the Exploration Extravehicular Mobility Unit (xEMU) Portable Life Support System (PLSS). The regulator provides the necessary oxygen pressure control for the crew member during prebreathe, Extra-Vehicular Activity (EVA), post EVA airlock operations, and Decompression Sickness (DCS) treatment. It has been over four decades since a new spacesuit oxygen regulator has been designed. The regulator and EMU that is presently used on the International Space Station (ISS) was developed for the space shuttle program without any significant changes made throughout its service life. The xEMU spacesuit oxygen regulator is based on the previous EMU Secondary Oxygen Pack (SOP). The new design integrates numerous improvements and changes including an innovative approach to regulator architecture, a more robust first stage pressure sensing mechanism, digital actuation control, and electronic pressure sensing. These upgrades replace manual control linkages, physical gauges, and enable infinitely variable pressure set points. The new setpoints can decrease prebreathe time and make in suit DCS treatment possible. Throughout its four iterations design concerns have been addressed, safety features have been added, and the envelope of the regulator designed to fit inside the xEMU PLSS package. This paper will review the history, design, testing, and lessons learned during the development of the xEMU PLSS Oxygen Regulator.

Ryan Eric Ogilvie↗

Space Suit Portable Life Support System (PLSS) Oxygen Regulator History, Development, & Testing Results

An oxygen regulator has been in development for the Exploration Extravehicular Mobility Unit (xEMU) Portable Life Support System (PLSS). The regulator provides the necessary oxygen pressure control for the crew member during prebreathe, Extra-Vehicular Activity (EVA), post EVA airlock operations, and Decompression Sickness (DCS) treatment. It has been over four decades since a new spacesuit oxygen regulator has been designed. The regulator and EMU that is presently used on the International Space Station (ISS) was developed for the space shuttle program without any significant changes made throughout its service life. The xEMU spacesuit oxygen regulator is based on the previous EMU Secondary Oxygen Pack (SOP). The new design integrates numerous improvements and changes including an innovative approach to regulator architecture, a more robust first stage pressure sensing mechanism, digital actuation control, and electronic pressure sensing. These upgrades replace manual control linkages, physical gauges, and enable infinitely variable pressure set points. The new setpoints can decrease prebreathe time and make in suit DCS treatment possible. Throughout its four iterations design concerns have been addressed, safety features have been added, and the envelope of the regulator designed to fit inside the xEMU PLSS package. This paper will review the history, design, testing, and lessons learned during the development of the xEMU PLSS Oxygen Regulator.

Ryan Ogilvie↗

Manufacturing and Scale-Up of Natural Fiber Composite eVTOL Propeller Skin and C-Channel

This report presents the manufacturing and scale-up of natural fiber composites for aerospace applications, conducted within NASA’s Convergent Aeronautics Solutions portfolio to advance aircraft capabilities and efficiency. The effort focused on the development and demonstration of two proof-of-concept articles, an Electric Vertical Take-off and Landing (eVTOL) propeller skin and a C-channel, produced through an iterative design and process optimization approach. Best practices and guidance on addressing key challenges with bio-based composite materials and manufacturing is provided. Ideally suited for non-load-bearing structural components, these emerging materials offer potential for weight reduction, vibration damping, noise mitigation, interference-free communication, and cost savings, without compromising the performance of safety-critical primary structures.

Natural fibers↗

Bridging the Gap Between Modern UX Design and Particle Accelerator Control Room Interfaces

Accelerator control systems often represent relatively complex and safety-sensitive human-machine interfaces within process control industries. These systems are technically robust and reflect the cumulative integration of solutions built and adapted across decades. One of the regular, unfortunate casualties of provisional accelerator control system updates is their human-system interfaces (HSIs) which often lag behind modern usability and design standards. An additional challenge is that although there is a multitude of established human factors (HF), and user experience (UX) principles for everyday digital applications, there are very few (if any) established principles for complex and safety-critical applications for an accelerator. This paper argues for the importance of established HF and UX principles (herein referred to as human-centered design principles) into the development of accelerator HSIs, emphasizing the need for clarity, consistency, responsiveness, and cognitive accessibility. Drawing from HF/UX best practices and human-centered design, this paper discusses how these approaches can enhance operator performance, reduce human error, and improve accelerator personnel collaboration. Case studies from Accelerator Control Operations Research Network (ACORN) at Fermilab are explored to demonstrate how interfaces built with human-centered design principles can scale with system complexity while remaining intuitive and efficient for diverse user roles including operators, machine experts, and engineers. By bridging the gap between traditional control system design and modern human-centered design methods, this paper provides a roadmap for evolving accelerator HSIs into more usable, maintainable, and effective tools.

Hill, Rachael [Idaho Natl. Lab.]↗

Status Report on Regulatory Criteria Applicable to the Use of Artificial Intelligence (AI) and Machine Learning (ML)

Although the interest in the use of artificial intelligence (AI) and machine learning (ML) in nuclear energy is increasing rapidly, at present their implementation is limited. This rapid increase in interest is not surprising considering that implementing AI and ML technology would allow for continuous monitoring, facilitate the implementation of predictive maintenance with optimized staffing plans, enable automation and autonomy opportunities that could drastically reduce fixed operation and maintenance costs, and provide training for operations and maintenance. Other industries are using AI for construction, and in the nuclear arena AI could provide great benefit in decommissioning activities. The ability of AI and ML to operate in real time vastly increases their potential impact. Before AI can be used in design, operations, or as a regulatory tool, the specifics on the regulations applicable to the use of AI for nuclear power applications need to be established. The difficulty is that the specific use cases will dictate the applicability of regulations. For example, even within the application domain associated with operations, the regulations might vary if the AI is used to create a virtual reference for plant operations or is used for training, optimization of maintenance intervals, prioritization of maintenance activities, etc. Different still is if the AI is to be used for design or setting technical specifications, which will introduce additional requirements. US Nuclear Regulatory Commission (NRC) licensing reviews are based on an applicant’s design meeting its performance assessment based on (1) safety goals and objectives, (2) deterministic and/or probabilistic analysis of accident scenarios, and (3) quantitative assessment of design alternatives against the safety goals and objectives using accepted engineering tools, methodologies, and performance criteria. The current regulatory framework does not explicitly address AI or autonomous control. However, as implementing AI technology will require the use of a digital platform, it must meet the requirements of an instrumentation and control (I&C) system. The regulatory requirements for AI, which will be incorporated into the I&C system, will be very dependent on how it is used (i.e., its functionality, safety classification, etc.). The licensing process is primarily risk-based with the identification of components and systems as nonsafety, important to safety, or safety related. A risk-informed approach allows further gradation of components and systems based on risk metrics such as core damage frequency or large early release fractions. Thus, the use cases and the risk categorization of impacted systems and components will determine the regulatory requirements. Regardless of how AI is used it presents new opportunities for risk-informing operating, maintenance, and regulatory decisions. Trustworthiness, transparency, and the ability to validate and verify the results will be paramount in showing that the systems and plant still meet their performance requirements. This report describes the results of research to identify regulatory implications of AI technologies and their uses. Specifically, this report reviews current regulatory guidance relevant to the application of AI for design (including design changes or new designs including advanced reactors), construction, operations, training, maintenance, research, testing, and as a regulatory tool. AI can be automated at different levels from purely informative purposes to autonomous controls. The focus of this review included determination of constraints on the application of AI technology, identification of any regulatory gaps or uncertainties, and clarification of anticipated technical basis information likely to be important for regulatory acceptance of these technologies. Currently, any use of AI at nuclear power plants is focused on nonsafety-related applications. The NRC and other regulatory bodies are evaluating providing guidance to address gaps rather than create new regulations to address the use of AI and ML. This approach seems to be the best to encourage AI development without adding regulatory uncertainty.

97 MATHEMATICS AND COMPUTING↗

Laser ablation of high-loading Li-ion battery electrodes improves accessible capacity and cycle life for Behind-the-Meter Storage

Adoption of Behind-the-Meter Storage (BTMS) requires design of batteries that enable high safety, long cycle life, and low cost at the system level. Pairing Li 4 Ti 5 O 12 (LTO) with LiMn 2 O 4 (LMO) achieves targets related to safety and cycle life, but these materials' low energy densities contribute to higher cost at the system scale. Increasing electrode loading is a simple approach to improve energy density, but comes with a trade-off in electrode utilization due to long, tortuous Li + diffusion pathways. Here, laser ablation is used to microstructure (pattern) high-loading electrodes to enhance electrode performance through improved Li + diffusion pathways. Four cell types, comprising combinations of standard or patterned anode and cathode, were prepared to evaluate the effects of laser ablation at each electrode. A rate test shows that patterning electrodes enhances active material utilization at ≳1C rates. Patterning the cathode yields the most benefit, as cells with a patterned cathode demonstrate a ~20% higher accessible capacity than those without at 1.4C. Additionally, 1C capacity retention of cells with patterned cathode (91% through 3000 cycles) is significantly improved over cells with only the anode patterned (64%) and non-patterned electrodes (50%). Characterization of post-mortem cells before and after refreshing their electrolyte suggests that 1C capacity retention is improved by mitigation of electrode "dry-out". We hypothesize that the microstructure acts as a reservoir of additional electrolyte, or a path for gas to escape, so that active material remains wetted throughout long-term cycling, and/or the microstructure may reduce localized, gas-forming overpotentials in the high-loading electrode.

25 ENERGY STORAGE↗

A High-Performance Computing GNSS-aware Path Planning Algorithm for Safe Urban Flight Operations

The emergence and development of advanced technologies and vehicle types have created a growing demand for new forms of flight operations. These new and increasingly complex operational paradigms, such as Advanced and Urban Air Mobility (AAM/UAM), present regulatory authorities and the aviation community with several design-and-implementation challenges – particularly for highly autonomous vehicles. An overarching and daunting task is to develop protocols that can integrate these operations without compromising safety or disrupting traditional airspace operations. A shift toward a more predictive, autonomous, risk mitigation capability becomes critical to meet this challenge. This paper proposes and evaluates a computationally-efficient path planning approach to perform pre-flight planning and autonomous in-flight re-routing to minimize exposures to selected hazards. In our evaluation, hazards associated with degraded and missing critical GPS navigation data are considered. In this paper, we first present a high-performance computing path planning approach based on an adapted Bellman-Ford algorithm, developed in the CUDA programming language. Using the adapted path planning algorithm, we test this algorithm when encountering issues with GPS quality, and deliver an implementation that can produce flight paths that minimize exposure to risks, while maintaining a low computational burden. In our evaluation, the computation of periodic and aperiodic path updates are evaluated, prioritizing specific events as triggers for updates, based on changes to satellite availability. These critical events can lead to significant exposure to navigational hazards if not dealt with correctly.

GNSS↗

A High-Performance Computing GNSS-aware Path Planning Algorithm for Safe Urban Flight Operations

The emergence and development of advanced technologies and vehicle types have created a growing demand for new forms of flight operations. These new and increasingly complex operational paradigms, such as Advanced and Urban Air Mobility (AAM/UAM), present regulatory authorities and the aviation community with several design-and-implementation challenges – particularly for highly autonomous vehicles. An overarching and daunting task is to develop protocols that can integrate these operations without compromising safety or disrupting traditional airspace operations. A shift toward a more predictive, autonomous, risk mitigation capability becomes critical to meet this challenge. This paper proposes and evaluates a computationally-efficient path planning approach to perform pre-flight planning and autonomous in-flight re-routing to minimize exposures to selected hazards. In our evaluation, hazards associated with degraded and missing critical GPS navigation data are considered. In this paper, we first present a high-performance computing path planning approach based on an adapted Bellman-Ford algorithm, developed in the CUDA programming language. Using the adapted path planning algorithm, we test this algorithm when encountering issues with GPS quality, and deliver an implementation that can produce flight paths that minimize exposure to risks, while maintaining a low computational burden. In our evaluation, the computation of periodic and aperiodic path updates are evaluated, prioritizing specific events as triggers for updates, based on changes to satellite availability. These critical events can lead to significant exposure to navigational hazards if not dealt with correctly.

GNSS↗

Testing of Advanced Capabilities to Enable In-time Safety Management and Assurance for Future Flight Operations

In order to refine an initial Concept of Operations, explore Concepts of Use, and expose/validate requirements for future In-Time Aviation Safety Management Systems (IASMS), testing architectures were created, along with a set of capabilities and underlying information exchange protocols. These systems were conceived and developed based on hazards associated with two envisioned urban area flight domains: (1) highly autonomous small uncrewed aerial systems (sUAS) operating at low altitudes, and (2) highly autonomous air taxis. The initial scope of this development is described in [1]; this report provides an update, focusing on the subsequent developments and test activities. As stated in [1], it is important to note that there are many capabilities already in use by the industry (or soon to be in use) that will play critical roles in future IASMS designs. Those reported here were developed to address a gap in the current state-of-the-art regarding specific hazards/risks, and/or to allow for investigation of the interplay between and across hazard types — particularly regarding how overall safety risk can be reduced or managed effectively. Results of testing and development activities are organized by the operational phase wherein a particular capability would be employed (i.e., preflight, in-flight, and post-flight/off-line). Pre-flight: A set of capabilities were developed to help mitigate safety risk prior to flight (e.g., during flight and mission planning). Results of testing summarize (1) validation activities to raise the Technology Readiness Level (TRL) and (2) evaluation activities where the capabilities were applied to flight/mission planning procedures and used by operators/pilots. For the latter, flight plans were automatically assessed, and operators/pilots were notified of hazardous flight segments so as to enable adjustment of the flight plan and re-evaluation, and/or to better inform go/no-go decisions. Capabilities addressed hazards associated with power consumption, third-party risk, wind, navigation system performance, radiofrequency interference, and proximity to geo-spatial threats (e.g., buildings, trees, and no-fly zones). In-flight: Flight experiments tested capabilities that detect and respond to hazards encountered during flight. In the first series, safety hazards were monitored and assessed onboard, and system-generated mitigation maneuvers were recorded (but not acted upon by the vehicle). In the second series, mitigation maneuver commands directed the aircraft in response to safety hazards (i.e., auto-mitigation). The sUAS used for testing is described in full, as is the test architecture, which included commercial avionics, research avionics, and onboard software designed to detect, assess, and respond to hazards. The onboard system was designed as a run-time assurance framework, consistent with [2] and supportive of both supervisory and automated modes. The primary functions included: real-time risk assessment (RTRA), auto-pilot monitoring, constraint monitoring, and contingency select/triggering. RTRA performs integrated risk assessment considering data from several hazard-related monitors (e.g., battery, motors, navigation, communications, population density, and loss-of-control). Post-flight/off-line: Data monitored and recorded during flights can enable IASMS capabilities that execute after flights have completed (or “off-line”). These include: (1) the ability to identify anomalies and trends that may only be observable when comparing data spanning a number of similar flights; (2) the ability to update and validate pre-flight and in-flight capabilities and any underlying models to improve their performance; (3) the ability to report anomalies/off-nominals that may indicate design changes or maintenance actions are needed; and (4) the ability for humans involved in operations to report safety-relevant observations to help in understanding the flight data and/or the operational context of a flight. Progress on three such capabilities is summarized; the first investigates anomaly detection given a limited set of flight logs and applies an approach previously used for space operations. The second explores what could be identified using a larger set of flight logs, including from web-based forums where flight logs are posted by sUAS autopilot users. The third creates a new means of collecting information on UAS incidents and accidents via the Aviation Safety Reporting System (ASRS).

sUAS↗

Postclosure Safety Assessment for the Nuclear Power Demonstration Closure Project - 19158

Following 30 years in a safe shutdown state, Canadian Nuclear Laboratories (CNL) is proposing the final decommissioning of the Nuclear Power Demonstration Waste Facility (NPDWF). A Postclosure Safety Assessment (PostSA) has been prepared as part of this process. The present PostSA represents the second assessment, following an iterative approach. The PostSA considered Normal Evolution of the facility, as well as several Disruptive Events and other cases to show robustness and account for uncertainties. The results of the PostSA show that the NPDWF is a robust design that will contain and limit release of contaminants long into the future. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

The Challenger tragedy was caused by an Apollo mistake, terminating risk analysis

NASA’s view of risk changed between early Apollo and the Space Shuttle. Risk was a known serious problem at the beginning of Apollo and the risk estimates were disturbingly high. To avoid public concern, risk analysis was discontinued. Risk analysis was avoided in Shuttle, leading to an unnecessarily risky design. The immediate cause of the Challenger tragedy was the mistaken decision to launch in cold weather. The fundamental cause was the high risk of the Shuttle design. Before Challenger, management thought and testified that the probability of an accident was 1 in 100,000. After Challenger, Probabilistic Risk Analysis (PRA) found a roughly 1 in 100 chance of a Shuttle failure. The recent Orion design uses the safer Apollo approach, with a hardened capsule, launch abort escape, and the crew placed above the rocket tanks and engines. During Apollo it was estimated that, “assuming all elements from propulsion to rendezvous and life support were done as well or better than ever before, that 30 astronauts would be lost before 3 were returned safely to the Earth.” The chance of astronaut survival was only 10%. After the Apollo 1 tragedy, the awareness of risk led to an intense focus on achieving safety. “The only possible explanation for the astonishing success – no losses in space and on time – was that every participant at every level in every area far exceeded the norm of human capabilities.” During Apollo, a NASA PRA found that the chance of success was “less than 5 percent.” The NASA Administrator felt that “the numbers could do irreparable harm,” and discontinued numerical risk assessment. This led to decreasing understanding of risk. The head of Apollo reliability and safety decided, “Statistics don’t count for anything,” and that risk is reduced by “attention taken in design.” The great and initially unexpected success of Apollo appeared to validate the neglect of PRA. Continuing to neglect the mathematical estimation of risk led Shuttle into a high risk design that produced tragic results. The initial design of the Shuttle emphasized increasing capability and reducing cost without analysis or even mention of risk. A retired NASA official stated, “some NASA people began to confuse desire with reality. … One result was to assess risk in terms of what was thought acceptable without regard for verifying the assessment. … Note that under such circumstances real risk management is shut out.” Not computing risk led to removing launch abort, removing crew escape, selecting less reliable Solid Rocket Boosters, placing the crew compartment next to the rocket boosters, and accepting more stressed shielding tile designs. Accepting these specific risks directly caused the shuttle disasters. The Challenger tragedy is frequently taught as a case of management failure. The focus is on the Challenger launch decision hours before, which is a dramatic example of bad management. However, the true cause of the Challenger disaster occurred decades earlier in the Apollo era. When the easily predictable failures occurred, failure investigations focused on how they might have been avoided. The Shuttle was cancelled after the space station was completed because of its high risk. The ultimate cause of the Shuttle tragedies was the choice by the Apollo-era NASA administrator to avoid a negative public reaction to realistic risk analysis.

Harry W. Jones↗

Engineering a tumor-selective prodrug T-cell engager bispecific antibody for safer immunotherapy

T-cell engaging (TCE) bispecific antibodies are potent drugs that trigger the immune system to eliminate cancer cells, but administration can be accompanied by toxic side effects that limit dosing. TCEs function by binding to cell surface receptors on T cells, frequently CD3, with one arm of the bispecific antibody while the other arm binds to cell surface antigens on cancer cells. On-target, off-tumor toxicity can arise when the target antigen is also present on healthy cells. The toxicity of TCEs may be ameliorated through the use of pro-drug forms of the TCE, which are not fully functional until recruited to the tumor microenvironment. This can be accomplished by masking the anti-CD3 arm of the TCE with an autoinhibitory motif that is released by tumor-enriched proteases. Here, we solve the crystal structure of the antigen-binding fragment of a novel anti-CD3 antibody, E10, in complex with its epitope from CD3 and use this information to engineer a masked form of the antibody that can activate by the tumor-enriched protease matrix metalloproteinase 2 (MMP-2). We demonstrate with binding experiments and in vitro T-cell activation and killing assays that our designed prodrug TCE is capable of tumor-selective T-cell activity that is dependent upon MMP-2. Furthermore, we demonstrate that a similar masking strategy can be used to create a pro-drug form of the frequently used anti-CD3 antibody SP34. This study showcases an approach to developing immune-modulating therapeutics that prioritizes safety and has the potential to advance cancer immunotherapy treatment strategies.

60 APPLIED LIFE SCIENCES↗

Technical Specification Surveillance Interval Extension Using Self-Diagnostics

As part of the Light Water Reactor Sustainability program, an ongoing research effort is being conducted on technical specifications surveillance interval extension of digital equipment in nuclear power plants. The research team is led by Idaho National Laboratory and includes Pacific Northwest National Laboratory, Technology Resources, and Oak Ridge National Laboratory. This research focuses on developing methods for applying the U.S. Nuclear Regulatory Commission (NRC)–approved guidance to implement a licensee-controlled, risk-informed surveillance frequency change program in digital instrumentation and control (I&C) systems that include self-diagnostics and online monitoring (OLM) capabilities. Although approved methods exist for extending technical specifications (TS) surveillance test intervals (STIs) for general equipment, including analog I&C equipment, gaps remain in technology and guidance on crediting newer digital equipment’s internal self-diagnostics and OLM characteristics. Previous research described a general methodology for crediting internal self-diagnostics for extending surveillance test intervals. The methodology used self-diagnostics to detect—and credited recovery from—failure. Self-diagnostics were also applied for performance monitoring during the extended surveillance interval. This report discusses the status of recent activities to evaluate the previously developed methodology using a pilot study. Although both a utility partner for a pilot study and a specific digital asset were identified in FY2020, delays in obtaining proprietary information resulted in a limited ability to fully evaluate the methodology, and further interactions were complicated by the COVID pandemic. Therefore, at that time, the use of public-domain information—along with current processes for surveillance interval extension through a surveillance frequency control program—identified the need to fully assess diagnostic coverage as part of the pilot study. Furthermore, self-diagnostics were also identified as a potential option to replace the drift analyses conducted as part of current STI extension procedures. In FY2022, the project was reconstituted with the industry partner, and information and data were made available by the industry partner to the research team for review. The shared information included failure event descriptions and data for a digital I&C system since its implementation, as well as recent STI extension interval reports developed by the utility partner on that digital I&C system. This report presents an evaluation of this information and data and describes an application of the proposed methodology cited above. The methodology seeks to take advantage of the self-diagnostics and OLM capabilities to reduce risk or reduce the level of qualitative monitoring assessment needed to perform a risk-informed STI extension using existing NRC approved guidance or both. Addressing these issues of STI extension by crediting self-diagnostics is likely to result in benefits for current and future nuclear power plant (NPP) operations, including lowering the barriers to adoption of digital I&C systems and increasing cost savings by deferring or eliminating unneeded preventive maintenance (tasks or checks or activities). Specifically, self-diagnostic and OLM capabilities of newer digital equipment being installed in non-safety and safety applications are designed to detect failures, provide early warning of potential failures, and notify plant operators to take appropriate action to reduce out of service (OOS) time thus protecting safety margins. Moreover, the equipment is expected to provide information that time-related operational degradation is identified early to ensure timely and planned corrective actions instead of a reactive and unplanned approach ahead of an extended-surveillance interval.

42 ENGINEERING↗