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Advanced Reactor Safeguards & Security Program: Cybersecurity Scenarios

The use of digital control systems and automation in advanced nuclear power systems introduces different types of vulnerabilities compared to legacy (i.e. analog) control systems that cyber adversaries can exploit. These vulnerabilities pose a challenge to reactor operators and cyber operations staff due to the dynamic nature of the event in which a human response or a lack of response can potentially evolve into a worsening plant condition. Using the Department of Homeland Security Cyber and Infrastructure Security Agency’s (CISA) critical infrastructure exercise framework, this document presents several cyber security scenarios typical of digital control systems that could be used in advanced reactor designs. These scenarios can be used in tabletop exercises to evaluate cyber security posture or conduct training on different aspects of cyber security, including detection, threat hunting using indicators of compromise, evaluating incident response, risk mitigation, incident reporting, information sharing and recovery.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Physical Security Timeline Analysis in Support of Advanced Reactor Demonstration and Deployment

This report presents the regulatory requirements and directions on the physical security of advanced nuclear reactors in USA. Presently, a rule is being proposed that allows for a performance-based analysis. In determining the physical security requirements for an advanced reactor, new tools may be desired to conduct a performance-based analysis. These tools should incorporate dynamic analysis methods to provide as much realism as possible. In comparison, the security requirements for existing light water reactors (LWRs) are much more prescriptive and the analysis conducted to establish the required physical security strategies were more easily performed with static analysis. In order to achieve the cost goals that advanced reactors require for adoption; the nuclear security force required should not be excessive. Dynamic physical security analysis methods and tools have been developed by the US Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program. This report details how the dynamic risk analysis tools developed in the LWRS program using the dynamic risk modelling tool, EMRALD, may be adapted for use in analyzing the physical security designs for advanced reactors accounting for variable performance-based requirements. This report provides an example analysis of a hypothetical SFR using publicly available information and generic assumptions to demonstrate the methods and potential presentation and analysis of the results. No actual plant information is used in this example analysis. Future work in this area will create additional models that can be adapted for any advanced reactor concept and use various security features to create a physical security system that provides adequate protection from radiological theft and sabotage.

97 MATHEMATICS AND COMPUTING↗

Nuclear Safety [Vol. 35, No. 2, July-December 1994]

Nuclear Safety is a journal that covers significant issues in the field of nuclear safety. Its primary scope is safety in the design, construction, operation, and decommissioning of nuclear power reactors worldwide and the research and analysis activities that promote this goal, but it also encompasses the safety aspects of the entire nuclear fuel cycle, including fuel fabrication, spent-fuel processing and handling, and nuclear waste disposal, the handling of fissionable materials and radioisotopes, and the environmental effects of all these activities. Table of Contents for this issue follows. GENERAL SAFETY CONSIDERATIONS: 179 Consideration of Postaccident Consequences in the Determination of Safety Objectives for Future Nuclear Power Plants in France, D. Queniart, A. Sugier, and J. Lochard; ACCIDENT ANALYSIS: 187 Nuclear Safety Research: The Phebus FP Severe Accident Experimental Program, P. von der Hardt, A. V. Jones, C. Lecomte, and A. Tattegrain; 205 Containment Performance Analysis of the Advanced Neutron Source Reactor at the Oak Ridge National Laboratory, S. H. Kim, R. P. Taleyarkhan, and V. Georgevich; 213 Assessment of Fission Product Deposits in the Reactor Coolant System: The DEVAP Program, G. Le Marois and M. Megnin; 222 Erratum to “A Review of the Available Information on the Triggering Stage of a Steam Explosion," Vol. 35, No. 1, CONTROL AND INSTRUMENTATION: 223 Effects of Normal Aging on Calibration and Response Time of Nuclear Plant Resistance Temperature Detectors and Pressure Sensors, H. M. Hashemian; DESIGN FEATURES: 235 Defense in Depth Against the Hydrogen Risk—A European Research Program, F. Fineschi; ENVIRONMENTAL EFFECTS: 246 Technical Note: A Preliminary Analysis of the Risks to Hong Kong Resulting from Potential Accidents of Daya Bay Nuclear Power Plant, Z. Shi and X. Wei; OPERATING EXPERIENCES: 253 Reactor Shutdown Experience, Compiled by J. W. Cletcher; SPECIAL SECTION ON TMI-2 VESSEL INVESTIGATION PROJECT: 256 Three Mile Island—New Findings 15 Years After the Accident A. M. Rubin and E. Beckjord; 269 Relocation of Molten Material to the TMI-2 Lower Head, J. R. Wolf, D. W. Akers, and L. A. Neimark; 280 Insight Into the TMI-2 Core Material Relocation Through Examination of Instrument Tube Nozzles, L. A. Neimark; 288 Physical and Radiochemical Examinations of Debris from the TMI-2 Lower Head, D. W. Akers and B. K. Schuetz; 301 Results of Metallographic Examinations and Mechanical Tests of Pressure Vessel Samples from the TMI-2 Lower Head, D. R. Diercks and G. E. Korth; 313 Margin-to-Failure Calculations for the TMI-2 Vessel, J. Rempe, L. Stickler, S. Chavez, G. Thinnes, R. Witt, and M. Corradini; U.S. NUCLEAR REGULATORY COMMISSION INFORMATION AND ANALYSES: 328 1993 Accident Sequence Precursor (ASP) Program Results, L. N. Vanden Heuvel, J. W. Cletcher, D. A. Copinger, J. W. Minarick, B. W. Dolan, and P. D. O’Reilley; RECENT DEVELOPMENTS: 339 Reports, Standards, and Safety Guides, D. S. Queener; 345 Proposed Rule Changes as of June 30, 1994; ANNOUNCEMENTS: 234 Thirty-First Annual Meeting of the National Council on Radiation Protection and Measurements; 356 1995 International Incineration Conference; 358 Fifth International Controls and Instrumentation Conference; 359 ANS International Topical Meeting on Safety of Operating Reactors; 359 Fifth International Conference on Nuclear Criticality Safety; 360 International Conference on Probabilistic Safety Assessment Methodology and Applications; 351 The Authors; 357 Reviewers of Nuclear Safety, Vol. 35.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Design of a Novel Information System for Semi-Automated Management of Cybersecurity in Industrial Control Systems

There is an urgent need in many critical infrastructure sectors, including the energy sector, for attaining detailed insights into cybersecurity features and compliance with cybersecurity requirements related to their Operational Technology (OT) deployments. Frequent feature changes of OT devices interfere with this need, posing a great risk to customers. One effective way to address this challenge is via a semi-automated cyber-physical security assurance approach, which enables verification and validation of the OT device cybersecurity claims against actual capabilities, both pre- and post-deployment. To realize this approach, this paper presents new methodology and algorithms to automatically identify cybersecurity-related claims expressed in natural language form in ICS device documents. Here, we developed an identification process that employs natural language processing (NLP) techniques with the goal of semi-automated vetting of detected claims against their device implementation. We also present our novel NLP components for verifying feature claims against relevant cybersecurity requirements. The verification pipeline includes components such as automated vendor identification, device document curation, feature claim identification utilizing sentiment analysis for conflict resolution, and reporting of features that are claimed to be supported or indicated as unsupported. Our novel matching engine represents the first automated information system available in the cybersecurity domain that directly aids the generation of ICS compliance reports.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

Consequence analyses of sabotage-induced radiological releases in high-temperature helium-cooled prismatic microreactors

Here, this study analyzes the radiological dose consequences of sabotage-induced accidents at three high-temperature helium-cooled prismatic microreactors (HTPMs) with thermal power ratings of 1, 10, and 50 MWt. Each HTPM employs uranium oxycarbide tristructural isotropic fuel enriched to 19.75 wt% high-assay low-enriched uranium. Simulations were conducted to estimate reactor core inventory at the point of fuel discharge––when the effective multiplication factor reduced to less than 1––representing peak radionuclide inventory. Postulated sabotage scenarios leading to reactor shutdown were analyzed at two intervals: immediately post-shutdown (0 h) and 3 days after shutdown using the SCALE code for radionuclide inventories and the RASCAL tool for dose consequences. Results show that although HTPMs benefit from inherent safety features and robust fuel design, radiological consequences scale with reactor power because of increased source term inventories. Smaller microreactors exhibited proportionally lower dose consequences. To support the economic and regulatory feasibility of microreactor deployment, this study emphasizes the value of a risk-informed, performance-based approach, as supported by regulations like 10 CFR Parts 100 and 53 in the United States. Microreactor developers should perform site-specific assessments of potential sabotage or low-probability, high-consequence events, especially when considering minimal on-site or full off-site emergency response.

Consequence↗

Cyber-Informed Engineering Case Study of an Integrated Hydrogen Generation Plant

Strategies for securing digital instrumentation and control (I&C) systems within the nuclear industry are provided by multiple standards and guidance documents. However, since selection and use of security controls outlined in these documents are frequently only considered during or after installation, there are often limitations on their use, such as technological constraints related to design or operation. Furthermore, alternative controls intended to provide the same or similar security countermeasure as the primary control may also be infeasible at these stages, leaving the I&C system vulnerable to cyber-attacks. The limitations associated with ‘bolting on’ security controls late in the systems engineering lifecycle can be reduced by integrating Cyber-Informed Engineering (CIE) into the process. This paper evaluates the use of CIE during the high-level design stage of a hydrogen generation project where heat and electricity are provided by a nuclear power plant. Applying CIE to this project highlighted potential cyber vulnerabilities of the initial design, leading to recommendations for process flow and I&C system design modifications to reduce, and at times eliminate, the risk from both deliberate and unintentional cyber incidents.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

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↗

The Cryptographic Obfuscation Sensor System Guarding Restricted Data (CrOSSGRD): Prototype Detailed Design Document

A prototype has been developed at Sandia National Laboratories to collect nominally sensitive data from a mock treaty accountable item, record that information as non-sensitive encrypted outputs, and allow inspectors to subsequently evaluate that information at a time and location of their choice without any risk of the host party’s data being inadvertently (or maliciously) revealed.

97 MATHEMATICS AND COMPUTING↗

Opportunities for Process Intensification with Membranes to Promote Circular Economy Development for Critical Minerals

Critical minerals are essential to the future of clean energy, especially energy storage, electric vehicles, and advanced electronics. In this paper, we argue that process systems engineering (PSE) paradigms provide essential frameworks for enhancing the sustainability and efficiency of critical mineral processing pathways. As a concrete example, we review challenges and opportu-nities across material-to-infrastructure scales for process intensification (PI) with membranes. Within critical mineral processing, there is a need to reduce environmental impact, especially con-cerning chemical reagent usage. Feed concentrations and product demand variability require flex-ible, intensified processes. Further, unique feedstocks require unique processes (i.e., no one-size-fits-all recycling or refining system exists). Membrane materials span a vast design space that allows significant optimization. Therefore, there is a need to rapidly identify the best opportunities for membrane implementation, thus informing materials optimization with process and infrastructure scale performance targets. Finally, scale-up must be accelerated and de-risked across the materials-to-process levels to fully realize the opportunity presented by membranes, thereby fostering the development of a circular economy for critical minerals. Tackling these challenges requires integrating efforts across diverse disciplines. We advocate for a holistic molecular-to-systems perspective for fully realizing PI with membranes to address sustainability challenges in critical mineral processing. The opportunities for PI with membranes are excellent applications for emerging research in machine learning, data science, automation, and optimization.

Dougher, Molly↗

A PROVEN APPROACH FOR EFFECTIVE COMPUTER SECURITY SELF-ASSESSMENTS AT NUCLEAR FACILITIES

A proven method for conducting cybersecurity self-assessments at nuclear power plants is now available for international use. This method was originally developed by Pacific Northwest National Laboratory, under the sponsorship of the U.S. Nuclear Regulatory Commission (NRC), for use at U.S. nuclear power plants. The “Method,” described in NUREG/CR-6847 “Cyber Security Self-Assessment Method for U.S. Nuclear Power Plants,” was originally a limited release document that was withheld from public disclosure but is now publicly available. The Method provides a systematic, phased, and risk-informed approach to help decision makers and security specialists understand their relative cybersecurity posture. Completed Method assessments may be used to support or validate selection of computer security controls to mitigate cyber threats as well as demonstrate compliance with regulations or statutes enacted by competent authorities. The Method assesses the cybersecurity posture of key systems at a nuclear facility with a focus on protection of design base functions. It considers both physical and digital elements of system vulnerabilities and the resulting potential consequences from exploitation. It is well-suited for addressing blended cyberattacks. A semi-quantitative analytical approach is used in the evaluation of potential vulnerabilities, consequences, and risks and provides a technical basis for the selection of security controls to mitigate cyberattacks. The Method’s application at U.S. nuclear power plants has been very encouraging. The only nuclear plant in the United States that did not have adverse findings during its initial NRC computer security inspection prepared for inspection through the diligent application of this self-assessment method and the implementation of recommendations that came out of that self-assessment. Nuclear facilities around the world might find application of the Method extremely helpful for making cost-effective, risk-based decisions regarding computer security and for preparing to pass computer security inspections by their competent authorities.

Cyber security, Nuclear security, Self-assessment↗

Improving and Automating Building Model Data Exchange

There are many instances throughout a project’s lifecycle where there arises a need for quick and accurate risk assessment of building designs. For example, an unexpected design change during construction may necessitate structural engineers to perform a seismic risk assessment on analytical models of the updated building design using high fidelity structural analysis software, such as ANSYS or Abaqus. However, the efficiency of such workflows often depends upon the interoperability of architectural design software and structural analysis software. When the quality of this interoperability is lacking or even non-existent, the efficiency of virtual engineering workflows is hampered, which increases project costs. A McGraw Hill industry survey of professional users of Building Information Modeling (BIM) technologies found that there is high demand for BIM interoperability for structural analysis, but that the value/difficulty ratio is currently too low for practical use. There have been efforts by the academic community to facilitate model data exchange between the architectural design and structural analysis domains, but such solutions have not been widely adopted by industry, face technical challenges, and oftentimes are limited in applicability for users of various BIM software. Therefore, INL is developing capabilities to improve, automate, and generalize model data exchange between architectural BIM software (e.g., Revit) and structural analysis software (e.g., SAP2000, ANSYS). The goal is to help expedite and automate as much of the pre-processing step for creating analytical models in finite element analysis software as reasonably as possible. Such a "BIM-to-FEA" conversion tool should provide direct benefit to end-users through accuracy, automation, quick turn-around, and wide applicability. To generalize the application of this BIM-to-FEA conversion tool and increase its useability among the many different commercial BIM software currently used by industry, the program is being developed with the concept of openBIM. OpenBIM is the application of non-proprietary, open data standards that allow for BIM model data exchange in a format that is accessible, retainable, and useable for all users. The most widely used open, non-proprietary data exchange format for BIM is the Industry Foundation Classes (IFC) schema. IFC is developed by buildingSMART international and is ISO certified (ISO 16739-1:2018). The BIM-to-FEA conversion tool is being developed for compatibility with typical commercial building designs of steel framed structures. The tool is currently capable of importing architectural BIM data of framed building structures, recognizing and extracting the aspects of the model that are required for structural analysis, adjusting the connectivity of frame members, and finally exporting to an analytical model stored in the IFC format. The exported IFC analytical model can then be imported into various openBIM compliant software, such as SAP2000. Such capabilities have already been tested on commercial software, as shown above, and continue to be improved. Work is underway to test the conversion on various commercial BIM software, develop a user-friendly interface, incorporate the program into the broader DeepLynx data warehouse project being developed by INL, and to eventually open-source the tool for the benefit of the community. Future development of the tool envisions the ability for efficient iterative risk assessment of generative building designs, all within a workflow utilizing open-source tools. One such open-source tool will be MOOSE, an advanced finite element analysis tool developed at INL. The conversion tool will also branch out from typical commercial building designs and will aim to incorporate nuclear construction. The aim will be to convert both structural and non-structural components of nuclear facilities, such as curved concrete containment structures and piping systems, respectively.

97 MATHEMATICS AND COMPUTING↗

EHR-BERT: A BERT-based model for effective anomaly detection in electronic health records

Objective: Physicians and clinicians rely on data contained in electronic health records (EHRs), as recorded by health information technology (HIT), to make informed decisions about their patients. The reliability of HIT systems in this regard is critical to patient safety. Consequently, better tools are needed to monitor the performance of HIT systems for potential hazards that could compromise the collected EHRs, which in turn could affect patient safety. In this paper, we propose a new framework for detecting anomalies in EHRs using sequence of clinical events. This new framework, EHR-Bidirectional Encoder Representations from Transformers (BERT), is motivated by the gaps in the existing deep-learning related methods, including high false negatives, sub-optimal accuracy, higher computational cost, and the risk of information loss. EHR-BERT is an innovative framework rooted in the BERT architecture, meticulously tailored to navigate the hurdles in the contemporary BERT method; thus, enhancing anomaly detection in EHRs for healthcare applications.Methods: The EHR-BERT framework was designed using the Sequential Masked Token Prediction (SMTP) method. This approach treats EHRs as natural language sentences and iteratively masks input tokens during both training and prediction stages. This method facilitates the learning of EHR sequence patterns in both directions for each event and identifies anomalies based on deviations from the normal execution models trained on EHR sequences.Results: Extensive experiments on large EHR datasets across various medical domains demonstrate that EHR-BERT markedly improves upon existing models. It significantly reduces the number of false positives and enhances the detection rate, thus bolstering the reliability of anomaly detection in electronic health records. This improvement is attributed to the model’s ability to minimize information loss and maximize data utilization effectively.Conclusion: EHR-BERT showcases immense potential in decreasing medical errors related to anomalous clinical events, positioning itself as an indispensable asset for enhancing patient safety and the overall standard of healthcare services. The framework effectively overcomes the drawbacks of earlier models, making it a promising solution for healthcare professionals to ensure the reliability and quality of health data.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

Pumped Storage Hydropower FAST Commissioning Technical Analysis

This report was developed in tandem with the Furthering Advancements to Shorten Time (FAST) to Commissioning PSH Challenge and represents the underlying technical analysis that informed the competition. Lead by Oak Ridge National Laboratory, the report is designed to address barriers and solutions to PSH development by establishing baseline project development knowledge, defining key aspects of project development, and identifying opportunities to reduce project timelines, costs, and risks. The document’s scope includes post-licensing activities and excludes factors related to permitting or licensing.

13 HYDRO ENERGY↗

A Multi-Criteria Impact Evaluation Methodology Applied to FLEX Strategies in Nuclear Power Plants

As responses to Fukushima Dai-ichi nuclear accident, several advanced, near-term technologies have been or are being introduced to enhance safety of operating nuclear power plants (NPPs) as well as improving their sustainability. Examples include Accident-Tolerant Fuel designs, Diverse and Flexible Coping Strategies (FLEX), and passive cooling system designs. The combinations of these technologies, coupled with enhancements to plant components and systems and improved fuel cycle efficiency, constitute a concept of Enhanced Resilient Plant Systems, which is proposed and being explored by Idaho National Laboratory (INL) under the Risk-Informed Systems Analysis Pathway of the U.S. Department of Energy’s Light Water Reactor Sustainability Program. To decide if introducing a technology is necessary or worthy, the impacts of this technology on NPPs should be evaluated, preferably in a quantitative manner, and provided to decision makers. This paper summarizes an on-going work conducted by the authors on developing a multi-criteria impact evaluation methodology. This methodology is expected to be applicable to evaluate a variety of technologies, while FLEX strategy is adopted as a case study for this paper.

99 GENERAL AND MISCELLANEOUS↗

Tactical Analysis for Calculating Contextual Risk at Boundaries: Summary of Laboratory Directed Research & Development Effort

The Tactical Analysis for Calculating Contextual Risk at Boundaries (TACCRAB) tool is an innovative digital twin (DT) platform and automated risk algorithm designed to transform operational decision-making in structured screening environments, with an initial focus on Southern Border Land Ports of Entry (POEs). The invention provides integration points for advanced artificial intelligence, predictive modeling, and real-time data analysis to produce a comprehensive risk management tool that enables proactive, data-informed security strategies. The core inventive features of TACCRAB center on its unique risk algorithm, which dynamically calculates contextual risk by synthesizing historical data, near real-time streaming data from the checkpoints themselves, and AI-generated predictions. Unlike traditional risk assessment methods, TACCRAB utilizes a DT to provide comprehensive operational insights, allowing stakeholders to visualize, simulate, and optimize checkpoint configurations with unprecedented speed and contextual awareness. TACCRAB's key innovation lies in its ability to combine multiple complex inputs - including technology detection probabilities, resource availability, screening pathway characteristics, and threat actor behavioral patterns - into a unified risk calculation and update these inputs based on changing operational and environmental conditions. By leveraging a DT that continuously updates and learns from linked data, TACCRAB can suggest adaptive mitigation strategies that minimize risk while maintaining operational efficiency. Particularly novel is the platform's approach to decision support, which goes beyond static risk assessment. The DT provides dynamic metrics such as wait times, resource allocation effectiveness, and potential emerging threat scenarios, enabling users to view sophisticated, relevant what-if simulations and optimize checkpoint operations in near real-time. The system's architecture allows for generalized application across different screening environments, such as secure facilities, ports of entry, and soft targets, making it a versatile tool for security and operational management. The invention distinguishes itself through its comprehensive integration of predictive modeling, AI-driven pattern discovery, and user-friendly interface design. By combining these elements, TACCRAB transforms complex risk data into actionable insights, supporting decision-makers at various organizational levels - from booth agents making split-second screening decisions to checkpoint managers optimizing the day's resource allocation to strategic planners managing long-term investments.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗

APPLICATION OF OBJECTIVES-DRIVEN ASSURANCE CASES TO SYSTEM DEVELOPMENT IN AN EVOLVING ACQUISITION MODEL

System properties such as “safety” and “dependability” cannot, in practice, be proven, and must be argued in an “assurance case” aimed at supporting risk-acceptance decisions that have to be made by system acquirers and/or regulatory authorities. The paper is concerned with applications of the “assurance case” idea early in design and development of new systems, when (apart from dedicated testing) the only available operating experience information derives from previous (non-identical) systems. Much of the discussion is based on an evolving acquisition model at the US National Aeronautics and Space Administration; previously, most major systems were developed in-house, but some major systems will now be developed by and acquired from commercial providers. Key points discussed include the following. (1) By promoting a particular kind of focused discussion between acquirers and providers, the use of assurance cases should be particularly valuable under the new acquisition model. (2) In principle, objectives-driven (sometimes called “performance-based”) approaches to assurance of performance have significant advantages in cases where they are applicable. (3) For truly novel systems, completeness of the safety analysis is a significant issue; it is important for the assurance case to include a commitment by the provider (or applicant) to seriously pursue analysis of operating experience, so that previously unrecognized hazards can be identified and addressed. (4) Inquiries into major accidents often point to deficiencies in management oversight in all parts of the life cycle; management processes need to be addressed in the formulation and the implementation of an assurance case. Under the new acquisition model, these considerations imply a serious reconsideration of the way in which the development process is managed by both providers and acquirers.

99 GENERAL AND MISCELLANEOUS↗

Application of Objectives-Driven Assurance Cases to System Development in an Evolving Acquisition Model

System properties such as “safety” and “dependability” cannot, in practice, be proven, and must be argued in an “assurance case” aimed at supporting risk-acceptance decisions that have to be made by system acquirers and/or regulatory authorities. The paper is concerned with applications of the “assurance case” idea early in design and development of new systems, when (apart from dedicated testing) the only available operating experience information derives from previous (non-identical) systems. Much of the discussion is based on an evolving acquisition model at the US National Aeronautics and Space Administration; previously, most major systems were developed in-house, but some major systems will now be developed by and acquired from commercial providers. Key points discussed include the following. (1) By promoting a particular kind of focused discussion between acquirers and providers, the use of assurance cases should be particularly valuable under the new acquisition model. (2) In principle, objectives-driven (sometimes called “performance-based”) approaches to assurance of performance have significant advantages in cases where they are applicable. (3) For truly novel systems, completeness of the safety analysis is a significant issue; it is important for the assurance case to include a commitment by the provider (or applicant) to seriously pursue analysis of operating experience, so that previously unrecognized hazards can be identified and addressed. (4) Inquiries into major accidents often point to deficiencies in management oversight in all parts of the life cycle; management processes need to be addressed in the formulation and the implementation of an assurance case. Under the new acquisition model, these considerations imply a serious reconsideration of the way in which the development process is managed by both providers and acquirers.

99 GENERAL AND MISCELLANEOUS↗

Structural basis for Zika envelope domain III recognition by a germline version of a recurrent neutralizing antibody

Recent epidemics demonstrate the global threat of Zika virus (ZIKV), a flavivirus transmitted by mosquitoes. Although infection is usually asymptomatic or mild, newborns of infected mothers can display severe symptoms, including neurodevelopmental abnormalities and microcephaly. Given the large-scale spread, symptom severity, and lack of treatment or prophylaxis, a safe and effective ZIKV vaccine is urgently needed. However, vaccine design is complicated by concern that elicited antibodies (Abs) may cross-react with other flaviviruses that share a similar envelope protein, such as dengue virus, West Nile virus, and yellow fever virus. This cross-reactivity may worsen symptoms of a subsequent infection through Ab-dependent enhancement. To better understand the neutralizing Ab response and risk of Ab-dependent enhancement, further information on germline Ab binding to ZIKV and the maturation process that gives rise to potently neutralizing Abs is needed. In this work, we use binding and structural studies to compare mature and inferred-germline Ab binding to envelope protein domain III of ZIKV and other flaviviruses. We show that affinity maturation of the light-chain variable domain is important for strong binding of the recurrent VH3-23/VK1-5 neutralizing Abs to ZIKV envelope protein domain III, and identify interacting residues that contribute to weak, cross-reactive binding to West Nile virus. These findings provide insight into the affinity maturation process and potential cross-reactivity of VH3-23/VK1-5 neutralizing Abs, informing precautions for protein-based vaccines designed to elicit germline versions of neutralizing Abs.

59 BASIC BIOLOGICAL SCIENCES↗