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A machine learning approach for identifying variables associated with risk of developing neutralizing antidrug antibodies to factor VIII

A key unmet need in the management of hemophilia A (HA) is the lack of clinically validated markers that are associated with the development of neutralizing antibodies to Factor VIII (FVIII) (commonly referred to as inhibitors). This study aimed to identify relevant biomarkers for FVIII inhibition using Machine Learning (ML) and Explainable AI (XAI) using the My Life Our Future (MLOF) research repository. The dataset includes biologically relevant variables such as age, race, sex, ethnicity, and the variants in the F8 gene. In addition, we previously carried out Human Leukocyte Antigen Class II (HLA-II) typing on samples obtained from the MLOF repository. Using this information, we derived other patient-specific biologically and genetically important variables. These included identifying the number of foreign FVIII derived peptides, based on the alignment of the endogenous FVIII and infused drug sequences, and the foreign-peptide HLA-II molecule binding affinity calculated using NetMHCIIpan. The data were processed and trained with multiple ML classification models to identify the top performing models. The top performing model was then chosen to apply XAI via SHAP, (SHapley Additive exPlanations) to identify the variables critical for the prediction of FVIII inhibitor development in a hemophilia A patient. Using XAI we provide a robust and ranked identification of variables that could be predictive for developing inhibitors to FVIII drugs in hemophilia A patients. These variables could be validated as biomarkers and used in making clinical decisions and during drug development. The top five variables for predicting inhibitor development based on SHAP values are: (i) the baseline activity of the FVIII protein, (ii) mean affinity of all foreign peptides for HLA DRB 3, 4, & 5 alleles, (iii) mean affinity of all foreign peptides for HLA DRB1 alleles), (iv) the minimum affinity among all foreign peptides for HLA DRB1 alleles, and (v) F8 mutation type.

60 APPLIED LIFE SCIENCES↗

Wind Supply Chain Security: Hardware Enumeration and Analysis

This project, undertaken by Idaho National Laboratory (INL) for the Department of Energy (DOE) Wind Energy Technologies Office (WETO), focused on the enumeration and analysis of six key devices important to wind technologies. The devices analyzed included Beckhoff Bus Terminal Controllers (BK1120 and BC9000), a Beckhoff Economy Built-in Panel PC (CP6231), an N-Tron Managed Industrial Ethernet Switch (711FX3), a Bachmann M1 Gateway, and a Bachmann Smart Power Plant Controller. Device selection was driven by availability and budget constraints, with several components sourced from existing wind farms and others procured through a co-agreement with another WETO-funded project. The project's primary objective was to create a hardware bill of materials (HBOM) for each device, identifying and documenting all components to assess potential security and supply chain risks. A detailed analysis revealed over 750 unique components across the six devices, with 80% successfully identified and accompanied by datasheets. Notably, Texas Instruments emerged as the leading supplier, providing over 16% of the components, followed by ON Semiconductor at 11.3%, Analog Devices at 5.3%, and Renesas Electronics Corp at 4.1%. Other notable vendors included Toshiba Corporation, iC-Haus Corporation, Atmel, Vishay, and STMicroelectronics. The enumeration process involved thorough documentation of each component, including its designation, quantity, identifiers, pin package, description, vendor, model, and country of origin. This process provided valuable insights into the complexity and diversity of the electronic systems within these wind devices. It also highlighted the distinct separation of components between vendors, suggesting a trend of vendor-specific component usage. Key findings from the project emphasized the importance of broadening the scope of vendor analysis in future research to gain a comprehensive understanding of component distribution and commonality. The identification of vendor-specific component usage patterns offers new avenues for research and underscores the significance of continued investigation in this field. Overall, this project provides critical insights into the component composition of wind devices, aiding in the development of improved supply chain management and component sourcing strategies. The results contribute valuable knowledge to the wind technology sector, laying the groundwork for enhanced security and resilience in wind energy systems.

17 - WIND ENERGY↗

Fault Management Architectures and the Challenges of Providing Software Assurance

The satellite systems Fault Management (FM) is focused on safety, the preservation of assets, and maintaining the desired functionality of the system. How FM is implemented varies among missions. Common to most is system complexity due to a need to establish a multi-dimensional structure across hardware, software and operations. This structure is necessary to identify and respond to system faults, mitigate technical risks and ensure operational continuity. These architecture, implementation and software assurance efforts increase with mission complexity. Because FM is a systems engineering discipline with a distributed implementation, providing efficient and effective verification and validation (VV) is challenging. A breakout session at the 2012 NASA Independent Verification Validation (IVV) Annual Workshop titled VV of Fault Management: Challenges and Successes exposed these issues in terms of VV for a representative set of architectures. NASA's IVV is funded by NASA's Software Assurance Research Program (SARP) in partnership with NASA's Jet Propulsion Laboratory (JPL) to extend the work performed at the Workshop session. NASA IVV will extract FM architectures across the IVV portfolio and evaluate the data set for robustness, assess visibility for validation and test, and define software assurance methods that could be applied to the various architectures and designs. This work focuses efforts on FM architectures from critical and complex projects within NASA. The identification of particular FM architectures, visibility, and associated VVIVV techniques provides a data set that can enable higher assurance that a satellite system will adequately detect and respond to adverse conditions. Ultimately, results from this activity will be incorporated into the NASA Fault Management Handbook providing dissemination across NASA, other agencies and the satellite community. This paper discusses the approach taken to perform the evaluations and preliminary findings from the research including identification of FM architectures, visibility observations, and methods utilized for VVIVV.

Fault Management↗

The Space Debris Sensor Experiment

The Space Debris Sensor (SDS) is a NASA Class 1E technology demonstration external payload aboard the International Space Station (ISS). With approximately one square meter of detection area, the SDS is attached to the European Space Agency Columbus module facing the ISS velocity vector with minimal obstruction from ISS hardware. The SDS is the first flight demonstration of the Debris Resistive/Acoustic Grid Orbital NASA-Navy Sensor (DRAGONS) technology developed and matured over 10 years by the NASA Orbital Debris Program Office (ODPO), in concert with the DRAGONS consortium, to provide information on the sub-millimeter scale orbital debris environment. The SDS demonstrated the capacity to read 4 resistive grids at 1 Hz, 40 acoustic sensors at 500 kHz, and record and downlink impact data to the ground. Observable and derived data from the SDS could provide information to models that are critical to understanding risks the small debris environment poses to spacecraft in low Earth orbit. The technology demonstrated by the SDS is a major step forward in monitoring and characterizing the space debris environment. This paper will address the technical performance of the SDS during its operational lifetime and its realization of technical and scientific goals. The SDS was intended to operate for 3 years; however, the payload incurred multiple anomalies during its operational life. Subsequently termed “Anomaly #1,” the first was the symptomatic loss of low data rate 1553 channel command and telemetry. The second, Anomaly #2, was loss of all low- and medium-data rate (Ethernet) telemetry. Anomaly #2 proved to be unrecoverable, leading to loss of the payload after approximately 26 days on-board the ISS. Therefore, this paper also addresses the anomalies that occurred during operation of the SDS, their attribution, and their resolution. Lessons learned are described when relevant to anomaly identification, attribution, and resolution.

Anz-Meador, P.↗

Systems Engineering and Management Applications of ISO 9001:2015 for Government

The manufacturing segment of the business world is busy assessing the impact of ISO 9001:2015, and updating their management systems to meet the required compliance date. What does the new revision mean for government agencies that deliver large engineering projects rather than mass production? In fact, the standard, especially the new revision, can be used quite readily for government agencies, or applied to specific projects, once it is understood in terms of the similarities with systems engineering and project management. From there it can be extrapolated to "mission realization" systems, and a Quality Management System (QMS) is a logical result that can bring order to processes and systems that likely already exist in some fashion. ISO 9001:2015 is less product-oriented than previous versions. It can be more broadly applied to public organizations as well as private; and to services (missions) as well as products. The emphasis on risk management in the revised standard provides the needed balance for weighing decisions with respect to cost, schedule, technical, safety, and regulatory compliance; so if this is not part of agency governance already, this is a good place to start, especially for large engineering projects. The Systems Engineering standard used for this analysis is from NASA's NPR 7123.1 NASA Systems Engineering Processes and Requirements; however, those who are more familiar with ISO/IEC 26702 Systems Engineering-application and management of the systems engineering process, or SAE/EIA 632 Processes for Engineering a System will also recognize the similarities. In reality, the QMS outlined by ISO 9001 reinforces the systems engineering processes, and serves to ensure that they are adequately implemented, although most of the ISO 9001 literature emphasizes the production and process aspects of the standard. Rather than beginning with ISO 9001and getting lost in the vocabulary, it is useful to begin with the systems engineering lifecycle. Identification of stakeholder expectations, identifying solutions, creating specific product or service designs, production of the product or service, delivery to the public, and the associated management, planning, and control processes, are a familiar place to begin thinking of the overall system of identifying, designing, and competing a project or mission. Lining up this lifecycle with the ISO requirements (see Figure 1) illustrates how a quality management system is concerned with the same processes, and provides a governance and assurance function. If implemented properly, there are cost savings resulting from less rework, repair, reprocessing, failures, misplaced documents, and similar types of deficiencies1. Starting with an organization's systems engineering processes allows the organization to use their own terminology for a QMS plan, and tailor the plan to their own project or organization, so that it is more easily developed, understood, and implemented.

Shepherd, Christena C.↗

Determining Simulation Fidelity Necessary for Evaluating Onboard Vehicle Capabilities and Crew Roles on Long Duration Exploration Missions Beyond Low-Earth Orbit

Identification of onboard vehicle capabilities and crew roles and responsibilities necessary for achieving effective human-systems collaboration will require iterative cycles of concept development and empirical evaluation of human performance in complex operations. This report presents the results of an effort to lay the groundwork for determining the level of fidelity of simulated environments most suitable for validating concepts and evaluating implementations of a new Human Systems Integration Architecture (HSIA) that will support the flight crew on long duration exploration missions beyond low-Earth orbit. To do that, we conducted a literature review on simulation fidelity and surveyed simulation capabilities inside and outside of NASA used in NASA-sponsored research. We also analyzed two International Space Station (ISS) vehicle anomalies to identify the types of scenario events and crew activities that may need to be simulated. Our survey findings reveal that most NASA simulation facilities are designed to achieve high physical fidelity while HSIA risk mitigation requires simulation emphasizing task and functional fidelity aspects. A trade analysis shows that, for standard and requirement development, evaluation conducted using synthetic task environments with inexperienced participants will support testing a wide variety of conditions and yield findings robust enough to be generalized to a wide variety of designs on which developed standards and requirements might be levied while allowing human performance standard measures to be collected using consistent methods across tasks and conditions. For technology/tool development, because findings will only need to be generalized to the actual target environment in which the technology/tool will be used, it is more suitable to evaluate the prototypes in a scaled world that preserves functional relationships present in the actual target environment with intended user populations. To wrap up, we give an overview of a well-known synthetical task environment in the space domain and discuss what it takes to construct a synthetic task environment.

simulation fidelity↗

Crew Launch Vehicle (CLV) Upper Stage Configuration Selection Process

The Crew Launch Vehicle (CLV), a key component of NASA's blueprint for the next generation of spacecraft to take humans back to the moon, is being designed and built by engineers at NASA s Marshall Space Flight Center (MSFC). The vehicle s design is based on the results of NASA's 2005 Exploration Systems Architecture Study (ESAS), which called for development of a crew-launch system to reduce the gap between Shuttle retirement and Crew Exploration Vehicle (CEV) Initial Operating Capability, identification of key technologies required to enable and significantly enhance these reference exploration systems, and a reprioritization of near- and far-term technology investments. The Upper Stage Element (USE) of the CLV is a clean-sheet approach that is being designed and developed in-house, with element management at MSFC. The USE concept is a self-supporting cylindrical structure, approximately 115' long and 216" in diameter, consisting of the following subsystems: Primary Structures (LOX Tank, LH2 Tank, Intertank, Thrust Structure, Spacecraft Payload Adaptor, Interstage, Forward and Aft Skirts), Secondary Structures (Systems Tunnel), Avionics and Software, Main Propulsion System, Reaction Control System, Thrust Vector Control, Auxiliary Power Unit, and Hydraulic Systems. The ESAS originally recommended a CEV to be launched atop a four-segment Space Shuttle Main Engine (SSME) CLV, utilizing an RS-25 engine-powered upper stage. However, Agency decisions to utilize fewer CLV development steps to lunar missions, reduce the overall risk for the lunar program, and provide a more balanced engine production rate requirement prompted engineers to switch to a five-segment design with a single Saturn-derived J-2X engine. This approach provides for single upper stage engine development for the CLV and an Earth Departure Stage, single Reusable Solid Rocket Booster (RSRB) development for the CLV and a Cargo Launch Vehicle, and single core SSME development. While the RSRB design has changed since the CLV Project's inception, the USE design has remained essentially a clean-sheet approach. Although a clean-sheet upper stage design inherently carries more risk than a modified design, it does offer many advantages: a design for increased reliability; built-in extensibility to allow for commonality/growth without major redesign; and incorporation of state-of-the-art materials, hardware, and design, fabrication, and test techniques and processes to facilitate a potentially better, more reliable system. Because consideration was given in the ESAS to both clean-sheet and modified USE designs, this paper will highlight the advantages and disadvantages of both approaches and provide a detailed discussion of trades/selections made that led to the final upper stage configuration.

Davis, Daniel J.↗

Preparing for Human Missions to Mars: The role of ISS and Artemis as Analogs for Research and Technology Testing

The hazards of spaceflight to the human system are present in in varying degrees on different spaceflight platforms: altered gravity, isolation and confinement, distance from Earth, radiation, and hostile closed environments. A strategic view of the fidelity of hazards experienced on different platforms can shape the testing plans for human research and technology demonstration related to crew health and performance. Working across the international partnership, the International Space Station (ISS) is planning periods of modified operations to improve the fidelity of Mars simulations. To understand transit durations as an independent variable, a series of 1-year, 6-month and 30-45 day missions are being planned on ISS. Standard measurements across ISS missions of different durations, lunar missions and ground analogs offers the opportunity to distinguish different hazards and their effects in the context of the relevance to future mission concepts. The ISS partnership is planning for additional test cases that are aligned with Mars mission plans. (1) Evaluating crew performance capabilities when transitioning to gravity after long durations in microgravity representative of a Mars transit. (2) Simulating crew medical care under Mars-like autonomous operations. (3) Identification and testing of operations under communications delay and autonomy expected for Mars missions and the linked effects on behavioral health and performance of the crew. Artemis missions serve as a valuable analogs for Mars surface operations, with partial gravity and deep space radiation hazards, but with crewmembers that are probably more physically capable than their counterparts would be after a Mars transit. Getting unobtrusive data from early Artemis missions, and knowledge gained from operational experience as Artemis operations develop can improve engineering design, medical requirements and countermeasures, and ultimately ensure mission success on Mars. Linking Mars architectures with the plans and capabilities for ISS and Artemis allows us to plan to most operationally relevant tests of crew health and performance on current spaceflight missions to inform planning for future missions to Mars. By using human spaceflight platforms as well as ground simulation in an integrated way, the international community can improve exploration readiness, develop countermeasures and reduce risks of future human space missions.

International Space Station↗

IM3 Projected US Data Center Locations

IM3 Projected US Data Center Locations This dataset contains model projections of new data center facilities in the contiguous United States (CONUS) through 2035 using the CERF – Data Centers model. Data center locations are modeled across four data center electricity demand growth scenarios (low, moderate, high, higher) and five market gravity scenarios (0%, 25%, 50%, 75%, 100%). Projected locations are intended to be regional representations of feasible siting locations in the future to assess potential grid and water stress impacts. The data center load growth scenarios correspond with the rates outlined in EPRI (2024) and include 3.71%, 5%, 10%, and 15% annual growth of electricity demand for data centers from 2023 values in 37 states across the CONUS. Market gravity scenarios correspond to the relative importance of proximity to data center markets or high population areas compared to locational cost in the siting algorithm. 0% market gravity means that siting decisions were entirely determined by the locational cost in each feasible location. 100% market gravity means that only market proximity was considered when siting. Other scenarios have weight placed on both components where total weight always equals 100%. Locational cost is dependent on facility cooling type and corresponding electricity cost, taxes, and other factors. Facility cooling type is spatially determined where high water stress and/or areas with high summer wet bulb temperatures are assumed to operate with mechanical cooling for a higher fraction of the year rather than evaporative cooling. Feasible data center siting areas are based on geospatial suitability raster data developed with open-source information. The following areas are excluded from siting: Areas within 300 m of a federal airport runway Waterbodies Areas with slope >16% Areas susceptible to sinkholes High coastal or inland flood risk areas Local, state, and federal parks, leisure areas, and cemeteries Areas >2 km away from electric substations Areas >5 km away from a municipal water supplier service area Areas >2 km away from high-speed fiber provider service territory Protected Areas Database of the United States (PAD-US) areas Railroads, major roadways, and minor roadways Military areas and training grounds NLCD developed lands Areas >0.8 km (0.5 miles) from NLCD developed lands Because we use open-source information, proprietary information that can influence siting decisions such as individual tax agreements with cities, detailed fiber line connectivity, electric grid power capacity agreements, and others, are not currently accounted for in the modeling process. Using specific building locations and footprints in the dataset for local planning purposes is not advised. Technical Information Geospatial data is provided in geojson format using the Albers Equal Area Conic (ESRI:102003) coordinate reference system. The datasets contain the following parameters: id - unique identification number within given scenario file growth_scenario – data center demand growth scenario market_gravity_weight – market gravity weight scenario (%) region – name of region (i.e., US State) total_cost_million_usd – locational siting cost ($million) campus_size_square_ft – total land acquired for data center facility (square ft) data_center_it_power_mw – IT power of data center facility (MW) mechanical_cooling_frac – fraction of year when data center uses mechanical cooling system water_cooling_frac– fraction of year when data center uses evaporative cooling system cooling_energy_demand_mwh – total annual facility energy demand for cooling (MWh) cooling_water_demand_mgy – total annual facility water demand for cooling (MG) cooling_water_consumption_mgy – total annual facility water consumed (MG) normalized_locational_cost – normalized total locational cost score for location normalized_gravity_score – normalized market gravity score for location weighted_siting_score – total weighted siting score of locational cost and gravity score geometry – polygon geometry of facility Acknowledgment IM3 is a multi-institutional effort led by Pacific Northwest National Laboratory and supported by the U.S. Department of Energy's Office of Science as part of research in MultiSector Dynamics, Earth and Environmental Systems Modeling Program. License This data is made available under a CCBY4.0 License Disclaimer This material was prepared as an account of work sponsored by an agency of the United States Government. Neither the United States Government nor the United States Department of Energy, nor the Contractor, nor any or their employees, nor any jurisdiction or organization that has cooperated in the development of these materials, makes any warranty, express or implied, or assumes any legal liability or responsibility for the accuracy, completeness, or usefulness or any information, apparatus, product, software, or process disclosed, or represents that its use would not infringe privately owned rights. Reference herein to any specific commercial product, process, or service by trade name, trademark, manufacturer, or otherwise does not necessarily constitute or imply its endorsement, recommendation, or favoring by the United States Government or any agency thereof, or Battelle Memorial Institute. The views and opinions of authors expressed herein do not necessarily state or reflect those of the United States Government or any agency thereof. PACIFIC NORTHWEST NATIONAL LABORATORYoperated byBATTELLEfor theUNITED STATES DEPARTMENT OF ENERGYunder Contract DE-AC05-76RL01830

Mongird, Kendall (ORCID:0000000328077088)↗

Error field measurements with rotating RMP fields for DIII-D H-mode

3D magnetic sensors are employed to identify the amplitude and toroidal phase of error fields (EF) by analyzing the torque balance for magnetic islands entrained by rotating resonant magnetic perturbations (RMPs) in DIII-D H-mode plasmas. This technique of torque balance allows for efficient error field identification, offering a valuable tool for scenario-specific and optimized error field compensation (EFC) and requires only magnetic diagnostics. The torque balance used in this work includes the contribution from electromagnetic torque due to error fields, wall response, RMP fields, and viscous. Results show that viscous torque plays a crucial role, particularly during locked modes and H-mode plasmas, ensuring accurate data fits with lower residuals. The torque balance technique reveals that the L- and H-mode plasmas have distinct EF configurations, and consistent with a model-based EF analysis including MHD response in IPEC and the SURFMN EF simulation. This technique shows great robustness in measuring the intrinsic EF amplitude regardless of its amplitude or toroidal phase. Repeated discharges with EFC disparities exhibit consistent results of intrinsic error field within a reasonable range near the “standard” error field compensation. Additionally, the use of a rotating n = 1 resonant magnetic perturbation offers the advantage of reducing disruption risks by entraining saturated magnetic islands. These findings are instrumental for optimizing EF correction in fusion devices, thereby enhancing tearing mode suppression and overall plasma stability.

3D magnetic sensors↗

Fault Management Architectures and the Challenges of Providing Software Assurance

Fault Management (FM) is focused on safety, the preservation of assets, and maintaining the desired functionality of the system. How FM is implemented varies among missions. Common to most missions is system complexity due to a need to establish a multi-dimensional structure across hardware, software and spacecraft operations. FM is necessary to identify and respond to system faults, mitigate technical risks and ensure operational continuity. Generally, FM architecture, implementation, and software assurance efforts increase with mission complexity. Because FM is a systems engineering discipline with a distributed implementation, providing efficient and effective verification and validation (V&V) is challenging. A breakout session at the 2012 NASA Independent Verification & Validation (IV&V) Annual Workshop titled "V&V of Fault Management: Challenges and Successes" exposed this issue in terms of V&V for a representative set of architectures. NASA's Software Assurance Research Program (SARP) has provided funds to NASA IV&V to extend the work performed at the Workshop session in partnership with NASA's Jet Propulsion Laboratory (JPL). NASA IV&V will extract FM architectures across the IV&V portfolio and evaluate the data set, assess visibility for validation and test, and define software assurance methods that could be applied to the various architectures and designs. This SARP initiative focuses efforts on FM architectures from critical and complex projects within NASA. The identification of particular FM architectures and associated V&V/IV&V techniques provides a data set that can enable improved assurance that a system will adequately detect and respond to adverse conditions. Ultimately, results from this activity will be incorporated into the NASA Fault Management Handbook providing dissemination across NASA, other agencies and the space community. This paper discusses the approach taken to perform the evaluations and preliminary findings from the research.

Fault Management↗

Virtual refrigerant charge sensing algorithm for residential CO₂ heat pumps

Natural refrigerants are increasingly adopted in next-generation heat pump systems, among which CO₂ heat pumps have attracted significant attention. However, due to their high operating pressures, the leakage risk is higher, resulting in undercharge conditions and degraded heat pump performance. Thus, developing an accurate refrigerant charge level detection technique is necessary to guarantee safe and efficient operation. Although virtual refrigerant charge (VRC) level calculation algorithms for CO₂ heat pumps exist, they typically rely on empirically selected features without a systematic selection framework, leading to multicollinearity and potential overfitting, which limit their prediction accuracy and generalizability. To address these issues, this study proposes a VRC algorithm framework with a systematic feature selection method that identifies physically meaningful and statistically significant features, and is applied using a residential CO₂ heat pump as a case study. The method is extended from previous work on conventional refrigerants to account for charge behavior in CO₂ gas coolers. The selected features include gas cooler outlet density, evaporator pressure, and superheat temperature. The results demonstrate that the proposed feature selection method significantly improves prediction accuracy compared to existing VRC approaches. A relatively small training dataset (∼30 samples) is sufficient for feature identification and model development. The developed algorithm achieves less than 3% prediction error under both undercharge and overcharge conditions, representing reductions of 46.7% and 35.3% compared to two recent reference VRC algorithms for transcritical CO₂ heat pumps reported in the literature. The proposed algorithm and feature selection method enhance leakage detection capability, facilitate the deployment of CO₂ heat pump systems, and contribute to reduced energy waste and maintenance costs.

Guo, Fangzhou [Lawrence Berkeley National Laborato↗

Basin-scale analysis of Mokelumne River Formation for multi-well CO 2 injection

Large-scale carbon sequestration will likely require multiple projects injecting CO 2 into the same subsurface formation, raising concerns about safe operation and efficient use of storage capacity. This study evaluates the long-term response of the Mokelumne River Formation in California’s Sacramento Basin to multi-megaton CO 2 injection using three geologic models of the formation and the open-source simulator GEOS. The analysis focuses on three aspects of reservoir performance: (1) average pressure increase and dissolved CO 2 mass after 30 years for varying well counts and injection rates, (2) pressure interference in a multi-well configuration, and (3) dynamic storage capacity with identification of overpressure-prone regions. The results show that average formation pressure increases linearly with injected mass, while CO 2 dissolution exhibits mixed scaling: approximately linear with the number of wells but sublinear with injection rate, indicating that distributing injection across more wells enhances dissolution more effectively than increasing per-well rates. Pressure-interference effects are significant, with lower-permeability conditions delaying their onset but amplifying their magnitude at later times. Dynamic capacity, defined by the first occurrence of pressure exceeding the local overburden-based limit anywhere in the formation, varies across geologic models and assumed overburden pressure gradients. A lower fidelity geologic model predicts nearly twice the storage capacity of the two higher fidelity models, which consistently estimate approximately 1 Gt under the upper-bound overburden pressure gradient considered for the Sacramento Basin. In all model scenarios, overpressure develops away from injection wells, particularly in higher-elevation regions, highlighting the importance of basin-scale modelling for identifying risks beyond the immediate well vicinity.

Basin-scale↗

Proteomic Tissue-Based Classifier for Early Prediction of Prostate Cancer Progression

Although ~40% of screen-detected prostate cancers (PCa) are indolent, advanced-stage PCa is a lethal disease with 5-year survival rates around 29%. Identification of biomarkers for early detection of aggressive disease is a key challenge. Starting with 52 candidate biomarkers, selected from existing PCa genomics datasets and known PCa driver genes, we used targeted mass spectrometry to quantify proteins that significantly differed in primary tumors from PCa patients treated with radical prostatectomy (RP) across three study outcomes: (i) metastasis ≥1-year post-RP, (ii) biochemical recurrence ≥1-year post-RP, and (iii) no progression after ≥10 years post-RP. Sixteen proteins that differed significantly in an initial set of 105 samples were evaluated in the entire cohort (n = 338). A five-protein classifier which combined FOLH1, KLK3, TGFB1, SPARC, and CAMKK2 with existing clinical and pathological standard of care variables demonstrated significant improvement in predicting distant metastasis, achieving an area under the receiver-operating characteristic curve of 0.92 (0.86, 0.99, p = 0.001) and a negative predictive value of 92% in the training/testing analysis. This classifier has the potential to stratify patients based on risk of aggressive, metastatic PCa that will require early intervention compared to low risk patients who could be managed through active surveillance.

60 APPLIED LIFE SCIENCES↗

Microbial Surveillance of Potable Water Sources of the International Space Station

To mitigate risk to the crew, the microbial surveillance of the quality of potable water sources of the International Space Station (ISS) has been ongoing since before the arrival of the first permanent crew. These water sources have included stored ground-supplied water, water produced by the shuttle fuel cells during flight, and ISS humidity condensate that is reclaimed and processed. Monitoring was accomplished using a self-contained filter designed to allow bacterial growth and enumeration during flight. Upon return to earth, microbial isolates were identified using 16S ribosomal gene sequencing. While the predominant isolates were common Gramnegative bacteria including Ralstonia eutropha, Methylobacterium fujisawaense, and Spingomonas paucimobilis, opportunistic pathogens such as Stenotrophomonas maltophilia and Pseudomonas aeruginosa were also isolated. Results of in-flight enumeration have indicated a fluctuation of bacterial counts above system design specifications. Additional in-flight monitoring capability for the specific detection of coliforms was added in 2004; no coliforms have been detected from any potable water source. Neither the bacterial concentrations nor the identification of the isolates recovered from these samples has suggested a threat to crew health.

Bruce, Rebekah J.↗

Identification and distribution of pathogens coinfecting with Brucella spp., Coxiella burnetii and Rift Valley fever virus in humans, livestock and wildlife

Zoonotic diseases, such as brucellosis, Q fever and Rift Valley fever (RVF) caused by Brucella spp., Coxiella burnetii and RVF virus, respectively, can have devastating effects on human, livestock, and wildlife health and cause economic hardship due to morbidity and mortality in livestock. Coinfection with multiple pathogens can lead to more severe disease outcomes and altered transmission dynamics. These three pathogens can alter host immune responses likely leading to increased morbidity, mortality and pathogen transmission during coinfection. Developing countries, such as those commonly afflicted by outbreaks of brucellosis, Q fever and RVF, have high disease burden and thus common coinfections. A literature survey provided information on case reports and studies investigating coinfections involving the three focal diseases. Fifty five studies were collected demonstrating coinfections of Brucella spp., C. burnetii or RVFV with 50 different pathogens, of which 64% were zoonotic. While the literature search criteria involved ‘coinfection’, only 24/55 studies showed coinfections with direct pathogen detection methods (microbiology, PCR and antigen test), while the rest only reported detection of antibodies against multiple pathogens, which only indicate a history of co-exposure, not concurrent infection. These studies lack the ability to test whether coinfection leads to changes in morbidity, mortality or transmission dynamics. We describe considerations and methods for identifying ongoing coinfections to address this critical blind spot in disease risk management.

60 APPLIED LIFE SCIENCES↗

Illinois Storage Corridor CarbonSAFE Phase III: Stakeholder Engagement and Outreach Plan

The Stakeholder Engagement and Outreach Plan provides a comprehensive framework for engaging stakeholders of the Illinois Storage Corridor (ISC) project. The ISC project is a CarbonSAFE Phase III project designed to facilitate commercial deployment of carbon capture, utilization, and storage (CCUS) in Illinois. The project aims to establish a multi-industry carbon storage corridor through development of storage sites near the One Earth Energy (OEE) ethanol production facility in north-central Illinois and the Prairie State Generating Company (PSGC) coal-fired power plant in south-central Illinois, with combined annual CO 2 capture ultimately exceeding 8.6 million tons per year. Stakeholder engagement is recognized as a critical component for successful CCUS deployment, alongside technical and economic considerations. As an emerging technology, CCUS may not be well understood by the general population, and lack of public awareness can lead to opposition that poses significant barriers to project development. This plan addresses this challenge through systematic stakeholder identification, analysis, planning, and implementation of engagement actions. The plan is structured around four main sections: Communication, Stakeholder Analysis, Stakeholder Engagement, and Environmental Justice. Activities will be conducted under Tasks 1 and 4 of the project's Statement of Project Objectives, with two key subtasks: (1) developing a stakeholder analysis and engagement plan through face-to-face meetings, facilitated discussions, and surveys; and (2) implementing stakeholder engagement and public outreach activities including meetings, open houses, and permit hearings. The Illinois State Geological Survey (ISGS) will manage engagement activities following DOE-NETL best practices, focusing on providing objective, fact-based information about CCUS and the ISC project. A comprehensive Communication Plan establishes protocols for media contacts, site visits, and crisis communications. The stakeholder analysis follows a structured workflow process divided into Pre-feasibility and Feasibility phases, incorporating contextual understanding, assessment, data collection, and analysis. Key stakeholder groups include government bodies, educational organizations, conservation and environmental groups, agricultural communities, and religious organizations. The plan addresses common stakeholder questions regarding project risks, benefits, safety, property values, liability, and environmental impacts. Recommendations emphasize developing clear messaging, creating informational materials, and preparing to address both project-specific and broader environmental concerns to ensure transparent communication and build stakeholder support throughout project implementation.

25 ENERGY STORAGE↗

Infrared Imaging of Boundary Layer Transition Flight Experiments

The Hypersonic Thermodynamic Infrared Measurement (HYTHIRM) project is presently focused on near term support to the Shuttle program through the development of an infrared imaging capability of sufficient spatial and temporal resolution to augment existing on-board Orbiter instrumentation. Significant progress has been made with the identification and inventory of relevant existing optical imaging assets and the development, maturation, and validation of simulation and modeling tools for assessment and mission planning purposes, which were intended to lead to the best strategies and assets for successful acquisition of quantitative global surface temperature data on the Shuttle during entry. However, there are longer-term goals of providing global infrared imaging support to other flight projects as well. A status of HYTHIRM from the perspective of how two NASA-sponsored boundary layer transition flight experiments could benefit by infrared measurements is provided. Those two flight projects are the Hypersonic Boundary layer Transition (HyBoLT) flight experiment and the Shuttle Boundary Layer Transition Flight Experiment (BLT FE), which are both intended for reducing uncertainties associated with the extrapolation of wind tunnel derived transition correlations for flight application. Thus, the criticality of obtaining high quality flight data along with the impact it would provide to the Shuttle program damage assessment process are discussed. Two recent wind tunnel efforts that were intended as risk mitigation in terms of quantifying the transition process and resulting turbulent wedge locations are briefly reviewed. Progress is being made towards finalizing an imaging strategy in support of the Shuttle BLT FE, however there are no plans currently to image HyBoLT.

Berry, Scott A.↗