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Phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors

Background The combination of antiangiogenic agents with immune checkpoint inhibitors could potentially overcome immune suppression driven by tumor angiogenesis. We report results from a phase IB study of ziv-aflibercept plus pembrolizumab in patients with advanced solid tumors. Methods This is a multicenter phase IB dose-escalation study of the combination of ziv-aflibercept (at 2–4 mg/kg) plus pembrolizumab (at 2 mg/kg) administered intravenously every 2 weeks with expansion cohorts in programmed cell death protein 1 (PD-1)/programmed death-ligand 1(PD-L1)-naïve melanoma, renal cell carcinoma (RCC), microsatellite stable colorectal cancer (CRC), and ovarian cancer. The primary objective was to determine maximum tolerated dose (MTD) and recommended dose of the combination. Secondary endpoints included overall response rate (ORR) and overall survival (OS). Exploratory objectives included correlation of clinical efficacy with tumor and peripheral immune population densities. Results Overall, 33 patients were enrolled during dose escalation (n=3) and dose expansion (n=30). No dose-limiting toxicities were reported in the initial dose level. Ziv-aflibercept 4 mg/kg plus pembrolizumab 2 mg/kg every 2 weeks was established as the MTD. Grade ≥3 adverse events occurred in 19/33 patients (58%), the most common being hypertension (36%) and proteinuria (18%). ORR in the dose-expansion cohort was 16.7% (5/30, 90% CI 7% to 32%). Complete responses occurred in melanoma (n=2); partial responses occurred in RCC (n=1), mesothelioma (n=1), and melanoma (n=1). Median OS was as follows: melanoma, not reached (NR); RCC, 15.7 months (90% CI 2.5 to 15.7); CRC, 3.3 months (90% CI 0.6 to 3.4); ovarian, 12.5 months (90% CI 3.8 to 13.6); other solid tumors, NR. Activated tumor-infiltrating CD8 T cells at baseline (CD8+PD1+), high CD40L expression, and increased peripheral memory CD8 T cells correlated with clinical response. Conclusion The combination of ziv-aflibercept and pembrolizumab demonstrated an acceptable safety profile with antitumor activity in solid tumors. The combination is currently being studied in sarcoma and anti-PD-1-resistant melanoma. Trial registration number NCT02298959 .

Rahma, Osama E.↗

Advanced Small Modular Reactor Economics Status Report

This report describes the data collection work performed for an advanced small modular reactor (AdvSMR) economics analysis activity at the Oak Ridge National Laboratory. The methodology development and analytical results are described in separate, stand-alone documents as listed in the references. The economics analysis effort for the AdvSMR program combines the technical and fuel cycle aspects of advanced (non-light water reactor [LWR]) reactors with the market and production aspects of SMRs. This requires the collection, analysis, and synthesis of multiple unrelated and potentially high-uncertainty data sets from a wide range of data sources. Further, the nature of both economic and nuclear technology analysis requires at least a minor attempt at prediction and prognostication, and the far-term horizon for deployment of advanced nuclear systems introduces more uncertainty. Energy market uncertainty, especially the electricity market, is the result of the integration of commodity prices, demand fluctuation, and generation competition, as easily seen in deregulated markets. Depending on current or projected values for any of these factors, the economic attractiveness of any power plant construction project can change yearly or quarterly. For long-lead construction projects such as nuclear power plants, this uncertainty generates an implied and inherent risk for potential nuclear power plant owners and operators. The uncertainty in nuclear reactor and fuel cycle costs is in some respects better understood and quantified than the energy market uncertainty. The LWR-based fuel cycle has a long commercial history to use as its basis for cost estimation, and the current activities in LWR construction provide a reliable baseline for estimates for similar efforts. However, for advanced systems, the estimates and their associated uncertainties are based on forward-looking assumptions for performance after the system has been built and has achieved commercial operation. Advanced fuel materials and fabrication costs have large uncertainties based on complexities of operation, such as contact-handled fuel fabrication versus remote handling, or commodity availability. Thus, this analytical work makes a good faith effort to quantify uncertainties and provide qualifiers, caveats, and explanations for the sources of these uncertainties. The overall result is that this work assembles the necessary information and establishes the foundation for future analyses using more precise data as nuclear technology advances.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

FY23 Progress on Computational Modeling of the Water-Based NSTF

This report summarizes the system-level modeling effort by Argonne National Laboratory (Argonne) of the Natural convection Shutdown heat removal Test Facility (NSTF) in FY23. As a continuation of the modeling effort from FY22, this year’s work focuses on improving the RELAP5-3D model developed previously for two-phase flow simulations. The RELAP5-3D model is updated to more accurately capture the heat loss experienced by the facility. The updated model is compared against experimental data for benchmarking purposes of the RELAP5-3D input model. By correctly accounting for heat loss, the updated RELAP5-3D model can now predict the two-phase baseline case more accurately. The onset and the duration of instability are captured well by the model. Furthermore, analyses are performed to better understand the instability mechanism experienced by the flow where the expansion of the boiling boundary in the chimney is studied in details and the fundamental frequencies of the oscillations are obtained. The updated RELAP5-3D model is further compared against four fault conditions, namely the reduction of riser header inlet flow area, depletion of system inventory, blocked riser channels, and static boiling scenario. For each fault condition, minor modifications and tuning are performed to improve the predictions of the model. The purpose of the analyses is to investigate the capability of RELAP5-3D in predicting complex two-phase flows in possible accident scenarios in actual Reactor Cavity Cooling System (RCCS). Overall, the model is able to capture the behaviors and trends of these fault conditions relatively well. Some discrepancies remain between the experimental data and the predictions, many of which are likely due to the differences in the predicted and experimental vapor generation rate. Future work will focus on the continued development of the current RELAP5-3D input model of the NSTF to both improve the accuracy of the model’s predictive capability and continue supporting the experimental program needs. The mutually beneficial relationship between analysis and experimental efforts has become integral to the parent NSTF program, and the greater objective to fully understand and accurately predict the heat removal performance of a full scale RCCS concept.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

A Conceptual Design of the Reactor Cavity Cooling System for the Horizontal Compact High Temperature Gas Reactor (HC-HTGR)

Horizontal Compact High Temperature Gas Reactor (HC-HTGR) is being designed by a multi-disciplinary team of nuclear, mechanical, and structural engineers under the support of a DOE-NE Advanced Reactor Demonstration Program’s Advanced Reactor Concepts-20 (ARC-20) award. The objective of this ARC-20 project is to deliver a conceptual design for the proposed HC-HTGR in 3 years and support its commercialization as a safe, low-cost HTGR. Argonne National Laboratory (Argonne) is responsible for the design and analysis of the reactor cavity cooling system (RCCS) as a safety system for passive decay heat removal of the reactor concept. This report documents the design study to derive a conceptual design study of the RCCS for the HC-HTGR. It includes the identification of the functions and requirements of the HC-HTGR RCCS, design analyses including high-level design consideration and the calculations for optimizing design space of the system with supporting component-level analysis to inform the material selection and performance of the water panel, the description of the conceptual design of the HC-HTGR RCCS derived based on the analyses results, and performance evaluation of the conceptual RCCS for the HC-HTGR. A detailed concept of the RCCS has been identified and high-level system requirements has been developed for the HC-HTGR. Design space focusing on the natural circulation loop portion of the RCCS has been investigated to optimize the system performance. The initial baseline dimensions were firstly derived based on the scoping calculations. A component level design analysis was conducted for the water panel to inform the material selection and to assess its conduction performance. A preliminary system-level performance analysis was performed for the 1/8th of the compartment of the initial baseline design of the RCCS using RELAP5-3D. To improve the system thermal performance, the RCCS design has been updated by exploring various design options by design parametric analyses. Based on the results, the conceptual design of the RCCS for the HC-HTGR has been derived, which satisfies the target performance of ~1 MWt at the elevated vessel wall temperature conditions. Transient simulations were conducted for the conceptual RCCS design for the HC-HTGR under various operation modes and heat load conditions using RELAP5-3D. The system dynamics in different operating states was investigated and the system performance under transients of interest was evaluated. The results demonstrated the overall system feasibility that the RCCS design maintains structures temperatures lower than maximum allowable temperature with sufficient system inventory without any active heat removal in the design process with certain transients addressed. The HC-HTGR RCCS will have additional design updates of subsystems or optimization of the system components during the preliminary and final design phases. Since the entire plant has not been integrated yet, this delivered conceptual design is subject to changes for integration, that require additional conceptual design activities and Quality and Assurance implementation (Q&A). The performance assessment of the RCCS for the HC-HTGR will be then revisited and optimized to finalize the system design, and the RCCS integrated primary system analysis will be utilized to simulate selective accident scenarios of interest where efforts are currently undergoing in the project.

21 SPECIFIC NUCLEAR REACTORS AND ASSOCIATED PLANTS↗

TH-C-18A-08: A Management Tool for CT Dose Monitoring, Analysis, and Protocol Review

Purpose: To develop a customizable tool for enterprise-wide managing of CT protocols and analyzing radiation dose information of CT exams for a variety of quality control applications Methods: All clinical CT protocols implemented on the 11 CT scanners at our institution were extracted in digital format. The original protocols had been preset by our CT management team. A commercial CT dose tracking software (DoseWatch,GE healthcare,WI) was used to collect exam information (exam date, patient age etc.), scanning parameters, and radiation doses for all CT exams. We developed a Matlab-based program (MathWorks,MA) with graphic user interface which allows to analyze the scanning protocols with the actual dose estimates, and compare the data to national (ACR,AAPM) and internal reference values for CT quality control. Results: The CT protocol review portion of our tool allows the user to look up the scanning and image reconstruction parameters of any protocol on any of the installed CT systems among about 120 protocols per scanner. In the dose analysis tool, dose information of all CT exams (from 05/2013 to 02/2014) was stratified on a protocol level, and within a protocol down to series level, i.e. each individual exposure event. This allows numerical and graphical review of dose information of any combination of scanner models, protocols and series. The key functions of the tool include: statistics of CTDI, DLP and SSDE, dose monitoring using user-set CTDI/DLP/SSDE thresholds, look-up of any CT exam dose data, and CT protocol review. Conclusion: our inhouse CT management tool provides radiologists, technologists and administration a first-hand near real-time enterprise-wide knowledge on CT dose levels of different exam types. Medical physicists use this tool to manage CT protocols, compare and optimize dose levels across different scanner models. It provides technologists feedback on CT scanning operation, and knowledge on important dose baselines and thresholds.

60 APPLIED LIFE SCIENCES↗

Wall Upgrades for Energy Retrofits: A Techno-Economic Study

Homes built before 1992, when the U.S. Department of Energy’s (DOE) Building Energy Codes Program was established, represent approximately 68% of the residential building stock in the country. Up to 43% of these homes have little to no insulation in the walls and have very high air leakage rates of 10 or more air changes per hour at 50 pascals of pressure (ACH50). These issues can represent a substantial portion of unnecessary money spent on utility bills for homeowners, especially in the colder climates. There is a significant need for cost-effective, reliable retrofit methods for these homes that include air, moisture, and vapor controls which are considered best practices for high-performance new home construction. Well-tested and documented wall retrofit systems can help to achieve substantial energy savings and also improve durability, comfort, health, and resilience. In 2018, DOE’s Building Technologies Office awarded Pacific Northwest National Laboratory, Oak Ridge National Laboratory, and the University of Minnesota funding to complete a 3-year project to compare a range of residential wall retrofit systems that prioritized affordability, durability and energy savings potential. In addition to these core criteria, the ease-of-construction and the wide-scale applicability of the solutions also were considered. In this project, the research team identified, constructed, tested, simulated, and analyzed the feasibility and economics of 16 wall retrofit assemblies (14 test configurations and two baseline configurations).

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Evaluating the potential of short-term instrument deployment to improve distributed wind resource assessment

Distributed wind projects, which are connected at the distribution level of an electricity system or in off-grid applications to serve specific or local energy needs, often rely solely on wind resource models to establish wind speed and energy generation expectations. Historically, anemometer loan programs have provided an affordable avenue for more accurate onsite wind resource assessment, and the lowering cost of lidar systems has shown similar advantages for more recent assessments. While a full 12 months of onsite wind measurement is the standard for correcting model-based long-term wind speed estimates for utility-scale wind farms, the time and capital investment involved in gathering onsite measurements must be reconciled with the energy needs and funding opportunities that drive expedient deployment of distributed wind projects. Much literature exists to quantify the performance of correcting long-term wind speed estimates with 1 or more years of observational data, but few studies explore the impacts of correcting with months-long observational periods. This study aims to answer the question of how short you can go in terms of the observational time period needed to make impactful improvements to model-based long-term wind speed estimates. Three algorithms, multivariable linear regression, adaptive regression splines, and regression trees, are evaluated for their skill at correcting long-term wind resource estimates from the European Centre for Medium-Range Weather Forecasts Reanalysis version 5 (ERA5) using months-long periods of observational data from 66 locations across the US. On average, correction with even 1 month of observations provides significant improvement over the baseline ERA5 wind speed estimates and produces median bias magnitudes and relative errors within 0.22 m s −1 and 4 percentage points of the median bias magnitudes and relative errors achieved using the standard 12 months of data for correction. However, in cases when the shortest observational periods (1 to 2 months) used for correction are not well correlated with the overlapping ERA5 reference, the resultant long-term wind speed errors are worse than those produced using ERA5 without correction. Summer months, which are characterized by weaker relative wind speeds and standard deviations for most of the evaluation sites, tend to produce the worst results for long-term correction using months-long observations. The three tested algorithms perform similarly for long-term wind speed bias; however, regression trees perform notably worse than multivariable linear regression and adaptive regression splines in terms of correlation when using 6 months or less of observational data for correction. Translating the analysis to wind energy, median relative errors in the capacity factor are on average within 10 % using 1 month of training. If the observation period used for correction is not well correlated with the reference data, however, misrepresentation of the observed capacity factor can be substantial. The risk associated with poor correlation between the observed and reference datasets decreases with increasing training period length. In the worst-correlation scenarios, the median capacity factor relative errors from using 1, 3, and 6 months are within 47 %, 26 %, and 16 %, respectively.

17 WIND ENERGY↗

Improving Efficiency of Off-Road Vehicles by Novel Integration of Electric Machines and Advanced Combustion Engines

Modern off-road equipment will increasingly rely on electrified implements that will deliver precision control with a smaller footprint than hydraulics. The primary energy converter, however, will be an onboard reciprocating internal combustion engine because of the power density of hydrocarbon fuels in comparison to electrical energy storage and the remote locations where much of this equipment is deployed. Adding energy storage and electric machines creates opportunities to improve efficiency while reducing emissions. This program investigated approaches to take advantage of the extra flexibility that an enhanced electrical system to enable high-efficiency, low-emissions combustion technologies. The current program evaluated hybridization of both the torque application and air-handling systems to maximize efficiency while minimizing cost. This program designed, analyzed and tested a hybrid off-road vehicle consisting of a series electric powertrain with energy storage, an electrified air system, and a 33% downsized diesel engine. Detailed comparisons were made between the base powertrain and the developed powertrain using powertrain simulations, engine testing, and vehicle testing. The key results of the study are: • The resulting vehicle reduces fuel consumption by 5% to 15% at equal productivity. The primary improvements were due to recovery of regenerative braking losses for cycles where large transients are encountered. • The electrified air system was an enabler to allow engine downsizing. This was most important for duty-cycles where the engine primarily operated at moderate loads and had few low speed high torque conditions. • Engine level improvements showed re-optimization of the powertrain is possible when electrified air handing is available. Increased exhaust gas recirculation and advanced injection timing allowed up to a 15% reduction in brake specific fuel consumption at equal NOx and transient response. Compared to the larger engine, the downsized engine achieves up to an 18% reduction in brake specific fuel consumption over the non-road transient cycle. • The life cycle analysis and total cost of ownership study showed that the hybrid powertrain has the potential to reduce 5-year CO2 and total cost of ownership by ~6% over the baseline vehicle. The results also indicated that a pure battery electric vehicle is not feasible in this application and is likely to increase the CO2 emissions due to the CO2 from battery production. A hybrid powertrain with low carbon fuels shows the potential to substantially reduce CO2 and total cost of ownership.

02 PETROLEUM↗

Iodine Distribution During Evaporation of Hanford Waste Treatment Plant Direct Feed Low Activity Waste Effluent Management Facility Simulant

The Hanford Waste Treatment and Immobilization Plant (WTP) Low Activity Waste (LAW) vitrification facility will generate an aqueous condensate recycle stream from the off-gas system. The baseline plan for disposition of this stream during full WTP operations is to send it to the WTP Pretreatment Facility, where it will be blended with LAW, concentrated by evaporation, and recycled to the LAW vitrification facility. However, during the Direct Feed LAW (DFLAW) scenario, planned disposition of this stream involves concentrating the condensate in a new evaporator at the Effluent Management Facility (EMF) and returning it to the LAW melter. The LAW melter condensate stream will contain components, e.g. halides and sulfates, that are volatile at melter temperatures, have limited solubility in glass waste forms, and present a material corrosion concern. Further, some minor constituents in the melter condensate, such as volatile organic compounds and iodine, have been found to be at least partially volatile in the EMF. The condensate from the EMF will be sent to the Hanford Effluent Treatment Facility (ETF). The presence of some recalcitrant organics and iodine, as 129I, are expected to be problematic in the ETF. In order to better predict and prepare for the distribution of organics and 129I in the flowsheet, it is key to understand their chemistry and experimentally determine their behavior during evaporation. To do this, modeling and testing were performed to examine the speciation of iodine under relevant conditions, as well as determine partitioning of iodine and the organics in the EMF evaporator. This overall program examines the potential treatment and immobilization of the LAW melter condensate stream to enable alternative disposal. The objective of this task was to (1) perform modeling to determine the speciation and fate of iodine species, (2) prepare a simulant of the LAW Melter Off-gas Condensate expected during DFLAW operations, (3) spike in the key volatile organics and non-radioactive iodine, and (4) demonstrate evaporation in order to predict the final composition of the effluents from the EMF evaporator to aid in planning for their disposition. The results of the modeling of iodine speciation indicate that the iodine is expected to remain in the evaporator pot as iodide and possibly iodate ion if the pH is raised to 11.5-12, which is the planned condition for the EMF. Experimental testing confirmed that the iodide remained in the evaporator concentrate and was below detection limits in all condensate and knock-out pot samples, indicating it was not volatile. The organic nitrile compounds that were added to the simulant were absent from the evaporator feed solution, either lost through evaporation, or more likely, decomposition. The acetone and methylene chloride were below the target values in the feed and condensate samples, and were presumably lost to evaporation or decomposition.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

SU-E-T-614: Plan Averaging for Multi-Criteria Navigation of Step-And-Shoot IMRT

Purpose: Step-and-shoot IMRT is fundamentally discrete in nature, while multi-criteria optimization (MCO) is fundamentally continuous: the MCO planning consists of continuous sliding across the Pareto surface (the set of plans which represent the tradeoffs between organ-at-risk doses and target doses). In order to achieve close to real-time dose display during this sliding, it is desired that averaged plans share many of the same apertures as the pre-computed plans, since dose computation for apertures generated on-the-fly would be expensive. We propose a method to ensure that neighboring plans on a Pareto surface share many apertures. Methods: Our baseline step-and-shoot sequencing method is that of K. Engel (a method which minimizes the number of segments while guaranteeing the minimum number of monitor units), which we customize to sequence a set of Pareto optimal plans simultaneously. We also add an error tolerance to study the relationship between the number of shared apertures, the total number of apertures needed, and the quality of the fluence map re-creation. Results: We run tests for a 2D Pareto surface trading off rectum and bladder dose versus target coverage for a clinical prostate case. We find that if we enforce exact fluence map recreation, we are not able to achieve much sharing of apertures across plans. The total number of apertures for all seven beams and 4 plans without sharing is 217. With sharing and a 2% error tolerance, this number is reduced to 158 (73%). Conclusion: With the proposed method, total number of apertures can be decreased by 42% (averaging) with no increment of total MU, when an error tolerance of 5% is allowed. With this large amount of sharing, dose computations for averaged plans which occur during Pareto navigation will be much faster, leading to a real-time what-you-see-is-what-you-get Pareto navigation experience. Minghao Guo and Hao Gao were partially supported by the NSFC (#11405105), the 973 Program (#2015CB856000) and the Shanghai Pujiang Talent Program (#14PJ1404500)

62 RADIOLOGY AND NUCLEAR MEDICINE↗

High-Efficiency Low-Cost Solar Receiver for Use Ina a Supercritical CO 2 Recompression Cycle

This project has performed solar receiver designs for two supercritical carbon dioxide (sCO 2 ) power cycles. The first half of the program focused on a nominally 2 MWe power cycle, with a receiver designed for test at the Sandia Solar Thermal Test Facility. This led to an economical cavity-type receiver. The second half of the program focused on a 10 MWe power cycle, incorporating a surround open receiver. Rigorous component life and performance testing was performed in support of both receiver designs. The receiver performance objectives are set to conform to the US DOE goals of 6¢/kWh by 2020 . Key findings for both cavity-type and direct open receiver are highlighted below: A tube-based absorber design is impractical at specified temperatures, pressures and heat fluxes for the application; a plate-fin architecture however has been shown to meet performance and life targets; the $148/kW th cost of the design is significantly less than the SunShot cost target with a margin of 30%; the proposed receiver design is scalable, and may be applied to both modular cavity-type installations as well as large utility-scale open receiver installations; the design may be integrated with thermal storage systems, allowing for continuous high-efficiency electrical production during off-sun hours; costs associated with a direct sCO 2 receiver for a sCO 2 Brayton power cycle are comparable to those of a typical molten salt receiver; lifetimes in excess of the 90,000 hour goal are achievable with an optimal cell geometry; the thermal performance of the Brayton receiver is significantly higher than the industry standard, and enables at least a 30% efficiency improvement over the performance of the baseline steam-Rankine boiler/cycle system; brayton’s patent-pending quartz tube window provides a greater than five-percent efficiency benefit to the receiver by reducing both convection and radiation losses.

14 SOLAR ENERGY↗

Initial Radiation of Nuclear Power Plant Components (CRADA NFE-17-06892 Final Report)

As advanced reactor concepts are developed, instrumentation and control (I&C) cables and sensors will play a significant role in assuring their operation is well understood, and safety-related process information can be collected reliably over the course of their design life. As a first step to develop acceptance criteria and define the limits of currently available nuclear I&C cable and sensor technology, a collaboration between Oak Ridge National Laboratory and Analysis and Measurement Services (AMS) Corporation was initiated under the Gateway for Accelerated Innovation in Nuclear (GAIN) Program. This collaborative effort focused on providing technical information related to the combined thermal and radiation aging of nuclear power plant (NPP) cables, companion NPP cable insulation samples, and two prototype temperature and two pressure sensors. This work was carried out using the instrumented gamma irradiation system that is part of the High Flux Isotope Reactor Gamma Irradiation Facility (HFIR GIF). This system provided the opportunity for the condition of the prototype sensors to be tracked during the irradiation in order to determine their functional limits with greater granularity when compared to a simple irradiation insertion at the HFIRGIF. Experimental assemblies for sensor irradiation were successfully completed, and sensor irradiation to accumulated dose of 3000 kGy at a rate of approximately 6 kGy/hr was carried out. Two prototype temperature assemblies were continuously monitored during exposure to 3000 kGy and found to have no observable degradation from the irradiation. Two pressure sensors were first irradiated to 1000 kGy. At which point, one of the sensors was found to operate normally; however, a second sensor failed the operability test. The operable pressure sensor output was then continuously monitored from 1000 kGy to 3000 kGy. The sensor output exhibited steady trendable drift versus the accumulated radiation dose. At the conclusion of the irradiation, the four test sensors were released for laboratory calibration checks. The calibration check of the temperature sensors found no significant change after irradiation compared to baseline measurements before irradiation; however, both pressure sensors failed the post-test calibration checks and both sensors were not functioning properly. These results will help inform sensor manufacturers and I&C design engineers of potential limitations of these types of sensors for use in high radiation environments associated with the compact configuration of new Small Modular Reactors (SMRs) such as NuScale’s reactor power module. Irradiations on NPP cables and companion samples were not completed due to programmatic delays, however a path forward that was based on lessons learned from this project was defined to accommodate future, comparable instrumented gamma irradiations at the HFIR GIF.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Leveraging FPGA Advantages for Quicker Data Processing for LBNF

The Long Baseline Neutrino Facility (LBNF) will deliver a 2.4 MW muon neutrino beam from Fermilab to the Deep Underground Neutrino Experiment (DUNE), requiring unprecedented precision in beamline alignment to achieve DUNE's neutrino oscillation measurement goals. Vertical misalignments of beamline components as small as 0.5 mm can contribute 6-7\% uncertainty in predicted neutrino flux, necessitating sub-0.1 mm alignment monitoring capabilities. The Horn Location Sensor (HLS) system employs frequency sweep interferometry (FSI) in a distributed hydrostatic leveling network to achieve the required precision under harsh radiation conditions up to 5000 kRad/year. Traditional FSI implementations suffer from laser sweep nonlinearities that degrade resolution and require computationally intensive post-processing corrections using gas reference cells. This work presents a real-time FPGA-based implementation of the HLS data acquisition and processing system using a sweep tracker interferometer for dynamic sweep linearization. The system utilizes a PYNQ-Z2 FPGA with programmable logic implementing parallel 16k-point FFT processing across four channels, synchronized by the sweep tracker signal to eliminate post-processing requirements. Spectral performance testing demonstrates significant improvements in peak sharpness compared to traditional fixed-frequency digitization. The FPGA implementation enables real-time displacement monitoring with processing speeds orders of magnitude faster than software-based approaches, essential for the operational requirements of LBNF's eventual distributed sensor network. This advancement in real-time FSI processing directly supports DUNE's precision neutrino physics program by providing the rapid feedback necessary for maintaining stringent beamline alignment tolerances during high-power beam operations.

Rossel, Jacob↗

Real-Time FPGA Implementation For Frequency Sweep Interferometry In The LBNF Complex

The Long Baseline Neutrino Facility (LBNF) will deliver a 2.4 MW muon neutrino beam from Fermilab to the Deep Underground Neutrino Experiment (DUNE), requiring unprecedented precision in beamline alignment to achieve DUNE's neutrino oscillation measurement goals. Vertical misalignments of beamline components as small as 0.5 mm can contribute 6-7\% uncertainty in predicted neutrino flux, necessitating sub-0.1 mm alignment monitoring capabilities. The Horn Location Sensor (HLS) system employs frequency sweep interferometry (FSI) in a distributed hydrostatic leveling network to achieve the required precision under harsh radiation conditions up to 5000 kRad/year. Traditional FSI implementations suffer from laser sweep nonlinearities that degrade resolution and require computationally intensive post-processing corrections using gas reference cells. This work presents a real-time FPGA-based implementation of the HLS data acquisition and processing system using a sweep tracker interferometer for dynamic sweep linearization. The system utilizes a PYNQ-Z2 FPGA with programmable logic implementing parallel 16k-point FFT processing across four channels, synchronized by the sweep tracker signal to eliminate post-processing requirements. Spectral performance testing demonstrates significant improvements in peak sharpness compared to traditional fixed-frequency digitization. The FPGA implementation enables real-time displacement monitoring with processing speeds orders of magnitude faster than software-based approaches, essential for the operational requirements of LBNF's eventual distributed sensor network. This advancement in real-time FSI processing directly supports DUNE's precision neutrino physics program by providing the rapid feedback necessary for maintaining stringent beamline alignment tolerances during high-power beam operations.

Rossel, A. Jacob [Fermilab; Unlisted]↗

High Temperature Steam Electrolysis Process Performance and Cost Estimates - DOE Hydrogen Program AMR Presentation

Technology readiness levels (TRLs) of electrolysis systems have dramatically increased in recent years as the interest in clean hydrogen production and decarbonization of transportation, industrial and other sectors increases across the globe. This is especially true of high temperature steam electrolysis (HTSE) / solid oxide electrolysis cell (SOEC) systems which show promise of much higher system efficiencies than other more developed electrolysis technologies. This possibility of higher efficiencies of HTSE / SOEC systems has been previously assumed to be theoretically possible but in recent years it has become less theoretical and more realistic as an increasing amount of suppliers complete lab and pilot tests showing very promising results. Research in the areas of manufacturing techniques, material selection, electrode and electrolyte compositions, and balance of plant size and integration continues at a fast pace as an increasing number of suppliers both internationally and domestically become involved. The advantages of HTSE become more pronounced when HTSE is coupled with nuclear power plants (NPPs). This is because thermal energy produced by the nuclear reactor can be used in a series of heat transfer loops and heat exchangers to vaporize HTSE feedwater, which drastically improves the economics of the process. Idaho National Laboratory (INL) has been very involved in the research and modeling of HTSE systems for a number of years, in collaboration with other national laboratories, academia, and industry stakeholders both on the hydrogen production as well as the hydrogen demand side. The modeling completed over the years on a large variety of projects has led to a wealth of knowledge at INL including in the area of the technoeconomic assessment (TEA) of HTSE systems. TEAs include process modeling of the HTSE systems to calculate system energy requirements and equipment sizing, followed by estimation of capital and operating costs to enable calculation of the levelized cost of hydrogen (LCOH). The TEA work performed has produced incremental improvements and tuning of the methods, assumptions, models, and results of the analyses as well as providing some opportunities for validating these results. The purpose of this document is to record the current baseline HTSE analyses led by INL to show the current status of assumptions and costs of these systems. Given the rapid development of this technology, the variety of suppliers entering the space, and the increasing attention government and industry are giving to such systems, this document may be updated on a periodic basis with updated analysis and assumptions. This document compiles various analyses results and approaches completed over a period of years into a single document to be used as a baseline going forward. It represents what the INL HTSE analysis group assumes to be the internal best estimate of the current operation, costs, and landscape of the HTSE industry state of the art capability for current SOEC technology in an Nth-of-a-Kind (NOAK) plant, which in this study is defined as existence of the manufacturing capacity to support previous deployment of N = 100 count of 25 MWe modular HTSE blocks (with modular equipment component cost reductions specified as following a 95% learning curve). That said, this is a public document and as such so no proprietary data was used or included in this report. There may be HTSE suppliers that have performance specifications, and cost estimates, and test data that differ from the analysis presented in this document. This document is meant to be a best conservative estimate of the technology and not an absolute reference.

08 HYDROGEN↗

Formulation and preparation of Hanford Waste Treatment Plant direct feed low activity waste Effluent Management Facility core simulant

The Hanford Waste Treatment and Immobilization Plant (WTP) Low Activity Waste (LAW) vitrification facility will generate an aqueous condensate recycle stream (LAW Melter Off-Gas Condensate, LMOGC) from the off-gas system. The baseline plan for disposition of this stream during full WTP operations is to send it to the WTP Pretreatment Facility, where it will be blended with LAW, concentrated by evaporation and recycled to the LAW vitrification facility. However, during the Direct Feed LAW (DFLAW) scenario, planned disposition of this stream is to evaporate it in a new evaporator in the Effluent Management Facility (EMF) and then return it to the LAW melter. It is important to understand the composition of the effluents from the melter and new evaporator so that the disposition of these streams can be accurately planned and accommodated. Furthermore, alternate disposition of the LMOGC stream would eliminate recycling of problematic components, and would enable less integrated operation of the LAW melter and the Pretreatment Facilities. Alternate disposition would also eliminate this stream from recycling within WTP when it begins operations and would decrease the LAW vitrification mission duration and quantity of glass waste, amongst the other problems such a recycle stream present. This LAW Melter Off-Gas Condensate stream will contain components that are volatile at melter temperatures and are problematic for the glass waste form, such as halides and sulfate. Because this stream will recycle within WTP, these components accumulate in the Melter Condensate stream, exacerbating their impact on the number of LAW glass containers that must be produced. Diverting the stream reduces the halides and sulfate in the recycled Condensate and is a key outcome of this work. This overall program examines the potential treatment and immobilization of this stream to enable alternative disposal. The objective of this task was to formulate and prepare a simulant of the LAW Melter Off-gas Condensate expected during DFLAW operations. That simulant can be used in evaporator testing to predict the composition of the effluents from the Effluent Management Facility (EMF) evaporator to aid in planning for their disposition. This document describes the method used to formulate a simulant of this LAW Melter Off-Gas Condensate stream, which, after pH adjustment, is the feed to the evaporator in the EMF.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Improving five-year survival prediction via multitask learning across HPV-related cancers

Oncology is a highly siloed field of research in which sub-disciplinary specialization has limited the amount of information shared between researchers of distinct cancer types. This can be attributed to legitimate differences in the physiology and carcinogenesis of cancers affecting distinct anatomical sites. However, underlying processes that are shared across seemingly disparate cancers probably affect prognosis. The objective of the current study is to investigate whether multitask learning improves 5-year survival cancer patient survival prediction by leveraging information across anatomically distinct HPV related cancers. Furthermore, data were obtained from the Surveillance, Epidemiology, and End Results (SEER) program database. The study cohort consisted of 29,768 primary cancer cases diagnosed in the United States between 2004 and 2015. Ten different cancer diagnoses were selected, all with a known association with HPV risk. In the analysis, the cancer diagnoses were categorized into three distinct topography groups of varying specificity. The most specific topography grouping consisted of 10 original cancer diagnoses differentiated by the first two digits of the ICD-O-3 topography code. The second topography grouping consisted of cancer diagnoses categorized into six distinct organ groups. Finally, the third topography grouping consisted of just two groups, head-neck cancers and ano-genital cancers. The tasks were to predict 5-year survival for patients within the different topography groups using 14 predictive features which were selected among descriptive variables available in the SEER database. The information from the predictive features was shared between tasks in three different ways, resulting in three distinct predictive models: 1) Information was not shared between patients assigned to different tasks (single task learning); 2) Information was shared between all patients, regardless of task (pooled model); 3) Only relevant information was shared between patients grouped to different tasks (multitask learning). Prediction performance was evaluated with Brier scores. All three models were evaluated against one another on each of the three distinct topography-defined tasks. The results showed that multitask classifiers achieved relative improvement for the majority of the scenarios studied compared to single task learning and pooled baseline methods. In this study, we have demonstrated that sharing information among anatomically distinct cancer types can lead to improved predictive survival models.

59 BASIC BIOLOGICAL SCIENCES↗

Emissions reduction scenarios in the Argentinean Energy Sector

Here in this paper the LEAP, TIAM-ECN, and GCAM models were applied to evaluate the impact of a variety of climate change control policies (including carbon pricing and emission constraints relative to a base year) on primary energy consumption, final energy consumption, electricity sector development, and CO 2 emission savings of the energy sector in Argentina over the 2010-2050 period. The LEAP model results indicate that if Argentina fully implements the most feasible mitigation measures currently under consideration by official bodies and key academic institutions on energy supply and demand, such as the ProBiomass program, a cumulative incremental economic cost of 22.8 billion US$(2005) to 2050 is expected, resulting in a 16% reduction in GHG emissions compared to a business-as-usual scenario. These measures also bring economic co-benefits, such as a reduction of energy imports improving the balance of trade. A Low CO 2 price scenario in LEAP results in the replacement of coal by nuclear and wind energy in electricity expansion. A High CO 2 price leverages additional investments in hydropower. An emission cap scenario (2050 emissions 20% lower than 2010 emissions) is feasible by including such measures as CCS and Bio CCS, but at a significant cost. By way of cross-model comparison with the TIAM-ECN and GCAM global integrated assessment models, significant variation in projected emissions reductions in the carbon price scenarios was observed, which illustrates the inherent uncertainties associated with such long-term projections. These models predict approximately 37% and 94% reductions under the High CO 2 price scenario, respectively. By comparison, the LEAP model, using an approach based on the assessment of a limited set of mitigation options, predicts a 11.3% reduction under the ‘high’ carbon tax. The main reasons for this difference are differences in assumptions about technology cost and availability, CO 2 storage capacity, and the ability to import bioenergy. In terms of technology pathways, the models agree that fossil fuels, in particular natural gas, will remain an important part of the electricity mix in the core baseline scenario. Finally, according to the models there is agreement that the introduction of a carbon price will lead to a decline in absolute and relative shares of aggregate fossil fuel generation. However, predictions vary as to the extent to which coal, nuclear and renewable energy play a role.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗