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At least 433 records · Page 24

Broadly neutralizing antibodies against sarbecoviruses generated by immunization of macaques with an AS03-adjuvanted COVID-19 vaccine

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has placed an imperative on the development of countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent monoclonal antibodies (mAbs) that neutralized multiple sarbecoviruses from macaques vaccinated with AS03-adjuvanted monovalent subunit vaccines. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells (MBCs) for at least 1 year after primary vaccination. Antibodies generated from these antigen-specific MBCs at 5 to 12 months after vaccination displayed greater potency and breadth relative to those identified at 1.4 months. Fifteen of the 338 (about 4.4%) antibodies isolated at 1.4 to 6 months after the primary vaccination showed potency against SARS-CoV-2 BA.1, despite the absence of serum BA.1 neutralization. 25F9 and 20A7 neutralized authentic clade 1 sarbecoviruses (SARS-CoV, WIV-1, SHC014, SARS-CoV-2 D614G, BA.1, and Pangolin-GD) and vesicular stomatitis virus–pseudotyped clade 3 sarbecoviruses (BtKY72 and PRD-0038). 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1, and XBB. Crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved sites within the RBD. Prophylactic protection of 25F9, 20A7, and 27A12 was confirmed in mice, and administration of 25F9 particularly provided complete protection against SARS-CoV-2, BA.1, SARS-CoV, and SHC014 challenge. These data underscore the extremely potent and broad activity of these mAbs against sarbecoviruses.

60 APPLIED LIFE SCIENCES↗

FRIB Beam Power Ramp-up: Status and Plans

After project completion on scope, on cost, and ahead of schedule, the Facility for Rare Isotope Beams began operations for scientific users in May of 2022. The ramp-up to a beam power of 400 kW is planned over a six-year period; 1 kW was delivered for initial user runs from in 2022, and 5 kW was delivered as of February 2023. Test runs with 10 kW 36Ar and 48Ca beams were conducted in July 2023. Upgrade plans include doubling the primary-beam energy to 400 MeV/nucleon for enhanced discovery potential (¿FRIB 400¿). This talk reports on the strategic plans towards high power operations emphasizing challenges and resolutions in beam-interception devices and targetry systems, radiation protection and controls, and legacy system renovation and integration.

43 PARTICLE ACCELERATORS↗

An Integrated Risk Assessment Process for Digital Instrumentation and Control Upgrades of Nuclear Power Plants

Most of the existing nuclear power plants (NPPs) in the world rely on traditional analog instrumentation and control (I&C) systems for monitoring, control, and protection functions. With the industrial base largely moving to digital systems, the operation and maintenance of plants involves managing issues including lack of needed analog spare parts, increasing maintenance costs, and the loss of vendor support. Compared with existing analog I&C systems, digital I&C systems have significant functional advantages, such as reliable system performance in terms of accuracy and computational capability, high data handling and storage capabilities to fully measure and display operating conditions, and improved capabilities (e.g., fault tolerance, self-testing, signal validation, process system diagnostics). Therefore, the U.S. nuclear power industry has initiated the replacement of existing, aging analog systems with digital I&C technology, and is developing new designs for advanced plants using digital systems in integrated control rooms to provide modern control and protection systems. However, the qualification of digital I&C systems remains a challenge, especially the issue of software common cause failure (CCF), which has been difficult to address. A CCF is the malfunction of two or more plant components or functions due to a single failure source. CCFs have the potential to generate unanalyzed events or sequences that may not be bounded by previous plant accident analyses, therefore, to challenge the plant safety. Existing analyses on CCF in I&C systems are mainly focusing on hardware failures. With the application and upgrades of new digital I&C systems, software CCFs due to design flaws have become a potential threat to plant safety considering most redundancy designs are using the similar digital platforms or software in the operating and application systems. With complex multi-layer redundancy designs to meet the single failure criterion, these I&C safety systems are of a particular concern in the U.S. Nuclear Regulatory Commission (NRC) licensing procedures. Therefore, there is a need to develop an integrated risk assessment strategy with digital CCF and plant transient responses considered to assure the long-term safety and reliability of vital digital systems and reduce uncertainties in costs, time, and support integration of digital systems in the plant. The overall goal of this project is to deliver a strong technical basis to support effective, licensable, and secure digital I&C technologies for the digital upgrades to existing NPPs. To deal with the expensive licensing justifications from regulatory insights, this technical basis is instructive for nuclear vendors and utilities to effectively lower the costs associated with digital compliance and speed-up industry advances by: (1) defining an integrated risk-informed analysis process for digital I&C upgrades including hazard analysis, reliability analysis, and consequence analysis; (2) applying systematic and risk-informed tools to address CCFs and quantify responding failure probabilities for digital I&C technologies; (3) evaluating the impact of digital failures at the individual level, system level, and plant level; and (4) providing insights and suggestions on designs to manage the risks, thus to support the development, licensing, and deployment of advanced digital I&C technologies on NPPs. Upgrading digital I&C (safety and non-safety related) systems in existing NPPs within a cost-effective and regulatory acceptable way offers the foremost means of performance improvements and cost-reductions for existing NPPs. One key outcome of this project is to perform plant-specific risk assessment to provide a sustainable scientific support for enabling industry to balance the digital-related risks, costs, reliability, and safety.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Cyber-Informed Engineering Research and Development Guide

This document provides guidance on incorporating Cyber Informed Engineering (CIE) principles into the research and development (R&D) of operational technology systems and tools, facilitating the creation and adoption of innovative technologies that are secure and resilient by design. As technological innovation and research are becoming pivotal for economic and national security, cybersecurity has emerged as a paramount concern across industries and sectors. The challenge of integrating robust cybersecurity measures is imperative to safeguard critical infrastructure, protect sensitive data, and preserve national security interests.

24 POWER TRANSMISSION AND DISTRIBUTION↗

20 kV Gallium Nitride pn Diode Electro-Magnetic Pulse Arrestor for Grid Reliability (Final Scientific/Technical Report)

This project developed vertical Gallium Nitride (GaN) pn diodes under two main thrusts: (1) A focus on relatively higher-voltage devices for use as fast EMP arrestors to protect the electric grid; and (2) A focus on a Foundry effort to establish the manufacturability of relatively lower voltage devices. For the first thrust, the aim was to develop devices that go into avalanche breakdown to clamp the voltage across sensitive grid equipment subject to voltage transients induced by electromagnetic pulses (EMPs). Devices with breakdown voltages exceeding 6.5 kV were achieved, and breakdown times shorter than 1 ns were demonstrated, which is sufficiently fast to protect against the fast component of an EMP-induced signal. Key challenges included the epitaxial growth of thick (50 µm or more), low-doped (low 10 15 cm -3 range) GaN layers comprising the drift regions of the diodes, as well as the design and fabrication of edge termination structures (step-etched junction termination extensions) to prevent premature breakdown. Midway through the project, an additional emphasis was put on large-area, high-current devices, and forward currents of approximately 400 A were achieved in composite devices towards the end of the project. Experimental and theoretical studies of impact ionization and avalanche ruggedness were also conducted. For the second thrust (the Foundry), the focus was primarily on 1.2-kV-class devices, although towards the end of the project outstanding results on 3.3-kV class devices were also achieved. The aim of the Foundry was to develop a high-yield, reliable, and economic vertical GaN pn diode process. The Foundry conducted characterization of incoming epitaxial material and correlated this information with the yield and performance of fully processed devices. Wafer maps of diode characteristics such as forward and reverse current as well as capacitance-voltage curves were measured using auto-probing. Several mask sets comprising different-area devices as well as multiple edge termination designs (implanted junction termination extensions, guard rings, and combinations thereof) were studied, and machine-learning-based approaches were utilized to analyze the data. Packaging and reliability efforts were also undertaken for the Foundry diodes, which are necessary for a viable commercial process.

20KV↗

20 kV Gallium Nitride pn Diode Electro-Magnetic Pulse Arrestor for Grid Reliability (Final Report)

This project developed vertical Gallium Nitride (GaN) pn diodes under two main thrusts: (1) A focus on relatively higher-voltage devices for use as fast EMP arrestors to protect the electric grid; and (2) A focus on a Foundry effort to establish the manufacturability of relatively lower-voltage devices. For the first thrust, the aim was to develop devices that go into avalanche breakdown to clamp the voltage across sensitive grid equipment subject to voltage transients induced by electromagnetic pulses (EMPs). Devices with breakdown voltages exceeding 6.5 kV were achieved, and breakdown times shorter than 1 ns were demonstrated, which is sufficiently fast to protect against the fast component of an EMP-induced signal. Key challenges included the epitaxial growth of thick (50 um or more), low-doped (low 10 15 cm -3 range) GaN layers comprising the drift regions of the diodes, as well as the design and fabrication of edge termination structures (step-etched junction termination extensions) to prevent premature breakdown. Midway through the project, an additional emphasis was put on large-area, high-current devices, and forward currents of approximately 400 A were achieved in composite devices towards the end of the project. Experimental and theoretical studies of impact ionization and avalanche ruggedness were also conducted. For the second thrust (the Foundry), the focus was primarily on 1.2-kV-class devices, although towards the end of the project outstanding results on 3.3-kV-class devices were also achieved. The aim of the Foundry was to develop a high-yield, reliable, and economic vertical GaN pn diode process. The Foundry conducted characterization of incoming epitaxial material and correlated this information with the yield and performance of fully processed devices. Wafer maps of diode characteristics such as forward and reverse current as well as capacitance-voltage curves were measured using auto-probing. Several mask sets comprising different-area devices as well as multiple edge termination designs (implanted junction termination extensions, guard rings, and combinations thereof) were studied, and machine-learning-based approaches were utilized to analyze the data. Packaging and reliability efforts were also undertaken for the Foundry diodes, which are necessary for a viable commercial process.

24 POWER TRANSMISSION AND DISTRIBUTION↗

Hazardous Waste Facility Permit Community Relations Plan

The mission of Los Alamos National Laboratory (LANL or the Laboratory) is to solve national security challenges through scientific excellence. Our vision is delivering science and technology to protect our nation and promote world stability.

54 ENVIRONMENTAL SCIENCES↗

Capacity of ETS-10 supported carbon nanosorbent for removal of multicomponent from off-gas stream

Nuclear fission results in fission and activation products, some of which are volatile under the conditions of used nuclear fuel (UNF) reprocessing. Several volatile radionuclides are released into the atmosphere through offgas stream, which includes {sup 3}H, {sup 14}C, {sup 129}I and noble gases, Kr and Xe. {sup 129}I is a highly mobile and volatile contaminant. It has half-life period about 1.57 x 107 years that tends to bioaccumulate, concentrating in the thyroid glands and affecting bio-metabolism in humans. {sup 85}Kr is a chemically inert radioisotope with a half-life of 10.7 years that continuously accumulate in the environment. Control of emissions of these contaminants is necessary to comply with the stringent regulatory limits placed on their releases to protect human health and environment. Removal of these contaminants has been a challenge since the 1950's, and several methods including cryogenic distillation, fluorocarbon absorption, wet scrubbing, and adsorption have been employed. Currently, adsorption on porous solid sorbent shows the most promise results. Up to now, several sorbents such as silver impregnated mordenite, silver ETS-10, chalcogen based aerogels, and metal organic framework, MOFs have been developed for this purpose. Despite these advances, development of economical and highly active sorbents for complete removal and immobilization of volatile radioactive gases remains a key challenge in realizing advanced fuel cycles. Present research work is focused on the determination of the removal capacity of C'at'ETS-10 sorbent for a multicomponent (iodine and krypton) off-gas stream at ambient temperature. Our previously reported work showed that the 10 wt% C'at'ETS-10 sorbent was active for adsorption of krypton as well as iodine at ambient temperature and pressure. Therefore, 10 wt% C'at'ETS-10 sorbent was synthesized by wet-impregnation technique. The performance evaluation of the prepared nanosorbent was examined for the removal of iodine and krypton from the breakthrough curves obtained using bench scale experimental setup. ETS-10 supported carbon nanoparticles, C'at'ETS-10 nanosorbent was successfully synthesized by wet-impregnation technique. The 1/8 inch pelletized sorbent was used to minimize the pressure drop in adsorption column. The capacity of sorbent was found to be 0.143 mg g{sup -1} for krypton and 24.5 mg g{sup -1} for iodine. This experimental results indicates the C'at'ETS-10 is the effect sorbent for removal of multicomponent, krypton as well as iodine from the off-gas stream at ambient temperature. (authors)

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Induced Radioactivity Analysis for the NSRL Linac in China Using Monte Carlo Simulations and Gamma Spectroscopy - Paper 141

The Synchrotron Radiation Facility of the National Synchrotron Radiation Laboratory (NSRL) located in Hefei, China consists of a 200-MeV electron linear accelerator and an 800-MeV electronic storage ring. Constructed in 1989, the 200-MeV Electron linac is one of the earliest high-energy electron linear accelerators in China. The NSRL is a large-scale experiment device, having been operated more than twenty years, so it is hard to give a historical recount about the injection of NSRL Linac. Lower-energy electrons emitted from the accelerator electron gun are progressively accelerated to about 200 MeV in five acceleration tubes, and then are injected into the electron storage ring, reaching the final energy of 800 MeV. The linear accelerator is a traveling wave linear accelerator, consisting of pre-injection, four 6-m acceleration segment, some beam sensing elements, and focusing inserts. The electrons are accelerated in the acceleration tubes to 32 MeV, 74 MeV, 116 MeV, 158 MeV, respectively, and the electronic energy reaches 200 MeV at the end of the acceleration trip. A scraper is used for beam collimation and is located at the end of each acceleration tube, with a length that increases with the energy to provide sufficient collimation. The NSRL Linac was retired in 2012 due to a plan to upgrade the facility. The decommissioning produced many real challenges related to the methods to handle the large size of the device and the time required to store structural materials until the radioactivity is reduced in the waste repository. These problems should be solved as soon as possible in order for the upgrade to proceed smoothly. At present, no prior decommissioning experience existed in China on such a high-energy electron linear accelerator. Therefore, the decommission project provided an opportunity to study and evaluate the challenges, in particular, involving the induced radioactivity for the purposes of radiation protection. For a well-shielded accelerator facility, the induced radioactivity is an important source of radiation for people who perform the decommissioning. In addition, information on the level of induced radioactivity is needed for disposing of the retired accelerator materials. Therefore it is significant to predict such radioactivity level accurately. However, the induced radioactivity study for such type high-energy electron linear accelerator is very seldom. Particle accelerators that operate at energy greater than 10 MeV will produce induced radioactivity due to well-known photonuclear interactions. However, the assessment of such as induced radioactivity of large-scale installations is a time-consuming process. Experimental methods are time-consuming and require special radiation safety measures to protection the investigators. On the other hand, empirical formula cannot yield sufficiently accurate results. Therefore, Monte Carlo simulation method is the primary means to study such problems. In the decommissioning process of the NSRL Linac, the induced radioactivity assessment will be based on Monte Carlo simulation method as the main auxiliary means to expand a series of studies. (authors)

43 PARTICLE ACCELERATORS↗

Residential (Secondary-Use) Energy Storage System with Modular Software and Hardware Power Electronic Interfaces

Secondary-use energy storage systems (ESS) are a potential low-cost energy storage system for the electric grid. These systems propose a low-cost solution to the challenge, what to do with electric vehicle batteries once EV end-of-life has been reached. However, the development of an ESS is complex by nature. Typically, the bidirectional power electronics conversion (PEC) system has hardware which includes power stages, auxiliary circuits, protection circuits, and the control interfaces all embedded and integrated as a system. This leads to interoperability challenges and vendor dependencies that increase balance of system costs. This paper proposes a modular approach of software and hardware interfaces to reduce the costs of an ESS.

Starke, Michael↗

User defined elements in ANSYS for 2D multiphysics modeling of superconducting magnets

Dynamic simulation of superconducting magnets is critical for the design of quench protection systems to prevent potentially damaging temperatures and high voltage from developing after magnet quench. Modeling these scenarios is challenging due to the many multiscale phenomena which impact magnet behavior. These range from conductor scale effects of quench and interfilament coupling currents up to the behavior of the magnet in its powering and protection circuit. In addition, a strong coupling between electromagnetic and thermal domains is required to capture temperature and field dependent material properties and quench behavior. We present a finite element approach which integrates the various effects into the commercial software ANSYS by means of programming new element types. This is shown capable of simulating the strongly coupled transient electromagnetic, thermal, and circuit behavior of superconducting magnets required for quench protection studies. A benchmarking study is presented which shows close agreement between the new ANSYS elements and a COMSOL Multiphysics implementation developed at CERN for dump resistor and coupling loss induced quench based magnet protection of a Nb 3 Sn block dipole. Following this, the ANSYS implementation is shown reproducing strongly coupled quench back behavior observed during the test of a Nb 3 Sn superconducting undulator prototype at Lawrence Berkeley National Laboratory.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Advanced Reactor Safeguards & Security 2024 Program Roadmap

The Advanced Reactor Safeguards and Security (ARSS) program was established to provide research support addressing near term challenges that advanced nuclear reactor vendors face in meeting domestic Material Control and Accounting (MC&A), Physical Protection System (PPS), and Cybersecurity requirements for U.S. construction. The technical work in the program is meant to (1) support nuclear reactor vendors with advanced MC&A, PPS, and Cybersecurity designs for next generation reactors, (2) provide technical bases for the regulator, and (3) promote the integration of Safeguards and Security by Design early in the design process. Existing domestic regulations for safeguards and security, as outlined in the Code of Federal Regulations, were written for large light water reactors, and rule-making efforts are underway to develop regulations more suited to different reactor designs. The ARSS program seeks to remove roadblocks in the deployment of new and advanced reactors by solving regulatory challenges, reducing safeguards and security costs, and utilizing the latest technologies and approaches for robust plant monitoring and protection. This roadmap discusses the goals of the ARSS program, current research, and program plan for the next five years.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Atomic layer deposition grown MO{sub x} thin films for solar water splitting: Prospects and challenges

The magnitude of energy challenge not only calls for efficient devices but also for abundant, inexpensive, and stable photoactive materials that can enable efficient light harvesting, charge separation and collection, as well as chemical transformations. Photoelectrochemical systems based on semiconductor materials have the possibility to transform solar energy directly into chemical energy the so-called “solar hydrogen.” The current challenge lies in the harvesting of a larger fraction of electromagnetic spectrum by enhancing the absorbance of electrode materials. In this context, atomically precise thin films of metal oxide semiconductors and their multilayered junctions are promising candidates to integrate high surface areas with well-defined electrode–substrate interface. Given its self-limited growth mechanism, the atomic layer deposition (ALD) technique offers a wide range of capabilities to deposit and modify materials at the nanoscale. In addition, it opens new frontiers for developing precursor chemistry that is inevitable to design new processes. Herein, the authors review the properties and potential of metal oxide thin films deposited by ALD for their application in photoelectrochemical water splitting application. The first part of the review covers the basics of ALD processes followed by a brief discussion on the electrochemistry of water splitting reaction. The second part focuses on different MO{sub x} films deposited by atomic layer deposition for water splitting applications; in this section, The authors discuss the most explored MO{sub x} semiconductors, namely, Fe{sub 2}O{sub 3}, TiO{sub 2}, WO{sub 3}, and ZnO, as active materials and refer to their application as protective coatings, conductive scaffolds, or in heterojunctions. The third part deals with the current challenges and future prospects of ALD processed MO{sub x} thin films for water splitting reactions.

36 MATERIALS SCIENCE↗

Maintenance of Maywood Laboratory Operations Support During Contractor Transition and Replacement of the Project Databases - 16329

In December 2013, Cabrera Services (Cabrera) executed transition of the FUSRAP Maywood Superfund Site remediation project operations, including an on-site accredited environmental lab, from a large business that had established technology infrastructure in place for over a decade which required updating to support the expected remediation scope and client needs. As of November 2015, Cabrera has shipped over 116,000 yd{sup 3} of contaminated soil to disposal facilities. During the transition, the USACE FUSRAP Maywood Laboratory (UFML) continued to support project operations, providing the expected timely and reliable results and maintaining their New Jersey Department of Environmental Protection certification for all parameters of concern, while having to cope with new challenges and additional tasks having the potential to disrupt the laboratory's ability to support project operations. This case study examines the challenges with maintaining a certified radiochemistry laboratory and an aggressive remediation schedule during a period of prime contractor transition which included a complete IT infrastructure overhaul, and conversion of the existing Microsoft Access laboratory database and project Electronic Data Management System (EDMS) to a customized commercial solution. Challenges: I. Procurement of a new database subcontractor and working closely with them to achieve the following: a. Migration of all environmental (including radiological, chemical, and quality control), health and safety, and spatial data as well as reports, queries, and analytical instrument software processes from a MS Access data management system to a SQL server system; and b. Verification that the functionality and data integrity of the databases remained intact. II. The onsite laboratory was changed over to a new onsite network and the following tasks were completed with little or no interruption to site operations by January 10, 2014: i. Installation of new instrument personal computers (PCs) and making them fully operational; ii. Configuration of the lab domain and server to host the LIMS (replaced all servers/domain/workstations with Windows 7 and Server 2012 machines). iii. Networking of the laboratory building into the rest of the project site via fiber optic cabling across the site. iv. Upgrade of the wide area network (WAN) data connection to high-speed Fiber Optic service; v. Upgrade of the telephones into voice over internet protocol (VOIP) phones. vi. Splitting of the database into front ends and a centralized back-end hosted on the new server to allow simultaneous access for fixes and improvements. III. Phone service interruption; phone systems were operational by January 10, 2014. Additional Tasks: I. Revision of the USACE FUSRAP Maywood Laboratory (UFML) Quality Systems Manual Rev. 1 Submitted 01/16/14; II. Writing of the Uniform Federal Policy Quality Assurance Project Plan Rev. 1 (UFP-QAPP) submitted 1/21/14. This document replaced the prior project data quality plan, the Chemical Data Quality Management Plan. III. Support of USACE communications to the New Jersey Department of Environmental Protection (NJDEP) on lab management and personnel transition to Cabrera. This work was important since it ensured a smooth transition and shows how critical project records infrastructure such as databases, can be upgraded with minimal interruption of project support. Such work may provide benefit to other similar projects, especially long term projects where database infrastructure upgrades may be beneficial in terms of improved efficiencies in data recording and transfer, and improved security in data storage. (authors)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Broadly neutralizing humanized SARS-CoV-2 antibody binds to a conserved epitope on Spike and provides antiviral protection through inhalation-based delivery in non-human primates

The COVID-19 pandemic represents a global challenge that has impacted and is expected to continue to impact the lives and health of people across the world for the foreseeable future. The rollout of vaccines has provided highly anticipated relief, but effective therapeutics are required to further reduce the risk and severity of infections. Monoclonal antibodies have been shown to be effective as therapeutics for SARS-CoV-2, but as new variants of concern (VoC) continue to emerge, their utility and use have waned due to limited or no efficacy against these variants. Furthermore, cumbersome systemic administration limits easy and broad access to such drugs. As well, concentrations of systemically administered antibodies in the mucosal epithelium, a primary site of initial infection, are dependent on neonatal Fc receptor mediated transport and require high drug concentrations. To reduce the viral load more effectively in the lung, we developed an inhalable formulation of a SARS-CoV-2 neutralizing antibody binding to a conserved epitope on the Spike protein, ensuring pan-neutralizing properties. Administration of this antibody via a vibrating mesh nebulization device retained antibody integrity and resulted in effective distribution of the antibody in the upper and lower respiratory tract of non-human primates (NHP). In comparison with intravenous administration, significantly higher antibody concentrations can be obtained in the lung, resulting in highly effective reduction in viral load post SARS-CoV-2 challenge. This approach may reduce the barriers of access and uptake of antibody therapeutics in real-world clinical settings and provide a more effective blueprint for targeting existing and potentially emerging respiratory tract viruses.

60 APPLIED LIFE SCIENCES↗

Toll-like Receptor Ligands Enhance Vaccine Efficacy against a Virulent Newcastle Disease Virus Challenge in Chickens

To enhance the efficacy of the current Newcastle disease vaccine, we have selected potential adjuvants that target well-characterized pattern recognition receptors: the toll-like receptors (TLRs). Imiquimod is a small-molecule activator of TLR7, which is a sensor of dsDNA. ODN-1826 is a mimetic of CpG DNA and ligates TLR21 (a chicken homologue of TLR9 in mammals). The activation of TLRs leads to antiviral responses, including the induction of type I interferons (IFNs). In this study, birds were vaccinated intranasally with a live LaSota strain with or without imiquimod or ODN-1826 (50 µg/bird). Two weeks after vaccination, the birds were challenged with a virulent Newcastle disease virus (chicken/CA/212676/2002). Both adjuvants (imiquimod or ODN-1826) induced higher and more uniform antibody titers among vaccinated birds compared with the live vaccine-alone group. In addition, adjuvanted vaccines demonstrated greater protective efficacy in terms of the reduction in virus-shedding titer and the number of birds shedding the challenge virus at 2 and 4 days post-challenge. A differential expression of antiviral and immune-related genes was observed among groups from tissues (Harderian gland, trachea, cecal tonsil, and spleen) collected 1 and 3 days after treatment. These results demonstrate the potential of TLR-targeted adjuvants as mucosal vaccine enhancers and warrant a further characterization of immune correlates and optimization for efficacy.

59 BASIC BIOLOGICAL SCIENCES↗

Advanced Reactor Safeguards: 2022 Program Roadmap

The Advanced Reactor Safeguards (ARS) program was established in 2020 as part of appropriations for the Advanced Reactor Demonstration Program (ARDP) through the Office of Nuclear Energy in the Department of Energy. The goal of this program is to help address near term challenges that advanced nuclear reactor vendors face in meeting domestic Material Control and Accountancy (MC&A) and Physical Protection System (PPS) requirements for U.S. construction. The technical work in the program is meant to (1) support nuclear reactor vendors with advanced MC&A and PPS designs for next generation reactors, (2) provide technical bases for the regulator, and (3) promote the integration of Safeguards and Security by Design early in the design process. Existing domestic regulations for safeguards and security, as outlined in the Code of Federal Regulations, were written for large light water reactors, and rule-making efforts are underway to develop regulations more suited to different reactor designs. The ARS program seeks to remove roadblocks in the deployment of new and advanced reactors by solving regulatory challenges, reducing safeguards and security costs, and utilizing the latest technologies and approaches for robust plant monitoring and protection. This roadmap discusses the goals of the ARS program, current research, and program plan for the next five years.

98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL P↗