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DOE OSTI2023

Crystal structure of dihydrofolate reductase from the filarial nematode W. bancrofti in complex with NADPH and folate

Lymphatic filariasis is a debilitating illness with an estimated 50 million cases as of 2018. The majority of cases are caused by the parasitic worm W. bancrofti and additional cases by the worms B. malayi and B. timori. Dihydrofolate reductase (DHFR) is an established target in the treatment of cancer, bacterial, and protozoal infections and may be a potential target for drugs targeting parasitic worm infections, including filariasis. Recent studies have shown that known antifolate compounds, including methotrexate, inhibit the activity of W. bancrofti DHFR (WbDHFR). However, the absence of structural information for filarial DHFRs has limited the study of more in-depth structure-function relationships. We report the structure of WbDHFR complexed with NADPH and folate using X-ray diffraction data measured to 2.47 Å resolution. The structure of WbDHFR reveals the usual DHFR fold and is currently only the second nematode DHFR structure in the Protein Data Bank. The equilibrium dissociation constants for NADPH (90 ± 29 nM) and folate (23 ± 4 nM) were determined by equilibrium titrations. The interactions of known antifolates with WbDHFR were analyzed using molecular docking programs and molecular dynamics simulations. Antifolates with a hydrophobic core and extended linker formed favorable interactions with WbDHFR. These combined data should now facilitate the rational design of filarial DHFR inhibitors, which in turn can be used to determine whether DHFR is a viable drug target for filariasis and whether existing antifolates may be repurposed for its treatment.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Evaluation of DNA extraction protocols from liquid-based cytology specimens for studying cervical microbiota

Cervical microbiota (CM) are considered an important factor affecting the progression of cervical intraepithelial neoplasia (CIN) and are implicated in the persistence of human papillomavirus (HPV). Collection of liquid-based cytology (LBC) samples is routine for cervical cancer screening and HPV genotyping and can be used for long-term cytological biobanking. We sought to determine whether it is possible to access microbial DNA from LBC specimens, and compared the performance of four different extraction protocols: (ZymoBIOMICS DNA Miniprep Kit; QIAamp PowerFecal Pro DNA Kit; QIAamp DNA Mini Kit; and IndiSpin Pathogen Kit) and their ability to capture the diversity of CM from LBC specimens. LBC specimens from 20 patients (stored for 716 ± 105 days) with CIN values of 2 or 3 were each aliquoted for each of the four kits. Loss of microbial diversity due to long-term LBC storage could not be assessed due to lack of fresh LBC samples. Comparisons with other types of cervical sampling were not performed. We observed that all DNA extraction kits provided equivalent accessibility to the cervical microbial DNA within stored LBC samples. Approximately 80% microbial genera were shared among all DNA extraction protocols. Potential kit contaminants were observed as well. Variation between individuals was a significantly greater influence on the observed microbial composition than was the method of DNA extraction. We also observed that HPV16 was significantly associated with community types that were not dominated by Lactobacillus iners.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Mining a human transcriptome database for chemical modulators of NRF2

Nuclear factor erythroid-2 related factor 2 (NRF2) encoded by the NFE2L2 gene is a transcription factor critical for protecting cells from chemically-induced oxidative stress. We developed computational procedures to identify chemical modulators of NRF2 in a large database of human microarray data. A gene expression biomarker was built from statistically-filtered gene lists derived from microarray experiments in primary human hepatocytes and cancer cell lines exposed to NRF2-activating chemicals (oltipraz, sulforaphane, CDDOIm) or in which the NRF2 suppressor Keap1 was knocked down by siRNA. Directionally consistent biomarker genes were further filtered for those dependent on NRF2 using a microarray dataset from cells after NFE2L2 siRNA knockdown. The resulting 143-gene biomarker was evaluated as a predictive tool using the correlation-based Running Fisher algorithm. Using 59 gene expression comparisons from chemically-treated cells with known NRF2 activating potential, the biomarker gave a balanced accuracy of 93%. The biomarker was comprised of many well-known NRF2 target genes (AKR1B10, AKR1C1, NQO1, TXNRD1, SRXN1, GCLC, GCLM), 69% of which were found to be bound directly by NRF2 using ChIP-Seq. NRF2 activity was assessed across ~9840 microarray comparisons from ~1460 studies examining the effects of ~2260 chemicals in human cell lines. A total of 260 and 43 chemicals were found to activate or suppress NRF2, respectively, most of which have not been previously reported to modulate NRF2 activity. Using a NRF2-responsive reporter gene in HepG2 cells, we confirmed the activity of a set of chemicals predicted using the biomarker. The biomarker will be useful for future gene expression screening studies of environmentally-relevant chemicals.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Biophysical and X-ray structural studies of the (GGGTT)3GGG G-quadruplex in complex with N-methyl mesoporphyrin IX

The G-quadruplex (GQ) is a well-studied non-canonical DNA structure formed by G-rich sequences found at telomeres and gene promoters. Biological studies suggest that GQs may play roles in regulating gene expression, DNA replication, and DNA repair. Small molecule ligands were shown to alter GQ structure and stability and thereby serve as novel therapies, particularly against cancer. In this work, we investigate the interaction of a G-rich sequence, 5’-GGGTTGGGTTGGGTTGGG-3’ (T1), with a water-soluble porphyrin, N- methyl mesoporphyrin IX (NMM) via biophysical and X-ray crystallographic studies. UV-vis and fluorescence titrations, as well as a Job plot, revealed a 1:1 binding stoichiometry with an impressively tight binding constant of 30–50 μM -1 and ΔG 298 of -10.3 kcal/mol. Eight extended variants of T1 (named T2 –T9) were fully characterized and T7 was identified as a suitable candidate for crystallographic studies. We solved the crystal structures of the T1- and T7-NMM complexes at 2.39 and 2.34 Å resolution, respectively. Both complexes form a 5’-5’ dimer of parallel GQs capped by NMM at the 3’ G-quartet, supporting the 1:1 binding stoichiometry. Our work provides invaluable details about GQ-ligand binding interactions and informs the design of novel anticancer drugs that selectively recognize specific GQs and modulate their stability for therapeutic purposes.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Structure of the EphB6 receptor ectodomain

Eph receptors are the largest group amongst the receptor tyrosine kinases and are divided into two subgroups, A and B, based on ligand binding specificities and sequence conservation. Through ligand-induced and ligand-independent activities, Ephs play central roles in diverse biological processes, including embryo development, regulation of neuronal signaling, immune responses, vasculogenesis, as well as tumor initiation, progression, and metastasis. The Eph extracellular regions (ECDs) are constituted of multiple domains, and previous structural studies of the A class receptors revealed how they interact with ephrin ligands and simultaneously mediate Eph-Eph clustering necessary for biological activity. Specifically, EphA structures highlighted a model, where clustering of ligand-bound receptors relies on two distinct receptor/receptor interfaces. Interestingly, most unliganded A class receptors also form an additional, third interface, between the ligand binding domain (LBD) and the fibronectin III domain (FN3) of neighboring molecules. Structures of B-class Eph ECDs, on the other hand, have never been reported. To further our understanding of Eph receptor function, we crystallized the EphB6-ECD and determined its three-dimensional structure using X-ray crystallography. EphB6 has important functions in both normal physiology and human malignancies and is especially interesting because this atypical receptor innately lacks kinase activity and our understanding of the mechanism of action is still incomplete. Our structural data reveals the overall EphB6-ECD architecture and shows EphB6-LBD/FN3 interactions similar to those observed for the unliganded A class receptors, suggesting that these unusual interactions are of general importance to the Eph group. We also observe unique structural features, which likely reflect the atypical signaling properties of EphB6, namely the need of co-receptor(s) for this kinase-inactive Eph. These findings provide new valuable information on the structural organization and mechanism of action of the B-class Ephs, and specifically EphB6, which in the future will assist in identifying clinically relevant targets for cancer therapy.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Tobacco-specific nitrosamine 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA) causes DNA damage and impaired replication/transcription in human lung cells

Thirdhand smoke (THS) is a newly described health hazard composed of toxicants, mutagens and carcinogens, including nicotine-derived tobacco specific nitrosamines (TSNAs), one of which is 1-(N-methyl-N-nitrosamino)-1-(3-pyridinyl)-4-butanal (NNA). Although TSNAs are generally potent carcinogens, the risk of NNA, which is specific to THS, is poorly understood. We recently reported that THS exposure-induced adverse impact on DNA replication and transcription with implications in the development of cancer and other diseases. Here, we investigated the role of NNA in THS exposure-induced harmful effects on fundamental cellular processes. We exposed cultured human lung epithelial BEAS-2B cells to NNA. The formation of DNA base damages was assessed by Long Amplicon QPCR (LA-QPCR); DNA double-strand breaks (DSBs) and NNA effects on replication and transcription by immunofluorescence (IF); and genomic instability by micronuclei (MN) formation. We found increased accumulation of oxidative DNA damage and DSBs as well as activation of DNA damage response pathway, after exposure of cells to NNA. Impaired S phase progression was also evident. Consistent with these results, we found increased MN formation, a marker of genomic instability, in NNA-exposed cells. Furthermore, ongoing RNA synthesis was significantly reduced by NNA exposure, however, RNA synthesis resumed fully after a 24h recovery period only in wild-type cells but not in those deficient in transcription-coupled nucleotide excision repair (TC-NER). Importantly, these cellular effects are common with the THS-exposure induced effects. Our findings suggest that NNA in THS could be a contributing factor for THS exposure-induced adverse health effect.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Phenopacket-tools: Building and validating GA4GH Phenopackets

The Global Alliance for Genomics and Health (GA4GH) is a standards-setting organization that is developing a suite of coordinated standards for genomics. The GA4GH Phenopacket Schema is a standard for sharing disease and phenotype information that characterizes an individual person or biosample. The Phenopacket Schema is flexible and can represent clinical data for any kind of human disease including rare disease, complex disease, and cancer. It also allows consortia or databases to apply additional constraints to ensure uniform data collection for specific goals. We present phenopacket-tools, an open-source Java library and command-line application for construction, conversion, and validation of phenopackets. Phenopacket-tools simplifies construction of phenopackets by providing concise builders, programmatic shortcuts, and predefined building blocks (ontology classes) for concepts such as anatomical organs, age of onset, biospecimen type, and clinical modifiers. Phenopacket-tools can be used to validate the syntax and semantics of phenopackets as well as to assess adherence to additional user-defined requirements. The documentation includes examples showing how to use the Java library and the command-line tool to create and validate phenopackets. We demonstrate how to create, convert, and validate phenopackets using the library or the command-line application. Source code, API documentation, comprehensive user guide and a tutorial can be found at https://github.com/phenopackets/phenopacket-tools. The library can be installed from the public Maven Central artifact repository and the application is available as a standalone archive. The phenopacket-tools library helps developers implement and standardize the collection and exchange of phenotypic and other clinical data for use in phenotype-driven genomic diagnostics, translational research, and precision medicine applications.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Structures of SARS-CoV-2 N7-methyltransferase with DOT1L and PRMT7 inhibitors provide a platform for new antivirals

The RNA N7-methyltransferase (MTase) activity of SARS-CoV-2’s nsp14 protein is essential for viral replication and is a target for the development of new antivirals. Nsp14 uses S-adenosyl methionine (SAM) as the methyl donor to cap the 5’ end of the SARS-CoV-2 mRNA and generates S-adenosyl homocysteine (SAH) as the reaction byproduct. Due to the central role of histone MTases in cancer, many SAM/SAH analogs with properties of cell permeability have recently been developed for the inhibition of these MTases. We have succeeded in identifying two such compounds (SGC0946 and SGC8158) that display significant antiviral activity and bind to the SARS-CoV-2 nsp14 N7-MTase core. Unexpectedly, crystal structures of SGC0946 and SGC8158 with the SARS-CoV-2 nsp14 N7-MTase core identify them as bi-substrate inhibitors of the viral MTase, co-occupying both the SAM and RNA binding sites; positing novel features that can be derivatized for increased potency and selectivity for SARS-CoV-2 nsp14. Taken together, the high-resolution structures and the accompanying biophysical and viral replication data provide a new avenue for developing analogs of SGC0946 and SGC8158 as antivirals.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2023

A Novel Platform for Evaluating Dose Rate Effects on Oxidative Damage to Peptides: Toward a High-Throughput Method to Characterize the Mechanisms Underlying the FLASH Effect

High dose rate radiation has gained considerable interest recently as a possible avenue for increasing the therapeutic window in cancer radiation treatment. The sparing of healthy tissue at high dose rates relative to conventional dose rates, while maintaining tumor control, has been termed the FLASH effect. Although the effect has been validated in animal models using multiple radiation sources, it is not yet well understood. Here, in this work, we demonstrate a new experimental platform for quantifying oxidative damage to protein sidechains in solution as a function of radiation dose rate and oxygen availability using liquid chromatography mass spectrometry. Using this reductionist approach, we show that for both X-ray and electron sources, isolated peptides in solution are oxidatively modified to different extents as a function of both dose rate and oxygen availability. Our method provides an experimental platform for exploring the parameter space of the dose rate effect on oxidative changes to proteins in solution.

61 RADIATION PROTECTION AND DOSIMETRY↗

DOE OSTI2020

Cellular Response to Proton Irradiation: A Simulation Study with TOPAS-nBio

The cellular response to ionizing radiation continues to be of significant research interest in cancer radiotherapy, and DNA is recognized as the critical target for most of the biologic effects of radiation. Incident particles can cause initial DNA damages through physical and chemical interactions within a short time scale. Initial DNA damages can undergo repair via different pathways available at different stages of the cell cycle. The misrepair of DNA damage results in genomic rearrangement and causes mutations and chromosome aberrations, which are drivers of cell death. This work presents an integrated study of simulating cell response after proton irradiation with energies of 0.5–500 MeV (LET of 60–0.2 keV/µm). A model of a whole nucleus with fractal DNA geometry was implemented in TOPAS-nBio for initial DNA damage simulations. The default physics and chemistry models in TOPAS-nBio were used to describe interactions of primary particles, secondary particles, and radiolysis products within the nucleus. The initial DNA double-strand break (DSB) yield was found to increase from 6.5 DSB/Gy/Gbp at low-linear energy transfer (LET) of 0.2 keV/µm to 21.2 DSB/Gy/Gbp at high LET of 60 keV/µm. A mechanistic repair model was applied to predict the characteristics of DNA damage repair and dose response of chromosome aberrations. It was found that more than 95% of the DSBs are repaired within the first 24 h and the misrepaired DSB fraction increases rapidly with LET and reaches 15.8% at 60 keV/µm with an estimated chromosome aberration detection threshold of 3 Mbp. The dicentric and acentric fragment yields and the dose response of micronuclei formation after proton irradiation were calculated and compared with experimental results.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

DOE OSTI2022

Production Pathways for Medically Interesting Isotopes

Radioisotopes are commonly used in nuclear medicine for treating cancer and new, more effective treatment options are always desired. As a result, there is a national need for new radioisotopes and ways to produce them. A computer program was created that evaluates the daughters for all known reactions of projectiles (gamma rays, protons or neutrons) with every stable target isotope by comparing the cross-sections for each reaction at a desired energy, and outputs a list of the potential daughter isotopes that are most likely to be generated. The program then evaluates the decay chains of these daughters to provide a list of the possible decay chains that contain the radioisotope of interest. By knowing the daughter production and decay chain for each isotope, it is possible to go from the desired radioisotope to the stable isotope that can be used as a target for its production. This project would facilitate the search for new pathways to creating useful theranostic isotopes.

Hutton, A.↗

DOE OSTI2025

Radioisotope production at the Spallation Neutron Source: Design concept of isotope production target

Upon completion of the Second Target Station (STS) Project in the mid 2030s, the Spallation Neutron Source accelerator at Oak Ridge National Laboratory will deliver a 2.7 MW proton beam to the neutron production targets. In the post-STS phase, the accelerator will have a reserve beam power capacity of at least 100 kW beyond what the two neutron production targets will receive, which could potentially be ramped up to 300 kW. In this paper, a design concept for a radioisotope production target that could utilize 250 kW of the reserve beam power capacity is presented. The target consists of thorium discs encapsulated in 316L austenitic steel shells that are cooled by water. The estimated post-irradiation activity of Ac-225 and Ra-225, critical medical radioisotopes used in targeted alpha therapy cancer treatment, is calculated at the end of bombardment after a 14 day long irradiation time. Thermal and structural analyses are performed on the basis of calculated nuclear heating data. The technical feasibility of a high-power target under a 250-kW beam load with an extremely low duty factor of $3.5\cdot 10^{-6}$ is presented from thermal, structural and fatigue lifetime perspectives.

Lee, Yong Joong [ORNL] (ORCID:0000000298381723)↗

DOE OSTI2020

SRF Cavity R&D - Enabling New Frontiers in High Energy Physics and Quantum Science

Advances in SRF research at Fermilab have potential for impact in a wide variety of scientific fields: High energy physics (e.g. PIP-II, proposed colliders), basic energy sciences (e.g. LCLS-II, LCLS-II HE), nuclear physics (e.g. proposed MaRIE, EIC), Quantum Science (see quantum lab for details), dark matter searches (e.g. ADMX g-2), and industrial particle accelerators for wastewater treatment, cancer treatment, isotope production, and more.

43 PARTICLE ACCELERATORS↗

DOE OSTI2020

Protein Factory on a Chip for Rapid Therapeutics

The potential for new, re-emerging, or engineered pandemic threats could challenge our nation's biosecurity, requiring rapid and flexible countermeasure development platforms. In healthcare, one of the main hindrances to the timely development of protein-based therapeutics for cancer, infectious disease, and other diseases has been a slow and expensive quality-controlled production stage. We present a protein-based technology that has the potential to address these crucial problems in biosecurity and healthcare by maximizing protein production and system portability, while minimizing production latency and cost. Specifically, we have developed a reusable, portable first-generation platform that leverages the advantages of cell-free protein synthesis (CFPS) and flow cells to create practical amounts of clinically relevant therapeutics. We have demonstrated that this technology is reusable and programmable, enabling a single platform that can synthesize multiple dosages of various therapeutics and vaccine in the field. Implementing this technology could mitigate pandemic threats by providing a rapidly-deployable (just-in-time), versatile (precision medicine) production of biologic therapeutics to the infected patient’s locale (point-of-care). In drug development, once promising drug variations are identified, the platform can be scaled to quickly produce practical amounts of protein for patient testing in the matter of days (vs. months) at a fraction of the cost of existing technology.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Compact, Achromatic Non-scaling FFAG Accelerator for HEP, Commercial and Medical Applications (CRADA FRA-2008-0005 Final Report)

Proton and light-ion accelerators have many research and medical applications, but the current state of technology in accelerators severely limits their widespread use: (1) synchrotrons have an intrinsic low duty cycle and become quite large for light ions; and (2) cyclotrons do not have energy variability and require complex superconducting magnets for high energy. A new concept in non-scaling Fixed-Field Alternating-Gradient (FFAGs) has been invented that incorporates both the energy variability of the synchrotron and the high duty cycle of the cyclotron. The concept uses normal-conducting, combined-function magnets that apply only constant (dipole) and linear-gradient (quadrupole) fields to stabilize the accelerator. This project will develop an optimized design for a new non-scaling and cost-effective innovation in FFAG accelerators. The accelerator design will have optics that can stably accelerate protons to 250 MeV (or higher) and carbon ions to =200 MeV, an energy considered ideal for radiation therapy. Phase I will optimize, fully simulate, and demonstrate the feasibility of this accelerator. Commercial Applications and other Benefits as described by the awardee: The fixed-field acceleration concept should eliminate some of the most pronounced technical difficulties, expense, maintenance, and required expertise faced in conventional proton and light-ion accelerators. In addition to the application for high energy physics, these accelerators should have application in cancer treatment, radiopharmaceuticals, and medical isotope production, and materials science.

43 PARTICLE ACCELERATORS↗

DOE OSTI2021

Performance Analysis of PIConGPU: Particle-in-Cell on GPUs using NVIDIA’s NSight Systems and NSight Compute

PIConGPU, Particle In Cell on GPUs, is an open source simulations framework for plasma and laser-plasma physics used to develop advanced particle accelerators for radiation therapy of cancer, high energy physics and photon science. While PIConGPU has been optimized for at least 5 years to run well on NVIDIA GPU-based clusters, there has been limited exploration by the development team of potential scalability bottlenecks using recently updated and new tools including NVIDIA’s NVProf tool and the brand-new NVIDIA NSight Suite (Systems and Compute) tools. PIConGPU is a highly optimized application that runs production jobs at scale on a system Oak Ridge Leadership Facility’s (OLCF) Summit supercomputer (using the full machine at 4600 nodes; at 98% of GPU utilization on all ~28000 NVIDIA Volta GPUs). PIConGPU has been selected as one of the the eight applications for OLCF’s coveted Center for Accelerated Application Readiness (CAAR) program aimed at the facility’s Frontier supercomputer (OLCF’s first exascale system to launch in 2021), to partner with our vendors (primary vendors: AMD and Cray/HPE) ensuring that Frontier will be able to perform large-scale science when it opens to users in 2022. To this effect, performance engineers on the PIConGPU team wanted to dive deep into the application to understand at the finest granularity, which portions of the code could be further optimized to exploit the hardware on Summit at it’s maximum potential and also to elucidate which key kernels should be tracked and optimized for the CAAR effort to port this code to Frontier. Any bottlenecks that are observed via performance profiling on Summit are likely to also impact scalability on the Frontier-dev system and the Frontier Early Access (EA) system. Additionally, the engineers wanted to take a closer look at the newest NVIDIA profiling tools which allows us to identify the most useful features on these tools and will provide an opportunity to compare it to new AMD and Cray’s performance analysis tool releases and provide feedback to our vendor partners on what features are most important and mission critical for CAAR efforts. The primary goal of this report is to focus on the evaluation of PIConGPU’s most time-intensive kernels using NVProf and NSight Suite. Three kernels, Current Deposition (also known as Compute Current), Particle Push (Move and Mark), and Shift Particles are known to be some of the most time-consuming kernels in PIConGPU. The Current xi Deposition kernel and Particle Push kernel both set up the particle attributes for running any physics simulation with PIConGPU, so it is crucial to improve the performance of these two kernels. In this report, we measure single GPU metrics for the three kernels, offer high level takeaways from the conducted analysis, and compare the profiling data from NSight Compute to that of NVProf. This analysis was performed using a grid size of 240 x 272 x 224, and 10 time steps with the Mid-November Figure of Merit (FOM) run setup. The Traveling Wave Electron Acceleration (TWEAC) science case used in this run is a representative science case for PIConGPU. This execution can also be used for baseline analysis on AMD MI50/ MI60 systems. As of the time of writing, the PIConGPU application has limited use for features of NSight Systems, so this report will mainly focus on insights garnered from NSight Compute. For this analysis, we run the “full” metric set available in NSight Compute version 2020.1.2 and use NSight Systems version 2020.3.1 to generate the application timeline.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

DOE OSTI2021

Radiological Handling and Containment Considerations in Support of an American Medical Isotope Producer

This work will discuss evaluation and design of new and modified facility level radiological containment, transfer, and handling systems in support of the United States’ American Medical Isotope Production Act. In the United States alone, Molybdenum-99 (Mo-99) is used as a precursor to locally generate its decay product, technetium-99m (Tc-99m), for use in approximately 40,000 medical procedures every day to detect cancer and heart disease. Currently, however, Mo-99 is primarily produced overseas and typically requires highly enriched uranium (HEU) which is classified as weapon -usable. This poses a serious security risk to the United States and, in 2012, Congress passed the American Medical Isotope ACT which aimed to cease all Mo-99 production that requires HEU and support American based companies who have found safer production methods. Through this effort, a system was designed and developed to access irradiated material in processing hot cells for ease of material introduction and removal in the confined area. The proposed solution uses a double-door design that allows for easy access to material while also providing shielding through a mechanically manipulated carousel. A system was also designed to transport irradiated materials from target reactors to a target receipt box using a rail guide system, pneumatic motor, and lead screw drive.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2021

LLNL Low dose-related research

LLNL has a long history of involvement in research into biological and biophysical methods for assessing ionizing radiation dose, and LLNL staff continue to participate in reviews of low dose related data as well as technology development for national security and population health purposes. A list of recent projects and funding agencies is provided in Table 1. LLNL has also maintained expertise in mammalian biology, radiobiology and cancer (computational and biological) over the last 5 years.

62 RADIOLOGY AND NUCLEAR MEDICINE↗