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At least 1,333 records · Page 74

A prototype scintillator real‐time beam monitor for ultra‐high dose rate radiotherapy

Background: FLASH Radiotherapy (RT) is an emergent cancer RT modality where an entire therapeutic dose is delivered at more than 1000 times higher dose rate than conventional RT. For clinical trials to be conducted safely, a precise and fast beam monitor that can generate out-of-tolerance beam interrupts is required. This paper describes the overall concept and provides results from a prototype ultra-fast, scintillator-based beam monitor for both proton and electron beam FLASH applications. Purpose: A FLASH Beam Scintillator Monitor (FBSM) is being developed that employs a novel proprietary scintillator material. The FBSM has capabilities that conventional RT detector technologies are unable to simultaneously provide: (1) large area coverage; (2) a low mass profile; (3) a linear response over a broad dynamic range; (4) radiation hardness; (5) real-time analysis to provide an IEC-compliant fast beam-interrupt signal based on true two-dimensional beam imaging, radiation dosimetry and excellent spatial resolution. Methods: The FBSM uses a proprietary low mass, less than 0.5 mm water equivalent, non-hygroscopic, radiation tolerant scintillator material (designated HM: hybrid material) that is viewed by high frame rate CMOS cameras. Folded optics using mirrors enable a thin monitor profile of ∼10 cm. A field programmable gate array (FPGA) data acquisition system generates real-time analysis on a time scale appropriate to the FLASH RT beam modality: 100–1000 Hz for pulsed electrons and 10–20 kHz for quasi-continuous scanning proton pencil beams. An ion beam monitor served as the initial development platform for this work and was tested in low energy heavy-ion beams ( 86 Kr +26 and protons). A prototype FBSM was fabricated and then tested in various radiation beams that included FLASH level dose per pulse electron beams, and a hospital RT clinic with electron beams. Results: Results presented in this report include image quality, response linearity, radiation hardness, spatial resolution, and real-time data processing. Furthermore, the HM scintillator was found to be highly radiation damage resistant. It exhibited a small 0.025%/kGy signal decrease from a 216 kGy cumulative dose resulting from continuous exposure for 15 min at a FLASH compatible dose rate of 237 Gy/s. Measurements of the signal amplitude versus beam fluence demonstrate linear response of the FBSM at FLASH compatible dose rates of >40 Gy/s. Comparison with commercial Gafchromic film indicates that the FBSM produces a high resolution 2D beam image and can reproduce a nearly identical beam profile, including primary beam tails. The spatial resolution was measured at 35–40 µm. Tests of the firmware beta version show successful operation at 20 000 Hz frame rate or 50 µs/frame, where the real-time analysis of the beam parameters is achieved in less than 1 µs. Conclusions: The FBSM is designed to provide real-time beam profile monitoring over a large active area without significantly degrading the beam quality. A prototype device has been staged in particle beams at currents of single particles up to FLASH level dose rates, using both continuous ion beams and pulsed electron beams. Using a novel scintillator, beam profiling has been demonstrated for currents extending from single particles to 10 nA currents. Radiation damage is minimal and even under FLASH conditions would require ≥50 kGy of accumulated exposure in a single spot to result in a 1% decrease in signal output. Beam imaging is comparable to radiochromic films, and provides immediate images without hours of processing. Real-time data processing, taking less than 50 µs (combined data transfer and analysis times), has been implemented in firmware for 20 kHz frame rates for continuous proton beams.

2D beam imaging↗

Molecular subtyping reveals immune alterations in IDH wild‐type lower‐grade diffuse glioma

Abstract Isocitrate dehydrogenase ( IDH ) wild‐type diffuse lower‐grade glioma (LGG) is usually associated with poor outcome, but there have been disputes over its clinical outcome and classification. We present here a robust gene expression‐based molecular classification of IDH wild‐type diffuse LGG into two subtypes with distinct biological and clinical features. A discovery cohort of 49 IDH wild‐type diffuse LGGs from the Chinese Glioma Genome Atlas (CGGA) was subjected to clustering and function analysis. Seventy‐three tumors from The Cancer Genome Atlas (TCGA) were used to validate our findings. Consensus clustering of transcriptional data uncovered concordant classification of two robust and prognostically significant subtypes of IDH wild‐type LGG. Subtype 1, associated with poorer outcomes, was characterized by significantly higher immune and cytolytic scores, M2 macrophages, and up‐regulation of immune exhaustion markers, while Subtype 2, which had elevated lymphocytes and plasma cells, showed relatively favorable survival. Somatic alteration analysis revealed that Subtype 1 showed more frequently deleted regions, such as the locus of CDKN2A / CDKN2B , DMRTA1 , C9orf53 , and MTAP . Furthermore, we developed and validated a five‐gene signature for better application of this acquired stratification. Our data demonstrate the biological and prognostic heterogeneity within IDH wild‐type diffuse LGGs and deepen our molecular understandi‐g of this tumor entity. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Wu, Fan↗

RCSB Protein Data bank: Tools for visualizing and understanding biological macromolecules in 3D

Abstract Now in its 52nd year of continuous operations, the Protein Data Bank (PDB) is the premiere open‐access global archive housing three‐dimensional (3D) biomolecular structure data. It is jointly managed by the Worldwide Protein Data Bank (wwPDB) partnership. The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) is funded by the National Science Foundation, National Institutes of Health, and US Department of Energy and serves as the US data center for the wwPDB. RCSB PDB is also responsible for the security of PDB data in its role as wwPDB‐designated Archive Keeper. Every year, RCSB PDB serves tens of thousands of depositors of 3D macromolecular structure data (coming from macromolecular crystallography, nuclear magnetic resonance spectroscopy, electron microscopy, and micro‐electron diffraction). The RCSB PDB research‐focused web portal ( RCSB.org ) makes PDB data available at no charge and without usage restrictions to many millions of PDB data consumers around the world. The RCSB PDB training, outreach, and education web portal ( PDB101.RCSB.org ) serves nearly 700 K educators, students, and members of the public worldwide. This invited Tools Issue contribution describes how RCSB PDB (i) is organized; (ii) works with wwPDB partners to process new depositions; (iii) serves as the wwPDB‐designated Archive Keeper; (iv) enables exploration and 3D visualization of PDB data via RCSB.org ; and (v) supports training, outreach, and education via PDB101.RCSB.org . New tools and features at RCSB.org are presented using examples drawn from high‐resolution structural studies of proteins relevant to treatment of human cancers by targeting immune checkpoints.

59 BASIC BIOLOGICAL SCIENCES↗

Structures of a synthetic antibody selected against and bound to the C‐terminal domain of Clostridium perfringens enterotoxin

Abstract Clostridium perfringensenterotoxin (CpE) causes cytotoxic gastrointestinal disease in mammalian epithelium by binding membrane protein receptors called claudins. Claudins direct the formation of cell/cell tight junctions through oligomerization and govern the transport of molecules between individual cells. CpE binds claudins through its C‐terminal domain (cCpE) and induces cytotoxicity through its N‐terminal domain. The non‐toxic cCpE is a useful tool to study claudins, tight junctions, and for translational applications, such as increasing the permeability of restrictive tissues like the blood–brain barrier or selective targeting of claudin overexpressing cancers. Conversely, there are no specialized molecular tools to study CpE or cCpE, or to modulate or inhibit their functions. We previously reported the development of synthetic antigen‐binding fragments (sFabs) that bind cCpE, and low‐resolution structures of them bound to claudin/cCpE complexes. Here, we determine high‐resolution structures of sFab COP‐2 bound to cCpE using X‐ray crystallography and cryogenic electron microscopy. The structures and biophysical findings provide the mechanism of COP‐2 binding to cCpE and the molecular determinants driving their interactions. These insights can advance the design of new antibody‐based tools from our COP‐2 scaffold to study or alter cCpE function and give rise to a “Trojan horse” strategy that exploits cCpE's tight junction barrier disrupting function to selectively deliver conjugated therapeutics through normally impermeable tissues.

Biochemistry & Molecular Biology↗

Molecular dynamics analysis of the binding of human interleukin-6 with interleukin-6 α-receptor

Human interleukin-6 (hIL-6) is a multifunctional cytokine that regulates immune and inflammatory responses in addition to metabolic and regenerative processes and cancer. hIL-6 binding to the IL-6 receptor (IL-6Rα) induces homodimerization and recruitment of the glycoprotein (gp130) to form a hexameric signaling complex. Anti-IL-6 and IL-6R antibodies are clinically approved inhibitors of IL-6 signaling pathway for treating rheumatoid arthritis and Castleman's disease, respectively. There is a potential to develop novel small molecule IL-6 antagonists derived from understanding the structural basis for IL-6/IL-6Rα interactions. In this work, we combine homology modeling with extensive molecular dynamics (MD) simulations to examine the association of hIL-6 with IL-6Rα. A comparison with MD of apo hIL-6 reveals that the binding of hIL-6 to IL-6Rα induces structural and dynamic rearrangements in the AB loop region of hIL-6, disrupting intraprotein contacts and increasing the flexibility of residues 48 to 58 of the AB loop. In contrast, due to the involvement of residues 59 to 78 in forming contacts with the receptor, these residues of the AB loop are observed to rigidify in the presence of the receptor. The binary complex is primarily stabilized by two pairs of salt bridges, Arg181 (hIL-6)- Glu182 (IL-6Rα) and Arg184 (hIL-6)- Glu183 (IL-6Rα) as well as hydrophobic and aromatic stacking interactions mediated essentially by Phe residues in both proteins. An interplay of electrostatic, hydrophobic, hydrogen bonding, and aromatic stacking interactions facilitates the formation of the hIL-6/IL-6Rα complex.

59 BASIC BIOLOGICAL SCIENCES↗

Case studies in bias reduction and inference for electronic health record data with selection bias and phenotype misclassification

Electronic health records (EHR) are not designed for population‐based research, but they provide easy and quick access to longitudinal health information for a large number of individuals. Many statistical methods have been proposed to account for selection bias, missing data, phenotyping errors, or other problems that arise in EHR data analysis. However, addressing multiple sources of bias simultaneously is challenging. We developed a methodological framework (R package, SAMBA ) for jointly handling both selection bias and phenotype misclassification in the EHR setting that leverages external data sources. These methods assume factors related to selection and misclassification are fully observed, but these factors may be poorly understood and partially observed in practice. As a follow‐up to the methodological work, we demonstrate how to apply these methods for two real‐world case studies, and we evaluate their performance. In both examples, we use individual patient‐level data collected through the University of Michigan Health System and various external population‐based data sources. In case study (a), we explore the impact of these methods on estimated associations between gender and cancer diagnosis. In case study (b), we compare corrected associations between previously identified genetic loci and age‐related macular degeneration with gold standard external summary estimates. These case studies illustrate how to utilize diverse auxiliary information to achieve less biased inference in EHR‐based research.

60 APPLIED LIFE SCIENCES↗

Metal–Organic Framework as a New Type of Magnetothermally‐Triggered On‐Demand Release Carrier

The development of external stimuli‐controlled payload systems has been sought after with increasing interest toward magnetothermally‐triggered drug release (MTDR) carriers due to their non‐invasive features. However, current MTDR carriers present several limitations, such as poor heating efficiency caused by the aggregation of iron oxide nanoparticles (IONPs) or the presence of antiferromagnetic phases which affect their efficiency. Herein, a novel MTDR carrier is developed using a controlled encapsulation method that fully fixes and confines IONPs of various sizes within the metal–organic frameworks (MOFs). This novel carrier preserves the MOF's morphology, porosity, and IONP segregation, while enhances heating efficiency through the oxidation of antiferromagnetic phases in IONPs during encapsulation. It also features a magnetothermally‐responsive nanobrush that is stimulated by an alternating magnetic field to enable on‐demand drug release. The novel carrier shows improved heating, which has potential applications as contrast agents and for combined chemo and magnetic hyperthermia therapy. It holds a great promise for magneto‐thermally modulated drug dosing at tumor sites, making it an exciting avenue for cancer treatment.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Enhanced Laser-Induced Graphene Microfluidic Integrated Sensors (LIGMIS) for On-Site Biomedical and Environmental Monitoring

The convergence of microfluidic and electrochemical biosensor technologies offers significant potential for rapid, in-field diagnostics in biomedical and environmental applications. Traditional systems face challenges in cost, scalability, and operational complexity, especially in remote settings. Addressing these issues, laser-induced graphene microfluidic integrated sensors (LIGMIS) are presented as an innovative platform that integrates microfluidics and electrochemical sensors both comprised of laser-induced graphene. This study advances the LIGMIS concept by resolving issues of uneven fluid transport, increased hydrophobicity during storage, and sensor biofunctionalization challenges. Key innovations include Y-shaped reservoirs for consistent fluid flow, hydrophilic polyethyleneimine coatings to maintain wettability, and separable microfluidic and electrochemical components enabling isolated electrode nanoparticle metallization and biofunctionalization. Multiplexed electrochemical detection of the neonicotinoid imidacloprid and nitrate ions in environmental water samples yields detection limits of 707 nm and 10 -5.4 m with wide sensing ranges of 5–100 µm and 10 -5 –10 -1 m, respectively. Similarly, uric acid and calcium ions are detected in saliva, demonstrating detection limits of 217 nm and 10 -5.3 m with sensing ranges of 10–50 µm, and 10 -5 –10 -2.5 m, respectively. Overall, this biosensing demonstrates the capability of the LIGMIS platform for multiplexed detection in biologically complex solutions, with applications in environmental water quality monitoring and oral cancer screening.

environmental monitoring↗

Identifying Heterogeneous Micromechanical Properties of Biological Tissues via Physics–Informed Neural Networks

The heterogeneous micromechanical properties of biological tissues have profound implications across diverse medical and engineering domains. However, identifying full-field heterogeneous elastic properties of soft materials using traditional engineering approaches is fundamentally challenging due to difficulties in estimating local stress fields. Recently, there has been a growing interest in data-driven models for learning full-field mechanical responses, such as displacement and strain, from experimental or synthetic data. However, research studies on inferring full-field elastic properties of materials, a more challenging problem, are scarce, particularly for large deformation, hyperelastic materials. Here, a physics-informed machine learning approach is proposed to identify the elasticity map in nonlinear, large deformation hyperelastic materials. This study reports the prediction accuracies and computational efficiency of physics-informed neural networks (PINNs) in inferring the heterogeneous elasticity maps across materials with structural complexity that closely resemble real tissue microstructure, such as brain, tricuspid valve, and breast cancer tissues. Further, the improved architecture is applied to three hyperelastic constitutive models: Neo-Hookean, Mooney Rivlin, and Gent. Furthermore, the improved network architecture consistently produces accurate estimations of heterogeneous elasticity maps, even when there is up to 10% noise present in the training data.

59 BASIC BIOLOGICAL SCIENCES↗

Fibrotic activity quantified in serum by measurements of type III collagen pro-peptides can be used for prognosis across different solid tumor types

Due to activation of fibroblast into cancer-associated fibroblasts, there is often an increased deposition of extracellular matrix and fibrillar collagens, e.g. type III collagen, in the tumor microenvironment (TME) that leads to tumor fibrosis (desmoplasia). Tumor fibrosis is closely associated with treatment response and poor prognosis for patients with solid tumors. To assure that the best possible treatment option is provided for patients, there is medical need for identifying patients with high (or low) fibrotic activity in the TME. Measuring unique collagen fragments such as the pro-peptides released into the bloodstream during fibrillar collagen deposition in the TME can provide a non-invasive measure of the fibrotic activity. Based on data from 8 previously published cohorts, this review provides insight into the prognostic value of quantifying tumor fibrosis by measuring the pro-peptide of type III collagen in serum of a total of 1692 patients with different solid tumor types and discusses the importance of tumor fibrosis for understanding prognosis and for potentially guiding future drug development efforts that aim at overcoming the poor outcome associated with a fibrotic TME.

59 BASIC BIOLOGICAL SCIENCES↗

Evaluating inkjet dispenser/liquid vortex capture-mass spectrometry for single-cell metabolomics in Hep G2 steatosis caused by tamoxifen

Single-cell mass spectrometry (MS) is advancing our understanding of metabolic pathways in heterogeneous cell populations; however, many techniques are slow or require disruptive sample preparations. This study evaluated coupling a modified HP D100 single-cell inkjet dispenser with liquid vortex capture-mass spectrometry (D100/LVC-MS). The D100 is a single-cell inkjet dispenser capable of titrating solutions and isolating single cells via disposable cassettes equipped with microfluidic channels and an impedance sensor. The LVC-MS enables high-throughput capture, lysis, and ionization of analytes for mass spectrometric analysis. The D100/LVC-MS system was characterized through titration and single-cell experiments. Propranolol titration demonstrated linearity across a broad concentration range using the D100/LVC-MS system. Additionally, Hep G2 hepatocarcinoma cells and Chlamydomonas reinhardtii algae were used to showcase the D100’s high-throughput or low-buffer-volume single-cell dispensing strategies. The D100/LVC-MS system’s performance was validated by evaluating tamoxifen-induced steatosis in Hep G2 cells. Tamoxifen, associated with nonalcoholic fatty liver disease in breast cancer patients following long-term use, was tested in Hep G2 cells at 20 µM for 72 h against DMSO-treated controls. High-throughput analysis of 500 cells per condition, completed in 25 min per run, demonstrated the system’s efficiency. The D100/LVC-MS system simultaneously quantified tamoxifen and measured triglycerides and phosphatidylcholines. Triglycerides were upregulated in the tamoxifen-treated cells and the results indicated two distinct cell populations, differing in tamoxifen and phosphatidylcholines levels, suggesting heterogeneity within the treated population. In conclusion, these findings highlight the D100/LVC-MS system as a cost-effective, high-throughput platform for single-cell metabolomics and lipidomics, with significant potential for evaluating metabolic alterations.

Chromatography↗

False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a prospective multi-center trial

Readers need to be informed about potential pitfalls of [ 68 Ga]Ga-PSMA-11 PET interpretation. Here we report [ 68 Ga]Ga-PSMA-11 PET findings discordant with the histopathology/composite reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer. Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy ( n = 11); other false positive findings were noted for prostate bed post prostatectomy (T, n = 2), pelvic nodes (N, n = 2), or extra pelvic lesions (M, n = 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) ( n = 5), pelvic nodes ( n = 1), and extra pelvic lesions ( n = 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake.[ 68 Ga]Ga-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of [ 68 Ga]Ga-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants.

Radiology, Nuclear Medicine & Medical Imaging↗

OFraMP: a fragment-based tool to facilitate the parametrization of large molecules

Abstract An Online tool for Fragment-based Molecule Parametrization (OFraMP) is described. OFraMP is a web application for assigning atomic interaction parameters to large molecules by matching sub-fragments within the target molecule to equivalent sub-fragments within the Automated Topology Builder (ATB, atb.uq.edu.au) database. OFraMP identifies and compares alternative molecular fragments from the ATB database, which contains over 890,000 pre-parameterized molecules, using a novel hierarchical matching procedure. Atoms are considered within the context of an extended local environment (buffer region) with the degree of similarity between an atom in the target molecule and that in the proposed match controlled by varying the size of the buffer region. Adjacent matching atoms are combined into progressively larger matched sub-structures. The user then selects the most appropriate match. OFraMP also allows users to manually alter interaction parameters and automates the submission of missing substructures to the ATB in order to generate parameters for atoms in environments not represented in the existing database. The utility of OFraMP is illustrated using the anti-cancer agent paclitaxel and a dendrimer used in organic semiconductor devices. Graphical abstract OFraMP applied to paclitaxel (ATB ID 35922).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Evaluation of two extraction chromatography resins for scandium and titanium separation for medical isotope production

Scandium-47 ( 47 Sc) can be used in nuclear medicine as a therapeutic-diagnostic, or "theragnostic," radioactive medical isotope for cancer detection and treatment. The 47 Sc isotope can be produced through the photonuclear reaction 48 Ti(γ,p) 47 Sc by irradiating enriched 48 Ti target material. The enriched target material necessary for production is costly; 48 TiO 2 costs ~ $\$$1550/g, and targets can be > 50 g ($\$$77,500) to produce medically relevant amounts of 47 Sc. In order to keep costs low, a highly efficient separation of scandium from bulk titanium is desired, along with efficient methods for recycling the target material. Here this research is focused on evaluating efficient methods for the separation of scandium from bulk quantities of titanium using commercially available diglycolamide-based and hydroxamate-based extraction chromatography resins (DGA resin and ZR resin, respectively). The sorption of 47 Sc and Ti on these resins were investigated at varying concentrations of HNO 3 , HCl, H 2 SO 4 , and HF to explore how they might be used in a large-scale production/processing setting.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Actinium purification from elemental components of stainless steel and aluminum

Radioisotopes of actinium are valuable because of their potential use in the medical industry. Actinium-225 shows promise for treating disease—like cancer—via targeted alpha therapy (TAT), and the longer-lived actinium-227 is the parent of two radionuclides with potential application in TAT radiopharmaceuticals, thorium-227 and radium-223. Continuing progress in the development of these medical applications requires robust and diverse methods for extracting and purifying actinium from a wide range of matrices. Further, to define the strengths and limitations of separation methods commonly employed in actinium processing, we characterized the performance of ion exchange and extraction chromatographic steps for removing contaminants found in stainless steel (chromium, iron, nickel, and silicon) and aluminum from actinium-227. While AG-MP1 anion exchange resin with HCl (aq) successfully removed iron, cation exchanger AG 50W-X8 removed most other contaminants. The most persistent contaminant was aluminum, which was removed using a DGA Normal extraction resin. These results are presented within the context of applying that methodology toward actinium purification strategies.

36 MATERIALS SCIENCE↗

Adiabatic quantum support vector machines

Adiabatic quantum computers can solve difficult optimization problems (e.g., the quadratic unconstrained binary optimization problem), and they seem well suited to train machine learning models. In this paper, we describe an adiabatic quantum approach for training support vector machines. We show that the time complexity of our quantum approach is an order of magnitude better than the classical approach. Next, we compare the test accuracy of our quantum approach against a classical approach that uses the Scikit-learn library in Python across five benchmark datasets (Iris, Wisconsin Breast Cancer (WBC), Wine, Digits, and Lambeq). We show that our quantum approach obtains accuracies on par with the classical approach. Finally, we perform a scalability study in which we compute the total training times of the quantum approach and the classical approach with an increasing number of features and an increasing number of data points in the training dataset. In conclusion, our scalability results show that the quantum approach obtains a 3.5–4.5x speedup over the classical approach on datasets with many (millions of) features.

Computational Complexity↗

Californium-252 production at the High Flux Isotope Reactor - I: Validation study using campaign data

This paper presents a series of 252 Cf production validation and code-to-code comparison studies performed based on data from the production campaigns at the High Flux Isotope Reactor (HFIR). These studies support efforts to convert HFIR from using highly enriched uranium (HEU) fuel to low-enriched uranium (LEU) fuel. HFIR must maintain its world-class performance and missions following this conversion, and because 252 Cf is a vital neutron-emitting radioisotope used for a variety of high-impact applications (e.g., reactor startup, cancer treatment), the ability to efficiently produce 252 Cf must be preserved. In this work, the HFIRCON, Shift, ORIGEN, and TCOMP codes were deployed, and several sets of data libraries were investigated to better understand the calculation codes and the data biases. As-loaded target composition data, as-run irradiation history data, and post-irradiation measurements from recent multi-cycle irradiation campaigns of the HEU core were used to validate and determine methodology biases. Further, the findings demonstrated a good agreement, with results falling within 3 standard deviations of measurements. This paper lays the ground work for the second paper, which evaluates and compares 252 Cf production and safety metrics with the HEU core and a proposed LEU core.

07 ISOTOPE AND RADIATION SOURCES↗