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At least 685 records · Page 38
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Correcting beam space charge effects in Active-Target Time Projection Chamber

By providing a large gaseous volume for nuclear interactions while simultaneously recording the tracks of resulting reaction products, an active target serves as both a thick target and a detector. Once a reaction occurs, the emitted charged fragments strip electrons from the target gas along their path as they transverse the detector. Collection of these stripped electrons allow for detection of the product tracks. As beam intensity increases, the resulting ionization in the active target can significantly distort this collection of electrons. If left uncorrected, the resulting measurements could be wrong. In this paper, we investigate the impact of the space charge produced by heavy radioactive beams within the Active Target - Time Projection Chamber at Michigan State University. The beams are injected parallel to the electric field of the time projection chamber which is operated without a magnetic field for this experiment. Furthermore, we analyze the rate dependence of the space charge effects and demonstrate that they can be modeled and effectively corrected.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2026

Chemoproteomic Elucidation of β-Lactam Drug Targets in Mycobacterium abscessus

The pathogen Mycobacterium abscessus (Mab) can cause severe and difficult-to-treat chronic lung infections. Despite the rising incidence and clinical concern of Mab infections, treatment options are limited and often ineffective. Treatment is complicated by Mab’s ability to persist in a nonreplicating, drug-resistant state. Several β-lactam antibiotics are potently bactericidal against Mab but are underutilized because their molecular mechanisms of action against Mab are incompletely understood. In the current study, we used β-lactam-derived activity-based probes and chemoproteomics to report the first comprehensive list of Mab enzymes targeted by β-lactams. We compared β-lactam targets across two Mab subspecies in actively replicating and nonreplicating cultures, using a new carbon starvation model of persistence. We identified 17 targets that were active in every condition tested, seven of which were previously unknown to bind β-lactams. Lastly, we characterized the β-lactamase activity and β-lactam inhibition profiles of nine Mab enzymes, demonstrating that imipenem inhibits these targets more effectively than cefoxitin. These findings demonstrate β-lactam target engagement in persistent Mab and provide clarity on the mechanisms of action of clinically relevant β-lactams in Mab, crucial steps toward fully realizing their potential for treating infections caused by this opportunistic pathogen.

Mycobacterium abscessus↗
DOE OSTI2013

Three dimensional effects on proton acceleration by intense laser solid target interaction

Multi-dimensional effects on ion acceleration by a normally incident linearly polarized intense laser pulse interacting with a thin solid target have been investigated numerically, where the laser has the peak intensity of 1.37×10{sup 20} W/cm{sup 2}, focused spot size of 6 μm, pulse duration of 33 fs, and total pulse energy about 3 J, which are commercially available now. We have checked the effects of simulation geometries by running one, two, and three dimensional (1D, 2D, 3D) particle-in-cell simulations. 3D simulation results show that, in the case of using a relatively thick target (in the opaque regime, i.e., 2 μm) with the so-called target normal sheath field acceleration mechanism, electrons spread almost uniformly along two transverse directions. While in the case of using an ultra-thin target (in the relativistic-induced transparent regime, i.e., 100 nm) with the so-called break-out afterburner mechanism, electrons spread more quickly along the direction orthogonal to the laser polarization direction especially at the early stage. The transverse spreading of electrons strongly decreases the electron density at the rear side of the target. Such an effect causes different estimation of electron temperatures in different simulation geometries. Usually, 1D and 2D simulations overestimate the temperature; and as a result, the maximum proton energy observed in 1D and 2D simulations is, respectively, about 3 and 2 times of that observed in 3D simulation.

43 PARTICLE ACCELERATORS↗
DOE OSTI2016

Acceleration of multiply charged ions by a high-contrast femtosecond laser pulse of relativistic intensity with the front surface of a solid target

It is shown that the acceleration efficiency of protons and multiply charged ions (and also the charge composition of the latter) accelerated backwards under irradiation of the front surface of thick solid targets by high-power femtosecond laser radiation with an intensity of 2 × 10{sup 18} W cm{sup -2} is determined by the contrast of this radiation. Thus, highly ionised ions up to C{sup 6+}, Si{sup 12+} and Mo{sup 14+} are recorded on polyethylene, silicon and molybdenum targets at a contrast of 10{sup -8}, the ions with charges up to C{sup 5+}, Si{sup 10+} and Mo{sup 10+} possessing an energy of more than 100 keV per unit charge. In the case of a metal target, the acceleration efficiency of protons is significantly reduced, which indicates cleaning of the target surface by a pre-pulse. The measurements performed at a contrast increased by two-to-three orders of magnitude show the presence of fast protons (up to 300–700 keV) on all targets, and also a decrease in the energy and maximum charge of multiply charged ions. (extreme laser radiation: physics and fundamental applications)

74 ATOMIC AND MOLECULAR PHYSICS↗
DOE OSTI2022

Plutonium-238 Production Program Results, Implications, and Projections from Irradiation and Examination of Initial NpO 2 Test Targets for Improved Production

An alternative target design with potential improvements, including a major increase in 238 Pu production rate and annual capacity; fewer targets to be fabricated, irradiated, and processed; and a significant replacement of a large volume of caustic-nitrate, aluminum-bearing radioactive liquid waste with a smaller volume of solid metal waste, has been conceived and evaluated using reactor physics and thermal-hydraulic analyses. The alternative target design uses pressed pellets of 237 NpO 2 , sintered to 92% to 93% of theoretical density, and stacked inside a Zircaloy-4 cladding tube. Additionally, four test targets were fabricated, irradiated, and examined. No melting or other potential problems were indicated. Projections from measured constituents indicated annual production could be increased by a factor of ~2, and the number of targets required to be fabricated, irradiated, and processed could be reduced by a factor of ~5.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗
DOE OSTI2026

Computational Thermal Hydraulics of a High-Performance Low-Enriched-Uranium Annular Target for HFIR Irradiation

Molybdenum-99 has historically been generated via isolation from fissioned highly enriched uranium (HEU) targets. Here, this isotope is in high demand due to its daily use across the world in radiopharmaceutical medical procedures. The primary objective of this work was to design and analyze an experimental target assembly containing one low-enriched-uranium (LEU) annular target for irradiation at the High Flux Isotope Reactor (HFIR). Efforts included incorporating spatially dependent energy sources from neutron and gamma interactions, quantifying thermal contact conductance at material interfaces, performing grid-independent studies, comparing turbulence models, and simulating various steady-state and transient scenarios relevant for irradiation qualification and eventual insertion. These models provide velocity, pressure, and temperature distributions in both space and time. Such results enable the selection of an appropriate irradiation location, fission rate density, and flow-limiting orifice size and demonstrate compliance with HFIR safety requirements such that insertion into the reactor can be approved. This analysis shows that across all scenarios, wetted surface temperatures remain below the coolant saturation temperature with no net vapor formation in the coolant. In every scenario, all components stay below 30% of the aluminum 6061 melting temperature. Computational fluid dynamics and system-level models predict peak target temperatures that agree within 4%, though the predicted axial location of the peak differs by about 10% of the heated length due to differences in flow development length. These results de-risk the irradiation of LEU (annular targets) and strengthen a domestic, HEU-independent 99 Mo supply by providing important fuel performance data to form the foundation for a robust licensing basis.

Molybdenum-99↗
DOE OSTI2020

Hybrid target design for imprint mitigation in direct-drive inertial confinement fusion

A target design for mitigating the Rayleigh-Taylor instability is proposed for use in high energy density and direct-drive inertial confinement fusion experiments. In this scheme, a thin gold membrane is offset from the main target by several-hundred microns. A strong picket on the drive beams is incident upon this membrane to produce x rays which generate the initial shock through the target. The main drive follows shortly thereafter, passing through the ablated shell and directly driving the main target. The efficacy of this scheme is demonstrated through experiments performed at the OMEGA EP facility, showing a reduction of the Rayleigh-Taylor instability growth which scales exponentially with frequency, suppressing development by at least a factor of 5 for all wavelengths below 100 μm. Furthermore, this results in a delay in the time of target perforation by ~40%.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2015

Thermonuclear targets for direct-drive ignition by a megajoule laser pulse

Central ignition of a thin two-layer-shell fusion target that is directly driven by a 2-MJ profiled pulse of Nd laser second-harmonic radiation has been studied. The parameters of the target were selected so as to provide effective acceleration of the shell toward the center, which was sufficient for the onset of ignition under conditions of increased hydrodynamic stability of the ablator acceleration and compression. The aspect ratio of the inner deuterium-tritium layer of the shell does not exceed 15, provided that a major part (above 75%) of the outer layer (plastic ablator) is evaporated by the instant of maximum compression. The investigation is based on two series of numerical calculations that were performed using one-dimensional (1D) hydrodynamic codes. The first 1D code was used to calculate the absorption of the profiled laser-radiation pulse (including calculation of the total absorption coefficient with allowance for the inverse bremsstrahlung and resonance mechanisms) and the spatial distribution of target heating for a real geometry of irradiation using 192 laser beams in a scheme of focusing with a cubo-octahedral symmetry. The second 1D code was used for simulating the total cycle of target evolution under the action of absorbed laser radiation and for determining the thermonuclear gain that was achieved with a given target.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2015

Simple model of the indirect compression of targets under conditions close to the national ignition facility at an energy of 1.5 MJ

The possibility of the analysis and interpretation of the reported experiments with the megajoule National Ignition Facility (NIF) laser on the compression of capsules in indirect-irradiation targets by means of the one-dimensional RADIAN program in the spherical geometry has been studied. The problem of the energy balance in a target and the determination of the laser energy that should be used in the spherical model of the target has been considered. The results of action of pulses differing in energy and time profile (“low-foot” and “high-foot” regimes) have been analyzed. The parameters of the compression of targets with a high-density carbon ablator have been obtained. The results of the simulations are in satisfactory agreement with the measurements and correspond to the range of the observed parameters. The set of compared results can be expanded, in particular, for a more detailed determination of the parameters of a target near the maximum compression of the capsule. The physical foundation of the possibility of using the one-dimensional description is the necessity of the closeness of the last stage of the compression of the capsule to a one-dimensional process. The one-dimensional simulation of the compression of the capsule can be useful in establishing the boundary behind which two-dimensional and three-dimensional simulation should be used.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2015

On the feasibility of increasing the energy of laser-accelerated protons by using low-density targets

Optimal regimes of proton acceleration in the interaction of short high-power laser pulses with thin foils and low-density targets are determined by means of 3D numerical simulation. It is demonstrated that the maximum proton energy can be increased by using low-density targets in which ions from the front surface of the target are accelerated most efficiently. It is shown using a particular example that, for the same laser pulse, the energy of protons accelerated from a low-density target can be increased by one-third as compared to a solid-state target.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2016

Multi-omics approach to infer cancer therapeutic targets on chromosome 20q across tumor types

The identification of good targets is a critical step for the development of targeted therapies for cancer treatment. Here, we used a multi-omics approach to delineate potential targets on chromosome 20q, which frequently shows a complex pattern of DNA copy number amplification in many human cancers suggesting the presence of multiple driver genes. By comparing the amounts of individual mRNAs in cancer from 11 different human tissues with those in their corresponding normal tissues, we identified 18 genes that were robustly elevated across human cancers. Moreover, we found that higher expression levels of a majority of these genes were associated with poor prognosis in many human cancer types. Using DNA copy number and expression data for all 18 genes obtained from The Cancer Genome Atlas project, we discovered that amplification is a major mechanism driving overexpression of these 18 genes in the majority of human cancers. Our integrated analysis suggests that 18 genes on chromosome 20q might serve as novel potential molecular targets for targeted cancer therapy.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

29 mm Diameter Test Target Design Report

The Northstar target for Mo99 production is made up of Mo100 disks in a stack separated by coolant gaps for helium flow. A number of targets have been tested at ANL for both production of Mo99 and for thermal-hydraulic performance. These have all been with a 12 mm diameter target, even while the production goals have increased the diameter to now 29 mm. A 29 mm diameter target has been designed that is consistent with the ANL beam capabilities and the capabilities of the helium circulation system currently in use at ANL. This target is designed for 500 μA at 35 MeV electrons. While the plant design calls for 42 MeV, the chosen design point is more favorable and higher power given the limits of the ANL accelerator. The intended beam spot size is 12 mm FWHM, but the thermal analysis presented herein conservatively assumed a 10 mm FWHM beam, which results in a 44% higher beam current density at beam center.

43 PARTICLE ACCELERATORS↗
DOE OSTI2021

Nuclear Targeting Terms for Engineers and Scientists Revised Edition

This is a revised version of LA-UR-17-20752, Nuclear Targeting Terms for Engineers and Scientists, March 1, 2017. The discussion of compounding for damage and compounding for reliability was reworded for clarity. The Department of Defense has a methodology for targeting nuclear weapons, and a jargon that is used to communicate between the analysts, planners, aircrews, and missile crews. The typical engineer or scientist in the Department of Energy may not have been exposed to the nuclear weapons targeting terms and methods. This report provides an introduction to the terms and methodologies used for nuclear targeting. Its purpose is to prepare engineers and scientists to participate in wargames, exercises, and discussions with the Department of Defense. Terms such as Circular Error Probable, probability of hit and damage, damage expectancy, and the physical vulnerability system are discussed. Methods for compounding damage from multiple weapons applied to one target are presented.

45 MILITARY TECHNOLOGY, WEAPONRY, AND NATIONAL DEF↗
DOE OSTI2020

Neutronics analyses for the conceptual design of the SNS Second Target Station

The Spallation Neutron Source, in operation at the Oak Ridge National Laboratory since 2006, was designed to allow the addition of a second target station and an upgrade of the accelerator proton power. Both upgrades are now underway. Here we describe the evolution of the design of the target of the second target station with the emphasis on the effects of the proton beam footprint on the energy deposition in the target, stresses induced by the pulsed operation, and the importance of the residual heat. The moderator configurations and their optimization are discussed. With the utilization of pure parahydrogen moderators, small neutron beam cross-sections, and the specific optimization, neutron beams of the second target station will achieve exceptionally high peak brightness and time-averaged brightness.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2021

CRISPR/Cas9-Mediated Multi-Allelic Gene Targeting in Sugarcane Confers Herbicide Tolerance

Sugarcane is the source of 80% of the sugar and 26% of the bioethanol produced globally. However, its complex, highly polyploid genome (2 n = 100 – 120) impedes crop improvement. Here, we report efficient and reproducible gene targeting (GT) in sugarcane, enabling precise co-editing of multiple alleles via template-mediated and homology-directed repair (HDR) of DNA double strand breaks induced by the programmable nuclease CRISPR/Cas9. The evaluation of 146 independently transformed plants from five independent experiments revealed a targeted nucleotide replacement that resulted in both targeted amino acid substitutions W574L and S653I in the acetolactate synthase (ALS) in 11 lines in addition to single, targeted amino acid substitutions W574L or S653I in 25 or 18 lines, respectively. Co-editing of up to three ALS copies/alleles that confer herbicide tolerance was confirmed by Sanger sequencing of cloned long polymerase chain reaction (PCR) amplicons. This work will enable crop improvement by conversion of inferior alleles to superior alleles through targeted nucleotide substitutions.

(Saccharum hybrid complex)↗
DOE OSTI2019

Relevance of the Preparation of the Target for PLD on the Magnetic Properties of Films of Iron-Doped Indium Oxide

This paper concerns the importance of the preparation of the targets that may be used for pulsed laser deposition of iron-doped indium oxide films. Targets with a fixed concentration of iron are fabricated from indium oxide and iron metal or one of the oxides of iron, FeO, Fe3O4 and Fe2O3. Films from each target were ablated onto sapphire substrates at the same temperature under different oxygen pressures such that the thickness of the films was kept approximately constant. The films were studied using X-ray diffraction, X-ray absorption (both XANES and EXAFS), optical absorption and magnetic circular dichroism. The magnetic properties were measured with a SQUID magnetometer. At the lowest oxygen pressure, there was evidence that some of the iron ions in the films were in the state Fe2+, rather than Fe3+, and there was also a little metallic iron; these properties were accompanied by a substantial magnetisation. As the amount of the oxygen was increased, the number of defect phases and the saturation magnetisation was reduced and the band gap increased. In each case, we found that the amount of the oxygen that had been included in the target from the precursor added to the effect of adding oxygen in the deposition chamber. It was concluded that the amount of oxygen in the target due to the precursor was an important consideration but not a defining factor in the quality of the films.

(InFe)2O3↗
DOE OSTI2020

Carrier-assisted One-pot Sample Preparation for Targeted Proteomics Analysis of Small Numbers of Human Cells

Protein analysis of small numbers of human cells is primarily achieved by targeted proteomics with antibody-based immunoassays, which have inherent limitations (e.g., low multiplex and unavailability of antibodies for new proteins). Mass spectrometry (MS)-based targeted proteomics has emerged as an alternative because it is antibody-free, high multiplex, and has high specificity and quantitation accuracy. Recent advances in MS instrumentation make MS-based targeted proteomics possible for multiplexed quantification of highly abundant proteins in single cells. However, there is a technical challenge for effective processing of single cells with minimal sample loss for MS analysis. To address this issue, we have recently developed a convenient protein carrier-assisted one-pot sample preparation coupled with liquid chromatography (LC) - selected reaction monitoring (SRM) termed cLC-SRM for targeted proteomics analysis of small numbers of human cells. This method capitalizes on using the combined excessive exogenous protein as a carrier and low-volume one-pot processing to greatly reduce surface adsorption losses as well as high-specificity LC-SRM to effectively address the increased dynamic concentration range due to the addition of exogeneous carrier protein. Its utility has been demonstrated by accurate quantification of most moderately abundant proteins in small numbers of cells (e.g., 10-100 cells) and highly abundant proteins in single cells. The easy-to-implement features and no need for specific devices make this method readily accessible to most proteomics laboratories. In this study, we have provided a detailed protocol for cLC-SRM analysis of small numbers of human cells including cell sorting, cell lysis and digestion, LC-SRM analysis, and data analysis. Further improvements in detection sensitivity and sample throughput are needed towards targeted single-cell proteomics analysis. We anticipate that cLC-SRM will be broadly applied to biomedical research and systems biology with the potential of facilitating precision medicine.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Development of CD46 targeted alpha theranostics in prostate cancer using 134 Ce/ 225 Ac-Macropa-PEG 4 -YS5

Rationale: 225 Ac, a long-lived α-emitter with a half-life of 9.92 days, has garnered significant attention as a therapeutic radionuclide when coupled with monoclonal antibodies and other targeting vectors. Nevertheless, its clinical utility has been hampered by potential off-target toxicity, a lack of optimized chelators for 225 Ac, and limitations in radiolabeling methods. In a prior study evaluating the effectiveness of CD46-targeted radioimmunotherapy, we found great therapeutic efficacy but also significant toxicity at higher doses. To address these challenges, we have developed a radioimmunoconjugate called 225 Ac-Macropa-PEG 4 -YS5, incorporating a stable PEGylated linker to maximize tumoral uptake and increase tumor-to-background ratios. Our research demonstrates that this conjugate exhibits greater anti-tumor efficacy while minimizing toxicity in prostate cancer 22Rv1 tumors. Methods: We synthesized Macropa.NCS and Macropa-PEG 4/8 -TFP esters and prepared Macropa-PEG 0/4/8 -YS5 (with nearly ~1:1 ratio of macropa chelator to antibody YS5) as well as DOTA-YS5 conjugates. These conjugates were then radiolabeled with 225 Ac in a 2 M NH 4 OAc solution at 30 °C, followed by purification using YM30K centrifugal purification. Subsequently, we conducted biodistribution studies and evaluated antitumor activity in nude mice (nu/nu) bearing prostate 22Rv1 xenografts in both single-dose and fractionated dosing studies. Micro-PET imaging studies were performed with 134 Ce-Macropa-PEG 0/4/8 -YS5 in 22Rv1 xenografts for 7 days. Toxicity studies were also performed in healthy athymic nude mice. Results: As expected, we achieved a >95% radiochemical yield when labeling Macropa-PEG 0/4/8 -YS5 with 225 Ac, regardless of the chelator ratios (ranging from 1 to 7.76 per YS5 antibody). The isolated yield exceeded 60% after purification. Such high conversions were not observed with the DOTA-YS5 conjugate, even at a higher ratio of 8.5 chelators per antibody (RCY of 83%, an isolated yield of 40%). Biodistribution analysis at 7 days post-injection revealed higher tumor uptake for the 225 Ac-Macropa-PEG 4 -YS5 (82.82 ± 38.27 %ID/g) compared to other conjugates, namely 225 Ac-Macropa-PEG 0/8 -YS5 (38.2 ± 14.4/36.39 ± 12.4 %ID/g) and 225 Ac-DOTA-YS5 (29.35 ± 7.76 %ID/g). The PET Imaging of 134 Ce-Macropa-PEG 0/4/8 -YS5 conjugates resulted in a high tumor uptake, and tumor to background ratios. In terms of antitumor activity, 225 Ac-Macropa-PEG 4 -YS5 exhibited a substantial response, leading to prolonged survival compared to 225 Ac-DOTA-YS5, particularly when administered at 4.625 kBq doses, in single or fractionated dose regimens. Chronic toxicity studies observed mild to moderate renal toxicity at 4.625 and 9.25 kBq doses. Conclusions: Our study highlights the promise of 225 Ac-Macropa-PEG 4 -YS5 for targeted alpha particle therapy. The 225 Ac-Macropa-PEG 4 -YS5 conjugate demonstrates improved biodistribution, reduced off-target binding, and enhanced therapeutic efficacy, particularly at lower doses, compared to 225 Ac-DOTA-YS5. Incorporating theranostic 134 Ce PET imaging further enhances the versatility of macropa-PEG conjugates, offering a more effective and safer approach to cancer treatment. Overall, this methodology has a high potential for broader clinical applications.

60 APPLIED LIFE SCIENCES↗