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DOE OSTI2014

Immortalization of normal human mammary epithelial cells in two steps by direct targeting of senescence barriers does not require gross genomic alterations

Telomerase reactivation and immortalization are critical for human carcinoma progression. However, little is known about the mechanisms controlling this crucial step, due in part to the paucity of experimentally tractable model systems that can examine human epithelial cell immortalization as it might occur in vivo. We achieved efficient non-clonal immortalization of normal human mammary epithelial cells (HMEC) by directly targeting the 2 main senescence barriers encountered by cultured HMEC. The stress-associated stasis barrier was bypassed using shRNA to p16INK4; replicative senescence due to critically shortened telomeres was bypassed in post-stasis HMEC by c-MYC transduction. Thus, 2 pathologically relevant oncogenic agents are sufficient to immortally transform normal HMEC. The resultant non-clonal immortalized lines exhibited normal karyotypes. Most human carcinomas contain genomically unstable cells, with widespread instability first observed in vivo in pre-malignant stages; in vitro, instability is seen as finite cells with critically shortened telomeres approach replicative senescence. Our results support our hypotheses that: (1) telomere-dysfunction induced genomic instability in pre-malignant finite cells may generate the errors required for telomerase reactivation and immortalization, as well as many additional “passenger” errors carried forward into resulting carcinomas; (2) genomic instability during cancer progression is needed to generate errors that overcome tumor suppressive barriers, but not required per se; bypassing the senescence barriers by direct targeting eliminated a need for genomic errors to generate immortalization. Achieving efficient HMEC immortalization, in the absence of “passenger” genomic errors, should facilitate examination of telomerase regulation during human carcinoma progression, and exploration of agents that could prevent immortalization.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2013

Optimization Studies for ISOL Type High-Powered Targets

The research studied one-step and two-step Isotope Separation on Line (ISOL) targets for future radioactive beam facilities with high driver-beam power through advanced computer simulations. As a target material uranium carbide in the form of foils was used because of increasing demand for actinide targets in rare-isotope beam facilities and because such material was under development in ISAC at TRIUMF when this project started. Simulations of effusion were performed for one-step and two step targets and the effects of target dimensions and foil matrix were studied. Diffusion simulations were limited by availability of diffusion parameters for UC x material at reduced density; however, the viability of the combined diffusion?effusion simulation methodology was demonstrated and could be used to extract physical parameters such as diffusion coefficients and effusion delay times from experimental isotope release curves. Dissipation of the heat from the isotope-producing targets is the limiting factor for high-power beam operation both for the direct and two-step targets. Detailed target models were used to simulate proton beam interactions with the targets to obtain the fission rates and power deposition distributions, which were then applied in the heat transfer calculations to study the performance of the targets. Results indicate that a direct target, with specification matching ISAC TRIUMF target, could operate in 500-MeV proton beam at beam powers up to ~40 kW, producing ~8 10 13 fission/s with maximum temperature in UCx below 2200 C. Targets with larger radius allow higher beam powers and fission rates. For the target radius in the range 9-mm to 30-mm the achievable fission rate increases almost linearly with target radius, however, the effusion delay time also increases linearly with target radius.

43 PARTICLE ACCELERATORS↗

DOE OSTI2015

Age and the means of bypassing stasis influence the intrinsic subtype of immortalized human mammary epithelial cells

Based on molecular features, breast cancers are grouped into intrinsic subtypes that have different prognoses and therapeutic response profiles. With increasing age, breast cancer incidence increases, with hormone receptor-positive and other luminal-like subtype tumors comprising a majority of cases. It is not known at what stage of tumor progression subtype specification occurs, nor how the process of aging affects the intrinsic subtype. We examined subtype markers in immortalized human mammary epithelial cell lines established following exposure of primary cultured cell strains to a two-step immortalization protocol that targets the two main barriers to immortality: stasis (stress-associated senescence) and replicative senescence. Cell lines derived from epithelial cells obtained from non-tumorous pre- and post-menopausal breast surgery tissues were compared. Additionally, comparisons were made between lines generated using two different genetic interventions to bypass stasis: transduction of either an shRNA that down-regulated p16INK4A, or overexpressed constitutive active cyclin D1/CDK2. In all cases, the replicative senescence barrier was bypassed by transduction of c-Myc. Cells from all resulting immortal lines exhibited normal karyotypes. Immunofluorescence, flow cytometry, and gene expression analyses of lineage-specific markers were used to categorize the intrinsic subtypes of the immortalized lines. Bypassing stasis with p16 shRNA in young strains generated cell lines that were invariably basal-like, but the lines examined from older strains exhibited some luminal features such as keratin 19 and estrogen receptor expression. Overexpression of cyclin D1/CDK2 resulted in keratin 19 positive, luminal-like cell lines from both young and old strains, and the lines examined from older strains exhibited estrogen receptor expression. Thus age and the method of bypassing stasis independently influence the subtype of immortalized human mammary epithelial cells.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2025

Automated shaker placement and regularized input estimation for MIMO testing.

Multi-input, multi-output (MIMO) testing is used in component qualification to reproduce operational responses in the laboratory. It is often preferred to single-input and base-shake testing because of the potential for equivalent or better tests using smaller actuators and shorter test suites. Given a target response, two key steps in MIMO test design are selecting actuator locations and solving for input loads. Actuator locations are often manually selected using expert judgment. If an automatic method is used, locations are usually determined by simulating the vibration control problem and minimizing a combination of the input energy and control residuals. To select a configuration, the relative importance of input energy and residuals must be specified. Specifying relative weights is, in general, a manual and subjective process. This paper develops an objective function that compares actuator configurations based on control accuracy and required input energy without any manual parameter tuning. The objective function uses an optimally selected tradeoff parameter for each candidate configuration. To choose actuator locations using the new objective function, a pivoting algorithm for integer programming problems is developed. Starting with an initial configuration (such as the one generated by a greedy algorithm), the pivoting algorithm guarantees an objective function decrease in each iteration until convergence is reached. In a simulation featuring a structure excited by a diffuse acoustic field, electrodynamic shaker locations and regularized inputs are solved for without any analyst-specified parameters. Simulations are performed in MIMO configurations where the number of target responses is less than, equal to, and greater than the number of actuators.

Multi-input multi-output↗

DOE OSTI2016

Robotic path-finding in inverse treatment planning for stereotactic radiosurgery with continuous dose delivery

Purpose: Continuous dose delivery in radiation therapy treatments has been shown to decrease total treatment time while improving the dose conformity and distribution homogeneity over the conventional step-and-shoot approach. The authors develop an inverse treatment planning method for Gamma Knife® Perfexion™ that continuously delivers dose along a path in the target. Methods: The authors’ method is comprised of two steps: find a path within the target, then solve a mixed integer optimization model to find the optimal collimator configurations and durations along the selected path. Robotic path-finding techniques, specifically, simultaneous localization and mapping (SLAM) using an extended Kalman filter, are used to obtain a path that travels sufficiently close to selected isocentre locations. SLAM is novelly extended to explore a 3D, discrete environment, which is the target discretized into voxels. Further novel extensions are incorporated into the steering mechanism to account for target geometry. Results: The SLAM method was tested on seven clinical cases and compared to clinical, Hamiltonian path continuous delivery, and inverse step-and-shoot treatment plans. The SLAM approach improved dose metrics compared to the clinical plans and Hamiltonian path continuous delivery plans. Beam-on times improved over clinical plans, and had mixed performance compared to Hamiltonian path continuous plans. The SLAM method is also shown to be robust to path selection inaccuracies, isocentre selection, and dose distribution. Conclusions: The SLAM method for continuous delivery provides decreased total treatment time and increased treatment quality compared to both clinical and inverse step-and-shoot plans, and outperforms existing path methods in treatment quality. It also accounts for uncertainty in treatment planning by accommodating inaccuracies.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

SU-F-J-66: Anatomy Deformation Based Comparison Between One-Step and Two-Step Optimization for Online ART

Purpose: This study investigated that how the quality of adapted plan was affected by inter-fractional anatomy deformation by using one-step and two-step optimization for on line adaptive radiotherapy (ART) procedure. Methods: 10 lung carcinoma patients were chosen randomly to produce IMRT plan by one-step and two-step algorithms respectively, and the prescribed dose was set as 60 Gy on the planning target volume (PTV) for all patients. To simulate inter-fractional target deformation, four specific cases were created by systematic anatomy variation; including target superior shift 0.5 cm, 0.3cm contraction, 0.3 cm expansion and 45-degree rotation. Based on these four anatomy deformation, adapted plan, regenerated plan and non-adapted plan were created to evaluate quality of adaptation. Adapted plans were generated automatically by using one-step and two-step algorithms respectively to optimize original plans, and regenerated plans were manually created by experience physicists. Non-adapted plans were produced by recalculating the dose distribution based on corresponding original plans. The deviations among these three plans were statistically analyzed by paired T-test. Results: In PTV superior shift case, adapted plans had significantly better PTV coverage by using two-step algorithm compared with one-step one, and meanwhile there was a significant difference of V95 by comparison with adapted and non-adapted plans (p=0.0025). In target contraction deformation, with almost same PTV coverage, the total lung received lower dose using one-step algorithm than two-step algorithm (p=0.0143,0.0126 for V20, Dmean respectively). In other two deformation cases, there were no significant differences observed by both two optimized algorithms. Conclusion: In geometry deformation such as target contraction, with comparable PTV coverage, one-step algorithm gave better OAR sparing than two-step algorithm. Reversely, the adaptation by using two-step algorithm had higher efficiency and accuracy as target occurred position displacement. We want to thank Dr. Lei Xing and Dr. Yong Yang in the Stanford University School of Medicine for this work. This work was jointly supported by NSFC (61471226), Natural Science Foundation for Distinguished Young Scholars of Shandong Province (JQ201516), and China Postdoctoral Science Foundation (2015T80739, 2014M551949).

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

Sinusoidal Siemens star spatial frequency response measurement errors due to misidentified target centers

Numerous methods are available to measure the spatial frequency response (SFR) of an optical system. A recent change to the ISO 12233 photography resolution standard includes a sinusoidal Siemens star test target. We take the sinusoidal Siemens star proposed by the ISO 12233 standard, measure system SFR, and perform an analysis of errors induced by incorrectly identifying the center of a test target. We show a closed-form solution for the radial profile intensity measurement given an incorrectly determined center and describe how this error reduces the measured SFR of the system. As a result, using the closed-form solution, we propose a two-step process by which test target centers are corrected and the measured SFR is restored to the nominal, correctly centered values.

79 ASTRONOMY AND ASTROPHYSICS↗

DOE OSTI2020

Similarity of Precursors in Solid-State Synthesis as Text-Mined from Scientific Literature

Collecting and analyzing the vast amount of information available in the solid-state chemistry literature may accelerate our understanding of materials synthesis. However, one major problem is the difficulty of identifying which materials from a synthesis paragraph are precursors or are target materials. In this study, we developed a two-step chemical named entity recognition model to identify precursors and targets, based on information from the context around material entities. Using the extracted data, we conducted a meta-analysis to study the similarities and differences between precursors in the context of solid-state synthesis. To quantify precursor similarity, we built a substitution model to calculate the viability of substituting one precursor with another while retaining the target. From a hierarchical clustering of the precursors, we demonstrate that the “chemical similarity” of precursors can be extracted from text data. Quantifying the similarity of precursors helps provide a foundation for suggesting candidate reactants in a predictive synthesis model.

36 MATERIALS SCIENCE↗

DOE OSTI2014

Genotyping‐in‐Thousands by sequencing (GT‐seq): A cost effective SNP genotyping method based on custom amplicon sequencing

Abstract Genotyping‐in‐Thousands by sequencing ( GT ‐seq) is a method that uses next‐generation sequencing of multiplexed PCR products to generate genotypes from relatively small panels (50–500) of targeted single‐nucleotide polymorphisms ( SNP s) for thousands of individuals in a single Illumina HiSeq lane. This method uses only unlabelled oligos and PCR master mix in two thermal cycling steps for amplification of targeted SNP loci. During this process, sequencing adapters and dual barcode sequence tags are incorporated into the amplicons enabling thousands of individuals to be pooled into a single sequencing library. Post sequencing, reads from individual samples are split into individual files using their unique combination of barcode sequences. Genotyping is performed with a simple perl script which counts amplicon‐specific sequences for each allele, and allele ratios are used to determine the genotypes. We demonstrate this technique by genotyping 2068 individual steelhead trout ( Oncorhynchus mykiss ) samples with a set of 192 SNP markers in a single library sequenced in a single Illumina HiSeq lane. Genotype data were 99.9% concordant to previously collected TaqMan ™ genotypes at the same 192 loci, but call rates were slightly lower with GT ‐seq (96.4%) relative to Taqman (99.0%). Of the 192 SNP s, 187 were genotyped in ≥90% of the individual samples and only 3 SNP s were genotyped in <70% of samples. This study demonstrates amplicon sequencing with GT ‐seq greatly reduces the cost of genotyping hundreds of targeted SNP s relative to existing methods by utilizing a simple library preparation method and massive efficiency of scale.

Campbell, Nathan R.↗

DOE OSTI2021

Transition Path Sampling Study of the Feruloyl Esterase Mechanism

Serine hydrolases cleave peptide and ester bonds and are ubiquitous in nature, with applications in biotechnology, in materials, and as drug targets. The serine hydrolase two-step mechanism employs a serine–histidine–aspartate/glutamate catalytic triad, where the histidine residue acts as a base to activate poor nucleophiles (a serine residue or a water molecule) and as an acid to allow the dissociation of poor leaving groups. This mechanism has been the subject of debate regarding how histidine shuttles the proton from the nucleophile to the leaving group. To elucidate the reaction mechanism of serine hydrolases, we employ quantum mechanics/molecular mechanics-based transition path sampling to obtain the reaction coordinate using the Aspergillus niger feruloyl esterase A (AnFaeA) as a model enzyme. The optimal reaction coordinates include terms involving nucleophilic attack on the carbonyl carbon and proton transfer to, and dissociation of, the leaving group. During the reaction, the histidine residue undergoes a reorientation on the time scale of hundreds of femtoseconds that supports the “moving histidine” mechanism, thus calling into question the “ring flip” mechanism. We find a concerted mechanism, where the transition state coincides with the tetrahedral intermediate with the histidine residue pointed between the nucleophile and the leaving group. Moreover, motions of the catalytic aspartate toward the histidine occur concertedly with proton abstraction by the catalytic histidine and help stabilize the transition state, thus partially explaining how serine hydrolases enable poor nucleophiles to attack the substrate carbonyl carbon. Rate calculations indicate that the second step (deacylation) is rate-determining, with a calculated rate constant of 66 s –1 . Altogether, these results reveal the pivotal role of active-site dynamics in the catalytic mechanism of AnFaeA, which is likely similar in other serine hydrolases.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2016

Real-time observation of DNA recognition and rejection by the RNA-guided endonuclease Cas9

Binding specificity of Cas9–guide RNA complexes to DNA is important for genome-engineering applications; however, how mismatches influence target recognition/rejection kinetics is not well understood. Here we used single-molecule FRET to probe real-time interactions between Cas9–RNA and DNA targets. The bimolecular association rate is only weakly dependent on sequence; however, the dissociation rate greatly increases from <0.006 s -1 to >2 s -1 upon introduction of mismatches proximal to protospacer-adjacent motif (PAM), demonstrating that mismatches encountered early during heteroduplex formation induce rapid rejection of off-target DNA. In contrast, PAM-distal mismatches up to 11 base pairs in length, which prevent DNA cleavage, still allow formation of a stable complex (dissociation rate <0.006 s -1 ), suggesting that extremely slow rejection could sequester Cas9–RNA, increasing the Cas9 expression level necessary for genome-editing, thereby aggravating off-target effects. We also observed at least two different bound FRET states that may represent distinct steps in target search and proofreading.

Science & Technology - Other Topics↗

DOE OSTI2013

Nanograting formation through surface plasmon fields induced by femtosecond laser pulses

Ablation of solid surfaces irradiated with superimposed multiple shots of low fluence femtosecond (fs) laser pulses often results in the formation of periodic nanostructures on the target surface. We demonstrate that the self-organization process of nanostructuring can be regulated to fabricate a homogeneous nanograting on the target surface in air. A simple two-step ablation process was used to control the nanoscale energy deposition that should be developed through the excitation of surface plasmon polaritons (SPPs) during the fs laser-surface interaction. The results obtained for crystalline gallium nitride represent exactly the nature of a single spatial standing wave mode of SPPs of which periodically enhanced near-fields ablate the target surface to form the nanograting with a period of ∼200 nm. The calculated results for a model target reproduce well the observed nanograting period and explain the origin of its characteristic properties.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DOE OSTI2016

An online replanning method using warm start optimization and aperture morphing for flattening-filter-free beams

Purpose: In a situation where a couch shift for patient positioning is not preferred or prohibited (e.g., MR-linac), segment aperture morphing (SAM) can address target dislocation and deformation. For IMRT/VMAT with flattening-filter-free (FFF) beams, however, SAM method would lead to an adverse translational dose effect due to the beam unflattening. Here the authors propose a new two-step process to address both the translational effect of FFF beams and the target deformation. Methods: The replanning method consists of an offline and an online step. The offline step is to create a series of preshifted-plans (PSPs) obtained by a so-called “warm start” optimization (starting optimization from the original plan, rather than from scratch) at a series of isocenter shifts. The PSPs all have the same number of segments with very similar shapes, since the warm start optimization only adjusts the MLC positions instead of regenerating them. In the online step, a new plan is obtained by picking the closest PSP or linearly interpolating the MLC positions and the monitor units of the closest PSPs for the shift determined from the image of the day. This two-step process is completely automated and almost instantaneous (no optimization or dose calculation needed). The previously developed SAM algorithm is then applied for daily deformation. The authors tested the method on sample prostate and pancreas cases. Results: The two-step interpolation method can account for the adverse dose effects from FFF beams, while SAM corrects for the target deformation. Plan interpolation method is effective in diminishing the unflat beam effect and may allow reducing the required number of PSPs. The whole process takes the same time as the previously reported SAM process (5–10 min). Conclusions: The new two-step method plus SAM can address both the translation effects of FFF beams and target deformation, and can be executed in full automation except the delineation of target contour required by the SAM process.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

SU-E-J-126: An Online Replanning Method for FFF Beams Without Couch Shift

Purpose: In a situation that couch shift for patient positioning is not preferred or prohibited (e.g., MR-Linac), segment aperture morphing (SAM) can address target dislocation and deformation. For IMRT/VMAT with flattening filter free (FFF) beams, however, SAM method would lead to an adverse translational dose effect due to the beam unflattening. Here we propose a new 2-step process to address both the translational effect of FFF beams and the target deformation. Methods: The replanning method consists of an offline and an online steps. The offline step is to create a series of pre-shifted plans (PSP) obtained by a so called “warm start” optimization (starting optimization from the original plan, rather from scratch) at a series of isocenter shifts with fixed distance (e.g. 2 cm, at x,y,z = 2,0,0 ; 2,2,0 ; 0,2,0; …;− 2,0,0). The PSPs all have the same number of segments with very similar shapes, since the warm-start optimization only adjusts the MLC positions instead of regenerating them. In the online step, a new plan is obtained by linearly interpolating the MLC positions and the monitor units of the closest PSPs for the shift determined from the image of the day. This two-step process is completely automated, and instantaneously fast (no optimization or dose calculation needed). The previously-developed SAM algorithm is then applied for daily deformation. We tested the method on sample prostate and pancreas cases. Results: The two-step interpolation method can account for the adverse dose effects from FFF beams, while SAM corrects for the target deformation. The whole process takes the same time as the previously reported SAM process (5–10 min). Conclusion: The new two-step method plus SAM can address both the translation effects of FFF beams and target deformation, and can be executed in full automation requiring no additional time from the SAM process. This research was supported by Elekta inc. (Crawley, UK)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2015

MO-F-CAMPUS-T-03: Continuous Dose Delivery with Gamma Knife Perfexion

Purpose: We propose continuous dose delivery techniques for stereotactic treatments delivered by Gamma Knife Perfexion using inverse treatment planning system that can be applied to various tumour sites in the brain. We test the accuracy of the plans on Perfexion’s planning system (GammaPlan) to ensure the obtained plans are viable. This approach introduces continuous dose delivery for Perefxion, as opposed to the currently employed step-and-shoot approaches, for different tumour sites. Additionally, this is the first realization of automated inverse planning on GammaPlan. Methods: The inverse planning approach is divided into two steps of identifying a quality path inside the target, and finding the best collimator composition for the path. To find a path, we select strategic regions inside the target volume and find a path that visits each region exactly once. This path is then passed to a mathematical model which finds the best combination of collimators and their durations. The mathematical model minimizes the dose spillage to the surrounding tissues while ensuring the prescribed dose is delivered to the target(s). Organs-at-risk and their corresponding allowable doses can also be added to the model to protect adjacent organs. Results: We test this approach on various tumour sizes and sites. The quality of the obtained treatment plans are comparable or better than forward plans and inverse plans that use step- and-shoot technique. The conformity indices in the obtained continuous dose delivery plans are similar to those of forward plans while the beam-on time is improved on average (see Table 1 in supporting document). Conclusion: We employ inverse planning for continuous dose delivery in Perfexion for brain tumours. The quality of the obtained plans is similar to forward and inverse plans that use conventional step-and-shoot technique. We tested the inverse plans on GammaPlan to verify clinical relevance. This research was partially supported by Elekta, Sweden (vendor of Gamma Knife Perfexion)

60 APPLIED LIFE SCIENCES↗

DOE OSTI2019

A new approach to Cas9-based genome editing in Aspergillus niger that is precise, efficient and selectable

Aspergillus niger and other filamentous fungi are widely used in industry, but efficient genetic engineering of these hosts remains nascent. For example, while molecular genetic tools have been developed, including CRISPR/Cas9, facile genome engineering of A. niger remains challenging. To address these challenges, we have developed a simple Cas9-based gene targeting method that provides selectable, iterative, and ultimately marker-free generation of genomic deletions and insertions. This method leverages locus-specific "popout" recombination to suppress off-target integrations. We demonstrated the effectiveness of this method by targeting the phenotypic marker albA and validated it by targeting the glaA and mstC loci. After two selection steps, we observed 100% gene editing efficiency across all three loci. This method greatly reduces the effort required to engineer the A. niger genome and overcomes low Cas9 transformations efficiency by eliminating the need for extensive screening. This method represents a significant addition to the A. niger genome engineering toolbox and could be adapted for use in other organisms. It is expected that this method will impact several areas of industrial biotechnology, such as the development of new strains for the secretion of heterologous enzymes and the discovery and optimization of metabolic pathways.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2015

Post-Irradiation Examination of 237Np Targets for 238Pu Production

Oak Ridge National Laboratory is recovering the US 238 Pu production capability and the first step in the process has been to evaluate the performance of a 237 Np target cermet pellet encased in an aluminum clad. The process proceeded in 3 steps; the first step was to irradiate capsules of single pellets composed of NpO 2 and aluminum power to examine their shrinkage and gas release. These pellets were formed by compressing sintered NpO 2 and aluminum powder in a die at high pressure followed by sintering in a vacuum furnace. Three temperatures were chosen for sintering the solution precipitated NpO 2 power used for pellet fabrication. The second step was to irradiate partial targets composed of 8 pellets in a semi-prototypical arrangement at the two best performing sintering temperatures to determine which temperature gave a pellet that performed the best under the actual planned irradiation conditions. The third step was to irradiate ~50 pellets in an actual target configuration at design irradiation conditions to assess pellet shrinkage and gas release, target heat transfer, and dimensional stability. The higher sintering temperature appeared to offer the best performance after one cycle of irradiation by having the least shrinkage, thus keeping the heat transfer gap between the pellets and clad small minimizing the pellet operating temperature. The final result of the testing was a target that can meet the initial production goals, satisfy the reactor safety requirements, and can be fabricated in production quantities. The current focus of the program is to verify that the target can be remotely dissembled, the pellets dissolved, and the 238 Pu recovered. Tests are being conducted to examine these concerns and to compare results to code predictions. Once the performance of the full length targets has been quantified, the pellet 237 Np loading will be revisited to determine if it can be increased to increase 238 Pu production.

07 ISOTOPE AND RADIATION SOURCES↗

DOE OSTI2025

Characterization of laser-accelerated proton beams from a 0.5 kJ sub-picosecond laser for radiography applications

Laser-accelerated ion beams show promise for many applications, including high-resolution flash imaging of static or dynamic objects in next-generation radiography to probe materials and plasmas in extreme environments and inertial confinement fusion. To scale up ion beam production for radiography applications, we conducted experiments using sub-picosecond lasers up to 0.5 kJ at the OMEGA-EP facility to characterize proton beams from solid targets, primarily CH/CD sub-micron thin films from which ion beams were also used for static and dynamic radiography for the first time. For standalone sub-micron thin CH films, the highest detected proton energy is in the range of 72–97 MeV. Proton beams with highest energy near or above 60 MeV at full laser energy and similar beam profiles are also measured from low-density CD foams and flat CH foil target of micrometer-scale thickness. The ~ 700–800 nm CH/CD foils achieve the highest ion yield among the targets tested. For sub-micron thin films, the laser prepulse can expand the target and lead to complex interactions, which is simulated using coupled hydrodynamic and two-step kinetic models. Simulations suggest the presence of a micrometer-scale preplasma plateau with near-critical density and further indicate that target normal sheath acceleration, electron heating from Relativistic transparency in the preplasma plateau, and background proton reflection from carbon ion front at the rear side contribute to the resulting proton spectrum from these sub-micron thin targets at various stages. These proton beams show strong potential for radiography and for production of secondary sources.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗