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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 379 records · Page 21
All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

Rejoining and misrejoining of radiation-induced chromatin breaks. IV. Charged particles

We have recently reported the kinetics of chromosome rejoining and exchange formation in human lymphocytes exposed to gamma rays using the techniques of fluorescence in situ hybridization (FISH) and premature chromosome condensation (PCC). In this paper, we have extended previous measurements to cells exposed to charged particles. Our goal was to determine differences in chromatin break rejoining and misrejoining after exposure to low- and high-linear energy transfer (LET) radiation. Cells were irradiated with hydrogen, neon, carbon or iron ions in the LET range 0.3-140 keV/microm and were incubated at 37 degrees C for various times after exposure. Little difference was observed in the yield of early prematurely condensed chromosome breaks for the different ions. The kinetics of break rejoining was exponential for all ions and had similar time constants, but the residual level of unrejoined breaks after prolonged incubation was higher for high-LET radiation. The kinetics of exchange formation was also similar for the different ions, but the yield of chromosome interchanges measured soon after exposure was higher for high-LET particles, suggesting that a higher fraction of DNA breaks are misrejoined quickly. On the other hand, the rate of formation of complete exchanges was slightly lower for densely ionizing radiation. The ratios between the yields of different types of aberrations observed at 10 h postirradiation in prematurely condensed chromosome preparations were dependent on LET. We found significant differences between the yields of aberrations measured in interphase (after repair) and metaphase for densely ionizing radiation. This difference might be caused by prolonged mitotic delay and/or interphase death. Overall, the results point out significant differences between low- and high-LET radiation for the formation of chromosome aberrations.

NASA Center JSC↗
DOE OSTI2019

Altered amplitude of low‐frequency fluctuation in basal ganglia correlates to pulmonary ventilation function in COPD patients: A resting‐state fMRI study

Abstract Introduction Patients under chronic obstructive pulmonary disease (COPD) has been reported to be associated with a higher prevalence of cognitive impairment (CI). However, it is still largely unknown whether the aberrant resting‐state spontaneous neuronal activity pattern reflected by the amplitude of low‐frequency fluctuation (ALFF) analysis will be associated with the CI in COPD patients. Materials A total of 28 COPD patients and 26 healthy controls were enrolled in this study. Of all the subjects, structural and functional MRI data, spirometry tests performance and neuropsychological assessments of different cognitive domains were collected. Voxel‐based two‐sample t tests were used to detect brain regions showing differences in the ALFF value between COPD patients and healthy controls. An additional fMRI runs with supplementary oxygen delivery were employed to explore the impact of elevated partial pressure of oxygen (PaO 2 ) or moderate hyperoxia on ALFF in COPD patients and healthy controls respectively. Results More extensive white matter lesion was detected in COPD patients. COPD patients exhibit decreased ALFF value in bilateral basal ganglia areas and right thalamus, and aberrant ALFF value is correlated with PaO 2 and pulmonary ventilation function (FEV1%pred). COPD patients performed worse in the Digit Span Test (reverse), Digit Symbol Substitution Test, Trail‐making test (A and B) than controls. After supplementary oxygen inhalation, the ALFF value of basal ganglia and right thalamus significantly increased in the controls, but not in the COPD patients. Conclusions COPD patients mainly exhibit impaired executive function but not long‐term memory in cognitive function assessment. Aberrant ALFF alteration in the deep brain may be directly related to lower PaO 2 in COPD patients.

Lu, Chun‐Qiang↗
DOE OSTI2015

Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling

Calcineurin (CaN) over-activation constrains synaptic plasticity and memory formation. Upon CaN activation, NFAT imports into the nucleus and guides its downstream genes, which also affect neuronal and synaptic function. Aberrant CaN/NFAT signaling involves in neurotoxicity and cognitive impairment in neurological disorders such as Alzheimer's disease, but its role in postoperative cognitive dysfunction (POCD) remains uninvestigated. Inhaled anesthetic isoflurane facilitates the development of POCD, and the present study investigated the role of CaN/NFAT signaling in isoflurane induced cognitive impairment of aged rats, and the therapeutic effects of CaN inhibitor cyclosporine A (CsA). The results indicated that hippocampal CaN activity increased and peaked at 6 h after isoflurane exposure, and NFAT, especially NFATc4, imported into the nucleus following CaN activation. Furthermore, phamacological inhibition of CaN by CsA markedly attenuated isoflurane induced aberrant CaN/NFATc4 signaling in the hippocampus, and rescued relevant spatial learning and memory impairment of aged rats. Overall, the study suggests hippocampal CaN/NFAT signaling as the upstream mechanism of isoflurane induced cognitive impairment, and provides potential therapeutic target and possible treatment methods for POCD. - Highlights: • Isoflurane induces hippocampal calcineurin activation. • Isoflurane induces hippocampal NFAT, especially NFATc4, nuclear import. • Cyclosporine A attenuates isoflurane induced aberrant calcineurin/NFAT signaling. • Cyclosporine A rescues isoflurane induced cognitive impairment. • Calcineurin/NFAT signaling is the upstream mechanism of isoflurane induced synaptic dysfunction and cognitive impairment.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Hypomyelinating leukodystrophy-associated missense mutation in HSPD1 blunts mitochondrial dynamics

Myelin-forming glial cells undergo dynamic morphological changes in order to produce mature myelin sheaths with multiple layers. In the central nervous system (CNS), oligodendrocytes differentiate to insulate neuronal axons with myelin sheaths. Myelin sheaths play a key role in homeostasis of the nervous system, but their related disorders lead not only to dismyelination and repeated demyelination but also to severe neuropathies. Hereditary hypomyelinating leukodystrophies (HLDs) are a group of such diseases affecting oligodendrocytes and are often caused by missense mutations of the respective responsible genes. Despite increasing identification of gene mutations through advanced nucleotide sequencing technology, studies on the relationships between gene mutations and their effects on cellular and subcellular aberrance have not followed at the same rapid pace. In this study, we report that an HLD4-associated (Asp-29-to-Gly) mutant of mitochondrial heat shock 60-kDa protein 1 (HSPD1) causes short-length morphologies and increases the numbers of mitochondria due to their aberrant fission and fusion cycles. In experiments using a fluorescent dye probe, this mutation decreases the mitochondrial membrane potential. Also, mitochondria accumulate in perinuclear regions. HLD4-associated HSPD1 mutant blunts mitochondrial dynamics, probably resulting in oligodendrocyte malfunction. This study constitutes a first finding concerning the relationship between disease-associated HSPD1 mutation and mitochondrial dynamics, which may be similar to the relationship between another disease-associated HSPD1 mutation (MitCHAP-60 disease) and aberrant mitochondrial dynamics. - Highlights: • The HLD4 mutant of HSPD1 decreases mitochondrial fission frequency. • The HLD4 mutant decreases mitochondrial fusion frequency. • Mitochondria harboring the HLD4 mutant exhibit slow motility. • The HLD4 mutant of HSPD1 decreases mitochondrial membrane potential. • HLD4-related diseases may be due to decreased mitochondrial dynamics.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Maternal trans-general analysis of the human mitochondrial DNA pattern

There is an intimate connection between mitochondrial DNA (mtDNA) methylation and some diseases, such as cancer. MtDNA is almost strictly maternally inherited. However, whether the aberrant mtDNA methylation involved in breast cancer progression and whether mtDNA methylation can be transmitted through maternal line are poorly understood. Here we applied bisulfite sequencing to global mitochondrial DNA and whole genomic DNA methylation array from fifteen members of five three-female-generation families with one breast cancer patient in each family. We found that mtDNA methylation was maternally inherited in D-loop region and eight aberrant mtDNA methylation sites were correlated with breast cancer. Furthermore, conjoint analysis showed that mtDNA methylation sites could be potential biomarkers combined with nuclear DNA methylation sites for breast cancer risk prediction. - Highlights: • MtDNA methylation was modestly maternally inherited, especially in D-loop region. • Eight aberrant mtDNA methylation sites were correlated with breast cancer. • Nine nDNA methylation sites were identified as potential breast cancer-related sites. • MtDNA-nDNA methylation sites could be potential biomarkers for breast cancer. • A hypothetical model of mtDNA methylation maternal inheritance was proposed.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Genetic variation and radiation quality impact cancer promoting cellular phenotypes in response to HZE exposure

There exists a wide degree of genetic variation within the normal human population which includes disease free individuals with heterozygote defects in major DNA repair genes. A lack of understanding of how this genetic variation impacts cellular phenotypes that inform cancer risk post heavy ion exposure poses a major limitation in developing personalized cancer risk assessment astronauts. We initiated a pilot study with Human Mammary Epithelial Cell strains (HMEC) derived from wild type, a p16 silenced derivative of wild type, and various genetic variants that were heterozygote for DNA repair genes; BRCA1, BRCA2 and ATM. Cells strains were exposed to different high and low LET radiation qualities to generate both simple and complex lesions and centrosome aberrations were examined as a surrogate marker of genomic instability and cancer susceptibility post different exposures. Our results indicate that centrosome aberration frequency is higher in the genetic variants under study. The aberration frequency increases with dose, complexity of the lesion generated by different radiation qualities and age of the individual. This increase in genomic instability correlates with elevated check-point activation post radiation exposure. These studies suggest that the influence of individual genetics on cell cycle regulation could modify the degree of early genomic instability in response to complex lesions and potentially define cancer predisposition in response to HZE exposure. These results will have significant implications in estimating cancer susceptibility in genetically variant individuals exposed to HZE particles.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

Studies on low energy beam transport for high intensity high charged ions at IMP

Superconducting Electron Cyclotron Resonance ion source with Advanced design in Lanzhou (SECRAL) is an advanced fully superconducting ECR ion source at IMP designed to be operational at the microwave frequency of 18–24 GHz. The existing SECRAL beam transmission line is composed of a solenoid lens and a 110° analyzing magnet. Simulations of particle tracking with 3D space charge effect and realistic 3D magnetic fields through the line were performed using particle-in-cell code. The results of the beam dynamics show that such a low energy beam is very sensitive to the space charge effect and significantly suffers from the second-order aberration of the analyzing magnet resulting in large emittance. However, the second-order aberration could be reduced by adding compensating sextupole components in the beam line. On this basis, a new 110° analyzing magnet with relatively larger acceptance and smaller aberration is designed and will be used in the design of low energy beam transport line for a new superconducting ECR ion source SECRAL-II. The features of the analyzer and the corresponding beam trajectory calculation will be detailed and discussed in this paper.

43 PARTICLE ACCELERATORS↗
DOE OSTI2015

A design study for a compact two stage in-flight separator with a high mass resolution and large acceptance

The rare isotope beam separator with a large angular acceptance and energy acceptance is essential for examining the characteristics of unstable nuclei and exotic nuclear reactions. Careful design, however, is required to compensate for the effects of high order aberrations induced by large aperture magnets, which are used to collect rare isotopes obtained from a high energy primary heavy-ion beam hitting a target. In order to minimize the effect of the high order aberration, the optics was based on the mirror symmetry optics, which provides smaller high order aberrations, for the separation of {sup 132}Sn produced by a fission reaction between the primary beam of {sup 238}U and a relatively thick Pb target. The designed optics provides energy acceptance (full), horizontal angular acceptance, and vertical acceptance of approximately 8%, 60 mrad, and 130 mrad, respectively.

43 PARTICLE ACCELERATORS↗
DOE OSTI2015

Impact of dynamic specimen shape evolution on the atom probe tomography results of doped epitaxial oxide multilayers: Comparison of experiment and simulation

The experimental atom probe tomography (APT) results from two different specimen orientations (top-down and sideways) of a high oxygen ion conducting Samaria-doped-ceria/Scandia-stabilized-zirconia multilayer thin film solid oxide fuel cell electrolyte was compared with level-set method based field evaporation simulations for the same specimen orientations. This experiment-simulation comparison explains the dynamic specimen shape evolution and ion trajectory aberrations that can induce density artifacts in final reconstruction, leading to inaccurate estimation of interfacial intermixing. This study highlights the importance of comparing experimental results with field evaporation simulations when using APT to study oxide heterostructure interfaces.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2016

Single atom visibility in STEM optical depth sectioning

The continuing development of aberration correctors for the scanning transmission electron microscope (STEM) offers the possibility of locating single atoms in crystals in 3D via optical depth sectioning. The main factors that determine the feasibility of such an approach are visibility and dose requirements. In this paper, we show how Poisson's statistics can be quantitatively incorporated into STEM image simulations and demonstrate that the 3D location of single cerium atoms in wurtzite-type aluminum nitride is indeed feasible under large-angle illumination conditions with a relatively low dose. We also show that chromatic aberration does not presently represent a limitation provided a cold field emission source is used. Finally, these results suggest efforts into improved aberration corrector designs for larger illumination angles that offer significant potential for 3D structure determination of materials.

36 MATERIALS SCIENCE↗
DOE OSTI2019

Preparing for the Next Generation of EUV Lithography at the Center for X-ray Optics

The introduction of EUV lithography into high-volume semiconductor manufacturing this year represents a monumental milestone for EUV technology. After nearly 30 years of development, the EUV research community has overcome many of the key obstacles required to enable the long-awaited integration of EUV lithography into the lab. These obstacles have included: the development of a stable, high-powered EUV source to ensure adequate exposure tool reliability; controlling EUV mask defects and mask contamination; and the development of EUV resists with adequate sensitivity, resolution, and line width roughness to meet the tolerances required for high-volume manufacturing. As EUV moves into its second generation, there will be new challenges facing the community as it works to push EUV technology into the future. Smaller feature sizes will be achieved using higher numerical aperture optics, which are planned to have an anamorphic geometry (asymmetric magnification and numerical aperture between horizontal and vertical axes) to overcome 3D effects at the mask. This new geometry and its larger angle ranges make understanding mask absorber and multilayer effects all the more important. New methods for high-NA wavefront metrology need to be tested to ensure that these optical systems can be aligned to operate with minimal aberrations. Mask defects need to continue to be studied, and the inclusion of EUV pellicles in the roadmap requires that mask inspection and review systems adapt accordingly. Finally, new resists must be developed to support the increased resolution of feature sizes below 8 nm half pitch. The Center for X-ray Optics (CXRO) at Berkeley Lab has been a leader in EUV research for the past 25 years. Leveraging 13.5 nm EUV light from the Advanced Light Source synchrotron facility, CXRO is home to several EUV and soft X-ray (SXR) research tools that have provided important insights into EUV resists, masks, and coatings. The 0.3 NA Microfield exposure tool (MET) and Dose Calibration Tool (DCT) have played an instrumental role in the development of the current generation of high-resolution EUV resists. The Actinic Inspection Tool (AIT) and its successor, SHARP, have enabled aerial image analysis, providing key insights into mask defects, 3D mask effects, illumination, and aberrations. And the CXRO Reflectometer continues to be the industry standard in multilayer coating and EUV mask scattering metrology. To address the new challenges facing the next generation of EUV lithography, CXRO has upgraded its suite of EUV research tools. The 0.5 NA MET5 is a newly commissioned projection lithography tool that is capable of printing feature sizes down to 8 nm half pitch. A new radiation chemistry program is deploying several techniques aimed at dissecting the role of primary photoelectrons and secondary electrons in EUV resists. The SHARP microscope has been outfitted with anamorphic zone plate lenses that can emulate the geometry of next-generation EUV scanners, and the reflectometer has been applied to new scattering experiments for the purpose of understanding the 3D effects of EUV mask multilayers, as well as determining mask properties using scattering profiles. In parallel with these tools, the CXRO High-NA Wavefront Sensing Program is developing high-resolution wavefront sensors suitable for measuring aberrations at high NA. This article presents an overview of these programs and describes how they will address the primary challenges that face the EUV community as it moves to the next generation of EUV lithography.

47 OTHER INSTRUMENTATION↗
DOE OSTI2026

Control Algorithms for Dual-wavefront Sensor Single-conjugate Adaptive Optics

High-contrast imaging systems using active control with adaptive optics (AO) are often limited by non-common path (NCP) aberrations that are seen only at the final science image. AO systems employing focal-plane wavefront sensors (FP-WFSs) are able to simultaneously correct NCP aberrations and measure science images, but they typically require a second stage of control that adds system cost and complexity. We present control algorithms to augment AO systems with FP-WFSs within their existing control setup. We demonstrate inter-arm NCP aberration transfer can be mitigated through temporal filtering, present frequency- and time-domain validation of controller stability and performance, and discuss the optimality of the chosen controllers. This work will enable the development, testing, and installation of FP-WFS technologies for direct imaging of exoplanets.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2017

Persistent in vivo cytogenetic effects of radioiodine therapy: a 21-year follow-up study using multicolor FISH

Abstract Our previous studies demonstrated the cytogenetic effects in the peripheral blood lymphocytes of a 34-year-old male patient who received ablative radioactive 131iodine therapy (RIT) on two different occasions in 1992 and 1994. Assessment of RIT-induced chromosomal damage by the cytokinesis-blocked micronucleus assay (CBMN) showed the persistence of elevated micronucleus frequency in this patient for more than two decades since the first RIT. Subsequent cytogenetic analysis performed in 2012 revealed both stable and unstable aberrations, whose frequencies were higher than the baseline reported in the literature. Here, we report the findings of our recent cytogenetic analysis peformed in 2015 on this patient using the multicolor fluorescence in situ hybridization (mFISH) technique. Our results showed that both reciprocal and non-reciprocal translocations persisted at higher frequencies in the patient than those reported in 2012. Persistence of structural aberrations for more than two decades indicate that these aberrations might have originated from long-lived T-lymphocytes or hematopoietic stem cells. Our study suggests that the long-term persistence of chromosome translocations in circulating lymphocytes can be useful for monitoring the extent of RIT-induced chromosomal instability several years after exposure and for estimating the cumulative absorbed dose after multiple RITs for retrospective biodosimetry purposes. This is perhaps the first and longest follow-up study documenting the persistence of cytogenetic damage for 21 years after internal radiation exposure.

micronuclei↗
DOE OSTI2021

A transmission hologram for slitless spectrophotometry on a convergent telescope beam. 1. Focus and resolution

We report in this paper the test of a plane holographic optical element to be used as an aberration-corrected grating for a slitless spectrograph, inserted in a convergent telescope beam. Our long-term objective is the optimization of a specific hologram to switch the auxiliary telescope imager of the Vera Rubin Observatory into an accurate slitless spectrograph, dedicated to the atmospheric transmission measurement. We present and discuss here the promising results of tests performed with prototype holograms at the CTIO $0.9\,$m telescope during a run of 17 nights in 2017 May–June. After their on-sky geometrical characterization, the performances of the holograms as aberration-balanced dispersive optical elements have been established by analysing spectra obtained from spectrophotometric standard stars and narrow-band emitter planetary nebulae. Thanks to their additional optical function, our holographic disperser prototypes allow us to produce significantly better focused spectra within the full visible wavelength domain $[370,1050]\,$nm than a regular grating, which suffers from strong defocusing and aberrations when used in similar conditions. We show that the resolution of our slitless on-axis spectrograph equipped with the hologram approaches its theoretical performance. While estimating the benefits of a hologram for the spectrum resolution, the roadmap to produce a competitive holographic element for the Vera Rubin Observatory auxiliary telescope has been established.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2017

Image-based pupil plane characterization via a space-domain basis

© 2017 Society of Photo-Optical Instrumentation Engineers (SPIE). Aberration characterization plays a critical role in the development of any optical system. State-of-the-art lithography systems have the tightest aberration tolerances. We present an approach to image-based pupil plane amplitude and phase characterization using models built with a space-domain basis, in which aberration effects are separable. A polynomial model is constructed between the projections of the image intensity for chosen binary mask targets onto this basis and pupil amplitude or phase variation. This method separates model building and pupil characterization into two distinct steps, thus enabling rapid pupil characterization following data collection. The basis is related to both the transmission cross-coefficient function and the principal components of the image intensity. The pupil plane variation of a zone-plate lens from the Semiconductor High-NA Actinic Reticle Review Project (SHARP) at Lawrence Berkeley National Laboratory is examined using this method. Results are compared to pupil plane characterization using a previously proposed methodology where inverse solutions are obtained through an iterative process involving least-squares regression.

Levinson, Zac↗
DOE OSTI2024

Binary pseudo-random array standards for calibration of 3D optical surface profilers used for metrology with significantly curved x-ray optics

High-accuracy metrology is vitally important in manufacturing ultra-high-quality free-form mirrors designed to manipulate X-ray light with nanometer-scale wavelengths. The current capabilities and possibility for improvements in X-ray mirror manufacturing are limited by inherent imperfections of the integrated metrology tools. In the case of Fizeau interferometry, metrology tools are currently calibrated with super-polished flat test-standard/reference mirrors. This is acceptable for measuring slightly curved X-ray optics. However, for even moderately curved aspherical X-ray mirrors the flat-reference calibration is not sufficiently accurate and stitching Fizeau interferometer-based surface metrology is used to mitigate the problem. But still, the retrace and aberration errors, as well as the limited spatial resolution, described with the instrument transfer function (ITF), can be transferred into the optical surface topography of X-ray mirrors obtained in stitching metrology. For ITF calibration, we have developed an original technique, based on test standards structured as two-dimensional (2D) highly-randomized (HR) binary pseudo-random arrays (BPRAs). The technique employs the unique properties of the HR BPRA patterns in the spatial frequency domain., i.e. the inherent 2D power spectral density of the HR BPRA pattern has a deterministic white-noise-like character that allows direct determination of the ITF with uniform sensitivity over the entire spatial frequency range and field-of-view of an instrument. Here, we explore technological, metrological, and analytical aspects essential for calibration of the retrace and aberration errors of Fizeau interferometers using different types of tilted test samples, including a super-polished reference mirror for the re-trace calibration and the uniformly redundant array (URA) BPRA standards for the geometrical distortion (aberration) calibration. While the first method was previously demonstrated by researchers at DIAMOND Light Source, a method based on the URA BPRA is described and demonstrated here for the first time. We outline the design and fabrication process used in fabrication of URA BPRA test standards, and present the results of application of the URA BPRA standards demonstrating the high efficacy of our approach to geometrical distortion calibration of Fizeau interferometers. We also discuss the possible sources of unexpected peculiarities of the systematic errors, including an astigmatic character of the retrace error, observed with Fizeau interferometers at the Advanced Light Source X-Ray Optics Laboratory.

Munechika, Keiko↗
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↗