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At least 235 records · Page 13

M-FISH Analysis of Chromosome Aberrations in Human Fibroblast Cells After In Vitro Exposure to Low- and High-LET Radiation

The recently commercialized multiplex fluorescence in situ hybridization (m-FISH) technique, which allows human chromosomes to be painted in 24 different colors, was used to analyze chromosome aberrations in diploid human fibroblast cells after in vitro radiation exposure. Confluent flasks of a normal primary fibroblast cell line (AG 1522) were irradiated at high dose rates with either gamma rays or 200 MeV/nucleon Fe ions (LET = 440 keV/micron), incubated at 37 C for 24 hours after exposure, and subsequently subcultured. A chemically induced premature chromosome condensation technique was used to collect chromosome samples 32 hours after subculture. Results showed that the fraction of exchanges which were identified as complex, i.e. involving misrejoining of three or more DSB, were higher in the Fe-irradiated samples compared with the gamma-irradiated samples, as has been shown previously using FISH with one or two painted chromosomes . The ratios of complex/simple type exchanges were similar for samples irradiated with 0.7 Gy and 3 Gy of Fe ions, although exchanges involving five or more breaks were found only in 3 Gy irradiated samples. The fraction of incomplete exchanges was also higher in Fe- than gamma-irradiated samples. Data on the distribution of individual chromosome involvement in interchromosomal exchanges will be presented.

Wu, Honglu↗

Analysis of Terminal Deletions using a Generalized Time-Dependent Model of Radiation-Induced Formation of Chromosomal Aberrations

We have developed a model that can simulate different types of radiation induced chromosomal aberrations (CA's) and can provide predictions on the frequency and size of chromosomes with terminal deletions. Chromosomes with terminal deletions lack telomeres and this can elicit sister chromatid unions and the prolonged breakage/fusion/bridge (B/F/B) cycles that have been observed in mammalian tumors. The loss of a single telomere has been shown to cause extensive genomic instability through the B/F/B cycle process. Our model uses a stochastic process of DNA broken end joining, in which a realistic spectrum of CA's is created from improperly joined DNA free ends formed by DNA double strand breaks (DSBs). The distribution of the DNA free ends is given by a mechanistic model that takes into account the chromatin structure and track structure for high-LET radiation. The model allows for DSB clustering from high-LET radiation and simulates the formation of CA's in stages that correspond to the actual time after radiation exposure. The time scale for CA formation is derived from experimental data on DSB repair kinetics. At any given time a nucleus may have intact chromosomes, CA's, and/or unrepaired fragments, some of which are defined as terminal deletions, if they are capped by one telomere. The model produces a spectrum of terminal deletions with their corresponding probabilities and size distributions for different heavy ions exposures for the first division after exposure. This data provides valuable information because there is limited experimental data available in the literature on the on the actual size of terminal deletions. We compare our model output to the available experimental data and make a reasonable extrapolation on the number of chromosomes lacking telomeres in human lymphocytes exposed to heavy ions. This model generates data which may lead to predictions on the rate of genomic instability in cells after exposure to high charge and energy nuclei affecting astronauts during space missions.

Ponomarev, Artem L.↗

Correcting for Beam Aberrations in a Beam-Waveguide Antenna

A method for correcting the aim of a beam-waveguide microwave antenna compensates for the beam aberration that occurs during radio tracking of a target that has a component of velocity transverse to the line of sight from the tracking station. The method was devised primarily for use in tracking of distant target spacecraft by large terrestrial beam-waveguide antennas of NASA's Deep Space Network (DSN). The method should also be adaptable to tracking, by other beam-waveguide antennas, of targets that move with large transverse velocities at large distances from the antennas.

Franco, Manuel↗

The Vector Vortex Coronagraph: Sensitivity to Low-Order Aberrations, Central Obscuration, Chromaticism, and Polarization

The Vector Vortex Coronagraph is a phase-based coronagraph, one of the most efficient in terms of inner working angle, throughput, discovery space, contrast, and simplicity. Using liquid-crystal polymer technology, this new coronagraph has recently been the subject of lab demonstrations in the near-infrared, visible and was also used on sky at the Palomar observatory in the H and K bands (1.65 and 2.2 micrometers, respectively) to image the brown dwarf companion to HR 7672, and the three extasolar planets around HR 8799. However, despite these recent successes, the Vector Vortex Coronagraph is, as are most coronagraphs, sensitive to the central obscuration and secondary support structures, low-order aberrations (tip-tilt, focus, etc), bandwidth (chromaticism), and polarization when image-plane wavefront sensing is performed. Here, we consider in detail these sensitivities as a function of the topological charge of the vortex and design properties inherent to the manufacturing technology, and show that in practice all of them can be mitigated to meet specific needs.

large ground-based telescopes↗

Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

Wu, Honglu↗

Pupil Aberrations in the LISA Transceiver Design

The LISA mission is a space-based gravitational wave detector consisting of three spacecraft with two transceiver telescopes per spacecraft. In addition to tight wavefront error control as expected for an interferometric system, there are tight pupil imaging and optical path length specifications. We use concepts gleaned from pupil aberration theory to understand these latter two constraints and show how these concepts led to a successful design for the LISA transceiver.

J. P. Lehan↗

The LUVOIR Extreme Coronagraph for Living Planetary Systems (ECLIPS) II. Performance Evaluation, Aberration Sensitivity Analysis and Exoplanet Detection Simulations

Future space missions such as the Large UV-Optical-Infrared Surveyor (LUVOIR) and the Habitable Exoplanet Observatory (HabEx) require coronagraphs with active wavefront control to suppress starlight to discover and characterize habitable exoplanets. The Extreme Coronagraph for Living Planetary Systems (ECLIPS) is the coronagraph instrument on the LUVOIR Surveyor mission concept, an 8–15m segmented telescope. ECLIPS is split into three channels: UV (200 to 400 nm), optical (400 nm to 850 nm), and NIR (850 nm to 2.0 microns), with each channel equipped with two deformable mirrors for wavefront control, a suite of coronagraph masks, a low-order/out-of-band wavefront sensor, and separate science imagers and spectrographs. The Apodized Pupil Lyot Coronagraph (APLC) and the Vector Vortex Coronagraph (VVC) are the baselined mask technologies for ECLIPS to enable the required 10 -10 contrast for observations in the habitable zones of nearby stars. Their performance depends on active wavefront sensing and control, as well as metrology subsystems to compensate for aberrations induced by segment errors (piston and tip/tilt, among others), secondary mirror misalignment, and global low-order wavefront errors. Here we present the latest results of the simulation of these effects for the two technologies and discuss the achieved contrast for exoplanet detection and characterization after closed-loop wavefront estimation and control algorithms have been applied. Finally, we show simulated observations using high-fidelity spatial and spectral input models of complete planetary systems generated with the Haystacks code framework.

Roser Juanola-Parramon↗

Modeling Space-Radiation Induced Chromosome Aberrations

Exposure to ionizing radiation is identified as one of the main hazards of space flight. Galactic cosmic rays (GCRs) are composed of energetic protons (87%), helium nuclei (12%) and high-charge and energy (HZE) ions. At the cellular scale, HZE ions have a pattern of energy deposition that depends on the ion linear energy transfer (LET), with high LET ions favoring the formation of complex DNA damages that induce chromosome aberrations (CAs). Understanding how physical (e.g., ion type and energy) and biological (e.g., cell type) parameters impact CA formation is required to assess space radiation risks such as carcinogenesis. The Monte Carlo tool RITCARD/RITRACKS [1,2] developed by NASA allows simulation of the transport of HZE ions and subsequent energy deposition at the cellular scale and models the creation of DNA double strand breaks (DSBs), DNA repair and formation of CAs. We used this radiation transport code to further understand how radiation quality and cell size affects CA formation.

Floriane Poignant↗

Monte Carlo Study of the Formation of Chromosome Aberrations by Direct Ion Traversal vs. Delta-Electrons

Space radiation constitutes a major risk for the safety of space travel. Galactic Cosmic Rays (GCRs) are made of high energy protons (87%), high energy helium ions (12%) and high-charge and energy (HZE) ions [1]. At a cellular scale, HZE ions display a characteristic pattern of energy deposition, known as the ion track, that correlates with the ion linear energy transfer (LET). These energy deposition events (ionizations/excitations) create DNA breaks that, if misrepaired, lead to the formation of chromosome aberrations (CAs). Compared to low-LET terrestrial radiations (X-rays and γ-rays), high LET ions are known to create complex, clustered DNA breaks that are particularly efficient at forming CAs. Indeed, ion tracks are usually described as a dense ionization core, where clustered breaks are formed, and a penumbra, made of low-LET δ-electrons that have sufficient energy to travel across many cells and induce breaks that are more homogeneously distributed. In this work, we investigated the formation of CAs, and separated them into two contributions (direct ion traversal of the nucleus vs.δ-electrons), to elucidate to which extent δ-electrons contribute to CA formation.

Floriane Poignant↗

Aberration-corrected X-ray spectrum imaging and Fresnel contrast to differentiate nanoclusters and cavities in helium-irradiated alloy 14YWT

Helium accumulation negatively impacts structural materials used in neutron-irradiated environments, such as fission and fusion reactors. Next-generation fission and fusion reactors will require structural materials, such as steels, resistant to large neutron doses yet see service temperatures in the range most affected by helium embrittlement. Previous work has indicated the difficulty of experimentally differentiating nanometer-sized helium bubbles from the Ti-Y-O rich nanoclustsers (NCs) in radiation-tolerant nanostructured ferritic alloys (NFAs). Because the NCs are expected to sequester helium away from grain boundaries and reduce embrittlement, experimental methods to study simultaneously the NC and bubble populations are needed. In this study, aberration-corrected scanning transmission electron microscopy (STEM) results combining high-collection-efficiency X-ray spectrum images (SIs), multivariate statistical analysis (MVSA), and Fresnel-contrast bright-field STEM imaging have been used for such a purpose. Results indicate that Fresnel-contrast imaging, with careful attention to TEM-STEM reciprocity, differentiates bubbles from NCs, and MVSA of X-ray SIs unambiguously identifies NCs. Therefore, combined Fresnel-contrast STEM and X-ray SI is an effective STEM-based method to characterize helium-bearing NFAs.

Miller, Michael K↗

Device and method for creating Gaussian aberration-corrected electron beams

Electron beam phase gratings have phase profiles that produce a diffracted beam having a Gaussian or other selected intensity profile. Phase profiles can also be selected to correct or compensate electron lens aberrations. Typically, a low diffraction order produces a suitable phase profile, and other orders are discarded.

43 PARTICLE ACCELERATORS↗

Numerical Studies of Optimization and Aberration Correction Methods for the Preliminary Demonstration of the Parametric Ionization Cooling (PIC) Principle in the Twin Helix Muon Cooling Channel

Muon colliders have been proposed for the next generation of particle accelerators that study high-energy physics at the energy and intensity frontiers. In this paper we study a possible implementation of muon ionization cooling, Parametric-resonance Ionization Cooling (PIC), in the twin helix channel. The resonant cooling method of PIC offers the potential to reduce emittance beyond that achievable with ionization cooling with ordinary magnetic focusing. We examine optimization of a variety of parameters, study the nonlinear dynamics in the twin helix channel and consider possible methods of aberration correction.

43 PARTICLE ACCELERATORS↗

Chromosome aberrations and cellular premature senescence as radiation-induced sub-lethal effects: Implications for laser-driven charged-particle radiotherapy

The use of charged particles significantly reduces the dose absorbed by normal cells due to the inverse dose-depth deposition profile. This is the physical pillar justifying hadrontherapy as the eligible treatment for deepseated tumours. However, a non-negligible amount of radiation is nevertheless absorbed in correspondence with the plateau region of the Bragg curve, which may result in the induction of sub-lethal effects. Very little experimental data exist on the induction of such effects. Moreover, reliable follow-up data on such adverse effects in hadrontherapy patients are limited since this type of treatment has been adopted relatively recently. A fortiori, the dependence of sub-lethal effects on unprecedented factors, such as the exceedingly high dose rates and/or the pulsed nature of beams originated by laser interaction with target materials, is unknown. This warrants investigation prior to a therapeutic use of such beams.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Aberrated electron probes for magnetic spectroscopy with atomic resolution: Theory and practical aspects

It was recently proposed that electron magnetic circular dichroism (EMCD) can be measured in scanning transmission electron microscopy (STEM) with atomic resolution by tuning the phase distribution of a electron beam. Here, we describe the theoretical and practical aspects for the detection of out-of-plane and in-plane magnetization utilizing atomic size electron probes. Here we present the calculated optimized astigmatic probes and discuss how to achieve them experimentally.

47 OTHER INSTRUMENTATION↗