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At least 631 records · Page 35

The Correlation of Interphase Chromatin Structure with the Radiation-Induced Inter- and Intrachromosome Exchange Hotspots

To investigate the relationship between chromosome aberrations induced by radiation and chromatin folding, we reconstructed three dimensional structure of chromosome 3 and measured the physical distances between different regions of the chromosome. Previously, we have investigated the location of breaks involved in inter- and intrachromosomal type exchange events in human chromosome 3, using the multicolor banding in situ hybridization (mBAND) technique. In human epithelial cells exposed to both low- and high-LET radiations in vitro, we reported that intra-chromosome exchanges occurred preferentially between a break in the 3p21 and one in the 3q11 regions, and the breaks involving in inter-chromosome exchanges occurred in two regions towards the telomeres of the chromosome. Exchanges were also observed between a break in 3p21 and one in 3q26, but few exchanges were observed between breaks in 3q11 and 3q26, even though the two regions are located on the same arm of the chromosome. In this study, human epithelial cells were fixed at G1 phase and the interphase cells were hybridized using the XCyte3 mBAND kit from MetaSystems. The z-section images of chromosome 3 were captured with a Leica and an LSM 510 Meta laser scanning confocal microscopes. A total of 100 chromosomes were analyzed. The reconstruction of three dimensional structure of interphase chromosome 3 with six different colored regions was achieved using the Imaris software. The relative distance between different regions was measured as well. We further analyzed fragile sites on the chromosome that have been identified in various types of cancers. The data showed that, in majority of the cells, the regions containing 3p21 and 3q11 are colocalized in the center of the chromosome, whereas, the regions towards the telomeres of the chromosome are either physically wrapping outside the chromosome center or with arms sticking out. Our results demonstrated that the distribution of breaks involved in radiation-induced inter and intra-chromosome aberrations depends upon both the location of fragile sites and the folding of chromatins.

Zhang, Ye↗

Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

Tumor formation in humans or animals is a multi-step process. 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. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

Sunagawa, Mayumi↗

Stitching of near-nulled subaperture measurements

A metrology system for measuring aspheric test objects by subaperture stitching. A wavefront-measuring gauge having a limited capture range of wavefront shapes collects partially overlapping subaperture measurements over the test object. A variable optical aberrator reshapes the measurement wavefront with between a limited number of the measurements to maintain the measurement wavefront within the capture range of the wavefront-measuring gauge. Various error compensators are incorporated into a stitching operation to manage residual errors associated with the use of the variable optical aberrator.

Murphy, Paul↗

Wavefront Sensing for WFIRST with a Linear Optical Model

In this paper we develop methods to use a linear optical model to capture the field dependence of wavefront aberrations in a nonlinear optimization-based phase retrieval algorithm for image-based wavefront sensing. The linear optical model is generated from a ray trace model of the system and allows the system state to be described in terms of mechanical alignment parameters rather than wavefront coefficients. This approach allows joint optimization over images taken at different field points and does not require separate convergence of phase retrieval at individual field points. Because the algorithm exploits field diversity, multiple defocused images per field point are not required for robustness. Furthermore, because it is possible to simultaneously fit images of many stars over the field, it is not necessary to use a fixed defocus to achieve adequate signal-to-noise ratio despite having images with high dynamic range. This allows high performance wavefront sensing using in-focus science data. We applied this technique in a simulation model based on the Wide Field Infrared Survey Telescope (WFIRST) Intermediate Design Reference Mission (IDRM) imager using a linear optical model with 25 field points. We demonstrate sub-thousandth-wave wavefront sensing accuracy in the presence of noise and moderate undersampling for both monochromatic and polychromatic images using 25 high-SNR target stars. Using these high-quality wavefront sensing results, we are able to generate upsampled point-spread functions (PSFs) and use them to determine PSF ellipticity to high accuracy in order to reduce the systematic impact of aberrations on the accuracy of galactic ellipticity determination for weak-lensing science.

Jurling, Alden S.↗

Discrete fourier transform (DFT) analysis for applications using iterative transform methods

According to various embodiments, a method is provided for determining aberration data for an optical system. The method comprises collecting a data signal, and generating a pre-transformation algorithm. The data is pre-transformed by multiplying the data with the pre-transformation algorithm. A discrete Fourier transform of the pre-transformed data is performed in an iterative loop. The method further comprises back-transforming the data to generate aberration data.

Dean, Bruce H.↗

Karyotyping of Transformed Human Epithelial Cells from Exposures of Heavy Ions

It is most likely that the untreated transformed single clone (clone #2) cell undergoes unequal segregation of chromosome in two daughter cell that result in 94 chromosome during mitosis, particularly in anaphase stage. Chromosome aberration observed. I. Breakage of part of chromosome 7. II. One additional number of chromosome 8 instead of the total chromosome can only be explained by early abnormal cell division. III. Complete lost of chromosome and translocation and fusion of chromosome 3 and X-chromosome. IV. Our result for translocation and fusion of chromosome 3 and X- Chromosome is conformed by mBAND pattern. There is no different between the transformed parental cell and the single cloned transformed cell. Both harbor the chromosome 5 and 16 translocation and both harbor has the trisomy chromosome 20. Transformed cells may have the number of chromosomes greater or less than 46. Doubling of chromosome numbers is a signature of tumor. Chromosomal aberration was observed on HBEC-3kt non-irradiated-soft agar (Clone #2) sample, and indication of chromosome instability in the tumor development process.

Yeshitla, Samrawit↗

Estimation of the Dose and Dose Rate Effectiveness Factor

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Chappell, L.↗

Overview of NASARTI (NASA Radiation Track Image) Program: Highlights of the Model Improvement and the New Results

This presentation summarizes several years of research done by the co-authors developing the NASARTI (NASA Radiation Track Image) program and supporting it with scientific data. The goal of the program is to support NASA mission to achieve a safe space travel for humans despite the perils of space radiation. The program focuses on selected topics in radiation biology that were deemed important throughout this period of time, both for the NASA human space flight program and to academic radiation research. Besides scientific support to develop strategies protecting humans against an exposure to deep space radiation during space missions, and understanding health effects from space radiation on astronauts, other important ramifications of the ionizing radiation were studied with the applicability to greater human needs: understanding the origins of cancer, the impact on human genome, and the application of computer technology to biological research addressing the health of general population. The models under NASARTI project include: the general properties of ionizing radiation, such as particular track structure, the effects of radiation on human DNA, visualization and the statistical properties of DSBs (DNA double-strand breaks), DNA damage and repair pathways models and cell phenotypes, chromosomal aberrations, microscopy data analysis and the application to human tissue damage and cancer models. The development of the GUI and the interactive website, as deliverables to NASA operations teams and tools for a broader research community, is discussed. Most recent findings in the area of chromosomal aberrations and the application of the stochastic track structure are also presented.

Ponomarev, Artem L.↗

Karyotyping of Chromosomes in Human Bronchial Epithelial Cells Transformed by High Energy Fe Ions

Lung cancer induced from exposures to space radiation is one of the most significant health risks for long-term space travels. Evidences show that low- and high- Linear energy transfer (LET)-induced transformation of normal human bronchial epithelial cells (HBEC) that are immortalized through the expression of Cdk4 and hTERT. The cells were exposed to gamma rays and high-energy Fe ions for the selection of transformed clones. Transformed HBEC are identified and analyzed chromosome aberrations (i.e. genomic instability) using the multi-color fluorescent in situ hybridization (mFISH), as well as the multi-banding in situ hybridization (mBAND) techniques. Our results show chromosomal translocations between different chromosomes and several of the breaks occurred in the q-arm of chromosome 3. We also identified copy number variations between the transformed and the parental HBEC regardless of the exposure conditions. We observed chromosomal aberrations in the lowand high-LET radiation-induced transformed clones and they are imperfectly different from clones obtain in spontaneous soft agar growth.

Yeshitla, Samrawit↗

Stability Error Budget for an Aggressive Coronagraph on a 3.8 m Telescope

We evaluate in detail the stability requirements for a band-limited coronagraph with an inner working angle as small as 2 lambda/D coupled to an off-axis, 3.8-m diameter telescope. We have updated our methodologies since presenting a stability error budget for the Terrestrial Planet Finder Coronagraph mission that worked at 4 lambda/D and employed an 8th-order mask to reduce aberration sensitives. In the previous work, we determined the tolerances relative to the total light leaking through the coronagraph. Now, we separate the light into a radial component, which is readily separable from a planet signal, and an azimuthal component, which is easily confused with a planet signal. In the current study, throughput considerations require a 4th-order coronagraph. This, combined with the more aggressive working angle, places extraordinarily tight requirements on wavefront stability and opto-mechanical stability. We find that the requirements are driven mainly by coma that leaks around the coronagraph mask and mimics the localized signal of a planet, and pointing errors that scatter light into the background, decreasing SNR. We also show how the requirements would be relaxed if a low-order aberration detection system could be employed.

error budget↗

Proximity Within Interphase Chromosome Contributes to the Breakpoint Distribution in Radiation-Induced Intrachromosomal Exchanges

Previously, we reported that breaks involved in chromosome aberrations were clustered in several regions of chromosome3 in human mammary epithelial cells after exposures to either low-or high-LET radiation. In particular, breaks in certain regions of the chromosome tended to rejoin with each other to form an intrachromosome exchange event. This study tests the hypothesis that proximity within a single chromosome in interphase cell nuclei contributes to the distribution of radiation-induced chromosome breaks. Chromosome 3 in G1 human mammary epithelial cells was hybridized with the multicolor banding in situ hybridization (mBAND) probes that distinguish the chromosome in six differently colored regions, and the location of these regions was measured with a laser confocal microscope. Results of the study indicated that, on a multi-mega base pair scale of the DNA, the arrangement of chromatin was non-random. Both telomere regions tended to be located towards the exterior of the chromosome domain, whereas the centromere region towards the interior. In addition, the interior of the chromosome domain was preferentially occupied by the p-arm of the chromatin, which is consistent with our previous finding of intrachromosome exchanges involving breaks on the p-arm and in the centromere region of chromosome3. Other factors, such as the fragile sites in the 3p21 band and gene regulation, may also contribute to the breakpoint distribution in radiation-induced chromosome aberrations. Further investigations suggest that the 3D chromosome folding is cell type and culture condition dependent.

Zhang, Ye↗

Presentation Annotated

This Report is not the latest word on an old idea but the first word on a new one. The new idea reverses the old one, the axiom that the best primary objective for an astronomical telescope exhibits the least chromatic aberration. That axiomatic distinction goes back to a young Isaac Newton who knew from experiments with prisms and mirrors in the 1660's that magnification with a reflection primary was completely free of the dispersion he saw with refraction. The superiority of reflection primary objectives for eyeball or photographic viewing is now considered obvious. It was this piece of wisdom on achromatic primary objectives that led to the dominance of the parabolic mirror as the means to collect star light. Newton was aware of the problem when he introduced his telescope to the scientific world in 1670.This Report is not the latest word on an old idea but the first word on a new one. The new idea reverses the old one, the axiom that the best primary objective for an astronomical telescope exhibits the least chromatic aberration. That axiomatic distinction goes back to a young Isaac Newton who knew from experiments with prisms and mirrors in the 1660's that magnification with a reflection primary was completely free of the dispersion he saw with refraction. The superiority of reflection primary objectives for eyeball or photographic viewing is now considered obvious. Actually, Newton's design innovation was in a secondary mirror, a plane mirror far more easily fabricated than Gregory's embodiment of 1663 which required two curved mirrors.

Astronomical telescope↗

An optical vortex coronagraph

In this manuscript, I will discuss the aberration sensitivity of an optical vortex coronagraph and the key advantages it may hold over other coronagraph architectures. I will also provide numerical simulations demonstrating high contrast imaging in the presence of low-order static aberrations.

Palacios, David M.↗

Interferometric Characterization of Keck Segment Edge Errors

The Keck telescope segments were manufactured by stressed mirror polishing of large circular pieces of Zerodur that were then cut into hexagons and finished by Ion Beam Figuring (IBF). It has long been believed that this process results in segments with little or no edge effects. As a result, this same general approach is planned for segment manufacturing for the Thirty Meter Telescope (TMT) and the European Extremely Large Telescope (E-ELT). However, recent measurements at the Keck telescope suggest that at least some of the Keck segments have significant aberrations within 60 mm of the edge. These aberrations impact the telescope phasing and the overall telescope image quality. We present interferometric measurements of multiple Keck segments, characterizing the surface errors near the edges over spatial periods from 5 cm down to 1 mm. We show that the largest phasing and image quality effects are due to plateaus of unremoved material, left behind after IBF as a result of obscuration by the IBF supports. Apart from these plateaus, the edge quality is relatively good, though not as good as in the segment interiors. Some residual phasing and image quality effects remain, and these are not currently understood.

Martinek, Stephen J.↗

First Generation Parabolic Deformable Mirror for the ExoSpec Project

The Exoplanet Spectroscopy (ExoSpec) project links four different tasks at Goddard Space Flight Center (GSFC) to facilitate efficient imaging and characterization of exoplanets. One of the tasks is the development of parabolic deformable mirrors to improve on the current state-of-the-art wavefront sensing and control implementations that are baselined to have two high-actuator count flat deformable mirrors (DMs). The current baseline has two DMs at a considerable separation distance to effectively control both amplitude and phase aberrations. This significant separation poses packaging challenges to the direct imaging missions. We can mitigate this issue by making the off-axis imaging elements in the optical train controllable. Besides addressing the packaging challenges, this technique reduces the risk of having the entire coronagraph instrument’s performance depend on two high-actuator count DMs. Simulations show that making imaging elements deformable increases the overall controllable bandwidth - it would be possible to control wavefront aberrations up to 35% bandwidth over a 5 - 12 λ/D. GSFC has worked with a commercial vendor to produce a first-generation parabolic DM and built a testbed in an environmentally controlled cleanroom to experimentally demonstrate the use of a parabolic DM in a coronagraph instrument. This versatile testbed is designed to test different DM architectures and various low-order wavefront schemes. This provides us with a basis for comparison with different DM configurations —1) flat DM, 2) parabolic DMs, and 3) flat DM and parabolic DMs. In this paper, we will provide an update on our parabolic DM work.

Deformable Mirror↗

A Bunch Compression Method for Free Electron Lasers that Avoids Parasitic Compressions

Virtually all existing high energy (>few MeV) linac-driven FELs compress the electron bunch length though the use of off-crest acceleration on the rising side of the RF waveform followed by transport through a magnetic chicane. This approach has at least three flaws: 1) it is difficult to correct aberrations--particularly RF curvature, 2) rising side acceleration exacerbates space charge-induced distortion of the longitudinal phase space, and 3) all achromatic "negative compaction" compressors create parasitic compression during the final compression process, increasing the CSR-induced emittance growth. One can avoid these deficiencies by using acceleration on the falling side of the RF waveform and a compressor with M 56 >0. This approach offers multiple advantages: 1) It is readily achieved in beam lines supporting simple schemes for aberration compensation, 2) Longitudinal space charge (LSC)-induced phase space distortion tends, on the falling side of the RF waveform, to enhance the chirp, and 3) Compressors with M 56 >0 can be configured to avoid spurious over-compression. We will discuss this bunch compression scheme in detail and give results of a successful beam test in April 2012 using the JLab UV Demo FEL

43 PARTICLE ACCELERATORS↗

Toward direct spatial and intensity characterization of ultra-high-intensity laser pulses using ponderomotive scattering of free electrons

Spatial distributions of electrons ionized and scattered from ultra-low-pressure gases are proposed and experimentally demonstrated as a method to directly measure the intensity of an ultra-high-intensity laser pulse. Analytic models relating the peak scattered electron energy to the peak laser intensity are derived and compared to paraxial Runge–Kutta simulations highlighting two models suitable for describing electrons scattered from weakly paraxial beams (f#>5) for intensities in the range of 1018−1021 W cm−2. Scattering energies are shown to be dependent on gas species, emphasizing the need for specific gases for given intensity ranges. Direct measurements of the laser intensity at full power of two laser systems are demonstrated, both showing a good agreement between indirect methods of intensity measurement and the proposed method. One experiment exhibited the role of spatial aberrations in the scattered electron distribution, motivating a qualitative study on the effect. We propose the use of convolutional neural networks as a method for extracting quantitative information on the spatial structure of the laser at full power. We believe the presented technique to be a powerful tool that can be immediately implemented in many high-power laser facilities worldwide.

47 OTHER INSTRUMENTATION↗

On the Localized Nature of the Structural Transformations of Li2MnO 3 Following Electrochemical Cycling

Although the Li-excess layered-oxide Li2MnO3 has a high theoretical capacity, structural transformations within the oxide during electrochemical cycling lead to relatively low experimental capacities, hindering its use in practical applications. Here, aberration-corrected scanning transmission electron microscopy/electron energy loss spectroscopy and high-resolution X-ray diffraction are used to characterize the oxide following electrochemical cycling. Microscopy reveals the coexistence of regions with local monoclinic, spinel, and rock-salt symmetries, indicating localized and inhomogeneous structural evolutions. Crystal structure transformations are observed both at the particle surface and in the bulk. At the surface, these transformed regions resemble spinel Mn3O4 or rock-salt MnO, consistent with oxygen loss. In the bulk, the regions resemble defect spinels, such as the layered-spinel LixMn4/3O4, which suggest a partial phase transformation consistent with oxygen retention. Both microscopy and diffraction data of the cycled sample indicate areas of pristine Li2MnO3; the presence of such areas, in close proximity to LixMn4/3O4 areas, suggests that the layered to spinel structure transformation is partially reversible. Spinel, disordered rock salt, and pristine areas are also observed in Li2MnO3 samples intentionally damaged by electron beam irradiation. This observation indicates that the dynamic processes resulting in phase transformations can be studied for a variety of oxide systems by a judicious selection of irradiation conditions.

aberration-corrected scanning transmission electro↗