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At least 361 records · Page 20

Radiation-induced chromosomal instability in BALB/c and C57BL/6 mice: the difference is as clear as black and white

Genomic instability has been proposed to be the earliest step in radiation-induced tumorigenesis. It follows from this hypothesis that individuals highly susceptible to induction of tumors by radiation should exhibit enhanced radiation-induced instability. BALB/c white mice are considerably more sensitive to radiation-induced mammary cancer than C57BL/6 black mice. In this study, primary mammary epithelial cell cultures from these two strains were examined for the "delayed" appearance of chromosomal aberrations after exposure to 137Cs gamma radiation, as a measure of radiation-induced genomic instability. As expected, actively dividing cultures from both strains showed a rapid decline of initial asymmetrical aberrations with time postirradiation. However, after 16 population doublings, cells from BALB/c mice exhibited a marked increase in the frequency of chromatid-type breaks and gaps which remained elevated throughout the time course of the experiment (28 doublings). No such effect was observed for the cells of C57BL/6 mice; after the rapid clearance of initial aberrations, the frequency of chromatid-type aberrations in the irradiated population remained at or near those of nonirradiated controls. These results demonstrate a correlation between the latent expression of chromosomal damage in vitro and susceptibility for mammary tumors, and provide further support for the central role of radiation-induced instability in the process of tumorigenesis.

NASA Discipline Radiation Health↗

Hepatic leukemia factor promotes resistance to cell death: Implications for therapeutics and chronotherapy

Physiological variation related to circadian rhythms and aberrant gene expression patterns are believed to modulate therapeutic efficacy, but the precise molecular determinants remain unclear. Here we examine the regulation of cell death by hepatic leukemia factor (HLF), which is an output regulator of circadian rhythms and is aberrantly expressed in human cancers, using an ectopic expression strategy in JB6 mouse epidermal cells and human keratinocytes. Ectopic HLF expression inhibited cell death in both JB6 cells and human keratinocytes, as induced by serum-starvation, tumor necrosis factor alpha and ionizing radiation. Microarray analysis indicates that HLF regulates a complex multi-gene transcriptional program encompassing upregulation of anti-apoptotic genes, downregulation of pro-apoptotic genes, and many additional changes that are consistent with an anti-death program. Collectively, our results demonstrate that ectopic expression of HLF, an established transcription factor that cycles with circadian rhythms, can recapitulate many features associated with circadian-dependent physiological variation. - Highlights: ► Circadian-dependent physiological variation impacts therapeutic efficacy. ► Hepatic leukemia factor inhibits cell death and is a candidate circadian factor. ► Hepatic leukemia factor anti-death program is conserved in murine and human cells. ► Transcriptomics indicates the anti-death program results from a systems response.

60 APPLIED LIFE SCIENCES↗

Adaptive optical correction for in vivo two-photon fluorescence microscopy with neural fields

Adaptive optics restore ideal imaging performance in complex samples by measuring and correcting optical aberrations but often require custom-built microscopes with carefully aligned wavefront sensing/shaping devices and can be susceptible to sample motion. Here we describe NeAT, a computational framework using neural fields for adaptive optics two-photon fluorescence microscopy. NeAT estimates wavefront aberration and recovers sample structure from a 3D image stack without requiring external datasets for training. Incorporating motion correction in learning and correcting conjugation errors commonly found in commercial microscopes, NeAT is designed for deployment in biological laboratories for in vivo imaging. We validate NeAT’s performance using a custom-built microscope with a wavefront sensor under varying signal-to-noise ratios, aberration and motion conditions. With a commercial microscope, we demonstrate real-time aberration correction for in vivo morphological and functional imaging in the living mouse brain, with NeAT improving the signal and accuracy of glutamate and calcium imaging of synapses and neurons.

Kang, Iksung↗

Extreme ultraviolet microscope characterization using photomask surface roughness

We demonstrate a method for characterizing the field-dependent aberrations of a full-field synchrotron-based extreme ultraviolet microscope. The statistical uniformity of the inherent, atomic-scale roughness of readily-available photomask blanks enables a self-calibrating computational procedure using images acquired under standard operation. We characterize the aberrations across a 30-um field-of-view, demonstrating a minimum aberration magnitude of smaller than λ/21 rms averaged over the center 5-um area, with a measurement accuracy better than λ/180 rms. The measured field variation of aberrations is consistent with system geometry and agrees with prior characterizations of the same system. In certain cases, it may be possible to additionally recover the illumination wavefront from the same images. Our method is general and is easily applied to coherent imaging systems with steerable illumination without requiring invasive hardware or custom test objects; hence, it provides substantial benefits when characterizing microscopes and high-resolution imaging systems in situ.

47 OTHER INSTRUMENTATION↗

Mutations in the Pectin Methyltransferase QUASIMODO2 Influence Cellulose Biosynthesis and Wall Integrity in Arabidopsis

Abstract Pectins are abundant in the cell walls of dicotyledonous plants, but how they interact with other wall polymers and influence wall integrity and cell growth has remained mysterious. Here, we verified that QUASIMODO2 (QUA2) is a pectin methyltransferase and determined that QUA2 is required for normal pectin biosynthesis. To gain further insight into how pectin affects wall assembly and integrity maintenance, we investigated cellulose biosynthesis, cellulose organization, cortical microtubules, and wall integrity signaling in two mutant alleles of Arabidopsis (Arabidopsis thaliana) QUA2, qua2 and tsd2. In both mutants, crystalline cellulose content is reduced, cellulose synthase particles move more slowly, and cellulose organization is aberrant. NMR analysis shows higher mobility of cellulose and matrix polysaccharides in the mutants. Microtubules in mutant hypocotyls have aberrant organization and depolymerize more readily upon treatment with oryzalin or external force. The expression of genes related to wall integrity, wall biosynthesis, and microtubule stability is dysregulated in both mutants. These data provide insights into how homogalacturonan is methylesterified upon its synthesis, the mechanisms by which pectin functionally interacts with cellulose, and how these interactions are translated into intracellular regulation to maintain the structural integrity of the cell wall during plant growth and development.

Biochemistry & Molecular Biology↗

Achieving sub-0.5-angstrom–resolution ptychography in an uncorrected electron microscope

Subangstrom resolution has long been limited to aberration-corrected electron microscopy, where it is a powerful tool for understanding the atomic structure and properties of matter. Here, we demonstrate electron ptychography in an uncorrected scanning transmission electron microscope (STEM) with deep subangstrom spatial resolution down to 0.44 angstroms, exceeding the conventional resolution of aberration-corrected tools and rivaling their highest ptychographic resolutions​. Our approach, which we demonstrate on twisted two-dimensional materials in a widely available commercial microscope, far surpasses prior ptychographic resolutions (1 to 5 angstroms) of uncorrected STEMs. We further show how geometric aberrations can create optimized, structured beams for dose-efficient electron ptychography. Our results demonstrate that expensive aberration correctors are no longer required for deep subangstrom resolution.

36 MATERIALS SCIENCE↗

Modal focal adaptive optics for Bessel-focus two-photon fluorescence microscopy

Adaptive optics (AO) improves the spatial resolution of microscopy by correcting optical aberrations. While its application has been well established in microscopy modalities utilizing a circular pupil, its adaptation to systems with non-circular pupils, such as Bessel-focus two-photon fluorescence microscopy (2PFM) with an annular pupil, remains relatively uncharted. Herein, we present a modal focal AO (MFAO) method for Bessel-focus 2PFM. Measuring and correcting aberration using a spatial light modulator placed in conjugation with the focal plane of the microscope objective, MFAO employs Zernike annular polynomials — a first in AO implementation — to achieve performance on par with a previous zonal AO method, but with a notably simplified optical configuration. We validated the performance of MFAO in correcting artificial and sample-induced aberrations, as well as in in vivo imaging of zebrafish larvae and mouse brains. By expanding the application of modal AO to annular pupils as well as aberration measurement and correction to a wavefront modulator at the objective focal plane, MFAO represents a notable advancement in the implementation of AO in microscopy.

47 OTHER INSTRUMENTATION↗

PSF–NET: A Nonparametric Point-spread Function Model for Ground-based Optical Telescopes

Ground-based optical telescopes are seriously affected by atmospheric turbulence induced aberrations. Understanding properties of these aberrations is important both for instrument design and image restoration method development. Because the point-spread function can reflect performance of the whole optic system, it is appropriate to use the point-spread function to describe atmospheric turbulence induced aberrations. Assuming point-spread functions induced by the atmospheric turbulence with the same profile belong to the same manifold space, we propose a nonparametric point-spread function—PSF–NET. The PSF–NET has a cycle convolutional neural network structure and is a statistical representation of the manifold space of PSFs induced by the atmospheric turbulence with the same profile. Testing the PSF–NET with simulated and real observation data, we find that a well trained PSF–NET can restore any short exposure images blurred by atmospheric turbulence with the same profile. Besides, we further use the impulse response of the PSF–NET, which can be viewed as the statistical mean PSF, to analyze interpretation properties of the PSF–NET. We find that variations of statistical mean PSFs are caused by variations of the atmospheric turbulence profile: as the difference of the atmospheric turbulence profile increases, the difference between statistical mean PSFs also increases. The PSF–NET proposed in this paper provides a new way to analyze atmospheric turbulence induced aberrations, which would benefit the development of new observation methods for ground-based optical telescopes.

79 ASTRONOMY AND ASTROPHYSICS↗

Coma of modified Gregorian and Cassegrainian mirror systems

The equivalence of the classical Newtonian, Cassegrainian, and Gregorian mirror systems with respect to the first two Seidel aberrations is rederived by means of a simple congruence. The effects of arbitrary small modifications of the two mirror systems are then studied and general formulas are derived for the effects of such modifications on the spherical aberration and coma. Spherical aberration is corrected to the third order if the amount of glass removed from one surface is replaced at the corresponding zone of the other surface. Modifications in which one surface is made spherical while the other is adjusted to eliminate spherical aberration result in large increases of coma for systems having the usual amplifying ratios.

Jones, R. T.↗

Zernike test. I - Analytical aspects. II - Experimental aspects

The Zernike phenomenon is interpreted in general interferometric terms to gain insight into the optimum design of disks suitable for a particular experimental situation. The design of Zernike disks for measuring small low-order aberrations is considered and evaluated; optimum parameters for disks 2, 3, 4, and 5 microns in radius are determined for an f/12 large-space-telescope system with an obscuration ratio of 0.4 at 0.6 micron. It is shown that optimization in this case provides sensitivities of better than one hundredth of a wavelength for the measurement of low-order aberrations. The procedure for manufacturing a Zernike disk is then described in detail, and results are reported for tests of a laboratory Zernike figure sensor containing a disk manufactured according to this procedure. In the tests, a laboratory wavefront-error simulator was used to introduce small aberration ranges, measurements of the changes in reimaged pupil intensity introduced by the disk were made for several aberration settings, and the measured changes were compared with the values predicted by the interferometric theory of Zernike tests. The results are found to agree within an error of one two-hundredth of a wavelength.

Golden, L. J.↗

Focal characteristics of spheroidal geodesic lenses for integrated optical processing

Aspheric shaping of geodesic lenses in optical waveguides is suggested as a means for correcting spherical aberrations. The technique is complementary to the method of Spiller and Harper, in which geodesic lens aberrations are reduced by thickening the waveguiding layer in the lens region. The properties of a family of oblate-spheroidal lenses with no third-order spherical aberrations are described theoretically. Diffraction-limited performance over apertures up to one-half the full lens aperture is predicted for lenses with true f/numbers (focal length divided by useful aperture) in the range 2-12. By combining spheroidal-shaping and mode-index correction techniques, geodesic lenses free from both third- and fifth-order aberrations can be designed. These lenses show diffraction-limited performance over apertures of a centimeter or more when true f/numbers are in the range 1.5-9.5.

Vahey, D. W.↗

Analysis and design of a refractive virtual image system

The optical performance of a virtual image display system is evaluated. Observation of a two-element (unachromatized doublet) refractive system led to the conclusion that the major source of image degradation was lateral chromatic aberration. This conclusion was verified by computer analysis of the system. The lateral chromatic aberration is given in terms of the resolution of the phosphor dots on a standard shadow mask color cathode ray tube. Single wavelength considerations include: astigmatism, apparent image distance from the observer, binocular disparities and differences of angular magnification of the images presented to each of the observer's eyes. Where practical, these results are related to the performance of the human eye. All these techniques are applied to the previously mentioned doublet and a triplet refractive system. The triplet provides a 50-percent reduction in lateral chromatic aberration which was the design goal. Distortion was also reduced to a minimum over the field of view. The methods used in the design of the triplet are presented along with a method of relating classical aberration curves to image distance and binocular disparity.

Kahlbaum, W. M.↗

Optical design of zero-power Hubble Space Telescope wave-front correctors for null testing

The optical design of the second-generation wide-field/planetary-camera instrument for the Hubble Space Telescope has been modified to compensate for the spherical aberration of the optical telescope assembly (OTA) by introduction of undercorrected spherical aberration into the wave front. This instrument can be tested in a simple manner to ensure that its aberration contribution has the proper sign and magnitude. We present designs for a near-zero power doublet lens that can be used to generate a spherically aberrated wave front that is similar to the OTA wave front. When this lens is used in combination with the instrument, a near-perfect or nulled wave front should be produced, resulting in a high-quality point image on axis. We also present lens designs for a similar test that can be performed on the OTA simulators now being built to verify the other second-generation instruments.

Hannan, Paul G.↗

Parameter dimension of turbulence-induced phase errors and its effects on estimation in phase diversity

The method of phase diversity has been used in the context of incoherent imaging to estimate jointly an object that is being imaged and phase aberrations induced by atmospheric turbulence. The method requires a parametric model for the phase-aberration function. Typically, the parameters are coefficients to a finite set of basis functions. Care must be taken in selecting a parameterization that properly balances accuracy in the representation of the phase-aberration function with stability in the estimates. It is well known that over parameterization can result in unstable estimates. Thus a certain amount of model mismatch is often desirable. We derive expressions that quantify the bias and variance in object and aberration estimates as a function of parameter dimension.

Thelen, Brian J.↗

Radiation-Induced Cytogenetic Damage as a Predictor of Cancer Risk for Protons and Fe Ions

We have successfully completed the series of experiments planned for year 1 and the first part of year 2 measuring the induction of chromosome aberrations induced in multiple cell types by three model space radiations: Fe-ions, protons and photons. Most of these data have now been compiled and a significant part subjected to detailed data analyses, although continuing data analysis is an important part of our current and future efforts. These analyses are directed toward defining the patterns of chromosomal damage induction by the three radiations and the extent to which such patterns are dependent on the type of cell irradiated. Our studies show significant differences, both quantitatively and qualitatively, between response of different cell types to these radiations however there is an overall pattern that characterizes each type of radiation in most cell lines. Thus our data identifies general dose-response patterns for each radiation for induction of multiple types of chromosomal aberrations but also identifies significant differences in response between some cell types. Specifically, we observe significant resistance for induction of aberrations in rat mammary epithelial cells when they are irradiated in vivo and assayed in vitro. Further, we have observed some remarkable differences in susceptibility to certain radiation-induced aberrations in cells whose genome has been modulated for two cancer- relevant genes, TP53 and CDKNIA. This data, if confirmed, may represent the first evidence of gene-specific differences in cellular metabolism of damage induced by densely-ionizing radiation that confers substantial sensitivity to protons compared to photons.

Williams, Jerry R.↗

Overcoming Dynamic Disturbances in Imaging Systems

We develop and discuss a methodology with the potential to yield a significant reduction in complexity, cost, and risk of space-borne optical systems in the presence of dynamic disturbances. More robust systems almost certainly will be a result as well. Many future space-based and ground-based optical systems will employ optical control systems to enhance imaging performance. The goal of the optical control subsystem is to determine the wavefront aberrations and remove them. Ideally reducing an aberrated image of the object under investigation to a sufficiently clear (usually diffraction-limited) image. Control will likely be distributed over several elements. These elements may include telescope primary segments, telescope secondary, telescope tertiary, deformable mirror(s), fine steering mirror(s), etc. The last two elements, in particular, may have to provide dynamic control. These control subsystems may become elaborate indeed. But robust system performance will require evaluation of the image quality over a substantial range and in a dynamic environment. Candidate systems for improvement in the Earth Sciences Enterprise could include next generation Landsat systems or atmospheric sensors for dynamic imaging of individual, severe storms. The technology developed here could have a substantial impact on the development of new systems in the Space Science Enterprise; such as the Next Generation Space Telescope(NGST) and its follow-on the Next NGST. Large Interferometric Systems of non-zero field, such as Planet Finder and Submillimeter Probe of the Evolution of Cosmic Structure, could benefit. These systems most likely will contain large, flexible optomechanical structures subject to dynamic disturbance. Furthermore, large systems for high resolution imaging of planets or the sun from space may also benefit. Tactical and Strategic Defense systems will need to image very small targets as well and could benefit from the technology developed here. We discuss a novel speckle imaging technique with the potential to separate dynamic aberrations from static aberrations. Post-processing of a set of image data, using an algorithm based on this technique, should work for all but the lowest light levels and highest frequency dynamic environments. This technique may serve to reduce the complexity of the control system and provide for robust, fault-tolerant, reduced risk operation. For a given object, a short exposure image is "frozen" on the focal plane in the presence of the environmental disturbance (turbulence, jitter, etc.). A key factor is that this imaging data exhibits frame-to-frame linear shift invariance. Therefore, although the Point Spread Function is varying from frame to frame, the source is fixed; and each short exposure contains object spectrum data out to the diffraction limit of the imaging system. This novel speckle imaging technique uses the Knox-Thompson method. The magnitude of the complex object spectrum is straightforward to determine by well-established approaches. The phase of the complex object spectrum is decomposed into two parts. One is a single-valued function determined by the divergence of the optical phase gradient. The other is a multi-valued function determined by the circulation of the optical phase gradient-"hidden phase." Finite difference equations are developed for the phase. The novelty of this approach is captured in the inclusion of this "hidden phase." This technique allows the diffraction-limited reconstruction of the object from the ensemble of short exposure frames while simultaneously estimating the phase as a function of time from a set of exposures.

Young, Eric W.↗

Overcoming Dynamic Disturbances in Imaging Systems

We develop and discuss a methodology with the potential to yield a significant reduction in complexity, cost, and risk of space-borne optical systems in the presence of dynamic disturbances. More robust systems almost certainly will be a result as well. Many future space-based and ground-based optical systems will employ optical control systems to enhance imaging performance. The goal of the optical control subsystem is to determine the wavefront aberrations and remove them. Ideally reducing an aberrated image of the object under investigation to a sufficiently clear (usually diffraction-limited) image. Control will likely be distributed over several elements. These elements may include telescope primary segments, telescope secondary, telescope tertiary, deformable mirror(s), fine steering mirror(s), etc. The last two elements, in particular, may have to provide dynamic control. These control subsystems may become elaborate indeed. But robust system performance will require evaluation of the image quality over a substantial range and in a dynamic environment. Candidate systems for improvement in the Earth Sciences Enterprise could include next generation Landsat systems or atmospheric sensors for dynamic imaging of individual, severe storms. The technology developed here could have a substantial impact on the development of new systems in the Space Science Enterprise; such as the Next Generation Space Telescope(NGST) and its follow-on the Next NGST. Large Interferometric Systems of non-zero field, such as Planet Finder and Submillimeter Probe of the Evolution of Cosmic Structure, could benefit. These systems most likely will contain large, flexible optormechanical structures subject to dynamic disturbance. Furthermore, large systems for high resolution imaging of planets or the sun from space may also benefit. Tactical and Strategic Defense systems will need to image very small targets as well and could benefit from the technology developed here. We discuss a novel speckle imaging technique with the potential to separate dynamic aberrations from static aberrations. Post-processing of a set of image data, using an algorithm based on this technique, should work for all but the lowest light levels and highest frequency dynamic environments. This technique may serve to reduce the complexity of the control system and provide for robust, fault-tolerant, reduced risk operation. For a given object, a short exposure image is "frozen" on the focal plane in the presence of the environmental disturbance (turbulence, jitter, etc.). A key factor is that this imaging data exhibits frame-to-frame linear shift invariance. Therefore, although the Point Spread Function is varying from frame to frame, the source is fixed; and each short exposure contains object spectrum data out to the diffraction limit of the imaging system. This novel speckle imaging technique uses the Knox-Thompson method. The magnitude of the complex object spectrum is straightforward to determine by well-established approaches. The phase of the complex object spectrum is decomposed into two parts. One is a single-valued function determined by the divergence of the optical phase gradient. The other is a multi-valued function determined by, the circulation of the optical phase gradient-"hidden phase." Finite difference equations are developed for the phase. The novelty of this approach is captured in the inclusion of this "hidden phase." This technique allows the diffraction-limited reconstruction of the object from the ensemble of short exposure frames while simultaneously estimating the phase as a function of time from a set of exposures.

Young, Eric W.↗

Exoplanet Yield Sensitivity for the Hybrid Lyot Coronagraph from end-to-end modeling for LUVOIR-A

NASA's future direct imaging flagship mission will require telescope mirror segmentation to survey a statistically significant population of nearby stellar systems by increasing aperture size beyond that achieved by traditional space-borne monolithic apertures thus far. Segmentation is a path for the size expansion, but it entails a challenge due to the introduction of temporal pupil discontinuities in terms of both phase and amplitude. Modeling of the integrated performance of the coronagraph with the expected dynamical profile of the telescope is an important step toward realistic estimates of the mission's science yields. We present results of a study using the hybrid Lyot coronagraph with a 15-m on-axis, segmented optical telescope assembly (OTA), akin to that of the Large UV / Optical /Infrared (LUVOIR) mission. We have developed a high-fidelity, end-to-end model as part of the Segmented Coronagraph Design and Analysis (SCDA) study that includes diffractive optical propagations at the 1e-10 contrast level across the optical train including the OTA and intermediate re-imaging optics inside the coronagraph instrument. We perform a sensitivity analysis to assess the contrast sensitivity to wavefront perturbations for a set of key telescope terms including segment-level low-order and mid-spatial frequency aberrations and evaluate expected exoplanet yields obtained in the presence of these sets of aberrations. Industry-provided segment-level wavefront aberration datasets involving the following mechanisms are input to the end-to-end model: (1) thermal gradients and accelerations, and (2) telescope dynamics including line-of-sight and segment jitter. Dynamically averaged PSFs in the presence of aberrations are fed into AYO (Altruistic Yield Optimization), a mission design reference simulator, that then assesses the scientific yield sensitivities.

high-contrast imaging↗