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335 records · Page 19

Probabilities of radiation-induced inter- and intrachromosomal exchanges and their dependence on the DNA content of the chromosome

A biophysical model has been developed that is based on the assumptions that an interphase chromosome occupies a spherical territory and that chromosome exchanges are formed by the misrejoining of two DNA double-strand breaks induced within a defined interaction distance. The model is used to explain the relative frequencies of inter- and intrachromosomal exchanges and the relationship between radiation-induced aberrations in individual chromosomes and the DNA content of the chromosome. Although this simple model predicts a higher ratio of inter- to intrachromosomal exchanges for low-LET radiation than for high-LET radiation, as has been suggested by others, we argue that the comparison of the prediction of the model with experimental results is not straightforward. With the model, we also show that the probability of the formation of interchromosomal exchanges is proportional to the "surface area" of the chromosome domain plus a correction term. The correction term is small if the interaction distance is less than 1 microm for both low- and high-LET radiations.

NASA Center JSC↗

Radiative equilibrium in rapidly expanding shells

The equation of radiative equilibrium for rapidly expanding spherical shells including the special relativistic terms is discussed, and a temperature-correction procedure for the solution of this equation is given. The temperature-correction scheme combines a partial linearization approach with the approximate Lambda-operator iteration method. For some test problems, the temperature structures of atmospheres in radiative equilibrium in the Lagrangian frame are calculated. The effects of the velocity field on the temperature stratification and the luminosity are also discussed. We find that the temperature structure of a moving photosphere in radiative equilibrium in the Lagrangian frame differs significantly from that of a static photosphere and that, at least, all first-order terms, in particular the advection and aberration terms, have to be included consistently both in the radiative transfer and the energy equation in studies of supernovae atmospheres and other high-speed radiating flows.

Hauschildt, P. H.↗

Optical Modeling Activities for NASA's James Webb Space Telescope (JWST): V. Operational Alignment Updates

This paper is part five of a series on the ongoing optical modeling activities for the James Webb Space Telescope (JWST). The first two papers discussed modeling JWST on-orbit performance using wavefront sensitivities to predict line of sight motion induced blur, and stability during thermal transients. The third paper investigates the aberrations resulting from alignment and figure compensation of the controllable degrees of freedom (primary and secondary mirrors), which may be encountered during ground alignment and on-orbit commissioning of the observatory, and the fourth introduced the software toolkits used to perform much of the optical analysis for JWST. The work here models observatory operations by simulating line-of-sight image motion and alignment drifts over a two-week period. Alignment updates are then simulated using wavefront sensing and control processes to calculate and perform the corrections. A single model environment in Matlab is used for evaluating the predicted performance of the observatory during these operations.

Howard, Joseph M.↗

Hypergravity-induced immunomodulation in a rodent model: lymphocytes and lymphoid organs

The major goal of this study was to quantify changes in lymphoid organs and cells over time due to centrifugation-induced hypergravity. C57BL/6 mice were exposed to 1, 2 and 3 G and the following assays were performed on days 1, 4, 7, 10, and 21: spleen, thymus, lung, and liver masses; total leukocyte, lymphocyte, monocyte/macrophage, and granulocyte counts; level of splenocyte apoptosis; enumeration of CD3+ T, CD3+/CD4+ T helper, CD3+/CD8+ T cytotoxic, B220+ B, and NK1.1+ natural killer cells; and quantification of cells expressing CD25, CD69, and CD71 activation markers. The data show that increased gravity resulted in decreased body, spleen, thymus, and liver, but not lung, mass. Significant reductions were noted in all three major leukocyte populations (lymphocytes, granulocytes, monocyte/macrophages) [correction of macrphages] with increased gravity; persistent depletion was noted in blood but not spleen. Among the various lymphocyte populations, the CD3+/CD8+ T cells and B220+ B cells were the most affected and NK1.1+ NK cells the least affected. Overall, the changes were most evident during the first week, with a greater influence noted for cells in the spleen. A linear relationship was found between some of the measurements and the level of gravity, especially on day 4. These findings indicate that hypergravity profoundly alters leukocyte number and distribution in a mammalian model and that some aberrations persisted throughout the three weeks of the study. In certain cases, the detected changes were similar to those observed after whole-body irradiation. In future investigations we hope to combine hypergravity with low-dose rate irradiation and immune challenge.

Non-NASA Center↗

Disruption of histone acetylation homeostasis reveals multilayered chromatin regulation for transcriptional resiliency

Background Epigenetic modifications, nucleosome occupancy, and three-dimensional chromatin architecture collectively create a multi-layered, highly interactive regulatory system for controlling genomic functionality. Dysregulation of epigenetic processes leads to a plethora of abnormalities including disease states. Therapies focused on epigenetic modulation can alter gene expression to correct dysfunction, though the perpetuation of these states and the relationships among chromatin regulatory layers is not well understood. Results Here, we investigated global and local chromatin structural and functional responses after acute histone deacetylase inhibitor treatment (suberoylanilide hydroxamic acid) in lung cancer cells across time. Treatment substantially increased global histone acetylation resulting in a pervasive but not distinctive signature. The spread of acetylation did not significantly impact global chromatin accessibility, and nucleosome remodeling largely occurred at finer scales in functionally relevant genomic regions. Indeed, both H 3 K 4 trimethylation, a mark of active transcription, and gene expression changes were altered in a controlled locus-specific manner, suggesting aberrant acetylation indirectly leads to balanced and bidirectional gene expression profiles from tighter regulation of other chromatin features. HDACi treatment induced (13%) genomic rearrangement in chromatin compartmentalization and moderate weakening of topologically associating domains. Conclusions Continuous wavelet analysis of these features demonstrates that scale-dependent, locus-specific factors influence the relationship between chromatin architecture and functional output, suggesting that regulation of transcription and nucleosome remodeling is not entirely (nor linearly) dependent upon large scale compartment exchange. Structural and functional responses are most pronounced early after treatment with partial persistence of differential local chromatin features and expression later in time; this highlights the plasticity of chromatin regulation, which may have implications for the efficacy of epigenetic treatments. These results demonstrate the effectiveness of multi-layered regulation of transcription: in resilient systems, disruption of one chromatin feature does not distort the regulation of other features in supporting a transcriptional program that allows for survival.

59 BASIC BIOLOGICAL SCIENCES↗

Cooled grating array spectrometer for 0.6-5 microns

A grating spectrometer, designed to illuminate an array of 122 InSb photodiodes with minimum aberrations and maximum speed, has been constructed. The instrument will be used on the 5 meter Hale telescope at Palomar Observatory, and is easily adaptable to telescopes of various focal ratios. A resolving power of 100-1000 can be obtained at wavelengths between 0.6 microns and 5 microns with remotely interchangeable gratings. The spectrometer is sufficiently compact to fit on the 8-inch work surface of a commercially available dewar, and uses simple on-axis spherical and paraboloidal optical elements. The camera mirror produces an f/2.5 beam which, with the 0.2 mm detectors, allows a 3-in. focal-plane aperture on the 5 meter telescope. All rays fall within a 100 microns blur circle at all points along the array. Distortions have been corrected with a tilted field flattening lens in front of the detector.

Nordholt, J. E.↗

Phase Retrieval for Radio Telescope and Antenna Control

Phase-retrieval is a general term used in optics to describe the estimation of optical imperfections or "aberrations." The purpose of this innovation is to develop the application of phase retrieval to radio telescope and antenna control in the millimeter wave band. Earlier techniques do not approximate the incoherent subtraction process as a coherent propagation. This approximation reduces the noise in the data and allows a straightforward application of conventional phase retrieval techniques for radio telescope and antenna control. The application of iterative-transform phase retrieval to radio telescope and antenna control is made by approximating the incoherent subtraction process as a coherent propagation. Thus, for systems utilizing both positive and negative polarity feeds, this approximation allows both surface and alignment errors to be assessed without the use of additional hardware or laser metrology. Knowledge of the antenna surface profile allows errors to be corrected at a given surface temperature and observing angle. In addition to imperfections of the antenna surface figure, the misalignment of multiple antennas operating in unison can reduce or degrade the signal-to-noise ratio of the received or broadcast signals. This technique also has application to the alignment of antenna array configurations.

Dean, Bruce↗

Surface science insight note: Optimizing XPS instrument performance for quantification of spectra

X-ray photoelectron spectroscopy (XPS) provides quantitative information from photoemission peaks and shapes observed within the background due to the inelastic scattering of photoelectrons. To quantify the signal, both photoemission peaks and background in spectra must be adjusted for instrumental transmission variations that are a consequence of changes in efficiency when recording electrons with different kinetic energy. While it is generally assumed that correcting spectroscopic data for transmission is a necessary part of quantification by XPS, there are consequences for the quantification of spectra measured using an instrument for which transmission has significant curvature. In this Insight, the implications of curvature in transmission characteristics are discussed and a method based on XPS microscopy is proposed that ensures the transmission response of an instrument is free from significant curvature. An example of an instrument for which a flat transmission response is presented is achieved through collecting spectra using lens modes designed to measure stigmatic images.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Adjustable Focus Optical Correction Lens (AFOCL)

This report describes the activities and accomplishments along with the status of the characterization of a PLZT-based Adjustable Focus Optical Correction Lens (AFOCL) test device. The activities described in this report were undertaken by members of the Center for Applied Optics (CAO) at the University of Alabama in Huntsville (UAH) under NASA Contract NAS8-00188. The effort was led by Dr. Bruce Peters as the Principal Investigator and supported by Dr. Patrick Reardon, Ms. Deborah Bailey, and graduate student Mr. Jeremy Wong. The activities outlined for the first year of the contract were to identify vendors and procure a test device along with performing the initial optical characterization of the test device. This activity has been successfully executed and test results are available and preliminary information was published at the SPIE Photonics West Conference in San Jose, January 2001. The paper, "Preliminary investigation of an active PLZT lens," was well received and generated response with several questions from the audience. A PLZT test device has been commercially procured from an outside vendor: The University of California in San Diego (UCSD) in partnership with New Interconnect Packaging Technologies (NIPT) Inc. The device has been subjected to several tests to characterize the optical performance of the device at wavelengths of interest. The goal was to evaluate the AFOCL similar to a conventional lens and measure any optical aberrations present due to the PLZT material as a deviation in the size of the diffraction limited spot (blur), the presence of diffracted energy into higher orders surrounding the focused spot (a variation in Strehl), and/or a variation or spread in the location of the focused energy away from the optical axis (a bias towards optical wedge, spherical, comma, or other higher order aberrations). While data has been collected indicative of the imaging quality of the AFOCL test device, it was not possible to fully characterize the optical performance of the AFOCL alone because there were significant optical distortions due to fabrication related issues.

Peters, Bruce R.↗

Probing Millisecond Pulsar Emission Geometry Using Light Curves From the Fermi Large Area Telescope

An interesting new high-energy pulsar sub-population is emerging following early discoveries of gamma-ray millisecond pulsars (MSPs) by the Fermi Large Area Telescope (LAT). We present results from 3D emission modeling, including the Special Relativistic effects of aberration and time-of-flight delays and also rotational sweepback of 13-field lines, in the geometric context of polar cap (PC), slot gap (SG), outer gap (OG), and two-pole caustic (TPC) pulsar models. In contrast to the general belief that these very old, rapidly-rotating neutron stars (NSs) should have largely pair-starved magnetospheres due to the absence of significant pair production, we find that most of the light curves are best fit by SG and OG models, which indicates the presence of narrow accelerating gaps limited by robust pair production -- even in these pulsars with very low spin-down luminosities. The gamma-ray pulse shapes and relative phase lags with respect to the radio pulses point to high-altitude emission being dominant for all geometries. We also find exclusive differentiation of the current gamma-ray MSP population into two MSP sub-classes: light curve shapes and lags across wavebands impose either pair-starved PC (PSPC) or SG / OG-type geometries. In the first case, the radio pulse has a small lag with respect to the single gamma-ray pulse, while the (first) gamma-ray peak usually trails the radio by a large phase offset in the latter case. Finally, we find that the flux correction factor as a function of magnetic inclination and observer angles is typically of order unity for all models. Our calculation of light curves and flux correction factor f(_, _, P) for the case of MSPs is therefore complementary to the "ATLAS paper" of Watters et al. for younger pulsars.

Venter, Christo↗

Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health

NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health.

NASA Discipline Radiation Health↗