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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 541 records · Page 30
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Modeling Damage Complexity-Dependent Non-Homologous End-Joining Repair Pathway

Non-homologous end joining (NHEJ) is the dominant DNA double strand break (DSB) repair pathway and involves several repair proteins such as Ku, DNA-PKcs, and XRCC4. It has been experimentally shown that the choice of NHEJ proteins is determined by the complexity of DSB. In this paper, we built a mathematical model, based on published data, to study how NHEJ depends on the damage complexity. Under an appropriate set of parameters obtained by minimization technique, we can simulate the kinetics of foci track formation in fluorescently tagged mammalian cells, Ku80-EGFP and DNA-PKcs-YFP for simple and complex DSB repair, respectively, in good agreement with the published experimental data, supporting the notion that simple DSB undergo fast repair in a Ku-dependent, DNA-PKcs-independent manner, while complex DSB repair requires additional DNA-PKcs for end processing, resulting in its slow repair, additionally resulting in slower release rate of Ku and the joining rate of complex DNA ends. Based on the numerous experimental descriptions, we investigated several models to describe the kinetics for complex DSB repair. An important prediction of our model is that the rejoining of complex DSBs is through a process of synapsis formation, similar to a second order reaction between ends, rather than first order break filling/joining. The synapsis formation (SF) model allows for diffusion of ends before the synapsis formation, which is precluded in the first order model by the rapid coupling of ends. Therefore, the SF model also predicts the higher number of chromosomal aberrations observed with high linear energy transfer (LET) radiation due to the higher proportion of complex DSBs compared to low LET radiation, and an increased probability of misrejoin following diffusion before the synapsis is formed, while the first order model does not provide a mechanism for the increased effectiveness in chromosomal aberrations observed.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Application of FISH based G2-PCC assay for the cytogenetic assessment of high radiation dose exposures: Potential implications for rapid triage biodosimetry

The main goal of this study is to test the utility of calyculin A induced G2-PCC assay as a biodosimetry triage tool for assessing a wide range of low and acute high radiation dose exposures of photons. Towards this initiative, chromosome aberrations induced by low and high doses of x-rays were evaluated and characterized in G2-prematurely condensed chromosomes (G2-PCCs) by fluorescence in situ hybridization (FISH) using human centromere and telomere specific PNA (peptide nucleic acid) probes. A dose dependent increase in the frequency of dicentric chromosomes was observed in the G2-PCCs up to 20 Gy of x-rays. The combined yields of dicentrics and rings in the G2-PCCs showed a clear dose dependency up to 20 Gy from 0.02/cell for 0.1 Gy to 14.98/cell for 20 Gy. Centric rings were observed more frequently than acentric ring chromosomes in the G2-PCCs at all the radiation doses from 1 Gy to 20 Gy. A head-to-head comparison was also performed by FISH on the yields of chromosome aberrations induced by different doses of x-rays (0 Gy -7.5 Gy) in colcemid arrested metaphase chromosomes and calyculin A induced G2-PCCs. In general, the frequencies of dicentrics, rings and acentric fragments were slightly higher in G2-PCCs than in colcemid arrested metaphase chromosomes at all the radiation doses, but the differences were not statistically significant. To reduce the turnaround time for absorbed radiation dose estimation, attempt was made to obtain G2-PCCs by reducing the culture time to 36 hrs. The absorbed doses estimated in x-rays irradiated (0,1,2 and 4 Gy) G2-PCCs after 36 hrs of culture were grossly like that of G2-PCCs and colcemid arrested metaphase chromosomes prepared after 48 hrs of culture. Our study indicates that the shortened version of calyculin A induced G2-PCC assay coupled with the FISH staining technique can serve as an effective triage biodosimetry tool for large-scale radiological/nuclear incidents.

Science & Technology - Other Topics↗
DOE OSTI2017

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer’s disease-related protein aggregation as an underlying mechanism of age-related memory impairment.

amyloid↗
DOE OSTI2017

Coordination of the Ser2056 and Thr2609 Clusters of DNA-PKcs in Regulating Gamma Rays and Extremely Low Fluencies of Alpha-Particle Irradiation to G 0 /G 1 Phase Cells

The catalytic subunit of DNA dependent protein kinase (DNA-PKcs) and its kinase activity are critical for mediation of non-homologous end-joining (NHEJ) of DNA double-strand breaks (DSB) in mammalian cells after gamma-ray irradiation. Additionally, DNA-PKcs phosphorylations at the T2609 cluster and the S2056 cluster also affect DSB repair and cellular sensitivity to gamma radiation. Previously we reported that phosphorylations within these two regions affect not only NHEJ but also homologous recombination repair (HRR) dependent DSB repair. In this study, we further examine phenotypic effects on cells bearing various combinations of mutations within either or both regions. Effects studied included cell killing as well as chromosomal aberration induction after 0.5–8 Gy gamma-ray irradiation delivered to synchronized cells during the G0/G1 phase of the cell cycle. Blocking phosphorylation within the T2609 cluster was most critical regarding sensitization and depended on the number of available phosphorylation sites. It was also especially interesting that only one substitution of alanine in each of the two clusters separately abolished the restoration of wild-type sensitivity by DNA-PKcs. Similar patterns were seen for induction of chromosomal aberrations, reflecting their connection to cell killing. To study possible change in coordination between HRR and NHEJ directed repair in these DNA-PKcs mutant cell lines, we compared the induction of sister chromatid exchanges (SCEs) by very low fluencies of alpha particles with mutant cells defective in the HRR pathway that is required for induction of SCEs. Finally, levels of true SCEs induced by very low fluence of alpha-particle irradiation normally seen in wild-type cells were only slightly decreased in the S2056 cluster mutants, but were completely abolished in the T2609 cluster mutants and were indistinguishable from levels seen in HRR deficient cells. Again, a single substitution in the S2056 together with a single substitution in the T2609 cluster abolished SCE formation and thus also effectively interferes with HRR.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Demonstration of Current Profile Shaping using Double Dog-Leg Emittance Exchange Beam Line at Argonne Wakefield Accelerator

Emittance exchange (EEX) based longitudinal current profile shaping is the one of the promising current profile shaping technique. This method can generate high quality arbitrary current profiles under the ideal conditions. The double dog-leg EEX beam line was recently installed at the Argonne Wakefield Accelerator (AWA) to explore the shaping capability and confirm the quality of this method. To demonstrate the arbitrary current profile generation, several different transverse masks are applied to generate different final current profiles. The phase space slopes and the charge of incoming beam are varied to observe and suppress the aberrations on the ideal profile. We present current profile shaping results, aberrations on the shaped profile, and its suppression.

43 PARTICLE ACCELERATORS↗
DOE OSTI2017

Lesion complexity drives age related cancer susceptibility in human mammary epithelial cells

Exposures to various DNA damaging agents can deregulate a wide array of critical mechanisms that maintain genome integrity. It is unclear how these processes are impacted by one's age at the time of exposure and the complexity of the DNA lesion. To clarify this, we employed radiation as a tool to generate simple and complex lesions in normal primary human mammary epithelial cells derived from women of various ages. We hypothesized that genomic instability in the progeny of older cells exposed to complex damages will be exacerbated by age-associated deterioration in function and accentuate age-related cancer predisposition. Centrosome aberrations and changes in stem cell numbers were examined to assess cancer susceptibility. Our data show that the frequency of centrosome aberrations proportionately increases with age following complex damage causing exposures. However, a dose-dependent increase in stem cell numbers was independent of both age and the nature of the insult. Phospho-protein signatures provide mechanistic clues to signaling networks implicated in these effects. Together these studies suggest that complex damage can threaten the genome stability of the stem cell population in older people. Propagation of this instability is subject to influence by the microenvironment and will ultimately define cancer risk in the older population.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Advanced Imaging Optics Utilizing Wavefront Coding

Image processing offers a potential to simplify an optical system by shifting some of the imaging burden from lenses to the more cost effective electronics. Wavefront coding using a cubic phase plate combined with image processing can extend the system's depth of focus, reducing many of the focus-related aberrations as well as material related chromatic aberrations. However, the optimal design process and physical limitations of wavefront coding systems with respect to first-order optical parameters and noise are not well documented. We examined image quality of simulated and experimental wavefront coded images before and after reconstruction in the presence of noise. Challenges in the implementation of cubic phase in an optical system are discussed. In particular, we found that limitations must be placed on system noise, aperture, field of view and bandwidth to develop a robust wavefront coded system.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2017

Foil focusing of relativistic electron beams

When an intense relativistic electron beams (IREB) passes through a grounded metal foil, the transverse electric field due to the beam space charge is locally shorted out, and the beam is focused by the magnetic field of its current. The effect can be treated as focusing by a thin lens with first order aberration. Expressions for the focal length and aberration coefficient of the equivalent thin lens are developed in this note. These are then applied to practical examples representative of IREB research at Los Alamos National Laboratory.

43 PARTICLE ACCELERATORS↗
DOE OSTI2023

New Collins Quad Design

The Collins quadrupoles are used on the DARHT 2nd axis to transform the elliptical beam from the septum quadrupole back to a round beam. They are also used to minimize kicker smear by producing a point-to-point focus from the kicker to the target. The present Collins quads introduce significant aberrations due to the design of the iron pole tip. The effect of these aberrations becomes particularly large as the beam size in the Collins quads increases. This note describes an improved 2D pole tip design for the Collins quads developed using POISSON.

43 PARTICLE ACCELERATORS↗
DOE OSTI2016

RELATIVISTIC MEASUREMENTS FROM TIMING THE BINARY PULSAR PSR B1913+16

We present relativistic analyses of 9257 measurements of times-of-arrival from the first binary pulsar, PSR B1913+16, acquired over the last 35 years. The determination of the “Keplerian” orbital elements plus two relativistic terms completely characterizes the binary system, aside from an unknown rotation about the line of sight, leading to a determination of the masses of the pulsar and its companion: 1.438 ± 0.001 M {sub ☉} and 1.390 ± 0.001 M {sub ☉}, respectively. In addition, the complete system characterization allows for the creation of relativistic gravitation test by comparing measured and predicted sizes of various relativistic phenomena. We find that the ratio of the observed orbital period decrease caused by gravitational wave damping (corrected by a kinematic term) to the general relativistic prediction is 0.9983 ± 0.0016, thereby confirms the existence and strength of gravitational radiation as predicted by general relativity. For the first time in this system, we have also successfully measured the two parameters characterizing the Shapiro gravitational propagation delay, and found that their values are consistent with general relativistic predictions. For the first time in any system, we have also measured the relativistic shape correction to the elliptical orbit, δ {sub θ} , although its intrinsic value is obscured by currently unquantified pulsar emission beam aberration. We have also marginally measured the time derivative of the projected semimajor axis, which, when improved in combination with beam aberration modeling from geodetic precession observations, should ultimately constrain the pulsar’s moment of inertia.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2023

Retinal microvascular and neuronal pathologies probed in vivo by adaptive optical two-photon fluorescence microscopy

The retina, behind the transparent optics of the eye, is the only neural tissue whose physiology and pathology can be non-invasively probed by optical microscopy. The aberrations intrinsic to the mouse eye, however, prevent high-resolution investigation of retinal structure and function in vivo. Optimizing the design of a two-photon fluorescence microscope (2PFM) and sample preparation procedure, we found that adaptive optics (AO), by measuring and correcting ocular aberrations, is essential for resolving putative synaptic structures and achieving three-dimensional cellular resolution in the mouse retina in vivo. Applying AO-2PFM to longitudinal retinal imaging in transgenic models of retinal pathology, we characterized microvascular lesions with sub-capillary details in a proliferative vascular retinopathy model, and found Lidocaine to effectively suppress retinal ganglion cell hyperactivity in a retinal degeneration model. Tracking structural and functional changes at high-resolution longitudinally, AO-2PFM enables microscopic investigations of retinal pathology and pharmacology for disease diagnosis and treatment in vivo.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Aneuploidy induces premature aging in yeast due to defects in Ribosome Quality Control [RNASeqData]

Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.

aneuploidy↗
DOE OSTI2024

Aneuploidy induces premature aging in yeast due to defects in Ribosome Quality Control [MoBYSeqData]

Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.

aneuploidy↗
DOE OSTI2024

Premature aging in aneuploid yeast is influenced by aneuploidy-induced defects in Ribosome Quality Control [RiboSeq]

Premature aging is a hallmark of Down syndrome, caused by trisomy of human chromosome 21; but the reason is unclear and difficult to study in humans. We used an aneuploid model in wild yeast to show that chromosome amplification disrupts nutrient-induced cell-cycle arrest, quiescence entry, and healthy aging, across genetic backgrounds and amplified chromosomes. We discovered that these defects are due in part to aneuploidy-induced dysfunction in Ribosome Quality Control (RQC). Aneuploids entering quiescence display aberrant ribosome profiles, accumulate RQC intermediates, and harbor an increased load of protein aggregates. Although they have normal proteasome capacity, aneuploids show signs of ubiquitin dysregulation, which impacts cyclin abundance to disrupt arrest. Remarkably, inducing ribosome stalling in euploids produces similar aberrations, while up-regulating limiting RQC subunits or proteins in ubiquitin metabolism alleviates many of the aneuploid defects. Our results raise major implications for other aneuploidy disorders including Down syndrome.

aneuploidy↗
NASA NTRS1971

Application of Monte Carlo techniques to optimization of high-energy beam transport in a stochastic environment

An algorithm employing a modified sequential random perturbation, or creeping random search, was applied to the problem of optimizing the parameters of a high-energy beam transport system. The stochastic solution of the mathematical model for first-order magnetic-field expansion allows the inclusion of state-variable constraints, and the inclusion of parameter constraints allowed by the method of algorithm application eliminates the possibility of infeasible solutions. The mathematical model and the algorithm were programmed for a real-time simulation facility; thus, two important features are provided to the beam designer: (1) a strong degree of man-machine communication (even to the extent of bypassing the algorithm and applying analog-matching techniques), and (2) extensive graphics for displaying information concerning both algorithm operation and transport-system behavior. Chromatic aberration was also included in the mathematical model and in the optimization process. Results presented show this method as yielding better solutions (in terms of resolutions) to the particular problem than those of a standard analog program as well as demonstrating flexibility, in terms of elements, constraints, and chromatic aberration, allowed by user interaction with both the algorithm and the stochastic model. Example of slit usage and a limited comparison of predicted results and actual results obtained with a 600 MeV cyclotron are given.

Parrish, R. V.↗
NASA NTRS1972

A general purpose wideband optical spatial frequency spectrum analyzer

The light scattered at various angles by a transparent media is studied. An example of these applications is the optical Fourier spectrum measurement resulting from various spatial frequencies which were recorded on a photographic emulsion. A method for obtaining these measurements consists of illuminating the test object with parallel monochromatic light. A stationary lens, placed in the resulting wavefield at a distance of one focal length from the object, will focus parallel waves emanating from the test object at a point lying in the focal plane of the lens. A light detector with a small filtering aperture is then used to measure the intensity variation of the light in the focal or transform plane of the lens. Such measurements require the use of a lens which is highly corrected for all of the common aberrations except chromatic aberration.

Ballard, G. S.↗
NASA NTRS1971

In-situ measurement of objective lens data of a high-resolution electron microscope.

Bragg-reflex images of small individual crystallites in the size range of 20-100 A diameter with known crystallographic orientation were used in a transmission electron microscope to determine in-situ: (a) the relationship between objective lens current (or accelerating voltage) changes in discrete steps and corresponding defocus, (b) the spherical aberration coefficient, and (c) the axial chromatic aberration coefficient of the objective lens. The accuracy of the described method is better than 5%. The same specimen can advantageously be used to properly aline the illuminating beam with respect to the optical axis.

Heinemann, K.↗
NASA NTRS1977

Anastigmatic three-mirror telescope

A three-mirror telescope arrangement that can be corrected for four aberrations (coma, spherical aberration, field curvature, and astigmatism) is described. Geometric spot size is less than 0.1 sec of arc, in an easily accessible flat field of 1.5 deg. The primary-secondary configuration is Cassegrain-like, with the real image formed closely behind the primary. This secondary image is re-imaged by a tertiary mirror at roughly unit magnification. A small, flat mirror at the exit pupil, located between primary and tertiary, folds the light rectangularly away from the telescope axis. The shape of the large image area is helpful in space applications where several instruments may share the focal plane.

Korsch, D.↗