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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 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Aberrant alternative splicing of RHOA is associated with loss of its expression and activity in diffuse-type gastric carcinoma cells

RhoA is a member of Rho family small GTPases that regulates diverse cellular functions. Recent large-scale sequencing studies have identified recurrent somatic mutations of RHOA in diffuse-type gastric carcinoma (DGC), indicating that RHOA is a driver of DGC. In this study, we investigated the possible abnormalities of RHOA in a panel of gastric carcinoma (GC) cell lines. Pulldown assay and immunoblot analysis showed that the activity and expression of RhoA were detectable in all GC cell lines tested, except for two DGC cell lines, HSC-59 and GSU. RHOA coding region sequencing revealed that aberrant alternative splicing of RHOA occurred in these cell lines. Quantitative real-time PCR analysis showed that the expression of wild-type RHOA was nearly undetectable, whereas splicing variants were almost exclusively expressed in HSC-59 and GSU cell lines. However, the expression levels of RHOA splicing variants were very low and the corresponding proteins were not detected by immunoblotting. Moreover, the splicing isoforms of RhoA protein were neither efficiently expressed nor activated even if ectopically expressed in cells. These results indicate that aberrant alternative splicing of RHOA results in the loss of its activity and expression in DGC cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Nicotine induces aberrant hypermethylation of tumor suppressor genes in pancreatic epithelial ductal cells

Highlights: • Nicotine can change the methylation status of tumor suppressor genes in normal human pancreatic ductal epithelial cells. • DNMT3A and 3B are overexpressed and are required for the nicotine-induced hypermethylation of tumor suppressor gene. • Nicotine induces hypermethylation of PENK and upregulation of DNMTs via activation of α7nAChR and MAPK signaling pathway. Tobacco smoking is an independent risk factor for the initiation of pancreatic cancer (PC). Hypermethylation of tumor suppressor genes has been demonstrated to be associated with smoking. This study aimed to find the relationship between nicotine exposure and hypermethylation of tumor suppressor genes in normal pancreatic epithelial cells. Human pancreatic epithelial cells ware cultured exposing to nicotine and the methylation status of tumor suppressor genes were detected. Proenkephalin (PENK) was chosen as the target gene and methylation level of PENK promoter region was measured. Expression of DNA methyltransferase (DNMT), nicotine acetylcholine receptor (α7nAChR) and signaling pathway downstream were analyzed. Nicotine induces overexpression of DNMT3A and 3B, and methylated-inactivation of PENK gene in normal pancreatic epithelial cells. An activation of α7nAChR and MAPK signaling pathway has been detected in the nicotine-treated group. Demethylated drug, antagonist of α7nAChR and inhibitor of p38 MAPK is verified to attenuate the overexpression of DNMTs stimulated by nicotine as well as inhibit aberrant hypermethylation-related silence of PENK gene. Nicotine stimulation can induce aberrant hypermethylation of tumor suppressor genes by α7nAChR and MAPK signaling pathway-mediated up-regulation of DNMTs in pancreatic epithelial cells, thus we can provide epigenetic evidence of the mechanisms by which smoking causes pancreatic cancer and find new therapeutic target.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

A spherical aberration-free microscopy system for live brain imaging

Highlights: • Deep-C is an automatic spherical aberration compensation system for in vivo imaging. • Deep-C is composed of ZlinC and Peak-C. • ZlinC coordinates the correction collar rotation and the Z-position of an objective. • Peak-C is a scanning algorithm processor for calculation of image contrast. • Deep-C allows quantitative, reproducible analysis of fine GFP-labeled structures. The high-resolution in vivo imaging of mouse brain for quantitative analysis of fine structures, such as dendritic spines, requires objectives with high numerical apertures (NAs) and long working distances (WDs). However, this imaging approach is often hampered by spherical aberration (SA) that results from the mismatch of refractive indices in the optical path and becomes more severe with increasing depth of target from the brain surface. Whereas a revolving objective correction collar has been designed to compensate SA, its adjustment requires manual operation and is inevitably accompanied by considerable focal shift, making it difficult to acquire the best image of a given fluorescent object. To solve the problems, we have created an objective-attached device and formulated a fast iterative algorithm for the realization of an automatic SA compensation system. The device coordinates the collar rotation and the Z-position of an objective, enabling correction collar adjustment while stably focusing on a target. The algorithm provides the best adjustment on the basis of the calculated contrast of acquired images. Together, they enable the system to compensate SA at a given depth. As proof of concept, we applied the SA compensation system to in vivo two-photon imaging with a 25 × water-immersion objective (NA, 1.05; WD, 2 mm). It effectively reduced SA regardless of location, allowing quantitative and reproducible analysis of fine structures of YFP-labeled neurons in the mouse cerebral cortical layers. Interestingly, although the cortical structure was optically heterogeneous along the z-axis, the refractive index of each layer could be assessed on the basis of the compensation degree. It was also possible to make fully corrected three-dimensional reconstructions of YFP-labeled neurons in live brain samples. Our SA compensation system, called Deep-C, is expected to bring out the best in all correction-collar-equipped objectives for imaging deep regions of heterogeneous tissues.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

CELF1 contributes to aberrant alternative splicing patterns in the type 1 diabetic heart

Dysregulated alternative splicing (AS) that contributes to diabetes pathogenesis has been identified, but little is known about the RNA binding proteins (RBPs) involved. We have previously found that the RBP CELF1 is upregulated in the diabetic heart; however, it is unclear if CELF1 contributes to diabetes-induced AS changes. Utilizing genome wide approaches, we identified extensive changes in AS patterns in Type 1 diabetic (T1D) mouse hearts. We discovered that many aberrantly spliced genes in T1D hearts have CELF1 binding sites. CELF1-regulated AS affects key genes within signaling pathways relevant to diabetes pathogenesis. Disruption of CELF1 binding sites impairs AS regulation by CELF1. In sum, our results indicate that CELF1 target RNAs are aberrantly spliced in the T1D heart leading to abnormal gene expression. These discoveries pave the way for targeting RBPs and their RNA networks as novel therapies for cardiac complications of diabetes.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Aberrant endoplasmic reticulum stress mediates coronary artery spasm through regulating MLCK/MLC2 pathway

Coronary artery spasm (CAS) is a pathophysiological phenomenon that may cause myocardial infarction and lead to circulatory collapse and death. Aberrant endoplasmic reticulum (ER) stress causes accumulation of misfolding proteins and has been reported to be involved in a variety of vascular diseases. The present study investigated the role of ER stress in the development of CAS and explored the possible molecular mechanisms. Initially, it was found that ER stress markers were elevated in response to drug-induced vascular smooth muscle cells (VSMCs) contraction. Pharmacologic activation of ER stress using Tunicamycin (Tm) persistently induced CAS and significantly promoted Pituitrin-induced CAS in mice as well as in a collagen gel contraction assay. On the contrary, pharmacologic inhibition of ER stress using 4-phenylacetic acid (4-PBA) completely blunted Pituitrin-induced CAS development in mice. Moreover, during the drug-induced VSMCs contraction, expression of ER stress markers were increased in parallel to those of myosin light chain kinase (MLCK) and phosphor-MLC2 (p-MLC2, at Ser19). After inhibiting MLCK activity by using its specific inhibitor ML-7, the ER stress activator Tm failed to activate the MLCK/MLC2 pathway and could neither trigger CAS in mice nor induce VSMCs contraction in vitro. Our results suggested that aberrant ER stress mediated CAS via regulating the MLCK/MLC2 pathway. ER stress activators might be more robust than the common drugs (Pituitrin or acetylcholine) as to induce vasocontraction and thus may serve as potential therapeutics against chronic bleeding, while its inhibitor might be useful for treatment of severe CAS caused by other medication.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Laser aberration signatures in expelled electrons from a tenuous gas

We describe a mechanism by which the aberration content of a focused, multiterawatt laser is imprinted upon the forward angular distribution of electrons ionized within and ponderomotively expelled from the focal volume. In our experiments, the laser aberration type and magnitude are controllably varied, and the measured electron distributions are correspondingly modified in a way consistent with predictions from numerical simulations. This imprint mechanism shows potential for enabling the development of accurate focal-spot characterization of intense lasers when fired at full power and is being developed for extension to petawatt laser systems.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2014

Criteria for admissible values of smooth aberrations for nondiffractive laser beams

We have derived analytical expressions, verified by the methods of numerical simulation, to evaluate the angular divergence of nondiffractive laser beams containing smooth aberrations, i.e., spherical defocusing, astigmatism and toroid. Using these expressions we have formulated the criteria for admissible values of smooth aberrations. (laser applications and other topics in quantum electronics)

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
DOE OSTI2023

Aberrant light sensing and motility in the green alga Chlamydomonas priscuii from the ice-covered Antarctic Lake Bonney

The Antarctic green alga Chlamydomonas priscuii is an obligate psychrophile and an emerging model for photosynthetic adaptation to extreme conditions. Endemic to the ice-covered Lake Bonney, this alga thrives at highly unusual light conditions characterized by very low light irradiance (<15 μmol m -2 s -1 ), a narrow wavelength spectrum enriched in blue light, and an extreme photoperiod. Genome sequencing of C. priscuii exposed an unusually large genome, with hundreds of highly similar gene duplicates and expanded gene families, some of which could be aiding its survival in extreme conditions. In contrast to the described expansion in the genetic repertoire in C. priscuii, here we suggest that the gene family encoding for photoreceptors is reduced when compared to related green algae. This alga also possesses a very small eyespot and exhibits an aberrant phototactic response, compared to the model Chlamydomonas reinhardtii. We also investigated the genome and behavior of the closely related psychrophilic alga Chlamydomonas sp. ICE-MDV, that is found throughout the photic zone of Lake Bonney and is naturally exposed to higher light levels. Our analyses revealed a photoreceptor gene family and a robust phototactic response similar to those in the model Chlamydomonas reinhardtii. These results suggest that the aberrant phototactic response in C. priscuii is a result of life under extreme shading rather than a common feature of all psychrophilic algae. We discuss the implications of these results on the evolution and survival of shade adapted polar algae.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2018

Non-axisymmetric Aberration Patterns from Wide-field Telescopes Using Spin-weighted Zernike Polynomials

If the optical system of a telescope is perturbed from rotational symmetry, the Zernike wavefront aberration coefficients describing that system can be expressed as a function of position in the focal plane using spin-weighted Zernike polynomials. Methodologies are presented to derive these polynomials to arbitrary order. This methodology is applied to aberration patterns produced by a misaligned Ritchey Chretian telescope and to distortion patterns at the focal plane of the DESI optical corrector, where it is shown to provide a more efficient description of distortion than conventional expansions.

79 ASTRONOMY AND ASTROPHYSICS↗
DOE OSTI2025

On-shot, high-intensity laser aberration measurements via ponderomotive electron ejection

We present a technique to assess the spatial aberration content of a focused multi-terawatt laser when fired at full power. This method leverages the direct detection of electrons ponderomotively accelerated from the focal volume formed in a low-pressure gaseous back-fill. Furthermore, our results show that the spatial distribution of emitted electrons exhibits distinct features correlated to the laser aberration type and magnitude. This work represents progress toward the complete and accurate in-situ spatiotemporal characterization of focused high-intensity lasers.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗
DOE OSTI2017

Complex Pupil Masks for Aberrated Imaging of Closely Spaced Objects

Current approach demonstrates the suppression of optical side-lobes and the contraction of the main lobe in the composite image of two object points of the optical system under the influence of defocusing effect when an asymmetric phase edges are imposed over the apodized circular aperture. The resolution of two point sources having different intensity ratio is discussed in terms of the modified Sparrow criterion, functions of the degree of coherence of the illumination, the intensity difference and the degree of asymmetric phase masking. Here we have introduced and explored the effects of focus aberration (defect-of-focus) on the two-point resolution of the optical systems. Results on the aberrated composite image of closely spaced objects with amplitude mask and asymmetric phase masks forms a significant contribution in astronomical and microscopic observations.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗
NASA NTRS1972

Concave holographic grating for spectrographic applications: Study of the aberrations

An analysis of reflecting diffraction gratings by the application of holographic techniques is presented. The subjects discussed are: (1) holographic grating properties, (2) calculation of aberrant optical path, (3) analytical expression of stigmatic points, (4) spherical aberration and limitation of grating width, and (5) determination of construction parameters.

Pieuchard, G.↗
NASA NTRS1977

Primary aberrations for grazing incidence

Beginning with exact relations between object and image coordinates for a single reflective surface, a systematic analysis of general grazing incidence systems is presented. A complete set of primary aberrations for single-element and two-element systems is developed. The importance of a judicious choice for a coordinate system in showing field curvature to be clearly the predominant aberration for a two-element system is discussed. The validity of the theory is verified through comparisons with the exact ray-trace results for the case of a telescope.

Winkler, C. E.↗
NASA NTRS1985

Holographic optical system for aberration corrections in laser Doppler velocimetry

An optical system containing multifaceted holographic optical elements (HOEs) has been developed to correct for aberrations introduced by nonflat windows in laser Doppler velocimetry. The multifacet aberration correction approach makes it possible to record on one plate many sets of adjacent HOEs that address different measurement volume locations. By using 5-mm-diameter facets, it is practical to place 10-20 sets of holograms on one 10 x 12.5-cm plate, so that the procedure of moving the entire optical system to examine different locations may not be necessary. The holograms are recorded in dichromated gelatin and therefore are nonabsorptive and suitable for use with high-power argon laser beams. Low f-number optics coupled with a 90-percent efficient distortion-correcting hologram in the collection side of the system yield high optical efficiency.

Kim, R. C.↗
NASA NTRS1987

Evaluation of an automated karyotyping system for chromosome aberration analysis

Chromosome aberration analysis is a promising complement to conventional radiation dosimetry, particularly in the complex radiation fields encountered in the space environment. The capabilities of a recently developed automated karyotyping system were evaluated both to determine current capabilities and limitations and to suggest areas where future development should be emphasized. Cells exposed to radiometric chemicals and to photon and particulate radiation were evaluated by manual inspection and by automated karyotyping. It was demonstrated that the evaluated programs were appropriate for image digitization, storage, and transmission. However, automated and semi-automated scoring techniques must be advanced significantly if in-flight chromosome aberration analysis is to be practical. A degree of artificial intelligence may be necessary to realize this goal.

Prichard, Howard M.↗
NASA NTRS1991

Ruling Blazed, Aberration-Corrected Diffraction Gratings

Proposed optoelectromechanical apparatus that functions partly as ruling engine and partly as pantograph rules blazed, aberration-corrected diffraction gratings. Makes possible to combine precision of aberration-corrected, holographically produced grating with diffraction efficiency of blazed grating by using holographically produced grating as model or master pattern that controls ruling engine making blazed grating. Surface of model holographic grating scanned by sensing head mounted on pantographic arm. Ruling stylus mounted on other end of pantographic arm with tip in grating blank.

Leviton, Douglas B.↗
NASA NTRS1991

Diffraction image formation in optical systems with polarization aberrations. II - Amplitude response matrices for rotationally symmetric systems

In the previous paper in this series (McGuire and Chipman, 1990), a formulation was established for the calculation and analysis of diffraction image quality in polarizing optical systems illuminated with partially polarized, partially coherent light. In the present paper, the effect of second- and fourth-order polarization aberrations on the image plane diffraction patterns are examined. The amplitude response matrix is calculated for optical systems with small numerical apertures. Numerical results are presented for optical systems with circular apertures for three of the aberration types.

Mcguire, James P., Jr.↗