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At least 91 records · Page 5

Chromosome aberrations of clonal origin are present in astronauts' blood lymphocytes

Radiation-induced chromosome translocations remain in peripheral blood cells over many years, and can potentially be used to measure retrospective doses or prolonged low-dose rate exposures. However, several recent studies have indicated that some individuals possess clones of cells with balanced chromosome abnormalities, which can result in an overestimation of damage and, therefore, influence the accuracy of dose calculations. We carefully examined the patterns of chromosome damage found in the blood lymphocytes of twelve astronauts, and also applied statistical methods to screen for the presence of potential clones. Cells with clonal aberrations were identified in three of the twelve individuals. These clonal cells were present in samples collected both before and after space flight, and yields are higher than previously reported for healthy individuals in this age range (40-52 years of age). The frequency of clonal damage appears to be even greater in chromosomes prematurely condensed in interphase, when compared with equivalent analysis in metaphase cells. The individuals with clonal aberrations were followed-up over several months and the yields of all clones decreased during this period. Since clonal aberrations may be associated with increased risk of tumorigenesis, it is important to accurately identify cells containing clonal rearrangements for risk assessment as well as biodosimetry. Copyright 2003 S. Karger AG, Basel.

Chromosomes, Human/radiation effects/ultrastructur↗

MiR-509-3-5p causes aberrant mitosis and anti-proliferative effect by suppression of PLK1 in human lung cancer A549 cells

MicroRNAs (miRNAs) are potent post-transcriptional regulators of gene expression and play roles in DNA damage response (DDR). PLK1 is identified as a modulator of DNA damage checkpoint. Although down-regulation of PLK1 by certain microRNAs has been reported, little is known about the interplay between PLK1 and miR-509-3-5p in DDR. Here we have demonstrated that miR-509-3-5p repressed PLK1 expression by targeting PLK1 3′-UTR, thereby causing mitotic aberration and growth arrest of human lung cancer A549 cells. Repression of PLK1 by miR-509-3-5p was further evidenced by over-expression of miR-509-3-5p in A549, HepG2 and HCT116p53{sup −/−} cancer cells, in which PLK1 protein was suppressed. Consistently, miR-509-3-5p was stimulated, while PLK1 protein was down-regulated in A549 cells exposed to CIS and ADR, suggesting that suppression of PLK1 by miR-509-3-5p is a component of CIS/ADR-induced DDR pathway. Flow cytometry and immunofluorescence labeling showed that over-expression of miR-509-3-5p in A549 induced G2/M arrest and aberrant mitosis characterized by abnormal bipolar mitotic spindles, condensed chromosomes, lagging DNA and chromosome bridges. In addition, over-expression of miR-509-3-5p markedly blocked A549 cell proliferation and sensitized the cells to CIS and ADR treatment. Taken together, miR-509-3-5p is a feasible suppressor for cancer by targeting PLK1. Our data may provide aid in potential design of combined chemotherapy and in our better understanding of the roles of microRNAs in response to DNA damage. - Highlights: • MiR-509-3-5p represses PLK1 expression by targeting PLK1 3ГЉВ№-UTR. • Expression of miR-509-3-5p is induced and PLK1 repressed upon DNA damage. • Overexpression of miR-509-3-5p induces G2/M arrest and aberrant mitosis. • MiR-509-3-5p inhibits cell proliferation and sensitizes cells to DNA damage agents.

60 APPLIED LIFE SCIENCES↗

microRNA-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant cell proliferation in human glioma

Highlights: • We examined the role of PHD Finger Protein 19 (PHF19) in human glioma. • PHF19 was upregulated in glioma tumors, correlating with miR-124a downregulation. • miR-124a suppressed PHF19 expression, EZH2 activation, and cell proliferation. • PHF19 knockdown suppressed EZH2 activation and glioma cell proliferation. • Xenograft tumor growth was inhibited by miRNA-124a or PHF19 shRNA. Enhancer of Zeste 2 (EZH2) is the key enzymatic factor in Polycomb Repressive Complex 2 (PRC2), a transcriptional repressor which contributes to oncogenesis. Recent research has revealed the key role of aberrant EZH2 hyper-activity in human gliomas. Here, we examined the role of the lesser-known PRC2-associated PHD Finger Protein 19 (PHF19) in human glioma. We found that PHF19 transcript and protein levels were significantly elevated in human glioma tumors, which was negatively associated with expression of the anti-PHF19 microRNA miR-124a. miR-124a over-expression in the A172 and U251MG glioma cell lines and patient glioma cells suppressed PHF19 expression, EZH2 activation, and cell proliferation. However, miR-124a did not suppress cell proliferation with PHF19 silencing or mutation. Knockdown of PHF19 suppressed EZH2 phosphorylation and proliferation of glioma cells. Co-immunoprecipitation confirmed that PHF19 forms the PRC2 with EZH2, EED, and SUZ12. In a nude murine model, subcutaneous and orthotopic xenograft tumor growth was significantly inhibited by miRNA-124a or PHF19 shRNA. In conclusion, miR-124a suppresses PHF19 over-expression, EZH2 hyper-activation, and aberrant glioma cell proliferation. Targeting PHF19 via miR-124a agomir therapy may block aberrant EZH2 hyper-activity in these tumors.

60 APPLIED LIFE SCIENCES↗

Aberration-Corrected Electron Beam Lithography at the One Nanometer Length Scale

Patterning materials efficiently at the smallest length scales has been a longstanding challenge in nanotechnology. Electron-beam lithography (EBL) is the primary method for patterning arbitrary features, but EBL has not reliably provided sub-4 nm patterns. The few competing techniques that have achieved this resolution are orders of magnitude slower than EBL. In this work, we employed an aberration-corrected scanning transmission electron microscope for lithography to achieve unprecedented resolution. Here we show aberration-corrected EBL at the one nanometer length scale using poly(methyl methacrylate) (PMMA) and have produced both the smallest isolated feature in any conventional resist (1.7 ± 0.5 nm) and the highest density patterns in PMMA (10.7 nm pitch for negative-tone and 17.5 nm pitch for positive-tone PMMA). We also demonstrate pattern transfer from the resist to semiconductor and metallic materials at the sub-5 nm scale. These results indicate that polymer-based nanofabrication can achieve feature sizes comparable to the Kuhn length of PMMA and ten times smaller than its radius of gyration. Use of aberration-corrected EBL will increase the resolution, speed, and complexity in nanomaterial fabrication.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Regulation of RNA-binding proteins affinity to export receptors enables the nuclear basket proteins to distinguish and retain aberrant mRNAs

Export of messenger ribonucleic acids (mRNAs) into the cytoplasm is a fundamental step in gene regulation processes, which is meticulously quality controlled by highly efficient mechanisms in eukaryotic cells. Yet, it remains unclear how the aberrant mRNAs are recognized and retained inside the nucleus. Using a new modelling approach for complex systems, namely the agent-based modelling (ABM) approach, we develop a minimal model of the mRNA quality control (QC) mechanism. Our results demonstrate that regulation of the affinity of RNA-binding proteins (RBPs) to export receptors along with the weak interaction between the nuclear basket protein (Mlp1 or Tpr) and RBPs are the minimum requirements to distinguish and retain aberrant mRNAs. Our results show that the affinity between Tpr and RBPs is optimized to maximize the retention of aberrant mRNAs. In addition, we demonstrate how the length of mRNA affects the QC process. Since longer mRNAs spend more time in the nuclear basket to form a compact conformation and initiate their export, nuclear basket proteins could more easily capture and retain them inside the nucleus.

Science & Technology - Other Topics↗

Correcting aberrations of a transverse-field neutron resonance spin echo instrument

Neutron resonance spin echo (NRSE) technique has the potential to increase the Fourier time and energy resolution in neutron scattering by using radio frequency (rf) neutron spin-flippers. However, aberrations arising from variations in the neutron path length between the rf flippers reduce the polarization. Here, we develop and test a transverse static-field magnet, a series of which are placed between the rf flippers, to correct for these aberrations. The prototype correction magnet was both simulated in an NRSE beamline using McStas, a Monte Carlo neutron ray-tracing software package, and measured using neutrons. The results from the prototype demonstrate that this static-field design corrects for transverse-field NRSE aberrations.

47 OTHER INSTRUMENTATION↗

UTILIZATION OF THE WAVEFRONT SENSOR AND SHORT-EXPOSURE IMAGES FOR SIMULTANEOUS ESTIMATION OF QUASI-STATIC ABERRATION AND EXOPLANET INTENSITY

Heretofore, the literature on exoplanet detection with coronagraphic telescope systems has paid little attention to the information content of short exposures and methods of utilizing the measurements of adaptive optics wavefront sensors. This paper provides a framework for the incorporation of the wavefront sensor measurements in the context of observing modes in which the science camera takes millisecond exposures. In this formulation, the wavefront sensor measurements provide a means to jointly estimate the static speckle and the planetary signal. The ability to estimate planetary intensities in as little as a few seconds has the potential to greatly improve the efficiency of exoplanet search surveys. For simplicity, the mathematical development assumes a simple optical system with an idealized Lyot coronagraph. Unlike currently used methods, in which increasing the observation time beyond a certain threshold is useless, this method produces estimates whose error covariances decrease more quickly than inversely proportional to the observation time. This is due to the fact that the estimates of the quasi-static aberrations are informed by a new random (but approximately known) wavefront every millisecond. The method can be extended to include angular (due to diurnal field rotation) and spectral diversity. Numerical experiments are performed with wavefront data from the AEOS Adaptive Optics System sensing at 850 nm. These experiments assume a science camera wavelength {lambda} of 1.1 {mu}, that the measured wavefronts are exact, and a Gaussian approximation of shot-noise. The effects of detector read-out noise and other issues are left to future investigations. A number of static aberrations are introduced, including one with a spatial frequency exactly corresponding the planet location, which was at a distance of Almost-Equal-To 3{lambda}/D from the star. Using only 4 s of simulated observation time, a planetary intensity, of Almost-Equal-To 1 photon ms{sup -1}, and a stellar intensity of Almost-Equal-To 10{sup 5} photons ms{sup -1} (contrast ratio 10{sup 5}), the short-exposure estimation method recovers the amplitudes' static aberrations with 1% accuracy, and the planet brightness with 20% accuracy.

79 ASTRONOMY AND ASTROPHYSICS↗

Interpreting the CMB aberration and Doppler measurements: boost or intrinsic dipole?

The aberration and Doppler coupling effects of the Cosmic Microwave Background (CMB) were recently measured by the Planck satellite. The most straightforward interpretation leads to a direct detection of our peculiar velocity β, consistent with the measurement of the well-known dipole. In this paper we discuss the assumptions behind such interpretation. We show that Doppler-like couplings appear from two effects: our peculiar velocity and a second order large-scale effect due to the dipolar part of the gravitational potential. We find that the two effects are exactly degenerate but only if we assume second-order initial conditions from single-field Inflation. Thus, detecting a discrepancy in the value of β from the dipole and the Doppler couplings implies the presence of a primordial non-Gaussianity. We also show that aberration-like signals likewise arise from two independent effects: our peculiar velocity and lensing due to a first order large-scale dipolar gravitational potential, independently on Gaussianity of the initial conditions. In general such effects are not degenerate and so a discrepancy between the measured β from the dipole and aberration could be accounted for by a dipolar gravitational potential. Only through a fine-tuning of the radial profile of the potential it is possible to have a complete degeneracy with a boost effect. Finally we discuss that we also expect other signatures due to integrated second order terms, which may be further used to disentangle this scenario from a simple boost.

79 ASTRONOMY AND ASTROPHYSICS↗

Multidimensional images and aberrations in STEM

Recent advances in scanning transmission electron microscopy (STEM) have led to increased development of multi-dimensional STEM imaging modalities and novel image reconstruction methods. This interest arises because the main electron lens in a modern transmission electron microscope usually has a diffraction-space information limit that is significantly better than the real-space resolution of the same lens. This state-of-affairs is sometimes shared by other scattering methods in modern physics and contributes to a broader excitement surrounding multidimensional techniques that scan a probe while recording diffraction-space images, such as ptychography and scanning nano-beam diffraction. However, the contrasting resolution in the two spaces raises the question as to what is limiting their effective performance. Here, we examine this paradox by considering the effects of aberrations in both image and diffraction planes, and likewise separate the contributions of pre- and post-sample aberrations. In conclusion, this consideration provides insight into aberration-measurement techniques and might also indicate improvements for super-resolution techniques.

Hoglund, Eric R.↗

Estimating field-dependent nodal aberration theory coefficients from Zernike full-field displays by utilizing eighth-order astigmatism

When using freeform surfaces in optical design, the field dependence of the aberrations can become quite complex and understanding these aberrations facilitates the design process. Here, we calculate the field dependence of low-order Zernike astigmatism (Z5/6) up to 8th order in Nodal Aberration Theory (NAT). Expansion of NAT astigmatism terms to 8th order facilitates a more accurate fit to the Zernike astigmatism data. We then show how this estimated field dependence can be used to quantitatively analyze a freeform telescope design. Lastly, this analysis tool adds to the optical designer’s arsenal when up against the challenge of designing with freeform optics.

36 MATERIALS SCIENCE↗

Aberration compensation in a Skew parametric-resonance ionization cooling channel

Skew Parametric-resonance Ionization Cooling (Skew PIC) represents a novel method for focusing of highly divergent particle beams, as in the final 6D cooling stage of a high-luminosity muon collider. In the muon collider concept, the resultant equilibrium transverse emittances from cooling with Skew PIC are an order of magnitude smaller than in conventional ionization cooling. The concept makes use of coupling of the transverse dynamic behavior, and the linear dynamics are well-behaved with good agreement between analytic solutions and simulation results. Compared to the uncoupled system, coupling of the transverse dynamic behavior purports to reduce the number of multipoles required for aberration compensation while also avoiding unwanted resonances. Aberration compensation is more complicated in the coupled case, especially in the high-luminosity muon collider application where equilibrium angular spreads in the cooling channel are on the order of 200 mrad. We present recent progress on aberration compensation for control of highly divergent muon beams in the coupled correlated optics channel, and a simple cooling model to test the transverse acceptance of the channel.

Sy, Amy V.↗

Spherical Aberrations - Final Focus and Solenoid Scans

Conclusions: Spherical aberrations in solenoids are unavoidable and problematic whenever the beam is focused; It may be possible to include a spherical aberration correction to the analysis of a solenoid scan in the manner described above although more accurate 2D PIC models should be studied to determine the accuracy of the very simple model used above. This correction would have to be iterated as the beam size in the solenoid is iterated; A quadrupole triplet final focus would not have aberrations (preliminary analysis shows improvement in spot size, very difficult to tune).

43 PARTICLE ACCELERATORS↗

Aberration corrected RF flipper for high resolution neutron spectroscopy

Project Summary Company: Adelphi Technology, Inc. Title: Aberration-corrected High Frequency RF Flipper for High-Resolution Neutron Spectroscopy PI: Dr. Jay Theodore Cremer Topic: C55-11 Enhancement of Scattering Instrumentation Technology Used at Pulsed and Continuous Sources Subtopic: d. Other Statement of the problem or situation that is being addressed. The quest to understand heterogeneous and hierarchical materials is gathering momentum, as described in a 2015 report by the Basic Energy Sciences Advisory Committee on Challenges at the Frontiers of Matter and Energy. For the past 40 years a technique called neutron spin echo (NSE) has been used to probe molecular motions in such non-crystalline materials over time scales from 10’s of picoseconds to 100’s of nanoseconds. The method has provided unique information about the dynamics of soft heterogeneous materials, including confirmation of the de Gennes model of polymer reptation and quantitative measurement of bending constants of biologically relevant lipid membranes. However, scientists continue to clamor for even higher resolution than NSE can provide. Biomaterials, polymers, glasses, and artificially nanostructured materials all manifest slow molecular motions because of weak or competing interactions between subunits and are amenable to study with neutrons, provided sufficiently long dynamical correlation times can be achieved. All these materials have important applications to advanced technologies so understanding them is key to technological progress. General statement of how this problem is being addressed. We will address the need for high-resolution neutron spectroscopy by using a technique called Neutron Resonance Spin Echo (NRSE). While similar to NSE in many respects, this method has the potential to exceed the NSE capabilities, if 2 technical hurdles can be overcome. The major impediments to successful high-resolution NRSE are the availability of two technologies: a very high frequency, efficient, radiofrequency (rf) flipper for neutrons and a method to correct certain magnetic aberrations. Based on previous STTR support and follow-on research we have developed a suitable rf flipper and we have invented a method to correct the magnetic aberrations. Both technologies need refinement to make them suitable for implementation at a neutron source such as the Oak Ridge National Laboratory nuclear reactor. In this proposal we seek to perfect the two technologies and to combine them into a single, operationally convenient device. Commercial Applications and Other Benefits In view of the increasing demand for the unique scientific information that high resolution neutron spectroscopy can provide, we expect several major instrumentation upgrades at both U.S. and foreign neutron centers will require make use of the NRSE method over the coming decade, creating a market for the devices we will design. These components will enhance scientists’ abilities to probe the time dependence of density fluctuations in a wide range of hierarchical and heterogeneous materials many of which are vital to existing and future technologies. Key Words – Polarized Neutrons, Neutron Spin Echo, Neutron Scattering, advanced materials. Summary for Members of Congress Neutron beams are a powerful materials-science probe that provide unique information about the structure of matter. The proposed devices will accelerate scientific discoveries required to achieve national goals for new technological materials.

36 MATERIALS SCIENCE↗

The correction of aberrations computed in the aperture plane of multifrequency microwave radiometer antennas

An analytical/numerical approach to identifying and correcting the aberrations introduced by a general displacement of the feed from the focal point of a single offset paraboloid antenna used in deployable radiometer systems is developed. A 15 meter reflector with 18 meter focal length is assumed for the analysis, which considers far field radiation pattern quality, focal region fields, and aberrations appearing in the aperture plane. The latter are obtained by ray tracing in the transmit mode and are expressed in terms of optical notation. Attention is given to the physical restraints imposed on corrective elements by real microwave systems and to the intermediate near field aspects of the problem in three dimensions. The subject of wave fronts and caustics in the receive mode is introduced for comparative purposes. Several specific examples are given for aberration reduction at eight beamwidths of scan at a frequency of 1.414 GHz.

Schmidt, R. F.↗

Polarization aberrations in optical systems

This paper examines the polarization aberrations in optical systems of isotropic radially symmetric weak polarizers in the paraxial approximation. Optical systems which fit this description are composed of uncoated and coated lenses and mirrors. Polarization aberrations are variations in phase, amplitude, and polarization state of the electromagnetic field across the exit pupil. Some are dependent on the incident polarization state and some are not. Expressions through fourth order for phase, amplitude, linear polarization, and linear retardance aberrations are derived in terms of the chief and marginal ray angles of incidence and Taylor series expansion coefficients of the Fresnel equations for reflection and transmission at interfaces.

Mcguire, James P., Jr.↗

Polarization aberrations in the solar activity measurements experiments (SAMEX) solar vector magnetograph

An optical design and polarization analysis of the Air Force/NASA Solar Activity Measurements Experiments solar vector magnetograph optical system is performed. Polarization aberration theory demonstrates that conventional telescope coating designs introduce unacceptably high levels of polarization aberrations into the optical system. Several ultralow polarization mirror and lens coatings designs for this instrument are discussed. Balancing of polarization aberrations at different surfaces is demonstrated.

Mcguire, James P., Jr.↗

Formula for the rms blur circle radius of Wolter telescope based on aberration theory

A formula for the rms blur circle for Wolter telescopes has been derived using the transverse ray aberration expressions of Saha (1985), Saha (1984), and Saha (1986). The resulting formula for the rms blur circle radius over an image plane and a formula for the surface of best focus based on third-, fifth-, and seventh-order aberration theory predict results in good agreement with exact ray tracing. It has also been shown that one of the two terms in the empirical formula of VanSpeybroeck and Chase (1972), for the rms blur circle radius of a Wolter I telescope can be justified by the aberration theory results. Numerical results are given comparing the rms blur radius and the surface of best focus vs the half-field angle computed by skew ray tracing and from analytical formulas for grazing incidence Wolter I-II telescopes and a normal incidence Cassegrain telescope.

Shealy, David L.↗

Effects of higher order aberrations on beam shape in an optical recording system

An unexpected irradiance pattern in the detector plane of an optical data storage system was observed. Through wavefront measurement and scalar diffraction modeling, it was discovered that the energy redistribution is due to residual third-order and fifth-order spherical aberration of the objective lens and cover-plate assembly. The amount of residual aberration is small, and the beam focused on the disk would be considered diffraction limited by several criteria. Since the detector is not in the focal plane, even this small amount of aberration has a significant effect on the energy distribution. We show that the energy redistribution can adversely affect focus error signals, which are responsible for maintaining sub-micron spot diameters on the spinning disk.

Wang, Mark S.↗