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At least 181 records · Page 10

DYNC1H1 regulates NSCLC cell growth and metastasis by IFN-γ-JAK-STAT signaling and is associated with an aberrant immune response

Highlights: • DYNC1H1 is upregulated and its high expression predicted poor outcomes in NSCLC. • Loss of function of DYNC1H1 inhibits cell growth and metastasis of NSCLC cells in vitro. • DYNC1H1 knockdown inhibited metastasis of NSCLC cells in vivo. • DYNC1H1 loss of function suppresses IFN-γ-JAK-STAT signaling pathway in NSCLC. • DYNC1H1 expression is correlated with aberrant immune response in NSCLC indicated by analysis of TCGA immune data. It is urgent to identify new biomarkers and therapeutic targets to ameliorate the clinical prognosis of patients with lung cancer. The functional significance and molecular mechanism of dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) in nonsmall cell lung cancer (NSCLC) progression is still elusive. In our current study, publicly available data and Western blotting experiments confirmed that DYNC1H1 expression was upregulated in lung cancer samples compared with noncancerous samples. Quantitative real-time PCR (qPCR) results indicated that high DYNC1H1 expression in lung cancer tissues was significantly associated with clinical tumor stage and distal metastasis; moreover, its high expression was negatively correlated with prognosis. Functional experiments demonstrated that DYNC1H1 loss of function caused a significant decrease in cell viability and cell proliferative ability, inhibition of the cell cycle, and promotion of both migration potential and invasion potential in vitro. Animal experiments by tail vein injection of lung cancer cells showed that DYNC1H1 knockdown significantly decreased lung cancer metastasis. Mechanistically, the results from a human protein array showed changes in the IFN-γ-JAK-STAT signaling pathway, and analysis of The Cancer Genome Atlas (TCGA) immune data demonstrated that disturbance of the immune microenvironment might be involved in the impaired growth and metastatic ability mediated by DYNC1H1 loss in NSCLC. DYNC1H1 might serve as a promising biological marker of prognosis and a potential clinical therapeutic target for patients with NSCLC.

60 APPLIED LIFE SCIENCES↗

X-ray Spectrometry in the Era of Aberration-Corrected Electron Optical Beam Lines

Abstract Aberration correction in the analytical transmission electron microscope is most closely associated with improvements in high-resolution imaging. In this paper, the combination of that technology with new system designs, which optimize both electron optics and x-ray detection, is shown to provide more than a tenfold increase in performance over the last 25 years.

Zaluzec, Nestor J. (ORCID:0000000248573487)↗

Electrochemical Degradation of Pt–Ni Nanocatalysts: An Identical Location Aberration-Corrected Scanning Transmission Electron Microscopy Study

The evolution of Pt–Ni nanoparticles supported on amorphous carbon is investigated before and after electrochemical potential cycling (0.6-1.1 V), using aberration-corrected scanning transmission electron microscopy (STEM) and energy dispersive X-ray spectroscopy (EDS). During voltage cycling and due to the dissolution of nanoparticles, single ions/atoms and ionic/atomic clusters emerge and diffuse across the carbon support toward larger nanoparticles, where they redeposit. We observe that the preferred locations for the dissolution are the steps and corners of the nanoparticles. On the other hand, the redeposition process happens often on {111} type planes. In addition, contrary to the conventional view, where larger particles grow isotropically from smaller ones, this research work shows that anisotropic growth of smaller particles occurs during potential cycling. The reason for this behavior seems to be related to the fact that smaller particles with thicker Pt-rich shells trigger the nucleation and deposition of Pt.

catalysts↗

Miniature optical planar camera based on a wide-angle metasurface doublet corrected for monochromatic aberrations

Optical metasurfaces are two-dimensional arrays of nano-scatterers that modify optical wavefronts at subwavelength spatial resolution. They are poised to revolutionize optics by enabling complex low-cost systems where multiple metasurfaces are lithographically stacked and integrated with electronics. For imaging applications, metasurface stacks can perform sophisticated image corrections and can be directly integrated with image sensors. Here we demonstrate this concept with a miniature flat camera integrating a monolithic metasurface lens doublet corrected for monochromatic aberrations, and an image sensor. The doublet lens, which acts as a fisheye photographic objective, has a small f-number of 0.9, an angle-of-view larger than 60° × 60°, and operates at 850 nm wavelength with 70% focusing efficiency. The camera exhibits nearly diffraction-limited image quality, which indicates the potential of this technology in the development of optical systems for microscopy, photography, and computer vision.

47 OTHER INSTRUMENTATION↗

Perfect X-ray focusing via fitting corrective glasses to aberrated optics

Due to their short wavelength, X-rays can in principle be focused down to a few nanometres and below. At the same time, it is this short wavelength that puts stringent requirements on X-ray optics and their metrology. Both are limited by today’s technology. In this work, we present accurate at wavelength measurements of residual aberrations of a refractive X-ray lens using ptychography to manufacture a corrective phase plate. Together with the fitted phase plate the optics shows diffraction-limited performance, generating a nearly Gaussian beam profile with a Strehl ratio above 0.8. As a result, this scheme can be applied to any other focusing optics, thus solving the X-ray optical problem at synchrotron radiation sources and X-ray free-electron lasers.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗

Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair

De novo point mutations and chromosomal structural aberrations (CSA) detected in offspring of unaffected parents show a preferential paternal origin with higher risk for older fathers. Studies in rodents suggest that heritable mutations transmitted from the father can arise from either paternal or maternal misrepair of damaged paternal DNA, and that the entire spermatogenic cycle can be at risk after mutagenic exposure. Understanding the susceptibility and mechanisms of transmission of paternal mutations is important in family planning after chemotherapy and donor selection for assisted reproduction. We report that treatment of male mice with melphalan (MLP), a bifunctional alkylating agent widely used in chemotherapy, induces DNA lesions during male mouse meiosis that persist unrepaired as germ cells progress through DNA repair-competent phases of spermatogenic development. After fertilization, unrepaired sperm DNA lesions are mis-repaired into CSA by the egg's DNA repair machinery producing chromosomally abnormal offspring. In conclusion, these findings highlight the importance of both pre- and post-fertilization DNA repair in assuring the genomic integrity of the conceptus.

59 BASIC BIOLOGICAL SCIENCES↗

Chromatic-aberration-corrected diffractive lenses for ultra-broadband focusing

We exploit the inherent dispersion in diffractive optics to demonstrate planar chromatic-aberration-corrected lenses. Specifically, we designed, fabricated and characterized cylindrical diffractive lenses that efficiently focus the entire visible band (450 nm to 700 nm) onto a single line. These devices are essentially pixelated, multi-level microstructures. Experiments confirm an average optical efficiency of 25% for a three-wavelength apochromatic lens whose chromatic focus shift is only 1.3 μm and 25 μm in the lateral and axial directions, respectively. Super-achromatic performance over the continuous visible band is also demonstrated with averaged lateral and axial focus shifts of only 1.65 μm and 73.6 μm, respectively. These lenses are easy to fabricate using single-step grayscale lithography and can be inexpensively replicated. Furthermore, these devices are thin (<3 μm), error tolerant, has low aspect ratio (<1:1) and offer polarization-insensitive focusing, all significant advantages compared to alternatives that rely on metasurfaces. Lastly, our design methodology offers high design flexibility in numerical aperture and focal length, and is readily extended to 2D.

36 MATERIALS SCIENCE↗

Nanowire growth kinetics in aberration corrected environmental transmission electron microscopy

Here, we visualize atomic level dynamics during Si nanowire growth using aberration corrected environmental transmission electron microscopy, and compare with lower pressure results from ultra-high vacuum microscopy. We discuss the importance of higher pressure observations for understanding growth mechanisms and describe protocols to minimize effects of the higher pressure background gas.

77 NANOSCIENCE AND NANOTECHNOLOGY↗

Separating strain from composition in unit cell parameter maps obtained from aberration corrected high resolution transmission electron microscopy imaging

Based on the evaluation of lattice parameter maps in aberration corrected high resolution transmission electron microscopy images, we propose a simple method that allows quantifying the composition and disorder of a semiconductor alloy at the unit cell scale with high accuracy. This is realized by considering, next to the out-of-plane, also the in-plane lattice parameter component allowing to separate the chemical composition from the strain field. Considering only the out-of-plane lattice parameter component not only yields large deviations from the true local alloy content but also carries the risk of identifying false ordering phenomena like formations of chains or platelets. Our method is demonstrated on image simulations of relaxed supercells, as well as on experimental images of an In{sub 0.20}Ga{sub 0.80}N quantum well. Principally, our approach is applicable to all epitaxially strained compounds in the form of quantum wells, free standing islands, quantum dots, or wires.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Probing the local environment of two-dimensional ordered vacancy structures in Ga{sub 2}SeTe{sub 2} via aberration-corrected electron microscopy

There has been considerable interest in chalcogenide alloys with high concentrations of native vacancies that lead to properties desirable for thermoelectric and phase-change materials. Recently, vacancy ordering has been identified as the mechanism for metal-insulator transitions observed in GeSb{sub 2}Te{sub 4} and an unexpectedly low thermal conductivity in Ga{sub 2}Te{sub 3}. Here, we report the direct observation of vacancy ordering in Ga{sub 2}SeTe{sub 2} utilizing aberration-corrected electron microscopy. Images reveal a cation-anion dumbbell inversion associated with the accommodation of vacancy ordering across the entire crystal. The result is a striking example of the interplay between native defects and local structure.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Direct imaging of light elements by annular dark-field aberration-corrected scanning transmission electron microscopy

In this report, we show that an annular dark-field detector in an aberration-corrected scanning transmission electron microscope allows the direct observation of light element columns in crystalline lattices. At specific imaging conditions, an enhancement of the intensities of light element columns in the presence of heavy element columns is observed. Experimental results are presented for imaging the nitrogen and carbon atomic columns at the GaN-SiC interface and within the GaN and SiC compounds. The crystal polarity of GaN at the interface is identified. The obtained findings are discussed and are well supported by image simulations.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Direct imaging of crystal structure and defects in metastable Ge{sub 2}Sb{sub 2}Te{sub 5} by quantitative aberration-corrected scanning transmission electron microscopy

Knowledge about the atomic structure and vacancy distribution in phase change materials is of foremost importance in order to understand the underlying mechanism of fast reversible phase transformation. In this Letter, by combining state-of-the-art aberration-corrected scanning transmission electron microscopy with image simulations, we are able to map the local atomic structure and composition of a textured metastable Ge{sub 2}Sb{sub 2}Te{sub 5} thin film deposited by pulsed laser deposition with excellent spatial resolution. The atomic-resolution scanning transmission electron microscopy investigations display the heterogeneous defect structure of the Ge{sub 2}Sb{sub 2}Te{sub 5} phase. The obtained results are discussed. Highly oriented Ge{sub 2}Sb{sub 2}Te{sub 5} thin films appear to be a promising approach for further atomic-resolution investigations of the phase change behavior of this material class.

36 MATERIALS SCIENCE↗

In situ observation on hydrogenation of Mg-Ni films using environmental transmission electron microscope with aberration correction

In situ transmission electron microscopy (TEM) was performed to observe the hydrogenation of Mg-Ni films in a hydrogen atmosphere of 80–100 Pa. An aberration-corrected environmental TEM with a differential pumping system allows us to reveal the Angstrom-scale structure of the films in the initial stage of hydrogenation: first, nucleation and growth of Mg{sub 2}NiH{sub 4} crystals with a lattice spacing of 0.22 nm in an Mg-rich amorphous matrix of the film occurs within 20 s after the start of the high-resolution observation, then crystallization of MgH{sub 2} with a smaller spacing of 0.15 nm happens after approximately 1 min. Our in situ TEM method is also applicable to the analysis of other hydrogen-related materials.

75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND↗

Evaluation of stacking faults and associated partial dislocations in AlSb/GaAs (001) interface by aberration-corrected high-resolution transmission electron microscopy

The stacking faults (SFs) in an AlSb/GaAs (001) interface were investigated using a 300 kV spherical aberration-corrected high-resolution transmission electron microscope (HRTEM). The structure and strain distribution of the single and intersecting (V-shaped) SFs associated with partial dislocations (PDs) were characterized by the [110] HRTEM images and geometric phase analysis, respectively. In the biaxial strain maps ε{sub xx} and ε{sub yy}, a SF can be divided into several sections under different strain states (positive or negative strain values). Furthermore, the strain state for the same section of a SF is in contrast to each other in ε{sub xx} and ε{sub yy} strain maps. The modification in the strain states was attributed to the variation in the local atomic displacements for the SF in the AlSb film on the GaAs substrate recorded in the lattice image. Finally, the single SF was found to be bounded by two 30° PDs. A pair of 30° PDs near the heteroepitaxial interface reacted to form a Lomer-Cottrell sessile dislocation located at the vertices of V-shaped SFs with opposite screw components. The roles of misfit dislocations, such as the PDs, in strain relaxation were also discussed.

36 MATERIALS SCIENCE↗

Anti-phase boundaries at the SrTiO{sub 3}/Si(001) interface studied using aberration-corrected scanning transmission electron microscopy

In this work, the atomic structure of anti-phase boundary defects at the SrTiO{sub 3}/Si (001) interface is investigated by aberration-corrected scanning transmission electron microscopy. Atomic-resolution images reveal an abrupt SrTiO{sub 3}/Si interface with no intermediate oxide layer. Both single and double Si atomic columns (“dumbbells”) from different terraces of the Si(001) surface are visible at the interface. Anti-phase boundaries (APB) consisting of two adjacent TiO{sub 2} planes in the SrTiO{sub 3} (STO) film resulting either from Si surface steps or from the merging of crystalline domains from different surface nucleation sites are identified. These APBs occur on either {110} or {010} planes and both types have displacement vectors of a{sub STO}/2〈110〉.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

APODIZED PUPIL LYOT CORONAGRAPHS FOR ARBITRARY APERTURES. IV. REDUCED INNER WORKING ANGLE AND INCREASED ROBUSTNESS TO LOW-ORDER ABERRATIONS

The Apodized Pupil Lyot Coronagraph (APLC) is a diffraction suppression system installed in the recently deployed instruments Palomar/P1640, Gemini/GPI, and VLT/SPHERE to allow direct imaging and spectroscopy of circumstellar environments. Using a prolate apodization, the current implementations offer raw contrasts down to 10{sup –7} at 0.2 arcsec from a star over a wide bandpass (20%), in the presence of central obstruction and struts, enabling the study of young or massive gaseous planets. Observations of older or lighter companions at smaller separations would require improvements in terms of the inner working angle (IWA) and contrast, but the methods originally used for these designs were not able to fully explore the parameter space. We propose a novel approach to improve the APLC performance. Our method relies on the linear properties of the coronagraphic electric field with the apodization at any wavelength to develop numerical solutions producing coronagraphic star images with high-contrast region in broadband light. We explore the parameter space by considering different aperture geometries, contrast levels, dark-zone sizes, bandpasses, and focal plane mask sizes. We present an application of these solutions to the case of Gemini/GPI with a design delivering a 10{sup –8} raw contrast at 0.19 arcsec and offering a significantly reduced sensitivity to low-order aberrations compared to the current implementation. Optimal solutions have also been found to reach 10{sup –10} contrast in broadband light regardless of the aperture shape, with effective IWA in the 2-3.5 λ/D range, therefore making the APLC a suitable option for the future exoplanet direct imagers on the ground or in space.

79 ASTRONOMY AND ASTROPHYSICS↗

CMB aberration and Doppler effects as a source of hemispherical asymmetries

Our peculiar motion with respect to the CMB rest frame represents a preferred direction in the observed CMB sky since it induces an apparent deflection of the observed CMB photons (aberration) and a shift in their frequency (Doppler). Both effects distort the multipoles a{sub ℓm}'s at all ℓ's. Such effects are real as it has been recently measured for the first time by Planck according to what was forecast in some recent papers. However, the common lore when estimating a power spectrum from CMB is to consider that Doppler affects only the ℓ = 1 multipole, neglecting any other corrections. In this work we use simulations of the CMB sky in a boosted frame with a peculiar velocity β≡v/c = 1.23 × 10{sup −3} in order to assess the impact of such effect on power spectrum estimations in different regions of the sky. We show that the boost induces a north-south asymmetry in the power spectrum which is highly significant and non-negligible, of about (0.58±0.10)% for half-sky cuts when going up to ℓ ≈ 2500. We suggest that these effects are relevant and may account for some of the north-south asymmetries seen in the Planck data, being especially important at small scales. Finally we analyze the particular case of the ACT experiment, which observed only a small fraction of the sky and show that it suffers a bias of about 1% on the power spectrum and of similar size on some cosmological parameters: for example the position of the peaks shifts by 0.5% and the overall amplitude of the spectrum is about 0.4% lower than a full-sky case.

79 ASTRONOMY AND ASTROPHYSICS↗

Space-Charge Aberrations in Single-Shot Time-Resolved Transmission Electron Microscopy

In this paper, we discuss effects of space-charge fields on imaging performance in a single-shot time-resolved transmission electron microscope. Using a Green’s function perturbation method, we derive analytical estimates for the effects of space-charge nonlinearity on the image formation process and the associated aberration coefficients. The dependence of these coefficients on the initial beam phase space distribution is elucidated. The results are validated by particle tracking simulations and provide fundamental scaling laws for the trade-off between temporal and spatial resolutions in single-shot time-resolved transmission electron microscopy.

43 PARTICLE ACCELERATORS↗