3D-Epigenomic Regulation of Gene Transcription in Hepatocellular Carcinoma.

The fundamental cause of transcription dysregulation in hepatocellular carcinoma (HCC) remains elusive. To investigate the underlying mechanisms, comprehensive 3D-epigenomic analyses are performed in cellular models of THLE2 (a normal hepatocytes cell line) and HepG2 (a hepatocellular carcinoma cell line) using integrative approaches for chromatin topology, genomic and epigenomic variation, and transcriptional output. Comparing the 3D-epigenomes in THLE2 and HepG2 reveal that most HCC-associated genes are organized in complex chromatin interactions mediated by RNA polymerase II (RNAPII). Incorporation of genome-wide association studies (GWAS) data enables the identification of non-coding genetic variants that are enriched in distal enhancers connecting to the promoters of HCC-associated genes via long-range chromatin interactions, highlighting their functional roles. Interestingly, CTCF binding and looping proximal to HCC-associated genes appear to form chromatin architectures that overarch RNAPII-mediated chromatin interactions. It is further demonstrated that epigenetic variants by DNA hypomethylation at a subset of CTCF motifs proximal to HCC-associated genes can modify chromatin topological configuration, which in turn alter RNAPII-mediated chromatin interactions and lead to dysregulation of transcription. Together, the 3D-epigenomic analyses provide novel insights of multifaceted interplays involving genetics, epigenetics, and chromatin topology in HCC cells

Visual Psychophysics and Physiological Optics Age-Related Changes in the Anterior Segment Biometry During Accommodation

PURPOSE. We investigated the dynamic response of human accommodative elements as a function of age during accommodation using synchronized spectral domain optical coherence tomography devices (SD-OCT). METHODS. We enrolled 33 left eyes from 33 healthy subjects (age range, 20-39 years, 17 males and 16 females). Two SD-OCT devices were synchronized to simultaneously image the anterior segment through pupil and the ciliary muscle during 6.00 diopter (D) accommodation for approximately 3.7 seconds in two repeated measurements. The anterior segment parameters included the lens thickness (LT), radius of curvature of the lens anterior surface (LAC), maximum thickness of ciliary muscle (CMTMAX), and anterior length of the ciliary muscle (CMAL). A first-order exponential equation was used to fit the dynamic changes during accommodation. The age-related changes in the dynamic response and their relationship were calculated and compared. RESULTS. The amplitude (r ¼ À0.40 and 0.53 for LT and LAC, respectively) and peak velocity (r ¼ À0.65 and 0.71 for LT and LAC, respectively) of the changes in LT and LAC significantly decreased with age (P < 0.05), whereas the parameters of the ciliary muscle remained unchanged (P > 0.05), except for the peak velocity of the CMAL (r ¼ 0.44, P ¼ 0.01). The difference in the time constant between the lens reshaping (LT and LAC) and CMTMAX increased with age (r ¼ 0.46 and 0.57 for LT and LAC, respectively, P < 0.01). The changes in LT and LAC per millimeter of CMTMAX change decreased with age (r ¼ À0.52 and À0.34, respectively, P < 0.05). The ciliary muscle forward movement correlated with the lens deformation (r ¼ À0.35 and 0.40 for amplitude, while r ¼ 0.36 and 0.58 for time constant, respectively, P < 0.05). CONCLUSIONS. Age-related changes in the lens reshaping and ciliary muscle forward movement were found. Lens reshaping was much slower than the contraction of the ciliary muscle, especially in aging eyes, and this process required the ciliary muscle to contract more to reach a given response

Topology hierarchy of transition metal dichalcogenides built from quantum spin Hall layers

The evolution of the physical properties of two-dimensional material from monolayer limit to the bulk reveals unique consequences from dimension confinement and provides a distinct tuning knob for applications. Monolayer 1T'-phase transition metal dichalcogenides (1T'-TMDs) with ubiquitous quantum spin Hall (QSH) states are ideal two-dimensional building blocks of various three-dimensional topological phases. However, the stacking geometry was previously limited to the bulk 1T'-WTe2 type. Here, we introduce the novel 2M-TMDs consisting of translationally stacked 1T'-monolayers as promising material platforms with tunable inverted bandgaps and interlayer coupling. By performing advanced polarization-dependent angle-resolved photoemission spectroscopy as well as first-principles calculations on the electronic structure of 2M-TMDs, we revealed a topology hierarchy: 2M-WSe2, MoS2, and MoSe2 are weak topological insulators (WTIs), whereas 2M-WS2 is a strong topological insulator (STI). Further demonstration of topological phase transitions by tunning interlayer distance indicates that band inversion amplitude and interlayer coupling jointly determine different topological states in 2M-TMDs. We propose that 2M-TMDs are parent compounds of various exotic phases including topological superconductors and promise great application potentials in quantum electronics due to their flexibility in patterning with two-dimensional materials

Observation of topological electronic structure in quasi-1D superconductor TaSe3

Topological superconductors (TSCs), with the capability to host Majorana bound states that can lead to non-Abelian statistics and application in quantum computation, have been one of the most intensively studied topics in condensed matter physics recently. Up to date, only a few compounds have been proposed as candidates of intrinsic TSCs, such as doped topological insulator CuxBi2Se3 and iron-based superconductor FeTe0.55Se0.45. Here, by carrying out synchrotron and laser based angle-resolved photoemission spectroscopy (ARPES), we systematically investigated the electronic structure of a quasi-1D superconductor TaSe3, and identified the nontrivial topological surface states. In addition, our scanning tunneling microscopy (STM) study revealed a clean cleaved surface with a persistent superconducting gap, proving it suitable for further investigation of potential Majorana modes. These results prove TaSe3 as a stoichiometric TSC candidate that is stable and exfoliable, therefore a great platform for the study of rich novel phenomena and application potentials.Comment: to appear in Matte

Analysis of water film thickness on contact lens by reflectometry technique

We report the use of optical reflectometry technique for evaluation of water film on contact lens. The water film can be measured through the spectral dependent reflectance evaluation, which is carried out by illuminating the contact lens with a white light and collecting the returning light with an optical fiber coupled to a spectrometer. Water film thinning process has been observed on different soft contact lenses and minimum measurable thickness is about 0.85 m. The measurement is fast and accurate. The water film measurement can be valuable for contact lens design to improve its hydrophilic properties. The technique can be extended for the study of tear film dynamics in an eye

The Watery Eye

The surface of the eye needs to be wet constantly to ensure its integrity in maintaining ocular comfort, clear vision, and ocular health. This article presents new findings in the tear dynamics of the human eye, with an emphasis on the tear meniscus and tear film through the day and in response to punctual occlusion and wearing of contact lenses. Recent advances in imaging technique are briefly discussed

Micrometer-scale contact lens movements imaged by ultrahigh-resolution optical coherence tomography

To dynamically evaluate contact lens movement and ocular surface shape using ultrahigh-resolution and ultralong-scan-depth optical coherence tomography (OCT). Clinical research study of a laboratory technique. Four different types of soft contact lenses were tested on the left eye of 10 subjects (6 male and 4 female). Lens edges at primary gaze and temporal and nasal gazes were imaged by ultrahigh-resolution OCT. Excursion lag was obtained as the distance between the lens edge at primary gaze and immediately after the eye was quickly turned either nasally or temporally. The inferior lens edges were imaged continuously to track vertical movements during blinking. Ultralong-scan-depth OCT provided quantifiable images of the ocular surface, and the contour was acquired using custom software. Excursion lag at the horizontal meridian was 366 ± 134 μm at temporal gaze and 320 ± 137 μm at nasal gaze (P > .05). The lens uplift at the vertical meridian was 342 ± 155 μm after blinking. There were significant differences in horizontal lags and vertical movements among different lenses (P < .05). Horizontal lags were correlated with radii of curvatures and sagittal heights at 6-mm and 14-mm horizontal meridian (P < .05). The blink-induced lens uplift first lowered by 104 ± 8 μm, and then lifted 342 ± 155 μm after the blink. Ultrahigh-resolution and ultralong-scan-depth OCT can assess micrometer-scale lens movements and ocular surface contours. Both lens design and ocular surface shape affected lens movements

Entire contact lens imaged in vivo and in vitro with spectral domain optical coherence tomography

OBJECTIVE: To demonstrate the capability of directly visualizing the entire ocular surface and the entire contact lens on the eye using spectral domain optical coherence tomography (SD-OCT). METHODS: A custom built, high speed and high resolution SD-OCT was developed with extended scan depth and width. The eye was imaged before and after wearing a toric soft contact lens (PureVision, Bausch & Lomb, Rochester, NY). A lubricant eye drop (Soothe, Bausch & Lomb) was instilled in the eye to enhance the image contrast on the lens. The same toric soft contact lens immersed in the contact lens solution was also imaged with a contrast enhancement medium (0.5% Intralipid). RESULTS: Cross-sectional OCT images of the entire ocular surface were acquired with high resolution 2048×2048 pixels. Quantitative surface height map of the ocular surface was obtained from a radial scan dataset containing 32 B-scans. With the contrast enhancement agent, the entire toric soft contact lens was clearly visualized both in vitro and on the eye. The surfaces of the lens were detected and used to generate the thickness maps of the soft contact lens. CONCLUSIONS: SD-OCT with extended scan depth and width is a promising tool for imaging the entire ocular surface shape and soft contact lenses. This successful demonstration suggests that the extended depth SD-OCT is effective in studying ocular surface shape and its interaction with a soft contact lens. The novel method is helpful for contact lens fitting evaluation and lens design