Loci specific epigenetic drug sensitivity.

Therapeutic targeting of epigenetic modulators offers a novel approach to the treatment of multiple diseases. The cellular consequences of chemical compounds that target epigenetic regulators (epi-drugs) are complex. Epi-drugs affect global cellular phenotypes and cause local changes to gene expression due to alteration of a gene chromatin environment. Despite increasing use in the clinic, the mechanisms responsible for cellular changes are unclear. Specifically, to what degree the effects are a result of cell-wide changes or disease related locus specific effects is unknown. Here we developed a platform to systematically and simultaneously investigate the sensitivity of epi-drugs at hundreds of genomic locations by combining DNA barcoding, unique split-pool encoding, and single cell expression measurements. Internal controls are used to isolate locus specific effects separately from any global consequences these drugs have. Using this platform we discovered wide-spread loci specific sensitivities to epi-drugs for three distinct epi-drugs that target histone deacetylase, DNA methylation and bromodomain proteins. By leveraging ENCODE data on chromatin modification, we identified features of chromatin environments that are most likely to be affected by epi-drugs. The measurements of loci specific epi-drugs sensitivities will pave the way to the development of targeted therapy for personalized medicine

Evaluation of Landsat-8 and Sentinel-2A Aerosol Optical Depth Retrievals Across Chinese Cities and Implications for Medium Spatial Resolution Urban Aerosol Monitoring

In urban environments, aerosol distributions may change rapidly due to building and transport infrastructure and human population density variations. The recent availability of medium resolution Landsat-8 and Sentinel-2 satellite data provide the opportunity for aerosol optical depth (AOD) estimation at higher spatial resolution than provided by other satellites. AOD retrieved from 30 m Landsat-8 and 10 m Sentinel-2A data using the Land Surface Reflectance Code (LaSRC) were compared with coincident ground-based Aerosol Robotic Network (AERONET) Version 3 AOD data for 20 Chinese cities in 2016. Stringent selection criteria were used to select contemporaneous data; only satellite and AERONET data acquired within 10 min were considered. The average satellite retrieved AOD over a 1470 m1470 m window centered on each AERONET site was derived to capture fine scale urban AOD variations. AERONET Level 1.5 (cloud-screened) and Level 2.0 (cloud-screened and also quality assured) data were considered. For the 20 urban AERONET sites in 2016 there were 106 (Level 1.5) and 67 (Level 2.0) Landsat-8 AERONET AOD contemporaneous data pairs, and 118 (Level 1.5) and 89 (Level 2.0) Sentinel-2A AOD data pairs. The greatest AOD values (>1.5) occurred in Beijing, suggesting that the Chinese capital was one of the most polluted cities in China in 2016. The LaSRC Landsat-8 and Sentinel-2A AOD retrievals agreed well with the AERONET AOD data (linear regression slopes > 0.96; coefficient of determination r(exp 2) > 0.90; root mean square deviation < 0.175) and demonstrate that the LaSRC is an effective and applicable medium resolution AOD retrieval algorithm over urban environments. The Sentinel-2A AOD retrievals had better accuracy than the Landsat-8 AOD retrievals, which is consistent with previously published research.The implications of the research and the potential for urban aerosol monitoring by combining the freely available Landsat-8 and Sentinel-2 satellite data are discussed

Dynamic metasurface lens based on MEMS Technology

In the recent years, metasurfaces, being flat and lightweight, have been designed to replace bulky optical components with various functions. We demonstrate a monolithic Micro-Electro-Mechanical System (MEMS) integrated with a metasurface-based flat lens that focuses light in the mid-infrared spectrum. A two-dimensional scanning MEMS platform controls the angle of the lens along the two orthogonal axes (tip-tilt) by +-9 degrees, thus enabling dynamic beam steering. The device can compensate for off-axis incident light and thus correct for aberrations such as coma. We show that for low angular displacements, the integrated lens-on-MEMS system does not affect the mechanical performance of the MEMS actuators and preserves the focused beam profile as well as the measured full width at half maximum. We envision a new class of flat optical devices with active control provided by the combination of metasurfaces and MEMS for a wide range of applications, such as miniaturized MEMS-based microscope systems, LIDAR scanners, and projection systems

Relating supercooling and glass-like arrest of kinetics for phase separated systems: studies on doped CeFe2_2 and (La,Pr,Ca)MnO3_3

Coexisting ferromagnetic and antiferromagnetic phases over a range of temperature as well as magnetic field have been reported in many materials of current interest, showing disorder-broadened 1st order transitions. Anomalous history effects observed in magnetization and resistivity are being explained invoking the concepts of kinetic arrest akin to glass transitions. From magnetization measurements traversing novel paths in field-temperature space, we obtain the intriguing result that the regions of the sample which can be supercooled to lower temperatures undergo kinetic-arrest at higher temperatures, and vice versa. Our results are for two diverse systems viz. the inter-metallic doped CeFe$_2$ which has an antiferromagnetic ground state, and the oxide La-Pr-Ca-Mn-O which has a ferromagnetic ground state, indicating the possible universality of this effect of disorder on the widely encountered phenomenon of glass-like arrest of kinetics

100-kHz Rate Rayleigh Imaging for Combustion and Flow Diagnostics

Two-dimensional (2D) Rayleigh scattering (RS) imaging at an ultrahigh repetition rate of 100 kHz is demonstrated in non-reacting and reacting flows employing a high-energy burst-mode laser system. Image sequences of flow mixture fraction were directly derived from high-speed RS images. Additionally, a 2D instantaneous flow velocity field at 100 kHz was obtained through optical-flow-based analysis of the RS images. The technique was also applied to study turbulent flames having a near-constant Rayleigh cross section. The demonstrated high-speed RS technique in conjunction with optical-flow-based analysis provides non-intrusive, simultaneous measurements of the flow mixing and velocity field, extending the measurement capability of the RS technique to high-speed non-reacting and reacting flows

Automated protein structure modeling in CASP9 by I‐TASSER pipeline combined with QUARK‐based ab initio folding and FG‐MD‐based structure refinement

I‐TASSER is an automated pipeline for protein tertiary structure prediction using multiple threading alignments and iterative structure assembly simulations. In CASP9 experiments, two new algorithms, QUARK and fragment‐guided molecular dynamics (FG‐MD), were added to the I‐TASSER pipeline for improving the structural modeling accuracy. QUARK is a de novo structure prediction algorithm used for structure modeling of proteins that lack detectable template structures. For distantly homologous targets, QUARK models are found useful as a reference structure for selecting good threading alignments and guiding the I‐TASSER structure assembly simulations. FG‐MD is an atomic‐level structural refinement program that uses structural fragments collected from the PDB structures to guide molecular dynamics simulation and improve the local structure of predicted model, including hydrogen‐bonding networks, torsion angles, and steric clashes. Despite considerable progress in both the template‐based and template‐free structure modeling, significant improvements on protein target classification, domain parsing, model selection, and ab initio folding of β‐proteins are still needed to further improve the I‐TASSER pipeline. Proteins 2011; © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/88077/1/23111_ftp.pd

Pathologic evaluation of tumor-associated macrophage density and vessel inflammation in invasive breast carcinomas

Tumor-associated macrophages (TAMs) are major constituents of the tumor microenvironment in solid tumors and have been implicated as mediators of tumor progression, invasion and metastasis. Correspondingly, accumulation of TAMs is associated with unfavorable clinical outcomes in numerous types of solid tumors. E-selectin is a hallmark of inflammation and a key adhesion molecule that accommodates the initial contact of circulating immune cells with the inflamed vessel surface. Currently, the association between E-selectin and TAMs is not fully elucidated; therefore, the present study investigated the association between vessel inflammation, TAM infiltration, and clinical outcome in breast cancer. A total of 53 procedure-naïve invasive breast cancer cases were immunohistochemically analyzed for the presence of cluster of differentiation (CD)68+ TAMs, E-selectin+ vessels and tumor inflammation. The association between CD68 and E-selectin expression, and tumor inflammation as well as overall survival was evaluated using Kaplan-Meier survival curves and multivariable Cox\u27s proportional hazards regression analysis. The abundance of TAMs was identified to be positively associated with tumor inflammation, estrogen receptor and E-selectin expression levels. A greater prevalence of TAMs and tumor inflammation was significantly associated with shorter overall survival times. E-selectin expression levels were significantly higher in tumor vessels among elderly patients, but were not associated with overall survival. The abundance of TAMs was associated with the presence of E-selectin-expressing inflamed tumor vessels and tumor inflammation, as well as overall survival in patients with invasive breast carcinoma. © 2017, Spandidos Publications. All rights reserved