142 research outputs found

    Texture Analysis of the Retinal Nerve Fiber Layer in Fundus Images via Markov Random Fields

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    Abstract-This paper describes method for analysis of the texture created by retinal nerve fibers (RNF) via Markov Random Fields. The Causal Autoregressive Random (CAR) model is used to create a feature vector describing the changes in texture due to losses in RNF layer. It is shown that features based on CAR model can be used for discrimination between healthy and glaucomatous tissue using simple linear classifier. The classification error is slightly below 4% for the tested dataset

    Magainin 2 and PGLa in bacterial membrane mimics III : membrane fusion and disruption

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    We previously speculated that the synergistically enhanced antimicrobial activity of Magainin 2 and PGLa is related to membrane adhesion, fusion, and further membrane remodelling. Here, we combined computer simulations with time-resolved in vitro fluorescence microscopy, cryogenic electron microscopy (cryo-EM), and small-angle X-ray scattering (SAXS) to interrogate such morphological and topological changes of vesicles at nanoscopic and microscopic length scales in real time. Coarse-grained simulations revealed the formation of an elongated and bent fusion zone between vesicles in the presence of equimolar peptide mixtures. Vesicle adhesion and fusion was observed to occur within few seconds by cryo-EM and corroborated by SAXS measurements. The latter experiments further indicated continued and time-extended structural remodelling also for individual peptides or chemically-linked peptide heterodimers, but with different kinetics. Fluorescence microscopy further captured peptide-dependent adhesion, fusion, and occasional bursting of giant unilamellar vesicles already few seconds after peptide addition. The synergistic interactions between the peptides shorten the time response of vesicles and enhance membrane fusogenic and disrupting properties of the equimolar mixture compared to the individual peptides

    Spin-locking in low-frequency reaction yield detected magnetic resonance

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    The purported effects of weak magnetic fields on various biological systems from animal magnetoreception to human health have generated widespread interest and sparked much controversy in the past decade. To date the only well established mechanism by which the rates and yields of chemical reactions are known to be influenced by magnetic fields is the radical pair mechanism, based on the spin-dependent reactivity of radical pairs. A diagnostic test for the operation of the radical pair mechanism was proposed by Henbest et al. [J. Am. Chem. Soc., 2004, 126, 8102] based on the combined effects of weak static magnetic fields and radiofrequency oscillating fields in a reaction yield detected magnetic resonance experiment. Here we investigate the effects on radical pair reactions of applying relatively strong oscillating fields, both parallel and perpendicular to the static field. We demonstrate the importance of understanding the effect of the strength of the radiofrequency oscillating field; our experiments demonstrate that there is an optimal oscillating field strength above which the observed signal decreases in intensity and eventually inverts. We establish the correlation between the onset of this effect and the hyperfine structure of the radicals involved, and identify the existence of ‘overtone’ type features appearing at multiples of the expected resonance field positio

    Nuclear MET requires ARF and is inhibited by carbon nanodots through binding to phospho-tyrosine in prostate cancer

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    Nuclear receptor tyrosine kinases (nRTKs) are aberrantly upregulated in many types of cancers, but the regulation of nRTK remains unclear. We previously showed androgen deprivation therapy (ADT) induces nMET in castration-resistant prostate cancer (CRPC) specimens. Through gene expression microarray profiles reanalysis, we identified that nMET signaling requires ARF for CRPC growth in Pten/Trp53 conditional knockout mouse model. Accordingly, aberrant MET/nMET elevation correlates with ARF in human prostate cancer (PCa) specimens. Mechanistically, ARF elevates nMET through binding to MET cytoplasmic domain to stabilize MET. Furthermore, carbon nanodots resensitize cancer cells to MET inhibitors through DNA damage response. The inhibition of phosphorylation by carbon nanodots was identified through binding to phosphate group of phospho-tyrosine via computational calculation and experimental assay. Thus, nMET is essential to precision therapy of MET inhibitor. Our findings reveal for the first time that targeting nMET axis by carbon nanodots can be a novel avenue for overcoming drug resistance in cancers especially prostate cancer

    Sodium dodecyl sulfate at water-hydrophobic interfaces: A simulation study

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    Using molecular dynamics simulations, we have studied the water-vapor and water-oil (decane) interfaces of aqueous solutions of sodium dodecyl sulfate (SDS). The water-vapor interface is often used as a model for water-oil (hydrophobic) interfaces, yet we observe that the behavior of amphiphilic DS - ions at these two interfaces is very different. Specifically, on a water-vapor interface, SDS forms aggregates at low coverages, while it is homogeneously distributed on the water-oil interface. Two decane parametrizations resulted in dramatically different conformations: decane parametrized based on a GROMOS force field "froze", while decane parametrized with a TraPPE force field remained liquid at 300 K. The calculated effective second-order susceptibilities and nonlinear sum frequency scattering intensities of DS - ions at the "frozen" decane-water agree well with experimental data of DS - ions at the hexadecane droplet-water interface. This suggests that the orientation of longer alkane molecules is predominantly parallel to the interface and that, at low coverages, DS - ions follow the orientation of oil molecules. © 2012 American Chemical Society

    Charge transfer between water molecules as the possible origin of the observed charging at the surface of pure water

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    Classical molecular dynamics simulations point to an anisotropy of water-water hydrogen bonding at the water surface. Approaching from the gas phase, a region of primarily dangling hydrogens is followed by dangling oxygens before the isotropic bulk region. Using ab initio calculations, we translate this hydrogen bonding anisotropy to charge transfer between water molecules, which we analyze with respect to both instantaneous and averaged positions of the water surface. Similarly to the oil/water interface, we show that there is a region of small net negative charge extending 0.2 to 0.6 nm from the Gibbs dividing surface in the aqueous phase. Using a simple continuum model, we translate this charge profile to a zeta potential, which acquires for realistic positions of the shear surface the same negative sign as that observed experimentally, albeit of a smaller absolute value. © 2011 American Chemical Society
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