5,362 research outputs found

    Methylation of CpG island is not a ubiquitous mechanism for the loss of oestrogen receptor in breast cancer cells.

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    Methylation has been shown to play an important role in the down-regulation of oestrogen receptors (ER) in breast cancer cells. One critical question that remains unclear is whether methylation can account for the loss of ER expression in cells derived from an ER-positive cell line. This laboratory has established an in vitro cell system using long-term growth of human ER-positive breast cancer cell line T47D in oestrogen-free medium. A clonal cell line, T47D:C4:2 (C4:2), has been characterized. Unlike T47D:A18 (A18), which is a T47D line maintained in oestrogen medium, C4:2 has lost the expression of ER and hormone responsiveness. DNA fingerprinting and restriction fragment length polymorphism (RFLP) analysis results confirmed that C4:2 was of the same lineage as A18. These cell lines provide an invaluable system to study the mechanism of ER expression and regulatory pathways leading to hormone-independent growth. The results here clearly demonstrate that the ER CpG island in C4:2 cells remains unmethylated. The loss of ER in the cell line must be due to mechanisms other than methylation. We also evaluated the ER CpG island in the MDA-MB-231:10A (10A) cell line, which is a clone from the MDA-MB-231 line obtained from ATCC and the DNA from the MDA-MB-231 cell line used in the original report. Unlike the cell line from the report, which showed a full methylation pattern in the island, the 10A line only showed a partial methylation pattern in the CpG island. Possible mechanisms pertaining to the heterogeneous methylation pattern of the ER CpG island in the breast cancer cells are discussed

    Active Learning with Statistical Models

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    For many types of machine learning algorithms, one can compute the statistically `optimal' way to select training data. In this paper, we review how optimal data selection techniques have been used with feedforward neural networks. We then show how the same principles may be used to select data for two alternative, statistically-based learning architectures: mixtures of Gaussians and locally weighted regression. While the techniques for neural networks are computationally expensive and approximate, the techniques for mixtures of Gaussians and locally weighted regression are both efficient and accurate. Empirically, we observe that the optimality criterion sharply decreases the number of training examples the learner needs in order to achieve good performance.Comment: See http://www.jair.org/ for any accompanying file

    Road to Recovery: Why Rhode Island Drivers Should Be Made Whole from Potholes

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    Trends in unsolicited dermatologic opinions: A national survey

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    In dermatology, a particularly common ethical dilemma can arise when the skin lesions of bystanders are inadvertently viewed in public settings. Dermatology is a unique field, where a person’s organ of interest is readily visible to others. When lesions are suspicious for skin disease, unsolicited medical opinions may or may not be given depending on several factors. This study examined the actions and attitudes of dermatologists with different levels of experience through the use of case scenarios with various settings and skin lesions. © 2017, Dermatology Online Journal. All rights reserved

    Homogenization induced by chaotic mixing and diffusion in an oscillatory chemical reaction

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    A model for an imperfectly mixed batch reactor with the chlorine dioxide-iodine-malonic acid (CDIMA) reaction, with the mixing being modelled by chaotic advection, is considered. The reactor is assumed to be operating in oscillatory mode and the way in which an initial spatial perturbation becomes homogenized is examined. When the kinetics are such that the only stable homogeneous state is oscillatory then the perturbation is always entrained into these oscillations. The rate at which this occurs is relatively insensitive to the chemical effects, measured by the Damkohler number, and is comparable to the rate of homogenization of a passive contaminant. When both steady and oscillatory states are stable, spatially homogeneous states, two possibilities can occur. For the smaller Damkohler numbers, a localized perturbation at the steady state is homogenized within the background oscillations. For larger Damkohler numbers, regions of both oscillatory and steady behavior can co-exist for relatively long times before the system collapses to having the steady state everywhere. An interpretation of this behavior is provided by the one-dimensional Lagrangian filament model, which is analyzed in detail

    Fluorescence near-field microscopy of DNA at Sub-10A nm resolution

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    Journal ArticleWe demonstrate apertureless near-field microscopy of single molecules at sub-10 nm resolution. With a novel phase filter, near-field images of single organic fluorophores were obtained with ~sixfold improvement in the signal-to-noise ratio. The improvement allowed pairs of molecules separated by ~15 nm to be reliably and repeatedly resolved, thus demonstrating the first true Rayleigh resolution test for near-field images of single molecules. The potential of this technique for biological applications was demonstrated with an experiment that measured the helical rise of A-form DNA

    Tip-Enhanced Fluorescence Microscopy at 10 Nanometer Resolution

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    We demonstrate unambiguously that the field enhancement near the apex of a laser-illuminated silicon tip decays according to a power law that is moderated by a single parameter characterizing the tip sharpness. Oscillating the probe in intermittent contact with a semiconductor nanocrystal strongly modulates the fluorescence excitation rate, providing robust optical contrast and enabling excellent background rejection. Laterally encoded demodulation yields images with <10 nm spatial resolution, consistent with independent measurements of tip sharpness
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