6,326 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

    Considerations for the use of medical devices in dermatology.

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    This manuscript addresses the significant considerations concerning the development and use of medical devices in dermatology. With the rapidly growing demand and booming market for medical devices, especially lasers, it is crucial that dermatologists become familiar with the nuances associated with supporting clinical studies, consumer-driven marketing strategies, and the complex relationships that exist between physicians, industry, and consumers. An examination of these relationships includes an overview of the potential biases pertaining to advisory panels and treating clinicians. The aim of this paper is to serve as an introduction to the background of medical devices and to offer dermatologists important information on what should be considered before recommending treatment

    Crisis in Latin America : infrastructure investment, employment and the expectations of stimulus

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    Infrastructure investment is a central part of the stimulus plans of the Latin American and the Caribbean (LAC) region as it confronts the growing financial crisis. This paper estimates the potential effects on direct, indirect, and induced employment for different types of infrastructure projects with LAC-specific variables. The analysis finds that the direct and indirect short-term employment generation potential of infrastructure capital investment projects may be considerable - averaging around 40,000 annual jobs per US1billioninLAC,dependinguponsuchvariablesasthemixofsubsectorsintheinvestmentprogram;thetechnologiesdeployed;localwagesforskilledandunskilledlabor;andthedegreesofleakagestoimportedinputs.Whilethesenumbersdonotaccountforsubstitutioneffect,theyarebuiltaroundanassumed"basket"ofinvestmentsthatcrossesinfrastructuresectorsmostofwhicharenotemployment−maximizing.Albeitlimitedinscope,ruralroadmaintenanceprojectsmayemploy200,000to500,000annualizeddirectjobsforeveryUS1billion in LAC, depending upon such variables as the mix of subsectors in the investment program; the technologies deployed; local wages for skilled and unskilled labor; and the degrees of leakages to imported inputs. While these numbers do not account for substitution effect, they are built around an assumed"basket"of investments that crosses infrastructure sectors most of which are not employment-maximizing. Albeit limited in scope, rural road maintenance projects may employ 200,000 to 500,000 annualized direct jobs for every US1billion spent. The paper also describes the potential risks to effective infrastructure investment in an environment of crisis including sorting and planning contradictions, delayed implementation and impact, affordability, and corruption.Transport Economics Policy&Planning,,Banks&Banking Reform,Non Bank Financial Institutions,Debt Markets

    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
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