1,478 research outputs found

    Evidence for linear extrachromosomal elements mediating gene amplification in the multidrug-resistant J774.2 murine cell line

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    Previous studies from our laboratory have demonstrated specific cytogenetic alterations accompanying development of colchicine resistance in the J774.2 murine cell line and in two sublines (J7.Cl-30 and J7.Cl-100) [1]. Although gene amplification is not observed in the parental J774.2 cell line, a ~35-fold amplification of the gene for p-glycoprotein (mdr) was noted in the J7.Cl-30 subline (770-fold CLCR) and a ~70-fold amplification in the J7.Cl-100 subline (2500-fold CLCR). In this study, we analyzed the localization and organization of the mdr gene. In the colchicine-resistant (CLCR) J7.Cl-30 subline, the p-glycoprotein domain was observed to reside on differently sized extrachromosomal elements. Our results indicate not only circular extrachromosomal elements but also linear extrachromosomal elements. By means of pulsed-field gel electrophoresis (PFGE), the sizes of the extrachromosomal elements were shown to be >2,500 kilobasepairs (kb), 800 kb, and 400 kb. In contrast, the J7.Cl-100 subline was characterized by the presence of homogeneously staining regions (HSRs). We have noted that with increasing colchicine resistance the extrachromosomal elements are replaced by HSRs. Our findings of linear elements that appear to be precursors of HSRs may offer a new way to interpret different theories of extrachromosomal gene amplification. The J7.Cl-30 cell line presents a unique system to analyze further the formation and structure of extrachromosomal elements.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30158/1/0000541.pd

    Studies in Astronomical Time Series Analysis. VI. Bayesian Block Representations

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    This paper addresses the problem of detecting and characterizing local variability in time series and other forms of sequential data. The goal is to identify and characterize statistically significant variations, at the same time suppressing the inevitable corrupting observational errors. We present a simple nonparametric modeling technique and an algorithm implementing it - an improved and generalized version of Bayesian Blocks (Scargle 1998) - that finds the optimal segmentation of the data in the observation interval. The structure of the algorithm allows it to be used in either a real-time trigger mode, or a retrospective mode. Maximum likelihood or marginal posterior functions to measure model fitness are presented for events, binned counts, and measurements at arbitrary times with known error distributions. Problems addressed include those connected with data gaps, variable exposure, extension to piecewise linear and piecewise exponential representations, multi-variate time series data, analysis of variance, data on the circle, other data modes, and dispersed data. Simulations provide evidence that the detection efficiency for weak signals is close to a theoretical asymptotic limit derived by (Arias-Castro, Donoho and Huo 2003). In the spirit of Reproducible Research (Donoho et al. 2008) all of the code and data necessary to reproduce all of the figures in this paper are included as auxiliary material.Comment: Added some missing script files and updated other ancillary data (code and data files). To be submitted to the Astophysical Journa

    Limits on Active to Sterile Neutrino Oscillations from Disappearance Searches in the MINOS, Daya Bay, and Bugey-3 Experiments

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    Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti) neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin(2) 2 theta(mu e) are set over 6 orders of magnitude in the sterile mass-squared splitting Delta m(41)(2). The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Delta m(41)(2) \u3c 0.8 eV(2) at 95% CLs
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