32 research outputs found

    Modelling the regulation of telomere length: the effects of telomerase and G-quadruplex stabilising drugs

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    Telomeres are guanine-rich sequences at the end of chromosomes which shorten during each replication event and trigger cell cycle arrest and/or controlled death (apoptosis) when reaching a threshold length. The enzyme telomerase replenishes the ends of telomeres and thus prolongs the life span of cells, but also causes cellular immortalisation in human cancer. G-quadruplex (G4) stabilising drugs are a potential anticancer treatment which work by changing the molecular structure of telomeres to inhibit the activity of telomerase. We investigate the dynamics of telomere length in different conformational states, namely t-loops, G-quadruplex structures and those being elongated by telomerase. By formulating deterministic differential equation models we study the effects of various levels of both telomerase and concentrations of a G4-stabilising drug on the distribution of telomere lengths, and analyse how these effects evolve over large numbers of cell generations. As well as calculating numerical solutions, we use quasicontinuum methods to approximate the behaviour of the system over time, and predict the shape of the telomere length distribution. We find those telomerase and G4-concentrations where telomere length maintenance is successfully regulated. Excessively high levels of telomerase lead to continuous telomere lengthening, whereas large concentrations of the drug lead to progressive telomere erosion. Furthermore, our models predict a positively skewed distribution of telomere lengths, that is, telomeres accumulate over lengths shorter than the mean telomere length at equilibrium. Our model results for telomere length distributions of telomerase-positive cells in drug-free assays are in good agreement with the limited amount of experimental data available

    Searches for R-parity-violating supersymmetry in pp collisions at √s=8  TeV in final states with 0–4 leptons

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    Measurements of electroweak Wjj production and constraints on anomalous gauge couplings with the ATLAS detector

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    Measurements of the electroweak production of a W boson in association with two jets at high dijet invariant mass are performed using root s = 7 and 8 TeV proton-proton collision data produced by the Large Hadron Collider, corresponding respectively to 4.7 and 20.2 fb(-1) of integrated luminosity collected by the ATLAS detector. The measurements are sensitive to the production of a W boson via a triple-gauge-boson vertex and include both the fiducial and differential cross sections of the electroweak process

    Identification and energy calibration of hadronically decaying tau leptons with the ATLAS experiment in pp collisions at root s=8 TeV

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    This paper describes the trigger and offline reconstruction, identification and energy calibration algorithms for hadronic decays of tau leptons employed for the data collected from pp collisions in 2012 with the ATLAS detector at the LHC center-of-mass energy root s = 8 TeV. The performance of these algorithms is measured in most cases with Z decays to tau leptons using the full 2012 dataset, corresponding to an integrated luminosity of 20.3 fb(-1). An uncertainty on the offline reconstructed tau energy scale of 2-4%, depending on transverse energy and pseudorapidity, is achieved using two independent methods. The offline tau identification efficiency is measured with a precision of 2.5% for hadronically decaying tau leptons with one associated track, and of 4% for the case of three associated tracks, inclusive in pseudorapidity and for a visible transverse energy greater than 20 GeV. For hadronic tau lepton decays selected by offline algorithms, the tau trigger identification efficiency is measured with a precision of 2-8%, depending on the transverse energy. The performance of the tau algorithms, both offline and at the trigger level, is found to be stable with respect to the number of concurrent proton-proton interactions and has supported a variety of physics results using hadronically decaying tau leptons at ATLAS

    Search for the lepton flavor violating decay Z -> e mu in pp collisions at root s=8 TeV with the ATLAS detector

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    Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.http://link.aps.org/doi/10.1103/PhysRevD.90.07201

    Search for the lepton flavor violating decay Z -> e mu in pp collisions at root s=8 TeV with the ATLAS detector

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    Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.http://link.aps.org/doi/10.1103/PhysRevD.90.07201

    Search for the lepton flavor violating decay Z -> e mu in pp collisions at root s=8 TeV with the ATLAS detector

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    Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.http://link.aps.org/doi/10.1103/PhysRevD.90.07201
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