416 research outputs found

    Shaping Epigenetic Memory via Genomic Bookmarking

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    Reconciling the stability of epigenetic patterns with the rapid turnover of histone modifications and their adaptability to external stimuli is an outstanding challenge. Here, we propose a new biophysical mechanism that can establish and maintain robust yet plastic epigenetic domains via genomic bookmarking (GBM). We model chromatin as a recolourable polymer whose segments bear non-permanent histone marks (or colours) which can be modified by "writer" proteins. The three-dimensional chromatin organisation is mediated by protein bridges, or "readers", such as Polycomb Repressive Complexes and Transcription Factors. The coupling between readers and writers drives spreading of biochemical marks and sustains the memory of local chromatin states across replication and mitosis. In contrast, GBM-targeted perturbations destabilise the epigenetic patterns. Strikingly, we demonstrate that GBM alone can explain the full distribution of Polycomb marks in a whole Drosophila chromosome. We finally suggest that our model provides a starting point for an understanding of the biophysics of cellular differentiation and reprogramming.Comment: Published in Nucleic Acids Research; Supplementary Movies can be found at this url: https://www2.ph.ed.ac.uk/~dmichiel/ShapingEpigeneticMemory.html or https://www.youtube.com/watch?v=xY-DNP58yB

    Study of cosolvent-induced α-chymotrypsin fibrillogenesis: Does protein surface hydrophobicity trigger early stages of aggregation reaction?

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    The misfolding of specific proteins is often associated with their assembly into fibrillar aggregates, commonly termed amyloid fibrils. Despite the many efforts expended to characterize amyloid formation in vitro, there is no deep knowledge about the environment (in which aggregation occurs) as well as mechanism of this type of protein aggregation. Alpha-chymotrypsin was recently driven toward amyloid aggregation by the addition of intermediate concentrations of trifluoroethanol. In the present study, approaches such as turbidimetric, thermodynamic, intrinsic fluorescence and quenching studies as well as chemical modification have been successfully used to elucidate the underlying role of hydrophobic interactions (involved in early stages of amyloid formation) in α-chymotrypsin-based experimental system. © 2009 Springer Science+Business Media, LLC

    Test and commissioning of the CARLOS control boards for the ALICE Silicon Drift Detectors

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    This paper presents the test strategy employed during the installation of the CARLOS end ladder boards developed for the Silicon Drift Detectors (SDD) of ALICE. Each CARLOS board compresses the data provided by the front-end electronics of one SDD and sends them via an optical link of 800 Mbit/s to the data concentrator card (CARLOSrx) located in the counting room. The paper describes the integration of the CARLOS boards in the final SDD system, including its cooling and mechanical support, the power supply distribution and the optical interconnections. The results of the tests performed after each step of the installation sequence are reported

    Technical Design Report for the PANDA Solenoid and Dipole Spectrometer Magnets

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    This document is the Technical Design Report covering the two large spectrometer magnets of the PANDA detector set-up. It shows the conceptual design of the magnets and their anticipated performance. It precedes the tender and procurement of the magnets and, hence, is subject to possible modifications arising during this process.Comment: 10 pages, 14MB, accepted by FAIR STI in May 2009, editors: Inti Lehmann (chair), Andrea Bersani, Yuri Lobanov, Jost Luehning, Jerzy Smyrski, Technical Coordiantor: Lars Schmitt, Bernd Lewandowski (deputy), Spokespersons: Ulrich Wiedner, Paola Gianotti (deputy

    Suppression of charged particle production at large transverse momentum in central Pb-Pb collisions at sNN=2.76\sqrt{s_{\rm NN}} = 2.76 TeV

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    Inclusive transverse momentum spectra of primary charged particles in Pb-Pb collisions at sNN\sqrt{s_{_{\rm NN}}} = 2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0-5% and 70-80% of the hadronic Pb-Pb cross section. The measured charged particle spectra in η<0.8|\eta|<0.8 and 0.3<pT<200.3 < p_T < 20 GeV/cc are compared to the expectation in pp collisions at the same sNN\sqrt{s_{\rm NN}}, scaled by the number of underlying nucleon-nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAAR_{\rm AA}. The result indicates only weak medium effects (RAAR_{\rm AA} \approx 0.7) in peripheral collisions. In central collisions, RAAR_{\rm AA} reaches a minimum of about 0.14 at pT=6p_{\rm T}=6-7GeV/cc and increases significantly at larger pTp_{\rm T}. The measured suppression of high-pTp_{\rm T} particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb-Pb collisions at the LHC.Comment: 15 pages, 5 captioned figures, 3 tables, authors from page 10, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/98
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