Leeds, W.Yorkshire, United Kingdom

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Leeds Institute of Health Sciences (LIHS)
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School of Dentistry
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School of Earth and Environment
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    ABSTRACT: The human AmphyphisinII/Bin1 N-BAR domain belongs to the BAR domain superfamily, whose members sense and generate membrane curvatures. The N-BAR domain is a 57 kDa homodimeric protein comprising a six helix bundle. Here we report the protein folding mechanism of this protein as a representative of this protein superfamily. The concentration dependent thermodynamic stability was studied by urea equilibrium transition curves followed by fluorescence and far-UV CD spectroscopy. Kinetic unfolding and refolding experiments, including rapid double and triple mixing techniques, allowed to unravel the complex folding behavior of N-BAR. The equilibrium unfolding transition curve can be described by a two-state process, while the folding kinetics show four refolding phases, an additional burst reaction and two unfolding phases. All fast refolding phases show a rollover in the chevron plot but only one of these phases depends on the protein concentration reporting the dimerization step. Secondary structure formation occurs during the three fast refolding phases. The slowest phase can be assigned to a proline isomerization. All kinetic experiments were also followed by fluorescence anisotropy detection to verify the assignment of the dimerization step to the respective folding phase. Based on these experiments we propose for N-BAR two parallel folding pathways towards the homodimeric native state depending on the proline conformation in the unfolded state.
    PLoS ONE 09/2015; 10(9):e0136922. DOI:10.1371/journal.pone.0136922
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    ABSTRACT: Three-dimensional adaptive mesh refinement hydrodynamical simulations of the wind–wind collision between the enigmatic supermassive star η Car and its mysterious companion star are presented which include radiative driving of the stellar winds, gravity, optically thin radiative cooling, and orbital motion. Simulations with static stars with a periastron passage separation reveal that the preshock companion star's wind speed is sufficiently reduced so that radiative cooling in the postshock gas becomes important, permitting the runaway growth of nonlinear thin-shell instabilities (NTSIs) which massively distort the wind–wind collision region (WCR). However, large-scale simulations, which include the orbital motion of the stars, show that orbital motion reduces the impact of radiative inhibition and thus increases the acquired preshock velocities. As such, the postshock gas temperature and cooling time see a commensurate increase, and sufficient gas pressure is preserved to stabilize the WCR against catastrophic instability growth. We then compute synthetic X-ray spectra and light curves and find that, compared to previous models, the X-ray spectra agree much better with XMM-Newton observations just prior to periastron. The narrow width of the 2009 X-ray minimum can also be reproduced. However, the models fail to reproduce the extended X-ray minimum from previous cycles. We conclude that the key to explaining the extended X-ray minimum is the rate of cooling of the companion star's postshock wind. If cooling is rapid then powerful NTSIs will heavily disrupt the WCR. Radiative inhibition of the companion star's preshock wind, albeit with a stronger radiation–wind coupling than explored in this work, could be an effective trigger.
    The Astrophysical Journal 08/2015; 726(2). DOI:10.1088/0004-637X/726/2/105
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    ABSTRACT: We report on the first completely simultaneous observation of a gamma-ray burst (GRB) using an array of Imaging Atmospheric Cherenkov Telescopes, which is sensitive to photons in the very high energy (VHE) γ -ray range (100 GeV). On 2006 June 2, the Swift Burst Alert Telescope (BAT) registered an unusually soft γ -ray burst (GRB 060602B). The burst position was under observation using the High Energy Stereoscopic System (HESS) at the time the burst occurred. Data were taken before, during, and after the burst. A total of 5 hr of observations were obtained during the night of 2006 June 2–3, and five additional hours were obtained over the next three nights. No VHE γ -ray signal was found during the period covered by the HESS observations. The 99% confidence level flux upper limit (> 1 TeV) for the prompt phase (9 s) of GRB 060602B is 2.9 × 10 −9 erg cm −2 s −1 . Due to the very soft BAT spectrum of the burst compared with other Swift GRBs and its proximity to the Galactic center, the burst is likely associated with a Galactic X-ray burster, although the possibility of it being a cosmological GRB cannot be ruled out. We discuss the implications of our flux limits in the context of these two bursting scenarios.


  • Address
    Woodhouse Lane, LS2 9JT, Leeds, W.Yorkshire, United Kingdom
  • Head of Institution
    Sir Alan Langland
  • Website
  • Phone
    +44 (0) 113 243 1751
  • Fax
    +44 (0) 113 244 3923
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Top publications last week by reads

SSRN Electronic Journal 09/2008; DOI:10.2139/ssrn.814285
325 Reads
British Journal of Social Psychology 12/2010; 40(4):471 - 499. DOI:10.1348/014466601164939
314 Reads

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