Now showing 1 - 4 of 4
  • Publication
    Coarse Master Equations for Binding Kinetics of Amyloid Peptide Dimers
    We characterize the kinetics of dimer formation of the short amyloid microcrystal-forming tetrapeptides NNQQ by constructing coarse master equations for the conformational dynamics of the system, using temperature replica-exchange molecular dynamics (REMD) simulations. We minimize the effects of Kramers-type recrossings by assigning conformational states based on their sequential time evolution. Transition rates are further estimated from short-time state propagators, by maximizing the likelihood that the extracted rates agree with the observed atomistic trajectories without any a priori assumptions about their temperature dependence. Here, we evaluate the rates for both continuous replica trajectories that visit different temperatures, and for discontinuous data corresponding to each REMD temperature. While the binding-unbinding kinetic process is clearly Markovian, the conformational dynamics of the bound NNQQ dimer has a complex character. Our kinetic analysis allows us a quantitative discrimination between short-lived encounter pairs and strongly bound conformational states. The conformational dynamics of NNQQ dimers supports a kinetically driven aggregation mechanism, in agreement with the polymorphic character reported for amyloid aggregates such as microcrystals and fibrils.
      317Scopus© Citations 26
  • Publication
    Validation of Scenario Modelling for Bridge Loading
    (Technika, Vilnius Gediminas Technical University, 2016-09) ; ; ;
    Accurate estimates of characteristic bridge load effects are required for efficient design and assessment of bridges, and long-run traffic simulations are an effective method for estimating the effects. For multi-lane same-direction traffic, truck weights and locations on the bridge are correlated and this affects the calculated load effects. Scenario Modelling is a recently developed method which uses weigh-in-motion (WIM) data to simulate multi-lane same-direction traffic while maintaining location and weight correlations. It has been unclear however whether the method may produce unrealistic driver behaviour when extrapolating beyond the weigh-in-motion measuring period. As weigh-in-motion databases with more than about a year of data are not available, a microsimulation traffic model, which can simulate driver behaviour, is used here to assess the accuracy of extrapolating traffic effects using Scenario Modelling. The microsimulation is used to generate an extended reference dataset against which the results of Scenario Modelling are compared. It is found that the characteristic load effects obtained using Scenario Modelling compare well with the reference dataset. As a result, for the first time researchers and practitioners can model two-lane same-direction traffic loading on bridges while being confident that the approach is generating accurate estimates of characteristic load effects as well as effectively reproducing the complex traffic correlations involved.
      375Scopus© Citations 3
  • Publication
    A Review of the HL-93 Bridge Traffic Load Model Using an Extensive WIM Database
    (American Society of Civil Engineers, 2014-10) ; ; ;
    HL-93, the current bridge traffic load model used in the United States is examined here. Weigh-in-motion (WIM) data from 17 sites in 16 states containing 74 million truck records are used to assess the level of consistency in the characteristic load effects (LEs) implied by the HL-93 model. The LEs of positive and negative bending moments and shear force are considered on single- and two-lane same-direction slab and girder bridges with a range of spans. It is found that the ratio of WIM-implied LE to HL-93 LE varies considerably from one LE to another. An alternative model is proposed that achieves improvements in consistency in this ratio for the LEs examined, especially for the single-lane case. The proposed model consists of a uniformly distributed load whose intensity varies with bridge length.
      443Scopus© Citations 17
  • Publication
    Identifying and Modelling Permit Trucks for Bridge Loading
    Accurate estimates of characteristic traffic load effects are essential in order to optimize bridge safety assessment. Permit trucks dominate the extreme upper tail of the truck loading distribution and as a result need careful examination. This paper proposes rules for filtering these trucks from Weigh-In-Motion data for both the US and Europe.  The importance of these trucks in critical bridge loading events is then examined for both regions. A Monte Carlo traffic simulation model is developed which focuses on the accurate simulation of permit trucks.
      362Scopus© Citations 6