Perturbation of the stability of amyloid fibrils through alteration of electrostatic interactions.

The self-assembly of proteins and peptides into polymeric amyloid fibrils is a process that has important implications ranging from the understanding of protein misfolding disorders to the discovery of novel nanobiomaterials. In this study, we probe the stability of fibrils prepared at pH 2.0 and composed of the protein insulin by manipulating electrostatic interactions within the fibril architecture. We demonstrate that strong electrostatic repulsion is sufficient to disrupt the hydrogen-bonded, cross-β network that links insulin molecules and ultimately results in fibril dissociation. The extent of this dissociation correlates well with predictions for colloidal models considering the net global charge of the polypeptide chain, although the kinetics of the process is regulated by the charge state of a single amino acid. We found the fibrils to be maximally stable under their formation conditions. Partial disruption of the cross-β network under conditions where the fibrils remain intact leads to a reduction in their stability. Together, these results support the contention that a major determinant of amyloid stability stems from the interactions in the structured core, and show how the control of electrostatic interactions can be used to characterize the factors that modulate fibril stability.

Uniform stability of a particle approximation of the optimal filter derivative

Sequential Monte Carlo methods, also known as particle methods, are a widely used set of computational tools for inference in non-linear non-Gaussian state-space models. In many applications it may be necessary to compute the sensitivity, or derivative, of the optimal filter with respect to the static parameters of the state-space model; for instance, in order to obtain maximum likelihood model parameters of interest, or to compute the optimal controller in an optimal control problem. In Poyiadjis et al. [2011] an original particle algorithm to compute the filter derivative was proposed and it was shown using numerical examples that the particle estimate was numerically stable in the sense that it did not deteriorate over time. In this paper we substantiate this claim with a detailed theoretical study. Lp bounds and a central limit theorem for this particle approximation of the filter derivative are presented. It is further shown that under mixing conditions these Lp bounds and the asymptotic variance characterized by the central limit theorem are uniformly bounded with respect to the time index. We demon- strate the performance predicted by theory with several numerical examples. We also use the particle approximation of the filter derivative to perform online maximum likelihood parameter estimation for a stochastic volatility model.

Global nonlinear dynamics of thin aerofoil wakes

In the present investigation of thin aerofoil wakes we compare the global nonlinear dynamics, obtained by direct numerical simulations, to the associated local instability features, derived from linear stability analyses. A given configuration depends on two control parameters: the Reynolds number Re and the adverse pressure gradient m (with m < 0) prevailing at the aerofoil trailing edge. Global instability is found to occur for large enough Re and |m|; the naturally selected frequency is determined by the local absolute frequency prevailing at the trailing edge. © 2010 Springer Science+Business Media B.V.

Surface tension-induced global instability of planar jets and wakes

The effect of surface tension on global stability of co-flow jets and wakes at a moderate Reynolds number is studied. The linear temporal two-dimensional global modes are computed without approximations. All but one of the flow cases under study are globally stable without surface tension. It is found that surface tension can cause the flow to be globally unstable if the inlet shear (or equivalently, the inlet velocity ratio) is strong enough. For even stronger surface tension, the flow is re-stabilized. As long as there is no change of the most unstable mode, increasing surface tension decreases the oscillation frequency. Short waves appear in the high-shear region close to the nozzle, and their wavelength increases with increasing surface tension. The critical shear (the weakest inlet shear at which a global instability is found) gives rise to antisymmetric disturbances for the wakes and symmetric disturbances for the jets. However, at stronger shear, the opposite symmetry can be the most unstable one, in particular for wakes at high surface tension. The results show strong effects of surface tension that should be possible to reproduce experimentally as well as numerically.

Feedback mechanisms for global oscillations in Lure systems

The paper presents two mechanisms for global oscillations in feedback systems, based on bifurcations in absolutely stable systems. The external characterization of the oscillators provides the basis for a (energy-based) dissipativity theory for oscillators, thereby opening new possibilities for rigorous stability analysis of high-dimensional systems and interconnected oscillators. © 2004 Elsevier B.V. All rights reserved.

Global modes with multiple saddle points

Significant progress has been made towards understanding the global stability of slowly-developing shear flows. The WKBJ theory developed by Patrick Huerre and his co-authors has proved absolutely central, with the result that both the linear and the nonlinear stability of a wide range of flows can now be understood in terms of their local absolute/convective instability properties. In many situations, the local absolute frequency possesses a single dominant saddle point in complex X-space (where X is the slow streamwise coordinate of the base flow), which then acts as a single wavemaker driving the entire global linear dynamics. In this paper we consider the more complicated case in which multiple saddles may act as the wavemaker for different values of some control parameter. We derive a frequency selection criterion in the general case, which is then validated against numerical results for the linearized third-order Ginzburg-Landau equation (which possesses two saddle points). We believe that this theory may be relevant to a number of flows, including the boundary layer on a rotating disk and the eccentric Taylor-Couette-Poiseuille flow. © 2014 Elsevier Masson SAS. All rights reserved.