106 resultados para solution affinity assay
Resumo:
The molecular chaperone αB-crystallin is a small heat-shock protein that is upregulated in response to a multitude of stress stimuli, and is found colocalized with Aβ amyloid fibrils in the extracellular plaques that are characteristic of Alzheimer's disease. We investigated whether this archetypical small heat-shock protein has the ability to interact with Aβ fibrils in vitro. We find that αB-crystallin binds to wild-type Aβ(42) fibrils with micromolar affinity, and also binds to fibrils formed from the E22G Arctic mutation of Aβ(42). Immunoelectron microscopy confirms that binding occurs along the entire length and ends of the fibrils. Investigations into the effect of αB-crystallin on the seeded growth of Aβ fibrils, both in solution and on the surface of a quartz crystal microbalance biosensor, reveal that the binding of αB-crystallin to seed fibrils strongly inhibits their elongation. Because the lag phase in sigmoidal fibril assembly kinetics is dominated by elongation and fragmentation rates, the chaperone mechanism identified here represents a highly effective means to inhibit fibril proliferation. Together with previous observations of αB-crystallin interaction with α-synuclein and insulin fibrils, the results suggest that this mechanism is a generic means of providing molecular chaperone protection against amyloid fibril formation.
A sequential Monte Carlo EM solution to the transcription factor binding site identification problem
Resumo:
This paper presents a numerical method for the simulation of flow in turbomachinery blade rows using a solution-adaptive mesh methodology. The fully three-dimensional, compressible, Reynolds-averaged Navier-Stokes equations with k-ε turbulence modeling (and low Reynolds number damping terms) are solved on an unstructured mesh formed from tetrahedral finite volumes. At stages in the solution, mesh refinement is carried out based on flagging cell faces with either a fractional variation of a chosen variable (like Mach number) greater than a given threshold or with a mean value of the chosen variable within a given range. Several solutions are presented, including that for the highly three-dimensional flow associated with the corner stall and secondary flow in a transonic compressor cascade, to demonstrate the potential of the new method.
Resumo:
Accurate and efficient computation of the nearest wall distance d (or level set) is important for many areas of computational science/engineering. Differential equation-based distance/ level set algorithms, such as the hyperbolic-natured Eikonal equation, have demonstrated valuable computational efficiency. Here, in the context, as an 'auxiliary' equation to the main flow equations, the Eikonal equation is solved efficiently with two different finite volume approaches (the cell vertex and cell-centered). Application of the distance solution is studied for various geometries. Moreover, a procedure using the differential field to obtain the medial axis transform (MAT) for different geometries is presented. The latter provides a skeleton representation of geometric models that has many useful analysis properties. As an alternative approach to the pure geometric methods (e.g. the Voronoi approach), the current d-MAT procedure bypasses many difficulties that are usually encountered by pure geometric methods, especially in three dimensional space. It is also shown that the d-MAT approach provides the potential to sculpt/control the MAT form for specialized solution purposes. Copyright © 2010 by the American Institute of Aeronautics and Astronautics, Inc.
Resumo:
An implementation of the inverse vector Jiles-Atherton model for the solution of non-linear hysteretic finite element problems is presented. The implementation applies the fixed point method with differential reluctivity values obtained from the Jiles-Atherton model. Differential reluctivities are usually computed using numerical differentiation, which is ill-posed and amplifies small perturbations causing large sudden increases or decreases of differential reluctivity values, which may cause numerical problems. A rule based algorithm for conditioning differential reluctivity values is presented. Unwanted perturbations on the computed differential reluctivity values are eliminated or reduced with the aim to guarantee convergence. Details of the algorithm are presented together with an evaluation of the algorithm by a numerical example. The algorithm is shown to guarantee convergence, although the rate of convergence depends on the choice of algorithm parameters. © 2011 IEEE.
Resumo:
We exfoliate graphite in both aqueous and non-aqueous environments through mild sonication followed by centrifugation. The dispersions are enriched with monolayers. We mix them with polymers, followed by slow evaporation to produce optical quality composites. Nonlinear optical measurements show similar to 5% saturable absorption. The composites are then integrated into fiber laser cavities to generate 630 fs pulses at 1.56 mu m. This shows the viability of solution phase processing for graphene based photonic devices. (C) 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim