Binding of the molecular chaperone αB-crystallin to Aβ amyloid fibrils inhibits fibril elongation.

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.

COMPARISON OF MILLISECOND ANNEALING OF B IMPLANTS AND ISOTHERMAL ANNEALING FOR TIMES OF A FEW SECONDS.

The annealing behaviour of B implants in the millisecond time regime using a combination of swept line beam and background heating is compared with isothermal annealing with heating cycles of a few seconds. Carrier concentration profiles show that under annealing conditions which restrict diffusion, millisecond processing gives higher activation of B implants than isothermal heating. Transmission electron microscopy shows that millisecond annealing also results in a lower defect density.

Learning feedforward commands to muscles using time-shifted sensory feedback

In adapting to changing forces in the mechanical environment, humans change the force being applied by the limb by reciprocal changes in the activation of antagonistic muscles. However, they also cocontract these muscles when interaction with the environment is mechanically unstable to increase the mechanical impedance of the limb. We have postulated that appropriate patterns of muscle activation could be learned using a simple scheme in which the naturally occurring stretch reflex is used as a template to adjust feedforward commands to muscles. Feedforward commands are modified iteratively by shifting a scaled version of the reflex response forward in time and adding it to the previous feedforward command. We show that such an algorithm can account for the principal features of changes in muscle activation observed when human subjects adapt to instabilities in the mechanical environment. © 2006.

Subdivision-stabilised immersed b-spline finite elements for moving boundary flows

An immersed finite element method is presented to compute flows with complex moving boundaries on a fixed Cartesian grid. The viscous, incompressible fluid flow equations are discretized with b-spline basis functions. The two-scale relation for b-splines is used to implement an elegant and efficient technique to satisfy the LBB condition. On non-grid-aligned fluid domains and at moving boundaries, the boundary conditions are enforced with a consistent penalty method as originally proposed by Nitsche. In addition, a special extrapolation technique is employed to prevent the loss of numerical stability in presence of arbitrarily small cut-cells. The versatility and accuracy of the proposed approach is demonstrated by means of convergence studies and comparisons with previous experimental and computational investigations.