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.

Turbine blade tip heat transfer in low speed and high speed flows

In this paper, high and low speed tip flows are investigated for a high-pressure turbine blade. Previous experimental data are used to validate a CFD code, which is then used to study the tip heat transfer in high and low speed cascades. The results show that at engine representative Mach numbers the tip flow is predominantly transonic. Thus, compared to the low speed tip flow, the heat transfer is affected by reductions in both the heat transfer coefficient and the recovery temperature. The high Mach numbers in the tip region (M>1.5) lead to large local variations in recovery temperature. Significant changes in the heat transfer coefficient are also observed. These are due to changes in the structure of the tip flow at high speed. At high speeds, the pressure side corner separation bubble reattachment occurs through supersonic acceleration which halves the length of the bubble when the tip gap exit Mach number is increased from 0.1 to 1.0. In addition, shock/boundary-layer interactions within the tip gap lead to large changes in the tip boundary-layer thickness. These effects give rise to significant differences in the heat-transfer coefficient within the tip region compared to the low-speed tip flow. Compared to the low speed tip flow, the high speed tip flow is much less dominated by turbulent dissipation and is thus less sensitive to the choice of turbulence model. These results clearly demonstrate that blade tip heat transfer is a strong function of Mach number, an important implication when considering the use of low speed experimental testing and associated CFD validation in engine blade tip design. Copyright © 2009 by ASME.