7 resultados para heat shock protein 90
em Cambridge University Engineering Department Publications Database
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.
Resumo:
An experimental investigation into the response of transonic SBLIs to periodic down-stream pressure perturbations in a parallel walled duct has been conducted. Tests have been carried out with a shock strength of M ∞ = 1.5 for pressure perturbation frequencies in the range 16-90 Hz. Analysis of the steady interaction at M∞ = 1.5 has also been made. The principle measurement techniques were high speed schlieren photography and laser Doppler anemometry. The structure of the steady SBLI was found to be highly three-dimensional, with large corner flows and sidewall SBLIs. These aspects are thought to influence the upstream transmission of pressure information through the interaction by affecting the post-shock flow field, including the extent of regions of secondary supersonic flow. At low frequency, the dynamics of shock motion can be predicted using an inviscid analytical model. At increased frequencies, viscous effects become significant and the shock exhibits unexpected dynamic behaviour, due to a phase lag between the upstream transmission of pressure information in the core flow and in the viscous boundary layers. Flow control in the form of micro-vane vortex generators was found to have a small impact on shock dynamics, due to the effect it had on the post-shock flow field outside the viscous boundary layer region. The relationship between inviscid and viscous effects is developed and potential destabilising mechanisms for SBLIs in practical applications are suggested. Copyright © 2009 by Paul Bruce and Holger Babinsky.
Resumo:
A combined experimental and numerical study of a transonic shock wave in a parallel walled duct subject to downstream pressure perturbations has been conducted. Experiments and simulations have been carried out with a shock strength of M∞ = 1.4 for pressure perturbation frequencies in the range 16-90 Hz. The dynamics of unsteady shock motion and the interaction structure between the unsteady transonic shock wave and the turbulent tunnel floor boundary layer have been investigated. It is found that the (experimentally measured) dynamics of shock motion are generally well predicted by the computational scheme, especially at relatively low (≈ 40 Hz) frequencies. However, at higher frequencies (≈ 90 Hz), some subtle differences between the shock dynamics measured in experiments and those predicted by Computational Fluid Dynamics (CFD) exist. There is evidence from experiments that variations in shock / boundary layer interaction (SBLI) structure caused by shock motion are responsible for a change in the nature of shock dynamics between low and high frequency. In contrast, numerical results at low and high frequencies do not differ significantly and this suggests that the numerical method is not fully capturing the physics of the unsteady flow. Possible reasons for this are considered and a number of areas where CFD is unable to replicate experimental observations are identified. Significantly, CFD predicts changes in SBLI structure due to shock motion that are much too large and this may explain why none of the subtle effects on shock dynamics seen in experiments occur in CFD. Further work developing numerical methods that demonstrate a more realistic sensitivity of SBLI structure to unsteady shock motion is required. Copyright © 2010 by P.J.K. Bruce.
Resumo:
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.