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No description available.

No description available.

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No description available.

The IKs current constitutes part of the repolarisation reserve in the human myocardium, and whilst it does not play a major role at resting heart rates, it becomes a crucial component of repolarisation in the setting of increased sympathetic tone and high heart rates. The formation of the IKs current requires the KCNQ1 α-subunit and the KCNE1 β-subunit. Mutations in either of these subunits can lead to long QT syndrome types 1 and 5, respectively. Loss-of-function mutations in the IKs channel can reduce the repolarisation reserve and lead to action potential prolongation, predisposing to lethal cardiac arrhythmias such as torsades de pointes and ventricular fibrillation. It is widely recognised that the IKs channel requires the minor membrane phospholipid PIP2 for its function, and previous work in this laboratory found that mutations in a PIP2-binding region in KCNQ1 led to retention of the channel in the endoplasmic reticulum, suggesting that PIP2 may play a role in anterograde trafficking. Here, the rapamycin-inducible dimerisation system was used to manipulate levels of PIP2 and/or PI4P at the plasma membrane or Golgi, and the effect of this on IKs channel trafficking and function was investigated using molecular biology, confocal microscopy and electrophysiology. Despite difficulties with optimising the rapamycin-induced dimerisation system, it was observed that the IKs channel does not require PIP2 for anterograde trafficking, but is heavily reliant on PIP2 for channel opening. In addition, activation of the β1-adrenergic receptor (β 1-AR) led to an increase in the IKs current amplitude. The potential interplay between β1-AR and PIP2 signalling was also explored by depleting PIP2 during β1-AR stimulation. PIP2 depletion was less effective at inhibiting the IKs current during β1-AR stimulation, but this requires further investigation. In conclusion, the results suggest that the IKs channel is reliant on PIP2 for function, but not anterograde trafficking.

This study analyzes the thermo-mechanical response of a composite cylinder made up of two layers of linear isotropic viscoelastic materials that belong to the class of non-Thermorheologically Simple Material. The effect of time-varying temperature field due to unsteady heat conduction phenomenon is analyzed on the short term and long term material response in terms of stress, strain and displacement fields. The material properties of the two layers of the composite cylinder at any given location and time are assumed to depend on the temperature at that location at that given instant of time. Sequentially coupled analyses of heat conduction and deformation of viscoelastic composite cylinder is carried out to obtain the overall response. The stress and strain field developed in the composite cylinder is evaluated as the discontinuity in hoop stress and radial strain at the interface of the two layers caused due to mismatch in material properties may lead to delamination if it exceeds critical value. Analytical solution for the stress, strain and displacement fields of the viscoelastic composite cylinder is developed from the corresponding solution of linear elasticity problem by using the Correspondence Principle. The analytical solution for determining the temperature dependent stress, strain and displacement fields is further developed by incorporating the temperature dependence on the material properties and modeling the material as non-TSM. To analyze more complex geometry with general loading and boundary conditions, Finite Element(FE) analysis of the composite cylinder is performed and the results of analytical and FE method are found to be in good agreement. Parametric studies are carried out to understand the effect of change in material parameters namely the Prony coefficients in the transient creep compliance, characteristic of creep time in transient creep compliance and the instantaneous elastic compliance, on the overall response of the composite cylinder. The effect of different temperature dependent functions of the material properties, namely linear temperature variation and quadratic polynomial variation on the overall material response is also analyzed. It is observed that the effect of change in elastic properties significantly increases the jump in hoop stress and radial strain. It is also observed that when the materials are highly dependent on temperature the jump in radial strain and hoop stress increases significantly. The radial displacement also increases by a significant amount in both the cases.

This study analyzes the thermo-mechanical response of a composite cylinder made up of two layers of linear isotropic viscoelastic materials that belong to the class of non-Thermorheologically Simple Material. The effect of time-varying temperature field due to unsteady heat conduction phenomenon is analyzed on the short term and long term material response in terms of stress, strain and displacement fields. The material properties of the two layers of the composite cylinder at any given location and time are assumed to depend on the temperature at that location at that given instant of time. Sequentially coupled analyses of heat conduction and deformation of viscoelastic composite cylinder is carried out to obtain the overall response. The stress and strain field developed in the composite cylinder is evaluated as the discontinuity in hoop stress and radial strain at the interface of the two layers caused due to mismatch in material properties may lead to delamination if it exceeds critical value. Analytical solution for the stress, strain and displacement fields of the viscoelastic composite cylinder is developed from the corresponding solution of linear elasticity problem by using the Correspondence Principle. The analytical solution for determining the temperature dependent stress, strain and displacement fields is further developed by incorporating the temperature dependence on the material properties and modeling the material as non-TSM. To analyze more complex geometry with general loading and boundary conditions, Finite Element(FE) analysis of the composite cylinder is performed and the results of analytical and FE method are found to be in good agreement. Parametric studies are carried out to understand the effect of change in material parameters namely the Prony coefficients in the transient creep compliance, characteristic of creep time in transient creep compliance and the instantaneous elastic compliance, on the overall response of the composite cylinder. The effect of different temperature dependent functions of the material properties, namely linear temperature variation and quadratic polynomial variation on the overall material response is also analyzed. It is observed that the effect of change in elastic properties significantly increases the jump in hoop stress and radial strain. It is also observed that when the materials are highly dependent on temperature the jump in radial strain and hoop stress increases significantly. The radial displacement also increases by a significant amount in both the cases.

Extr. de--Physique appliquée--Göteborg (Suède)--Université de Göteborg, 2003. / Bibliogr. p. 111-126.

Thèse de doctorat : Images et Systèmes : Villeurbanne, INSA : 2002. / Titre provenant de l'écran-titre. Bibliogr. p.140.