No description available.

No description available.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Ryanodine receptors (RyRs) are intracellular homotetrameric Ca2+-release channels constituting a family of three different isoforms, named RyRl, RyR2 and RyR3. RyRl and RyR2 are highly expressed in skeletal and cardiac muscles respectively, where they localize in the terminal cisternae of the sarcoplasmic reticulum (SR). Although RyRl and RyR2 have been found to be expressed in several other tissues at much lower level than in striated muscles, their major functional role is related to Ca2+-release from the SR following electrical depolarization of the plasma membrane, a process referred to as excitation-contraction (e-c) coupling and known to regulate striated muscle contraction. The third isoform, RyR3, is characterized by a wide pattern of expression, without any specific association to a tissue or a cell-type. The finding that RyR3 is also expressed in mammalian skeletal muscles parallels the presence of two distinct isoforms, o- and P-RyR, in non-mammalian vertebrate skeletal muscles, and suggests that two functionally distinct RyRs may be involved in the regulation of skeletal muscle contraction. The expression of RyR3 was analyzed in murine skeletal muscle from late foetal stages to adult, throughout neonatal phases of development. RyR3 was expressed widely during skeletal muscle post-natal development, disappearing in all muscles analyzed except diaphragm and soleus. RyR3 knockout mice were generated, and contractile properties of skeletal muscles were analyzed. Skeletal muscle contraction in RyR3-/- mice was impaired during the neonatal phase of development. In skeletal muscles isolated from RyR3-1- mice, the twitch elicited by electrical stimulation was strongly depressed. A significant reduction of the contractile activity was also elicited after stimulation with caffeine, an activator of Ca2+-release through RyRs. In the adults, no differences were detected between wild-type and mutant mice. These results are the first demonstrations of a physiological role of RyR3 in excitation-contraction coupling mechanisms of skeletal muscle, and support the model of a two-channel system regulating skeletal muscle contraction. In order to further characterize the RyR3-1- mouse, [3H]ryanodine binding experiments were performed on diaphragm and total hindlimb skeletal muscles from RyR3+/+ and RyR3-1- mice. Preliminary results will be presented and discussed.

No description available.

A method called SRICOS-EFA is presented in this dissertation for scour prediction. The method is based on the calculation of two basic parameters: the maximum depth of scour and the initial rate of scour. The maximum depth of scour is based on an equation obtained from flume tests and the initial rate is based on an equation giving the initial shear stress obtained from numerical simulations. The initial scour rate is then read on the Erosion Function Apparatus (EFA) erosion function curve at the corresponding value of the calculated shear stress. A hyperbola is used to connect the initial scour rate to the maximum scour depth and describes the complete scour depth vs. time curve. The erodibility function curve can be measured in the EFA. As the results show, the SRICOS-EFA method can handle the multi-flood hydrograph and multilayer soil system. It can be used to solve the complex pier and contraction scour alone; it can also handle the superposition of complex pier scour and contraction scour. A simplified SRICOS-EFA method was developed based on the case histories for contraction scour. EFA tests were performed to investigate the influence of different pH values and different levels of salinity on the soil erodibility. An attempt was made to find the correlation between the critical shear stress, and the initial slope of the erodibility function on the one hand and some geotechnical parameters on the other. A solution for future hydrograph prediction was developed in this dissertation. The prediction consists of using a past hydrograph, preparing the frequency distribution plot for the daily stream flows, sampling the distribution randomly and preparing a future hydrograph, which has the same mean and standard deviation as the measured hydrograph. A frequency distribution plot of scour depths can be used to quote a scour depth with a corresponding probability of occurrence and risk level based on future hydrographs. In the verification process, 10 bridge case histories and 3 scour databases were used to check whether the method is good enough to provide sound results in real cases.

Standard local control theory, which describes Ca²⁺ release during excitation-contraction coupling (ECC), assumes that all Ryanodine Receptor (RyR) complexes are equivalent. Recent data from our laboratory has called this assumption into question. Specifically, we have shown that RyR complexes in ventricular myocytes differ depending on their location within the cell. This, and other data, has led us to hypothesize that similar differences occur within the rat atrial cell. To test this hypothesis, we have triple-labeled enzymatically-isolated, fixed myocytes to examine the distribution and colocalization of RyR, calsequestrin (CSQ), voltage-gated Ca²⁺ channels (Cav1.2), sodium-calcium exchangers (NCX), and caveolin-3 (cav-3). All images were acquired on a wide-field microscope, deconvolved, and subject to extensive analysis, including a novel method of measuring statistical significance of the recorded colocalization values. Overall, eight surface RyR populations were identified, depending on its binding partners. One of these groups, in which RyR, Cav1.2, and NCX colocalize, may provide the structural basis for ‘eager’ sites of Ca²⁺ release in atria, while other groups were defined based on their association with cav-3, and are therefore highly likely to be under the influence of other signaling molecules located within caveolae. Importantly, although a small portion of the surface RyR in atria do colocalize with NCX alone, the majority are tightly linked to Cav1.2 alone or Cav1.2 and NCX together. Therefore, it appears likely that Cav1.2-mediated calcium-induced calcium release (CICR) is the primary method of initiating Ca²⁺ release from the SR during EC coupling.

The engineering design of a hydraulic structure such as a river bridge requires consideration of the factors that affect the safety of the structure. Among them, one of the most important variables is bridge foundation scour. However, engineering experience seems to indicate that computation of scour depth using current scour formulas tends to overpredict scour in comparison to field measurements. The result can be an overdesigned bridge foundation that increases the cost of the bridge. One possible reason for the overprediction is the current practice of adding separate estimates of contraction scour and pier scour when in fact these processes occur simultaneously and interact. During the occurrence of a flood, velocities and depths increase but they are affected by changes in the distribution of discharge between the main channel and floodplain. In addition, the time history or time development of contraction scour and local pier scour is not the same. As a result, the influence of contraction scour on pier scour, for example, is time dependent. Laboratory experiments are proposed using a 1:45 scale hydraulic model of the Ocmulgee River bridge at Macon, Georgia. Initially, the contraction scour will be measured without the bridge piers in place. In this experiment, the time history of the scour and the velocity distributions at the equilibrium state will be measured. Then the piers will be placed at the bridge cross-section in the flume, and the same measurements will be made. The sensitivity of the measurements to small changes in depth at the same discharge will also be determined, and comparisons will be made with field measurements of scour depth. The results will be used to assess the relative contribution of contraction scour and local pier scour to the final design of the bridge foundation depth.

Bridge scour, which is the removal of bed materials from near the bridge foundations, is observed to be the most predominant cause of bridge failures in the United States. Scour in cohesive soils is greatly different from scour in cohesionless soils owing to the differences in critical shear stresses, scour extents and the time taken to reach the maximum scour depth in the scour process. The present solutions available for the cohesionless soils cannot be applied to cohesive soils because of the above crucial reasons. Also, a compound channel model with main channel and flood plain arrangement represents more closely the field stream conditions rather than a simple rectangular prismatic model. In this study, a systematic investigation of the scour process due to flow contractions in a compound channel with cohesive soil bed is made by conducting a series of flume tests representing typical field conditions. The effect of the most crucial factors causing contraction scour namely flow velocity, depth of flow and the shape of the abutment is examined. Correction factors are developed for changes in flow geometries incorporating simulation results from the one dimensional flow simulation model HEC RAS. Most importantly, a methodology to predict the depth of the deepest scour hole and its location in the vicinity of the contraction structure is developed for compound channels through an extension of the presently available methodology to predict maximum scour depths in simple rectangular channels. A prediction method to identify the extent of the uniform scour depth is also developed. Finally, an investigation of precision of the proposed methodology has been carried out on the field data from a number of real life contraction scour cases. The results obtained from this study indicate that depth of flow and geometry of the contraction section significantly influence final scour depth in cohesive soils with deeper flows and harsh contractions resulting in increased scour depths. However, corrections for different contraction inlet skew angles and long contractions need to be further explored in future studies.

Bridge scour, which is the removal of bed materials from near the bridge foundations, is observed to be the most predominant cause of bridge failures in the United States. Scour in cohesive soils is greatly different from scour in cohesionless soils owing to the differences in critical shear stresses, scour extents and the time taken to reach the maximum scour depth in the scour process. The present solutions available for the cohesionless soils cannot be applied to cohesive soils because of the above crucial reasons. Also, a compound channel model with main channel and flood plain arrangement represents more closely the field stream conditions rather than a simple rectangular prismatic model. In this study, a systematic investigation of the scour process due to flow contractions in a compound channel with cohesive soil bed is made by conducting a series of flume tests representing typical field conditions. The effect of the most crucial factors causing contraction scour namely flow velocity, depth of flow and the shape of the abutment is examined. Correction factors are developed for changes in flow geometries incorporating simulation results from the one dimensional flow simulation model HEC RAS. Most importantly, a methodology to predict the depth of the deepest scour hole and its location in the vicinity of the contraction structure is developed for compound channels through an extension of the presently available methodology to predict maximum scour depths in simple rectangular channels. A prediction method to identify the extent of the uniform scour depth is also developed. Finally, an investigation of precision of the proposed methodology has been carried out on the field data from a number of real life contraction scour cases. The results obtained from this study indicate that depth of flow and geometry of the contraction section significantly influence final scour depth in cohesive soils with deeper flows and harsh contractions resulting in increased scour depths. However, corrections for different contraction inlet skew angles and long contractions need to be further explored in future studies.