Glaucoma is characterized by retinal ganglion cell apoptosis leading to a corresponding loss of the visual field. Elevated intraocular pressure is the principal clinical association of this disease and its reduction remains the mainstay of current therapy. This research established an in-vitro glaucoma model and investigated the direct effects of increased hydrostatic pressure on retinal ganglion cell survival as well as the cellular response to changes in pressure. In the first part of this thesis (chapter 3) the direct effects of pressure on retinal ganglion cell survival was established. The differentiated RGC5 cell line was subjected to elevated pressure 100 mmHg for a period of two hours in a pressure chamber. Cell apoptosis was then detected by TdT-mediated dITP Nick-End Labelling (TUNEL). Quantitative analysis of the percentage of apoptotic cells between the control and pressure groups by Laser Scanning Cytometry (LSC) revealed that pressure alone induced significant apoptosis. Furthermore, caspase-3 cleavage was detected in the pressure treated cells by Western blot analysis. The next three chapters investigated how the applied pressure may be mediated through cellular mechno-sensitive structures. TWIK Related Arachiodonic Acid stimulated K+ channel (TRAAK) is a mechano-gated neuronal potassium channel, which can be opened by pressure and arachidonic acid. In chapter 4, TRAAK was identified as expressed on the rat RGC5 cell line. This was determined by both immunostaining and RT-PCR. Opening this channel by arachidonic acid induced significant apoptosis in RGC5 neurons; elevated extracellular K+ concentration and blockage of TRAAK by gadolinium inhibited both arachidonic acid and pressure-induced apoptosis. These results indicated that elevated pressure resulted in opening of the outward potassium channel-TRAAK and consequently potassium ion efflux and apoptotic volume decrease (AVD). Data from chapter 5 revealed that pressure also caused actin reorganization with both F- and G-actin shifts. At the early stage (following 2 hours pressure treatment), actin polymerization led to G-actin pool decrease and disinhibition of DNase1 in the cytoplasm. This has been suggested to lead to DNase1 nuclear translocation and contribution to DNA fragmentation associated with apoptosis. The preliminary microarray results of chapter 6 revealed pressure effects on gene expression Included in the many up- and down-regulated genes was; down-regulation of antiapoptotic gene- BcL-x and up- regulation of Damage-Induced Neuronal Endopeptidase (DINE) after pressure treatment. This study showed that elevated pressure induced RGC5 apoptosis and affected multi cellular mechanosnesitive structures. These results may indicate new mechanisms of RGC neuron apoptosis and further therapeutic strategies.

Thesis (Ph. D.)--Washington State University. / Includes bibliographical references.

No description available.

No description available.

Glaucoma is characterized by retinal ganglion cell apoptosis leading to a corresponding loss of the visual field. Elevated intraocular pressure is the principal clinical association of this disease and its reduction remains the mainstay of current therapy. This research established an in-vitro glaucoma model and investigated the direct effects of increased hydrostatic pressure on retinal ganglion cell survival as well as the cellular response to changes in pressure. In the first part of this thesis (chapter 3) the direct effects of pressure on retinal ganglion cell survival was established. The differentiated RGC5 cell line was subjected to elevated pressure 100 mmHg for a period of two hours in a pressure chamber. Cell apoptosis was then detected by TdT-mediated dITP Nick-End Labelling (TUNEL). Quantitative analysis of the percentage of apoptotic cells between the control and pressure groups by Laser Scanning Cytometry (LSC) revealed that pressure alone induced significant apoptosis. Furthermore, caspase-3 cleavage was detected in the pressure treated cells by Western blot analysis. The next three chapters investigated how the applied pressure may be mediated through cellular mechno-sensitive structures. TWIK Related Arachiodonic Acid stimulated K+ channel (TRAAK) is a mechano-gated neuronal potassium channel, which can be opened by pressure and arachidonic acid. In chapter 4, TRAAK was identified as expressed on the rat RGC5 cell line. This was determined by both immunostaining and RT-PCR. Opening this channel by arachidonic acid induced significant apoptosis in RGC5 neurons; elevated extracellular K+ concentration and blockage of TRAAK by gadolinium inhibited both arachidonic acid and pressure-induced apoptosis. These results indicated that elevated pressure resulted in opening of the outward potassium channel-TRAAK and consequently potassium ion efflux and apoptotic volume decrease (AVD). Data from chapter 5 revealed that pressure also caused actin reorganization with both F- and G-actin shifts. At the early stage (following 2 hours pressure treatment), actin polymerization led to G-actin pool decrease and disinhibition of DNase1 in the cytoplasm. This has been suggested to lead to DNase1 nuclear translocation and contribution to DNA fragmentation associated with apoptosis. The preliminary microarray results of chapter 6 revealed pressure effects on gene expression Included in the many up- and down-regulated genes was; down-regulation of antiapoptotic gene- BcL-x and up- regulation of Damage-Induced Neuronal Endopeptidase (DINE) after pressure treatment. This study showed that elevated pressure induced RGC5 apoptosis and affected multi cellular mechanosnesitive structures. These results may indicate new mechanisms of RGC neuron apoptosis and further therapeutic strategies.

Thesis (Ph. D. engineering science)--Washington State University, December 2007. / Includes bibliographical references.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1992. / Vita. Abstract. Includes bibliographical references (leaves 196-198). Also available via the Internet.

Mesoscale processes in the atmosphere refer to the atmospheric processes that take place within a scale of a few to several hundred kilometres. Atmospheric phenomena like thunderstorms, inertia-gravity waves, jet streaks, fronts and many others have length scales within the range of Mesoscale dynamics. In the study of these processes, because the horizontal length scales are very large as compared to the vertical scales, often vertical acceleration is ignored. Such type of processes are termed as hydrostatic mesoscale processes. If the vertical accelerations are not ignored, then the mesoscale processes are known as nonhydrostatic mesoscale processes. This research work gives a study of the convectively forced nonhydrostatic mesoscale processes. Comparison is made between the results of both hydrostatic and nonhydrostatic mesoscale processes. To do so, a stably stratified, two-dimensional, Boussinesq, nonrotating, inviscid fluid experiencing a thermal forcing is considered under both hydrostatic and nonhydrostatic assumptions. While explicit analytic solutions are available for the hydrostatic cases under both a constant and a shear (linear in z) background profile, to understand the nonhydrostatic cases, a complete discritization of the governing linearized set of equations is carried out for the same background profiles. It has been found that the hydrostatic assumption does not depict the complete dynamics of the process. A horizontal propagation of a wave which is found to be present in the nonhydrostatic cases, is completely missing in the hydrostatic cases. Further, we show that for both, hydrostatic and nonhydrostatic, cases a sinusoidal shear background profile is nonlinearly unstable. However, because of mathematical difficulties, this work is done for a more specific convectively forced mesoscale processes. More specifically, a sinusoidal background profile is chosen and the external forcing is also treated in a more specific manner. Different from the study of flows forced by an external heating source, where the impacts of the forced wave modes with the atmosphere are studied, for various processes we need to allow the feedback of the atmosphere to the latent heating and a well known way to get such a feedback of the atmosphere is to assume that the diabatic heating is everywhere proportional to the vertical velocity. This kind of treatment of the external forcing is appropriate, for instance, for the processes like moist convection. Under such an assumption, the heating will respond to the motion of an air parcel. If the parcel rises upward, latent heat will be released and evaporative cooling will be observed if the parcel of air undergoes a downward motion. To prove the nonlinear instability for a sinusoidal background profile, first the well-posedness of the governing set of nonlinear equations is established. Then, a linear unstable mode is constructed using a method of continued fractions and then finally, following Grenier's idea, it is shown that the constructed linear unstable mode is also nonlinearly unstable. / Graduate / 0280 / 0346 / 0725 / 0373 / awais.qu@live.ca

Adaption to environmental stresses is vital for the survival of all organisms living in any environment. Two of the major environmental factors in the deep sea environment are high hydrostatic pressure and high salt concentration. Hydrostatic pressure and osmotic pressure share similarities in their effects on organisms living in the deep sea but this overlap has been little explored. Major studies from Japan and California over the last 40 years have shown the effects of hydrostatic pressure on bacteria from the deep sea (see [1] for a review). These are complemented by work by Yancey et al. [2] showing that specific solutes accumulated in response to osmotic pressure in fish have the ability to enhance resistance to hydrostatic pressure. However, this work has been done in vitro or with larger organisms and not much is known about the overlap of osmotic and hydrostatic pressure in bacteria. In this study I investigated the effects of osmotic and hydrostatic pressure on two model organisms: Photobacterium profundum and Escherichia coli. In order to accomplish this task I developed novel imaging equipment which allows for high resolution imaging of bacteria at pressure. I also developed a new method of growing bacteria in 96-well plates at high pressure, which lead to the identification of a hierarchy of genes essential for the growth of E. coli at pressure. I used the same 96-well plate technique to monitor the growth of P. profundum at differing osmotic and hydrostatic pressures. Furthermore I also attempted to analyse the solutes accumulated by different strains of P. profundum in response to osmotic and hydrostatic pressures.

The object of this study is to explore the deformation pattern of axisymmetric clad materials composed of the single-core and the sleeve during hydrostatic extrusion, and discuss the relations between processing condition factors and extrusion pressure in hydrostatic extrusion of axisymmetric clad materials. In the FEM simulation of composite materials during hydrostatic extrusion, this paper describes a technique that can be used for predicting whether core bursting of composite materials occurs or not. The effect of several extrusion parameters on the damage value of the core is examined: extrusion ratio(R), die semicone angle(£\¢X), bonding friction factor(mi), material strength ratio. By performing FEM simulations and discussing the effect of parameters on distribution of damage value obtained, it is possible to establish a data base for prevention of fracture of the core. The paper has designed and constructed an experimental receiver pressure of hydrostatic apparatus with a maximum working pressure of 7000 kgf/cm2. In experiment, extrusion of Cu-Al composite rods with different of core radius ratio was carried out. It has been found that uniform deformation always occurs under the combination of hard sleeve and soft core and the core layer usually fails due to the tension under the combination of hard core and soft sleeve.