Thesis (Ph. D.)--University of Hawaii at Manoa, 1995. / Includes bibliographical references (leaves 104-124). / Microfiche. / xii, 124 leaves, bound photos. 29 cm

Acute quadriplegic myopathy (AQM), or critical illness myopathy, is a common debilitating acquired disorder in critically ill intensive care unit (ICU) patients characterized by generalized muscle wasting and weakness of limb and trunk muscles. A preferential loss of the thick filament protein myosin is considered pathognomonic of this disorder, but the myosin loss is observed relatively late during the disease progression. In attempt to explore the potential role of factors considered triggering AQM in sedated mechanically ventilated (MV) ICU patients, we have studied the early effects, prior to the myosin loss, of neuromuscular blockade (NMB), corticosteroids (CS) and sepsis separate or in combination in a porcine experimental ICU model. Specific interest has been focused on skeletal muscle gene/protein expression and regulation of muscle contraction at the muscle fiber level. This project aims at improving our understanding of the molecular mechanisms underlying muscle specific differences in response to the ICU intervention and the role played by the different triggering factors. The sparing of masticatory muscle fiber function was coupled to an up-regulation of heat shock protein genes and down-regulation of myostatin are suggested to be key factors in the relative sparing of masticatory muscles. Up-regulation of chemokine activity genes and down-regulation of heat shock protein genes play a significant role in the limb muscle dysfunction associated with sepsis. The effects of corticosteroids in the development of limb muscle weakness reveals up-regulation of kinase activity and transcriptional regulation genes and the down-regulation of heat shock protein, sarcomeric, cytoskeletal and oxidative stress responsive genes. In contrast to limb and craniofacial muscles, the respiratory diaphragm muscle responded differently to the different triggering factors. MV itself appears to play a major role for the diaphragm muscle dysfunction. By targeting these genes, future experiments can give an insight into the development of innovative treatments expected at protecting muscle mass and function in critically ill ICU patients.

En aquesta tesi s'han dut a terme dos tipus d'estudis diferents. L'objectiu del primer era la preservació del semen de porcí a 15ºC i el del segon eren els co-cultius homòlegs de cèl·lules epitelials de l'oviducte i espermatozoides de porcí. Pel que fa al primer estudi, s'ha observat que l'addició de la prostaglandina F2α i àcid hialurònic a les dosis seminals no malmena la qualitat espermàtica i que la tolerància dels espermatozoides als canvis d'osmolalitat del medi es pot correlacionar proves de fertilitat i prolificitat..Respecte el segon, s'ha determinat que les cèl·lules oviductals afecten els paràmetres espermàtics i que la presència d'espermatozoides sobreexpressa els gens que codifiquen per les proteïnes de xoc tèrmic. Així, se suggereix que aquestes proteïnes tenen algun paper en els processos reproductius que tenen lloc a l'oviducte, malgrat que s'hagi observat, mitjançant la tècnica de la interferència de l'RNA, que la HSP90AA1 no està implicada en el perllongament de la viabilitat espermàtica. / In this thesis, two different studies have been conducted. The aim of the first experimental chapter was boar sperm preservation at 15ºC, the second dealing with in vitro homologous co-culture of oviductal epithelial cells (OEC) and spermatozoa. Regarding the first, it has been observed that the addition of prostaglandin F2α and hyaluronic acid do not cause any harm on sperm quality, and the osmotic tolerance of spermatozoa can be correlated with fertility and prolificacy rates of a given ejaculate.As far as the second study is concerned, OEC specifically affect sperm functional parameters and the presence of spermatozoa upregulates the expression of some genes encoding for heat shock proteins. Some role in the reproductive processes taking place in the oviduct is therefore suggested for this protein family, even though it has been observed, by means of RNA interference, that HSP90AA1 is not the protein involved in prolonging sperm survival.

The urokinase receptor (uPAR) plays a central role in metastatic process. It???s evident uPAR is overexpressed across a variety of tumour cells and leads to the increased aggressiveness and poor prognosis of cancer. Inhibition of uPAR expression can block metastatic potential in many tumours. In addition, besides uPA, there are several other proteins which have been confirmed to interact with uPAR, such as vitronectin and integrins. These interactions also contribute to signal transduction and the functions of uPAR complex. Therefore, downregulation of uPAR expression by targeting uPAR mRNA or protein, or by regulating the uPAR partners would be potential therapeutic strategies for prevention of cancer metastasis. There are two main aspects contained in this thesis. Firstly, three specific DNAzymes targeting uPAR mRNA were designed to downregulate uPAR expression in vitro and their effects to decrease cancer cell invasion studied in a human osteosarcoma cell line Saos-2. The results showed that two of them (Dz483 and Dz720) cleaved uPAR transcript in vitro with high efficacy and specificity and the Dz720 inhibited uPAR protein levels by 55% in Saos-2 cells. Besides, the Dz720 significantly suppressed Saos-2 cell invasion using an in vitro matrigel assay. Secondly, two potential uPAR partners from yeast two-hybrid screening, a heat shock protein MRJ and an anti-apoptosis protein HAX-1, were characterised and their functions binding with uPAR investigated. The interactions were confirmed by co-immunoprecipitation, GST-pull down assay and confocal microscopy in cancer cells. In addition, there was a 50% increase in cell adhesion after transfection with MRJ. This increase in adhesion is dependent on the uPAR/full length MRJ interaction as cells transfected with the mutant construct containing only N-terminal region or C-terminal region of MRJ had no increase in cell adhesion. The observed increase in adhesion to vitronectin by MRJ was also blocked by an anti-uPAR domain I antibody suggesting that the induced adhesion is at least in part contributed by uPAR on the cell surface. Together, the identification of both MRJ and HAX-1 as uPAR interactors provides further insight into the intricate relationship between uPAR and other proteins which may develop potential approaches for cancer therapy.

A comprehensive understanding of high-speed liquid jets is required for their introduction into engine and combustion applications. Their transient nature, short lifetime, unique characteristics and the inability to take many experimental readings, has inhibited this need. This study investigates the outflow of a high-speed liquid jet into quiescent atmospheric air. The key characteristics present are, a bow shock wave preceding the jet head, an enhanced mixing layer and the transient deformation of the liquid jet core. The outflow regime is studied in an experimental and numerical manner. In the experimental investigation, a high-speed liquid water jet is generated using the momentum exchange by impact method. The jet velocity is supersonic with respect to the impinged gaseous medium. The resulting jet speed is Mach 1.8. The jet is visualised with the use of shadowgraph apparatus. Visualisation takes place over a variety of time steps in the liquid jet???s life span and illustrates the four major development stages. The stages progress from initial rapid core jet expansion to jet stabilisation and characteristic uniform gradient formation. The visualisation shows that at all stages of the jet???s life it is axi-symmetric. One dimensional nozzle analysis and a clean bow shock wave indicate that the pulsing jet phenomenon can be ignored. In the numerical investigation, a time marching finite volume scheme is employed. The bow shock wave characteristics are studied with the use of a blunt body analogy. The jet at a specific time frame is considered a solid body. The jet shape is found to have an important influence on the shock position and shape. Analysis of the results indicates a shock stand-off similar to that seen in experimental observations and the prediction of shock data. The jet life span is modelled using a species dependent density model. The transient calculations reproduce the key jet shape characteristics shown in experimental visualisation. The mushrooming effect and large mixing layer are shown to develop. These effects are strongest when the shock wave transience has yet to stabilise. Quantitative analysis of the mixing layer at varying time steps is presented.

Bibliography: leaves 172-185. / xii, 185 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Investigates the induction of heat shock protein (HSP) by some of the anti-inflammatory agents and antirheumatic agents used in the management of rheumatoid arthritis. Presents HSP induction in peripheral white blood cells cultured in vitro. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1995?

This study investigates the stress wave force balance technique for the measurement of forces on a fuelled hypersonic flight vehicle in an impulse-type test facility. A three component force balance for the measurement of lift, thrust and pitching moment on a supersonic combustion ramjet engine was designed, built, calibrated and tested. The force balance was designed using finite element analysis and consisted of four stress bars instrumented for the measurement of strain. Relative errors of less than 2% were obtained for the recovered simulated calibration loads, while errors of less than 3% were obtained for lift and thrust components for simulated fuel-on and fuel-off force loading distributions. Tests in a calibration rig showed that the balance was capable of recovering the magnitude of point loads to within 3% and their lines of action to within 1% of the chord of the model. Additional errors result when testing in a wind tunnel. The uncertainties for the experiments with fuel injection are estimated at 9%, 7% and 9% for the coefficients of lift, thrust and pitching moment. The scramjet vehicle was 0.566m long and weighed approximately 6kg. It consisted of an inlet, combustion chamber and thrust surface. Fuel could be injected through a series of injectors located on the scramjet inlet. The scramjet model was set at zero angle of attack. Experiments were performed in the T4 Free Piston Shock Tunnel at a total enthalpy of 3.3MJ/kg, a nozzle supply pressure of 32MPa and a Mach number of 6.6, with equivalence ratios up to 1.4. Fuel-off force coefficients were measured to within 2% of theoretical values based on predictions using CFD and hypersonic theory. The fuel-off centre-of-pressure was measured to within 4% of the predicted value. The force coefficients varied linearly with equivalence ratio. Good comparison of the measured lift and thrust forces with theoretical values was obtained with increasing flow rates of fuel. The lift-to-drag ratio increased from 3.0 at the fuel-off condition to 17.2 at an equivalence ratio of 1.0. Poor agreement between the measured pitching moment and theoretical values was obtained due to difficulties in predicting the pressure distribution with heat addition on the latter parts of the thrust surface. A shift in the centre-of-pressure of approximately 10% of model chord was measured as the equivalence ratio varied from 0.0 to 1.0. For the design tested, the thrust produced was not enough to overcome drag on the vehicle, even at the highest equivalence ratio tested. Tests at higher stagnation enthalpies (up to 4.9MJ/kg) showed the lift and pitching moment coefficients remained constant with an equivalence ratio of 0.8 but the thrust coefficient decreased exponentially with increasing stagnation enthalpies. Good agreement of experimental values of lift and thrust force with predicted values was obtained for equivalence ratios of 0.0 and 0.8. Choking occurred at stagnation enthalpies of less than 3.0MJ/kg and a nozzle supply pressure of 32MPa with fuel injection at an equivalence ratio of approximately 0.8, resulting in a drag force of approximately 2.5 times the fuel-off drag force. Tests at a nozzle supply enthalpy of 3.3MJ/kg and nozzle supply pressures of 32, 26 and 16MPa were performed at equivalence ratios of 0.0 and 0.8. The fuel-off lift coefficient remained constant but the thrust coefficient increased. This is attributed to a reduction in skin friction associated with longer lengths of laminar boundary layers as the Reynolds number was decreased. The measured fuel-off lift and thrust coefficients agreed with the predicted values to within the known test flow and force prediction uncertainties. Combustion did not occur at a nozzle supply pressure of 16MPa. This work has demonstrated that overall scramjet vehicle performance measurements (such as lift-to-drag ratio and shifts in centre-of-pressure) can be made in a free piston shock tunnel.

This study investigates the stress wave force balance technique for the measurement of forces on a fuelled hypersonic flight vehicle in an impulse-type test facility. A three component force balance for the measurement of lift, thrust and pitching moment on a supersonic combustion ramjet engine was designed, built, calibrated and tested. The force balance was designed using finite element analysis and consisted of four stress bars instrumented for the measurement of strain. Relative errors of less than 2% were obtained for the recovered simulated calibration loads, while errors of less than 3% were obtained for lift and thrust components for simulated fuel-on and fuel-off force loading distributions. Tests in a calibration rig showed that the balance was capable of recovering the magnitude of point loads to within 3% and their lines of action to within 1% of the chord of the model. Additional errors result when testing in a wind tunnel. The uncertainties for the experiments with fuel injection are estimated at 9%, 7% and 9% for the coefficients of lift, thrust and pitching moment. The scramjet vehicle was 0.566m long and weighed approximately 6kg. It consisted of an inlet, combustion chamber and thrust surface. Fuel could be injected through a series of injectors located on the scramjet inlet. The scramjet model was set at zero angle of attack. Experiments were performed in the T4 Free Piston Shock Tunnel at a total enthalpy of 3.3MJ/kg, a nozzle supply pressure of 32MPa and a Mach number of 6.6, with equivalence ratios up to 1.4. Fuel-off force coefficients were measured to within 2% of theoretical values based on predictions using CFD and hypersonic theory. The fuel-off centre-of-pressure was measured to within 4% of the predicted value. The force coefficients varied linearly with equivalence ratio. Good comparison of the measured lift and thrust forces with theoretical values was obtained with increasing flow rates of fuel. The lift-to-drag ratio increased from 3.0 at the fuel-off condition to 17.2 at an equivalence ratio of 1.0. Poor agreement between the measured pitching moment and theoretical values was obtained due to difficulties in predicting the pressure distribution with heat addition on the latter parts of the thrust surface. A shift in the centre-of-pressure of approximately 10% of model chord was measured as the equivalence ratio varied from 0.0 to 1.0. For the design tested, the thrust produced was not enough to overcome drag on the vehicle, even at the highest equivalence ratio tested. Tests at higher stagnation enthalpies (up to 4.9MJ/kg) showed the lift and pitching moment coefficients remained constant with an equivalence ratio of 0.8 but the thrust coefficient decreased exponentially with increasing stagnation enthalpies. Good agreement of experimental values of lift and thrust force with predicted values was obtained for equivalence ratios of 0.0 and 0.8. Choking occurred at stagnation enthalpies of less than 3.0MJ/kg and a nozzle supply pressure of 32MPa with fuel injection at an equivalence ratio of approximately 0.8, resulting in a drag force of approximately 2.5 times the fuel-off drag force. Tests at a nozzle supply enthalpy of 3.3MJ/kg and nozzle supply pressures of 32, 26 and 16MPa were performed at equivalence ratios of 0.0 and 0.8. The fuel-off lift coefficient remained constant but the thrust coefficient increased. This is attributed to a reduction in skin friction associated with longer lengths of laminar boundary layers as the Reynolds number was decreased. The measured fuel-off lift and thrust coefficients agreed with the predicted values to within the known test flow and force prediction uncertainties. Combustion did not occur at a nozzle supply pressure of 16MPa. This work has demonstrated that overall scramjet vehicle performance measurements (such as lift-to-drag ratio and shifts in centre-of-pressure) can be made in a free piston shock tunnel.

This study investigates the stress wave force balance technique for the measurement of forces on a fuelled hypersonic flight vehicle in an impulse-type test facility. A three component force balance for the measurement of lift, thrust and pitching moment on a supersonic combustion ramjet engine was designed, built, calibrated and tested. The force balance was designed using finite element analysis and consisted of four stress bars instrumented for the measurement of strain. Relative errors of less than 2% were obtained for the recovered simulated calibration loads, while errors of less than 3% were obtained for lift and thrust components for simulated fuel-on and fuel-off force loading distributions. Tests in a calibration rig showed that the balance was capable of recovering the magnitude of point loads to within 3% and their lines of action to within 1% of the chord of the model. Additional errors result when testing in a wind tunnel. The uncertainties for the experiments with fuel injection are estimated at 9%, 7% and 9% for the coefficients of lift, thrust and pitching moment. The scramjet vehicle was 0.566m long and weighed approximately 6kg. It consisted of an inlet, combustion chamber and thrust surface. Fuel could be injected through a series of injectors located on the scramjet inlet. The scramjet model was set at zero angle of attack. Experiments were performed in the T4 Free Piston Shock Tunnel at a total enthalpy of 3.3MJ/kg, a nozzle supply pressure of 32MPa and a Mach number of 6.6, with equivalence ratios up to 1.4. Fuel-off force coefficients were measured to within 2% of theoretical values based on predictions using CFD and hypersonic theory. The fuel-off centre-of-pressure was measured to within 4% of the predicted value. The force coefficients varied linearly with equivalence ratio. Good comparison of the measured lift and thrust forces with theoretical values was obtained with increasing flow rates of fuel. The lift-to-drag ratio increased from 3.0 at the fuel-off condition to 17.2 at an equivalence ratio of 1.0. Poor agreement between the measured pitching moment and theoretical values was obtained due to difficulties in predicting the pressure distribution with heat addition on the latter parts of the thrust surface. A shift in the centre-of-pressure of approximately 10% of model chord was measured as the equivalence ratio varied from 0.0 to 1.0. For the design tested, the thrust produced was not enough to overcome drag on the vehicle, even at the highest equivalence ratio tested. Tests at higher stagnation enthalpies (up to 4.9MJ/kg) showed the lift and pitching moment coefficients remained constant with an equivalence ratio of 0.8 but the thrust coefficient decreased exponentially with increasing stagnation enthalpies. Good agreement of experimental values of lift and thrust force with predicted values was obtained for equivalence ratios of 0.0 and 0.8. Choking occurred at stagnation enthalpies of less than 3.0MJ/kg and a nozzle supply pressure of 32MPa with fuel injection at an equivalence ratio of approximately 0.8, resulting in a drag force of approximately 2.5 times the fuel-off drag force. Tests at a nozzle supply enthalpy of 3.3MJ/kg and nozzle supply pressures of 32, 26 and 16MPa were performed at equivalence ratios of 0.0 and 0.8. The fuel-off lift coefficient remained constant but the thrust coefficient increased. This is attributed to a reduction in skin friction associated with longer lengths of laminar boundary layers as the Reynolds number was decreased. The measured fuel-off lift and thrust coefficients agreed with the predicted values to within the known test flow and force prediction uncertainties. Combustion did not occur at a nozzle supply pressure of 16MPa. This work has demonstrated that overall scramjet vehicle performance measurements (such as lift-to-drag ratio and shifts in centre-of-pressure) can be made in a free piston shock tunnel.

This study investigates the stress wave force balance technique for the measurement of forces on a fuelled hypersonic flight vehicle in an impulse-type test facility. A three component force balance for the measurement of lift, thrust and pitching moment on a supersonic combustion ramjet engine was designed, built, calibrated and tested. The force balance was designed using finite element analysis and consisted of four stress bars instrumented for the measurement of strain. Relative errors of less than 2% were obtained for the recovered simulated calibration loads, while errors of less than 3% were obtained for lift and thrust components for simulated fuel-on and fuel-off force loading distributions. Tests in a calibration rig showed that the balance was capable of recovering the magnitude of point loads to within 3% and their lines of action to within 1% of the chord of the model. Additional errors result when testing in a wind tunnel. The uncertainties for the experiments with fuel injection are estimated at 9%, 7% and 9% for the coefficients of lift, thrust and pitching moment. The scramjet vehicle was 0.566m long and weighed approximately 6kg. It consisted of an inlet, combustion chamber and thrust surface. Fuel could be injected through a series of injectors located on the scramjet inlet. The scramjet model was set at zero angle of attack. Experiments were performed in the T4 Free Piston Shock Tunnel at a total enthalpy of 3.3MJ/kg, a nozzle supply pressure of 32MPa and a Mach number of 6.6, with equivalence ratios up to 1.4. Fuel-off force coefficients were measured to within 2% of theoretical values based on predictions using CFD and hypersonic theory. The fuel-off centre-of-pressure was measured to within 4% of the predicted value. The force coefficients varied linearly with equivalence ratio. Good comparison of the measured lift and thrust forces with theoretical values was obtained with increasing flow rates of fuel. The lift-to-drag ratio increased from 3.0 at the fuel-off condition to 17.2 at an equivalence ratio of 1.0. Poor agreement between the measured pitching moment and theoretical values was obtained due to difficulties in predicting the pressure distribution with heat addition on the latter parts of the thrust surface. A shift in the centre-of-pressure of approximately 10% of model chord was measured as the equivalence ratio varied from 0.0 to 1.0. For the design tested, the thrust produced was not enough to overcome drag on the vehicle, even at the highest equivalence ratio tested. Tests at higher stagnation enthalpies (up to 4.9MJ/kg) showed the lift and pitching moment coefficients remained constant with an equivalence ratio of 0.8 but the thrust coefficient decreased exponentially with increasing stagnation enthalpies. Good agreement of experimental values of lift and thrust force with predicted values was obtained for equivalence ratios of 0.0 and 0.8. Choking occurred at stagnation enthalpies of less than 3.0MJ/kg and a nozzle supply pressure of 32MPa with fuel injection at an equivalence ratio of approximately 0.8, resulting in a drag force of approximately 2.5 times the fuel-off drag force. Tests at a nozzle supply enthalpy of 3.3MJ/kg and nozzle supply pressures of 32, 26 and 16MPa were performed at equivalence ratios of 0.0 and 0.8. The fuel-off lift coefficient remained constant but the thrust coefficient increased. This is attributed to a reduction in skin friction associated with longer lengths of laminar boundary layers as the Reynolds number was decreased. The measured fuel-off lift and thrust coefficients agreed with the predicted values to within the known test flow and force prediction uncertainties. Combustion did not occur at a nozzle supply pressure of 16MPa. This work has demonstrated that overall scramjet vehicle performance measurements (such as lift-to-drag ratio and shifts in centre-of-pressure) can be made in a free piston shock tunnel.