<p>The worldwide increase in antibiotic resistance is a concern for public health. When the appropriate antibiotic dosage is determined, the priorities are efficacy and toxicity. The aim of this thesis was to gain knowledge about the most efficient dosing regimens in order to minimize the emergence and selection of antibiotic-resistant mutants. We also wanted to assess the impact of antibiotic selective pressure and host to host transmission for the dissemination of resistance.</p><p><i>Escherichia coli </i>bacteria with different levels of cefotaxime susceptibility were competed in an in vitro kinetic model, demonstrating a complex selection of low-level resistance influenced e.g. by the time duration of selective concentrations and the rise of new mutants. We also constructed a mathematical model incorporating biologically relevant parameters and showed its usefulness when assessing the risks of resistance development.</p><p>When <i>E. coli </i>populations with pre-existing fluoroquinolone-resistant mutants were exposed to simulated serum concentrations, several currently used doses of fluoroquinolones clearly enhanced the development and selection of resistance. </p><p>The mutant prevention concentration (MPC) was measured for several <i>E. coli</i> isolates with different fluoroquinolone susceptibilities, and because of fluctuating antibiotic concentrations in the human body, the pharmacokinetics was considered when evaluating MPC. Results indicate that the area under the serum concentration time curve in relation to the MPC may be a useful predictor for emergence of resistance.</p><p>In the commensal flora of healthy human couples we noted a high frequency of trimethoprim-resistant <i>E. coli.</i> There was also an extensive sharing and transmission of <i>E. coli</i> clones. Treating the female with trimethoprim reduced the number of intestinal <i>E. coli</i> which might have facilitated the transmission from the male partner. These findings suggest that the rate of transmission is high and effectively contributes to the spread of both susceptible and antibiotic-resistant <i>E. coli</i> in intrafamilial settings.</p>

The objective of this study was to investigate the physiology and productivity in Escherichia colicultures with emphasis on the temperature-limited fed-batch (TLFB) culture. The TLFB techniquecontrols the oxygen consumption rate of the growing culture by a gradually declining temperaturefrom 37-35 °C down to 20-18 °C. The temperature regulated the DOT around a set-point (30 % airsat.), and all nutrients were in excess. Glucose was fed into the culture continuously, however, highacetate formation was avoided by keeping the glucose at a low, yet excessive, concentration. Thebiomass productivity was approximately the same in TLFB as in glucose-limited fed-batch (GLFB)cultures, since the specific growth rate and the oxygen consumption rate are limited by the oxygentransfer capacity of the reactor in both techniques.High concentrations of endotoxins were found in the medium of E. coli fed-batch cultures at lowspecific growth rates (below 0.1 h-1) and severe glucose limitation. In this thesis the TLFB techniquewas found to suppress the endotoxin release even at low specific growth rates. The repressed release of endotoxins in TLFB cultures was due to the high availability of glucose and not to the low growthrate or the lower temperature. The conclusion was drawn from comparing with the GLFB technique performed at 20 °C, which resulted in high endotoxin release.Extensive release of endotoxin, accompanied with high concentrations of soluble proteins was foundin a TLFB culture exposed to a higher energy dissipation rate, 16 kW m-3, instead of 2 kW m-3, due toa higher stirrer speed (1000 instead of 500 rpm). The hypothesis that this is a result of mechanicalstress is discussed in context with the common view that cells like E. coli, which are smaller than the Kolmogoroff’s microscale of turbulence, should not be influenced by the turbulence.TLFB cultured cells exhibited more stable cytoplasmic membranes when treated with osmotic shockas compared to the GLFB cultured cells. The concentrations of DNA and soluble proteins in the periplasmic extracts from the TLFB cultured cells were lower than from GLFB cultured cells. Inaddition, the specific productivity of periplasmic β-lactamase was higher in the TLFB cultures,suggesting that this technique could be an alternative for protein production. The solubility of apartially aggregated recombinant protein increased in the TLFB compared to the GLFB cultures.However some time after induction, in spite of the gradually declining temperature, the solublefraction decreased.For obtaining better understanding of the performance of the process and for identifying criticalparameters, a mathematical model was developed based on the growth, energy and overflowmetabolism at non-limiting nutrient conditions. The temperature-dependent maximum specific glucoseand oxygen uptake rates were determined in pH-auxostat cultures for temperatures ranging from 18 to37 °C. A dynamic simulation model of the TLFB technique was developed and the results were compared to experimental data. The simulation program was also used for sensitivity analysis of some physiological and process parameters to study the impact on biomass concentration and temperatureprofiles. An effect on the biomass concentration profile but not on the temperature profile wasobserved when changing the oxygen transfer coefficient. If the maximum specific glucose uptake ratewas altered, or if the glucose concentration was permitted to assume other values, the temperatureprofile but not the biomass concentration profile was influenced. Cell death affected both the biomassconcentration profile and the temperature profile. / QC 20100922

The aim of the present thesis was to study the heat flows in the blast furnace hearth lining by experimental measurements and numerical modeling. Thermocouple data from an operating furnace have been used throughout the work, to verify results and to develop methodologies to use the results in further studies. The hearth lining were divided into two zones based on the thermocouple readings: a region with regular temperature variations due to the tapping of the furnace, and another region with slow temperature variations. In an experimental study, the temperatures of the outer surfaces of the wall and bottom were measured and compared with lining temperature measured by thermocouples. Expressions to describe the outer surface temperature profiles were derived and used as input in a two-dimensional steady state heat transfer model. The aim of the study was to predict the lining temperature profiles in the region subjected to slow temperature variations. The methodology to calculate a steady state lining temperature profile was used as input to a three-dimensional model. The aim of the three-dimensional model was primarily to study the region with dynamic lining temperature variations caused by regular tappings. The study revealed that the replacement of original lining with tap clay has an effect when simulating the quasi-stationary temperature variations in the lining. The study initiated a more detailed study of the taphole region and the size and shape of the tap clay layer profile. It was concluded, that in order to make a more accurate heat transfer model of the blast furnace hearth, the presence of a skull build-up below the taphole, erosion above the taphole and the bath level variations must to be taken into consideration. / QC 20100706

Neighbouring plants can interact strongly, competing for resources including light, water, animal mutualists, and local germination sites. From an evolutionary perspective, this implies that a plant’s best resource acquisition strategy will usually depend on the traits of its neighbours, and for plants in particular, neighbours are often genealogical relatives. Here, I use a combination of theory and experiments to expose some important consequences of social interactions among plants. The first model analyzes selection on traits used to attract pollinators, showing that competitive interactions (in the absence of local relatedness) can select for exaggerated secondary sexual characters. To complement this model, I performed experiments that confirm the mechanisms by which adaptive pollinator foraging naturally leads to interactions among plants. The observed foraging behaviour (of bumble bees) also provides unique evidence for ‘Bayesian foraging’, a sophisticated type of resource assessment that depends on prior experience in a particular environment. A second model considers how selection on the sex allocation of cosexual, animal-dispersed plants leads to competition and cooperation over local germination sites, sometimes leading to the origin of gender dimorphism. The model reveals novel ecological contexts in which disruptive selection on sex allocation can arise, and in general, illustrates how selection for cooperation can facilitate or inhibit evolutionary diversification. In the models considered here, cooperation is indiscriminant, but plants might also assess the relatedness of neighbours and cooperate with kin over non-kin. In the final chapter, I present experimental evidence that is consistent with preferential cooperation over soil resources among sibling plants. This study is the first to link a potentially cooperative resource allocation strategy with an increase in the mean fitness of related plants.

The aim of this project is to provide a manual wheelchair simulator for advanced wheelchair research within Toronto Rehabilitation Institute‘s Challenging Environment Assessment Laboratory (CEAL). To achieve this, a comprehensive mathematical model of the wheelchair/user system and a fully adjustable physical interface (which mimics various wheelchair configurations) have been developed. The mathematical model is unique in its ability to predict complex motions such as wheelies, and is able to update the wheelchair‘s position in a virtual environment, and calculate the force-feedback required for simulating various slopes and surfaces. The physical interface is used to measure the inputs required by the mathematical model (hand-rim input torques, hand and torso positions, and user centre-of-mass position), and utilizes servo motors to provide force-feedback at the wheelchair‘s hand-rims. Preliminary results comparing real-world wheelchair motion data to the mathematical model‘s predictions are presented, along with the physical interface design and mathematical model development.

A mathematical model to simulate the reaction kinetics of dust–carbon composite agglomerates in an RHF was developed. Major chemical, thermal and physical phenomena taking place during RHF treatment were formulated and the corresponding equations were solved to yield the trend of solid composition, temperature and gas composition of the agglomerates. The model calculation results indicate that the pellet reduction is accelerated by the reducing gas from high–volatile reductants if the gas is released after the pellet temperature is sufficiently high for reduction. The reduction of zinc oxide can also be represented using the model by implementing its small particle size caused by the inherent vaporization/re–oxidization process that zinc comes through in a melter. It was demonstrated that the proposed model can be used as an engineering tool to determine the optimum operating conditions for the RHF process to promote recycling a wide range of waste materials.

The aim of this project is to provide a manual wheelchair simulator for advanced wheelchair research within Toronto Rehabilitation Institute‘s Challenging Environment Assessment Laboratory (CEAL). To achieve this, a comprehensive mathematical model of the wheelchair/user system and a fully adjustable physical interface (which mimics various wheelchair configurations) have been developed. The mathematical model is unique in its ability to predict complex motions such as wheelies, and is able to update the wheelchair‘s position in a virtual environment, and calculate the force-feedback required for simulating various slopes and surfaces. The physical interface is used to measure the inputs required by the mathematical model (hand-rim input torques, hand and torso positions, and user centre-of-mass position), and utilizes servo motors to provide force-feedback at the wheelchair‘s hand-rims. Preliminary results comparing real-world wheelchair motion data to the mathematical model‘s predictions are presented, along with the physical interface design and mathematical model development.

A mathematical model to simulate the reaction kinetics of dust–carbon composite agglomerates in an RHF was developed. Major chemical, thermal and physical phenomena taking place during RHF treatment were formulated and the corresponding equations were solved to yield the trend of solid composition, temperature and gas composition of the agglomerates. The model calculation results indicate that the pellet reduction is accelerated by the reducing gas from high–volatile reductants if the gas is released after the pellet temperature is sufficiently high for reduction. The reduction of zinc oxide can also be represented using the model by implementing its small particle size caused by the inherent vaporization/re–oxidization process that zinc comes through in a melter. It was demonstrated that the proposed model can be used as an engineering tool to determine the optimum operating conditions for the RHF process to promote recycling a wide range of waste materials.

The purpose of this thesis was to determine how shaft stiffness affects clubhead speed and how it alters clubhead orientation at impact. For the first time, a 3D, six-segment forward dynamics model of a golfer and club was developed and optimized to answer these questions. A range of shaft stiffness levels from flexible to stiff were evaluated at three levels of swing speed (38, 45 and 53 m/s). At any level of swing speed, the difference in clubhead speed did not exceed 0.1 m/s across levels of shaft stiffness. Therefore, it was concluded that customizing the stiffness of a golf club shaft to perfectly suit a particular swing will not increase clubhead speed sufficiently to have any meaningful effect on performance. The magnitude of lead deflection at impact increased as shaft stiffness decreased. The magnitude of lead deflection at impact also increased as swing speed increased. For an optimized swing that generated a clubhead speed of 45 m/s, with a shaft of regular stiffness, lead deflection of the shaft at impact was 6.25 cm. The same simulation resulted in a toe-down shaft deflection of 2.27 cm at impact. Using the model, it was estimated that for each centimeter of lead deflection of the shaft, dynamic loft increased by approximately 0.8 degrees. Toe-down shaft deflection had relatively no influence on dynamic loft. For every centimeter increase in lead deflection of the shaft, dynamic closing of the clubface increased by approximately 0.7 degrees. For every centimeter increase in toe-down shaft deflection, dynamic closing of the clubface decreased by approximately 0.5 degrees. The results from this thesis indicate that improvements in driving distance brought about by altering shaft stiffness are the result of altered clubhead orientation at impact and not increased clubhead speed.

Neighbouring plants can interact strongly, competing for resources including light, water, animal mutualists, and local germination sites. From an evolutionary perspective, this implies that a plant’s best resource acquisition strategy will usually depend on the traits of its neighbours, and for plants in particular, neighbours are often genealogical relatives. Here, I use a combination of theory and experiments to expose some important consequences of social interactions among plants. The first model analyzes selection on traits used to attract pollinators, showing that competitive interactions (in the absence of local relatedness) can select for exaggerated secondary sexual characters. To complement this model, I performed experiments that confirm the mechanisms by which adaptive pollinator foraging naturally leads to interactions among plants. The observed foraging behaviour (of bumble bees) also provides unique evidence for ‘Bayesian foraging’, a sophisticated type of resource assessment that depends on prior experience in a particular environment. A second model considers how selection on the sex allocation of cosexual, animal-dispersed plants leads to competition and cooperation over local germination sites, sometimes leading to the origin of gender dimorphism. The model reveals novel ecological contexts in which disruptive selection on sex allocation can arise, and in general, illustrates how selection for cooperation can facilitate or inhibit evolutionary diversification. In the models considered here, cooperation is indiscriminant, but plants might also assess the relatedness of neighbours and cooperate with kin over non-kin. In the final chapter, I present experimental evidence that is consistent with preferential cooperation over soil resources among sibling plants. This study is the first to link a potentially cooperative resource allocation strategy with an increase in the mean fitness of related plants.