Antidepressants are generally believed to exert their clinical efficacy by enhancing 5-HT transmission. Interestingly, sustained administration of selective serotonin (5-HT) reuptake inhibitors (SSRIs) strongly suppresses in the first few days the firing activity of 5-HT neurons in the dorsal raphe nucleus (DRN), thereby severely hampering the increase of 5-HT in target regions. Remarkably, the firing activity of 5-HT neurons gradually recovers over the time course of treatment and this recovery is believed to be accounted for by the desensitization of 5-HT1A somatodendritic autoreceptors. Here, we sought to investigate whether additional mechanisms might contribute to the dynamic regulation of excitability of 5-HT neurons during the course of SSRI treatments. Borrowing from the well-described homeostatic strengthening of glutamatergic synapses onto cortical pyramidal neurons following prolonged periods of inactivity, we hypothesized that a similar homeostatic-like regulation of synaptic strength might be operant on 5-HT cells during an SSRI treatment. To test this possibility, we used whole-cell electrophysiological recordings on acute midbrain slices to monitor glutamatergic synapses onto 5-HT neurons. We found that a two-day treatment with the SSRI citalopram induced a robust reduction in both the amplitude and frequency of AMPAR-mediated mEPSCs. We also show that this depression in synaptic strength, induced by an SSRI, is transient since excitatory drive onto 5-HT neurons was enhanced by 7 days of treatments. Altogether, these results document a dynamic regulation of glutamatergic synaptic transmission during the time course of a prolonged treatment with an SSRI. Further elucidation of the cellular and molecular mechanisms driving this synaptic plasticity might identify novel pharmacological target to shorten the delay of antidepressant action.

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The primary objective of this dissertation is to investigate whether Canadian whole farm programs with both income-supporting and income-stabilizing attributes, which are considered as decoupled based on the WTO criterion, are actually decoupled from production. The dissertation began with the review of the existing theoretical and empirical literature on the impact of programs designed to be decoupled payments on acreage response including studies related to the wealth and insurance effects. The review revealed that previous studies lack a detailed theoretical model of how acreage decisions will be affected by stabilizing the farm profit (insurance effect) as well as the higher expected profit (wealth effect). Given the nature of Canadian whole farm programs which attempt to smooth income, to examine the whole farm programs, a model is needed to capture the insurance effect arising from these programs as well as the wealth effect.<p> To address this gap, the theoretical framework developed by Chavas and Holt (1990) was extended, in this dissertation, to incorporate the insurance effect into the farmers' acreage decisions under uncertainty. In particular, by developing theoretical restrictions, which consider the relationship between income stabilization compensated and uncompensated acreage decision functions, the insurance effect emphasized in the literature was explicitly derived within the theoretical model. The acreage allocated to each crop was derived as a function of expected crop profits, elements of the variance-covariance matrix of crop profits, expected total wealth (initial wealth plus market profit), and variance of total wealth. The government payments were incorporated into the model through truncation of the probability distribution of profits. Specifically, the whole-farm programs truncated the total (farm) profit distribution which affected the expected total wealth and variance of total wealth.<p> The theoretical model was then used to develop an empirical model. The econometric model was applied to acreage data in the Canadian Prairies from 1970 to 2006 in order to statistically test if the whole farm programs were really decoupled. The results revealed that coefficients of expected total wealth (wealth effect) and variance of total wealth (insurance effect) were statistically significant in the whole system, which implied the whole-farm programs were production and therefore trade distorting and were not actually decoupled, even if they satisfied the WTO criteria. The statistically significant coefficients for expected total wealth and variance of total wealth variables were then used to simulate the impact of recent whole-farm programsthe Western Grain Stabilization Act (WGSA), the Net Income Stabilization Account (NISA) and the Canadian Agricultural Income Stabilization (CAIS)on crop choices.<p> The results suggested that the WGSA, NISA and CAIS programs have increased the acreage allocated to spring wheat and peas (through both wealth and insurance effects, although the insurance effect appears to dominate) while they have decreased the acreage for barley (through the wealth effect), canola and hay (through the insurance effect) in the prairie provinces. In general, the size of the wealth effect was quite small, while the insurance effect was always significant. Specifically, the acreage allocated to wheat increased by 7.79 percent on average across Prairies while canola acreage decreased by 8.86 percent under the CAIS. Thus, the empirical results revealed that for Canadian whole-farm programs the impact of the effects related to risk is important. Particularly, the results showed the inherent difficulty in divorcing the stabilization effect received by Canadian whole-farm programs from farmers' production decisions.

The Royal Canadian Mounted Police (RCMP) Forensic Laboratory Services (FLS) needed a method to confirm positive lysergic acid diethylamide (LSD) immunoassay screening results. As a result, an ultra performance liquid chromatography tandem mass spectrometry (UPLC¢â/MS/MS) method was validated for the confirmation and quantitation of LSD, iso-LSD, N-demethyl-LSD (nor-LSD), and 2-oxo-3-hydroxy-LSD (O-H-LSD). The method was validated in urine and whole blood, where linearity, accuracy, precision, sensitivity, stability, selectivity, recovery, matrix effects, and reproducibility were evaluated. <p>The method involved a liquid-liquid extraction (LLE) of the analytes and the deuterated internal standard from 1 mL of urine or whole blood with dichloromethane:isopropyl alcohol after being basified. The average recovery for all analytes was ¡Ã 62%, and the matrix effect was found to be insignificant. MS/MS analysis was conducted with a triple quadrupole mass spectrometer by positive electrospray ionization (ESI+) in multiple reaction monitoring (MRM) mode. The lowest limit of quantitation (LLOQ) was 20 pg/mL for LSD and iso-LSD, and 50 pg/mL for nor-LSD and O-H-LSD. The method was linear, accurate, precise, selective, and reproducible from 20 to 2000 pg/mL for LSD and iso-LSD, and from 50 to 2000 pg/mL for nor-LSD and O-H-LSD with an r2 ¡Ã 0.99. <p>The refrigerated and frozen long term stability was investigated for 90 days. LSD was stable at all temperatures for 90 days. Iso-LSD in blood was also stable at all temperatures for 90 days, but iso-LSD in urine showed an initial decrease followed by a gradual increase back to day 0 concentrations. Nor-LSD was stable at all temperatures up to day 14, with >43% decrease by day 30, with no additional decrease for the next 60 days. O-H-LSD in urine was stable at all temperatures for 90 days, but by day 90 O-H-LSD in whole blood stored refrigerated decreased in concentration by >37%. Additionally, a case sample that was stored at -50¡ÆC for ten years was found to still contain measurable amounts of each compound. <p>The method was applied to blind samples and a case that screened positive with immunoassay. Retention time, relative retention time, and ion ratios were used as identification parameters and found to correctly identify the analytes 100% of the time with no false positives. The case sample showed that the concentration of O-H-LSD was 4 times greater than LSD in urine. Furthermore, both the detection of O-H-LSD in a blood case sample, and LSD in a vitreous humor case sample were the first to be documented.

Field pea is the most produced and exported pulse crop in Canada, and makes a major contribution to Western Canadian agricultural diversification programs. Canada is now the world largest exporter of pea, lentil and chickpea and is fourth in dry bean. The demand for Canadian pulse products is steadily rising and the export market would continue to rise with the expected increased in production. Field pea exported to countries with tropical climates is at particular risk due to rapid loss of quality. It is therefore important to develop practical strategies for safe storage of feed pea. Knowledge on the moisture adsorption and spoilage characteristics of pea stored in adverse storage conditions is important in the transportation and storage of this export commodity. <p> This study was initiated to examine the conditions that lead to quality losses in storage and transport of pea. Tropical and subtropical conditions were simulated in airtight chambers. Relative humidities (RH) of 60, 70, 80 and 90% were created by saturated salt solutions in airtight chambers at temperatures of 10, 20 and 30°C, while the same range of humidity was provided by dilute sulphuric acid in airtight chambers at 40°C in environmental cabinets. The four RH levels at each temperature for both whole and feed-grade pea were tested in duplicate. The samples were observed for changes in moisture content (MC), mold appearance and RH in specific time intervals. The amount of produced carbon dioxide (CO2) was measured in airtight chambers during storage to control the condition existing in sealed airtight chambers. Also, all components of feed-grade pea were exposed to RH of 90% and temperature of 40°C in separate airtight chambers to find the effect of each component on mold appearance. Molds were identified after appearance on the samples in order to pinpoint potential toxicity. <p> Both feed and whole sound peas became molded after a short time of storage at high temperatures and high RH, but those stored at 70% and below did not develop mold after 175 days at 30 and 40°C (experiment duration) and 216 days at 10 and 20°C (experiment duration). Molds were identified mostly as species of Aspergillus and Penicillium. The amount of CO2 in the airtight chambers showed almost no difference from the ambient CO2 except at high temperature and high RH when samples had gone molded. <p> Moisture adsorption equations were developed based on the moisture adsorption data in dynamic environment. Although the Page model showed to fit the data better, the exponential model was chosen to fit the data because its parameters can be better expressed as a function of temperature and RH of the storage environment. <p> The mold-free days for both feed pea and clean pea were modeled at temperatures of 10, 20, 30 and 40°C and RH of 80 and 90%.

Commercial building owners spent $167 billion for energy in 2006. Building commissioning services have proven to be successful in saving building energy consumption. However, the optimal energy performance obtained by commissioning may subsequently degrade. The persistence of savings is of significant interest. For commissioning persistence, two statistical approaches, Days Exceeding Threshold-Date (DET-Date) method and Days Exceeding Threshold-Outside Air Temperature (DET-Toa) method, are developed to detect abnormal whole building energy consumption, and two approaches called Cosine Similarity method and Euclidean Distance Similarity method are developed to isolate the possible fault reasons. The effectiveness of these approaches is demonstrated and compared through tests in simulation and real buildings. The impacts of the factors including calibrated simulation model accuracy, fault severity, the time of fault occurrence, reference control change magnitude setting, and fault period length are addressed in the sensitivity study. The study shows that the DET-Toa method and the Cosine Similarity method are superior and more useful for the whole building fault detection and diagnosis.

The purpose of this research was, in order to forestall future failures of foresight, to provoke those responsible for risk governance into new ways of thinking through a greater exposure to and understanding of the body of existing academic knowledge. The research, which focused on the scholarship of application, synthesised the existing knowledge into a ―coherent whole‖ in order to assess its practical utility and to examine what is to be learnt about existing knowledge by trying to use it in practice. The findings are in two parts. The first focuses on how one ―thinks about thinking‖ about an issue. Early work identified three issues that were seen as being central to the understanding of risk governance. The first is the concept of risk itself, the second is to question whether there is a single paradigm used and the third is what is meant by the term ―risk indicator‖. A ―coherent whole‖, structured around seven-dimensions, was created from the range of definitions used within existing literature. No single paradigm was found to be used when discussing risk issues. Three paradigms were identified and labelled ―Line‖, ―Circle‖ and ―Dot‖. It was concluded that Risk Indicators were used to performance manage risk mitigation barriers rather than as a mechanism by which organisations may identify emerging risks. The second focus was the synthesis of academic work relevant to risk governance. It produced a list of statements which encapsulated the concerns of previous writers on this subject. The research then operationalised the issues as questions, which were seen to have practical utility. The elements of the ―coherent whole‖ suggest a way to provide access into the original research. The research suggests that it is unlikely that practitioners would wish to access the original research in its academic format. Further work therefore needs to be done to present the original work in a format that is more digestible to the practitioner community if it is to be used effectively. The results of this research are considered to be preliminary. No claim is being made that these questions are definitive. The research is however addressing an area which is of concern to those in practice and has not been previously examined.

Microfluidic chips have gained wide applications in various fields, including medicine, environmental sciences and forensic investigations. They are used for the separation of proteins, blood, bacterial cell suspensions, antibody solutions, and drugs. Microfluidic chips display significant advantages, which include faster analysis time, reduced amounts of samples and reagents volumes, flexibility in design and increased separation efficiency. Whole column imaging detection (WCID) exhibits significant advantages compared to other detection methods that are widely used for detecting analytes after the separation of these analytes using isoelectric focusing. With these other methods, there is a need to mobilize the focused sample bands past the detector after separation but with WCID, there is no need for mobilization step. The aim of this research is further development of WCID by characterizing microfluidic chips fabricated for the detection system, to enhance its detection so that high efficiency can be obtained. The chips were fabricated using soft lithography technology at the Microfluidic laboratory, University of Waterloo and they were used to perform isoelectric focusing of various proteins in our laboratory. The fabricated chips with straight channel design were used to carry out isoelectric focusing of some proteins and the results obtained were compared with the results obtained using commercial cartridges. The chips with tapered channel design were used to carry out isoelectric focusing of proteins in which thermally generated pH gradient principle was employed. The samples after separation were sprayed into a mass spectrometer using nano-electrospray interface to obtain their molecular masses. Compatible cartridges for nano-electrospray mass spectrometer were developed and these cartridges were used to carry out capillary isoelectric focusing of low molecular pI markers and proteins. These cartridges were also connected to the nano-electrospray mass spectrometer to obtain the mass to charge ratios of some proteins. The fabricated microfluidic chips with straight channel design were also used to investigate the interaction between drugs and protein.

Hospitals have limited budgets, making the cost of an examination important. A whole-body MRI scan is much less expensive than a PET-CT scan, making the MRI desirable in cases when the result from the MR machine will be sufficient. Also, unlike CT, MRI does not rely on ionizing radiation, which is known to increase the risk of developing cancer. To make the most out of the MRI results, an efficient visualization of the data is important. The goal of this project was to develop an application that would facilitate radiologists’ evaluation of whole-body MRI data of lymphoma patients. This was achieved by introducing a fused image between two types of MRI images, offering simplified loading of all the study MRI data and creating a rotatable maximum intensity projection from which points can be selected and zoomed to in other types of images. Unfortunately the loading of the data and some parts of the interaction is somewhat slow, which is something that needs to be addressed before this application could become a possibly useful tool for the radiologists.

Microfluidic chips have gained wide applications in various fields, including medicine, environmental sciences and forensic investigations. They are used for the separation of proteins, blood, bacterial cell suspensions, antibody solutions, and drugs. Microfluidic chips display significant advantages, which include faster analysis time, reduced amounts of samples and reagents volumes, flexibility in design and increased separation efficiency. Whole column imaging detection (WCID) exhibits significant advantages compared to other detection methods that are widely used for detecting analytes after the separation of these analytes using isoelectric focusing. With these other methods, there is a need to mobilize the focused sample bands past the detector after separation but with WCID, there is no need for mobilization step. The aim of this research is further development of WCID by characterizing microfluidic chips fabricated for the detection system, to enhance its detection so that high efficiency can be obtained. The chips were fabricated using soft lithography technology at the Microfluidic laboratory, University of Waterloo and they were used to perform isoelectric focusing of various proteins in our laboratory. The fabricated chips with straight channel design were used to carry out isoelectric focusing of some proteins and the results obtained were compared with the results obtained using commercial cartridges. The chips with tapered channel design were used to carry out isoelectric focusing of proteins in which thermally generated pH gradient principle was employed. The samples after separation were sprayed into a mass spectrometer using nano-electrospray interface to obtain their molecular masses. Compatible cartridges for nano-electrospray mass spectrometer were developed and these cartridges were used to carry out capillary isoelectric focusing of low molecular pI markers and proteins. These cartridges were also connected to the nano-electrospray mass spectrometer to obtain the mass to charge ratios of some proteins. The fabricated microfluidic chips with straight channel design were also used to investigate the interaction between drugs and protein.