ROGDI was a novel gene with unknown function, located on human chromosome 16p13.3. The coding region of the gene is 864 bp that encodes 287 amino acids. According to GenBank database, ROGDI contains leucine zipper domain. Previous studies in our laboratory showed that ROGDI increases cell proliferation in cell lines. In addition, overexpression of ROGDI induces p53 and p27 mRNA levels in human glioma cell line T98G and U251. In this study, we use two hepatocellular carcinoma cell lines, Hep G2 and Hep 3B, which contains wild-type and deleted tumor suppressor protein p53 respectively to investigate the expression of p53 and the response of anticancer drugs treatment in ROGDI overexpression cells. In addition, we compare the relation between the cell apoptosis the expression of p53 and ROGDI. Hence, we found that expression of p53 and ROGDI influences the cell response to anticancer drugs and induces apoptosis.

Osteoarthritis is the 12th leading cause of years lived with disability globally and by 2040 more than 10 million Canadians will have knee osteoarthritis (KOA). Pain in persons with KOA is well-recognized, persistent and chronic with central sensitization (CS) being prevalent in ~30%. CS is measured by psychophysical testing and patient-reported methods such as the Central Sensitization Inventory (CSI). The CSI was developed using subgroups of people with chronic pain, but not those with KOA. Therefore, validity of the CSI in people with KOA is lacking. CS as indicated by psychophysical tests is associated with CSI scores lower than the recommended cut score. Therefore, we aimed to evaluate the validity of the CSI through Rasch analysis in persons with KOA. We then sought to determine the agreement of the Rasch calibrated (RC-CSI) version of the CSI with the original and to evaluate the validity of the RC-CSI with psychophysical tests in people with KOA. In the first study, the CSI was able to fit Rasch model. After iterative analysis, we found the CSI to be a singular construct with acceptable unidimensionality while retaining all 25 items. Only two items - frequent urination (item 21) and Skin problems (item 19) showed a pattern of uniform differential item functioning by age and sex respectively. Moreover, we generated a RC-CSI cut score of 31.37 that we used to compare with the original cut score of 40. In second study, the findings suggested a lack of agreement between the two versions of the CSI demonstrating small bias. When exploring sensitivity and specificity with psychophysical tests, the RC-CSI showed little clinical value over the original CSI. We therefore recommend that the original CSI should be used with individual clients as our preliminary findings suggest that there is no added benefit to using the RC- CSI. / Thesis / Master of Science Rehabilitation Science (MSc)

An AA5083 aluminium alloy sensitized in service after 40 years exposure to ground atmosphere temperature is studied. Nitric acid mass loss test (NAMLT) is used to determine the susceptibility to intergranular corrosion (IGC). The degree of sensitization in various areas through the alloy thickness was found different, which can be associated with non-homogeneous Mg distribution through the alloy plate thickness. Structure characterisation confirmed that the in-service sensitization is associated with the formation of the ' phase and a cubic Al-Mg transition phase with magnesium content between the GP zones and the '' phase at the grain boundaries. In order to simulate the in-service sensitization process and to gain insight into the sensitization mechanism, the sensitization of AA5083 alloy at relatively low temperatures, namely 70 and 100°C, is studied. For the AA5083 alloy sensitized at 70°C, although the mass loss value is below 15 mg/cm2, ' phase is observed as individual precipitates at grain boundaries. The AA5083 alloy after exposure to 100°C for 240 hours is susceptible to IGC since the ' precipitates have grown continuously at the grain boundaries. Additionally, the effect of sensitization in AA5083 alloy on stress corrosion cracking (SCC) is also investigated using constant displacement double cantilever beam (DCB) testing. It is found that the cracking length increases with the degree of sensitization. The population density of the crack branches also increases with the degree of sensitization. The metal between different small branches is known as ligament. And with high degree of sensitization, the ligaments between crack branches have become brittle. Therefore, small branches became connected to form a continuous crack with the crack propagating.

Ghrelin is a 28 amino acid peptide that interacts with ghrelin receptors (GHS-Rs) to modulate brain reinforcement circuits. Systemic ghrelin infusions augment cocaine (COC) stimulated locomotion and conditioned place preference (CPP) in rats, whereas genetic or pharmacological ablation of GHS-Rs has been shown to attenuate the acute locomotor-enhancing effects of nicotine (NIC) and COC, and to blunt the CPP induced by food, alcohol, amphetamine and COC in mice. The stimulant NIC can induce CPP and like COC, repeated administration of NIC induces locomotor sensitization in rats. In experiment 1, we examined the effects of GHS-R antagonism with JMV 2959 on COC-induced locomotion and found that JMV 2959 suppresses COC-induced locomotor sensitization. In experiment 2, we examined the effects of GHS-R antagonism with JMV 2959 on NIC-induced locomotion and found that JMV 2959 suppresses NIC-induced locomotor sensitization. In experiment 3, we examined the effects of GHS-R knockout on COC-induced locomotion and found that animals sustaining GHS-R knockout display a suppression of COC-induced locomotor sensitization. In experiment 4, we examined the effects of GHS-R knockout on COC-induced locomotion and found that animals sustaining GHS-R knockout display a suppression of COC-induced locomotor sensitization. In experiment 5, we examined the effects of JMV 2959 on NIC-enhanced intracranial self-stimulation (ICSS) responding and found that JMV 2959 alone had no effect, but when combined with NIC,JMV 2959 pretreatment reversed the enhancement of responding produced by NIC. In experiment 6, we examined the effects of GHS-R knockout on ICSS responding and found that animals sustaining GHS-R knockout were unable to acquire ICSS at current intensity levels that would support responding by WT animals. It was not until the intensity was ramped up four fold that these knockout rats were able to acquire responding. These results show that antagonism of GHS-Rs diminishes the reinforcing effects of NIC and COC. This provides evidence that antagonists of GHS-Rs could be useful in the treatment of drug addiction, particularly that involving nicotine.

The sensitization of stainless steel describes the process by which a high-carbon steel alloy is heated above a certain threshold (either naturally or artificially) followed by a cooling period during which chromium (one of the elements most responsible for providing stainless steel with its corrosion-inhibiting properties) forms new compounds with the carbon present in the steel. With the chromium being taken from the parent material to form these compounds, the corrosion-resistant properties are compromised, which can lead to corrosion, cracking, and broader failure. Currently, the accepted techniques used to test for the presence of sensitization are qualitative and/or destructive in nature. Attempts have been made to non-destructively detect and characterize sensitization through various means, but all with mixed results. With the use of these high-carbon alloys in a range of industries, a comprehensive, in-place process is desirable. This thesis will focus specifically on non-destructive evaluation of sensitization seen as a result of welding steel plates using induction infrared thermography (IIRT). This process uses an induction coil to generate heat within a sample whose resulting heat signature can then be detected with an infrared (IR) camera and analyzed. Previous IIRT experimental results have shown higher levels of heating in the HAZ when sensitization is present as it modifies the original microstructure of the material. New IIRT experiments have been conducted on both welded and unwelded 440C alloy samples to establish quantitative data on the heating profiles. These results (in conjunction with the appropriate experimental parameters) were then used to create a numerical model to replicate them. Despite some limitations in populating the model with accurate parameters, the results obtained were in good agreement with the experiments and provide a foundation for future work. Future work will focus on establishing a predictive tool that can detect and quantify the level of sensitization in an arbitrary steel sample in the field. / Master of Science / The sensitization of stainless steel describes the process by which a high-carbon steel alloy is heated above a certain threshold (either naturally or artificially) followed by a cooling period during which chromium (one of the elements most responsible for providing stainless steel with its corrosion-inhibiting properties) forms new compounds with the carbon present in the steel. With the chromium being taken from the parent material to form these compounds, the corrosion-resistant properties are compromised, which can lead to corrosion, cracking, and broader failure. Currently, the accepted techniques used to test for the presence of sensitization are qualitative and/or destructive in nature. Attempts have been made to non-destructively detect and characterize sensitization through various means, but all with mixed results. With the use of these high-carbon alloys in a range of industries, a comprehensive, in-place process is desirable. This thesis will focus specifically on non-destructive evaluation of sensitization seen as a result of welding steel plates using induction infrared thermography (IIRT). This process uses an induction coil to generate heat within a sample whose resulting heat signature can then be detected with an infrared (IR) camera and analyzed. Previous IIRT experimental results have shown higher levels of heating in the HAZ when sensitization is present as it modifies the original microstructure of the material. New IIRT experiments have been conducted on both welded and unwelded 440C alloy samples to establish quantitative data on the heating profiles. These results (in conjunction with the appropriate experimental parameters) were then used to create a numerical model to replicate them. Despite some limitations in populating the model with accurate parameters, the results obtained were in good agreement with the experiments and provide a foundation for future work. Future work will focus on establishing a predictive tool that can detect and quantify the level of sensitization in an arbitrary steel sample in the field.

Behavioural sensitization models are useful for understanding many disorders, including obsessive-compulsive disorder and drug addiction. Many of these models are produced by sensitization of dopamine neurotransmission, resulting in behaviours which include increased locomotor activity. Alterations to dopamine-mediated locomotor sensitization may be possible via activation of serotonergic neurotransmission, and there is evidence to suggest this may be through repeated activation of serotonin 1A receptors. The current study examines the development of locomotor sensitization in an animal model via repeated exposure of both a dopamine (D2R/D3R) and serotonin 1A (5-HT1A) agonist. To examine this, male Long-Evans rats were exposed to 10 injections of a combination of different doses of quinpirole and 8-OH-DPAT and tested in activity chambers for locomotor stimulation (measured by total distance travelled). Animals were then exposed to challenges of quinpirole, and 8-OH-DPAT and tested again for locomotor activity. Results showed that high doses of quinpirole or 8-OH-DPAT induced locomotor sensitization. However, when the two drugs were co-administered, 8-OH-DPAT displayed some initial disruption of quinpirole-induced sensitization. Animals sensitized to either quinpirole or 8-OH-DPAT did show higher locomotion when challenged with the drug to which they were sensitized. However, simultaneous quinpirole and 8-OH-DPAT sensitization seemed to prevent maximal responding when challenged with quinpirole. In all, our data suggests that sensitization to quinpirole and 8-OH-DPAT is occurring via separate neural mechanisms, with 5-HT1A agonism interfering with development of dopaminergic (D2R) sensitization. / Thesis / Master of Science (MSc)

No description available.

No description available.

The current study was designed to analyze the roles of both α7 and α4β2 nicotinic receptors (nAChRs) in behavioral sensitization and its effects on Brain Derived Neurotrophic Factors (BDNF) and the mammalian target of rapamycin (mTOR) in the neonatal quinpirole model of schizophrenia. Animals were treated neonatally with either quinpirole (1 mg/kg) or saline starting on P1 and treatment persisted through P21. Starting on P33, animals were sensitized to nicotine (0.5 mg/kg free base) every other day up to P49. Following sensitization, brains were harvested at 1 h and 24 h post-drug treatment and BDNF protein and total mTOR activity were assessed in the nucleus accumbens. Results revealed that α7 antagonism failed to block nicotine sensitization regardless of neonatal quinpirole treatment, and appears to block the initial hypoactive response to nicotine in males but not females. In addition, α7 antagonism effectively blocked the enhanced BDNF response to nicotine in both saline and quinpirole treated animals but was ineffective at blocking mTOR at the 1 h time point, and resulted in decreases of mTOR at the 24 h time point. Antagonism of the α4β2 nAChR effectively blocked nicotine sensitization in both males and females but the higher dose resulted in a significant initial hypoactive response to nicotine. In addition, α4β2 nAChR antagonism blocked nicotine induced increases in BDNF. Total mTOR revealed that neonatal quinpirole produced a decrease in mTOR that was reversed by nicotine at the 1h but not the 24h time point and antagonism of nAChRs resulted in sex dependent effects. There results have implication towards the mechanisms underlying enhanced smoking in schizophrenia.

Pathological gambling is a serious disorder with lifetime prevalence between 1.1-3.5%. Evidence suggests commonalities in the neurochemical basis of pathological gambling and psychostimulant addiction. However, parallel effects of gambling and a stimulant drug have not been assessed in the same subjects. This study employed a cross-priming strategy in which 12 male pathological gamblers and 11 male controls were exposed to a 15-minute slot machine game and d-amphetamine (0.4 mg/kg). Subjective, cognitive, electrophysiological, and physiological responses were assessed. Gamblers reported greater desire to gamble after both reinforcers, when baseline motivation was controlled. Conversely, gamblers exhibited diminished cardiovascular response to amphetamine. Gamblers also exhibited decreased pre-pulse inhibition (impaired sensorimotor gating), and deficits on this index predicted greater post-amphetamine desire to gamble and decreased heart rate response to the dose. Results are consistent with possible dopaminergic sensitization in pathological gamblers, but also suggest that central noradrenergic receptor deficits contribute importantly to these effects.