Over-expression of both hepatocyte growth factor (HGF) and its receptor Met frequently occurs in invasive human breast cancer, suggesting that the establishment of an HGF “autocrine loop” may be linked to breast tumour progression. We have recently shown a novel activating function of two signaling molecules, Src tyrosine kinase and the signal transducer and activator of transcription-3 factor (Stat3), on HGF expression in breast epithelial cells. Interestingly, Stat3 is also important in normal breast development,but this function does not require Src. In addition, β1-integrin adhesion occurs minimally in differentiated breast epithelium, but is upregulated during oncogenic progression and is required for transformation by Src. We therefore hypothesize that β1-integrin engagement is necessary for Src/Stat3-dependent activation of HGF transcription and breast tumourigensis. Using specific inhibitors of Src (Dasatinib) and Stat3 (CPA7) we demonstrated that autocrine HGF expression is linked to activation of Src/Stat3 in a malignant breast cell line. Phenotypic reversion (e.g., cell rounding and loss of filopodial extensions) and inhibition of pY705Stat3, HGF and pYMet expression as determined by immunofluorescence was achieved with both inhibitor treatments separately, and a synergistic effect was observed with combined treatment. Furthermore, β-catenin localization was nuclear in malignant cells, but shifted to cortical cytoplasmic following inhibitor treatment, similar to non-malignant mouse breast epithelial cells (EPH4). We are currently extrapolating these findings to a 3D Matrigel culture model in which EPH4 cells form acini-like spheroids with hollow lumen surrounded by a well-polarized outer layer of cells. Under these conditions, Stat3 levels are decreased followed by a reduction in cyclin D1 expression, while Src activation remains at a low baseline level. Interestingly,expression of Stat5, which has a reciprocal relationship with Stat3 in breast development and involution, is increased concomitant with elevated β-casein expression. Moreover, Fibronectin and HGF in combination stimulate tubular outgrowths with lumen filling. These findings suggest that aberrant changes in extracellular matrix milieu may stimulate integrin cross talk resulting in a switch of HGF/Met signaling to a transformation phenotype. Information from this study may lead to novel cancer therapies through targeting the HGF/Met and integrin signaling cascades. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2008-09-19 18:19:22.744

No description available.

No description available.

No description available.

No description available.

No description available.

No abstract available. / Thesis (M.A.)-University of Natal, Durban, 1965.

The process of fish migration within rivers and streams is important, especially during the spawning season which often coincides with peak spring discharges in Manitoba. Current environmental regulations for fish passage through culverts require that the average velocity be limited to the prolonged swimming speed of the fish species present. In order to examine the validity of this approach, physical model results were used to calibrate and test a commercially available Computational Fluid Dynamics (CFD) model. Detailed analysis showed that CFD models and the empirical equations used were both able to give a better representation of the flow field than the average velocity. However, the empirical equations were able to provide a more accurate velocity distribution within the fully developed region. A relationship was then developed, to estimate the cumulative percent area less than a threshold velocity within CSP culverts, to be used as a guideline during the design phase.

No description available.

Outcomes related to students’ reading comprehension and higher-order critical thinking skills, and students’ academic and intellectual engagement following the implementation of a Three-Block Model of UDL-based literature circles pedagogical model were investigated. Fifty-nine (59) students attending three suburban public middle schools took part in the study. The study adopted a mixed-design approach to data collection and analysis, with quantitative data collected from all students, and qualitative data collected from a purposively selected sub-sample of 24 students (12 in each of treatment and control classes). Intervention and control groups were assessed pre and post for measures of reading comprehension using classroom-based assessments, which were triangulated by qualitative data from pre and post semi-structured student interviews to explore students’ academic and intellectual engagement. Quantitative data were analyzed using repeated measures MANOVA’s to determine treatment effects for both groups while qualitative data were transcribed and analyzed thematically using a case study approach. Quantitative results showed a small but significant increase in reading comprehension outcomes for proficient and typical readers in treatment groups compared to their counterparts in control classes, and showed a significantly greater increase in reading comprehension outcomes for students in treatment classes who are culturally and linguistically diverse (CLD) and struggling readers. These findings were corroborated by the qualitative results, which showed that students’ academic and intellectual engagement increased in the treatment classes both for proficient readers and struggling readers.