Nucelophilic substitution at selenium is examined using the B3LYP and MP2 methods. Various nucleophiles (HS -, CH 3 S -, HSe -, and CH 3 Se -) and substrates (R 1 SSeR 2 and R 1 SeSeR 2 with R 1 and R 2 ) H or Me) are used to model substitution at selenium in diselenides and selenosulfides. In all cases, the mechanism is additionelimination. A stable hypercoordinate selenium intermediate lies in a well that is 8-14 kcal mol -1 deep. Nucleophilic attack at selenium is both kinetically and thermodynamically more favorable than at sulfur.

Background Eosinophilic esophagitis (EoE) is a chronic antigen mediated disease in children and adults associated with substantial esophageal remodeling and fibrosis. The expression of the remodeling-associated matrix metalloproteinases (MMPs) has not been previously detailed in EoE. Methods MMP-2 and -14 expression and cellular localization was assessed using qPCR and immunohistochemistry/immunofluorescence in EoE fibroblasts, active and inactive pediatric EoE biopsies, and non-diseased control biopsies. The effect of TGFβ1 treatment on MMP-2 expression in cultured esophageal epithelial (HET1A) cells was analyzed. Results MMP-2 and -14 mRNA were expressed in EoE fibroblasts and biopsies. Proliferating epithelial cells produced MMP-14 more abundantly in EoE than in controls (p<0.001) and the degree of epithelial MMP-14 expression correlated positively with basal zone hyperplasia (r=0.65, p=0.002). EoE lamina propria had higher numbers of MMP-2 and -14 positive cells (906 ± 167 and 701 ± 93 cells/mm2) as compared with controls (258 ± 93 p<0.01 and 232 ± 54 cells/mm2 p<0.01) and MMP-14 expression correlated with the severity of fibrosis. Following therapy with topical corticosteroids, MMP-14 and MMP-2 were significantly diminished (p<0.01). TGFβ1 increased the expression and secretion of MMP-2 from esophageal epithelial HET1A cells. Conclusions MMP-2 and -14 are elevated in pediatric EoE subjects and significantly decrease following topical corticosteroid therapy. TGFβ1 increases MMP-2 in esophageal epithelial cells. This alludes to previously unappreciated role for MMPs in EoE associated esophageal remodeling and a potential positive feedback loop via TGFβ1.

In the midwifery and obstetrics, accurate diagnosis of labour progression is critical to ensure maternal and fetal wellbeing. In light of this, simulation systems have been designed to train practitioners. However, existing simulators lack a dynamic cervix to simulate the varying compliance of cervical ripening. In this thesis, characteristics of ex vivo human cervical tissue were studied and a pneumatically controlled compliant cervix phantom was designed. Cervical tissue exhibited strain of 0.50 for an applied stress of 325 kPa. The phantom demonstrated 35% effacement, 1 cm dilation and was capable of becoming 22 times softer. At maximum vacuum pressure, strain of 0.23 was achieved for an externally applied stress of 419 kPa. At atmospheric pressure, strain of 0.50 was achieved for an applied stress of 117 kPa. Results yield a deeper understanding of cervix characteristics and establishes the groundwork for the design of a dynamic human birth simulation training system.

In the midwifery and obstetrics, accurate diagnosis of labour progression is critical to ensure maternal and fetal wellbeing. In light of this, simulation systems have been designed to train practitioners. However, existing simulators lack a dynamic cervix to simulate the varying compliance of cervical ripening. In this thesis, characteristics of ex vivo human cervical tissue were studied and a pneumatically controlled compliant cervix phantom was designed. Cervical tissue exhibited strain of 0.50 for an applied stress of 325 kPa. The phantom demonstrated 35% effacement, 1 cm dilation and was capable of becoming 22 times softer. At maximum vacuum pressure, strain of 0.23 was achieved for an externally applied stress of 419 kPa. At atmospheric pressure, strain of 0.50 was achieved for an applied stress of 117 kPa. Results yield a deeper understanding of cervix characteristics and establishes the groundwork for the design of a dynamic human birth simulation training system.