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Membrane technology has been actively used as a separation tool in the chemical, environmental, and biopharmaceutical industries for several decades. As membrane quality requirement in the industry has increased, efforts have been directed towards enhancement in mechanical strength, chemical durability and functionality of membranes. One of the approaches for membrane quality enhancement is based on the combination of hydrogel technology with membrane technology. This thesis focused on the application and development of hydrogel based membranes, notably hydrophilized PVDF (polyvinylidene fluoride) membrane for hydrophobic interaction membrane chromatography; the fabrication of paper-hydrogel composite membranes for membrane chromatography; development of a technique for coating alginate (a natural hydrogel) on the outer surface of a hollow fiber membrane for potential application in bioreactors and the use of hollow fiber membranes as mold for fabrication calcium alginate fibers for biomedical and tissue engineering applications. A membrane chromatography-based polishing technique was developed for removing leached protein-A and aggregates from monoclonal antibody (mAb). A commercial synthetic membrane that is known to be hydrophilized by hydrogel grafting was employed to develop this polishing process that resulted in highly pure mAb, free from aggregates and protein-A. This mAb polishing technique could easily be integrated with a hydrophobic interaction membrane chromatography based mAb purification process. A paper-hydrogel composite membrane was developed as an inexpensive alternative to commercial synthetic membranes used for carrying hydrophobic interaction membrane chromatography. Poly(N-vinylcaprolactam) or PVCL hydrogel was coated on Whatman filter paper to prepare these membranes. These environment responsive membrane which responded to changes in salt concentration, gave excellent fractionation of multi-component protein mixtures. As case study, a mixture of immunoglobulin G, human serum albumin and insulin was fractionated. A technique for modifying the surface of synthetic hollow fiber membranes with alginate (a natural hydrogel) was developed. This manner of surface modification led to the improvement in membrane mass transport. The alginate was cross-linked on the outer surface of the membrane by diffusion of the cross-linker (calcium ions) through the membrane pores. The calcium alginate coating layer was characterized by optical and transmission electron microscopy, contact angle measurement, hydraulic permeability measurement and by examining solute transport. Hollow and solid calcium alginate fibers were fabricated using a novel hollow fiber membrane based moulding technique. The pore present on the hollow fiber membrane served as the reservoir for the calcium chloride solution with cross-linked the alginate within the lumen. The calcium alginate fibers produced were characterized by optical, transmission electron, and scanning electron microscopy. Cell immobilization experiments were carried out to demonstrate biocompatibility and potential for tissue engineering applications. / Thesis / Doctor of Philosophy (PhD)

Receptors and signal transduction complexes are assembled in a precise manner at specific subdomains of the plasma membrane. Recent research has implicated scaffolding proteins in organizing these receptor and signaling complexes. One well characterized example is the C. elegans LIN-2/LIN-7 /LIN-1 0 complex. This complex is essential in the proper localization of LET -23, the EGFR ortholog, to the basolateral membrane surface of vulval epithelial cells. The mammalian orthologs of the LIN-2/LIN-7 /LIN-10 complex have been identified. CASKIVELI!Mintl/Xllalpha function as a tripartite complex in neurons, presynaptically and postsynaptically. Presynaptically, the multi protein complex aids in linking cell adhesion to ion influx, synaptic vesicle fusion with the presynaptic membrane. and subsequent neurotransmitter release. At the post-synaptic membrane, the CASKIVELI!Mintl/Xllalpha complex is hypothesized to function in the sorting and proper localization of the NMDA type glutamate receptor, reflecting the function of the C. elegans orthologs in receptor localization. We have identified the Drosophila orthologs ofLIN-2/CASK, LIN-7NELI, and LIN-10/Mintl/Xllalpha, termed CMG, dVELI and dMINT. respectively. These proteins were found to be highly conserved among species. The Drosophila YELl protein was initially identified by the McGlade laboratory, University of Toronto, where it was found to bind phosphorylated Drosophila EGFR (DER). We have mapped the chromosomal location of dveli, determined RNA transcript distribution and protein localization, and initiated a P-element mutagenesis screen to generate a dveli mutant. Furthermore, candidate genes for other proteins known to associate with LIN-7 (PALS) have been identified by sequence analysis. dVELI expression begins early in the larval stage. It is concentrated mostly in neuropil areas, sites of synaptic connections. This expression pattern continues into adult development. Within the larval CNS, dVELI protein is localized to the neuropil areas of the ventral nerve cord and brain. NMJ staining further localizes dVELI almost exclusively to the post-synaptic density. This post-synaptic localization resembles that of mammalian YELls, wherein the complex is thought to aid in glutamate receptor sorting and localization. The similarity in structure and expression patterns of dVELI to that of its mammalian orthologs suggests a model in which the Drosophila complex aids in the localization of receptors to post -synaptic specializations in neurons. / Thesis / Master of Science (MSc)

The purpose of this study was to relate femoral venous plasma potassium concentrations ([K⁺]) following a fatiguing submaximal isometric quadriceps contraction, to the excitability of the muscle cell membrane as assessed by the compound muscle action potential (M-Wave) . Ten healthy male volunteers (22. 0 ± . 5 yrs) performed a unilateral 3 minute (min) sustained isometric quadriceps contraction at 30% of their maximum voluntary contraction (MVC) . M-Waves, peak evoked twitch torque, plasma lactate concentration ([La⁻]), and plasma potassium concentration ([K⁺]) were measured before, and at predetermined times over the course of a 15 min recovery period following the fatigue paradigm. Immediately post-exercise, twitch torque decreased to 58% of baseline, femoral venous [La⁻] had risen to 10 ± 0.8 mmol/1, and [K⁺] was significantly increased from 4.0 ± 0.1 mmol/1 to 5.9 ± 0.2 mmol/1. M-Wave amplitude illustrated a trend for potentiation increasing 9.5%-from 13.9 ± 2.4 mV pre-exercise, to 15.3 ± 2.8 mV at 1 min 20 seconds post-exercise. M-Wave area exhibited a similar trend from baseline, but values showed no statistical significance during this time. These results suggest that in spite of increased extracellular [K⁺] following this type of fatiguing exercise, muscle membrane excitability is maintained, which is probably due to the electrogenic nature of the highly active Na⁺ /K⁺ pump. This study was supported by the Natural Sciences and Engineering Research Council of Canada. / Thesis / Master of Science (MSc)