Polymer thin films are ubiquitous in a variety of everyday applications from cookware to packaging. Light can be used to both probe and manipulate the mobility of polymers in thin films. The first project involves the self-diffusion of poly(isobutyl methacrylate) (PiBMA) in thin films using fluorescence recovery after patterned photobleaching (FRAPP). PiBMA is an ideal polymer for this study because it exhibits a film thickness-independent glass transition temperature (Tg) on silicon oxide substrates in film thicknesses down to 14 nm. Since the diffusion coefficient of a polymer depends on the proximity of the experimental temperature to its Tg, nanoconfined diffusion can be measured without superimposed influence from Tg nanoconfinement effects. In this study, self-diffusion of PiBMA parallel to the confining interfaces was found to be film thickness independent to ~30 nm. The reason for the film thickness independence of the Tg of PiBMA is the balance between enhanced mobility at the free interface and hydrogen bonding with the substrate. However, when hydroxyls on the substrate are masked, the Tg of PiBMA decreases with decreasing film thickness. In this case, the diffusion coefficient increases with decreasing film thickness in a way consistent with additional distance from Tg. The second project involves a new approach for creating topographic patterns in thin films via the Marangoni effect, which describes how small variations in surface energy can promote dramatic movement of fluids. Topographic patterns created using this method are potentially useful in a variety of applications, such as the creation of soft lithography stamps. Using a photomask, surface energy gradients can be patterned into solid polymer films. Upon heating the polymer film to a liquid state the Marangoni effect causes the polymer to flow creating three-dimensional topography. This technique was first demonstrated in polystyrene, which undergoes a partial dehydrogenation of the polymer backbone upon photoexposure. However, as exposed and unexposed regions inter-diffuse the topographic features decay. A solution to this problem is to use two orthogonally acting photosensitizers in the polymer film, one for topography creation, and the other for cross-linking which stabilizes the topography at high temperature. / text

This dissertation details the development of a block model for the movement of submarine slides with emphasis on possible hydroplaning. Unlike previous models, the block model simulated the mechanism of hydroplaning by monitoring the contact condition between the bottom surface of the slide mass and the underlying ground. The effect of hydroplaning on the movement of the slide mass is considered by changing the forces applied on the slide mass by the underlying ground according to the contact condition. The hydrodynamic stresses applied on the slide mass by the surrounding fluid are determined based on the numerical simulations of the flow around a sliding mass. The sliding process of the block is disretisized in a step-by-step manner using a Newmark scheme. A computer program is also written to implement the block model. The block model is validated by comparisons between the numerical results and data reported by Mohrig, et al (1999) for laboratory experiments on subaqueous slides. An illustrative study is also conducted using the block model for the movement of the sediment slabs during the Storegga Slide. The block model has successfully predicted the occurrence of hydroplaning and run-out distances of subaqueous slides. Numerical results with the block model supports the mechanism of hydroplaning for subaqueous slides with greater run-out distances than comparable subaerial slides.

Aim: This study looks at the effect of orthokeratology on a number of biometric parameters and refractive error in an adult population. Method: Forty three myopic subjects were recruited to a twelve month study into the effects of orthokeratology on ocular biometry and refractive error. Two different back surface lens designs were applied right eye) pentacurve and left eye) aspheric. The aspheric design was chosen to more closely mimic the cornea's natural shape. Anterior and posterior apical radii and p-values; corneal thickness and anterior chamber depth were measured using the Orbscan IIz; together with ocular biometry by IOL Master and a standard clinical refraction. All measurements were repeated at one night, one week, one, three, six and twelve months. Refractive changes were analysed against biometric changes. Results: Twenty seven participants completed one month of lens wear. Twelve subjects completed twelve months of lens wear. Subjects with myopia ≤ -4.00DS were successfully treated with orthokeratology. Both anterior and posterior apical radii and p values were altered by orthokeratology. Corneal thickness changes were in agreement with previously published studies. Axial length and anterior chamber depth were unaffected by the treatment. Conclusion: Orthokeratology should be available as an alternative to laser refractive surgery. It is best restricted to myopes of up to -4.00DS with low levels of with the rule corneal astigmatism. The use of an aspheric back design contact lens did not produce a significant benefit over that of a pentacurve.

<p>The recent discovery that fibroblasts can be reprogrammed directly to functional neurons with lentivirus has reinvigorated the belief that autologous human cell therapies against many neurodegenerative diseases may be achievable in the near future. To increase the clinical translatability of this approach, we have developed a technique to perform this direct conversion without the use of virus. We transfected fibroblasts with plasmids condensed into non-viral nanoparticulate carriers with a bioerodible peptidomimetic polymer, pCBA-ABOL. Gene delivery with pCBA-ABOL was exceptionally effective and nontoxic, producing high transfection efficiencies and enabling serial dosing of plasmid cocktails. We delivered plasmids encoding neural lineage-instructive transcription factors to primary mouse embryonic fibroblasts (PMEFs), eliciting: drastic morphological changes, activation of endogenous neuronal transcription factor expression, neuronal promoter activity, and the appearance of neuronal proteins. Serial dosing of pCBA-ABOL complexes produced increasingly higher yields of these non-virally induced neurons (NiNs). The majority of NiNs fired action potentials under patch clamp. This is the first description of a method capable of directly inducing functional neuronal cells from fibroblasts without the use of virus.</p><p>We then moved on to further increase the yield of NiN generation, in an effort to produce a sufficient quantity of neurons for cell therapies. Informed by neurodevelopmental cues and by precedents set by the induced pluripotent stem cell (iPSC) field, we performed non-viral neuronal reprogramming in the presence of soluble microenvironmental factors that either inhibited GSK-3beta; and SMAD signaling, or induced chronic membrane depolarization. Chronic depolarization doubled the number of cells expressing neuronal markers produced with glutamatergic as well as with dopaminergic transcription factor cocktails. Inhibition of GSK-3beta; and SMAD signaling similarly doubled the yield of glutamatergic NiNs, and enabled induction of neuronal markers and morphological transformation in human fibroblasts.</p><p>In addition to soluble microenvironmental factors, the physical microenvironment can also strongly influence various cellular phenotypes. This list includes many phenotypes related to endocytosis - the transit mechanism of nanoparticulate gene carriers entering cells during non-viral transfection. As such, we set out to determine if patterned physical substrate topography could be used to increase non-viral transfection. We employed a high-throughput screen of micropitted substrate topographies, and indeed found that larger, denser micropits could support significantly higher transfection efficiencies in fibroblasts, compared to smooth substrates. The same topographies produced higher reverse transfection efficiencies, and greater siRNA-mediated knockdown of a reporter gene. The control of transfection with substrate topography is a new design parameter that could find broad application in in vitro non-viral reprogramming strategies, as well as in the intelligent design of nucleic acid-eluting scaffolds in vivo. </p><p>Encouraged by our success with direct neuronal reprogramming, and armed with a greater understanding of some microenvironmental mediators thereof, we attempted to produce non-virally-induced oligodendroglial progenitor cells (NiOPCs), which has been historically challenging for other investigators. We discovered the fibroblastic intracellular microenvironment is a significant barrier to the function of Olig2 - a master regulator of OPC phenotype - in direct reprogramming. Fibroblasts do not express Olig2 chaperones which are normally expressed in OPCs, causing Olig2 to become sequestered in the cytoplasm of transfected PMEFs. We relieved this barrier through fusion of a strong nuclear localization sequence (NLS) to Olig2, which repartitioned Olig2-NLS from the cytoplasm to the nucleus in transfected fibroblasts. The use of Olig2-NLS in iOPC reprogramming cocktails resulted in a drastic improvement in the yield of OPC-specific marker expression. The improvement associated with Olig2-NLS was insufficient to elicit significant myelin protein expression with the non-viral system, but the yield of virally-induced oligodendrocyte-like cells (iOLs) was improved dramatically. Further enhancements will be required to generate fully-reprogrammed NiOPCs, but the increased efficiency of viral iOPC generation is immediately useful for disease modeling and potentially in cell replacement therapies if human cells can be converted for the first time using this technique. During direct reprogramming, CNS-specific transcription factors are delivered to foreign intracellular contexts as a rule, which may reduce their ability to function effectively; we have shown this can be a critical yet under-appreciated determinant of the success or failure of a direct reprogramming system.</p><p>Taken together, the technological and intellectual advancements we describe herein represent significant improvements to non-viral transfection and reprogramming systems. These techniques can find broad appeal to the many researchers and clinicians deploying these systems. More specifically, we present significant steps towards realization of the dream of safe and effective autologous cell therapies against devastating and currently-intractable neurodegenerative diseases.</p> / Dissertation

No description available.

By studying volcanoes on Venus, Mark Jellinek is advancing the science of predicting volcanic activity on earth.

This qualitative research study focuses explicitly on understanding the experiences and perceptions of urban Aboriginal women living with HIV/AIDS. Stigmatizing attitudes and language have serious impacts upon the lives of HIV-positive Aboriginal women. The ways our society presently addresses the women needs to change. With the insights and assistance of four Aboriginal women living with HIV, this project adds to the presently sparse qualitative literature in this research area. Current research indicates that there are many factors associated with urban Aboriginal women being at higher risk for infection and lower physical and mental health, such as race, socio-economic conditions, isolation, oppression and violence, family history, substance abuse, discrimination, and often the responsibilities of childrearing. However, current research analysis and presentation is insufficient, and more in-depth questions arise. Material was collected using semi-structured, open-ended questioning conversations with the participants. Two guiding research questions were asked: 1) What is it like for you, living with HIV right now? and 2) What would you want other people to learn from your experiences? The women’s stories provide an avenue for participants to voice some of their triumphs and challenges about being an Aboriginal woman living with HIV/AIDS. For the community at large, this is also an opportunity to hear first hand, important information such as this. In this work, I have tried to adhere to the tenets of Indigenous methodologies by allowing the life-stories to resonate as holistic representations. Rather than deconstructing the women’s stories through naturalistic analysis (which continues to categorize and to objectify participants), the stories are viewed through a Health Narrative Topography whereby thematic genres such as Restitution, Chaos, and Quest are illuminated, while also being critically aware of some of the limitations to this framework. Three overarching themes are revealed through the women’s stories: 1) the empowerment and resiliency demonstrated by the participants; 2) the need for cultural competency in a society that continues to stigmatize Aboriginal and HIV-positive women; and, 3) the need for a more holistic approach within society when it comes to education, learning, and healing.

Tracheal epithelium is organized along two axes: apicobasal, seen through apical ciliogenesis, and planar seen through organized ciliary beating, which moves mucus out of the airway. Diseased patients with affected ciliary motility have serious chronic respiratory infections. The standard method to construct epithelium is through air liquid interface culture which creates apicobasal polarization, not planar organization. Nanogrooved surface topography created in diffusible substrates for use in air liquid interface culture will induce planar organization of the cytoskeleton. We have created a nanogrooved gelatin device which allows basal nutrient diffusion. Multiple epithelial cells have been found to align in the direction of the nanogrooves in both sparse and confluent conditions. This device is also congruent with ALI culture as seen through formation of tight junctions and ciliogenesis. Thus, we have created nanogrooved surface topography in a diffusible substrate that induces planar alignment of epithelial cells and cytoskeleton.

Tracheal epithelium is organized along two axes: apicobasal, seen through apical ciliogenesis, and planar seen through organized ciliary beating, which moves mucus out of the airway. Diseased patients with affected ciliary motility have serious chronic respiratory infections. The standard method to construct epithelium is through air liquid interface culture which creates apicobasal polarization, not planar organization. Nanogrooved surface topography created in diffusible substrates for use in air liquid interface culture will induce planar organization of the cytoskeleton. We have created a nanogrooved gelatin device which allows basal nutrient diffusion. Multiple epithelial cells have been found to align in the direction of the nanogrooves in both sparse and confluent conditions. This device is also congruent with ALI culture as seen through formation of tight junctions and ciliogenesis. Thus, we have created nanogrooved surface topography in a diffusible substrate that induces planar alignment of epithelial cells and cytoskeleton.

In 2011, Calgary, Alberta based Borealis Geopower bought the geothermal rights to the Canoe Reach arm of Kinbasket Lake, near Valemount, British Columbia. New to Canada, a pilot project of a 2 megawatt geothermal power facility will begin within the next five years. The project is a positive addition to the area, as it is a non-polluting energy source with an effluent of clean hot water. This thesis proposes a maximization of this energy source by combining the power facility with an education center and bathing facility. Included in this bathing experience are ancillary cabins and paths to promote the users’ interaction and enjoyment of the project and landscape. Finally, this thesis develops a material strategy, choreographing the visitors’ experience of the geothermal resource within the site’s mountainous topography.