UNCERTAINTY QUANTIFICATION IN ENGINEERING OPTIMIZATION APPLICATIONS

Ph.DDOCTOR OF PHILOSOPH

Developing a new generation of neuro-prosthetic interfaces: structure-function correlates of viable retina-CNT biohybrids

PhD ThesisOne of the many challenges in the development of neural prosthetic devices is the choice of electrode material. Electrodes must be biocompatible, and at the same time, they must be able to sustain repetitive current injections in a highly corrosive physiological environment. We investigated the suitability of carbon nanotube (CNT) electrodes for retinal prosthetics by studying prolonged exposure to retinal tissue and repetitive electrical stimulation of retinal ganglion cells (RGCs). Experiments were performed on retinal wholemounts isolated from the Cone rod homeobox (CRX) knockout mouse, a model of Leber congenital amaurosis. Retinas were interfaced at the vitreo-retinal juncture with CNT assemblies and maintained in physiological conditions for up to three days to investigate any anatomical (immunohistochemistry and electron microscopy) and electrophysiological changes (multielectrode array stimulation and recordings; electrodes were made of CNTs or commercial titanium nitride). Anatomical characterisation of the inner retina, including RGCs, astrocytes and Müller cells as well as cellular matrix and inner retinal vasculature, provide strong evidence of a gradual remodelling of the retina to incorporate CNT assemblies, with very little indication of an immune response. Prolonged electrophysiological recordings, performed over the course of three days, demonstrate a gradual increase in signal amplitudes, lowering of stimulation thresholds and an increase in cellular recruitment for RGCs interfaced with CNT electrodes, but not with titanium nitride electrodes. These results provide for the first time electrophysiological, ultrastructural and cellular evidence of the time-dependent formation of strong and viable bio-hybrids between the RGC layer and CNT arrays in intact retinas. We conclude that CNTs are a promising material for inclusion in retinal prosthetic devices

James Monroe’s White House: The Genius of Politics and Place

This research endeavor has discerned the origins of an enduring American nationalistic distinctiveness perpetuated by President James Monroe’s White House. A careful scholarly examination of Monroe’s White House as a cultural landscape enquires into the genesis of interdependence between place and politics. It also studies the depth of the American people’s ability to embrace, as their own, the symbolism and national vision fashioned in these spaces. The juxtaposition of James Monroe’s election as the first United States president after the War of 1812 with the resurrection of the White House manifested for him an exclusive opportunity, still fraught with perils, to define national identities and interiors for the early republic and its posterity. Early attempts to write about the White House compartmentalized the historical context by architecture, social aspects, executive functions, political power, and biographical literature. Self-imposed confinement in historical discourse prohibits a comprehensive narrative while encouraging the autonomy of places, events, ideals, and people. Interpreting the White House as a cultural landscape illuminates the agency of culture as a force in shaping the visible features within those spaces. Reciprocally, the physical environment retains a central significance as the medium through which human cultures act. Consequently, Monroe’s White House transubstantiated disaffection into a maturing national consciousness. Emphasizing and interpreting primary resources permits the examiner to expose a seemingly mutually exclusive trajectory of James Monroe’s early political career with the White House’s architectural evolution. In contrast, their paths reveal a diminishing parallel. At the point of infinity, the newly elected President Monroe refurbished the interiors and nurtured administrative protocols to foster domestic public and foreign diplomacy while encouraging national respect and integrity for the country