Doctor of Philosophy

dissertationIt is surprising that there are only about 80 described congenital diseases that result from mutations in any of the 1% of genes in the human genome (~200-250 genes) dedicated to protein glycosylation. It is these glycosylation events that provide tremendous protein diversity and contribute to proper protein folding, function, and subcellular localization. Thus, the rarity with which human congenital disorders of glycosylation (CDGs) are observed despite the myriad of genes involved in this process and the apparent critical role for proper protein form and function suggests that glycosylation is critical for proper development. However, the role of glycans in development has been largely understudied and there are only a few genetic models of human CDGs in existence. Glycosylation occurs by the enzymatic addition of sugar-derived molecules and is estimated to provide 10-104 times more diversity than the unmodified proteome alone. Glycans are present on the surface of nearly every cell within multicellular organisms and are capable of facilitating communication with the cell and its environment and with other cells and also have structural roles as critical components of extracellular matrix. However, the complexity of glycan formation makes it difficult to understand the diverse and pleiotropic roles glycans play in cellular biology. The utility of Drosophila to elucidate the role of glycans in development as well as disease has only been appreciated recently. Herein, I further demonstrate the utility of Drosophila to understand the roles of both N- and O-glycans in development and cell signaling. Furthermore, I utilize the fly to understand the biology of glycans in a human disorder of congenital disease, Peters Plus Syndrome. I demonstrate that the previously reported Dpp signal antagonism achieved by the sugar derivative UDP-N-Acetyglucosamine (GlcNAc) is carried out by the synthesis of a chondroitin-sulfate sink produced in the embryonic cardiac mesoderm and by the addition of GlcNAc to the type I receptor Saxophone to limit Dpp signal through Tkv exclusively. Furthermore, loss of the Drosophila ortholog of the human B3GLCT gene, sugarcoated, demonstrates a critical role for O-linked mucins in cell hypertrophic growth during larval development and oogenesis and demonstrates a potential role for human mucins in chondrocyte hypertrophy-an event required for the majority of human bone growth-and a potential mechanistic reason for growth defects observed in Peters Plus Syndrome patients

A Novel and Inexpensive Solution to Build Autonomous Surface Vehicles Capable of Negotiating Highly Disturbed Environments

This dissertation has four main contributions. The first contribution is the design and build of a fleet of long-range, medium-duration deployable autonomous surface vehicles (ASV). The second is the development, implementation, and testing of inex-pensive sensors to accurately measure wind, current, and depth environmental vari- ables. The third leverages the first two contributions, and is modeling the effects of environmental variables on an ASV, finally leading to the development of a dynamic controller enabling deployment in more uncertain conditions. The motivation for designing and building a new ASV comes from the lack of availability of a flexible and modular platform capable of long-range deployment in current state of the art. We present a design of an autonomous surface vehicle (ASV) with the power to cover large areas, the payload capacity to carry sufficient batteries to power components and sensor equipment, and enough fuel to remain on task for extended periods. An analysis of the design, lessons learned during build and deployments, as well as a comprehensive build tutorial is provided in this thesis. The contributions from developing an inexpensive environmental sensor suite are multi-faceted. The ability to monitor, collect, and build models of depth, wind, and current in environmental applications proves to be valuable and challenging, where we illustrate our capability to provide an efficient, accurate, and inexpensive data collection platform for the community’s use. More selfishly, in order to enable our end- state goal of deploying our ASV in adverse environments, we realize the requirement to measure the same environmental characteristics in real-time and provide them as inputs to our effects model and dynamic controller. We present our methods for calibrating the sensors and the experimental results of measurement maps and prediction maps from a total of 70 field trials. Finally, we seek to inculcate our measured environmental variables along with previously available odometry information to increase the viability of the ASV to maneuver in highly dynamic wind and current environments. We present experimen- tal results in differing conditions, augmenting the trajectory tracking performance of the original way-point navigation controller with our external forces feed-forward algorithm

An Autonomous Surface Vehicle for Long Term Operations

Environmental monitoring of marine environments presents several challenges: the harshness of the environment, the often remote location, and most importantly, the vast area it covers. Manual operations are time consuming, often dangerous, and labor intensive. Operations from oceanographic vessels are costly and limited to open seas and generally deeper bodies of water. In addition, with lake, river, and ocean shoreline being a finite resource, waterfront property presents an ever increasing valued commodity, requiring exploration and continued monitoring of remote waterways. In order to efficiently explore and monitor currently known marine environments as well as reach and explore remote areas of interest, we present a design of an autonomous surface vehicle (ASV) with the power to cover large areas, the payload capacity to carry sufficient power and sensor equipment, and enough fuel to remain on task for extended periods. An analysis of the design and a discussion on lessons learned during deployments is presented in this paper.Comment: In proceedings of MTS/IEEE OCEANS, 2018, Charlesto

STM and Electrochemical Investigation of Homoepitaxial Boron-Doped CVD Diamond Films

Homoepitaxial growth of boron-doped CVD diamond films was carried out on (100) and (111) oriented substrates. Atomic resolution images were obtained for both (100) and (111) surfaces using scanning tunneling microscopy. STM images reveal the presence of a 2x1-monohydride reconstruction for the untreated (100) surface and a lxl reconstruction for the untreated (111) surface. No other atomically resolved reconstructions were observed under a wide range of growth conditions. Non-aqueous electrochemical investigations were carried out on the films exhibiting atomically resolved reconstructions. Evidence for potential-induced surface-reconstruction and surface chemical modification of the (100) 2xl-monohydride surface has been observed

Boron-Doped Homoepitaxial Diamond (100) Film Investigated by Scanning Tunneling Microscopy

Conducting epitaxial diamond films of high quality are essential for many diamond studies and diamond electronic device fabrication. We have grown boron-doped epitaxial diamond films on type Ila natural diamond (100) substrates by microwave plasma chemical vapor deposition. A gas mixture of H2/CH4 was used. Boron doping was done by placing solid sources of pure boron in the microwave plasma. Homoepitaxial films with atomic smoothness were achieved under the following growth conditions: substrate temperature 900 °C, gas pressure 40 Torr, and gas flow rates of H2/CH4 = 900/7.2 seem. The growth rate was 0.87 µm/hr. Surfaces of the homoepitaxial films were studied by scanning tunneling microscopy (STM). STM images show smooth and continuous surface with ripple-like features on micrometer scale. On nanometer scale, alternating terraces of 2x1 and 1x2 dimerization were clearly observed

Incorporating Human Readiness Levels at Sandia National Laboratories

Since 2010, the concept of human readiness levels has been under development as a possible supplement to the existing technology readiness level (TRL) scale. The intent is to provide a mechanism to address safety and performance risks associated with the human component in a system that parallels the TRL structure already familiar to the systems engineering community. Sandia National Laboratories in Albuquerque, New Mexico, initiated a study in 2015 to evaluate options to incorporate human readiness planning for Sandia processes and products. The study team has collected the majority of baseline assessment data and has conducted interviews to understand staff perceptions of four different options for human readiness planning. Preliminary results suggest that all four options may have a vital role, depending on the type of work performed and the phase of product development. Upon completion of data collection, the utility of identified solutions will be assessed in one or more test cases