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<b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">PhD DEFENSE STUDENT: </span></b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">Bryan Gencianeo Alamani</span><span style="font-family:"Calibri","sans-serif"; color:black"></span></p>
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<b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">DATE: </span></b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">Monday, December 3, 2018</span><span style="font-family:"Calibri","sans-serif"; color:black"></span></p>
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<b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">TIME: </span></b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">10:00 AM</span><span style="font-family:"Calibri","sans-serif"; color:black"></span></p>
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<b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">PLACE:</span></b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black"> MREB Building, Room 320</span><span style="font-family:"Calibri","sans-serif"; color:black"></span></p>
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<b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">DISSERTATION CHAIR: </span></b><span style="font-size:14.0pt; line-height:200%; font-family:"Arial","sans-serif"; color:black">Dr. Jeffrey D. Rimer</span><span style="font-family:"Calibri","sans-serif"; color:black"></span></p>
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<p class="x_MsoNormal" align="center" style="text-align:center"><b><span style="font-size:18.0pt; line-height:105%; font-family:"Arial","sans-serif"">TITLE:</span></b></p>
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<p class="x_MsoNormal" align="center" style="text-align:center"><b><span style="font-size:18.0pt; line-height:105%">Growth and Nucleation Modifiers of Calcium Oxalate Mineralization</span></b></p>
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<p class="x_MsoListParagraph">Crystallization is a ubiquitous process essential in various chemical, biological, physical and geological phenomena. The resulting crystalline material originates from the ensemble of interactions that persist in their growth
environments. The kinetics and thermodynamics facilitating crystallization are important metrics that allow understanding of the underlying mechanisms in determining the structure and property of the crystal. Insights from such fundamental studies of growth
establishes rules or heuristics useful to control and tune the structure and property of the crystals to transition into functional materials and assemblies that find applications in energy, environment, and health. This dissertation focuses on the mineralization
of calcium oxalate monohydrate (COM), the most common constituent of human kidney stones, and the mechanisms by which various modifiers alter the rate of COM formation with concomitant changes in crystal properties (e.g. size and shape). Emphasis has been
placed on modifiers that can inhibit nucleation and growth of COM, which can be potential candidates for new therapeutics of pathological calcification in humans. In certain cases, promoters of growth and intergrowth formation have been identified, which can
be insightful in understanding COM formation in plants. </p>
<p class="x_MsoListParagraph">We employed combined macroscopic and molecular scale approaches to investigate the influence of divalent ions (Zn<sup>2+</sup>, Sr<sup>2+</sup>, and Mg<sup>2+</sup>) and polyphosphates (Hexametaphosphate, Linear tripolyphosphate,
and Cyclic trimetaphosphate) on COM mineralization. These ions and molecules interact with the crystal through mechanisms dominated by thermodynamic and/or kinetic processes. We examined the impact of these modifiers on COM crystallization through bulk assays
that provide information on changes in size, habit and morphology. Furthermore, we probed changes in the kinetic rates of crystallization to classify the modifiers as inhibitors, promoters, or combinations thereof. To elucidate the underlying molecular level
processes driving modifier-crystal interactions, we employ <i>in situ</i> atomic force microscopy (AFM) to monitor the processes occurring on the crystal surface spatiotemporally. Furthermore, using brownian microscopy, we monitor the dynamics calcium oxalate
clusters in undersaturated solution to understand relevant dynamics that may contribute to nucleation of COM.</p>
<p class="x_MsoListParagraph">In these studies, we have uncovered unique modes of action for several modifiers where ions (e.g. Zn<sup>2+</sup> and Sr<sup>2+</sup>) can have dual modes of action in modulating COM crystallization. Cyclic polyphosphates (HMP),
on the other hand, can be effective nucleation inhibitors, but only moderately effective growth inhibitors, while linear polyphosphates (LTPP) are only effective growth inhibitors. Some modifiers (e.g. Mg<sup>2+</sup> and CTMP) do not impact the overall crystallization
rate, which cannot be easily explained from our experiments. Overall, our understanding of modifier-crystal interactions that mediate COM crystallization can be useful in obtaining guidelines or heuristics in designing processes to regulate materials assembly.
Specifically, the combination of bulk and interfacial approaches in deciphering modifier-crystal interactions may find use in screening preventative drug candidates that are capable of inhibiting pathological calcification.</p>
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