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<div><a name="_Ref72178745" style="font-family: "Times New Roman", serif; font-size: 14pt; text-transform: uppercase;">Name:
</a><span style="font-family: "Times New Roman", serif; font-size: 14pt; text-transform: uppercase;"><span style="text-transform: none;">Do Young Kim</span></span><br>
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<p class="MsoNormal"><span style=""> </span></p>
<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt">COMMITTEE CHAIR:
</span></b></span><span style=""><span style="font-size:14.0pt">Prof. Jeffrey Rimer</span></span></p>
<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt"> </span></b></span></p>
<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt">DATE: </span>
</b></span><span style=""><span style="font-size:14.0pt">Thursday, May 27, 2021</span></span></p>
<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt"> </span></b></span></p>
<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt">TIME: </span>
</b></span><span style=""><span style="font-size:14.0pt">1:00pm</span></span></p>
<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt"> </span></b></span></p>
<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt">LOCATION: </span>
</b></span><span style=""><span style="font-size:14.0pt">Zoom meeting:</span> </span>
<a href="https://urldefense.com/v3/__https:/uofh.zoom.us/j/97659988664?pwd=WG9JT3pLQ2hocXZIclBVdGI5Qmg4dz09__;!!LkSTlj0I!VpzZ9RT6ERehMcBOmXHWV_S4-bvxFxvFlv6aUIItqPGaYEJQBEZMlMbSfIFMqS_qYf2z$" target="_blank"><span style=""><span style="font-family:"Calibri",sans-serif">https://uofh.zoom.us/j/97659988664?pwd=WG9JT3pLQ2hocXZIclBVdGI5Qmg4dz09</span></span><span style=""></span></a><span style=""><span style="font-size:14.0pt"></span></span></p>
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<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt">TITLE: </span>
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<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt">Controlling Pathological Mineralization Using Molecular Modifiers</span></b></span></p>
<p class="MsoNormal"><span style=""><b><span style="font-size:14.0pt"> </span></b></span></p>
<h1 align="left" style="text-align:left"><span style="">ABSTRACT</span>:</h1>
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The development of new methods to prevent mineral scale formation can have significant impact on natural, biological, and industrial process. A ubiquitous approach to regulating crystal formation is through the use of modifiers, which are (macro)molecules that
interact with crystals to inhibit nucleation and/or growth. Understanding the fundamental mechanisms of crystallization inhibitors is relevant to a broad range of fields, including their frequent use in crystal engineering and biomineralization. This dissertation
focuses on two types of pathological crystals: calcium oxalate monohydrate (COM), the primary component of kidney stones, and magnesium ammonium phosphate hexahydrate (struvite). Struvite is a key constituent of infection stones (e.g. kidney stones); and it
is also a common scale in water purification and transport. Despite considerable interest in this material, the fundamental understanding of struvite growth is still at its infancy due to the lack of appropriate platforms to assess growth over multiple length
scales. The use of flow systems to study infection stone formation is promising, as they can simulate the flow conditions where struvite naturally forms (e.g. urinary tract systems, catheter, pipelines, etc.). This dissertation has established a new method
of evaluating struvite crystal growth under flow using a combination of microfluidics and
<i>in situ</i> atomic force microscopy (AFM). Through these synergistic approaches, we quantified anisotropic kinetics of crystallization over a broad range of conditions and resolved the molecular mechanism of growth and its inhibition whereby layers on crystal
surfaces advance from either screw dislocations or 2-dimensional generation and spreading of islands – both of which are classical pathways.
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Growth modifiers range from small ions and molecules to large macromolecules. Here, we examined the impact of bio-inspired small molecules on both struvite and COM crystallization. Several phosphate-based molecules exhibit an unparalleled dual mode of action
capable of suppressing both nucleation and growth of crystals. Time-resolved AFM images of struvite surface at varying inhibitor concentration revealed a unique mode of crystal growth inhibition, wherein surfaces become laden with an amorphous layer that leads
to roughened interfaces and growth succession through dynamic sequences that are not commonly witnessed for other minerals. In studies of COM, we observed that modifiers irreversibly stunt crystal growth in timescales that are relevant to pathological COM
kidney stone formation. Comparisons between phosphate-based modifiers and two reference compounds previously identified as highly effective COM inhibitors, carboxylate-based hydroxycitrate and the urinary protein osteopontin, revealed that phosphate-based
inhibitors suppress COM crystallization at substantially lower concentrations than both conventional modifiers, thus highlighting the unique efficacy of these newly evaluated bio-inspired molecules. In addition, the results presented in this dissertation address
knowledge gaps that are beneficial to the development of effective inhibitors with the potential to replace existing therapeutics for these widespread maladies.
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Collectively, <a name="_Hlk72130490">this dissertation presents research efforts aimed at inhibiting the formation of pathological crystals, focusing on an understanding of crystal growth under dynamic conditions and pathways to arrest growth via modifiers
(i.e. inhibitors) that may serve as model compounds for preventative drugs.</a></p>
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