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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif; text-transform:uppercase">Name:</span></b><span style="font-size:14.0pt; font-family:"Times New Roman",serif; text-transform:uppercase">
</span><span style="font-size:14.0pt; font-family:"Times New Roman",serif">Yuechuan Xu</span><span style="font-family:"Times New Roman",serif; color:windowtext"></span></p>
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<span style="font-size:18.0pt; font-family:"Times New Roman",serif"> <b> </b></span><span style="font-family:"Times New Roman",serif"></span></p>
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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">DATE: </span>
</b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">Friday, October 22, 2021</span><span style="font-family:"Times New Roman",serif"></span></p>
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<b><span style="font-size:18.0pt; font-family:"Times New Roman",serif"> </span></b><span style="font-family:"Times New Roman",serif"></span></p>
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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">TIME: </span>
</b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">1:00 PM</span><span style="font-family:"Times New Roman",serif"></span></p>
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<b><span style="font-size:18.0pt; font-family:"Times New Roman",serif"> </span></b><span style="font-family:"Times New Roman",serif"></span></p>
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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">COMMITTEE CHAIR:
</span></b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">Prof. Peter Vekilov</span><span style="font-family:"Times New Roman",serif"></span></p>
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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">FACE to FACE:
</span></b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">Mechanical Engineering Large Conference Room</span></p>
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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif; color:red">and
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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">ZOOM MEETING:</span></b><span style="font-size:14.0pt; font-family:"Times New Roman",serif"></span></p>
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<span style="font-size:11.0pt; font-family:"Times New Roman",serif; color:#39394D"><a href="https://urldefense.com/v3/__https://uh-edu-cougarnet.zoom.us/j/91659911328?pwd=OUx2bklkZ1dkVHJidnVIV3o3eXI4QT09__;!!LkSTlj0I!RiGmPELvJIi-5J97zM7q4WL7tR4_eh52dNJGbWOHp6SBSuz48Lp3Eh4FjR-NQCjXGUk$">https://uh-edu-cougarnet.zoom.us/j/91659911328?pwd=OUx2bklkZ1dkVHJidnVIV3o3eXI4QT09</a>
</span></p>
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<b><span style="font-family:"Times New Roman",serif; color:windowtext">Meeting ID:</span></b><span style="font-family:"Times New Roman",serif; color:#39394D">
</span><span style="font-family:"Times New Roman",serif; color:windowtext">916 5991 1328</span></p>
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<b><span style="font-family:"Times New Roman",serif; color:windowtext">Passcode:</span></b><span style="font-family:"Times New Roman",serif; color:windowtext"> 291107</span></p>
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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">TITLE: </span>
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<b><span style="font-size:14.0pt; font-family:"Times New Roman",serif">Microscopic Dynamics of Amyloid beta Fibrillization</span></b></p>
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Amyloid fibrils are â-sheet-rich protein assemblies, which could trigger various diseases, including Alzheimer’s. One crucial step in searching for cures is to understand the aggregation mechanism; yet despite ever-developing techniques and tools, it remains
poorly understood. Common experimental methods bear certain limitations. In this study, we employed time-resolved in situ scanning probe microscopy to directly probe the fibrillization pathway of amyloid-<span style="font-family:Symbol">b
</span>40, a short peptide believed to be responsible for Alzheimer’s.<span style="color:black"></span></p>
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Amyloid plaque deposition is the hallmark of Alzheimer’s. The fibrillization pathway is extraordinarily complex. Numerous fundamental questions remain unanswered. To elucidate the nature of the intermediate state for A<span style="font-family:Symbol">b</span>
monomer incorporation into fibril, we employed time-resolved in situ atomic force microscopy to monitor the growth of single fibrils at various peptide and urea concentrations. We proved that AFM is a reliable tool for direct measurement of individual fibril
growth rates. The growth rates do not correlate with the fibril thickness, indicating lack of cooperativity between adjacent protofilaments during growth. The opposite ends on a fibril grow at similar rates and are steady, in contrast to the “stop-and-go”
mechanism. Most importantly, the bimolecular rate constant for monomer incorporation into fibril is significantly smaller than the diffusion limit, indicating an intermediate state with relatively high free energy. With urea in the system, we discovered that
both the A<span style="font-family:Symbol">b </span>peptide solubility and the fibril growth rate constant increase. We attribute this behavior to the presence of a frustrated complex supported by nonnative contacts in the equilibrium structure of the fibril
tip.</p>
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Further investigation of the role of frustrated complex in intermediate state focused on the “Dutch variant” E22QA<span style="font-family:Symbol">b</span>, which is responsible for early-onset Alzheimer’s. The E22QA<span style="font-family:Symbol">b</span>
peptide exhibits a lower solubility and a significantly higher growth rate constant, confirming the role of E22 residue in the frustrated contacts that impedes fibrillization<span style="font-family:Symbol">.</span> Fibrils nucleated on supported phospholipid
bilayers were also investigated, for their distinct polymorphism and toxic nature, and possible relationship to a modified frustrated fibrillization intermediate state. We found that lipid bilayers interact with A<span style="font-family:Symbol">b</span> oligomers
and fibrils, and different curvatures induce different polymorphisms and kinetics of fibrillization.</p>
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