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Chapter 1 focuses on the inhibition of the β-catenin/B-Cell lymphoma 9 proteinprotein interaction. This protein-protein interaction is found in Wnt signaling and has been strongly linked to cancer. To inhibit the interaction, molecules were computationally designed, synthesized and tested. A series of 33 final compounds was synthesized, resulting in a lead molecule with an inhibition constant of 5.2 μM. The binding mode of this molecule was validated through the structure activity relationship of the series as well as mutational studies. The lead molecule was shown to exhibit 98-fold selectivity for the β-catenin/B-Cell lymphoma 9 interaction over the β-catenin/E-cadherin interaction, inhibit the Wnt pathway in a cell based assay and inhibit the growth of Wnt/β-catenin-dependent cancer cells. Chapter 2 describes an attempt to overexpress and purify the ethylene receptor, a membrane protein found in plants critical to all stages of plant life. There are major unanswered questions involving the ethylene receptor, but most important is the nature of the binding interaction between ethylene and the receptor. We intended to characterize the interaction using a variety of spectral techniques, which would require large amounts of protein. Several strategies to express and purify the receptor were pursued. Chapter 3 lays the foundation for using Stark vibrational spectroscopy to more thoroughly understand the mechanism of proton pumping. Stark vibrational probes were installed in the proton pump ubiquinol oxidase. Functional protein containing the probes iv was successfully expressed and purified. The probes were then utilized to survey the electric field within the proton pump. Changes in electric field were detected in multiple locations and synchronistic results were observed for probes positioned in the same region of the protein. The presented work was highly decoupled and covered a broad area. Completion required efforts in organic synthesis, molecular biology, protein chemistry and spectroscopy. Overall, important foundational achievements were made on several challenging and significant systems.
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dissertation
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honors thesis
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report
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health and environmental sciences
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triggers
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1
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1
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1
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1
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1
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1
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1
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1
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1
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1
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1
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1
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1
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1
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401
Page 233
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410
Florinas, Stelios
Ultrasound-assisted nonviral antiangiogenic small interfering RNA delivery for the treatment of cancer
2014-05
dissertation
411
Page 63
412
Krah, Nathan Michael
Maintenance of acinar cell differentiation by PTF1A inhibits pancreatic cancer initiation
Molecular biology; Physiology; Public health; Oncology; Epidemiology
2017
dissertation
413
Rahman, Mumtahena
Development of pathway-based biomarker in breast cancer and assessment of feasibility of integrating transcriptomics data in electronic health record
Bioinformatics; Information science
2015-12
dissertation
414
Reynolds, Mary Anne Hales
Hopeful adults with advanced stage cancer : nature, influences, focus, and patterns of hope over time
Psychology; Demographic
1997-08
dissertation
415
Powers, Matthew A.
Modulation of the Tumor Supressor Programmed Cell Death 4 by the Protein Arginine Methyl Transferase 5: From Biology to Biomarker
2010-12
dissertation
416
Donohue, Rebecca Bordelon
Use of evidence-based practice by outpatient oncology nurses in the management of cancer-related pain and fatigue
Cancer-related fatigue; Cancer-related pain; Evidence-based practice; Nursing; Oncology; Outpatient
2012-12
dissertation
417
Sewell, Kelsey K.
It's not all about the erection: examining sexual functioning and patterns of sexual activity after radical prostatectomy
Psychology; Oncology; Health and Environmental Sciences; Prostate Cancer; Quality of Life; Sexual Activity
2016
dissertation
418
Page 16
419
Page 51
420
Tavernier, Susan Skinner
Individualized health-related quality of life in radiation oncology
Cancer; Quality of Life
2010
dissertation
421
Page 207
422
Page 114
423
Page 139
424
Page 139
425
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