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Design And Synthesis Of Nanomaterials For Surface-Enhanced Raman Scattering, Fuel Cell Technology, And Photonics, Pedro Camargo
Design And Synthesis Of Nanomaterials For Surface-Enhanced Raman Scattering, Fuel Cell Technology, And Photonics, Pedro Camargo
All Theses and Dissertations (ETDs)
In the first part of my dissertation, I developed two approaches for selectively probing the SERS activities of individual hot spots, i.e., experimentally detect the SERS signals only for the molecules that are trapped within the hot-spot region in individual Ag nanoparticle dimers. Then, I performed a systematic investigation on the SERS activity of individual dimers composed of two closed spaced Ag nanoparticles. By utilizing Ag nanoparticles displaying a variety of well-defined shapes, sizes and orientations to construct the dimers, I were able to precisely correlate the detected SERS signals to the specific geometry of individual hot spots. In the …
Growth Factor Delivery From Fibrin Matrics Containing Affinity-Based Delivery Systems To Treat Peripheral Nerve Injury, Matthew Wood
Growth Factor Delivery From Fibrin Matrics Containing Affinity-Based Delivery Systems To Treat Peripheral Nerve Injury, Matthew Wood
All Theses and Dissertations (ETDs)
This thesis work sought to develop a biomaterial to further the understanding of affinity-based delivery and to serve as a potential treatment for peripheral nerve injury. The use of an affinity-based delivery system: ABDS) with growth factors in a nerve guidance conduit: NGC) was hypothesized to promote nerve regeneration and functional recovery following a critical nerve defect. Evaluation of affinity-based delivery using peptides with varying binding affinity for heparin determined that peptide binding affinity for heparin affected the release rate and biological activity of nerve growth factor: NGF) in vitro. The ABDS presented biologically active NGF, which promoted neurite extension …
Evaluation Of Pbr In Breast Cancer, Stephany Shockley
Evaluation Of Pbr In Breast Cancer, Stephany Shockley
All Theses and Dissertations (ETDs)
The utility of Positron Emission Tomography: PET) in the detection of cancer began with the radiopharmaceutical 2-[18F]fluoro-2-deoxyglucose: FDG) used for measuring altered cellular metabolism. Specific radioligands are being developed to allow non-invasive analysis of protein expression to further characterize tumors. One protein that has been identified as a promising target is the Peripheral Benzodiazepine Receptor: PBR). PBR expression is up-regulated in several cancers, and in many there has been a correlation drawn between increased malignancy and protein expression levels. Therefore, developing PET methodologies to apply for PBR imaging could be an important step in understanding individual tumors as we move …
Engineering The Optical Properties Of Gold Nanostructures For Biomedical Applications, Leslie Au
Engineering The Optical Properties Of Gold Nanostructures For Biomedical Applications, Leslie Au
All Theses and Dissertations (ETDs)
This research investigated the synthesis and optical properties of Au nanostructures with an aim to use them as imaging agents and photothermal transducers for the diagnosis and treatment of cancer. I have produced Au nanocages with hollow interiors and porous walls using the galvanic replacement reaction between Ag nanocubes and AuCl4-. I have engineered these Au nanocages to have localized surface plasmon resonance: LSPR) peaks in the near-infrared region with strong absorption. These optical properties allow for the imaging of biological tissues at deeper penetration and the photoablation of cancer. By replacing AuCl4- with AuCl2 …
Discovery Of Inactive E* Conformations In Thrombin And Other Vitamin K- Dependent Clotting Proteases, Alaji Bah
Discovery Of Inactive E* Conformations In Thrombin And Other Vitamin K- Dependent Clotting Proteases, Alaji Bah
All Theses and Dissertations (ETDs)
Serine proteases of the chymotrypsin family play important roles in the regulation and function of numerous biological processes including digestion, blood coagulation, fibrinolysis, development, fertilization, apoptosis and immunity. For many of these proteases, activity unfolds when a zymogen is activated by limited proteolysis and the associated conformational changes result in the formation of a proper active site and oxyanion hole, both of which are required for efficient hydrolysis of peptide bonds. The transition from zymogen to active enzyme, E, thus provides critical temporal and spatial regulatory mechanism of protease function. Catalytic activity of serine proteases belonging to Vitamin K-dependent clotting …
An Investigation Of Acetobacter Aceti N5-Carboxyaminoimidazole Ribonucleotide Mutase And Its Pure-Purk Operon, Charles Constantine
An Investigation Of Acetobacter Aceti N5-Carboxyaminoimidazole Ribonucleotide Mutase And Its Pure-Purk Operon, Charles Constantine
All Theses and Dissertations (ETDs)
Acetobacter aceti oxidizes ethanol to acetic acid. While the membrane-permeable acetic acid is toxic to many bacteria, A. aceti survives exposure to acetic acid by tolerating cytoplasmic acidification. The ability to tolerate an acidic cytoplasm suggests that proteins from A. aceti are unusually suited to function in an acidic environment. The ability to tolerate an acidic cytoplasm raises additional questions about biosynthetic pathways that employ acid-labile intermediates. To examine how A. aceti metabolism may have adapted to function under acidic conditions, a biosynthetic conversion involving an acid-labile metabolite has been selected for study. The enzyme N5-carboxyaminoimidazole ribonucleotide mutase: PurE) catalyzes …
Accurate Docking Is Achieved By Decoupling Systematic Sampling From Scoring, Jianwen Feng
Accurate Docking Is Achieved By Decoupling Systematic Sampling From Scoring, Jianwen Feng
All Theses and Dissertations (ETDs)
This dissertation discusses two main projects from my thesis work. The first project focuses on the development of a small molecule docking program, SKATE, for drug discovery. The second project focuses on the critical analysis of the thermal stability of a mini-protein, FSD-1. SKATE is a novel approach to small molecule docking. It removes any inter-dependence between sampling and scoring to improve docking accuracy. SKATE systematically and exhaustively samples a ligand's conformational, rotational and translational degrees of freedom, as constrained by a receptor pocket, to find sterically allowed poses. A total of 266 ligands were re-docked to their respective receptors …
Structually Diverse Cu-64-Labeled Rgd Peptide Conjugates For Pet Imaging Of Αvβ3 Expression, Ashley Fiamengo
Structually Diverse Cu-64-Labeled Rgd Peptide Conjugates For Pet Imaging Of Αvβ3 Expression, Ashley Fiamengo
All Theses and Dissertations (ETDs)
Radiolabeled receptor-binding peptides have emerged as an important class of radiopharmaceuticals for diagnostic imaging and cancer therapy. Following radionuclide labeling, the specific receptor-binding properties of the ligand can be exploited to guide the radioactivity to tissues expressing a particular receptor. This dissertation reports on the development of integrin αvβ3-targeting radiopharmaceuticals for medical imaging applications from the perspective of both the radiometal-labeled chelator as well as the targeting peptide. Several macrocyclic copper(II) chelators have been studied with the goal of improving kinetic and in vivo stability. Structurally diverse bifunctional RGD: arginine-glycine-aspartic acid) peptides were investigated for α …
Investigations Into Building Block Structure And Method Of Preparation On The Properties Of Nanomaterials, Zicheng Li
Investigations Into Building Block Structure And Method Of Preparation On The Properties Of Nanomaterials, Zicheng Li
All Theses and Dissertations (ETDs)
This dissertation research is primarily focused on the preparation of polymer-based nanostructures as potential diagnostic agents and therapeutics delivery vehicles. Various polymers, nanoparticles and conjugation techniques were developed to meet the specific requirements of each application. Shell crosslinked nanoparticles: SCKs) are characterized by their structural integrity and available functionality to attach multiple agents on the shell, such as receptor-recognizing or receptor-specific ligands, .imaging agents, Cell transduction components, etc. In this work, SCKs derived from amphiphilic poly(acrylic acid)-block-polystyrene: PAA-b-PS) have been studied as potential diagnostic and therapeutic agent delivery vehicles: Chapters 2 and 4). SCK nanoparticles bearing a cyclic KCRGDC peptide …
Making Metal And Semiconductor Contacts On Alkanethiolate Self-Assembled Monolayer Adsorbed On Au, Peng Lu
Making Metal And Semiconductor Contacts On Alkanethiolate Self-Assembled Monolayer Adsorbed On Au, Peng Lu
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Understanding and controlling the interactions of metals and semiconductors with organic substrates is critical to many technological applications. The primary goal of the research described in this dissertation is to understand the metal/organic and semiconductor/organic interactions and to develop methods to fabricate stable and robust metallic and semiconducting contacts on organic thin layers. Alkanethiolate self-assembled monolayers: SAMs) adsorbed on Au, which have highly organized structures with a uniform density of terminal organic functional groups, were employed as model organic systems. Chemical vapor deposition: CVD) was employed to deposit selectively aluminum and alumina on functionalized SAMs. Methods were also developed to …
Developing New Methodologies For Crosslinked Polymeric Nanostructure Syntheses, Chemoselective Modifications, And Applications As Imaging And Delivery Agents, Guorong Sun
All Theses and Dissertations (ETDs)
The overall emphasis of this dissertation research includes the syntheses of amphiphilic block copolymers bearing functional groups through controlled radical polymerization techniques, followed by the aqueous assembly of these block copolymer precursors to construct polymeric nanostructures with different sizes and morphologies. Further chemical modification of the nanostructures afforded functional crosslinked nano-objects with reporting probes for imaging and biocompatible "stealth" materials for tuning the in vivo fate of nanostructures. Amphiphilic block copolymers poly(acrylic acid)-block-polystyrene: PAA-b-PS) with well-defined structures were prepared through nitroxide-mediated radical polymerization: NMP). Using novel pre-functionalization strategies, these block copolymer precursors were functionalized with DOTA for chelating 64Cu and …
Colloidal Cdse Quantum Nanowires: Synthesis, Photo-Induced Photoluminescence Enhancement And Fabrication Of Core/Shell, Water-Dispersible Structures, Rui Tang
All Theses and Dissertations (ETDs)
Solution-liquid-solid: SLS) mechanism is applied to the growth of colloidal CdSe quantum wires. The synthetic conditions are optimized to control the morphology and optical properties of the quantum wires. The effects of the impurities of solvent TOPO during the synthesis were also explored. Photo-induced photoluminescence enhancement phenomenon is observed and studied for the CdSe nanowires. The quantum yield of the ensemble CdSe quantum wires can reach up to 10% after photo-enhanced. Type-I CdSe/CdS core/shell structures were synthesized to improve the emission efficiency of the nanowires. Polymer or silica coated CdSe nanostructures were also synthesized to achieve the water-dispersibility.
Discovery Of A Novel Metalloregular Family: Structure/Function Studies Of E. Coli Rcnr, Jeffrey Iwig
Discovery Of A Novel Metalloregular Family: Structure/Function Studies Of E. Coli Rcnr, Jeffrey Iwig
All Theses and Dissertations (ETDs)
The first row transition metal ions- Mn, Fe, Co, Ni, Cu and Zn are vital cofactors for proteins involved in diverse processes including photosynthesis, oxidative respiration and protein translation. Despite these essential functions, excess metal ions can lead to cell death through the generation of oxidative damage or the occupation of non-native metal sites. Acquiring metal ions from the environment while limiting possible toxic effects requires the coordinated regulation of metal uptake, trafficking and efflux, which in bacteria is often carried out by metal-responsive transcription factors: metalloregulators). Nickel homeostasis in E. coli is an ideal model system for understanding the …
Computational And Experimental Investigation Of Allosteric Communication In The Transcriptional Regulator Nikr, Michael Bradley
Computational And Experimental Investigation Of Allosteric Communication In The Transcriptional Regulator Nikr, Michael Bradley
All Theses and Dissertations (ETDs)
The Ni2+ and DNA binding protein NikR is involved in nickel regulation in Escherichia coli through transcriptional repression of the NikABCDE nickel permease. NikR is a homotetramer and each chain contains both a DNA binding ribbon-helix-helix: RHH) domain and a Ni2+ binding regulatory ACT: aspartokinase, chorismate mutase, TyrA) fold. Work herein combines computational modeling of NikR structure with experimental studies aimed at understanding allosteric communication between the ACT and RHH domains. Hydrogen/deuterium exchange mass spectrometry shows a Ni2+ specific NikR conformational change relative to bound Cu2+, Co2+, and Zn2+. Concurrent coordination geometry and in vivo repressor function studies show that …
Improving Biocompatibility By Controlling Protein Adsorption: Modification And Design Of Biomaterials Using Poly(Ethylene Glycol) Microgels And Microspheres, Evan Scott
All Theses and Dissertations (ETDs)
Guided by the clinical needs of patients and developments in biology and materials science, the primary focus of the biomaterials field remains at the solid/liquid interface between biomaterial surfaces and biological fluids. For blood-contacting devices, biological responses are initially elicited and directed by proteins that adsorb from this multicomponent solution to form thin films on their surfaces. The identity, conformation, and quantity of adsorbed proteins are related to the properties of a material's surface. For example, hydrophobic surfaces tend to be thrombotic via interactions between platelets and adsorbed fibrinogen, while surface-activation of specific enzymes initiates the coagulation cascade on hydrophilic …
Characterization Of Ligand-Induced Conformational Changes In The Egf Receptor, Katherine Yang
Characterization Of Ligand-Induced Conformational Changes In The Egf Receptor, Katherine Yang
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ABSTRACT OF DISSERTATION Characterization of ligand-induced conformational changes in the EGF receptor by Katherine S. Yang Doctor of Philosophy in Biochemistry Washington University in St. Louis, 2009 Professor Linda Pike, Chairperson The epidermal growth factor: EGF) receptor is a classical receptor tyrosine kinase that mediates cellular processes such as proliferation, migration, and differentiation in response to growth factor stimulation. Crystal structures of the EGF receptor suggest that its activation is associated with extensive conformational changes in both the extracellular and intracellular domains. However, evidence of these structural dynamics in intact cells has been lacking. This thesis describes the characterization of …
Development Of Shell-Crosslinked Knedel-Like Nanoparticles As Intracellular Delivery Vehicles And Gene Regulation Agents, Ke Zhang
All Theses and Dissertations (ETDs)
This dissertation focuses on the development of polymer-based nanomaterials, termed shell-crosslinked knedel-like: SCK) nanoparticles, as vehicles to carry specific guest molecules or guest structures into the cell. Detailed synthetic procedures for and characterization of well-defined block copolymers, as well as the nanostructures resulted from their self-assembly are reported. The nanoparticles exhibited different but controlled sizes and shapes, depending on the conditions for their preparation. To incorporate functionality into these materials, both pre- and post-particle functionalization methods, as well as their combination, were used. The nanostructures involved in this dissertation include protein transduction domain: PTD)-functionalized SCK, folate-functionalized SCK and cationic SCK: …
The Evolution And Regulation Of Dna-Binding By The Nickel-Dependent Transcription Factor Nikr, Erin Benanti
The Evolution And Regulation Of Dna-Binding By The Nickel-Dependent Transcription Factor Nikr, Erin Benanti
All Theses and Dissertations (ETDs)
Transition metal homeostasis is critical for all cells to balance cellular metal requirements with metal availability. One common homeostatic mechanism in bacteria is metal-dependent transcriptional regulation. The Ni2+-dependent transcription factor NikR is a member of the ribbon-helix-helix: RHH) family of DNA-binding proteins and is widespread among bacteria and archea with vastly different nickel physiologies. The goal of this thesis was to better understand basic aspects of cellular transition metal homeostasis by examining the activity and regulatory properties of NikR family members from different bacterial species. One organism that exhibits a prominent and well-defined nickel physiology is Helicobacter pylori, making it …