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Essays On Accelerated Failure Time Models For Recurrent Event Data, Emmanuel Masavo Djegou

Doctoral Dissertations

Recurrent event data arise in many fields such as medicine, reliability, insurance, and economics, where the same event may occur repeatedly for a subject. Accelerated Failure Time (AFT) models provide an intuitive framework for relating covariates to event times and offer a useful alternative to proportional hazards models, allowing direct prediction of event timing under right censoring. However, existing AFT extensions for recurrent events, such as accelerated gap time (AGT) models, often fail to account for interventions between events and may not capture complex temporal patterns.

In this work, we first propose a class of semiparametric AGT models incorporating an …

Selective Targeting Of Microglia By Quantum Dots And Green Synthesis Of Metal Organic Biohybrids; Applications In Dynamic Cell And Assay Systems, Navya Uppu

Doctoral Dissertations

Neurological disorders are the leading cause of physical and cognitive disability across the globe, currently affecting approximately 15% of the worldwide population. Part of the glioma microenvironment are microglia, resident immune cells of the CNS that were thought to be involved in the pathogenesis of diverse neurodegenerative diseases. Though it remains uncertain what triggers microglial activation in these disorders, targeting and tracking microglial functions using nanotools like Quantum Dots (QDs) could help us elucidate them in such neurological diseases. This research focuses on the comparative study of different QDs formulations and their selective uptake by brain microglia in primary cultures …

A Qualitative Study Identifying A School Leadership Model Promoting And Fostering Technology-Enhanced Teaching And Learning, Lisa Flanders-Dick

Doctoral Dissertations

Technology-enhanced teaching and learning (TETL) is the integration of technology into teaching and learning practices to improve the quality of learning outcomes. This is an essential strategy for improving educational quality. School leaders significantly affect the integration of effective TETL in the classroom. The International Society for Technology in Education (ISTE) provides Standards for Leaders that serve as a framework for innovation in education. Situational Leadership Theory contends that one leadership style cannot be applied to all leadership tasks. This study expands upon the current use of SLT to help derive characteristics needed to develop a school leadership model that …

Enzyme-Responsive Nucleic Acid Nanocapsules (Nans) For The Delivery Of Therapeutic Oligonucleotides And Small Molecule Drugs, Alyssa Hartmann

Doctoral Dissertations

The first chapter of this work describes a novel, enzyme-responsive nanocapsule for the intracellular delivery of therapeutic nucleic acids and small molecule drugs. The stepwise assembly of this new construct, referred to as a nucleic acid nanocapsule (NAN), is presented. The cellular uptake properties of the NAN are investigated through confocal microscopy. Additionally, the functionalization of the NAN with a therapeutic nucleic acid is described. For these experiments, the NAN was functionalized with a DNAzyme, a catalytically active DNA molecule that can specifically bind and cleave a target mRNA sequence. The DNAzyme utilized in these studies is specific for the …

Development Of A Low Profile, Endoscopic Implant For Long Term Brain Imaging, Benjamin Scott Kemp

Doctoral Dissertations

The increased public awareness of concussion and traumatic brain injury has motivated continued research into the brain, its functions, and especially its response to injury, with a focus on improving the brain’s repair capabilities. However, due to the critical nature of the tissue, it is currently difficult for researchers to acquire high resolution images below the cortex without sacrificing a lab animal. Sacrificing an animal greatly reduces the amount of data that can be obtained from it, making longitudinal studies unappealing or unfeasible because a large number of animals is needed to obtain useful data over multiple time points. Additionally, …

Novel Antifolates To Target Antibiotic Resistant Gram-Negative Pathogens, Michael Lombardo

Doctoral Dissertations

Antibiotic resistance has limited our ability to treat life-threatening infections putting pressure on the scientific community to discover new effective therapeutics. There have been significant research efforts to develop drugs for the treatment of infections caused by Gram-negative pathogens as they are the leading cause of healthcare-associated infections and have a high propensity to accumulate antibiotic resistance genes. The two major challenges to Gram-negative antibiotic development are finding drug chemotypes that are able to penetrate the cell envelope and accounting for plasmid-associated resistance genes. We have developed a novel class of antifolates, designated as propargyl-linked antifolates, as effective antimicrobials against …

Synthesis Of Alpha-Galactosylceramide Analogs For Th1 Biased Inkt Cell Activation And Novel Reactions With Ketiminium Salts, Nicole Sassu

Doctoral Dissertations

Natural killer T (NKT) cells are a subset of T cells that recognizes and is activated by glycolipid antigens. Glycolipids, specifically alpha-galactosylceramides, are a primary focus due to their ability to modulate immune responses based on interactions with NKT cells. KRN7000, the first synthetic glycolipid shown to potently activate NKT cells, has been the foundation of structure-activity relationship (SAR) studies, providing insight to how glycolipids interact with components of the immune system to elicit specific responses. A glycolipid can produce a Th1 and/or Th2 response from NKT cells. A primary goal of many researchers is to produce a potent glycolipid, …

New Developments Of Dimension Reduction, Lei Huo

Doctoral Dissertations

"Variable selection becomes more crucial than before, since high dimensional data are frequently seen in many research areas. Many model-based variable selection methods have been developed. However, the performance might be poor when the model is mis-specified. Sufficient dimension reduction (SDR, Li 1991; Cook 1998) provides a general framework for model-free variable selection methods.

In this thesis, we first propose a novel model-free variable selection method to deal with multi-population data by incorporating the grouping information. Theoretical properties of our proposed method are also presented. Simulation studies show that our new method significantly improves the selection performance compared with those …

Synthesis Of Alpha-Galcer Analogues As Inkt-Cell Agonists And Reactions Of 2-Methyleneoxetanes, Donald Raymond Caldwell

Doctoral Dissertations

Glycolipids, particularly a-galactosylceramides, have gained considerable attention due to their ability to modulate immune responses. The discovery of a synthetic glycolipid antigen, KRN7000, has enhanced our understanding of iNKT cell function. Since KRN7000 stimulates iNKT cells to release both Th1 and Th2 cytokines in relative amounts at which the biological activity of either one is antagonized by the other, tremendous effort has been devoted toward synthesizing analogues of KRN7000 that bias cytokine release, as such targets may offer new approaches to treating viral infections, bacterial infections, cancer, and autoimmune conditions. The first part of this proposal describes the synthesis of …

Expanding The Applications Of Poly(Dimethylsiloxane) In Biomicrofluidics, Sawyer D. Stone

Doctoral Dissertations

This work aims to create novel applications for poly(dimethylsiloxane) (PDMS) in the field of biomicrofluidics through oxidative stress detection, doping of the polymer for intentional leaching into microdevices, and the development of low-cost implements for fabricating PDMS microfluidic devices. PDMS has become the polymer of choice for research in microfluidics due to its optical clarity, ease of fabrication, flexibility in design, good mechanical properties, and the ability to chemically modify the surface.

Biomicrofluidics enables the rapid throughput and analysis of small biological samples requiring less time investment and reagent use than traditional macroscale laboratory techniques. Polymer devices are inexpensive, easily …

Advanced Analytical Strategies To Determine Biomedical Parameters For Medical Diagnostics, Drug Delivery, And Therapy, Sisi Chen

Doctoral Dissertations

"Biomedical parameters are critical for diseases prognosis, diagnosis and therapy. Many research groups have dedicated their studies to develop analytical instrumentation and apply analytical methods to determine biomedical parameters that have the potential to help with disease control and increase public health. This dissertation focuses on three major aspects of analytical strategies development and applications: 1) detection of pH changes caused by nanotoxicity (induced by TiO₂ nanoparticles) using newly developed micro-pH sensor, 2) quantification of renal cell carcinoma (RCC) biomarkers by high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS), and 3) nuclear magnetic resonance (NMR) studies of porous wall …

Lab-On-A-Chip Nucleic-Acid Analysis Towards Point-Of-Care Applications, Varun Lingaiah Kopparthy

Doctoral Dissertations

Recent infectious disease outbreaks, such as Ebola in 2013, highlight the need for fast and accurate diagnostic tools to combat the global spread of the disease. Detection and identification of the disease-causing viruses and bacteria at the genetic level is required for accurate diagnosis of the disease. Nucleic acid analysis systems have shown promise in identifying diseases such as HIV, anthrax, and Ebola in the past. Conventional nucleic acid analysis systems are still time consuming, and are not suitable for point-ofcare applications. Miniaturized nucleic acid systems has shown great promise for rapid analysis, but they have not been commercialized due …

A Non-Invasive Fluorescence-Based Oxygen Sensor And Platform For Studying Cell Responses To Metabolic Agents In Real-Time, Koutilya Reddy Buchapudi

Doctoral Dissertations

A fluorescence-based sensor in a transverse flow/stop measurement platform has been developed to determine real-time changes in oxygen consumption rates for cell metabolic studies. The oxygen sensitive fluorophore platinum octaethylporphyrin was embedded in a cellulose acetate matrix and affixed to a fiber optic bundle, which provided for transmission of the excitation and emission wavelengths of the film. The fiber optic bundle was sealed in a sensor head that can be used in standard 24-well plates common to research labs. The utility of the sensor and sensing platform were determined by measuring the changes in oxygen consumption rates of Candida albicans …

Using Computer Simulations As A Pre-Training Activity In A Hands-On Lab To Help Community College Students Improve Their Understanding Of Physics, Blanca Pineda

Doctoral Dissertations

The purpose of this study was to investigate the effectiveness of using computer simulations as a pre-training activity to a hands-on lab to improve students’ understanding of induction topics in physics. The computer simulation activity was compared to an overview presentation. Conceptual understanding and spatial ability were measured. A two-group descriptive repeated measures design was implemented with a convenience sample of 35 community college physics students in the Bay Area. Participants were randomly assigned to a simulation group (n = 17) or a presentation group (n = 18). A 30-item spatial ability assessment was given to all participants one week …

Structure-Based Drug Design And Synthesis Of Anti-Infective And Anticancer Agents, Narendran Gummudipundi Dayanandan

Doctoral Dissertations

Resistance to antibiotics is on the rise at an alarming pace. The problem is exacerbated by the lack of new class of therapeutic agents and targets. Modes of resistance include alteration of drug target, modification of ligand, and reduction of the intracellular concentration of drug. Dihydrofolate reductase (DHFR) is a validated drug target for the treatment of infectious diseases and cancer. The binding of ligands to DHFR inhibits the downstream folate pathway that is vital for purine and thymidylate synthesis. Trimethoprim (TMP), a clinically used antifolate exhibits resistance in both gram-positive and gram-negative bacteria. In this thesis, methods have been …

Morphology And Function Of The Drinking Apparatus In Hummingbirds, Alejandro Rico-Guevara

Doctoral Dissertations

My research aims to answer the questions: How do hummingbirds feed? And, how do the mechanics of feeding define the limits and adaptive values of feeding behaviors? I meticulously study every step of nectar capture and ingestion. My dissertation chapters are organized following a morpho-functional and feeding sequence approach: 1) Feeding Apparatus Morphology; with emphasis on the understudied morphology of the tongue grooves and bill tongue coupling. 2) Tongue Tip Dynamics; how hummingbird tongues entrap nectar. 3) Tongue Grooves Functioning: how the tongue acts as an elastic micropump while collecting nectar. 4) Bill Tip Mechanics; internal bill structures that aid …

Mouse Models Of Neuroanatomical, Behavioral, And Genetic Correlates Of Language-Related Impairments: An Investigation Of Core Phenotypes., Dongnhu Truong

Doctoral Dissertations

The development of the brain is an immensely complicated process that is highly regulated by numerous genetic pathways. Disruption within any stage of this operation—from proliferation, to neuronal migration, to synaptogenesis—could ultimately lead to deleterious behavioral outcomes, ranging from severe intellectual disability and gross motor developmental delays to more subtle cognitive impairments such as language disability. It is therefore no surprise that neuroanatomical anomalies resulting from of altered cortical development are associated with a number of language related neurodevelopmental disorders such as specific language impairment (SLI), dyslexia, and autism spectrum disorders (ASD). Over the past decade, genetic association studies have …

Nanostructured Aluminum Oxide (Nao): Enhanced Fluorescence Imaging And Sensing, Xiang Li

Doctoral Dissertations

A new fluorescence enhancement technical platform based on nanostructured aluminum oxide (NAO) has been discovered. Experiments reveal that this new platform can enhance the fluorescence signals up to two or three orders of magnitude compared to a traditional glass substrate platform. In order to realize a large-scale arrayed fluorescence biosensing platform for high throughput applications, a rapid and cost-effective process has been developed to fabricate the micropatterned NAO of a variety of shapes. An optical characterization technology, by introducing UV light irradiance, has been found for the first time to determine if the NAO has been formed from Al and …

Understanding The Impact Of Iron Availability On Bacillus Anthracis Metabolism, Eddy Johana Bautista Bautista

Doctoral Dissertations

Bacillus anthracis, the causative agent of anthrax, has to be able to adapt to different physical conditions encountered during the beginning and establishment of the infection process inside the host. One of these conditions is the availability of nutrients like iron. B. anthracis secretes siderophores capable of competing with the iron transport/storage proteins of the host. Previous studies have been dedicated to the analysis of these systems. However, the impact of iron availability on B. anthracis metabolism from a global perspective remains as unclear. In this dissertation, I combined an in silico genome-scale metabolic analysis with experimental studies for B. …

Design, Synthesis, And Application Of Photoactive Complexes Of Biologically Relevant Metals, Celina Gwizdala

Doctoral Dissertations

Photo-labile organic molecules have been broadly utilized as photoprotective groups (PPGs) in “caging compounds”. Inactive caged analyte can be easily introduced in its active form to the system under investigation by photolysis of the PPG. This light induced manipulation permits release of the analyte and allows for spatial and temporal control of its concentration. Photocages presented within utilize specific strategy of metal release that relies on decrease in metal-ligand interaction triggered by delocalization of lone pair of electrons on the metal coordinating nitrogen(s). Synthesis and photochemical properties of nitrobenzhydrol based photocages of Zn²⁺ and Ni²⁺ are presented and …

A Novel Microfluidic Enrichment Technique For Carbonylated Proteins, Bryant C. Hollins

Doctoral Dissertations

Proteins are the building blocks of cells in living organisms, and are composed of amino acids. The expression of proteins is regulated by the processes of transcription and translation. Proteins undergo post-translational modifications in order to dictate their role physiologically within a cell.

Not all post-translational modifications are beneficial for the protein or the cell. One type of post-translational modification, called carbonylation, irreversibly places a carbonyl group onto an amino acid residue, most commonly proline, lysine, arginine, and threonine. This modification can have severe consequences physiologically, including loss of solubility, loss of function, and protein aggregation.

Carbonylated proteins have commonly …

Manipulating Cellular Growth Responses To Patterning, Apoptotic, And Environmental Cues, James N. Mcnamara

Doctoral Dissertations

In this work, various methods of controlling cell growth are examined. Cell-cell interaction, apoptotic cues, three dimensional scaffolds, and non-adherent environments are evaluated for their ability to affect the differentiation, morphology, and growth rate of different cell types. Previous work has shown that cell growth and cell morphology can be influenced by patterns of polymers coated on surfaces in two dimensions, designated here as the x and y dimensions of a standard Cartesian coordinate system. Tissue engineering and regenerative medicine studies have shown limited success in modifying growth in the third, z dimension. This work considers not only the x, …

Modeling And Its Numerical Method For Micro-Scaled Diffusion -Reaction Systems In The Neuromuscular Junction, Abdul Khaliq

Doctoral Dissertations

The main subject of this research is the neuromuscular junction (NMJ). The NMJ is a biological structure composed of the interface between a neuron and a muscle cell. Currently, there is not a fully three dimensional model of diffusion-reaction processes occurring in the NMJ. Developing a useful predictive model of this structure will assist in the therapeutic efforts to restore and rehabilitate NMJ function to humans and in developing strategies to prevent damage to the NMJ. This research work developed 1D mass transport and full 3D reaction diffusion models. A new finite difference scheme is presented for solving 1D mass …

Gonadotropin Releasing Hormone In Agnathans, Scott Ira Kavanaugh

Doctoral Dissertations

Hagfish and lampreys are the only two representatives of Agnathans among extant vertebrates. The regulatory hypothalamic neurohormone, gonadotropin-releasing hormone (GnRH), regulates reproduction in all vertebrates through the hypothalamic-pituitary-gonadal axis. Most vertebrates have at least two forms of GnRH in the brain. In hagfish the primary amino acid structure of GnRH has not been identified as yet, however, indirect methods have shown an immunoreactive GnRH or a GnRH-like peptide in the brain of hagfish. In addition concentrations of brain immunoreactive-GnRH have been correlated with reproductive stages in the Atlantic hagfish ( Myxine glutinosa). Therefore the objective of the first study was …

An Experimental And Numerical Investigation Of Flapping And Plunging Wings, Taylor A. Swanson

Doctoral Dissertations

"Micro air vehicles, or MAVs, are of current interest for a multitude of uses to which they, being small, unmanned vehicles, are uniquely suited. Among the proposed uses are exploration, reconnaissance, and communications. They can be deployed inside buildings, where their small size, hovering capability, and maneuverability, are important factors. Due to their small size, they operate at low Reynolds numbers where conventional flying mechanisms are not advantageous. Thus, attempts have been made to learn from natural flyers like insects and birds. Natural flight is accomplished by flapping wings, and this idea has been proposed for certain types of MAVs …

Negotiating For Nature: Conservation Diplomacy And The Convention On Nature Protection And Wildlife Preservation In The Western Hemisphere, 1929--1976, Keri Lewis

Doctoral Dissertations

In 1941, as the United States entered the Second World War, leaders from twenty American nations signed into effect a broad-based treaty for the protection of migratory wildlife at the Convention on Nature Protection and Wild Life Preservation in the Western Hemisphere. This dissertation examines the unique set of questions, problems, and concerns framers of the Convention dealt with in the development of a conservation program to ensure the protection of migratory wildlife as it crossed political borders. Although it provided no solid system of enforcement, the provisions of the Convention opened the door for new, more specific conservation treaties …

Gene Synthesis, Cloning, Expression, Purification And Biophysical Characterization Of The C2 Domain Of Human Tensin, Kiran Sukumar Gajula

Doctoral Dissertations

Tensin is a large "docking" protein found in the adhesive junctions of animal cells and recruited early in the development of cell-substrate contacts. There it binds to the cytoplasmic domain of integrin β1 and caps the barbed ends of filamentous actin. This forms a rational basis for its implication in a direct role in the mechanics of membrane-cytoskeleton interactions. Tensin provides a physical link between the actin cytoskeleton, integrins, and other proteins at the cell-substrate contacts. Its overall biochemical properties are a function of its domain composition and architecture, i.e., the domains that are present and their relative positions in …

Development Of Self-Assembled Monolayer-Based Cell Culture Platform Towards Fabrication Of A Three-Dimensional Bioreactor, Rajendra Kandoor Aithal

Doctoral Dissertations

The extracellular matrix (ECM) plays an important role in regulating a number of cellular properties and functions like cell differentiation, cell synthesis and degradation, cell viability and proliferation, cell function, and cell aging. Surface modification of planar substrates with self-assembled monolayers (SAMs) is a promising technique to achieve stable ECMs.

In this work, substrates such as silicon (Si), gallium arsenide (GaAs) and indium tin oxide (ITO) substrates were modified with SAMS containing amino (-NH2), methyl (-CH3), thiol (-SH) and carboxylic (-COOH) end groups and characterized using contact angle measurements, surface infrared (IR) spectroscopy and atomic force microscopy (AFM). Different cell …

The Taxonomic And Systematic Relationships Of Several Salt Marsh Fucus Taxa (Heterokontophyta, Phaeophyceae) Within The Gulf Of Maine And Ireland Examined Using Microsatellite Markers, Aaron L. Wallace

Doctoral Dissertations

The present thesis utilizes microsatellite markers to examine genetic affinities between several salt marsh Fucus ecads in order to ascertain their relationships with attached parental species. Chapter I provides an introduction to the genus Fucus and discusses morphological plasticity, systematic difficulties, and studies of hybridization between different Fucus species.

Chapter II describes my development of microsatellite markers for Fucus. Four polymorphic microsatellite loci were used to determine the origin of a dwarf muscoides-like Fucus from the Brave Boat Harbor (ME) salt marsh. Similar forms were originally described in Europe, and appear to be derived from F. vesiculosus L. However, my …

Fabrication Of Cell Culture Scaffolds Using Micro/Nanotechnologies To Study The Attachment And Alignment Of Smooth Muscle Cells, Mengyan Li

Doctoral Dissertations

This dissertation elaborates the design and fabrication of in vitro cell culture scaffolds using microfabrication and electrostatic layer-by-layer self-assembly (LbL) technologies, and develops the so-called layer-by-layer lift-off (LbL-LO) technique to control surface topography, surface properties, and underlying architectures of the scaffolds. Smooth muscle cells were cultured on the fabricated scaffolds with gelatin, fibronectin, and polyelectrolytes (PSS, PDDA, PAH, and PEI) as surface materials, multilayer polyelectrolytes as architectures, deposited in strip- and square-patterns. It was found that the exposed surface materials, which have different charge, hydrophobicity, and chemical structure (e.g., amino acid sequence), affect the adhesion of smooth muscle cells. Cells …