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Nanotube Spectral Fingerprinting And Machine Learning For Optimized Bioimaging/Sensing Applications, Aceer Nadeem

Open Access Dissertations

This thesis presents a multifaceted exploration of the optimization and application of single-walled carbon nanotubes (SWCNTs) in biomedical contexts, with a specific focus on enhancing their stability, functionality, and use as optical biosensors. The research spans several key areas, including the development of innovative techniques that couple machine learning with spectral fingerprinting for advanced diagnostics, the investigation of SWCNT chirality and its implications for cellular interactions, and the optimization of lyophilization processes to improve long-term stability and reproducibility.

The first section of the thesis delves into the fundamental properties of SWCNTs, emphasizing their unique electronic and optical characteristics. These properties, …

Chemical Investigation Of Metabolites Produced By Marine Pseudoalteromonas Spp., Margaret Rosario

Open Access Dissertations

In natural environments, bacteria are surrounded by other organisms such as eukaryotic phytoplankton and other bacterial species. Specialized metabolites are encoded within bacterial genomes and are expected to play a large role in mediating interactions with other cells. Furthermore, chemical communication in bacterial communities is a key component to controlling group behaviors including virulence. Marine Pseudoalteromonas spp. Produce a plethora of specialized metabolites, suggesting a reliance on the biosynthesis, secretion, and response to chemical cues. This dissertation explores the prevalence and function of signaling molecules and specialized metabolites produced by two species of Pseudoalteromonas.

The first study, which is …

Probing Interactions Of Single-Walled Carbon Nanotubes At The Nano-Bio Interface, Mitchell Gravely

Open Access Dissertations

Non-covalent hybrids of single-stranded DNA and single-walled carbon nanotubes (DNA-SWCNTs) have demonstrated applications in biomedical imaging and sensing due to their enhanced biocompatibility and photostable, environmentally-responsive near-infrared (NIR) fluorescence. Significant progress has been made in developing robust biological probes based on the sensitive optical properties of SWCNTs, however biological environments introduce complex and dynamic conditions that interact with, and ultimately modulate, their intrinsic properties. These fundamental interactions within biological settings can determine whether a nanomaterial is biocompatible and robust, or cytotoxic and disruptive to biological processes. Thus, a mechanistic understanding of such interactions and their effect on cellular function is …

How Landscape Change Affects Commercial And Recreational Fishermen’S Perceptions And Place Meanings, Talya Syvann Ten Brink

Open Access Dissertations

It is critical to plan for environmental change in order to mitigate its adverse effects on human wellbeing. This series of manuscripts examines the impacts of landscape change on commercial and recreational fishermen. Each manuscript provides a unique perspective on place meaning and place change. Using a mixed methods approach, data were collected and analyzed on fishermen’s perceptions of familiar places and on the changes that these places undergo. The first manuscript investigates the impact of offshore wind farms on commercial and recreational fishermen, using the first offshore wind farm in North America – the Block Island Wind Farm (Rhode …

The Characterization Of Xanthene Dyes On A Glass Substrate From Different Coating Techniques, Elsa Ortega

Open Access Dissertations

Chapter 1 of this dissertation is an investigation of rhodamine 560 (Rh560), a cationic dye similar to the well-studied rhodamine 6G (Rh6G). The spectral properties of Rh560 and Rh6G have similar changes as a function of thickness. At low surface coverage the spectra indicate monomers, at 1-2 monolayers dimers dominate, and thicker films show larger aggregates. The difference between Rh6G and Rh560 is that the transition from monomer to dimer occurs at different thickness, ~1.2 nm for Rh6G and ~0.5 nm for Rh560. This difference is accounted for by the molecular size. Chapters 2 and 3 describe photophysical investigations of …

Chemical Synthesis, Characterization And Biological Evaluation Of Methylation And Glycation Dna Adducts, Qi Tang

Open Access Dissertations

The integrity of genomic DNA is constantly challenged by endogenous and environmental agents with the formation of DNA adducts. Some of these adducts are toxic and mutagenic to replication, thus potentially leading to cancer and other genetic diseases. To counteract the undesired DNA modifications from damaging agents, cells have evolved a number of repair pathways, such as base-excision repair, nucleotide-excision repair, mismatch repair, and direct reversal repair, to restore the intact DNA. However, DNA repair is not always efficient, there are many interfering factors, such as inherited deficiency in DNA repair pathways, or the abnormal uptake of substance with inhibitory …

Dietary Polyphenols And Their Gut Microbiota Metabolites As Potential Treatments For Alzheimer's Disease, Kenneth N. Rose

Open Access Dissertations

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that has no cure, no therapies to stop the disease progression, and limited palliative care options. As the 6th leading cause of death in the United States, it is necessary to discover therapeutics which can alter disease progression to alleviate the burden on patients, caregivers, and healthcare systems. In the search of therapeutics for AD, dietary polyphenols have become the topic of research as epidemiological evidence suggests that exposure to dietary polyphenols, such as a Mediterranean diet, over one’s life, reduces the risk of dying from AD. Additionally, evidence from rodent models …

Caged Molecules Released From Capsules: Photochemical And Photophysical Studies Of Coumarin Triggers, Nareshbabu Kamatham

Open Access Dissertations

This thesis comprises a detailed investigation on the photochemical and photophysical properties of various organic molecules encapsulated in molecular containers. Exploiting these photochemical and photophysical properties of fascinating organic molecules are often frustrating and tricky as they tend to get influenced by several environmental factors. For instance, in the solution phase, solvent can influence the properties of short-lived and reactive intermediates that are generated upon excitation. In order to control these properties, one of the promising approaches is to encapsulate them in an inert and confined environment. This strategy involves the encapsulation of the desired molecule in a stable enclosure, …

From Pieces To Paths: Combining Disparate Information In Computational Analysis Of Rna-Seq., Yifan Yang

Open Access Dissertations

As high-throughput sequencing technology has advanced in recent decades, large-scale genomic data with high-resolution have been generated for solving various problems in many felds. One of the state-of-the-art sequencing techniques is RNA sequencing, which has been widely used to study the transcriptomes of biological systems through millions of reads. The ultimate goal of RNA sequencing bioinformatics algorithms is to maximally utilize the information stored in a large amount of pieced-together reads to unveil the whole landscape of biological function at the transcriptome level. Many bioinformatics methods and pipelines have been developed for better achieving this goal. However, one central question …

Understanding The Molecular Mechanism Of Arsenic Tolerance And Accumulation In Pteris Vittata, Chao Cai

Open Access Dissertations

Arsenic is a toxic metalloid that is naturally occurring and widely distributed. The consumption of arsenic-contaminated food and water is threatening the health of millions of people in the world. The fern Pteris vittata is unusual in its ability to tolerate and hyperaccumulate exceptionally high concentrations of arsenic in its fronds. How P. vittata tolerates and accumulates arsenic is fundamentally different from that in angiosperms; however, the molecular mechanism underlying this trait in P. vittata is not well-defined. Because the haploid phase of the fern (the gametophyte) is morphologically simple, easy to grow and also tolerates and hyperaccumulates arsenic, the …

Hemodynamic And Hormonal Responses To An Exercise Test In Parkinson's Disease Patients Without Orthostatic Hypotension, Kirk B. Roberson

Open Access Dissertations

The aim of this investigation was to examine how heart rate, hemodynamics, and norepinephrine are affected by an exercise stress test in Parkinson’s disease (PD) patients. Fourteen individuals with PD (mean age, 68±12 yrs; Hoehn and Yahr stage 1-3) and sixteen healthy individuals (mean age, 66±7 yrs) performed a sub-maximal exercise test on a cycle ergometer. Heart rate (HR), norepinephrine (NE), blood pressure (BP), and other hemodynamic variables including cardiac output (Q), stroke volume (SV), systemic vascular resistance (SVR), and end-diastolic volume (EDV) were measured in a fasted state during supine rest, active standing, exercise, and supine recovery in all …

Physical Characterization Of Warburg Effect In Cancer Cells, Da Wei

Open Access Dissertations

Cancer is the second leading cause of death in the United States after heart disease. Because the frequency of cancer diagnoses is correlated with life expectancy, we can expect the rate of cancer diagnosis to increase with the increase of life expectancy. Additionally, cancer treatments are notoriously costly and challenging due to the heterogeneity of the cancer cell population. For these reasons, devising methods to study the characteristics, efficiently diagnose and treat cancer is extremely important.

Warburg effect has been considered as the most unique mechanism that differ cancer cells from normal cells. Normally, most of the healthy cells predominantly …

The Evolution Of The Krüppel-Like Factor Gene Family And Their Function During Embryonic Development In The Ctenophore Mnemiopsis Leidyi, Jason Scott Presnell

Open Access Dissertations

How modifications during development influence large-scale evolutionary changes is a major emphasis in the field of evolutionary developmental biology (evo-devo). Comparing the underlying cellular and molecular basis of development in diverse organisms can provide insight into how alterations of these processes contribute to morphological diversity. Ctenophores, or comb jellies, are a phylum of marine invertebrates and, due to their unique phylogenetic position as one of the earliest branching lineages of extant animals, are an ideal system for investigating the origin and evolution of metazoan character traits. For example, the animal through-gut is thought to have originated in the metazoan stem …

Role Of An Upwelled Coastal Area In Northeastern Colombia In The Distribution, Population Dynamics And Genetic Diversity Of The Migratory Habitat-Shifting Chelonia Mydas, Catalina Vasquez Carrillo

Open Access Dissertations

The Caribbean is generally an oligotrophic sea; however, in the southern portion between Venezuela and Colombia, a yearly, moderate, coastal upwelling fuels a very productive marine ecosystem, the Southern Caribbean Upwelling System. Extensive submerged aquatic vegetation (SAV) ecosystems are found in the Colombian side of the system, by La Guajira peninsula. SAV ecosystems constitute key habitat for multiple marine fauna species, specially at juvenile/larval stages. La Guajira’s SAV unique, upwelled ecosystems are hypothesized as important foraging and developmental habitat for the endangered, migratory sea turtle Chelonia mydas. The complex habitat-shifting behavior and very long-lasting juvenile stage traits of the species …

Development Of Novel Proteomic Strategies To Dissect Plant Phosphoproteomic Signaling Under Environmental Stresses, Chuan-Chih Hsu

Open Access Dissertations

Protein phosphorylation is one of the important signaling mechanisms in plants which transduces environmental stimuli such as salinity, microbes, and hormones into intracellular signals and activates plant defense mechanisms. Thus, understanding the correlation between environmental stresses and alteration of plant phosphorylation requires system-wide phosphoproteomic analysis, which includes identification of kinase-substrate complexes and measurement of phosphorylation-mediated signaling changes. However, identification and quantification of plant phosphoproteome remains challenging due to the highly dynamic nature of plant proteome, interferences of cell wall, pigments, and secondary metabolites. Recently, mass spectrometry (MS) has been integrated with phosphopeptide enrichment approaches for identifying thousands of phosphorylation sites …

Design And Statistical Analysis Of Mass Spectrometry Imaging Experiments, April Janae Harry

Open Access Dissertations

The goal of mass spectrometry-based imaging (MSI) is to characterize the chemical composition of biological samples such as tissues in spatial resolution, and changes in the composition between conditions such as the status of a disease. A single mass spectrometry image is a collection of mass spectra at gridded locations on a tissue. When acquired over multiple biological individuals, tissues, and conditions, the resulting datasets are tremendously complex in both scale and in the stochastic structure of the quantified spectral features. Accurate characterization of the biological and technical variation in these experiments is therefore key for deriving sensitive and reproducible …

Imaging Cholesterol Metabolism And Trafficking By Stimulated Raman Scattering Microscopy, Hyeon Jeong Lee

Open Access Dissertations

Cholesterol is an essential component of mammalian cells which is tightly regulated. However, our understanding of cholesterol transport and metabolism is still incomplete, partly due to lack of suitable tools for studying cholesterol dynamics in living cells and organisms with spatio-temporal information. My dissertation work applied spectroscopic imaging of cholesterol in human tissues, living cells, and model organisms to unravel new insights of cholesterol metabolism and trafficking. Using stimulated Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues, we observed an aberrant accumulation of cholesteryl ester in metastatic lesions. Inhibition of cholesterol esterification in prostate cancer cells …

Wavetda: Bayesian Statistics, Wavelets And Topological Data Analysis To Title Assess Statistical Shape, Patrick S. Medina

Open Access Dissertations

Advanced imaging and scanning technologies are providing an abundance of shape-based data that require novel approaches to understand the factors that generate them. This is especially true in modern agricultural practices where large quantities of highly detailed morphometric data are collected and used for studying genetic associations. Toward this end there is an immediate need for efficient algorithms that extract relevant geometric information from images in a form that can be used within a statistical framework. Topological Data Analysis (TDA) has shown to be both fast and effective for studying complex shapes, and can simultaneously reduce dimensionality into simpler topological …

Modulation Of Bcr Signaling By The Induced Dimerization Of Receptor- Associated Syk, Mark L. Westbroek

Open Access Dissertations

Clustering of the B cell antigen receptor (BCR) by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, I developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, I fused SYK with E. coli dihydrofolate reductase (eDHFR), which binds the small molecule trimethoprim (TMP) with high affinity and selectivity, and synthesized a dimer of TMP with a flexible linker. The binding of …

Photoactivatable Bodipys For Bioimaging Applications, Yang Zhang

Open Access Dissertations

Self-assembling nanoparticles of amphiphilic polymers can transport hydrophobic molecules across hydrophilic media and, as a result, can be valuable delivery vehicles for a diversity of biomedical applications. We designed molecular guests with photoactivatable fluorescence for these supramolecular hosts and demonstrated that the activation of the fluorescent cargo, under optical control, permits the tracking of the nanocarrier translocation across hard and soft matrices with the sequential acquisition of fluorescence images. In addition, the supramolecular delivery of these photoactivatable probes into the cellular blastoderm of Drosophila melanogaster embryos allows the real-time visualization of translocating molecules with no detrimental effects on the developing …

Error Resilient Video Coding Using Bitstream Syntax And Iterative Microscopy Image Segmentation, Neeraj Jayant Gadgil

Open Access Dissertations

There has been a dramatic increase in the amount of video traffic over the Internet in past several years. For applications like real-time video streaming and video conferencing, retransmission of lost packets is often not permitted. Popular video coding standards such as H.26x and VPx make use of spatial-temporal correlations for compression, typically making compressed bitstreams vulnerable to errors. We propose several adaptive spatial-temporal error concealment approaches for subsampling-based multiple description video coding. These adaptive methods are based on motion and mode information extracted from the H.26x video bitstreams. We also present an error resilience method using data duplication in …

Early Parental Loss, Socioeconomic Stressors, And Health In Later Life: Evidence For Gender Disparity, Rong Fu

Open Access Dissertations

Drawing from the stress process model and the cumulative disadvantage theory, this dissertation examined how childhood and later life stressors affected cognitive and subjective health in older adults. Using three main articles, this dissertation investigated (1) the effect of early parental loss on cognitive well-being in Chinese oldest old; (2) the effect of intergenerational socioeconomic mobility on cognitive and subjective health in advanced age; and (3) the effect of different dimensions of socioeconomic status and perceived financial strain on subjective health in later life. Data were derived from the 2002 and 2005 waves of the Chinese Longitudinal Healthy Longevity Survey. …

Affinity Cryo-Electron Microscopy: Methods Development And Applications, Guimei Yu

Open Access Dissertations

Single particle cryo-electron microscopy (cryo-EM) is an emerging powerful tool for structural studies of macromolecular assemblies. Although less concentrated and smaller amounts of samples are required for single particle cryo-EM compared to X-ray crystallography, it remains challenging to study specimens that are low-abundance, low-yield, or short-lived. The recent development of affinity grid techniques holds great promise to tackle these challenging samples by combining the sample purification and freezing on TEM grids steps in cryo-EM grid preparation into a single step, revolutionize the grid preparation of cryo-EM, and extend single particle cryo-EM to a routine structural biology tool to characterize structures …

Is Metabolism Goal-Directed? Investigating The Validity Of Modeling Biological Systems With Cybernetic Control Via Omic Data, Frank T. Devilbiss

Open Access Dissertations

Cybernetic models are uniquely juxtaposed to other metabolic modeling frameworks in that they describe the time-dependent regulation of cellular reactions in terms of dynamic "metabolic goals." This approach contrasts starkly with purely mechanistic descriptions of metabolic regulation which seek to explain metabolic processes in high resolution — a clearly daunting undertaking. Over a span of three decades, cybernetic models have been used to predict metabolic phenomena ranging from resource consumption in mixed-substrate environments to intracellular reaction fluxes of intricate metabolic networks. While the cybernetic approach has been validated in its utility for the prediction of metabolic phenomena, its central feature, …

Analysis Of Region-Specific Transcriptomic Changes In The Autistic Brain, Dmitry Velmeshev

Open Access Dissertations

Autism is a highly prevalent neurodevelopmental disorder that affects 1 in every 68 children in the US. Autism comprises a spectrum of highly heterogeneous disorders defined by characteristic deficits of communication and by presence of repetitive and stereotyped behavior. At the same time the disease is highly heritable and genetically heterogeneous, with hundreds of genetic variants that have been associated with it. Previous systems biology studies have provided first insights into convergence of various disease-associated genetic variants onto specific pathways, developmental windows and cell types in the brain. Additionally, transcriptomic and epigenetic studies have identified genes and pathways affected by …

Studies Of Nicotinic Acetylcholine Receptors Containing Α4 And Α6 Subunits In Nicotine-Induced Synaptic Plasticity In Brain Reward Areas, Staci Engle

Open Access Dissertations

Tobacco addiction is a serious threat to public health in the United States and abroad, and development of new therapeutic approaches is a major priority. Nicotine, the primary psychoactive compound in tobacco smoke, activates and/or desensitizes nicotinic acetylcholine receptors (nAChRs) throughout the brain. nAChRs in ventral tegmental area (VTA) dopamine (DA) neurons are crucial for the rewarding and reinforcing properties of nicotine. Nicotine causes cellular changes in VTA DA neurons, including the enhancement of AMPA receptor (AMPAR) function. This enhancement sensitizes the VTA to excitatory input and promotes drug seeking in animal models. However, which nAChR subtype(s) are responsible for …

Dissecting The Spatiotemporal Regulation Of Yeast Kinetochore Interactions, Kriti Shrestha Thapa

Open Access Dissertations

Kinetochores are conserved protein complexes that bind the centromeres in replicated chromosomes to the mitotic spindle and then direct their segregation. To better comprehend Saccharomyces cerevisiae kinetochore function, we investigated the phospho-regulated dynamic interaction between the conserved kinetochore protein Cnn1CENP-T, the centromere region and the Ndc80 complex through the cell cycle. Cnn1 localizes to kinetochores at basal levels from G1 through metaphase but accumulates abruptly at anaphase onset. How Cnn1 is recruited and which activities regulate its dynamic localization is unclear. We show that Cnn1 harbors two kinetochore-localization activities: a C-terminal histone-fold domain that associates with centromere region, and a …

Investigations On Biologically Active Carbohydrates From Natural Sources, Jiadong Sun

Open Access Dissertations

Complex carbohydrates exist in almost all species of plants, animals and microorganisms. Because of their physiochemical properties, they have been traditionally applied as emulsifiers and stabilizers in food, cosmetics, textiles and as pharmaceutical ingredients. Complex carbohydrates generally exist as a layer of thick, sequential, hydrous polymers consisting of monosaccharides and non-carbohydrate substituents such as acetate, pyruvate, and phosphate. While complex carbohydrates are generally believed to serve as structural support or energy sources for the producing organisms, their potential biomedical properties have been less investigated. Our understanding of the biological activities of complex carbohydrates is further complicated since most have been …

Study Of The Role Of Circulating Tumor Cells (Ctc) And Circulating Cellular Microenvironment Components In Metastasis Formation And Their Clinical Value, Zheng Ao

Open Access Dissertations

Circulating Tumor Cells (CTC) are tumor cells found in cancer patients’ peripheral blood. They hold significant clinical value for cancer prognosis and management. While enumeration of CTC has been proven to provide reliable prognosis value for cancer management, further molecular and functional characterization of CTC may provide insights into both the biology of metastasis and critical clinical information such as the dynamic changes in molecular expression of tumor cells during treatment. Here, we will discuss how molecular and functional characterization of CTC can be utilized for such clinical applications, and the methodology development for such applications including a thermo-responsive release …

Pathway To Autism Spectrum Disorders: Finding Patterns Of Common Genetic Variation Underlying The Complex Disorder, Yo Son Park

Open Access Dissertations

The field of genetics has witnessed a tremendous increase in the amount of information in the past decade resulting from genotyping and resequencing technologies. There has been an explosion in the development, application and optimization of statistical and computational methods to analyze these data. In particular, genome-wide scanning of common or rare genetic variants and their associations to a phenotypic trait has been successfully applied in several studies. For complex diseases such as Autism Spectrum Disorders (ASD), however, interrogating single locus associations by genome-wide association studies (GWAS) has been unable to unambiguously identify disorder causing genes. In this dissertation, an …