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Design And Synthesis Of Purine Based Neuroprotectors And Novel Synthetic Methods For The Trifluoromethylation Of Aldehyde Hydrazones, Puspa Aryal

Doctoral Dissertations

"Purine-derived compounds are widely investigated as cyclin-dependent kinase inhibitors that have broad applications in the design of pharmaceuticals for treating diseases, such as diabetes, atherosclerosis, and cancers. Towards the goal of effective AGE-inhibitors, and neuroprotector compounds we have synthesized a series of novel purine-based triazoles and investigated their neuroprotective effects, using SHSY-3Y human neuroblastoma cell line. Through these studies, we have identified purine-based neuroprotector compounds that favorably modulate oxidative stress induced by the Fenton reaction-generated reactive oxygen species (ROS).

The C(sp²−H)-trifluoromethylation of hydrazones would give access to the αtrifluoromethylated hydrazones that can serve as intermediates in the synthesis …

High Throughput Analysis To Study Emerging Pollutants And Nanoparticle Fate In Biological Systems, Xiaolong He

Doctoral Dissertations

”The increasing applications of emerging and fugitive contaminants (EFCs) and engineered nanoparticles (ENPs) attract significant research interest for their potential risks to human health and the environment. In order to assess the health risks of these emerging contaminants, rapid and reliable analytical methods to measure the concentrations and fates of these contaminants are imperative. This dissertation focuses on the developments of advanced analytical methods and their applications to study those emerging contaminants in crop plant and simulated gastric fluid (SGF). Three types of mass spectrometry based methodologies have been developed, one is freeze-thaw/centrifugation extraction followed by high performance liquid chromatography …

Multimodal Neuroscience Data Modeling And Inference, Sima Azizi

Doctoral Dissertations

“Mathematical models can be combined with deep learning and machine learning methods to provide new insights in neuroscience. The field of neuroscience is characterized by rich datasets that include fluid biomarkers, EEG signals, and advanced neuroimages. Recent advances in natural language processing have led to the opportunity to gain additional insights from rapidly growing text databases as well as electronic health records. In this research, we focus on applying computational intelligence methods to the analysis of three different complex data sources: blood levels of disease biomarkers, EEG signals from schizophrenic patients, and disease phenotypes encoded in electronic health records. First, …

Exposure Assessment Of Emerging Contaminants: Rapid Screening And Modeling Of Plant Uptake, Majid Bagheri

Doctoral Dissertations

"With the advent of new chemicals and their increasing uses in every aspect of our life, considerable number of emerging contaminants are introduced to environment yearly. Emerging contaminants in forms of pharmaceuticals, detergents, biosolids, and reclaimed wastewater can cross plant roots and translocate to various parts of the plants. Long-term human exposure to emerging contaminants through food consumption is assumed to be a pathway of interest. Thus, uptake and translocation of emerging contaminants in plants are important for the assessment of health risks associated with human exposure to emerging contaminants. To have a better understanding over fate of emerging contaminants …

An Investigation On The Regulation Of The Tweak–Fn14–Nf-Kb Pathway, Jawahar Khetan

Doctoral Dissertations

“Dysregulation of inflammatory pathways is strongly implicated in cancers and autoimmune diseases. The most consequential of these pathways involves the nuclear translocation of NF-kB, a transcription factor that induces the transcription of multiple proteins associated with cell survival, inflammation, proliferation and death. It is activated when the fibroblast growth factor-inducible 14 kDa protein (Fn14), a trimeric receptor recruits its ligand, TWEAK. Studies have shown that Fn14 is over-expressed in many tumors, the aggressiveness of which is often correlated with the degree of upregulation. Furthermore, TWEAK-Fn14 activation has been shown to result in persistent NF-kB activation. Using a mechanistic model of …

Critical Behavior In Evolutionary And Population Dynamics, Stephen Walter Ordway

Doctoral Dissertations

“This study is an exploration of phase transition behavior in evolutionary and population dynamics, and techniques for predicting population changes, across the disciplines of physics, biology, and computer science. Under the looming threat of climate change, it is imperative to understand the dynamics of populations under environmental stress and to identify early warning signals of population decline. These issues are explored here in (1) a computational model of evolutionary dynamics, (2) an experimental system of decaying populations under environmental stress, and (3) a machine learning approach to predict population changes based on environmental factors. Through the lens of critical phase …

Tools To Evaluate Nanodiamond-Mediated Delivery Of Tiopronin For Cataract Prevention, Justin Beltz

Doctoral Dissertations

”There is a growing demand for non-surgical means of cataract treatment. This dissertation presents three bodies of work that reflect the early-stage development of eye drop formulations aimed at delaying cataract progression. These formulations consist of the antioxidant 2-mercaptopropionylglycine (MPG) loaded onto nanodiamond particles.

Cataractogenesis is linked to oxidative damage to lens proteins. To investigate the potential of MPG for protection against oxidative damage, A549 cells were incubated in 0.6 mM tert-butylhydroperoxide (tBHP). Cells exposed to tBHP without MPG exhibited elevated levels of reactive oxygen species, which led to the depletion of the vital antioxidant glutathione and, ultimately, apoptosis. Co-administration …

Spatiotemporal Modeling And Model Restructuration Approaches In Studies Of Intracellular Signalling Pathways, Md Shahinuzzaman

Doctoral Dissertations

"The main focus of the research is to understand the complex phenomena of cell transduction pathways and cell biology in a single cell. Mathematical modeling and experimental evaluation are widely used approaches for this kind of research. Firstly, A multiscale framework for protein-protein interaction has been established using Brownian dynamics algorithm. Sit specific feature, steric collision, diffusion, co-localization and complex formation with time and space has been included in this spatial modeling framework. By implementation of the time adaptive feature in this framework, the computation time reduces in an order of magnitude compared with traditional modeling framework. This multiscale Brownian …

Machine Learning Techniques Implementation In Power Optimization, Data Processing, And Bio-Medical Applications, Khalid Khairullah Mezied Al-Jabery

Doctoral Dissertations

"The rapid progress and development in machine-learning algorithms becomes a key factor in determining the future of humanity. These algorithms and techniques were utilized to solve a wide spectrum of problems extended from data mining and knowledge discovery to unsupervised learning and optimization. This dissertation consists of two study areas. The first area investigates the use of reinforcement learning and adaptive critic design algorithms in the field of power grid control. The second area in this dissertation, consisting of three papers, focuses on developing and applying clustering algorithms on biomedical data. The first paper presents a novel modelling approach for …

Contributing Factors To Child Stunting In Guatemala: A Systems Analysis Focused On Enteric Disease Transmission And Mycotoxin Exposure, Lee Emerson Voth-Gaeddert

Doctoral Dissertations

"Child stunting -- low height-for-age -- is a United Nation's indicator for chronic malnutrition that has been linked to both acute and chronic health problems. Data from Guatemala suggests for children under five years of age, 49% are classified as stunted. This dissertation tests the following hypotheses, among children in Guatemala 1) environmental enteric dysfunction (EED) is correlated with height-for-age, 2) aflatoxin B (AFB) exposure is correlated with height-for-age, and 3) AFB exposure is correlated with EED. A network analysis was conducted on data from the US Agency for International Development (USAID) collected in 2012 to identify trends in a …

The Maculoprotective Effect Of A Thiol Antioxidant In Retinal Degeneration Models, Hsiu-Jen Wang

Doctoral Dissertations

"Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among adults, age 60 and older, in developed countries. While oxidative stress is implicated in the pathogenesis of AMD, clinical studies have shown that dietary antioxidants can delay progression of AMD. Currently, there is no FDA-approved treatment for AMD. Therefore, we hypothesized that N-acetylcysteine amide (NACA), a thiol antioxidant, would protect retinal pigment epithelium and impede the progression of retinal degeneration. The goal of this work was to evaluate the efficacy of NACA in preventing retinal pigment epithelial cell and photoreceptor death in AMD models. To achieve this, we …

A Functional Data Analytic Approach For Region Level Differential Dna Methylation Detection, Mohamed Salem F. Milad

Doctoral Dissertations

"DNA methylation is an epigenetic modification that can alter gene expression without a DNA sequence change. The role of DNA methylation in biological processes and human health is important to understand, with many studies identifying associations between specific methylation patterns and diseases such as cancer. In mammals, DNA methylation almost always occurs when a methyl group attaches to a cytosine followed by a guanine (i.e. CpG dinucleotides) on the DNA sequence. Many statistical methods have been developed to test for a difference in DNA methylation levels between groups (e.g. healthy vs disease) at individual cytosines. Site level testing is often …

Bioactivity/Cytotoxicity Of Micro-/Nano-Materials And Novel Development Of Fiber-Optic Probes For Single Cell Monitoring, Qingbo Yang

Doctoral Dissertations

"Manufactured nano-/micro-materials (MNMs) have been widely used and their interactions with niche biological environment are highly concerned for both of their biohazardous and bioactive effects, whereas no available comprehensive evaluations or regulations have been provided yet. This dissertation thus focuses on three major aspects: 1) fundamental toxicity understandings of a typical MNMs (zinc oxide nanoparticles), 2) bioactivity evaluations of representative bioactive MNMs, and 3) development of novel micro-probes for high spatial resolution monitoring. Firstly, the NP's concentration, irradiation, hydrodynamic size, and the localized pH, ionic strength, NP zeta-potential as well as dissolved oxygen levels were found correlated with the production …

Lifetime And Effectiveness Evaluation Of Ceramic Pot Filters, Carlo Salvinelli

Doctoral Dissertations

"Poor water quality is a major contributing factor to disease in developing countries. Ceramic pot filters (CPFs) represent an effective and sustainable technology for poor communities, but the characterization of CPF lifetimes is on-going, and the water production seems to be the limiting factor. This dissertation describes laboratory and field investigations conducted to characterize the parameters that impact CPF effectiveness and lifetime in terms of water production and treatment efficacy, both under controlled and real use conditions.

CPF initial flow rate is the most common quality control parameter, but it may not be representative of the long-term effectiveness of the …

Constitutive Activity In Orphan G Protein Coupled Receptors, Adam Lee Martin

Doctoral Dissertations

"The goal of this research was to use a distal signaling pathway analysis to evaluate the extent of agonist independent constitutive signaling among orphan class-A G protein coupled receptors (GPCRs). These receptors translate extracellular signals via conformational change into intracellular activation of different G proteins and subsequent second messenger synthesis. These small molecules regulate cellular biochemistry, eventually leading to nuclear signaling that results in changes in gene expression. Some GPCRs are capable of signaling in the absence of an activating ligand, a phenomenon called constitutive activity that is inhibited via an "inverse-agonist". The use of cAMP dependent Luciferase expression is …

Evolutionary Dynamics Of Speciation And Extinction, Dawn Michelle King

Doctoral Dissertations

Presented here is an interdisciplinary study that draws connections between the fields of physics, mathematics, and evolutionary biology. Importantly, as we move through the Anthropocene Epoch, where human-driven climate change threatens biodiversity, understanding how an evolving population responds to extinction stress could be key to saving endangered ecosystems. With a neutral, agent-based model that incorporates the main principles of Darwinian evolution, such as heritability, variability, and competition, the dynamics of speciation and extinction is investigated. The simulated organisms evolve according to the reaction-diffusion rules of the 2D directed percolation universality class. Offspring are generated according to one of three reproduction …

Effects Of N-Acetylcysteine Amide In Preventing/Treating Cataracts, Sri Krishna Yasaswi Maddirala

Doctoral Dissertations

"Cataract, the opacification of an eye lens, is a common pathological abnormality of the lens accounting for approximately 50% of all blindness. The only effective treatment currently available for a cataract is the surgical removal of the affected lens and replacement with an artificial lens for the restoration of vision. Although, cataract surgery is considered to be a very successful procedure in terms of visual outcome, the cost of surgery, need for trained personnel and surgeons, and postsurgical complications, limit the worldwide availability and accessibility of this procedure. Hence, alternative preventive and treatment procedures are worthy of investigation. The lens …