<p dir="ltr">Neurodegenerative disease (ND) is a debilitating neurological disorder characterized by progressive loss of neurons in central nervous system (CNS), resulting in the decline in memory, cognition and motor functions. Alzheimer's disease (AD) and Parkinson's disease (PD) are the two of the most prevalent NDs, affecting millions of individuals in the United States. While hundreds of genetic risk factors have been identified in association with ND, familial cases with genetic origin only account for 10% and 15% of diagnosed AD and PD incidences, respectively. The majority of ND cases occur sporadically. Mounting evidence from epidemiology studies suggests that environmental stressors are one of the key ND associated risk factors where exposure to environmental stressors leads to the on-set of ND years or decades later. Little is known about the molecular mechanism facilitating the establishment of the persistent and potentially permanent neurotoxic state after exposures, particularly at a developmental stage. Hence, there is a pressing need in understanding the cellular machineries involved in establishment of a persistent neurotoxic state resulting from early-life exposure to environmental toxins. Subcellular compartments are crucial for the maintenance of neuronal homeostasis. Alterations in various subcellular compartments, including the nucleus, mitochondria, and lysosomes, have been commonly noted in cases of AD and PD; and are believed to play a crucial role in the establishment of a persistent neurotoxic state. The primary goal of my thesis is thus to uncover the dysregulation in multiple subcellular compartments and their contributes to ND pathogenesis induced by early-in-life exposure to environmental stressors, including atrazine (ATZ), per-and polyfluoroalkyl substances (PFAS), and neurofibrillary tangles.</p><p dir="ltr">I started by developing live-cell compatible tools to track cellular and sub-cellular changes. Mitochondria DNA methylation is of particular interest, due to its potential regulatory role in the expression of electron transport chain (ETC) subunits and thus mitochondrial activity. Thus, I started expanding the mitochondria probe tool set by designing a novel probe targeting methylated CpGs of mitochondrial DNA (mtDNA). We demonstrated the capability of our probe to reveal spatial distribution of methylated mtDNA and capture mtDNA methylation change at single cell level. Combined with our previously developed probe for nuclear DNA methylation, we monitored mtDNA and nuclear DNA methylation simultaneously on the single-cell level where unsynchronized dynamics of DNA methylation from nucleus and mitochondria were discovered.</p><p dir="ltr">Our tool offers a unique opportunity to understand epigenetic regulation of mtDNA and its dynamic response to microenvironment and cellular changes. Later, I further extended these efforts to develop in situ probes for tracking the formation of tau aggregates based on fluorescence resonance energy transfer (FRET); and demonstrated the superior performance of our engineered probes compared to the current state-of-the-art.</p><p dir="ltr">I explored two neuronal culture systems, namely SH-SY5Y- and human induced pluripotent stem cell (hiPSC)-derived neurons; and their feasibility in studying neurotoxic effects of developmental exposure to environmental stressors. Specifically, I used SH-SY5Y derived neuron-like cells to study the impact of pre-differentiation exposure to PFOA, abundant chemical in environment due to its historical uses in consumer products and industrial applications. hiPSC-derived neurons were used to study the effects of developmental exposure to ATZ. Both studies identified cellular changes, for example neurite morphology and expression of enzyme catalyzing the production of neurotransmitters, that last after completion of differentiation. We also identified changes of pathogenic markers aligning with increased PD risks associated with developmental PFOA and ATZ exposure. Compared to SH-SY5Y, hiPSC-derived neurons were more advantageous due to their ability to recapitulate neuronal activity and pathogenic changes related to ND, and thus were used in my follow-up studies.</p><p dir="ltr">I adopted hiPSC derived neuron model to study the molecular mechanism of ND using established ND etiology. Patients with neurodegenerative disorders (ND) exhibit varying levels and temporal patterns of aggregated β-amyloid (Aβ) and tau protein. We exposed neurons derived from hiPSC with preformed fibrils (PFFs) of Aβ, tau and Aβ+tau, respectively. These treatments result in significant alterations in neurite network morphology, nuclear morphology, chromatin compactness and synaptic density. Interestingly, Aβ and tau fibrils seem to have opposite effects on mitochondrial membrane potential on neurites. Increased quantity of lysosomes was found in neurons treated with Aβ, tau and Aβ+tau, while decrease of lysosomal acidity was only observed in neurons treated with Aβ and tau sequentially. Collectively, our data suggests the potential synergy between Aβ and tau in establishing a neurotoxic state.</p><p dir="ltr">In summary, my thesis work has developed enabling engineering tools to monitor cellular and subcellular changes in neurons; identified hiPSC-derived neurons as a promising platform for studying developmental neurotoxicity; and paved the way towards understanding multi-etiology and its molecular underpinning for ND.</p>

This study is focused on the challenges in puzzle video games. Based on several previous studies, the researcher created seven different types of challenges in puzzle games. To study the key of challenging levels in puzzle games, three games were chosen, then walkthrough videos of these games were watched and challenges were noted and categorized into different types. The collected data showed that different puzzle games have different challenge types while abstract reasoning is the most common challenge in every puzzle game. The total challenge numbers and pacing in puzzle video games strongly depend on the design intention of the game. And The number of challenge types has no direct connection with difficulty. The category of seven types of challenges and the results of this study may bring reference and inspiration to future studies. It may also shed some light on puzzle game design.

Streets provide the framework of a city and they are necessary for human life. Some underlying patterns of street networks cannot be directly recognized by people. In this study, topological analysis of urban street networks was adopted to build up new insight into urban morphology. Space syntax, which has been integrated into GIS, was applied for the analysis of spatial configuration, and fifty Swedish cities were chosen as samples to uncover various urban patterns. Street connectivity was the focus of the analysis and axial lines were the main analytical tools. The aim of this study was to hierarchically represent the cities’ streets and classify the sample cities into different types by urban morphology. Street data for Swedish cities were collected from OpenStreetMap. ArcGIS 10, with the Axwoman extension, provided a platform to carry out the topological analysis. Natural roads, axial lines and space syntax parameters were generated automatically with the functions of Axwoman. Hierarchical levels of streets were visually represented and the underlying pattern of each city was gotten from the hierarchical representation. Based on street hierarchy, the fifty sample cities were classified into nine groups, wherein cities of the same group had uniform hierarchical levels. Using the hierarchical pattern of each group’s axial lines, the nine city groups were further reclassified into three types. It was found that, for the street network of most sample cities represented with axial lines, not more than 40% of their streets have connectivity larger than the average value. The hierarchical representation also revealed that streets with high connectivity, which provide greater accessibility, were only minorities in the sample cities. Moreover, minor streets with high connectivity were almost distributed in city centers. In some of the studied cities, axial lines made better representation of the hierarchical patterns of streets, while in others, it did not provide a suitable way of uncovering urban patterns compared to natural roads. A limitation of axial lines manifested in this study was that it chopped curved roads into several segments, thus, disrupting the continuity of streets. In general, axial lines can provide a way to uncover urban patterns. They have meaningful effect to city residents and these patterns can help people gain better understanding of the urban structure. In addition, the hierarchical patterns of streets can be used to model pedestrian and traffic flows, predict crime occurrences, and make spatial plans. The hierarchical representation of streets can also contribute to people’s wayfinding performance.

InAs/InP multiwavelength quantum dash lasers are promising solutions to rising data loads in our telecommunications systems, as one laser chip can replace many lasers operating at a single wavelength. Quantum dashes are quasi-one-dimensional nanoparticles that offer equal or increased performance as laser gain media when compared to equivalent quantum well devices. InAs/InP quantum dashes are ideal for laser devices emitting in the C-band region, centred around 1550 nm. The quantum dashes in this thesis are epitaxially grown via the self assembled Stranski-Krastanow mode. Characterizing how structure and composition of these quantum dashes affect the energy level spacing and emission wavelengths is crucial for designing better performing telecommunications lasers. In this thesis a method for determining the average heights and widths of these nanoparticles from atomic force microscopy measurements of uncapped InAs/InGaAsP/InP quantum dashes is developed. Single quantum dash simulations are built in Crosslight Photonic Integrated Circuit Simulator (PICS3D) with the lowest energy transition tuned to photoluminescence peak wavelengths provided by National Research Council Canada. These simulations are used to determine the impact of quantum dash dimensions, compositions, and heterostructure changes to the overlap integrals and emission energies. Phosphorus concentration within the quantum dash and wetting layer can modify the predicted emission wavelength by ∼200 nm, and increasing quantum dash lengths beyond 200 nm has negligible effect on emission energy and energy level spacing. The sublayer thickness is increased from 0.1 to 1 nm, and shows that emission energy will increase for GaP sublayers and decrease for GaAs sublayers by up to 30 meV. The role of the wetting layer on energy level spacing is discussed and determined to increase the emission energy by ∼15 meV when the 0.5 nm wetting layer is removed for a 2 nm quantum dash. The role of As/P intermixing is investigated in three ways: by incorporating phosphorus concentration in (1) the quantum dash and wetting layer, (2) the wetting layer, and (3) the lower portion of the quantum dash without a wetting layer. There is negligible change in the overlap integral for these three cases with all other variables held constant, and the trends between each case remain the same. Further experimental analysis of buried InAs quantum dashes is recommended for compositional information. The implementation of variable strain profiles in this model is also recommended, in addition to developing vertically coupled quantum dash simulations. Finally, performing these simulations at varying temperatures will better represent the operating conditions of quantum dash lasers.

While the adverse health risks associated with smoking have been well-documented, few studies have examined the cardiovascular outcomes associated with secondhand smoking. The purpose of the study was to assess the distributions and association of cardiovascular diseases (CVDs) in nonsmokers exposed to secondhand smoke (SHS). Data were extracted from the National Health and Nutrition Examination Survey (NHANES) 2015-2016 cycle. Self-reported smoking status and cotinine levels were used to identify exposure groups (smokers, nonsmokers, and secondhand smokers), and medical history of several cardiovascular diseases such as coronary heart diseases and stroke were also collected via self-report survey. The association between exposure to SHS and seven cardiovascular outcomes were analyzed using chi-square analysis and odd ratios (OR) with 95% confidence intervals (CIs) were calculated using two logistic regression models. The data included 5,709 subjects including 18.5% smokers, 23.6% secondhand smokers, and 57.9% nonsmokers. There was statistically significant association between exposure to SHS and only two out of seven cardiovascular outcomes, hypertension (OR 1.554, 95% CI [1.066, 2.265]) and cholesterol levels (OR 1.213, 95% CI [1.017, 1.446]). This study is one of the first to determine an association between SHS and seven cardiovascular outcomes, thus highlighting the importance of reducing SHS exposure and can be used for further research on SHS and cardiovascular health.

Creation of semi-insulating layers in SiC is highly desirable for high voltage device fabrication. Specifically PiN diodes can be fabricated with a compensated semi-insulating layer that would be capable of blocking a large reverse voltage. Semi-insulating (SI) behavior in SiC has been traditionally achieved via passivation of shallow dopants with vanadium-related deep levels. Degraded electrical properties of SiC devices result from the use of vanadium compensated SiC because unintentional formation of additional defects due to vanadium segregation and stress generation in the material occur. In this work, the possibility of low doped or SI epilayers via engineering of the boron related defects in SiC is investigated. High temperature treatment (up to 2000°C) of boron doped samples is used to stimulate boron diffusion and formation of deep boron centers in concentration sufficient for compensation of shallow dopants, without simultaneous formation of undesirable shallow boron levels. High temperature annealing of both epitaxial layers in-situ doped with boron and boron implanted 4H-SiC is investigated. The possibility of diffusion from highly boron doped substrate is also investigated. The diffusion profiles are modeled and the diffusion coefficients extracted to give information about diffusion mechanisms. The boron D-center was observed using photoluminescence (PL) after high temperature annealing of the implanted samples. Clear temperature dependence of the creation of the D-center was observed. Compensated material was revealed after an Inductively Coupled Plasma (ICP) etch on an epi-over grown sample.

10,291 participants, aged 20 to 85 years of age, available from the 1999 through 2002 NHANES databases participated in this study. Only 8,485 (82%) of these participants were included in the data analysis. Participants who were pregnant (n = 603), not examined at a mobile examination center (n = 820), or had missing values for height (n = 164) and/or weight (n = 125) were eliminated. Individuals were classified into four groups (underweight, normal, overweight and obese) based on body mass index (BMI). Variables measured in the study included body mass index, physical fitness, dietary folic acid, c-reactive protein, homocysteine, folate, serum total cholesterol, serum triglycerides, HDL-C, and glucose. All data was collected at Mobile Examination Centers (MEC). The results of the present study showed that being overweight and obese were associated with a poor serum lipid profile, higher serum glucose levels, lower participation in physical activity and a lower physical fitness level. Being overweight and obese was also associated with higher serum levels of inflammatory markers for cardiovascular disease (CVD). Overweight and obese individuals are also being diagnosed with coronary heart disease (CHD) at a younger age.

Retention and matriculation are topics of heavy debate and inquiry in higher education as rising tuition costs, coupled with declining state support, have fueled the need for increased accountability. In Mississippi, few studies have been conducted that are unique to the public universities in the state in order to analyze success factors in higher education. The purpose of this study was to analyze these success factors at Mississippi’s public universities as measured by successful degree completion within a six-year time period. This study analyzed High School GPA, ACT Scores, Parental Income Levels, Parental Education Levels, Ethnicity, and Gender. Academic, demographic and socioeconomic data were gathered on two cohorts of resident first-time, full-time students attending a Mississippi Institution of Higher Learning. A total of 5,603 students were included in the study from the fall 2001 and 2002 semesters. Transfer students were not included in the study. A successful completer was defined as completing a bachelor’s degree within six-years of enrollment. Students still enrolled in the seventh year were not included. In addition, students seeking an Associate’s Degree were also not included. Descriptive statistics revealed that graduation rates fluctuated depending on high school GPA, ACT scores, income and parental education levels. The most significant differences in graduation rates occurred when analyzing high school GPA and income statistics. These findings were supported when logistic regression analysis was employed. Logistic regression analysis was used to analyze these factors compared to graduation rates for the state, and by type of institution. In Mississippi, there are four regional universities and four research universities. High school GPA and parental income were significant predictors in all three models, while ACT was significant when analyzing data for the system. For research universities, the education level of the father was significant. For regional universities, ethnicity was a significant predictor. In all, universities should develop a deeper understanding of the socioeconomic background of students in order to ensure that proper scaffolding is in place to ensure successful matriculation.

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