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Defining Replication-Coupled Chromatin Assembly Pathways And Their Effect On Silencing And Responses To Dna Damage In Saccharomyces Cerevisiae, Tiffany J. Young
Defining Replication-Coupled Chromatin Assembly Pathways And Their Effect On Silencing And Responses To Dna Damage In Saccharomyces Cerevisiae, Tiffany J. Young
Open Access Dissertations
The genetic information of a cell is organized in a DNA and protein structure referred to as chromatin. Chromatin consists of repeating units called nucleosomes, which consists of 147 base pairs of DNA wrapped around an octamer of histone proteins. These histone proteins are post-translationally modified at specific residues that are important gene regulation and genomic stability. Altered histone modification patterns are strongly associated with multiple cancers, underlying the importance of better understanding the pathways that regulate these modifications. During DNA replication, chromatin must be disassembled, and then reassembled behind the replication fork. Defects in this process can cause alterations …
Scalable Bayesian Nonparametrics And Sparse Learning For Hidden Relationship Discovery, Shandian Zhe
Scalable Bayesian Nonparametrics And Sparse Learning For Hidden Relationship Discovery, Shandian Zhe
Open Access Dissertations
Real-world data often encompass hidden relationships, such as interactions between modes in multidimensional arrays (or tensors), subsets of features correlated to specifc responses, and associations between heterogeneous data sources. Uncovering these relationships is a key problem in machine learning and data mining, and relates to numerous applications ranging from information security to imaging genetics and to computational advertisement. However, to mine these relationships, we have to face several signifcant challenges. First, how can we design powerful models to capture the complicated, potentially highly nonlinear patterns in data? Second, how can we develop effcient model estimation algorithms to deal with real-world …
The Regulation Of Calcium Oscillations In Porcine Eggs At Fertilization, Lu Zhang
The Regulation Of Calcium Oscillations In Porcine Eggs At Fertilization, Lu Zhang
Open Access Dissertations
As the most abundant mineral in organisms, ionized calcium (Ca2+) plays a crucial role in cellular signaling, regulating a great number of physiological activities. In this study, the Ca2+ entry mechanism that sustains the long-lasting Ca2+ oscillations in fertilized pig eggs was investigated. Porcine eggs matured in vitro were used for the experiments. In some eggs, the intracellular Ca2+ stores were depleted using cyclopiazonic acid (CPA, a SERCA pump blocker), others were inseminated with boar spermatozoa. To identify the mechanism that mediates the Ca2+ influx, various inhibitors of store-operated Ca2+ entry (SOCE) were used. We found that the inhibitors blocked …
Investigation And Analysis Of The Effects Of Manual Lifting And Carrying Activities On Postural And Gait Stability In Normal Subjects, Mohammed Alamoudi
Investigation And Analysis Of The Effects Of Manual Lifting And Carrying Activities On Postural And Gait Stability In Normal Subjects, Mohammed Alamoudi
Open Access Dissertations
Manual material handling (MMH) contributes to a large percentage of musculoskeletal disorders. Examples of its fundamental activities are lifting and carrying tasks that can be accomplished in several strategies, with each one imposing different types of stresses on the musculoskeletal system. These types of stresses may perturb the stability of the human body and may cause falls. Therefore, the goal of this study was to investigate the effect of MMH tasks on postural and locomotion stability using motion capturing system. Postural and dynamic stability were measured using new stability measures that were introduced in this study. A point inside the …
C-Jun Dna Binding During Axon Regeneration, Matt C. Danzi
C-Jun Dna Binding During Axon Regeneration, Matt C. Danzi
Open Access Dissertations
Axons in the Peripheral Nervous System are able to regenerate after injury, unlike axons in the Central Nervous System. We examined the Dorsal Root Ganglion (DRG) model of Peripheral Nervous System axon regeneration. First, we surveyed the transcriptomic response of DRG neurons to peripheral axotomy as measured by several different RNAseq experiments and examined which transcriptional regulators drive that response. We found that independent RNAseq experiments can yield highly replicative results at both the levels of differentially expressed genes as well as transcription factor regulators when the data sets are properly normalized. Next, we used chromatin immunoprecipitation followed by high-throughput …
A Combinatorial Approach To Cns Regeneration Using Activated Transcription Factors, Saloni T. Mehta
A Combinatorial Approach To Cns Regeneration Using Activated Transcription Factors, Saloni T. Mehta
Open Access Dissertations
Approximately 300,000 Americans are living today with permanent disability related to traumatic spinal cord injury (SCI), with almost 12,000 new cases each year. There are no current methods to promote robust regeneration and long-term functional recovery in SCI patients. This is partially because, following SCI, axon regeneration in the CNS is poor, owing both to neuron intrinsic factors and to external inhibitory factors. One major intrinsic limitation on axon regeneration is the altered activities of regeneration-associated transcription factors (TFs) in mature neurons of the central nervous system (CNS); these factors fail to be activated post-injury. In contrast, axons in the …
Data-Driven Identification Of Patient-Specific Drug Combinations For The Treatment Of Glioblastoma, Vasileios Stathias
Data-Driven Identification Of Patient-Specific Drug Combinations For The Treatment Of Glioblastoma, Vasileios Stathias
Open Access Dissertations
Glioblastoma is the most common malignant primary adult brain tumor with a standard of care consisting of maximal surgical resection followed by radiotherapy and adjuvant temozolomide (TMZ) chemotherapy. However, despite medical advances in the field, recurrence is almost universal. As with most cancers, heterogeneity and adoptive reprogramming upon therapy, which often leads to resistance, represent huge barriers to clinical care. Novel targeted therapies, which are the foundation of precision medicine, are therefore urgently required. During the last decade, several large research consortia have generated unprecedented amounts of data to characterize and model complex biological systems and disease, in particular, cancer. …
Human Brain Transcriptome Profiles In Obesity, Chun Wu
Human Brain Transcriptome Profiles In Obesity, Chun Wu
Open Access Dissertations
Obesity is one of the leading causes of global deaths. WHO estimates that 39% of adults over 18 years of age are overweight (BMI ≥ 25kg/m2) and, currently 13% meet criteria for obesity (BMI ≥ 30kg/m2). Increased food-energy supply and a mismatched biological response patterns that evolved in a scare environment, were suggested to be major drivers of the obesity epidemic. The palatable energy dense food is excessively consumed for its hedonic characteristics; its ubiquitous availability has increased the relevance of brain reward systems in controlling food intake. Increasing evidence shows that obesity shares many mechanisms with addiction. Food addiction …
Cadmium Explains, In Part, The Cardiovascular Toxicity Of Cigarette Smoking, Eric M. Hecht
Cadmium Explains, In Part, The Cardiovascular Toxicity Of Cigarette Smoking, Eric M. Hecht
Open Access Dissertations
Cigarette smoking is a well-known cardiovascular risk factor associated with an estimated 311 premature cardiovascular deaths per 100,000 smokers in the United States each year. The mechanism of arterial damage due to tobacco smoke is not fully elucidated. One plausible theory suggests that toxic exposure to one or more chemical constituents found in tobacco smoke causes persistent inflammatory changes at the level of the endothelial cell, which leads to arterial damage and atherosclerosis. The toxic elements found in tobacco smoke currently thought to be most responsible for cardiovascular toxicity include nicotine, carbon monoxide (CO), oxidant gases, polycyclic aromatic hydrocarbons (PAHs), …
Spasticity And Pain After Spinal Cord Injury: Relationships To Physiological, Functional, And Quality Of Life Measures, Jacqueline Anne Tibbett
Spasticity And Pain After Spinal Cord Injury: Relationships To Physiological, Functional, And Quality Of Life Measures, Jacqueline Anne Tibbett
Open Access Dissertations
Spasticity and chronic pain are both prevalent consequences of spinal cord injury (SCI), are commonly considered problematic, and are associated with reduced quality of life after SCI. This study investigated factors that contribute to the perceived impact of spasticity on daily life and how pain and spasticity are related. Analysis to characterize the strength of relationships between the impact of spasticity on life and physiological, environmental, and psychosocial factors can aid in identifying factors most strongly related to negative or positive impacts of spasticity. These factors may become candidates for experimental interventions aimed at reducing the problematic impact of spasticity …
Age By Stage Modeling Of Dynamic Heterogeneity, Shayna Bernstein
Age By Stage Modeling Of Dynamic Heterogeneity, Shayna Bernstein
Open Access Dissertations
Mortality modeling has come a long way since the demographer Benjamin Gompertz (1779-1865). We address populations where mortality is structured by the joint effects of age and state and individuals can change state at each age. Dynamic states are the most complex and interesting states to consider and we focus on three categories of states: being married or unmarried, being below or above a particular income threshold, or being in one of four income states. We examine how the transience of our particular states at each age drives the cohort dynamics such as the demographic structure and lifespan inequalities within …
Structural Optimization And Behavioral Analysis Of Antagonists Of The Insect Odorant Receptor Co-Receptor Subunit, Devin Kepchia
Structural Optimization And Behavioral Analysis Of Antagonists Of The Insect Odorant Receptor Co-Receptor Subunit, Devin Kepchia
Open Access Dissertations
Response to volatile environmental chemosensory cues is essential for insect survival. The odorant receptor (OR) family is an important class of receptors that detects volatile molecules. Importantly, olfaction is a key component of the multimodal approach used by mosquitoes to target and feed on humans. Current repellents have drawbacks, necessitating development of more effective agents. Insect ORs are odorant-gated ion channels, consisting of a variable odorant specificity subunit and a conserved odorant receptor co-receptor (Orco) subunit. The Orco subunit possesses an allosteric site to which modulators can bind and inhibit odorant activation of ORs. All insect ORs contain Orco, and …
Role Of C-Kit In Atherosclerosis: A Mechanistic Study, Lei Song
Role Of C-Kit In Atherosclerosis: A Mechanistic Study, Lei Song
Open Access Dissertations
Rationale: c-Kit, as a receptor tyrosine kinase (RTK), is present in multiple cell types including vascular smooth muscle cells (SMCs). However, so far, limited progress has been made to understand how c-Kit mediates SMC biology, and whether the presence of this receptor is critical for vascular pathogenesis such as atherosclerosis. Objectives: In this dissertation, I investigated the roles of c-Kit in atherosclerosis and underlying mechanisms. Methods: c-Kit distribution was determined in both murine and human aortae using a combination of KitBac-eGFP reporter mice, immunofluorescence (IF), and Western blot. c-Kit deficiency studies were performed in c-Kit mutant (KitW/W-v) mice on an …
Modeling The Il-2-Related Risk In Type One Diabetes By Selectively Lowering Il-2r Signaling In T Lymphocytes In Nod Mice, Connor Jude Dwyer
Modeling The Il-2-Related Risk In Type One Diabetes By Selectively Lowering Il-2r Signaling In T Lymphocytes In Nod Mice, Connor Jude Dwyer
Open Access Dissertations
The contribution of polymorphisms in IL2 and the IL-2R subunits, which are associated with several prominent autoimmune diseases including type 1 diabetes (T1D), is difficult to determine because the development of autoimmunity depends on variation of multiple genes, where the contribution of any one is small. To investigate the mechanisms whereby a modest reduction in IL-2R signaling influences diabetes in NOD mice, we co-expressed a mutant IL-2Rβ (IL-2RβY3) with wild-type IL-2Rβ selectively in T lymphocytes (designated NOD-Y3). In NOD-Y3 mice, the sensitivity of IL-2R signaling, measured as the EC50 for tyrosine phosphorylation of STAT5, was reduced approximately 2-3-fold in Tregs. …
Neuroprotective Mechanisms Of Ischemic Tolerance Induced By Resveratrol Preconditioning, Kevin B. Koronowski
Neuroprotective Mechanisms Of Ischemic Tolerance Induced By Resveratrol Preconditioning, Kevin B. Koronowski
Open Access Dissertations
Ischemic stroke is a devastating neurological disorder that currently has no clinically approved neuroprotective treatments. Resveratrol is a naturally occurring polyphenol that protects against cerebral ischemic injuries when administered in a prophylactic manner. Yet, the molecular underpinnings of resveratrol-induced neuroprotection are still unclear. This is partly because the metabolic adaptations induced by a major target of resveratrol, the NAD+-dependent deacetylase Sirt1, have not been characterized in the brain. The goal of this study was to better understand the efficacy of resveratrol as a therapeutic agent in ischemic stroke and the metabolic pathways regulated by brain Sirt1 that promote ischemic tolerance. …
Fibroblast Growth Factor 21 Induces Cardiac Hypertrophy, Karla Schramm
Fibroblast Growth Factor 21 Induces Cardiac Hypertrophy, Karla Schramm
Open Access Dissertations
Diabetic cardiomyopathy is a diabetes-associated cardiovascular disease (CVD), which causes heart dysfunction. Left ventricular hypertrophy (LVH) is a key feature of diabetic cardiomyopathy. Molecular mechanisms underlying this condition are largely unknown. Fibroblast growth factor (FGF) 21, an adipokine that regulates metabolism, has been found to be elevated in the circulation of type 2 diabetic patients. This thesis evaluates the long-term effects of increased serum FGF21 levels on the heart. It reveals that FGF21 induces hypertrophy of cardiac myocytes via FGF receptor (FGFR) 4-dependent activation of the pathological and pro-hypertrophic PLCγ/calcineurin/NFAT pathway, but independently of β-klotho, the canonical co-receptor for FGF21 …
Toward A Law Of The Underground: Assessing The Physical And Perceptual Risks Of Geologic Carbon Capture And Storage, Caitlin Marina Augustin
Toward A Law Of The Underground: Assessing The Physical And Perceptual Risks Of Geologic Carbon Capture And Storage, Caitlin Marina Augustin
Open Access Dissertations
Carbon capture and storage (CCS) technologies have both potential economic benefits and potential climate change mitigation impacts. However, CCS is not without physical and perceptual risks. In this dissertation, I followed two parallel research tracks regarding potential leakage of carbon dioxide out of CCS storage reservoirs. I completed three technical projects using data from the global-to-local level. First, I used Bayesian modeling to understand the potential for a surface release of carbon dioxide. These models allowed me to conclude that discrete, large-volume events are unlikely but not impossible events and draw similar risk conclusions as research from other disciplines. Second, …
Towards Bio-Inspired Cementitious Materials: The Effect Of Organic Polymeric Materials On The Nanostructure And Nanomechanical Properties Of Calcium-Silicate-Hydrate, Mahsa Kamali
Open Access Dissertations
This study aims to obtain a fundamental understanding of the effect of polymeric materials with distinct functional groups on the nanostructure and nanomechanical response of calcium-silicate-hydrate (C-S-H). Nature has created biological materials with hierarchical microstructure and superior mechanical and functional properties. This is achieved in nature through certain biopolymers with specific structures and functionalities directing growth, microstructure and macroscopic performance of biological materials. C-S-H comprises the primary component of the cement hydration product and plays a fundamental role in determining the mechanical and long-term characteristics of cement-based materials. The different size and molecular structure of polymers, and the complex structure …
The Role Of Cochlin In The Trabecular Meshwork, Teresia Angelica Carreon
The Role Of Cochlin In The Trabecular Meshwork, Teresia Angelica Carreon
Open Access Dissertations
Glaucoma affects over 70 million people worldwide and can result in irreversible progressive vision loss if left untreated. Primary open angle glaucoma is the most common form of the disease. This disease is characterized by an uncontrolled increase in intraocular pressure (IOP) and this characteristic remains the only modifiable risk factor. The trabecular meshwork (TM) is a filter-like structure responsible for aqueous humor filtration into Schlemm’s canal (SC) and into the episcleral veins (EV). It is believed that obstruction in the TM leads to impeded aqueous humor outflow resulting in an increase in IOP. It has previously been demonstrated that …
Enhancement Of Nutrient Transport And Energy Production Of The Intervertebral Disc By The Implantation Of Polyurethane Mass Transfer Device, Yu-Fu Wang
Open Access Dissertations
Low back pain is a common problem that most people experience at some point in their life. Intervertebral disc (IVD) degeneration has been considered closely associated with low back pain. Since the IVD is the largest avascular tissue in the human body, insufficient nutrient supply has been suggested to be one of the etiologies for IVD degeneration. Therefore, enhancing the nutrient transport into the IVD could be a potential treatment strategy for disc degeneration. Mass transfer devices have been used for the purpose of drug delivery and hemodialysis, and similar concept could be applied to the IVD. A porous material …
The Neuroprotective Compound P7c3-A20 Promotes Neurogenesis And Improves Functional Outcomes After Focal Cerebral Ischemia, Zachary Balmuth-Loris
The Neuroprotective Compound P7c3-A20 Promotes Neurogenesis And Improves Functional Outcomes After Focal Cerebral Ischemia, Zachary Balmuth-Loris
Open Access Dissertations
Ischemic stroke is the second leading cause of death worldwide and the leading cause of adult long-term disability in the United States. Despite its prevalence, there are few therapeutic interventions available. The neuroprotective compound P7C3-A20 (A20) has been shown to reduce mature neuronal cell death while also increasing the net magnitude of postnatal neurogenesis in models of neurodegeneration and acute brain injury. A20 compounds demonstrate protection by enhancing the flux of nicotinamide adenine dinucleotide (NAD) in mammalian cells, a proposed therapeutic approach to treating cerebral ischemia. The studies carried out in this dissertation sought to investigate the effectiveness of A20 …
The Role Of P16 In Controlling Mammary Epithelial Cell Senescence And Brca1-Deficient Tumorigenesis, Alexandria Scott
The Role Of P16 In Controlling Mammary Epithelial Cell Senescence And Brca1-Deficient Tumorigenesis, Alexandria Scott
Open Access Dissertations
A major risk factor of breast cancer is aging. Aging is caused partly by cellular senescence, a tumor suppressive mechanism that prevents the proliferation of cells at risk of transformation. p16INK4A (p16), an inhibitor of CDK4 and CDK6, plays a critical role in controlling senescence. Functional inactivation of p16 is frequently detected in human breast cancers. However, loss of p16 alone in mice does not result in mammary tumorigenesis. How p16 loss contributes to mammary cell aging and tumorigenesis in vivo is not fully understood. We reported that senescence was induced in mammary epithelial cells (MECs) during aging with increased …
Mitochondrial Dna (Mtdna) Variant-Nuclear Dna Variant Interactions And Gene-Dietary Exposure Interactions In Age-Related Macular Degeneration (Amd), Patrice J. Persad
Mitochondrial Dna (Mtdna) Variant-Nuclear Dna Variant Interactions And Gene-Dietary Exposure Interactions In Age-Related Macular Degeneration (Amd), Patrice J. Persad
Open Access Dissertations
Age-related macular degeneration (AMD) is shaped by genetic and non-genetic factors. Examining such factors—along with interactions between these factors—that contribute to AMD is crucial because permanent vision loss can arise, and better understanding the disease pathogenesis will foster potential treatments. Consideration of gene-gene and gene-environment interactions may identify additional risk factors and explain some of the variability in disease presentation and progression. Several studies have revealed associations between AMD risk and mitochondrial (mt) variants [mt single nucleotide polymorphisms (SNPs)]; additionally, mtDNA damage or mt dysfunction in retinal pigment epithelium (RPE) cells can affect AMD-related processes. Overall diet quality has been …
Ecohydrology Of Coastal Wetland In South Florida Under Sea Level Rise: A Combination Of Stable Isotope Analysis, Mathematical Modeling, And Spatial Analysis, Lu Zhai
Open Access Dissertations
In southern Florida, conservation of coastal wetlands is facing two challenges under sea level rise (SLR): (1) How to estimate and predict encroachment of mangroves and other halophyte vegetation into the areas previously covered by freshwater species? (2) How to allocate more freshwater from Lake Okeechobee in middle Florida to the coastal wetlands (e.g., Everglades) to counteract increasing saltwater intrusion? Fundamental to the above challenges is saltwater intrusion associated with SLR, which can increase the soil pore water salinity to levels where freshwater species cannot survive. The overall aim of my dissertation is to access the potential changes in vegetation …
Spatiotemporal Variation In Frugivore Assemblages And Population Dynamics Of An Invasive Shrub, Schinus Terebinthifolius, Kelley D. Erickson
Spatiotemporal Variation In Frugivore Assemblages And Population Dynamics Of An Invasive Shrub, Schinus Terebinthifolius, Kelley D. Erickson
Open Access Dissertations
Multiple introductions of an exotic species can facilitate invasion success by allowing for a wider range of expressed trait values in the adventive range. Schinus terebinthifolius Raddi (Brazilian Pepper) is an invasive shrub that was introduced into Florida in two separate introductions and has subsequently hybridized, resulting in three distinct lineages (eastern, western and hybrid). In the first chapter, to determine whether allocation of above ground biomass differed by introduction history we destructively sampled 257 stems from each of 6 populations with differing introduction histories. The proportion of aboveground biomass allocated to fruit, wood and leaves differed among the three …
Risk And The Response To Sea Level Rise In South Florida, Galen Treuer
Risk And The Response To Sea Level Rise In South Florida, Galen Treuer
Open Access Dissertations
South Florida’s low elevation, intensive urban development, and delicate ecosystems make it vulnerable to sea level rise. A gap exists between the current policies local governments in South Florida pursue and adaptation that could significantly reduce their exposure to climate change risks. One reason for this gap is that climate adaptation requires a transition away from the status quo, and barriers impede change. This dissertation presents three studies that aim to help communities in the region embrace and address their climate change risks. Chapter 2 reports the findings of an immersive simulation experiment that accelerates South Florida homeowners through thirty-five …
Development Of Nucleic Acid Sensing Technologies For Clinical Applications, David B. Broyles
Development Of Nucleic Acid Sensing Technologies For Clinical Applications, David B. Broyles
Open Access Dissertations
The importance of nucleic acids detection to biological science has expanded as new technology enables historically unprecedented insight into their form and function. Additional challenges to assay development have resulted from the need to detect everything from enormous genomic sequences to miniscule non-coding RNA. The focus of this work centers on a recognition of the complexity required of modern analytical techniques and a strategy to eliminate as much technical surplus as can be achieved without detrimental performance. Initially, a laboratory-based technique has been developed to directly detect miRNA in complex matrices using fluorescence, and this was applied to quantitation of …
Classified Mixed Model Prediction: Theory And Application, Jie Fan
Classified Mixed Model Prediction: Theory And Application, Jie Fan
Open Access Dissertations
Many practical problems are related to prediction, where the main interest is at subject or sub-population level. In such cases, it is possible to make substantial gains in prediction accuracy by identifying a class that a new subject belongs to. In this way, the new subject is potentially associated with a random effect corresponding to the same class in the training data, so that method of mixed model prediction can be used to make the best prediction. We propose a new method, called classified mixed model prediction (CMMP), to achieve this goal. We develop CMMP for both prediction of mixed …
The Trajectory Of Sedentary Behavior From Adolescence To Emerging Adulthood, Marissa D. Alert
The Trajectory Of Sedentary Behavior From Adolescence To Emerging Adulthood, Marissa D. Alert
Open Access Dissertations
US adolescents spend up to 8 hours daily in screen time. Efforts to reduce sedentary time have often focused on identifying its correlates. However, little is known about the trajectory of adolescents’ screen time or factors that predict it. This study examined change in screen time from age 13 to 23 and its predictors in a representative US sample. Adolescents (N = 3,705; 46.3% boys) from the National Longitudinal Study of Adolescent to Adult Health’s public-use data self-reported their screen time (hours/week watching TV and videos, and playing video/computer games) in 1994, 1996, 2001 and 2008. Piecewise latent growth models …
Utilization Of Genomics For Risk Assessment And Molecular Subtyping To Improve Treatment Strategy In Breast Cancer, Lisa Eileen Blumencranz
Utilization Of Genomics For Risk Assessment And Molecular Subtyping To Improve Treatment Strategy In Breast Cancer, Lisa Eileen Blumencranz
Open Access Dissertations
Death from breast cancer began a decline in the 1990’s. One widely accepted reason for this reduction was the discovery that breast cancer can be uniquely defined at the molecular level by oncogenes and tumor suppressor genes including, but not limited to, EGFR, AKT, ErbB2, PI3K, TP53, BRCA1/2, and PTEN. These genes and potential mutations within, can drive constitutive activation of aberrant signaling that can induce and sustain tumorigenesis. More importantly, these genes represent new avenues for possible markers and therapies. In the wake of this molecular biology discovery, there was an influx of new breast cancer treatments to the …