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Articles 1 - 30 of 61
Full-Text Articles in Medicine and Health Sciences
Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty
Epidermal Growth Factor Receptor (Egfr) Inhibition By Polychlorinated Biphenyls Contributes To Non-Alcoholic Fatty Liver Disease (Nafld)., Josiah Hardesty
Electronic Theses and Dissertations
This dissertation describes how poly-chlorinated biphenyls (PCBs) exacerbate the pathogenesis of non-alcoholic fatty liver disease (NAFLD). While PCBs were banned in 1979, they still persist in contaminated biota, including food, and are detected in human plasma and adipose. The body burden of PCBs is associated with elevation of liver enzymes and necrosis markers in humans, characteristic of NAFLD. PCB exposure in high-fat diet fed mice leads to steatohepatitis that recapitulate the findings seen in exposed humans. The global estimate of people diagnosed with NAFLD is up to 1 in 4 people, unrelated to dietary or genetic factors. The hepatic mechanisms …
Innate Immunity, The Hepatic Extracellular Matrix, And Liver Injury: Mathematical Modeling Of Metastatic Potential And Tumor Development In Alcoholic Liver Disease., Shanice V. Hudson
Innate Immunity, The Hepatic Extracellular Matrix, And Liver Injury: Mathematical Modeling Of Metastatic Potential And Tumor Development In Alcoholic Liver Disease., Shanice V. Hudson
Electronic Theses and Dissertations
The overarching goals of the current work are to fill key gaps in the current understanding of alcohol consumption and the risk of metastasis to the liver. Considering the evidence this research group has compiled confirming that the hepatic matrisome responds dynamically to injury, an altered extracellular matrix (ECM) profile appears to be a key feature of pre-fibrotic inflammatory injury in the liver. This group has demonstrated that the hepatic ECM responds dynamically to alcohol exposure, in particular, sensitizing the liver to LPS-induced inflammatory damage. Although the study of alcohol in its role as a contributing factor to oncogenesis and …
The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis
The Migration And Developmental Remodeling Of Intrinsic Interneurons In Visual Thalamus And The Role Of Retinal Signaling., Naomi E. Charalambakis
Electronic Theses and Dissertations
The dorsal lateral geniculate nucleus (dLGN) of the mouse is a model system to study the development of thalamic circuitry. While most studies focus on relay neurons of dLGN, little is known about the factors regulating the development of the other principal cell type, intrinsic interneurons. To date, the targeting and migratory path of dLGN interneurons as well as their morphological development remains unclear. Here we examined whether the migration, structure, and function of interneurons relies on retinal signaling. We took a loss-of-function approach and crossed GAD67-GFP mice, which express green fluorescent protein (GFP) in dLGN interneurons, with math5 nulls …
Cholesterol Metabolism And Statin Effects On An Fh Class Ii Ldl-Receptor Mutation., Linda Omer
Cholesterol Metabolism And Statin Effects On An Fh Class Ii Ldl-Receptor Mutation., Linda Omer
Electronic Theses and Dissertations
Familial hypercholesterolemia (FH) is a common genetic disease and has been studied with the aim of finding a curative measure for decades. FH is caused by mutations in the low-density lipoprotein receptor (LDLR) resulting in defects in LDL-cholesterol (LDL-C)-receptor mediated endocytosis and development of premature cardiovascular disease (CVD). Here I describe the use of a corrected and non-corrected LDLR FH cell model to investigate receptor-mediated endocytosis and statin effects. For these studies, we reprogrammed FH fibroblast cells to induced pluripotent stem cells (iPSC) and confirmed their pluripotency and ability to differentiate to hepatocyte-like cells (HLC). A clustered regularly interspaced short …
Evaluation Of The Predictive Ability Of A Screening Instrument Used To Diagnose Co-Occurrence Of Anxiety In Children With High-Functioning Autism., Austin Zachary
Electronic Theses and Dissertations
Anxiety has shown to have a high co-occurrence in children with Autism Spectrum Disorder (ASD), but has been difficult to co-diagnose. This study analyzed the ability of the Screen for Child Anxiety-Related Emotional Disorders (SCARED) to predict positive ASD screenings of the Social Responsiveness Scale (SRS). Parents and children ages 8 to 18 years (N = 100) were screened for anxiety using the SCARED and autism using the SRS. Moderate correlation was found between parent-reported SCARED and positive screening of the SRS (r = .579), with weak correlation found in the child-reported SCARED (r = .105). LASSO regression was conducted …
Influences Of Porphyromonas Gingivalis On The Viability Of Esophageal Cancer Cells., Muddasir Mohammed
Influences Of Porphyromonas Gingivalis On The Viability Of Esophageal Cancer Cells., Muddasir Mohammed
Electronic Theses and Dissertations
A recent study demonstrated an association between the Porphyromonas gingivalis (Pg)infection and the progression of ESCC (Gao et al., 2016). However, how Pg infection affects the nature of ESCC remains unknown. We examined the effects of Pg on the proliferation and chemotherapy drug-induced apoptosis of ESCC cells and elucidated the signaling molecules involved in these processes. Method: Apoptosis and cell proliferation were tested using Flow cytometry and Tetrazolium salt based proliferation assays respectively. Western Blot was utilized to detect the protein expression. CDK2 and Cyclin E were knocked down in the ESCC cells through transfection. Unpaired T-test and …
Characterizing The Gut Microbiota During Plasmodium Infection And Antimalarial Treatment., Joshua E. Denny
Characterizing The Gut Microbiota During Plasmodium Infection And Antimalarial Treatment., Joshua E. Denny
Electronic Theses and Dissertations
Plasmodium, the parasitic cause of malaria, is a global pathogen, annually causing 216 million infections and 445,000 deaths. As drug resistance continues develop and no effective vaccine is available, it is critical to understand the factors underlying the severity of this disease. Plasmodium is an extra-gastrointestinal tract infection where the parasite infects red blood cells causing clinical malaria. However, recent publications have pointed to interactions between the gut microbiota and malaria. With this in mind, the role of the gut microbiota in malaria infection was studied. C57BL/6 mice from different vendors displayed differential resistance and susceptibility to severe malaria, …
Lead And Crime: An Ecological Study Between Lead Contaminated Topsoil And Violent Crime., Brian Guinn
Lead And Crime: An Ecological Study Between Lead Contaminated Topsoil And Violent Crime., Brian Guinn
Electronic Theses and Dissertations
Lead is a known neurotoxicant. Human exposure to lead comes primarily through environmental exposures, including remnant lead paint, lead contaminated topsoil and lead contaminated water. Prenatal and early life lead exposure has been associated with numerous neurocognitive and neuropsychiatric disorders. This dissertation presents findings from an ecological study which evaluated the geospatial association between topsoil lead content and the incidence of FBI designated violent crime in Jefferson County, Kentucky. A total of 412 topsoil samples were collected along roadways (n=300) and from Louisville Metro Parks (n=112). Jefferson County crime data was obtained from the Louisville Metro Police Department – Crime …
Association Between Cigarette Smoking And Ovarian Reserve Among Women Seeking Fertility Treatment With Effect Modification By Race And Nat2 Genotype., Islamiat A. Oladipupo
Association Between Cigarette Smoking And Ovarian Reserve Among Women Seeking Fertility Treatment With Effect Modification By Race And Nat2 Genotype., Islamiat A. Oladipupo
Electronic Theses and Dissertations
Cigarette smoking in women has been associated with adverse reproductive outcomes such as reduced ovarian reserve, poorer in vitro fertilization (IVF) outcomes and increased adverse pregnancy outcomes. This study examined the association of smoking with ovarian reserve in a cross-sectional study of women seeking fertility treatment, and potential effect modification by race and NAT2 acetylator phenotype. Data from 265 women from the Louisville Tobacco Smoke, Genetic Susceptibility, and Infertility (LOUSSI) Study were analyzed. A total of 265 women were recruited through a single infertility clinic between September 2016 and June 2018. Information on current smoking status was assessed using a …
Influence Of Bilberry-Derived Anthocyanidins On Key Regulators Of Colorectal Cancer Development., Ashley M. Mudd
Influence Of Bilberry-Derived Anthocyanidins On Key Regulators Of Colorectal Cancer Development., Ashley M. Mudd
Electronic Theses and Dissertations
Colorectal cancer (CRC) is the third leading cause of cancer-related deaths within the United States. A variety of factors including exposure to environmental carcinogens, such as benzo[a]pyrene (B[a]P), dysbiosis of the gut microbiome and hereditary influences, including APC mutations, have been shown to lead to an increased risk of developing colorectal cancer. Given the recent alarming rise in cases of colorectal cancer diagnosed in individuals under the age of 40, further insight into developing novel and effective prevention and treatment strategies are warranted. The family of plant pigments known as the anthocyanins has been identified with …
Assessing The Role Of Arsenite In Disrupting The Egfr Signaling Axis., Christine Kim
Assessing The Role Of Arsenite In Disrupting The Egfr Signaling Axis., Christine Kim
Electronic Theses and Dissertations
The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase localized on the cell surface. Overexpression of EGFR has been used as biomarkers for many different types of cancers, including lung cancer. There is a strong association between arsenic and lung cancer development, although the mechanism is unclear. We hypothesize that chronic exposure of “a physiologically relevant” level of arsenite disrupts the EGFR endocytic trafficking. The goal of this project is to identify molecular mechanisms and roles of chronic arsenite-induced EGFR overexpression in lung cancer development. A non-malignant human bronchial epithelial cell line, Beas-2B cells were exposed to 100 …
Effect Of Grape Components On Periodontal Disease., Juili Subodh Shivde
Effect Of Grape Components On Periodontal Disease., Juili Subodh Shivde
Electronic Theses and Dissertations
Background: Half of the adult American population (47 %) are victims of periodontitis, a chronic inflammatory disease which leads to destruction of the tissues supporting the tooth. Periodontitis is initiated by periodontal pathogens and caused by excessive or prolonged host mediated inflammation. Porphyromonas gingivalisis one important agent implicated in the etiopathogenesis of chronic periodontitis. Pro-inflammatory cytokines induced by periodontal pathogens can cause alveolar bone loss and periodontitis. Bone loss is caused by the imbalance of bone formation and bone resorption. Osteoclasts are major cells that cause bone resorption. Moreover, periodontal inflammation also leads to bone resorption. Grapes are rich …
Adolescent Sexual And Reproductive Health In The Gambia., Sandhya Lohani
Adolescent Sexual And Reproductive Health In The Gambia., Sandhya Lohani
Electronic Theses and Dissertations
Adolescence is a crucial period in human development. Knowledge and awareness about when to have children, when to have sex, and use of contraceptives impacts the chances of teenage pregnancy and risk of sexually transmitted diseases. The objective of this study is to determine the prevalence and associated risk factors related to age of sexual debut, teenage pregnancy, and use of contraceptives in the Gambia. This study also compares the data with 2014 survey research conducted in the Gambia. The total study population were 50 adolescents aged 13-21 years from Bafuluto and surrounding communities in the Gambia. Among 50 respondents, …
Effects Of Hydrogen Sulfide In Hyperhomocysteinemia-Mediated Skeletal Muscle Myopathy., Avisek Majumder
Effects Of Hydrogen Sulfide In Hyperhomocysteinemia-Mediated Skeletal Muscle Myopathy., Avisek Majumder
Electronic Theses and Dissertations
Although hyperhomocysteinemia (HHcy) occurs due to a deficiency in cystathionine-β-synthase (CBS), causing skeletal muscle myopathy, it is still unclear whether this effect is mediated through oxidative, endoplasmic reticulum (ER) stress, both or something else. Cystathionine γ-lyase (CSE) and CBS are the main H2S producing enzymes, which produce Hydrogen sulfide (H2S) from Hcy in the transsulfuration reaction. H2S is an anti-oxidant compound and patients with a CBS deficiency cannot produce enough H2S, thus rendering them vulnerable to excess Hcy-mediated damage. Both in-vitro (C2C12 cells) and in-vivo (CBS+/- mice) models were used to …
Synthesis And Characterization Of Targeted Bar Encapsulated Polylactic-Co-Glycolic Acid Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Ranjith Radha Krishnan
Synthesis And Characterization Of Targeted Bar Encapsulated Polylactic-Co-Glycolic Acid Nanoparticles To Inhibit Porphyromonas Gingivalis Biofilm Formation., Ranjith Radha Krishnan
Electronic Theses and Dissertations
Periodontal disease is one of the most prevalent infectious diseases worldwide. Between 30-50% of the global adult population suffers from periodontal disease. Some form of periodontitis is present in 46% of American adults, corresponding to annual expenditures in excess of 14 billion dollars for treatment and prevention. Current treatments for periodontal diseases involve mechanical removal of plaque, correction of risk factors, gingival surgery and/or antibiotic therapy. To our knowledge there is no effective therapeutic approach that aims to limit pathogen colonization of the oral biofilm or re-colonization after treatment. Interaction of the pathogen Porphyromonas gingivalis with oral streptococci is critical …
Is Macrolide And Beta-Lactam Combination Therapy Associated With Early Clinical Stability Or 30 Day Mortality In Hospitalized Patients With Pneumonia? An Assessment Of Confounding By Indication., Evangeline Pierce
Electronic Theses and Dissertations
Pneumonia and influenza are one of the leading causes of infectious disease-related deaths worldwide. Current guidelines for the treatment of hospitalized patients with community acquired pneumonia (CAP) include empiric antimicrobial therapy with a macrolide and a beta-lactam. There is little consensus among studies as to which antimicrobial regimen is best. The confusing results seen may very well be due to lack of assessment of confounding by indication (CBI). This analysis was a secondary analysis from Hospitalized Adults with Pneumococcal Pneumonia: Incidence Study (HAPPI). The study participants were those in HAPPI who had received either macrolide and beta-lactam combination therapy or …
Wnt/Β-Catenin Mediated Cancer Stem Cell Activation In Hepatocellular Carcinoma., Harshulkumar M. Pandit
Wnt/Β-Catenin Mediated Cancer Stem Cell Activation In Hepatocellular Carcinoma., Harshulkumar M. Pandit
Electronic Theses and Dissertations
Hepatocellular carcinoma (HCC) is one of the deadliest cancers, with variable presentation, high chemotherapy resistance and early tumor recurrence. In this dissertation, we have systematically enriched, identified and characterized HCC cancer stem cells (CSCs) from 3 different HCC cell lines (Hepa1-6, HepG2, and Hep3B) using in vitro serum-free culture method. Enriched spheroids acquired CSC properties, primarily self-renewal capability, spheroid formation ability, and drug resistance. Heterogeneous CSCs enriched from Hepa1-6 cells demonstrated higher tumor initiation and proliferation capability in vivo, compared to control HCC cells in orthotopic immunocompetent mouse model. EpCAM+ CSCs were significantly enriched within heterogeneous Hepa1-6 CSC spheroids. Consequently, …
A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz
A Cancer-Targeted Gold Nanoparticle-Based Mri Contrast Agent., Nagwa El-Baz
Electronic Theses and Dissertations
In oncology, imaging plays a major role in terms of early detection and treatment of most types of cancer. Magnetic resonance imaging (MRI) is mostly used for cancer diagnosis due to its excellent contrast resolution. However, MRI for cancer diagnosis is somewhat limited by its sensitivity. In this thesis, we assessed the ability of theranostic platform consisting of gold nanoparticles functionalized with a cancer targeting aptamer; AS1411 and gadolinium chelate (Dotarem thiol derivative; Gd (III)-DO3A) as a MRI contrast agent to target malignant tumors by enhancing the MRI contrast of the detected tumor. The proposed technology is a novel injectable …
Social Determinants Of Health And A Grounded Mixed-Methods Approach To Explain Declining Life Expectancy In Eastern Kentucky : 1980 – 2014., William Renda
Electronic Theses and Dissertations
Trends in life expectancy for the United States from 1980-2014 suggest general improvement overall. However, eastern Kentucky stands out with a cluster of counties experiencing declining life expectancy. Given that life expectancy is an excepted indicator of overall population health, this anomaly in eastern Kentucky warrants investigation. This thesis uses a grounded mixed methods approach to explore this trend across the greater Appalachian region. Content and discourse analysis of interviews with public health and medical professionals in the study area revealed key themes perceived as being related to declining life expectancy, which informed variable selection for regression analysis. Regression models …
The N-Terminal Methyltransferase Homologs Nrmt1 And Nrmt2 Exhibit Novel Regulation Of Activity Through Heterotrimer Formation., Jon David Faughn
The N-Terminal Methyltransferase Homologs Nrmt1 And Nrmt2 Exhibit Novel Regulation Of Activity Through Heterotrimer Formation., Jon David Faughn
Electronic Theses and Dissertations
Protein, DNA, and RNA methyltransferases have an ever-expanding list of novel substrates and catalytic activities. Even within families and between homologs, it is becoming clear the intricacies of methyltransferase specificity and regulation are far more diverse than originally thought. In addition to specific substrates and distinct methylation levels, methyltransferase activity can be altered through formation of complexes with close homologs. This work involves the N-terminal methyltransferase homologs NRMT1 and NRMT2. NRMT1 is a ubiquitously expressed distributive trimethylase. NRMT2 is a monomethylase expressed at low levels and in a tissue-specific manner. They are both nuclear methyltransferases with overlapping target consensus sequences …
Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert
Unfolded Protein Response Pathways In Skeletal Muscle Homeostasis., Kyle R. Bohnert
Electronic Theses and Dissertations
Skeletal muscle mass, contractile properties, and metabolic function are regulated through the coordinated activation of multiple intracellular signaling pathways and genetic reprogramming. The endoplasmic reticulum (ER) plays a pivotal role in protein folding and calcium homeostasis in many cell types, including skeletal muscle. Disruption of calcium levels or accumulation of misfolded proteins in the ER lumen leads to stress, which results in the activation of a signaling network called the unfolded protein response (UPR). Further, recent studies have suggested that in certain conditions, UPR pathways can be activated independent of ER stress. However, the role of ER stress and the …
Investigating The Impact Of Nrmt1 Cancer Mutants On Catalytic Specificity And The Dna Damage Response., Kaitlyn Marie Shields
Investigating The Impact Of Nrmt1 Cancer Mutants On Catalytic Specificity And The Dna Damage Response., Kaitlyn Marie Shields
Electronic Theses and Dissertations
Protein methylation is an established and critical posttranslational modification controlling multiple cellular events. Alterations in protein methylation have been implicated in many diseases, including cancer. My work focused on the N-terminal trimethylase NRMT1 and the N-terminal monomethylase NRMT2. Previous work proposed that NRMT2 assists NRMT1 by priming its substrates for trimethylation. Importantly, NRMT1 mutations have been found in cancers, and loss of NRMT1 has been shown to promote oncogenic phenotypes in cancer cells. Together, this suggests that altered activities of NRMT1/2 may play a role in cancer progression. Although NRMT1/2 are 50% identical, they differ in key aromatic residues in …
Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle
Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle
Electronic Theses and Dissertations
Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences …
Coal Ash Exposure And Behavioral Impairments Among Children In Louisville, Kentucky., Chisom Nmesoma Odoh
Coal Ash Exposure And Behavioral Impairments Among Children In Louisville, Kentucky., Chisom Nmesoma Odoh
Electronic Theses and Dissertations
Introduction: Coal ash, generated from the combustion of coal is principally made up of fly ash, which consists of small particles and metals that can affect the development of children. Coal ash is predominately stored in landfills and surface impoundments, of which many are in proximity to residential areas. According to the Environmental Protection Agency, 25% of residents in proximity to electric power plants are children. Few studies have reported a positive association between coal ash and its by-products and neurobehavioral disorders. The purpose of this study was to explore the relationship between coal ash and its components and …
A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp
A Clinically Relevant Mouse Model Of Cisplatin-Induced Kidney Injury., Cierra Nichole Sharp
Electronic Theses and Dissertations
Cisplatin is a potent chemotherapeutic used for the treatment of many solid cancers, including testicular, ovarian, and lung cancer. Cisplatin causes many adverse side effects, of which nephrotoxicity leading to acute kidney injury is dose-limiting. Approximately 30% of patients will develop nephrotoxicity with cisplatin, and will either have their next dose of cisplatin lowered, skipped, or be switched to a less nephrotoxic chemotherapeutic altogether. These outcomes are not ideal when trying to treat cancer. Previously, it was believed that patients could recover from cisplatin-induced acute kidney injury with little to no lasting effects, but recent longitudinal studies have shown this …
Cannabidiol Alters The Immune Response To Porphyromonas Gingivalis In Mice., Shilpa Singh
Cannabidiol Alters The Immune Response To Porphyromonas Gingivalis In Mice., Shilpa Singh
Electronic Theses and Dissertations
Background: Porphyromonas gingivalis is an important etiologic agent of chronic periodontitis, an infectious disease defined by destruction of supporting tissues of the teeth. Marijuana is a risk factor for chronic periodontitis, although underlying mechanisms are poorly understood. As phytocannabinoids have been ascribed antiinflammatory properties, we hypothesized that cannabidiol exposure would lead to altered immune response to P. gingivalis infection facilitating bacterial persistence and, subsequently, increased alveolar bone loss in cannabidiol (CBD)-exposed mice. Methods: P. gingivalis-infected cannabinoid receptor 2 (CB2) knockout and wild type C57/Bl6 mice were exposed, or not exposed, to cannabidiol. Oral swabs from mice were used to monitor …
Combination Oral Immunotherapy With Il-10 And Il-12 Effectively Treats Colon Tumors Via Synergistic Effects On Il-17 Producing T Cells And Colon Epithelial Barrier Integrity., Neal Bhutiani
Electronic Theses and Dissertations
In this dissertation, the relationship between colon cancer and inflammation, the utility of novel imaging modalities for diagnosis of colitis and cancer, and the therapeutic efficacy of orally delivered, particle-based immunotherapy for the treatment of colon cancer are evaluated. In Chapters One and Two, multispectral optoacoustic tomography (MSOT) is demonstrated to effectively detect colon inflammation without the use of exogenous contrast prior to detection using conventional colonoscopy. Oral particle uptake is demonstrated in the distal small intestine and proximal colon, confirming site-specific delivery. In Chapter Three, administration of IL-10 and IL-12 containing particles is shown to act synergistically to significantly …
Post-Diagnosis Quality Of Life And Mortality In Non-Hispanic White And Hispanic Women Diagnosed With Invasive Breast Cancer., Delvon T. Mattingly
Post-Diagnosis Quality Of Life And Mortality In Non-Hispanic White And Hispanic Women Diagnosed With Invasive Breast Cancer., Delvon T. Mattingly
Electronic Theses and Dissertations
The prevalence of breast cancer is increasing, and the health-related quality of life (HRQOL) of breast cancer survivors may help to further understand survivorship. This study evaluated HRQOL as a potential prognostic factor for mortality among Non-Hispanic White (NHW) and Hispanic women diagnosed with invasive breast cancer. Data were used from the Health, Eating, Activity, and Lifestyle (HEAL) Study. Data for 351 participants were analyzed for associations between HRQOL scores (subscale, component) and mortality. Cox proportional hazards regression was conducted to assess the relationship between HRQOL and mortality outcomes (all-cause, breast cancer-specific, non-cancer). Median follow-up time from HRQOL assessment (approximately …
Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor
Electronic Theses and Dissertations
Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics, …
Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller
Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller
Electronic Theses and Dissertations
The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug …