Medicine and Health Sciences Commons^™

Predictive Modeling Of Influenza In New England Using A Recurrent Deep Neural Network, Alfred Amendolara

Theses

Predicting seasonal variation in influenza epidemics is an ongoing challenge. To better predict seasonal influenza and provide early warning of pandemics, a novel approach to Influenza-Like-Illness (ILI) prediction was developed. This approach combined a deep neural network with ILI, climate, and population data. A predictive model was created using a deep neural network based on TensorFlow 2.0 Beta. The model used Long-Short Term Memory (LSTM) nodes. Data was collected from the Center for Disease Control, the National Center for Environmental Information (NCEI) and the United States Census Bureau. These parameters were temperature, precipitation, wind speed, population size, vaccination rate and …

Characterizing The Combination Of Rpa Inhibitors With Parp Inhibitors In High-Grade Serous Ovarian Cancer, Yat Tang

Theses & Dissertations

High-grade serous ovarian cancer (HGSC) is the most common and deadly gynecologic malignancy. HGSC patients with BRCA1/2 mutations have homologous recombination deficiency (HRD), requiring parallel pathways to maintain genome integrity (e.g., PARP1, PARP2). Approximately 50% of ovarian carcinomas are estimated to exhibit HRD. For the remaining 50% and the large percentage of HRD patients with acquired or innate resistance to single-agent PARP inhibitors, there is a need to develop alternative therapeutic strategies.

Replication Protein A (RPA) is a heterotrimeric protein crucial for genome maintenance. Phosphorylation of RPA in DNA damage response (DDR) is a negative regulator of DNA end resection. …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Hiv-1 Elimination In Humanized Mice, Hang Su

Theses & Dissertations

Human immunodeficiency virus type one (HIV-1) exclusively infects humans and chimpanzees. Therefore, animal models are required for all investigations of viral pathogenesis, therapy and cure. Immunodeficient mice transplanted with human hematopoietic stem cells, termed humanized mice, support the development of multiple human cell lineages throughout the cell’s life span. To this end, we used humanized mice to evaluate the dynamic changes of host immunologic and viral profiles during both acute and chronic HIV-1 infection. We identified the temporal and spatial distribution of HIV-1 cell and tissue compartment infections and outlined correlations made between viral progression and host immunity by comparing …

Defining The Role Of Tyrosine Phosphorylation In The Regulation Of Connexin43 In Cardiac Diseases, Li Zheng

Theses & Dissertations

Connexins are integral membrane proteins that oligomerize to form gap junction channels. Ions and small molecules diffuse intercellularly through these channels, allowing individual cellular events to synchronize into the functional response of an entire organ. Gap junction channels composed of Connexin43 (Cx43) mediate electrical coupling and impulse propagation in the normal working myocardium. In the failing heart, Cx43 remodeling (decreased expression, altered phosphorylation state, loss at intercalated discs, and increased presence at lateral membranes) contributes to rhythm disturbances and contractile dysfunction. While there is considerable information regarding key interactions of Cx43 in the regulation of gap junction channels, unfortunately, the …

Delivery Of Small Molecule And Rna Using Synthetic Polymeric Micelles And Multifunctional Exosomes For The Treatment Of Type 1 Diabetes, Yang Peng

Theses & Dissertations

Type 1 diabetes is one of the most challenging chronic autoimmune diseases. The destruction and dysfunction of insulin-secreting β cells are the results of inflammatory infiltration and the synergistic effect of multiple immune cells. The aim of this dissertation is to develop novel and reliable therapeutic approaches to advance the treatment of T1D: including chemical modification of a broad-spectrum immunosuppressant, co-application of small molecule based immune intervention and siRNA based β cell preservative therapy, and administration of a PI3K-δ/γ dual inhibitor to specifically target immune cells, utilizing synthetic polymeric micelles or natural produced multi-functional exosomes derived from human bone marrow …

Evaluating The Occurrence Of Age-Related Peripheral Neuropathy In Het3 Mice And Development Of A Whole Tissue Imaging Technique For Analyzing Total Innervation In The Subcutaneous Adipose Depot, Jake Willows

Electronic Theses and Dissertations

Adipose tissue can be characterized as either being a white (energy storing) depot or a brown (energy expending) depot and both have been found to contain dense networks of neural innervation. This adipose nerve supply regulates numerous metabolic functions and likely plays an important role in the function of adipose blood vessels. Recently our lab has shown in the C57BL/6 mouse model that peripheral neuropathy, or the dying back and dysfunction of the nerves in the superficial tissues such as the skin, can extend into the subcutaneous adipose tissue in conditions commonly associated with the neuropathic phenotype (i.e. diabetes, obesity, …

The Role Of Histone Chaperone Fact Complex In Base Excision Repair Pathway And Its Therapeutic Potential In Colon Cancer And Medulloblastoma, Heyu Song

Theses & Dissertations

Base excision repair (BER) pathway is required for the removal of damaged bases caused by alkylation, oxidation and ring-saturation. Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in BER pathway. Although repair of damaged bases by recombinant APE1 has been well investigated in vitro, how APE1 gains access to damaged bases in the context of chromatin is largely unknown. A prominent member of the histone chaperone family, FACT (Facilitates Chromatin Transcription) is thought to reorganize nucleosomes through the destabilization of multiple intra-nucleosome contacts. FACT complex is composed of two polypeptides identified as SPT16 (Suppressor of Ty 16) and SSRP1 …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Targeted Inhibition Of Histone Deacetyltransferases For Pancreatic Cancer Therapy, Richard Laschanzky

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease with a dismal five-year survival rate of less than 10%. One major obstacle in PDAC treatment is acquired drug resistance. Pan-histone deacetylase inhibitors (pan-HDACi) are a relatively new class of anti-cancer drugs, with demonstrated ability to overcome drug resistance and re-sensitize PDAC tumors to Gemcitabine (Gem). These agents target HDACs, a family of 18 enzymes (divided into four classes, I-IV) that catalyze the deacetylation of histones and other cellular proteins and have multiple effects on cell growth, differentiation, survival, and tumorigenesis. Although pan-HDACi have shown significant efficacy in preclinical analysis, and some …

The Development Of Novel Apurinic/Aprymidinic Endonuclease/Redox-Factor 1 Inhibitors For The Treatment Of Human Melanoma, Bella Sharifi

Pharmaceutical Sciences (MS) Theses

Apurinic/apyrimidinic DNA repair endonuclease-1 (APE1), first recognized as an important DNA excision repair enzyme, is also known as Redox Factor-1 (Ref-1) involved in the activation of many nuclear transcription factors in both redox-dependent and independent manner. It has been well-documented that the overexpression of APE/Ref-1 contributes to the development of chemo-resistance and is associated with tumor progression in many human malignancies [1].

Our previous study in melanoma demonstrated that the development of novel inhibitors targeting the redox regulation domain of APE/Ref-1 is a promising strategy for melanoma treatment. To date, limited successes have been reported in developing novel …

Putting A Face To Cancer, Lenn Robbins

Capstones

About one month after I began my studies at the Craig Newmark Graduate School of Journalism, I was diagnosed with a rare form of cancer, Langerhans Cell Histiocytosis (LCH). Three years and three relapses later, I have my MA, I defiant will to fight this disease and the hope that by chronicling my experience I might help others. If this project helps just one person, it's been worth the ride.

https://lennrobbins.wixsite.com/facetocancer

An In-Depth Review Of Retinitis Pigmentosa Development And Pathologies Overtime In Patients, Abdul Harris

Honors College Theses

Retinitis Pigmentosa is a disease which can cause blindness and affects around 2.5 million people worldwide. It is a disorder that has a multitude of ways of being inherited, such as autosomal dominant, autosomal recessive as well as X-linked and mitochondrial linked disorder. While some versions of RP may be syndromic (20%-30%), a majority of cases are in fact non-syndromic. The majority of non-syndromic cases inherited via autosomal dominant RP having RHO gene mutations, and X-linked means of inheritance having majority of patients with RPGR gene mutations. Ushers Syndrome, a syndromic version of retinitis pigmentosa and autosomal recessive RP having …

Air Pollution & Asthma Prevalence: Hotspot Analysis On Environmental Injustice In Buffalo, New York, Zuveria Shaguphta

Graduate Dissertations and Theses

This research aims to focus on the historical impacts of segregation in these communities (with Census Bureau data) and whether we see that these are the areas with continued segregation and a disproportionate number of TRI facilities. The third part of this research will be to investigate the presence of asthma in these neighborhoods as documented by the New York State Health Department. Asthma is a chronic disease in which the airways are inflamed due to some kind of external factor causing this reaction. Literature shows that there is a relationship between outdoor air pollution from combustion of fossil fuels …

Junctophilin-2 Protects Cardiomyocytes Against Palmitate-Induced Injury, Xiaoyun Ji

Electronic Thesis and Dissertation Repository

Cardiac lipotoxicity may induce cardiomyocyte apoptosis, eventually leading to myocardial dysfunction and heart failure. This study investigated whether and how junctophilin-2 (JPH2) plays a role in palmitate-induced apoptosis in cardiomyocytes. Here, we found palmitate incubation reduced JPH2 protein levels, increased cytosolic Ca²⁺ and induced apoptosis in cardiomyocytes. JPH2 over-expression prevented the increased cytosolic Ca²⁺ and apoptosis in palmitate-stimulated cardiomyocytes. JPH2 over-expression also attenuated palmitate-induced CCAAT-enhancer-binding protein homologous protein (CHOP) expression and CHOP deletion alleviated palmitate-induced apoptosis. Furthermore, blocking Ca²⁺ release from ryanodine receptor-2 (RyR2) prevented palmitate-stimulated CHOP induction and apoptosis. Additionally, JPH2 silencing elevated cytosolic Ca^{2+ …}

Identifying The Risk Factors To Postpartum Depression, Jannica Bondoc Santos

Senior Theses

A woman’s life instantly changes after the birth of their child. Furthermore, culture influences the stigma that a mother is the primary caregiver of their children and are accountable for the health and upbringing of the child. Giving birth to a baby and taking up the responsibility of another human life is a great impact in a female’s existence. In addition to the new tasks that come with motherhood, women are also challenged to cope with their emotional and mental state after giving birth. The most chronic mental illness that can develop after labor is postpartum depression (PPD). Women who …

Using The Adam Questionnaire In Primary Care To Identify Hypoandrogenism In Males Aged 40 Years Or Older, Jeremy Burns

Doctor of Nursing Practice

Testosterone replacement therapy (TRT) has been shown to improve the symptoms of metabolic syndrome by reducing Hemoglobin A1C, belly fat, cholesterol, and blood pressure (Cunningham, 2015). The ultimate goal for testosterone-deficient patients is to have an improved quality of life by starting TRT. This quality improvement project was conducted at a small primary care clinic in South Texas. The project was started by screening 84 male patients ≥ 40 years of age using the Androgen Deficiency in Aging Males (ADAM) questionnaire. The ADAM questionnaire was considered positive for anyone who answered “yes” to 3 or more questions or “yes” to …

The Manipulation Of Host Transcription By The Ankh Effector Of Legionella., Juanita E. Von Dwingelo

Electronic Theses and Dissertations

Legionella pneumophila is a Gram-negative facultative intracellular bacterium that can be found dispersed throughout freshwater environments, where it primarily parasitizes amoebae and other protozoan species. Humans are an accidental host for L. pneumophila, and infection occurs upon inhalation of aerosolized water droplets that contain the bacteria. L. pneumophila is the causative agent of Legionnaires’ Disease, which is the result of intracellular proliferation within alveolar macrophages. Pathogenesis of L. pneumophila is dependent on the Dot/Icm type 4 secretion system (T4SS) apparatus, which is comprised of 27 proteins and is responsible for translocating over 330 effector proteins into the host cell. Many …

Computational Model For Pedestrian Movement And Infectious Diseases Spread During Air Travel: A Molecular Dynamics-Like Numerical Approach, Pierrot Derjany

Doctoral Dissertations and Master's Theses

There is direct evidence of the transmission of fatal infectious pathogens in large human gatherings. Air transportation is no exception. The mixing of susceptible and infectious individuals in this high-density man-made environment involves pedestrian movement which is generally not taken into account in modeling studies of disease dynamics. This thesis addresses this problem through a multiscale model that combines pedestrian dynamics with stochastic infection spread models. This generic model is applicable to several directly transmitted diseases. Through this multiscale framework, the effectiveness of certain layout and strategies in suppressing the disease spread in highly crowded locations such as airplanes, airports …

Methods To Evaluate Ruminant Animal Production Responses, Jose Manuel Diaz Gomez

Graduate Theses and Dissertations

In experiment 1, 80 steers (197.0 kg initial body weight; BW for fall, 116.9 kg for spring), were stocked at 2.45 and 4.1 calves/ha in fall and spring, respectively in 16 tall fescue pastures [fall ergovaline (EV) = 1,475 ppb and spring EV = 1,173 ppb] under 2 treatments, mineral (MIN) (n = 8) and cumulative management (CM) (n = 8). Forage allowance did not differ (P = 0.76) between CM and MIN during fall but differed during spring (P ≤ 0.05, 2.55 vs. 3.22 kg DM/kg BW, for MIN and CM, respectively). For fall, average daily gain (ADG) resulted …

Estimation Of Genetic Components Related To Infectious Bovine Keratoconjunctivitis Susceptibility In Angus And Angus Derived Cattle Produced In The Southern United States, Eric Oxford

Graduate Theses and Dissertations

The economic impact of infectious bovine keratoconjunctivitis (IBK) has been documented in many parts of the world. Many researchers have observed that prevention of this disease is very difficult given current methodologies. This is primarily due to the multifactorial nature of this disease. The objective of this dissertation was to determine the impact of IBK on calf performance and estimate genetic parameters, heritability and estimated breeding values for IBK susceptibility. Data were analyzed using PROC GLIMMIX of SAS; while genetic parameters were estimated using a linear animal model for both single- and two-traits through MTDFREML. Additional evaluations calculated heritability using …

Association Between Gastroduodenal Ulcer And Age Of Diagnosis Of Head And Neck, Gastroduodenal And Pancreatic Cancer, Rukevwe Madusor

Capstone Experience

Background: Cancer is the second leading cause of death in the United States and remains a major public health problem worldwide. Epidemiological studies have demonstrated that insulin like growth factor-1 (IGF-1) is linked to ulcers and most cancers. Although studies have investigated the role of IGF1 in ulcer healing and cancer pathogenesis, the link between ulcer and cancer remains unclear. Hence, we assessed the relationship between ulcers and cancers.

Methods: This study consists of a sample of 180 cancer patients obtain by convenience sampling who were seen at Nebraska Medicine and were enrolled in the integrated cancer repository for cancer …

Quantitative Study Of The Antimicrobial Effects Of Silver On The Motility Of Escherichia Coli, Benjamin Russell

Graduate Theses and Dissertations

In recent decades, the number of antibiotic-resistant bacterial infections has grown to become a serious global threat. This rise can be attributed to the widespread misuse of antibiotics and the lack of newly developed drugs to fight resistant organisms. Novel bactericidal substances have, therefore, garnered significant research interest. Silver, due to its powerful antimicrobial effects, is one such substance. Silver is typically most effective in cationic form; however, advancements in nanotechnology have paved the way for the controlled fabrication of nano-silver. Silver nanoparticles have been shown to have increased antibacterial potency for a variety of reasons, including the release of …

Evidence-Based Foot Care For Persons With Type 2 Diabetes, Nicole Gutierrez

Doctor of Nursing Practice

Unmanaged Type 2 diabetes leads to macrovascular changes that affect the lower extremities, thereby damaging the sensory nerve fibers and leading to diabetic peripheral neuropathy. These patients may not be able to feel pain, heat, or cold in their lower extremities and often describe feelings of numbness and tingling. This sensory deficit may lead to the development of diabetic foot ulcers which often result in amputation. These preventable foot complications may be identified promptly with adequate diabetic foot exams. Comprehensive diabetic foot examinations reduce the occurrences of foot complications associated with uncontrolled glucose management and improves health outcomes for patients …

A Quality Improvement Initiative To Facilitate Provider Adherence To Type Ii Diabetes Mellitus Guidelines, Yazmin Valencia

Doctor of Nursing Practice

Background:A significant number of individuals with type 2 diabetes mellitus do not receive comprehensive diabetes care management to maintain optimal health.

Purpose:This project was designed to facilitate provider adherence to the type 2 diabetes mellitus evidence-based practice standards of care. A primary care practice needs assessment indicated opportunities to improve care management processes which promote adherence to current clinical practice guidelines.

Methods:This 10-week quality improvement project provided the clinical staff and provider with the necessary tools to implement best practices of diabetes care. Objectives assessed throughout project implementation included the design and use of an electronic health …

It's A Hard Nacht Life: Understanding How Nlrp12 Ticks, Abbigale Julia Brown

MSU Graduate Theses

The protein NOD- like receptor pyrin domain containing 12 (NLRP12) comes from a family of protein receptors with a wide range of functions including fertility as well as anti-inflammatory properties. The biological role of NLRP12 is poorly understood: research on the mechanisms behind its function and/or activation remains contradictory between different cell models. Current research suggests its involvement in a multi-protein complex named the inflammasome. The alternative hypothesis that has also been proposed is that NLRP12 is not a part of the inflammasome, rather it negatively regulates a transcription factor known as NF-��B down stream of Toll-like receptors. NLRP12 is …

The Effects Of Nicotine And Cigarette Smoking On Cardiac Electrophysiology., Affan B. Irfan

Electronic Theses and Dissertations

Cigarette smoking is a leading cause of preventable disease and premature death worldwide. The adverse effects of cigarette smoking, including proarrhythmia, are related to the mixture of chemicals, including nicotine (which sustains tobacco addiction). However, it remains unclear which individual tobacco smoke constituents and biological pathways mediate this increased risk. The purpose of this research was to explore the chronic effects of cigarette smoking, as well as compare the acute effects of nicotine and cigarette smoking, and the possible role of β-adrenoreceptors, on human cardiac electrophysiology. Chapter 1 is a comprehensive literature review of (a) the ex vivo and in …

The Acute Effect Of Water Intake On Glucose Regulation In Low Drinkers, Adam David Seal

Graduate Theses and Dissertations

Previous evidence suggests the hormone arginine vasopressin (AVP) may be a modifiable factor contributing to hyperglycemia. Significant differences in urine concentration and copeptin, a marker for AVP, have been observed between low and high water drinkers. Purpose: The purpose was to investigate the acute effect of adequate water intake on glucose regulation in low drinkers. Methods: 7 healthy (5 males, 2 female) low drinkers were recruited using a water frequency questionnaire (WFQ), spot and 24-h urine sample (age 43±6 y, BMI 30.9±3, WFQ volume 823±403 mL∙d-1, 24 h Uosm 961±105 mmol∙kg-1, copeptin 8.17±3.05 pmol∙L-1). During two experimental protocols, participants remained …

The Difference In A1c Of Children And Adolescents With Type 1 Diabetes Mellitus Using Carbohydrate Counting Compared To Those Using A Structured Meal Plan, Alia El Kubbe

Electronic Thesis and Dissertation Repository

Carbohydrate counting (CHO) is a nutrition education tool used by patients with type 1 diabetes mellitus (T1DM). The primary objective was to assess glycated hemoglobin (A1C) in participants with T1DM using CHO counting vs. those using a structured meal plan (SMP). The secondary objectives were to determine if BMI-for-age, parental income, parental involvement, and mothers’ educational level were associated with their children’s glycemic control. A cross sectional study was conducted, where participants aged 4-18 years, or their parents completed a survey. Total sample size was 88 participants (77 in the CHO counting group and 11 in the SMP group). There …

Utilizing Fiv (Feline Immunodeficiency Virus) To Develop A Novel Animal Model To Study Hiv (Human Immunodeficiency Virus), Ankita Suryakant Kambli

Electronic Thesis and Dissertation Repository

This project sought to perform the in vitro work needed to accomplish the long-term vision of harnessing the similarities between HIV (Human Immunodeficiency Virus) and FIV (Feline Immunodeficiency Virus) to develop an animal model whereby cats can be used to study HIV pathogenesis and therapeutics. We transfected CRFK (Crandell Rees Feline Kidney) fibroblasts with plasmids that could express human or feline CD4, CCR5, or both, and determined receptor surface expression through flow cytometry. We discovered that HIV envelope expressed on 293T can fuse with huCD4/huCCR5 on CRFK. These cat cell lines were also capable of supporting HIV infection. Additionally, we …