Digital Commons Network^™

Synthesis And Biochemical Evaluation Of Heteroaryl Cjoc42 Derivatives For Gankyrin Binding, Yi-Chih Juang

Theses and Dissertations

Gankyrin is an oncogenic protein directly involved in various biological processes, such as cellular growth, cell cycle progression, cell proliferation, and invasion. Gankyrin overexpression has been observed in many cancer types, and gankyrin either directly or indirectly regulates key biochemical pathways related to cancer progression through its various protein-protein interactions (PPIs). Gankyrin interacts with retinoblastoma protein (pRb), cyclin-dependent kinase 4 (CDK4), mouse double minute2 (MDM2) and the S6 ATPase of the 19S regulatory cap of the 26S proteasome. Each of these PPIs controls the degradation of key tumour suppressor proteins, which in turn controls cell proliferation, migration and metastasis. Overexpression …

Synthesis, Conformational Analysis, And Thermodynamic Study Of N1-Cyclic Inosine Diphosphate Ribose And Its Analogs: Towards The Sar Of A Calcium Ion Releasing Second Messenger, Wenjie Lyu

Theses and Dissertations

N1-cyclic inosine 5’-diphosphate ribose, another class of the well-known calcium second messenger cyclic adenosine 5’-diphospate ribose, reveals nearly identical concentration-response calcium releasing activity intracellularly in a Jurkat T-cells (JTC) system. In this study, a three steps synthetic route is proposed to synthesize cIDPR analog 8-bromo-N1-cIDPR (8-Br-N1-cIDPR), the first 8-substitued analog has agonistic activity. The structure-activity relationship (SAR) of this messenger was investigated by the knowledge of its conformational landscapes, determined by variable-temperature NMR spectroscopy, in conjunction with PSEUROT and population analysis, allowing the study of thermodynamic parameters. A pure in-phase (PIP) heteronuclear correlation NMR experiment was adopted for direct extraction …

Positive Family Intervention For Families Of Children With Fragile X Syndrome: Using Telehealth To Reduce Problem Behavior And Improve Maternal Mental Health, Carmen Ann Kemper Mootz

Theses and Dissertations

The present study was designed to evaluate the effectiveness of Positive Family Intervention (PFI), delivered via teletherapy, for a family of a child diagnosed with Fragile X syndrome (FXS). PFI combines elements of cognitive-behavioral therapy (CBT) and positive-behavior support (PBS). A single-subject AB design was used across one participant to evaluate changes in observed problem behavior. Following nine weeks of baseline data collection, the participating mother was administered PFI via WebEx for eight 90-minute sessions, once per week. After the treatment was complete, three weeks of post-treatment follow-up data on problem behavior were collected from video- recordings. The participant uploaded …

Agal Antigen And Rutinose Glycosides As Model Compounds For The Design Of Classical And Conformational Glycomimetics, Dhwani Ashish Mehta

Theses and Dissertations

αGal or Galili epitope (αGal(1→3)βGal(1→4)GlcNAc) is a natural trisaccharide associated with cell-surface glycoproteins of certain mammalian and non-mammalian cells. The saccharide is not expressed by humans and anti-αGal antibodies account for ~1% of the total circulating antibodies in sera as a result of our constant exposition to the antigen from food and intestinal flora. Our interest in αGal relies on its involvement in a variety of pathologies including red meat allergy, hyperacute xenotransplant rejection, and parasitic and bacterial infections. In particular, we have an interest in developing structurally simple glycomimetics for engaging in high-affinity binding αGal-recognizing receptors such as the …

Cognitive Performance In A Retired Nfl Population: Does Position Played And Racial Identity Impact Cognition?, Kimberly Chantelle Diah

Theses and Dissertations

Cognitive functioning is integral to everyday life as it involves mental processes crucial to everyday survival. Over the last decade, there has been increasing focus and controversy surrounding concussions sustained by players in popular contact sports. This attention has sparked national debates that continue to polarize both the sports and scientific communities on the long-standing neuroanatomical, cognitive, and psychiatric challenges that many retired NFL players experience later in life (Alosco et al., 2017; Hart et al., 2013). While studies have been conducted on the predictors of long-term neuropsychiatric and psychosocial outcomes following a traumatic brain injury, there are few studies …

Psychometric Analyses Of A Comprehensive Neuropsychological Battery For Retired Nfl Players, Kimberly Ethridge Fitzgibbon

Theses and Dissertations

This study examined psychometric properties of the NFL Concussion Battery used to examine neuropsychological functioning in retired NFL players who were part of the NFL’s concussion settlement. This battery assesses multiple areas of cognitive functioning; executive functioning, language, processing speed, attention and memory. The study included 117 participants who were male with at least 16 years of education. The sample was 75.9% African-American and average age was 47. All participants completed the entire battery and passed the majority of effort measures. Those that did not pass the majority of effort measures or complete the entire battery were excluded.

T-test analyses …

The Effects Of Sleep Restriction On Biological, Psychological, And Neurocognitive Measures Of Health, Margaret S. Lorenzetti

Theses and Dissertations

Chronic sleep restriction impacts a significant proportion of the population, even though health is optimized following a minimum of seven hours of sleep. A preponderance of the literature examining the effects of sleep loss focuses on males and total sleep deprivation. Sleep restriction paradigms provide more ecological validity, as they are more consistent with sleep loss characterized in epidemiological studies. Moreover, enhancing the understanding of sleep loss among women, who are generally the gender most likely to encounter negative health as a result of poor sleep quality, is crucial. Thus, this investigation aimed to examine sleep restriction amongst a female …

Toward A Biopsychosocial Model Of Obesiy: Can Psychological Well-Being Be The Bridge To Integration?, Alexia Holovatyk

Theses and Dissertations

The complications associated with obesity are some of the most pressing health concerns facing the United States. At present, cardiovascular disease, stroke, and certain types of cancer are some of the leading causes of death, and researchers have cited obesity as one related factor (NIH, 2000). The topic of obesity has typically been approached through two seemingly contradictory lenses: The biomedical model that views obesity as a disease risk factor (e.g. Huxley, Mendis, Zheleznyakov, Reddy, & Chan, 2010) and the psychosocial model that considers the stigma associated with obesity to be more harmful than weight itself (e.g., Hatzenbuehler, Keyes, & …

A Novel Cognitive Stress Test For The Detection Of Early Alzheimer’S Disease In African Americans, Kimberly Capp

Theses and Dissertations

The U.S. population is currently undergoing a major demographic transition, with increasing racial and ethnic diversity of the older adult population. As the growing population of older adults advances in age, memory complaints are projected to increase in prevalence particularly among African Americans and present a challenge to clinicians who must differentiate between normal aging and progressive neurocognitive conditions (Celsis, 2000; Sherwin, 2000). As targeted therapeutic interventions and emerging therapies for AD are much more likely to be effective in the earlier stages of the disease (Loewenstein, Curiel, Duara & Buschke, 2017), early assessment and detection of AD, especially in …

Breaking Away: The Role Of Homeostatic Drive In Perpetuating Depression, Jonathan Tory Toole

Theses and Dissertations

The brain can be considered a complicated system of feedback mechanisms that maintain physiological homeostasis. Through psychological activity, neurochemicals act as homeostatic regulators. This study proposes that these components are part of a regulatory system that is capable of supporting multiple homeostatic regimes that, in turn, give rise to self-sustaining psychological behaviors. This project hypothesizes that such alternate regulatory programs may play a role in perpetuating psychological dysfunction. Interactions within and between components of the neurotransmitter network are represented as a set of discrete logic circuits. Neurotransmitter levels are linked to psychological constructs such as depression based on current literature. …

The Effects Of A Pathogenic Mutation And A Binding Partner On The Activity Of Polycystin Ion Channels, Haroon Alam Chaudhry

Theses and Dissertations

Mutations within polycystin-1 (PC1) and transcient receptor potential polycystin channel 2 (TRPP2) are the leading causes for development of the most common kidney disease, Autosomal Dominant Polycystic Kidney Disease (ADPKD). Although significant efforts have been made to investigate properties and characteristics of these proteins over the last three decades, their roles in ADPKD and how mutations in these proteins lead to cystogenesis is still largely unknown. In the current work, I have studied a novel TRPP2 mutation found in a patient family diagnosed with ADPKD that removes the stop codon and results in adding an additional twelve amino acids on …

Effectiveness And Mechanisms Of Change Of Mindfulness And Relaxation Training Delivered In A High School, Lana Tenaglia

Theses and Dissertations

This study addresses the lack of research on the effectiveness of two major treatments for an adolescent sample. Both mindfulness and relaxation training are two major interventions that can be utilized to improve symptomology for aggression, disruptive behavior, anxiety, depression, perceived stress, as well as for the improvement of self-concept and academic performance. The focus of this study is to compare the effectiveness of mindfulness and relaxation training in a non-clinical sample of adolescents. It was hypothesized that the participants in the mindfulness group would have greater decreased levels in all facets assigned with the exception of self-concept and academic …

Does Inhibitory Control And Emotion Regulation Alter The Degree To Which Aggressogenic Thought Is Expressed?, Jessica Lindsey Held

Theses and Dissertations

The effects of emotion dysregulation and inhibitory control on aggressogenic thought-behavior associations were investigated among 362 fifth- and sixth-grade boys (n = 195) and girls (n = 167) on Long Island, New York. Other-reported anger dysregulation and inhibitory control significantly qualified the relationship between all three cognitions (hostile attributions of intent, revenge goals in both ambiguous and unambiguous situations, and self-efficacy) and aggression. However, our predicted pattern for these 3-way interaction was supported only when the cognition involved self-efficacy—self-efficacy for aggression was most strongly associated with aggressive behavior under high levels of anger dysregulation and low levels of inhibitory control. …

One-To-One Ipad Technology: Perceptions Versus Practice, Christopher Pipala

Theses and Dissertations

This study sought to determine how iPads were used for instruction in the secondary schools of a suburban school district as well as determine if a relationship existed between teacher beliefs about technology and the potential level of transformative integration of the devices in classroom instruction. The Technological Pedagogical Content Knowledge (TPACK) and Substitution, Augmentation, Modification, and Redefinition (SAMR) models comprised the theoretical framework for this study to facilitate discussion about the level of instructional transformation that resulted from the use of iPad technology.

This study utilized the Technology Uses and Perceptions Survey (TUPS) and Technology Integration Matrix Reflection (TIM-R) …

Women For Ireland: Republican Feminism In The Northern Ireland Troubles, Laura Jacobsen

Theses and Dissertations

This paper studies the involvement of republican women in the Northern Ireland conflict, a struggle which defined life in Northern Ireland from 1969-1998. Too often, the Troubles, as the conflict is known, has been conceptualized as a struggle of men, while women are seen to be little more than suffering wives, girlfriends, and mothers. The image of “Mother Ireland” reinforces this notion: in this trope, Ireland is a woman begging for her sons to save her from British subjectivity. Similarly, contemporary feminist critics did not consider republican women to be equal to men. It was their belief that republican women …

Identifying Mcmi-Iv Personality Disorder Subgroups Using Exploratory Factor Analysis And Latent Class Analysis, Amanda Fisher

Theses and Dissertations

Patients diagnosed with personality disorders (PDs) have higher morbidity and mortality rates than those without PDs. The DSM-5 PD diagnoses and the cluster system lack a theoretical and empirical basis, which hinders the development of knowledge about PDs and interventions for PDs. This present study attempts to add to this literature by forming PD groups using a combination of exploratory factor analysis (EFA) and latent class analysis (LCA) based on PD scores from the Millon Clinical Multiaxial Inventory-IV (MCMI-IV), a method recommended by Gorman and Primavera (1983). Participants were 251 English speaking males and females ages 18 to 75 seeking …

Examining The Relationship Between Alzheimer’S Disease, Depression, And Social Support, Marko Lamela

Theses and Dissertations

This study examined the relationship between Alzheimer’s Disease and depression to determine whether a correlation existed and whether depression led to greater outcomes of Alzheimer’s Disease. Depression-Alzheimer’s relations have been mixed in previous research. Data from an existing data set of visitors to the Alzheimer’s Disease Centers with three or more visits (N= 19, 652) was used to test correlations between depression and Alzheimer’s, later odds of developing Alzheimer’s, and possible moderating effects of social support. A positive correlation was found between depression and Alzheimer’s Disease. Patients with depression were found to be more likely to have Alzheimer’s. There was …

Connections Between Parental Marital Status, Parental Involvement And Literacy Achievement Of Kindergarten Children, Saumendra Nath De

Theses and Dissertations

Marital relations and family structure have evolved over the years. Transformations in marriage, divorce, and cohabitation have altered family life in many parts of the world including the United States. Single-parent families are on the rise. Social scientists are concerned with the diminishing role of family and imminent decline in parental involvement in child’s education. This demands a closer look into the effects of parental marital relationships on parents’ involvement and children’s literacy outcomes. The current study examined the connections between parental marital status, parental involvement, and literacy outcomes of kindergarten children by using the nationally representative, Early Childhood Longitudinal …

Chemical Space Exploration Around Thieno[3,2-D]Pyrimidin-4(3h)-One Scaffold Led To A Novel Class Of Highly Active Clostridium Difficile Inhibitors, Xuwei Shao

Theses and Dissertations

Clostridium difficile infection (CDI) is the leading cause of healthcare-associated infection in the United States. Therefore, development of novel treatments for CDI is a high priority. Toward this goal, we began in vitro screening of a structurally diverse in-house library of 67 compounds against two pathogenic C. difficile strains (ATCC BAA 1870 and ATCC 43255), which yielded a hit compound, 2-methyl-8-nitroquinazolin-4(3H)-one (2) with moderate potency (MIC = 312/156 µM). Optimization of 2 gave lead compound 6a (2-methyl-7-nitrothieno[3,2-d]pyrimidin-4(3H)-one) with improved potency (MIC = 19/38 µM), selectivity over normal gut microflora, CC50s >606 µM against mammalian cell lines, and acceptable stability in …

Chemical Synthesis And Biological Evaluation Of Benzimidazoles As Chemotherapeutics, Leonard Barasa

Theses and Dissertations

Nitrogen-containing heterocycles are among the most important structural motifs of chemical substances, which are well represented among natural products, and pharmaceuticals. The presence of nitrogen in heterocycles help to modulates physicochemical properties and the pKa profile of therapeutic leads.

Benzimidazole is a heterocyclic structure and a privileged scaffold that is routinely used during drug discovery efforts. The benzimidazole scaffold has structural similarity to purine which makes it a useful structural motif for the development of pharmaceutical or biological interesting molecules. Benzimidazole derivatives possess a wide variety of biological activities, including anti-bacterial, anti-cancer, and anti-inflammatory activities. Development of synthetic methods to …

Continuous Salt Synthesis And Granulation Using Single Step Twin Screw Extrusion Process, Jaydip Vasoya

Theses and Dissertations

In the present investigation, a continuous, and novel organic solvent-free approach for the synthesis of pharmaceutical salts using the twin screw extruder (TSE) is reported. Although the method offers distinct advantages such as solvent free synthesis and short processing time over the conventional salt synthesis, the produced salts usually require further processing into granules before they can be compressed into tablets or filled into capsules, which makes the final product manufacturing non-continuous. This report, for the first time, describes a process of combining salt synthesis and granulation into a single-step using a TSE. Cinnarizine, a model poorly water-soluble weakly basic …

Oil/Water Nanoemulsion Biodistribution In Mice Upon Intravenous Administration, Jiayi Chen

Theses and Dissertations

The present study aimed to explore the biodistribution of O/W nanoemulsions (NE) upon intravenous administration. Three NEs were prepared with distinctive droplet sizes: SE (29 ± 1 nm), ME (214 ± 2 nm) and LE (883 ± 16 nm) without overlapping of the size distribution. Kolliphor® HS15 was used as the only surfactant for these three NEs, so that their droplets had similar surface structure. The NEs droplet size was stable under room temperature for minimum 3 days in phosphate buffer saline (PBS) and in mice plasma in vitro for 4-hour at 37°C. A lipophilic fluorescent dye, 1, 1’-dioctadecyl-3, 3, …

Acetoacetate Enhances Oxidative Metabolism And Response To Toxicants Of Cultured Renal Cells, Trudi Maria Denoon

Theses and Dissertations

In vitro methods can be cost effective and facilitate large scale drug screening in the pharmaceutical industry. Renal proximal tubular cells have been a prime target for drug induced toxicity. LLC-PK1 cells possess many transport functions of the proximal tubule epithelia, however, its energy metabolism differs from the highly oxidative tubule metabolism in vivo. This may impact its reliability in predicting toxicity. Modulating the growth media composition has been shown to shift cultured liver and muscle cells from high glycolytic activity to increased oxidative metabolism, but few studies have been done on renal cells. This study is designed to test …

Development, Evaluation And Application Of Insulin Solution And Film Dosage Forms For Sublingual Administration, Anuja Paprikar

Theses and Dissertations

The major barrier for sublingual absorption of large molecules like insulin is low permeability owing to the hydrophilic nature of insulin. One approach to overcome this barrier is to sublingually co-administer insulin with permeation enhancers (HPβCD and poloxamer 188). In vitro performance of permeation enhancers was screened across cellulose acetate membrane to select the concentrations of both enhancers, which were further evaluated across four models (MatTek tissue model, MDCK cell line, rat and porcine esophagus). The insulin solution with combination of HPβCD (5%) and poloxamer 188 (0.5%) indicates higher permeation as compared to that of only insulin across all the …

Chronic Exposure To Opioids Down-Regulates Genomic Histone Modifications And Disrupts Stat3 Gene Expression In Human Induced Pluripotent Stem Cells, Anirudh Jagannadh Chintalapati

Theses and Dissertations

Examining epigenetic (EG) manifestations and genomic heterogeneity is a novel perspective to understand opioid induced toxicity. Aberrations in histone protein post-translational modifications (HP-PTM) induce perturbations in chromatin integrity resulting in consequences for genomic expression patterns. In the current study, we hypothesize that chronic exposure to morphine sulfate (MS) alters histone-3-protein (H3)-PTM and disrupts STAT3 gene expression in human induced pluripotent stem cells (iPSC). We analyzed 21 genomic H3-PTM following exposure to 1 and 10 uM MS for 2 and 5 days. The results showed decreases in levels of repressive H3-PTM, namely H3K9me1 (2 day) and H3K27me3 (5 day). To confirm …

Chemical Synthesis And Evaluation Of Azotochelin Analogs As Anticancer Agents And Their Ability To Reverse Anticancer Drug Resistance, Nishant Karadkhelkar

Theses and Dissertations

Cancer has been plaguing the humanity for several decades. In the meanwhile, multi-drug resistance (MDR) is causing abatement of effective therapeutic drugs, necessitating discovery of new class of anticancer agents. Natural products have been proved to be a promising source of structurally new anticancer agents. A specific class of bacterial secondary metabolites, named siderophores have been explored as potential anticancer agents. Enterobactin is one of the most studied siderophores as a potential anticancer agent. Azotochelin is a structurally similar but structurally simpler siderophore compared to enterobactin. Our research project focused on the evaluation of the structure activity relationship assessment of …

The Ion Channel Function Of Polycystin‐1 In The Polycystin‐1/Polycystin‐2 Complex, Zhifei Wang

Theses and Dissertations

Autosomal dominant polycystic kidney disease is caused by mutations in polycystin-1 (also known as PKD1), a polycystic kidney disease protein, or polycystin-2 (also known as PKD2 or TRPP2), a transient receptor potential channel. Polycystin-1 and polycystin-2 form a receptor-ion channel complex located in primary cilia. The function of this complex, especially the role of polycystin-1, is largely unknown due to the lack of a reliable function assay. In this study, we dissect the role of polycystin-1 by directly recording current from a gain-of-function polycystin-1/polycystin-2 channel. Our data show that this channel has distinct properties from that of the homomeric polycystin-2 …

Neurocognition In Individuals At High Familial Risk For Major Depressive Disorder, Rachel Gaia Venezia

Theses and Dissertations

Neurocognitive deficits may qualify as vulnerability markers in individuals at risk for developing MDD. We examined the extent to which characteristic neurocognitive difficulties in MDD may be apparent in early to late adolescence in the offspring of a parent with MDD, as well as the extent to which other factors, such as a history of comorbid diagnoses (e.g., ADHD), a history of MDD, and a current depressive episode, might confound to these differences. Offspring of patients with MDD (n=184) and a healthy normative sample (n=88) were compared on measures assessing attention, working memory, impulse control, and visual memory. The two …

Gat107 Improves Survival By Attenuating Hyperoxia-Compromised Host Defense In Bacterial Clearance In The Lungs Via Alleviating Redox Imbalance In Macrophages, Alex Gauthier

Theses and Dissertations

Prolonged exposure to hyperoxia can compromise macrophage bacterial clearance functions, contributing to the increased susceptibility to pulmonary infections observed in hospital and ventilator-associated pneumonia (HAP/VAP). Previously studies in our lab demonstrate that activation of the α7 nicotinic acetylcholine receptor (α7nAChR) has protective effects against proinflammatory lung injury in animals subjected to prolonged hyperoxic exposure and bacterial infections. In this study, we demonstrated that administration of GAT107, an α7nAChR agonistic positive allosteric modulator (ago-PAM), improved survival by attenuating hyperoxia-compromised bacterial clearing functions of mice with Pseudomonas aeruginosa (PA) lung infection. GAT107 decreased the bacterial burden in mice lungs by attenuating the …

Ptsd And Immunological Correlations Of Attention And Working Memory In Gulf War Illness, Mary Jeffrey

Theses and Dissertations

Gulf War Illness (GWI) impacts 25 to 32 percent of those deployed in the 1991 Gulf War (White et al., 2016) and includes symptoms related to fatigue and mood/neurological disturbances. Therefore, it is difficult to ascertain the influence of trauma exposure and chemical exposure when investigating neuropsychological symptoms. This cross-sectional study utilized a group of veterans with and without GWI (n=61) to investigate: 1) the unique impact that GWI has on a survey measure of attention and memory or the Paced Auditory Serial Addition Test (PASAT). We also investigated how PTSD symptoms, followed by fatigue levels, improved the GWI model …