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Articles 61 - 90 of 393
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Ethnic Effects On Biological, Psychosocial And Disease Care Factors In African-American Youth With Type 1 Diabetes, Priscilla Powell
Ethnic Effects On Biological, Psychosocial And Disease Care Factors In African-American Youth With Type 1 Diabetes, Priscilla Powell
Theses and Dissertations
Person-oriented and variable-oriented analyses were conducted to investigate sociodemographic differences in biological, psychosocial and disease care factors in youth with type 1 diabetes. Additionally, diabetes knowledge was evaluated as a potential mediator of SES effects on HbA1c and disease care. The sample included 349 youth, age 9-17 years (79.9% Caucasian, 71.3% lived with two biological parents, M SES = 46.24). Person-oriented t-tests confirmed commonly reported ethnic differences in HbA1c and disease care behaviors. However, variable-oriented analyses controlling for confounding sociodemographic influences showed most disease care effects attributed to ethnicity were better explained by SES. While diabetes knowledge was not a …
Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia
Optimization Of Functional Mri Methods For Olfactory Interventional Studies At 3t, Vishwadeep Ahluwalia
Theses and Dissertations
Functional MRI technique is vital in investigating the effect of an intervention on cortical activation in normal and patient population. In many such investigations, block stimulation paradigms are still the preferred method of inducing brain activation during functional imaging sessions because of the high BOLD response, ease in implementation and subject compliance especially in patient population. However, effect of an intervention can be validly interpreted only after reproducibility of a detectable BOLD response evoked by the stimulation paradigm is first verified in the absence of the intervention. Detecting a large BOLD response that is also reproducible is a difficult task …
Examining The Mindfulness – Stress Resistance Relation: The Mediational Role Of Autonomy, Melissa Holt
Examining The Mindfulness – Stress Resistance Relation: The Mediational Role Of Autonomy, Melissa Holt
Theses and Dissertations
Mindfulness – a receptive attentiveness to present experience – has been shown to promote more adaptive emotion regulation (Brown, et al. 2007) and predict autonomy - motivation to behave in a self-directed manner. In turn, autonomy has been shown to predict self-regulation (Ryan & Deci, 2000). This suggests a psychological pathway from mindfulness to autonomy to emotion regulation. To better understand the regulatory potential of a mindful disposition and the possible mediating role of autonomy in healthy adult participants (N = 69), a laboratory social evaluative threat was used called the Trier Social Stress Task (Kirschbaum, et al., 1993). Results …
Robust Protective Factors That Help Youths With A Parent Experiencing Depression Achieve Positive Adjustment, Hsing-Jung Chen
Robust Protective Factors That Help Youths With A Parent Experiencing Depression Achieve Positive Adjustment, Hsing-Jung Chen
Theses and Dissertations
Based on a resilience framework, the purpose of this study was to address knowledge gaps about minority youths who lived in rural and poor areas, had a primary caregiver with a diagnosis of depression, and faced multiple psychosocial stressors. Three research objectives included: 1) To explore the association between ecological protective factors and four developmental outcomes-emotional adjustment, behavioral adjustment, school performance, and educational aspiration; 2) To identify the robust protective factors; and 3) To explore the interactive relationships between risk and robust protective factors. Families (N=126) where the primary caregiver had a diagnosis of major depression and had a child …
Quantitative Analysis Of Tobacco Specific Nitrosamine In Human Urine Using Molecularly Imprinted Polymers As A Potential Tool For Cancer Risk Assessment, Kumar Shah
Theses and Dissertations
Measuring urinary tobacco specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronide conjugate may provide the best biomarker of tobacco smoke lung carcinogen metabolism. Existence of differences in the extent of NNAL metabolism rates may be potentially related to an individuals’ lung cancer susceptibility. Low concentrations of NNAL in smokers urine (<1 ng/mL) require sensitive and selective methods for analysis. Traditionally, this involves extensive, time-consuming sample preparation that limits throughput and adds to measurement variability. Molecularly imprinted polymers (MIPs) have been developed for the analysis of urinary NNAL by offline cartridge extraction combined with LC-MS/MS. This method when reproduced demonstrated problems with matrix effects. In the first part of this work, investigation of matrix effects and related problems with sensitivity for the published offline extraction method has been conducted. In order to address the need to improve throughput and other analytical figures of merit for the original method, the second part of this work deals with development of a high-throughput online microfluidic method using capillary-columns packed with MIP beads for the analysis of urinary NNAL. The method was validated as per the FDA guidance, and enabled low volume, rapid analysis of urinary NNAL by direct injection on a microfluidic column packed with NNAL specific MIP beads. The method was used for analysis of urinary NNAL and NNAL-Gluc in smokers. Chemometric methods were used with this data to develop a potential cancer-risk-assessment tool based on pattern recognition in the concentrations of these compounds in urine. In the last part, method comparison approaches for the online and the offline sample extraction techniques were investigated. A ‘fixed’ range acceptance criterion based on combined considerations of method precision and accuracy, and the FDA bioanalytical guidance limits on precision and accuracy was proposed. Data simulations studies to evaluate the probabilities of successful transfers using the proposed criteria were performed. Various experimental designs were evaluated and a design comprised of 3 runs with 3 replicates each with an acceptance range of ±20% was found appropriate. The off-line and the on-line sample extraction methods for NNAL analysis were found comparable using the proposed fixed range acceptance criteria.
Nonlinear Models In Multivariate Population Bioequivalence Testing, Bassam Dahman
Nonlinear Models In Multivariate Population Bioequivalence Testing, Bassam Dahman
Theses and Dissertations
In this dissertation a methodology is proposed for simultaneously evaluating the population bioequivalence (PBE) of a generic drug to a pre-licensed drug, or the bioequivalence of two formulations of a drug using multiple correlated pharmacokinetic metrics. The univariate criterion that is accepted by the food and drug administration (FDA) for testing population bioequivalence is generalized. Very few approaches for testing multivariate extensions of PBE have appeared in the literature. One method uses the trace of the covariance matrix as a measure of total variability, and another uses a pooled variance instead of the reference variance. The former ignores the correlation …
Unseen, Sohee Kwon
Unseen, Sohee Kwon
Theses and Dissertations
Photography conveys informative data, aesthetic value, and a conceptual message very much like graphic design. In the hands of the photographer, the viewfinder of a camera becomes an editing tool. Editing by point of view, use of color and cropping determines a great deal about the communication made by imagery. In my creative project, I will explore photography as a means to generate form, concept, and content. As a result of this exploration, I expect to find new ways of approaching graphic design problems. My goal is to develop themes that combine aspects of photography and graphic design. Themes could …
Seasons, Paula Golden
Seasons, Paula Golden
Theses and Dissertations
A sense of place and time has been the unconscious focus of my adult life. While living in Hawaii I often searched for ancient rock carving sites. These art forms have the ability to convey the mystery, magic and history of previous times. I use human figures, beads and various textiles with similarities to these petroglyphs as a powerful metaphor for my search to find a place that is home
The Genetic Epidemiology Of Purging Disorder, Anorexia Nervosa, And Obsessive Compulsive Personality Disorder, Sara Trace
Theses and Dissertations
Although a variety of factors influence the development of eating disorders, genetic factors contribute notably to their etiology. Understanding genetic factors associated with eating disorders is important, as they can influence how these disorders are recognized, researched, and treated. This dissertation included two studies addressing important questions within the fields of eating disorders and genetics; specifically, Study 1 addressed the prevalence and heritability of purging and purging disorder in a population-based sample of female twins from the United States; and Study 2 investigated the nature of the co-morbidity between anorexia nervosa and obsessive compulsive personality disorder in a population-based sample …
A Study Of The Impact Of The Alternative Intervention Program On Improving Student Achievement, Attendance, And Discipline, Beverly Allen-Hardy
A Study Of The Impact Of The Alternative Intervention Program On Improving Student Achievement, Attendance, And Discipline, Beverly Allen-Hardy
Theses and Dissertations
This mixed methods study sought to examine student perceptions of the impact of an alternative intervention program (AIP), and provide a framework meant to inspire programs in other locations. Focusing on attendance, discipline, and academic achievement data, this study examined what factors motivate successful alternative education students to succeed upon their return to the comprehensive setting, and identify support factors that foster resiliency. Qualitative data were collected through three focus groups of students who were either new to the program, enrolled in the program for at least a nine-week period, and students who successfully completed a nine-week placement. Six adult …
Dilute Sulfuric Acid Pretreatment Of Switchgrass In Microwave Reactor For Biofuel Conversion: An Investigation Of Yields, Kinetics,, Oscar Martin
Theses and Dissertations
Lignocellulosic materials provide a raw material source for biofuel conversion and offer several advantages over fossil fuels- usage of a renewable resource, reduced greenhouse emissions, a decreased dependence on foreign oil, and stimulation of the agricultural sector. However, a primary technological challenge in converting lignocellulosic biomass into fuel is overcoming the recalcitrance of its matrix to enzymatic hydrolysis. To overcome these problems for chemical processing, naturally occurring cellulose biomass must be pretreated before it can be further processed using enzymatic hydrolysis or bioconversion. The goal of this work was to develop a model that predicts the glucose yield (pretreatment and …
Nonhomologous End-Joining: Tdp1-Mediated Processing, Atm-Mediated Signaling, Amy Hawkins
Nonhomologous End-Joining: Tdp1-Mediated Processing, Atm-Mediated Signaling, Amy Hawkins
Theses and Dissertations
This thesis investigates two separate features of nonhomologous end-joining (NHEJ) DNA repair: end processing, and DNA repair kinase signaling. DNA end processing was investigated in a mouse model of hereditary spinocerebellar ataxia with axonal neuropathy (SCAN1), a congenital neurodegenerative disease. SCAN1 is caused by a homozygous H493R mutation in the active site of tyrosyl-DNA phosphodiesterase (TDP1). To address how the H493R mutation elicits the specific pathologies of SCAN1 and to further elucidate the role of TDP1 in processing DNA end modifications, we generated a Tdp1 knockout mouse and characterized their behavior and specific repair deficiencies in extracts of embryonic fibroblasts …
The Effectiveness Of Religiously Tailored Couple Counseling, Joshua Hook
The Effectiveness Of Religiously Tailored Couple Counseling, Joshua Hook
Theses and Dissertations
Large numbers of couples seek treatment from religious counselors who integrate religion and spirituality (R/S) into counseling. The present dissertation reviewed the literature examining the effectiveness of R/S counseling. Several R/S treatments were helpful in treating psychological problems. There was little evidence that R/S treatments outperformed secular treatments. In Study 1, a nationwide survey was conducted that examined the beliefs of Christian counselors about integrating R/S into couple counseling. Christian counselors (N = 630) completed measures of religious commitment, experience in couple counseling, attitudes toward using religious techniques in couple counseling, and the use of theory in couple counseling. Counselors …
Joint Mixed-Effects Models For Longitudinal Data Analysis: An Application For The Metabolic Syndrome, John Thorp Iii
Joint Mixed-Effects Models For Longitudinal Data Analysis: An Application For The Metabolic Syndrome, John Thorp Iii
Theses and Dissertations
Mixed-effects models are commonly used to model longitudinal data as they can appropriately account for within and between subject sources of variability. Univariate mixed effect modeling strategies are well developed for a single outcome (response) variable that may be continuous (e.g. Gaussian) or categorical (e.g. binary, Poisson) in nature. Only recently have extensions been discussed for jointly modeling multiple outcome variables measures longitudinally. Many diseases processes are a function of several factors that are correlated. For example, the metabolic syndrome, a constellation of cardiovascular risk factors associated with an increased risk of cardiovascular disease and type 2 diabetes, is often …
Denitration In Colonic Smooth Muscle, Seemab Malick
Denitration In Colonic Smooth Muscle, Seemab Malick
Theses and Dissertations
Tyrosine nitration results in altered function of smooth muscle voltage-gated L-type calcium channel. We explored the possibility that smooth muscle contains denitrase activity to allow functional recovery of the calcium channel without requiring synthesis of new channel proteins. Following peroxynitrite treatment of mouse colonic smooth muscle strips, CaCl2 (1 mM)-induced smooth muscle contraction was significantly reduced by 67% (P ≤ 0.05), which reversed by approximately 86% upon periodic washing within 2 hr period (P ≤ 0.001). The effect of the c-Src kinase inhibitor, PP2, on muscle contraction was also restored after 2 hr post-peroxynitrite treatment consistent with the thesis that …
Development Of Rapid Die Wear Test Method For Assessment Of Die Life And Performance In Stamping Of Advanced/Ultra High Strength Steel (A/Uhss) Sheet Materials, Omer Necati Cora
Development Of Rapid Die Wear Test Method For Assessment Of Die Life And Performance In Stamping Of Advanced/Ultra High Strength Steel (A/Uhss) Sheet Materials, Omer Necati Cora
Theses and Dissertations
Automotive companies are actively pursuing to increase the use of high-strength-lightweight alloys such as aluminum, magnesium, and advanced/ultra high-strength steels (A/UHSS) in body panel and structural part applications to achieve fuel efficiency while satisfying several environmental and safety concerns. A/UHSS sheet materials with higher strength and crashworthiness capabilities, in comparison to mild steel alloys, are considered as a near-term (i.e., ~5 years) choice of material for body and structural components due to their relatively low cost when compared with other lightweight materials such as aluminum and magnesium. However, A/UHSS materials present an increased level of die wear and springback in …
Loving You Saved My Life, Laine Bowen
Loving You Saved My Life, Laine Bowen
Theses and Dissertations
When I create art it is as though I am building a metaphorical cathedral. Although there is serenity and faith within the process, there simultaneously exists an equal measure of frustration and mystery in the final outcome. At times I am like an ancient Chinese monk who, scrambling to please a merciless emperor, stumbles at last upon his pet cricket’s cage and using this accidental inspiration designs the perfect plan for the Forbidden City. My art then, at its best, possesses the rigidity of ritual, the flexibility of enlightenment and the joy of invention. I believe in the power of …
Facing Faces, John Luck
Facing Faces, John Luck
Theses and Dissertations
I am a surrealist at heart. I enjoy the creative process of making a visual story that uses unusual imagery. Every work is a reflection of some part of my aesthetic belief: an outgrowth of my individuality. The art I produce is a direct reflection of my personality, beliefs, values, and experiences. I wear my emotions on my sleeve and I have a strong sense of identity. My work exhibits intense colors and strong contrasts. Each has its own underlying subtleties that express the inner depth of the concept. A little attention-deficient and a little bipolar, I am an erratic …
Age-Related Genetic And Epigenetic Chromosomal Changes: A Twin Study, Kimberly Jones
Age-Related Genetic And Epigenetic Chromosomal Changes: A Twin Study, Kimberly Jones
Theses and Dissertations
The primary aims of this study were to examine acquired genetic and epigenetic changes that occur in individuals with increasing age and to determine how these changes are influenced by genetic/environmental factors. Acquired genetic changes were assessed by determining the frequency and chromosomal contents of spontaneously occurring micronuclei in identical and fraternal twins. A total of 115 individuals (48 twin pairs and 19 singletons) were evaluated, ranging in age from 7 to 85 years. As expected, micronuclei frequencies, which are indicative of genomic damage, significantly increased with age (p<0.0001, r=0.446). The majority of micronuclei (32%) contained sex chromosomes and the frequency of sex chromosome-bearing micronuclei significantly increased with age (p<0.0001). The frequency of autosome-containing micronuclei was not significantly influenced by age or gender. However, some autosomes were seen more (chromosomes 4, 8, and 9) or less (chromosomes 17 and 22) frequently than expected by chance (p<0.05). An evaluation of the numerical contents of the sex chromosome-containing micronuclei and their corresponding binucleates showed that the majority of the binucleates had an abnormal chromosomal complement (either hypodiploid or hyperdiploid), with the subset of binucleates having a normal chromosomal complement decreasing with age for both the Y chromosome in males and the X chromosome in females. Model fitting, implemented in Mx, showed the variation in the frequency of micronuclei to be best explained by either additive genetic and unique environmental components, or common and unique environmental factors. Specific environmental exposures and health conditions that were shown to influence micronuclei frequencies, included: multivitamins, leafy green vegetables, fruit, vitamin E supplements, arthritis, heart disease, allergies, and alcohol. To assess acquired epigenetic changes, global methylation profiles of two identical twin pairs were compared and found to differ, indicating that individuals do develop alterations in their methylation profiles with age. Furthermore, the twin pair having a significant difference in their micronuclei frequencies and environmental exposures had more differences in their methylation pattern compared to the twin pair whose micronuclei frequencies and environmental factors did not differ. Overall, genetic and epigenetic changes were shown to occur with age and to be influenced by genetic and lifestyle factors.
Design And Development Of A Pvdf Sensor To Monitor Intracranial Pressure (Icp), Vivek Vijaywargi
Design And Development Of A Pvdf Sensor To Monitor Intracranial Pressure (Icp), Vivek Vijaywargi
Theses and Dissertations
Monitoring ICP non-invasively is a challenge. A novel method to measure ICP using actuators and sensors has been proposed where the skull is vibrated at high frequencies and the receiving signal is measured at the surface eyelid. A design of experiments approach is used to develop the sensor part of the ICP monitoring device so that gain can be maximized using factors such as area, thickness, electrode, and applied pressure. Statistical analysis showed that thickness has the biggest effect on overall gain. Numerical analysis confirmed these results. In addition, sensor packaging is optimized to minimize dampening of the signal and …
Mechanical Behavior And Length Adaptation Of Rabbit Bladder Smooth Muscle, Atheer Almasri
Mechanical Behavior And Length Adaptation Of Rabbit Bladder Smooth Muscle, Atheer Almasri
Theses and Dissertations
Overactive bladder (OAB), involuntary contractions during bladder filling, is a common condition affecting 17% of the adult population worldwide, and in the U.S. ranks ahead of diabetes in a list of the 10 most common chronic disorders (Mullins 2009). Mechanical mechanisms contributing to OAB are not completely understood and because of the unique function and broad volume range of the bladder, there may be mechanical characteristics that distinguish detrusor smooth muscle (DSM) in bladder from other smooth muscles. Recent studies have shown that the length-passive tension curve in DSM exhibits adjustable passive stiffness (APS) characterized by a passive curve that …
Impact Of Statin Therapy On Outcomes In Aneurysmal Subarachnoid Hemorrhage Patients, Abdulkhaliq Alsalman
Impact Of Statin Therapy On Outcomes In Aneurysmal Subarachnoid Hemorrhage Patients, Abdulkhaliq Alsalman
Theses and Dissertations
There is conflicting data on the effects of statins on cerebral vasospasm and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH) patients. In this retrospective cohort study, patients were divided into those who received pravastatin (PRAV group) 40mg/d and those who did not (NP group). Data were analyzed using multivariate logistic regression. Eighty-one patients met inclusion criteria. There was a statistically significant decreased in the incidence of vasospasm in the PRAV group; however, this association did not retain significance after adjusting for WFNS, race, elevated WBC, and clipping (59% PRAV vs. 88% NP, p=0.08). There was no statistically significant difference in …
Environmental And Organizational Factors Influencing Similarities And Differences Between Nonprofit Human Service Providers That Are Faith-Based And Those With No Religious Affiliation, Geraldine Lewis Meeks
Environmental And Organizational Factors Influencing Similarities And Differences Between Nonprofit Human Service Providers That Are Faith-Based And Those With No Religious Affiliation, Geraldine Lewis Meeks
Theses and Dissertations
The American social welfare system is a mixed system consisting of loosely coupled government programs, private nonprofit and for-profit organizations, grassroots and religious entities. Although religious entities historically played a key role in the development of the social welfare system, the faith-based initiative of President George W. Bush targeted religious service providers to receive government funding and take on a larger role in service delivery to at-risk populations based on the belief that these providers were substantially different from traditional providers. Using a cross-sectional research design and a survey instrument created for the study, data was collected from 121 nonprofit …
Systematics And Biogeography Of The Didymopanax Group Of Schefflera (Araliaceae), Pedro Fiaschi
Systematics And Biogeography Of The Didymopanax Group Of Schefflera (Araliaceae), Pedro Fiaschi
Theses and Dissertations
Schefflera is the largest genus in the angiosperm family Araliaceae, with about 900 species, of which c. 300 belong to five subgeneric groups in the Neotropical region. Previous phylogenetic studies of Schefflera have been limited to a small number of species from this region, and very little is know about phylogenetic relationships in the Brazilian-centered Didymopanax group of this genus. Therefore, to gain a better understanding of the diversity and evolution of the Didymopanax group of Schefflera, I investigated the systematics of these plants in the broader context of the entire Neotropical clade. The main goals were (1) to investigate …
Sphingolipid-Induced Activation Of The Volume-Sensitive Cl− Current Is Mediated By Mitochondrial Reactive Oxygen Species, Frank Raucci
Sphingolipid-Induced Activation Of The Volume-Sensitive Cl− Current Is Mediated By Mitochondrial Reactive Oxygen Species, Frank Raucci
Theses and Dissertations
Swelling-activated Cl− current (ICl,swell) is an outwardly-rectifying current that plays an important role in cardiac electrical activity, cellular volume regulation, apoptosis, and acts as a potential effector of mechanoelectrical feedback. Persistent activation of ICl,swell has been observed in a number of models of cardiovascular disease. Previously we showed that angiotensin II (Ang II), endothelin-1 (ET-1), endothelial growth factor receptor (EGFR), and reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and mitochondria are involved in the activation of ICl,swell by both osmotic swelling and Beta1 integrin stretch. Sphingolipid metabolism is modulated in several cardiopathologies and because sphingolipids are bioactive lipids …
The Design And Validation Of A Computational Rigid Body Model Of The Elbow., Edward Spratley
The Design And Validation Of A Computational Rigid Body Model Of The Elbow., Edward Spratley
Theses and Dissertations
The use of computational modeling is an effective and inexpensive way to predict the response of complex systems to various perturbations. However, not until the early 1990s had this technology been used to predict the behavior of physiological systems, specifically the human skeletal system. To that end, a computational model of the human elbow joint was developed using computed topography (CT) scans of cadaveric donor tissue, as well as the commercially available software package SolidWorks™. The kinematic function of the joint model was then defined through 3D reconstructions of the osteoarticular surfaces and various soft-tissue constraints. The model was validated …
Development Of A Mechanical Cavopulmonary Assist Device For The Failing Fontan Patients, Jugal Kapadia
Development Of A Mechanical Cavopulmonary Assist Device For The Failing Fontan Patients, Jugal Kapadia
Theses and Dissertations
The long term objective of this research is to develop a collapsible, percutaneously inserted, axial flow blood pump to improve blood flow in the cavopulmonary circulation. Through this research, the experimental evaluation of five blood pump prototypes and hemolysis testing of one blood pump prototype were performed. All prototypes demonstrated acceptable hydraulic performance. A comparison of the experimental results with numerical predictions demonstrated a 10-20% deviation, an acceptable range per industry standard. Hemolysis testing of a four bladed adult blood pump showed plasma free hemoglobin level of 20.04 mg/dL and maximum NIH (normalized index of hemolysis) level was 0.017 g/100L. …
The Influence Of Parental Verbal Messages About Fighting And Nonviolent Responses On Adolescent Aggressive And Effective Nonviolent Behavior, Alison Kramer
Theses and Dissertations
Research suggests that adolescent health requires both reducing problem behavior and promoting the development of social competence. There is strong support for the influence of parenting practices on both aggressive and competent behavior. However, there has been little research to date focused on parental messages, or the verbal communication parents provide to their children, about aggressive and effective nonviolent responses to conflict. The present study used hierarchical regression to examine parental messages supporting fighting and parental messages supporting effective nonviolent responses to problem situations in relation to adolescent aggressive and effective nonviolent behavior. These relations were expected to be moderated …
Parent-Adolescent Discrepancies In Ratings Of Youth Victimization: Associations With Psychological Adjustment, Kimberly Goodman
Parent-Adolescent Discrepancies In Ratings Of Youth Victimization: Associations With Psychological Adjustment, Kimberly Goodman
Theses and Dissertations
Epidemiological research indicates that parents report lower levels of youths’ exposure to violence than youth self-report, and theory suggests that such discrepancies reflect parents’ lack of knowledge of youth victimization and impaired ability to help children cope with victimization. This study extends prior research examining the implications of parent-youth informant discrepancies on ratings of victimization. Latent class analysis (LCA) was employed to identify groups of dyads distinguished by patterns of parent and youth report of victimization, uncovering heterogeneity based on patterns of parent-youth ratings of victimization. Analyses examined how latent classes reflecting parent-youth agreement on victimization were related to adjustment …
The Regulation Of Alternative Splicing By Oncogenic Signaling Pathways., Jacqueline Shultz
The Regulation Of Alternative Splicing By Oncogenic Signaling Pathways., Jacqueline Shultz
Theses and Dissertations
In the presented study, we demonstrate that the alternative splicing of caspase 9 was dysregulated in a large percentage of NSCLC tumors and cell lines. These findings led to the hypothesis that survival pathways activated by oncogenic mutation regulated this mechanism. Indeed, the oncogenic PI3-Kinase/Akt pathway was demonstrated to regulate the alternative splicing of caspase 9. Further mechanistic studies demonstrate that multiple Akt isoforms can regulate the alternative splicing of caspase 9 in NSCLC. Akt was additionally shown to mediate the exclusion of the exon 3,4,5,6 cassette of caspase 9 via the phospho-state of the RNA trans-factor, SRp30a. Mutagenesis studies …