Digital Commons Network^™

Impact Of Kras/Nras Mutational Heterogeneity On Clinical Outcomes In Colorectal Cancer, Jonathan M. Loree

Dissertations and Theses (Open Access)

Introduction: Mutations in KRAS/NRAS (RAS) predict a lack of benefit from anti-EGFR agents in metastatic colorectal cancer (mCRC). As next generation sequencing (NGS) has advanced, we are discovering atypical and low allele frequency mutations. We aimed to evaluate how NGS can optimally define RAS mutant CRC and the role of relative mutant allele frequency (rMAF) as a biomarker.

Methods: Using institutional and public cohorts of mCRC patients with NGS results, we described the prevalence and clinical impact of atypical (not in current guidelines) and low rMAF RAS mutations (RAS MAF by the MAF of the mutated gene with …

Quality Of Life: Socio-Demographic And Genetic Determinants As Well As Links With Cancer Outcomes, Jeanne Pierzynski

Dissertations and Theses (Open Access)

Quality of life (QOL) is an independent prognostic factor for cancer. Lung cancer is the leading cause of cancer death. Breast cancer is the most diagnosed. Bladder cancer is the most expensive cancer to treat because of its high recurrence rate. We set to perform comprehensive analyses of predictors of QOL in these cancer sites with the future goal of improving QOL and outcomes.

In 6,456 newly diagnosed lung cancer patients, we investigated the relationship between baseline patient characteristics and QOL to identify determinants of QOL. A QOL questionnaire (SF-12v1) measured patients’ physical component summary (PCS) and mental component summary …

Dynamic Assessment Of Nk Cell Interactions With Pediatric Tumor Cells To Predict Response To Immunotherapy, Arianexys Aquino Lopez

Dissertations and Theses (Open Access)

Due to Natural Killer (NK) cells’ capacity to target tumor cells without prior sensitization, adoptive NK cell therapy represents a promising immunotherapy approach for pediatric cancer patients. Our laboratory has developed an NK cell expansion protocol that generates large quantities of NK cells for therapeutic infusion. Given that NK cells are heterogeneous, with variable receptor expression and potential to target tumor cells, the purpose of my study was to determine whether subpopulations of NK cells with enhanced anti-tumor potential could be identified for increased potency of the NK cell infusion product. In addition, we previously showed that our expanded NK …

Characterization Of Notch1 And Pi3k-Pten-Akt/Mtor Pathway Interaction In Head And Neck Squamous Cell Carcinoma, Kyriante' Henry

Dissertations and Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) affects various mucosal sites of the upper aerodigestive tract, including the nasal and oral cavities, the nasopharynx, and the oropharynx. More than five hundred thousand new cases of HNSCC occurred in 2011 alone, with 50,000 reported cases in the United States. This trend made HNSCC the seventh most common non-skin cancer worldwide (Ferlay et al., 2015). Although significant epidemiological and pathological advancements have been made, survival rates have not improved much over the last 40 years, leaving a mortality rate that remains at approximately 50%. An unbiased drug screen demonstrated that HNSCC cell …

The Functions Of Setd5 And Mir-221 In Embryonic Stem Cell Differentiation, Tsai-Yu Chen

Dissertations and Theses (Open Access)

Embryonic stem cells (ESCs) are a widely used model system to study cellular differentiation because of their pluripotent characteristics, and ESC differentiation is an epigenetic process. In an effort to identify a new epigenetic factor that is required for ESC differentiation, the function of SETD5 in ESCs was studied for this thesis. Results show that SETD5 is essential for retinoic acid (RA)-induced differentiation of mouse ESCs and for RA-induced expression of critical developmental genes (e.g., Hoxa1 and Hoxa2) and neuron-related genes (e.g., Nestin and Pax6). SETD5 was upregulated during ESC differentiation. Additional results demonstrated that SETD5 bound to …

Circulating Autoantibodies In Human Traumatic Spinal Cord Injury Subjects And Their Relationship To The Development Of Neuropathic Pain, Georgene Hergenroeder

Dissertations and Theses (Open Access)

Background:

Approximately 17,500 spinal cord injuries (SCI) occur yearly in the U.S. causing considerable morbidity and mortality. Neuropathic pain (NP) ensues in 40-70% of SCI. An autoimmune response resulting from disruption of the blood-spinal cord-barrier may be a contributor to NP. However, the relationship between autoantibodies and NP after SCI in humans has not been thoroughly characterized nor have autoantigens been identified. Glial fibrillary acidic protein (GFAP) and collapsin response mediator protein2 (CRMP2) were identified as candidate autoantigens. The hypothesis is that proteins from the injured spinal cord released by SCI trigger autoantibody production which can lead to the development …

Modeling Post Stroke Respiratory Dysfunction, Apneas And Cognitive Decline, Anthony Patrizz

Dissertations and Theses (Open Access)

Modeling Post Stroke Respiratory Dysfunction,

Apneas and Cognitive Decline

Anthony Patrizz, B.A.

Advisory Professor: Louise McCullough M.D., Ph.D.

Stroke is a major cause of mortality and the leading cause of long-term disability in the US. More than 60% of individuals suffering a first time stroke develop respiratory dysfunction, prolonging recovery and increasing mortality. Post-stroke cognitive decline is a major contributor to disability and nursing home placement, therefore the cognitive consequences of Stroke Induced Respiratory Dysfunction (SIRD) need to be explored if we hope to enhance functional recovery. The first step towards treatment of the negative consequences of SIRD is the …

Insights Into The Therapeutic Potential Of Salt Inducible Kinase 1: A Novel Mechanism Of Metabolic Control, Randi Fitzgibbon

Dissertations and Theses (Open Access)

Salt inducible kinase 1 (SIK1) has been considered a stress-inducible kinase since it was first cloned in 1999. Continued efforts since this time have been dedicated to characterizing the structure and function of SIK1. Such research has laid the ground work for our understanding of SIK1 action and regulation in tissue and stimuli dependent manners. The fundamental findings of this dissertation continue in this tradition and include investigations of SIK1 regulatory mechanisms in skeletal muscle cells, the cellular and physiological effects of SIK1 loss of function in vitro and in vivo, and intracellular metabolic and mitochondrial regulation by this …

Cytoplasmic Cyclin E Mediates Resistance To Aromatase Inhibitors In Breast Cancer, Iman Doostan

Dissertations and Theses (Open Access)

Almost seventy percent of patients with breast cancer have tumors that express hormone receptors and need hormonal therapy. Aromatase inhibitors (AIs) block estrogen biosynthesis and are considered as the first line hormonal therapy for ER⁺ post-menopausal patients. However, resistance to these drugs remains a major challenge in clinic and the biology of such resistance is not completely understood. Cyclin E is deregulated in breast cancer through generation of low molecular weight isoforms that renders patients to a poor survival. Herein, we show that HR+ patients with LMW-E expressing tumors show diminished early response to neo-adjuvant AIs as well as …

Endocytic Trafficking Of The Amyloid Precursor Protein In Rat Cortical Neurons, Sahily Reyes

Dissertations and Theses (Open Access)

Amyloid-beta (Aβ) aggregation and deposition into extracellular plaques is a hallmark of the most common forms of dementia, including Alzheimer’s disease. The Aβ-containing plaques result from pathogenic cleavage of amyloid precursor protein (APP) by secretases resulting in intracellular production of Aβ peptides that are secreted and accumulate extracellularly. Despite considerable progress towards understanding APP processing and Aβ aggregation, the mechanisms underlying endosomal production of Aβ peptides and their secretion remain unclear. Using endosomes isolated from cultured primary neurons, we determined that the trafficking of APP from the endosomal membrane into internal vesicles of late endosome/multivesicular bodies (MVB) is dependent on …

Membrane Bound Il21 Promotes Natural Killer Cell Expansion Through Mir 124-3p Mediated Regulation, Anitha Somanchi

Dissertations and Theses (Open Access)

Natural Killer (NK) cells are cells of the innate immune system that act as first line of defense against viral infections and participate in tumor immune surveillance. NK cells do not cause graft versus host disease (GvHD), or require prior antigen exposure to exert anti-tumor activity, hence are an attractive choice for immunotherapy applications. Owing to small numbers of NK cells in peripheral blood (1-32%, with a 6% median), ex vivo expansion of NK cells is critical for NK cell adoptive immunotherapy, various expansion platforms have been explored over the decades. We developed a robust platform for ex vivo expansion …

"To You I Give Myself, For I Am Yours": Editorial Giving And Taking In Shakespeare's As You Like It, Jennifer Jean Thorup

Theses and Dissertations

In As You Like It 5.4.107-08 we receive Rosalind returning as herself”a woman”no longer in the guise of Ganymede, the boy page. Her first lines upon returning are repetitive: To you I give myself, for I am yours [To Duke Senior] / To you I give myself, for I am yours [To Orlando]. However, comparing Folio versions of these lines produces a provocative variant. In the third and fourth folios, these lines are no longer a repetitious patriarchal pledging, but a tender dialogic exchange "much like vows" between Rosalind and Orlando. While none of our modern Shakespeare editions make a …

An Analysis Of The Size And Impact Of Digital Footprints, Whitney Nielsen Maxwell

Theses and Dissertations

Personal information available online is known as a digital footprint. While many have a digital footprint, few if any, know what it encapsulates or how to control it. Technology and personal information are becoming more intertwined as technology becomes more integrated with everyday activities. Personal information can be defined as details that apply to a person such as race or shopping habits. Shopping habits are considered personal information by many corporations who spend money to track, or even predict purchases of individuals, whereas more traditional forms of personal information are details like gender, birthdate, and home town. With a wide …

Project Management: Skills, Tools, And Knowledge Construction Professionals Consider Important For Keeping Projects On Schedule, Lyle Scott Davies

Theses and Dissertations

Project managers have a major role in the construction and completion of projects. Much of their work consists of reviewing, clarifying, and coordinating information required by the field management and subcontractors performing the work on the job site. The assistance they give with the transfer of information helps with successfully completing projects. For many people, the largest indicator that a project was successful is that construction activities were completed on schedule. While finishing on schedule may be the primary focus of those involved with construction activities, projects still struggle to finish on time. The purpose of this study is to …

Advancements In Radio Astronomical Array Processing: Digital Back End Development And Interferometric Array Interference Mitigation, Mitchell Costus Burnett

Theses and Dissertations

The Brigham Young University (BYU) Radio Astronomy Systems group, in collaboration with the National Radio Astronomy Observatory (NRAO), the Center for Astrophysics at West Virginia University (WVU), and the Green Bank Observatory (GBO) have developed, and commissioned, a broadband real-time digital back end processing system for a 38-element phased array feed (PAF) with 150 MHz of instantaneous bandwidth. This system is capable of producing coarse and fine channel correlations, and implements a real-time beamformer that forms 7 simultaneous dual-polarized beams. This thesis outlines the hardware and software development for the digital back end and presents on-telescope commissioning results. This system …

Longitudinal Relations Between Interparental Conflict And Adolescent Self-Regulation: The Moderating Role Of Attachment To Parents, Lisa Tensmeyer Hansen

Theses and Dissertations

This study used growth curve analysis to investigate associations between interparental conflict, attachment to parents, and adolescent self-regulation outcomes. Using data from 681 families in the Flourishing Families survey obtained in two western U.S. cities, associations between interparental conflict, mother and father attachment, and initial and growth levels of adolescent self-regulation were analyzed across five time points. Adolescent self-regulation showed steady growth across a five-year period during adolescence, suggesting that self-regulation may continue to develop generally throughout adolescence, a finding not revealed in prior research. Adolescent self-regulation increased significantly more in the first city over the five years of the …

Virtue Conquered By Fortune: Cato In Lucan's Pharsalia, Nathaniel Brent Pribil

Theses and Dissertations

This thesis looks at how the Roman poet Lucan uses the character of Cato to elucidate his beliefs about Fortune and Stoicism. The traditional Stoic view of Fortune views it as a force for good that allows people to improve through hardship. Lucan portrays Fortune as a purely antagonistic force that actively seeks to harm the Roman people and corrupt even good individuals like Cato. Lucan's Fortune arranges events to place Cato in a situation where it is impossible to maintain his virtue. Rather than providing him an opportunity to improve in the civil war, Fortune makes it so that …

Investigating If Multidisciplinary Or Homogenous Teams Are More Innovative In A Higher Education Setting, Blake Howard Hoover

Theses and Dissertations

This study is derived from the claim that multidisciplinary groups are more innovative than homogeneous groups; a claim that has flooded the business industry and has become criteria for accreditation in higher education. However, the impact of disciplinary diversity in work groups is a growing area of research; therefore, it is yet to be thoroughly understood. The purpose of this study is to answer the question: are multidisciplinary teams more innovative than homogenous teams. To accomplish this university students from differing majors were sorted into multidisciplinary and homogeneous groups while participating in a two-day innovation course. The course taught the …

Analysis Of Safety Impacts Of Access Management Alternatives Using The Surrogate Safety Assessment Model, Kyung Min Kim

Theses and Dissertations

In a traditional safety impact analysis, it is necessary to have crash data on existing roadway conditions in the field and a few years must pass before accumulating reliable crash data. This is a time-consuming approach and there remains uncertainty in the crash data due to the random nature of crash occurrences. The Surrogate Safety Assessment Model (SSAM) was developed for resolving these issues. With SSAM, a conflict analysis is performed in a simulated environment. A planned improvement alternative under study is modeled and no physical installation of the alternative is needed. Hence, the method using a simulation software along …

Emotional And Cognitive Engagement In Higher Education Classrooms, Kristine C. Manwaring

Theses and Dissertations

This is a multi-article format dissertation that explores emotional and cognitive engagement in higher education classrooms. Student engagement in higher education classrooms has been associated with desired outcomes such as academic achievement, retention, and graduation. Student engagement is a multi-faceted concept, consisting of behavioral, emotional, and cognitive components. A deeper understanding of how these components interact would allow instructors and course designers to facilitate more engaging learning experiences for students. The first article is an extended literature review that investigates the extant empirical research on the relationship between emotional and cognitive engagement, and between emotional engagement and academic outcomes in …

Association Between Latent Toxoplasma Gondii Infection And Alzheimer's Disease, Cynthia Elizabeth Wyman

Theses and Dissertations

Introduction: Many studies have found an association between Toxoplasma gondii seropositivity and behavioral and cognitive changes in animal models and in humans. In addition, early findings have suggested an association between T. gondii seropositivity and Alzheimer's disease (AD). We sought to determine whether there is an association between T. gondii seropositivity and AD as well as cognitive functioning (including memory, working memory, processing speed, language functioning, executive functioning) in a large, well-characterized sample of subjects with AD and matched controls without dementia. Method: Using ELISA assays, we determined anti-T. gondii IgG antibody titers in 114 control subjects and in …

"To You I Give Myself, For I Am Yours": Editorial Giving And Taking In Shakespeare's As You Like It, Jennifer Jean Thorup

Theses and Dissertations

In As You Like It 5.4.107-08 we receive Rosalind returning as herself—a woman—no longer in the guise of Ganymede, the "boy" page. Her first lines upon returning are repetitive: "To you I give myself, for I am yours [To Duke Senior] / To you I give myself, for I am yours [To Orlando]." However, comparing Folio versions of these lines produces a provocative variant. In the third and fourth folios, these lines are no longer a repetitious patriarchal pledging, but a tender dialogic exchange—much like vows—between Rosalind and Orlando. While none of our modern Shakespeare editions make a note of …

Tribopairs In Wellbore Drilling: A Study Of Pcd Tilting Pad Bearings In An Electric Submersible Pump, Cameron B. Ellis

Theses and Dissertations

A polycrystalline diamond was tested as a bearing material for a tilting pad thrust bearing to be used in an electric submersible pump, which elevates process fluids from the bottom of well bores. The goal of this study was to compare the PCD to a current best of technology, which is stainless steel with an engineering polymer.This study found that PCD can handle larger loads than current technology but is limited in size due to diamond sintering and manufacturing constraints. The maximum size is Ø75mm.

An Investigation Of Elementary Teachers<'> Self-Efficacy For And Beliefs About The Importance Of Engineering Education, Khristen Lee Massic

Theses and Dissertations

In order for the United States to regain its global standing in science and engineering, educational and governmental organizations have started to re-emphasize science, technology, engineering, and math content in k-12 classrooms.While some preliminary research has been conducted on student and teacher perceptions related to engineering, there has been little research conducted related to teachers beliefs about the importance of engineering content in their classrooms and relatively few studies have investigated elementary teachers teaching engineering self-efficacy. Current studies have investigated the impact of professional development on teachers teaching engineering self-efficacy but these studies were conducted with limited sample sizes, for …

Foxes At The Henhouse: Occupational Licensing Boards Up Close, Rebecca Haw Allensworth

Vanderbilt Law School Faculty Publications

The dark side of occupational licensing-its tendency to raise prices to consumers with dubious effects on service quality, its enormous payout to licensees, and its ability to shut many willing workers out of the workforce-has begun to receive significant attention. But little has been said about the legal institutions that create and administer this web of professional entry and practice rules. State-level licensing boards regulate nearly one-third of American workers, yet, until now, there has been no systematic attempt to understand who serves on these boards and how they operate. This Article undertakes an ambitious and comprehensive study of all …

International Law In The Post-Human Rights Era, Ingrid (Wuerth) Brunk

Vanderbilt Law School Faculty Publications

International law is in a period of transition. After World War II, but especially since the 1980s, human rights expanded to almost every corner of international law. In doing so, they changed core features of international law itself, including the definition of sovereignty and the sources of international legal rules. But what might be termed the golden-age of international human rights law is over, at least for now. Whether measured in terms of the increasing number of authoritarian governments, the decline in international human rights enforcement architecture such as the Responsibility to Protect and the Alien Tort Statute, the growing …

The Production Function Of The Regulatory State, J.B. Ruhl, Jonathan R. Nash, James Salzman

Vanderbilt Law School Faculty Publications

How much will our budget be cut be this year? This question has loomed ominously over regulatory agencies for over three decades. After the 2016 presidential election, it now stands front and center in federal policy, with the Trump administration pledging over $50 billion in cuts. Yet very little is known about the fundamental relationship between regulatory agencies budgets and the social welfare outcomes they are charged to produce. Indeed, the question is scarcely studied in scholarship from law, economics, or political science. This article lays the groundwork for a new field of theoretical and empirical research, using what we …

Transforming (Perceived) Rigidity In Environmental Law Through Adaptive Governance, J.B. A. Ruhl, Hannah Gosnell, Brian C. Chaffin, Craig A. Arnold, Et Al.

Vanderbilt Law School Faculty Publications

The Endangered Species Act (ESA) is often portrayed as a major source of instability and crisis in river basins of the U. S. West, where the needs of listed fish species frequently clash with agriculture dependent on federal irrigation projects subject to ESA Section 7 prohibitions on federal agency actions likely to jeopardize listed species or adversely modify critical habitat. Scholarship on Section 7 characterizes the process as unwaveringly rigid, the legal hammer forcing federal agencies to consider endangered species needs when proposing operations and management plans for federally funded irrigation. In this paper, we identify barriers to an integrated …

Patients’ Willingness To Participate In Rapid Hiv Testing: A Pilot Study In Three New York City Dental Hygiene Clinics, Susan H. Davide, Anthony J. Santella, Winnie Furnari, Petal Leuwaisee, Marilyn Cortell, Bhuma Krishnamachari

Publications and Research

Purpose: One in eight people living with an HIV infection in the United States is unaware of their status. Rapid HIV testing (RHT) is an easily used and accepted screening tool that has been introduced in a limited number of clinical settings. The purpose of this study was to investigate patient acceptability, certainty of their decision, and willingness to pay for screening if RHT was offered in university-based dental hygiene clinics.

Methods: A cross-sectional survey was administered to 426 patients at three dental hygiene clinics in New York City over a period of four months. The survey questionnaire was based …

Linking Centralized And Decentralized Nursing Education, Sarah Nagy, Shellie Scribner

General Submissions: Presentations (Oral and Poster)

A large multi-hospital system adopted an innovative strategy to unite the system NPD practitioners in the centralized education department and decentralized unit based NPD practitioners. The goals of this approach were to: develop a standardized approach and process to professional development and training across the system; create and promulgate effective training and development to advance the mission and strategy of the organization; and to share knowledge and best practices across the organization.

Several strategies were developed. First, was the development of the Clinical Education Team Lead (CETL) role. This position serves as liaison between the centralized system education department and …