Digital Commons Network^™

The Role Of The Arched Helicases In Exosome-Mediated Function, A. Alejandra Klauer

Dissertations and Theses (Open Access)

RNA processing and degradation are two important functions that control gene expression and promote RNA fidelity in the cell. A major ribonuclease complex, called the exosome, is involved in both of these processes. The exosome is composed of ten essential proteins with only one catalytically active subunit, called Rrp44. While the same ten essential subunits make up both the nuclear and cytoplasmic exosome, there are nuclear and cytoplasmic exosome cofactors that promote specific exosome functions in each of the cell compartments. To date, it is unclear how the exosome distinguishes between RNA substrates. We hypothesize that compartment specific cofactors may …

Induction Of Stronger And Long Lasting Vaccine Immunity To Tuberculosis, Pearl Bakhru

Dissertations and Theses (Open Access)

Tuberculosis is a major cause of death due to an infection in mankind. BCG vaccine protects against childhood tuberculosis although, it fails to protect against adult tuberculosis. BCG vaccine localizes to immature phagosomes of macrophages, and avoids lysosomal fusion, which decreases peptide antigen production. Peptides are essential for macrophage-mediated priming of CD4 and CD8 T cells respectively through MHC-II and MHC-I pathways. Furthermore, BCG reduces the expression of MHC-II in macrophages of mice after infection, through Toll-like receptor-1/2 (TLR-1/2) mediated signaling. In my first aim, I hypothesized that BCG-induced reduction of MHC-II levels in macrophages can decrease CD4 T cell …

Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells, Teresa T. Yiu

Dissertations and Theses (Open Access)

In this dissertation, I discovered that function of TRIM24 as a co-activator

of ERα-mediated transcriptional activation is dependent on specific histone

modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first

part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated

histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.

Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of

TRIM24-regulated ERα target genes is greatly impaired. Importantly, I

demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen

responsive elements (EREs) in a time-dependent manner upon estrogen

induction, and depletion of their expression exert corresponding time-dependent

effect …

Design, Calibration, And Evaluation Of Depth-Of-Interaction-Capable Pet Detector Modules, Chad J. Bircher

Dissertations and Theses (Open Access)

High-resolution, small-bore PET systems suffer from a tradeoff between system sensitivity, and image quality degradation. In these systems long crystals allow mispositioning of the line of response due to parallax error and this mispositioning causes resolution blurring, but long crystals are necessary for high system sensitivity. One means to allow long crystals without introducing parallax errors is to determine the depth of interaction (DOI) of the gamma ray interaction within the detector module. While DOI has been investigated previously, newly available solid state photomultipliers (SSPMs) well-suited to PET applications and allow new modules for investigation. Depth of interaction in full …

Regulation Of The Heat Shock Response By Thiol-Reactive Compounds In The Yeast Saccharomyces Cerevisiae, Yanyu Wang

Dissertations and Theses (Open Access)

Cells govern their activities and modulate their interactions with the environment to achieve homeostasis. The heat shock response (HSR) is one of the most well studied fundamental cellular responses to environmental and physiological challenges, resulting in rapid synthesis of heat shock proteins (HSPs), which serve to protect cellular constituents from the deleterious effects of stress. In addition to its role in cytoprotection, the HSR also influences lifespan and is associated with a variety of human diseases including cancer, aging and neurodegenerative disorders. In most eukaryotes, the HSR is primarily mediated by the highly conserved transcription factor HSF1, which recognizes target …

Exploring The Impact Of Decreased Ampk Pathway Activity On Brain Injury Outcome, Julia L. Hill

Dissertations and Theses (Open Access)

Each year, 150 million people sustain a Traumatic Brain Injury (TBI). TBI results in life-long cognitive impairments for many survivors. One observed pathological alteration following TBI are changes in glucose metabolism. Altered glucose uptake occurs in the periphery as well as in the nervous system, with an acute increase in glucose uptake, followed by a prolonged metabolic suppression. Chronic, persistent suppression of brain glucose uptake occurs in TBI patients experiencing memory loss. Abberant post-injury activation of energy-sensing signaling cascades could result in perturbed cellular metabolism. AMP-activated kinase (AMPK) is a kinase that senses low ATP levels, and promotes efficient cell …

Cellular Uptake Of Neutrohpil Elastase Links Inflammation To Adaptive Immunity, Elizabeth A. Mittendorf

Dissertations and Theses (Open Access)

Many tumors arise from sites of inflammation providing evidence that innate immunity is a critical component in the development and progression of cancer. Neutrophils are primary mediators of the innate immune response. Upon activation, an important function of neutrophils is release of an assortment of proteins from their granules including the serine protease neutrophil elastase (NE). The effect of NE on cancer has been attributed primarily to its ability to degrade the extracellular matrix thereby promoting invasion and metastasis. Recently, it was shown that NE could be taken up by lung cancer cells leading to degradation of insulin receptor substrate-1 …

Characterization Of A Novel Role For The To Usled- Like Kinase In Kinetochore Assembly And Function In Caenorhabditis Elegans, Jessica M. De Orbeta

Dissertations and Theses (Open Access)

Chromosome segregation is a critical step during cell division to avoid aneuploidy and promote proper organismal development. Correct sister chromatid positioning and separation during mitosis helps to achieve faithful transmission of genetic material to daughter cells. This prevents improper chromosome partitioning that can potentially result in extrachromosomal fragments, increasing the tumorigenic potential of the cells. The kinetochore is a protenaicious structure responsible for the initiation and orchestration of chromosome movement during mitosis. This highly conserved structure among eukaryotes is required for chromosome attachment to the mitotic spindle and failure to assemble the kinetochore results in aberrant chromosome segregation. Thus elucidating …

Evaluation Of Polymer Gel Dosimeters For Measurements Of Dose And Let In Proton Beams, Kevin M. Vredevoogd

Dissertations and Theses (Open Access)

This project assessed the effectiveness of polymer gel dosimeters as tools for measuring the dose deposited by and LET of a proton beam. A total of three BANG® dosimeter formulations were evaluated: BANG®-3-Pro-2 BANGkits™ for dose measurement and two BANG®-3 variants, the LET-Baseline and LET-Meter dosimeters, for LET measurement. All dosimeters were read out using an OCT scanner. The basic characteristics of the BANGkits™ were assessed in a series of photon and electron irradiations. The dose-response relationship was found to be sigmoidal with a threshold for response of approximately 15 cGy. The active region of the dosimeter, the volume in …

Characterization Of Selective Inhibition Of Adenylyl Cyclase Activity By Small Molecule Inhibitor Nky80, Cameron S. Brand

Dissertations and Theses (Open Access)

The nine membrane-bound isoforms of adenylyl cyclase (AC), via synthesis of the signaling molecule cyclic AMP (cAMP), are involved in many isoform specific physiological functions. Decreasing AC5 activity has been shown to have potential therapeutic benefit, including reduced stress on the heart, pain relief, and attenuation of morphine dependence and withdrawal behaviors. However, AC structure is well conserved, and there are currently no isoform selective AC inhibitors in clinical use.

P-site inhibitors inhibit AC directly at the catalytic site, but with an uncompetitive or noncompetitive mechanism. Due to this mechanism and nanomolar potency in cell-free systems, attempts at ligand-based drug …

Tet1: A Unique Dna Demethylase For Maintenance Of Dna Methylation Pattern, Chunlei Jin

Dissertations and Theses (Open Access)

DNA methylation at the C5 position of cytosine (5-methylcytosine, 5mC) is a crucial epigenetic modification of the genome and has been implicated in numerous cellular processes in mammals, including embryonic development, transcription, X chromosome inactivation, genomic imprinting and chromatin structure. Like histone modifications, DNA methylation is also dynamic and reversible. However, in contrast to well defined DNA methyltransferases, the enzymes responsible for erasing DNA methylation still remain to be studied. The ten-eleven translocation family proteins (TET1/2/3) were recently identified as Fe(II)/2-oxoglutarate (2OG)-dependent 5mC dioxygenases, which consecutively convert 5mC into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine both in vitro and in mammalian …

Homology Cloning, Heterologous Expression And Characterization Of A New Channelrhodopsin, Sing-Yi Hou

Dissertations and Theses (Open Access)

Channelrhodopsins are phototaxis receptors in the plasma membranes of motile unicellular algae. They function as light-gated cation channels and this channel activity has been exploited to trigger action potentials in neurons with light to control neural circuits (“optogenetics"). Four channelrhodopsins were identified in two algal species, Chlamydomonas reinhardtii and Volvox carteri, with known genome sequences; each species contains 2 channelrhodopsins, one absorbing at longer wavelengths and one at shorter wavelengths, named CrChR1 and CrChR2, respectively. Our goals are to expand knowledge of channelrhodopsin mechanisms and also to identify new channelrhodopsins from various algal species with improved properties …

Development Of A Beam-Specific Planning Target Volume And A Robust Plan Analysis To Ol For Proton Therapy, Peter Park

Dissertations and Theses (Open Access)

Proton therapy is growing increasingly popular due to its superior dose characteristics compared to conventional photon therapy. Protons travel a finite range in the patient body and stop, thereby delivering no dose beyond their range. However, because the range of a proton beam is heavily dependent on the tissue density along its beam path, uncertainties in patient setup position and inherent range calculation can degrade thedose distribution significantly. Despite these challenges that are unique to proton therapy, current management of the uncertainties during treatment planning of proton therapy has been similar to that of conventional photon therapy. The goal of …

Immunological Mechanisms Of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma And Graft Versus Host Disease, Lisa Shiue

Dissertations and Theses (Open Access)

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

Publication No.___________

Lisa Harn-Ging Shiue, B.S.

Supervisory Professor: Madeleine Duvic, M.D.

Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before …

Neural Responses To Food Pictures And Their Association With Dietary Intake, Edward Christenson

Theses and Dissertations

BACKGROUND: Food-related visual cues may affect eating behavior and energy intake. The purpose of this study was to determine the neural response to pictures of food and whether or not the neural responses were associated with energy intake. METHODS: Using a cross-sectional design, 60 adults participated in this study. Each participant reported to the laboratory in a fasted state, were fitted with a 128-electrode electroencephalogram (EEG) net, and were shown pictures grouped into three categories: high-calorie foods, low-calorie foods, and distractor pictures. These pictures were shown in random order. Furthermore, participants were shown these pictures in one passive condition and …

What’S To Know? Puzzles In The Literature On The Value Of Statistical Life, W. Kip Viscusi

Vanderbilt Law School Faculty Publications

Notwithstanding the general acceptance of the value of statistical life (VSL) estimates for policy assessment purposes, several important unresolved issues remain. First, the results from revealed preference studies are systematically higher than those from stated preference studies, potentially limiting the usefulness of stated preference studies in generalizing the VSL estimates to different populations and kinds of risks. Second, extrapolating the results of meta-analyses to project the VSL for different population groups requires that such generalization be reflective of the underlying economic content of what average VSL estimates reflect. Third, government agencies within and across countries place differing emphasis on types …

The Incredible Shrinking Confrontation Clause, Jeffrey Bellin

Vanderbilt Law School Faculty Publications

Sharp turns in the Supreme Court's recent Confrontation Clause jurisprudence have left scholars reeling from conflicting emotions: exhilaration, despair, denial, and soon, perhaps, cynical acceptance. While most commentators celebrated the demise of the incoherent Ohio v. Roberts framework, their excitement largely faded as the Court's decisions in Davis v. Washington and Bryant v. Michigan revealed nascent flaws in the evolving doctrine and sharply curtailed the newly revitalized confrontation right.

Recent scholarship strives to reanimate the jurisprudence by expanding the doctrinal definition of "testimonial" statements - the sole form of evidence Associate Professor, William & Mary Law School. I would like …

Interpreting Regulations, Kevin M. Stack

Vanderbilt Law School Faculty Publications

The age of statutes has given way to an era of regulations, but our jurisprudence has fallen behind. Despite the centrality of regulations to law, courts have no intelligible approach to regulatory interpretation. The neglect of regulatory interpretation is not only a shortcoming in interpretive theory but also a practical problem for administrative law. Canonical doctrines of administrative law ” Chevron, Seminole Rock/Auer, and Accardi ” involve interpreting regulations, and yet courts lack a consistent approach. This Article develops a method for interpreting regulations and, more generally, situates regulatory interpretation within debates over legal interpretation. It argues that a purposive …

What Is The Essential Fourth Amendment?, Christopher Slobogin

Vanderbilt Law School Faculty Publications

In More Essential Than Ever: The Fourth Amendment in the Twenty-First Century, Stephen Schulhofer provides a strong, popularized brief for interpreting the Fourth Amendment as a command that judicial review precede all non-exigent police investigative actions that are more than minimally intrusive. This review points out a few places where Schulhofer may push the envelope too far or not far enough, but concludes that More Essential Than Ever is a welcome reminder for scholars and the public at large that the Fourth Amendment is a fundamental bulwark of constitutional jurisprudence and deserves more respect than the Supreme Court has given …

Can The States Keep Secrets From The Federal Government?, Robert A. Mikos

Vanderbilt Law School Faculty Publications

States amass troves of information detailing the regulated activities of their citizens, including activities that violate federal law. Not surprisingly, the federal government is keenly interested in this information. It has ordered reluctant state officials to turn over their confidential files concerning medical marijuana, juvenile criminal history, immigration status, tax payments, and employment discrimination, among many other matters, to help enforce federal laws against private citizens. Many states have objected to these demands, citing opposition to federal policies and concerns about the costs of breaching confidences, but the lower courts have uniformly upheld the federal government’s power to commandeer information …

مدخل محاسبي لجدوى المشاريع الاستثمارية دراسة تطبيقية في مدرسة أوروك الابتدائية الأهلية, محمد محمود جاسم الطائــي

Muthanna Journal of Administrative and Economics Sciences

تسعى هذه الدراسة لتحقيق هدفين رئيسين ، فأما الأول فأنه يتمثل بتسليط الضوء على دراسات الجدوى وماهية القرار الاستثماري العقلاني في قطاع من القطاعات الاستثمارية والذي يحتاج إلى درجة من الاطمئنان على رأس المال المستثمر ، إذ تعد تلك الدراسات والتي تسبق ذلك القرار من الأمور المهمة والعلمية والعملية لصحة اتخاذ ذلك القرار من عدمه ، إذ إن تلك الدراسات إذا ما أعدت وفقاً لأسس صحيحة بتعددها وتنوعها كجوانبها الفنية والتسويقية والمالية وغيرها تتسم بالتكامل . والهدف الثاني يتمثل بتوضيح العلاقة بين دراسات الجدوى والقرارات الاستثمارية ، إذ كلما كانت تلك الدراسات صحيحة وجدية كلما كانت عملية اتخاذ القرار الاستثماري …

A Study Of The Effects Of Charter Schools On Achievement, Attendance And Selected Mitigating Factors In A Midwestern State’S Small Urban School Districts, Frederick C. Clarke

Dissertations

The purpose of this study was to determine whether students attending urban charter schools did better, or worse, than students attending traditional public schools, over a five-year time period, in a Midwestern state. Thirty-one urban school districts affiliated with a Midwestern Urban Education Association, and corresponding charter schools, located within these Midwestern school districts, were selected to participate in this study.

This study utilized a quasi-experimental research design and was supported by the earlier research of Dr. Gary Miron and Dr. Jerry Horn from Western Michigan University (Miron & Horn, 2000; Miron & Horn, 2002; Miron, 2005) and Dr. Scott …

Plea Bargaining And The Right To The Effective Assistance Of Counsel: Where The Rubber Hits The Road In Capital Cases, John H. Blume

Cornell Law Faculty Publications

No abstract provided.

Chapter 11: Genome-Wide Association Studies, William S. Bush, Jason H. Moore

Dartmouth Scholarship

Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.

Community By [Design] By Community: Product & Process, Aaron Bowman

All Theses

In his seminal work De Architectura (The Ten Books on Architecture), the Roman architect Vitruvius proposed a definition that became a lasting benchmark for the elements of [DESIGN] -Firmness, Commodity, and Delight. While this three-part definition provided a common lens through which to view [DESIGN], it also created a divide between the trained 'specialists' who create [DESIGN] and the Community who experience and interact with it. For Vitruvius, [DESIGN] provided a physical demarcation of place and created a shared association that was collectively understood as a Community. As the idea of Community has become increasingly dissociated with place in the …

Bioswellable Amphiphilic Copolymers, David Ingram

All Theses

The suture is one of the most commonly used medical devices, consisting of a fiber, a surgical needle and the packaging in which it is stored. The fiber itself remains after implantation for a defined time and is responsible for the approximation of the wound during the healing process. The needle merely serves to aid in insertion, and preferably has a diameter larger than the diameter of the fiber .
The 1970's marked the birth of a new family of fibrous materials for the approximation of wounds: synthetic absorbable sutures. This family has the ability to provide wound support during …

Can The Application Of A Landscape Designed Learning Environment Enhance Education?, Virginia Bailey

All Theses

There is a need for a restructuring the way that a child's learning environment is designed. Currently, the mainstream educational design process ignores the notion that children have different ways of learning. Furthermore, when there are so many distractions, how we successfully reach a child's mind has become a challenge. The current school system is structured in a manner that does not address the presence of these distractions, often causing overstimulation and inattentiveness. Designing for children should be approached in a way that all senses are engaged. Having opportunities for hands-on learning inside and outside of the classroom is important …

Reverse Osmosis Desalination With Integrated Compressed Air Energy Storage: Conceptual Design And Modeling, Pooja Mahajan

All Theses

Growing fresh water needs have led to an interest in water desalination using reverse osmosis (RO) membranes. Energy consumption has a large share in the expenses incurred to drive a reverse osmosis desalination system. With depleting fossil fuel reserves, tapping renewable sources of energy is a promising alternative to meet the energy requirements. Wind power coupled to an RO desalination system is a potential means of delivering clean water using sustainable energy. This work investigates modeling of a conceptual wind-energy-driven RO desalination system that is made possible because of an air-pressure energy storage mechanism. Bench-scale experiments were performed on an …

Characteristics Of Public Alternative High Schools Specifically For Students Placed At-Risk: A National Study Using The 2003-04 And 2007-08 Schools And Staffing Survey, Masashi Izumi

Dissertations

In this study I investigated determinants of the average daily attendance (ADA) and graduation rate of public alternative high schools specifically for students placed at-risk by analyzing the nationally representative data from Schools and Staffing Surveys of 2003-04 and 2007-08. I built three models via successive block entry, predicting the ADA and graduation rate by (a) student demographics, (b) staffing characteristics, and (c) school processes. Through multiple regression analyses on ADA, I found (a) a positive relationship between career technical education and ADA; and (b) a negative relationship between teacher-student ratio and ADA. Through the set of multiple regression analyses …

From Crisis To Stability: A Case Study Of Presidential Leadership At A Christian College, Jeffrey Gill

Dissertations

Despite healthy growth in past decades, in a time of national and global economic instability small, private Christian colleges now find themselves in a precarious position. Leading effectively in such colleges and universities in a time of external and/or internal crisis is a great challenge.

This research is about a small, Christian college with documented evidence of having survived two significant enrollment and financial crises (early 1990s and 2008-09), and is now stable, all under the leadership of a president who served during the 19 year time period of crisis and stability. The purpose of this study is to investigate …