Digital Commons Network^™

Alternative Strategies To Inhibit Lysine Methyltransferases And Deubiquitinases In Human Cancers, Nicholas Spellmon

Wayne State University Dissertations

X-ray crystallography is the gold standard method for imagining macromolecules to atomic resolution. Three dimensional data is central to understanding the molecular mechanism how DNA, RNA and proteins function in biological events. Structural insights into these events provide a molecular window to visualize how biological molecules influence human health. Visualizing the architecture of these molecules set the stage for rational and selective drug design. The following dissertation utilizes biochemical and biophysical tools, including X-ray crystallography, to shed light on poorly understood mechanisms related to SMYD2 activity and regulation, USP10 architecture and function, and PDZ-RhoGEF dimerization. SMYD2 is one member of …

Magnetic Moment And Susceptibility Quantification In Mri: Additional Frequency Shifts From Materials And Background Phase Removal Using A Reference Phantom, He Xie

Wayne State University Dissertations

The first part of this thesis was to utilize existing methods to remove the unwanted background phase from phantom studies. Magnetic moments of straws filled by three different materials (gadolinium, ferritin, and nanoparticles) with four different concentrations of each material were subsequently quantified at 10 different echo times, with straws perpendicular to the main magnetic field. As the radius of each straw was known, susceptibility was calculated from each measured magnetic moment. Results from different echo times agreed within uncertainties. In addition, near perfect linear relation between quantified susceptibility and concentration was obtained for each material. However, phase values inside …

Making Home: Directing Reintegration Plays, Katherine Alaina Skoretz

Wayne State University Dissertations

This doctoral study explores three American post-combat reintegration plays written and produced in 2010 and 2011 in the United States. Using script analysis and production research, the dissertation describes some of the major themes of reintegration and strengths of theatrical production as revealed by the critically alternative narratives in the scripts and performances of Time Stands Still by Donald Margulies, American Soldiers by Matt Morillo, and Oohrah! by Bekah Brunstetter.

Engineering Hyaluronic Acid Carbon Nanotube Nanofibers: A Peripheral Nerve Interface To Electrically Stimulate Regeneration, Elisabeth M. Steel

Wayne State University Dissertations

Peripheral nerve injuries annually affect hundreds of thousands of people globally. Current treatments like the gold standard autograft and commercially available nerve guide conduits (NGC) are insufficient to repair long gap peripheral nerve injuries. NGCs can aid recovery but lack key microenvironment cues that promote nerve regeneration. We hypothesized that providing topographical, mechanical, and electrical guidance cues through a nanofibrous composite biopolymer would result in improved neuron growth metrics using an in vitro model. We embedded hydrophilic carbon nanotubes (CNT) within hyaluronic acid (HA) nanofibers by electrospinning. The aims of this study were (1) to define the topographical, nanomechanical, and …

Arabic Women’S Experience Of Childhood Sexual Abuse: A Mixed-Methods Study, Shahrazad Mahmoud Timraz

Wayne State University Dissertations

Background and purpose: Childhood sexual abuse (CSA) is an existing social problem that affects children worldwide, leading to poor psychological outcomes in adulthood. Childhood adversities including CSA account for 44.6% of childhood and 26%–32% of adult-onset psychiatric disorders. Furthermore, CSA is the second leading cause of posttraumatic stress disorder (PTSD) and influences an array of other outcomes such as depression, anxiety, hostility, and low self-esteem. Worldwide, approximately 8%–13% of girls have experienced sexual abuse. According to the few studies conducted in Arabic countries, CSA ranges from 7%–27%. Coping with CSA is a well-studied factor in regard to its impact on …

Toward Better Keys For Lectin Locks: Glycoconjugates Versus Glycomimetics, Peng Wen

Wayne State University Dissertations

As one of the four major classes of macromolecule in living systems, the roles of carbohydrates as energy storage substances and structural components have long been recognized. However, the unique role of carbohydrates in cellular recognition processes has only been scrutinized since the 1960s, thanks to the progress in the research in both cell surface carbohydrates and carbohydrate-binding proteins (lectins). The advances in the research of such process demand the use of carbohydrates as basic tools. Therefore, the primary goal of glycochemistry has been to obtain complex carbohydrates and their analogs effectively. One common approach to the problem involves the …

Applications Of Molecular And Quantum Mechanical Methods For Studying The Chemical Reactions Of Inorganic And Organic Systems, Yi-Jung Tu

Wayne State University Dissertations

Computational studies can assist chemists to interpret experimental observations and to predict the properties and behaviors of molecules. The work presented in this dissertation applies different computational methods to study the molecular properties and reaction paths for various inorganic and organic systems. The second and third chapters discuss the force field development using “Gaussian Electrostatic Model (GEM)” and its amenability for use in the AMOEBA force field. The forth and fifth chapters discuss the density functional theory (DFT) studies of photodissociation behaviors for inorganic molecules. The sixth chapter explores the oxidation mechanisms of ascorbic acid and its antioxidant properties in …

Trailer Park Kids: An Ethnographic Study Of Identity Formation In An Affluent Suburban Middle School, Jeanne Marie Vanlaan

Wayne State University Dissertations

The purpose of this dissertation was determining influences behind identity formation, social reproduction, and resistance of students residing in a local manufactured home community and attending a suburban majority White, middle-and upper-middle class middle school. Narratives from participants were included to assist in disseminating intersecting lives of students (the trailer park kids) with their parents and teachers. The lives of the trailer park kids at home and at school were portrayed. Research before this study focused on similar themes, but unique was examination of effects on students attending school as a minority by social class standing and their place of …

Synthesis Of Volatile And Thermally Stable Aluminum Hydride Complexes And Their Use In Atomic Layer Deposition Of Metal Thin Films, Kyle Blakeney

Wayne State University Dissertations

The research discussed in this dissertation spans both synthetic inorganic and nanomaterials chemistry. Aluminum hydride complexes have been synthesized and characterized which are highly volatile and thermally stable and their potential as reducing agents for ALD of electropositive metal and metal-containing films was evaluated. A major discovery has been the deposition of aluminum metal films by thermal ALD using an aluminum dihydride complex supported by a simple amido-amine ligand (Chapters 2). Aluminum is the most electropositive element deposited by purely thermal ALD to date and represents a significant breakthrough for this field. This process may have important industrial applications and …

Data-Driven Modeling For Decision Support Systems And Treatment Management In Personalized Healthcare, Milad Zafar Nezhad

Wayne State University Dissertations

Massive amount of electronic medical records (EMRs) accumulating from patients and populations motivates clinicians and data scientists to collaborate for the advanced analytics to create knowledge that is essential to address the extensive personalized insights needed for patients, clinicians, providers, scientists, and health policy makers. Learning from large and complicated data is using extensively in marketing and commercial enterprises to generate personalized recommendations. Recently the medical research community focuses to take the benefits of big data analytic approaches and moves to personalized (precision) medicine. So, it is a significant period in healthcare and medicine for transferring to a new paradigm. …

The Relationship Between Knowledge, Attitudes, And Behaviors Regarding Eco-Justice Issues Among Middle And High School Students In Eco-Schools In Puerto Rico, Elsie Aquino

Wayne State University Dissertations

The conservation, preservation, and protection of the environment are responsibilities that must be globally shared by human beings to “meet the needs of the present without compromising the ability of future generations to meet their own needs” (World Commission on Environment and Development (WCED, 1987, p. 43). When citizens acquire the knowledge and skills needed to become agents of change, the lack of interconnectedness – a relationship to nature as one of dominion and control – that presently exists between humans and nature might subside (Winograd, 2016). Through the re-orientation of the present educational system and the development of curricula …

A Data-Driven And Mixed Methods Analysis Of Automotive Retail Operations Management, Mark Allen Colosimo

Wayne State University Dissertations

The importance of effective retail operations management has never been more significant. Our research aims to expand the understanding for efficiency and dynamics of franchise outlets within retail networks with a focus on sales performance and profitability. The focus and contribution is the development of an actionable data analytics driven process by which automotive dealerships (retail outlets) can be analyzed to identify areas of opportunity for improvement. In general, automotive dealerships aim to sell product to make a profit, the manufacturer of the product/brand desires to sell vehicles to make a profit, and the customer desires to find a suitable …

3d Momentum Imaging Spectroscopy Probing Of Strong-Field Molecular And Surface Dynamics, Lin Fan

Wayne State University Dissertations

Electron-ion coincidence measurements in combination with 3-dimensional (3D) momentum imaging can provide comprehensive 3D-momentum information to unravel multichannel photoionization/dissociation processes, and thus is an effective tool to investigate atomic/molecular dynamics. A camera-based 3D coincidence momentum imaging system and the velocity mapping imaging (VMI) based machine were introduced in Chapter 2. Studies of strong field dissociative single and double ionization of relatively large molecules camphor and 2-phenylethyl-N, N-dimethylamine (PENNA) were carried out and illustrated in Chapter 3. We demonstrated the main products of double ionization of PENNA were singlet diradicals. In Chapter 4, a novel angle resolved-photoemission spectroscopy based on VMI …

Snowden Is (Not) A Whistleblower: An Analysis Of Ideographs And Anti-Democratic Rhetorical Strategies Within The U.S. Government’S Response To Edward Snowden, Joshua Guitar

Wayne State University Dissertations

This dissertation is a rhetorical criticism of the U.S. government’s response to Edward Snowden, the whistleblower who exposed illegal and unethical surveillance tactics of the National Security Agency and U.S. government. Informed by contemporary theories of democracy, this synchronic ideographic analysis examines the rhetorical strategies of U.S. government officials following Snowden’s disclosures. This dissertation contends that in laboring to absolve themselves of culpability, U.S. officials obfuscated Snowden and operationalized as an ideograph. This reification provides methodological development to ideographic analysis as it demonstrates how a political figure can become a rhetorical abstraction used for ideological purposes. The rhetorical interplay between …

Study Of Mri Signal In The Presence Of Discrete Spherical Magnetic Particles, Paul Kokeny

Wayne State University Dissertations

Simulating signal behavior in Magnetic Resonance imaging (MRI) is often a necessary step in being able to understand how signal relates to certain physiological parameters. One such parameter of interest in the body is magnetic susceptibility since it is related to iron content. The bulk magnetic susceptibility of an object is a property that describes how magnetized it becomes when placed in an external magnetic field. When the bulk susceptibility of an object arises from the presence of discrete magnetic inclusions, the MRI phase signal inside the object can no longer be determined analytically by assuming it has a continuous …

Comparison Of Readability Indices With Grades 1-5 Narrative And Expository Texts, Susan Beth Harden

Wayne State University Dissertations

The problem that exists when using one or more readability indexes to ascertain a text grade level is the varied outcomes received on any given text from readability indexes that purport to measure the same construct. This study aims to provide practitioners with data to make informed decisions regarding interchangeability of readability indexes. A total of n = 244 narrative (n = 116) and expository texts (n = 128) passages from grades 1-5 were evaluated using the following readability indexes: Flesch-Kincaid Grade Level, Fry Graph, Spache, Dale-Chall, Gunning Fog, and Smog. Fifteen (15) comparison sets were analyzed using Bland-Altman method …

Design, Synthesis And Biological Evaluation Of Pyrido[2,3-D]Pyrimidines As Inhibitors Of N5-Cair Synthetase, Qian Lin

Wayne State University Dissertations

The spread of drug-resistant bacterial infections has increased the need for novel antimicrobial agents. One potential but unexplored target is the de novo purine biosynthetic pathway. PurK, found only in bacteria, yeast, and fungi, catalyzes the sixth step in purine biosynthesis and has no human homolog. Herein we disclose the discovery of the first PurK inhibitor with submicromolar potency.

PurK is a member of the ATP-grasp superfamily of enzymes and recently, nanomolar inhibitors of biotin carboxylase, a related enzyme, were published. We hypothesized that those inhibitors, which target the ATP-binding site, could also inhibit PurK. To explore this hypothesis, four …

Design And Synthesis Of Oligo-(3,5-Dithio-Β-D-Glucopyranoside) As Β-(1→3)-Glucan Mimetics, Xiaoxiao Liao

Wayne State University Dissertations

This dissertation presents the design and synthesis of oligo-(3,5-dithio-β-D-glucopyranoside) as β-(1 → 3)-D-glucan mimetics. The synthesized dimeric, trimeric and tetrameric mimetics were tested for their binding affinities to Dectin-1 and CR3 and their abilities to activate phagocytosis and pinocytosis.

The first chapter gives an introduction of β-(1 → 3)-D-glucan. It gives an introduction about the structure and origin of β-(1 → 3)-D-glucan as well as the immunostimulating effect of natural β-(1 → 3)-D-glucan. The study of interaction between β-(1 → 3)-D-glucan and the receptors leads to a conclusion that the hydrophobicity of β-(1 → 3)-D-glucan is crucial to its immunostimulating …

To What Extent Does Clinical Supervision And Experience Relate To The Self-Efficacy Of Counselors-In-Training, Thomas Michalos

Wayne State University Dissertations

TO WHAT EXTENT DOES CLINICAL SUPERVISION AND EXPERIENCE RELATE TO THE SELF-EFFICACY OF COUNSELORS-IN-TRAINING

by

THOMAS MICHALOS

December 2018

Advisor: Dr. John Pietrofesa

Major: Counselor Education

Degree: Doctor of Philosophy

Clinical supervision is an integral part of the education and formation of a counselor. The following study focuses on measuring to what degree clinical supervision and experiences relates to the self-efficacy of counselors-in-training. A sample of 106 graduate level counselor education students were surveyed. Those students who have received clinical supervision had significantly higher levels of self-efficacy than who have never experienced clinical supervision. Additionally for those students in the …

Democratic Communication: Lessons From The Flint Water Crisis, Mindy Myers

Wayne State University Dissertations

This dissertation develops an approach to institutional critique that re-works Porter, Sullivan, Blythe, Grabill, and Miles’ foundational configuration. This project argues that John Dewey’s concept of democratic communication articulated in his debate with Walter Lippmann provides a useful heuristic for developing democratic communicative practices that allow citizens and experts to communicate with one another about technical issues such as water quality and safety. Through an analysis of Michigan’s emergency manager law, the relationship between citizens and experts that exposed the crisis, and the Flint Water Advisory Task Force’s Final Report, this dissertation establishes that citizens must participate in technical decision-making …

Characterization Of Protonated Modified Nucleosides And Amino Acid-Linked Cisplatin Analogues Using Tandem Mass Spectrometry Complemented By Theoreticical Approaches, Chenchen He

Wayne State University Dissertations

The chemical difference between DNA and RNA nucleosides is their 2′-hydrogen versus 2′-hydroxyl substituents. The 2′-O-methylation is common among natural posttranscriptional modifications of RNA. The structures and relative glycosidic bond stabilities of the protonated forms of the 2′-O-methylated nucleosides, 2′-O-methyladenosine (Adom), 2′-O-methylguanosine (Guom), 2′-O-methycytidine (Cydm), 2′-O-methyluridine (Urdm), and 5,2′-O-dimethyluridine (Thdm) are examined using two complementary tandem mass spectrometry approaches, infrared multiple photon dissociation (IRMPD) action spectroscopy and energy-resolved collision-induced dissociation (ER-CID). Theoretical calculations are also performed to predict the structures and relative stabilities of stable low-energy conformations of the protonated forms of the 2′-O-methylated nucleosides and their infrared spectra in …

Non-Invasive Mitochondrial Modulation With Near-Infrared Light Reduces Brain Injury After Stroke, Christos Dionisos Strubakos

Wayne State University Dissertations

Acute ischemic stroke is a debilitating disease that causes significant brain injury.

While rapid restoration of blood flow is critical to salvage the ischemic brain, reperfusion

of tissue can further drive brain damage by inducing generation of mitochondrial reactive

oxygen species (Chouchani et al., 2014a). Recent studies by our group found that noninvasive

mitochondrial modulation (NIMM) with near-infrared (NIR) light can limit the

production of reactive oxygen species following global brain ischemia (T. H. Sanderson

et al., 2018). NIR interacts with the rate limiting step of the mitochondrial electron

transport chain (ETC), cytochrome c oxidase (COX), and modulates mitochondrial

respiration. …

Representation Learning With Convolutional Neural Networks, Haotian Xu

Wayne State University Dissertations

Deep learning methods have achieved great success in the areas of Computer Vision and Natural Language Processing. Recently, the rapidly developing field of deep learning is concerned with questions surrounding how we can learn meaningful and effective representations of data. This is because the performance of machine learning approaches is heavily dependent on the choice and quality of data representation, and different kinds of representation entangle and hide the different explanatory factors of variation behind the data.

In this dissertation, we focus on representation learning with deep neural networks for different data formats including text, 3D polygon shapes, and brain …

Analysis Of Micromixers To Minimize Scaling Effects On Reverse Osmosis Membranes, Jeremy Walker

Wayne State University Dissertations

ABSTRACT

ANALYSIS OF MICROMIXERS TO MINIMIZE SCALING EFFECTS ON REVERSE OSMOSIS MEMBRANES

by

Jeremy Walker

December 2018

Advisor: Dr. Shawn McElmurry

Major: Civil Engineering

Degree: Doctor of Philosophy

Structural elements, typically mesh spacers, are required between membrane leaves in spiral

wound elements to ensure flow through reverse osmosis (RO) modules. The standard diamond-shaped

mesh spacer results in non-ideal hydrodynamics that can lead to fouling, which ultimately reduces the

flux of water through the membrane and the operational life of the unit. Additionally, traditional mesh

feed spacers do not allow for reverse flow cleaning due to obstructed flow paths and, once …

Modification Of 4,5- Aminoglycosides To Overcome Drug Resistance Bacteria And Toxic Side Effect, Guanyu Yang

Wayne State University Dissertations

ABSTRACT

MODIFICATION OF 4,5- AMINOGLYCOSIDES TO OVERCOME DRUG RESISTANCE BACTERIA AND TOXIC SIDE EFFECT

by

Guanyu Yang

September 2018

Advisor: Professor David Crich

Major: Chemistry

Degree: Doctor of Philosophy

Infectious diseases causing by antibiotic resistant pathogen are one of the major threat to human health and society today. Many researchers tried to develop next generation of antibiotics by reinvesting the existing antibacterial drugs. Aminoglycosides have long been used as highly potent and broad-spectrum antibiotics for treating bacterial infections. But their side effect, especially the irreversible ototoxicity, and the fast-growing resistant problem limit their application. The goal of this research was …

Stereoselective Synthesis Of Legionaminic Acid And Pseudaminic Acid Glycosides, Bibek Dhakal

Wayne State University Dissertations

Legionaminic acid (Leg) and pseudaminic acid (Pse) are deoxy acetamido analogues of the most common sialic acid, N-acetylneuraminic acid (NeuAc) that are found in microorganisms. Leg and Pse are rare but important class of sialic acids, as their glycosides are found in lipopolysaccharides and glycoproteins of several pathogenic Gram-negative bacteria including Pseudomonas aeruginosa, Legionella pneumophila serogroup 1, Campylobacter jejuni, and Campylobacter coli. As such, the stereoselective glycosylation of the equatorial Leg and Pse donors, and the role played by their side chain conformations in anomeric reactivity and selectivity are the focus of this thesis.

Chapter two describes the synthesis of …

Hydroxylamines And Hydrazines As Surrogates Of Sp3 Carbons In Medicinal Chemistry, Sandeep Dhanju

Wayne State University Dissertations

Current compound libraries that are used in high-throughput screening (HTS) are populated by low molecular weight and relatively planar compounds with high sp2 character and little stereochemical complexity. Unfortunately, such planar compounds cover only a very small corner of chemical space. In order to increase the diversity, structurally complex molecules with high fractions of sp3-hybridized atoms should be included in compound libraries. However, generating a large number of architecturally complex molecules using the current organic synthesis toolbox is considered tedious due to the requirement of multi-step synthesis. Recognizing this need, several creative strategies, like diversity-oriented synthesis, have been developed with …

Validating Functional Mechanisms For Non-Coding Genetic Variants Associated With Complex Traits, Cynthia Ann Kalita

Wayne State University Dissertations

Genome-wide association studies (GWAS) have identified a large number of genetic variants associated with disease as well as normal phenotypic variation for complex traits. However challenges remain in determining the functional relevance of human DNA sequence variants. Even after fine mapping, most variants are located in non-coding regions making it difficult to infer mechanisms linking individual genetic variants with the disease trait. In addition, we do not know under which environmental conditions the sequence variants have a functional impact, and whether they become one of many factors involved in complex phenotypes at the organismal level.

Chapter 1 describes computational methods …

A Pre-Registered Multi-Replication Examination Of The Independent And Interdependent Effects Of Big Five Traits And Facets In Predicting Physical Activity Via A Cybernetic Framework, Phuong Vo

Wayne State University Dissertations

Personality traits are important and reliable predictors of health outcomes and health-related behaviors, yet examining only main effects does not allow an examination of possible synergistic effects of traits (and their related lower-order facets) on health behaviors (Hampson & Friedman, 2008). Guided by Cybernetic Big Five Theory (CB5T; DeYoung, 2015), the present study examined three samples of U.S. adults recruited through Amazon Mechanical Turk (total N = 2879) to test main and moderated effects of broad Big Five traits and trait facets on physical activity while accounting relevant background factors such as age, sex, education, income, body mass index, health …

Characterizing Novel Radiologic And Pathologic Tissue-Based Risk Factors For Breast Cancer In African American Women With Benign Breast Disease, Asra N. Shaik

Wayne State University Dissertations

African American women (AAW) suffer a higher breast cancer mortality burden than women of other ethnicities in the US. More likely to be diagnosed with aggressive subtypes resistant to therapy and with rapidly fatal course than European American women (EAW), AAW may benefit greatly from earlier detection of breast cancers. However, it remains difficult to predict with a high degree of accuracy which women will develop breast cancer. Current risk assessment is especially poor for AAW, where models consistently underestimate risk in the subset of women with a prior biopsy. Risk assessment can be improved with the inclusion of new …