Physical Sciences and Mathematics Commons^™

Methodologies For Attaching Polypyridyl Ligands Into Amino Acids And Synthesis And Biological Evaluation Of Novel Light Activated Peptidomimetic Cysteine Protease Inhibitors Caged By Ruii(Bpy)2, Tomasz Respondek

Wayne State University Dissertations

Two separate subjects are described in this dissertation. The first part describes novel methodologies for attaching polypyridyl ligands into unnatural amino acids. The first chapter describes the different possibilities for attaching metal ligands to peptides and their applications as potential imaging and therapeutic agents covered so far in the literature. It is followed in the second chapter by the description of a new method for the construction of metal-peptide conjugates through the use of three unnatural amino acids, and their adaptation to solid phase synthesis. The third chapter describes the synthesis of a novel, "optimal" substrate for the enantioselective alkylation …

Investigating Hfq-Mrna Interactions In Bacteria, Martha Audra Faner

Wayne State University Dissertations

Regulatory RNAs (sRNAs) are essential for bacteria to thrive in diverse environments and they also play a key role in virulence [11]. Trans-sRNAs affect the stability and/or translation of their target mRNAs through complementary base-pairing. The base-pairing interaction is not perfect and requires the action of an RNA binding protein, Hfq. Hfq facilitates these RNA-RNA interactions by stabilizing duplex formation, aiding in structural rearrangements, increasing the rate of structural opening, and/or by increasing the rate of annealing [18-21]. Hfq has two well characterized binding surfaces: the proximal surface, which binds AU rich stretches typical of sRNAs, and the distal surface, …

Advanced Optimization Techniques For Monte Carlo Simulation On Graphics Processing Units, Eyad Hailat

Wayne State University Dissertations

The objective of this work is to design and implement a self-adaptive parallel GPU optimized Monte Carlo algorithm for the simulation of adsorption in porous materials. We focus on Nvidia's GPUs and CUDA's Fermi architecture specifically. The resulting package supports the different ensemble methods for the Monte Carlo simulation, which will allow for the simulation of multi-component adsorption in porous solids. Such an algorithm will have broad applications to the development of novel porous materials for the sequestration of CO2 and the filtration of toxic industrial chemicals.

The primary objective of this work is the release of a massively parallel …

Design, Synthesis, And Luminescence Properties Of Bridged Dimetallic Lanthanide Coordination Compounds, Jeremiah David Moore

Wayne State University Dissertations

I synthesized and characterized new homo- and heterodimetallic Eu3+- and Tb3+-containing complexes. Solution-phase luminescence measurements and density functional theory (DFT)-optimized structures indicated that all complexes were nearly isostructural and contained a dimetallic lanthanide core bridged by three oxygen atoms that are covalently bound to the ligand backbone. The homodimetallic Eu3+ complex behaved as a concentration-independent pH sensor that correlates the luminescence-decay rate of the complex to pH. The probable mechanism of pH sensing was attributed to the modulation of a hydroxyl oscillator in the Eu3+ coordination sphere, which was a previously unreported method to sense pH. The heterodimetallic Tb3+/Eu3+ complex …

Single-Molecule Studies Of Local And Global Nucleic-Acid Dynamics, Eric Muthuri Patrick

Wayne State University Dissertations

Nucleic acids undergo both global and local conformational changes that are important for their function. Structural studies have over the decades been invaluable in elucidation of various biomolecular mechanisms, hence contributing significantly to the understanding of biological events. However, a clear understanding of how molecules function in the cellular context requires investigation of their interconversion between multiple conformations, including mapping the folding landscape and any coupled changes in conformation. Work in this thesis focuses on fluorescence experiments, mainly at a single-molecule level to investigate such processes.

First, a novel single-molecule approach is described focusing on local dynamics within nucleic acids …

Power Operations In The Kunneth And C_2-Equivariant Adams Spectral Sequences With Applications, Sean Michael Tilson

Wayne State University Dissertations

We construct Power operations in the K"unneth spectral sequence and the $C_2$ equivariant Adams spectral sequence. While the operations in the K"unneth spectral sequence are 0 in $Tor$, they still detect operations in the target of the spectral sequence. We then interpret these computations of the homotopy of relative smash products as being related to obstructions to having $E_infty$ ring maps. The operations in the $C_2$-equivariant Adams spectral sequence are a partial extension of the work of Bruner in cite{HRS} and have applications to motivic homotopy theory.

Full Stability In Optimization, Nghia Tran

Wayne State University Dissertations

The dissertation concerns a systematic study of full stability in general optimization models including its conventional Lipschitzian version as well as the new Holderian one. We derive various characterizations of both Lipschitzian and Holderian full stability in nonsmooth optimization, which are new in finite-dimensional and infinite-dimensional frameworks. The characterizations obtained are given in terms of second-order growth conditions and also via second-order generalized differential constructions of variational analysis. We develop effective applications of our general characterizations of full stability to

parametric variational systems including the well-known generalized equations and variational inequalities. Many relationships of full stability with the conventional notions …

Discrete Littlewood-Paley-Stein Theory And Wolff Potentials On Homogeneous Spaces And Multi-Parameter Hardy Spaces, Yayuan Xiao

Wayne State University Dissertations

This dissertation consists of two parts:

In part I, We establish a new atomic decomposition of the multi-parameter Hardy spaces of homogeneous type and obtain the associated $H^p-L^p$ and $H^p-H^p$ boundedness criterions for singular integral operators. On the other hand, we compare the Wolff and Riesz potentials on spaces of homogenous type, followed by a Hardy-Littlewood-Sobolev type inequality. Then we drive integrability estimates of positive solutions to the Lane-Emden type integral systems on spaces of homogeneous type.

In part II, We establish a $(p,2)$-atomic decomposition of the Hardy space associated with different homogeneities for $0

Exergetic Analysis Of Hydrogen Combustion Involving Electronically Excited Species, Devon Alan Washington

Wayne State University Dissertations

Plasma-assisted combustion (PAC) is a growing field of research that involves using nonthermal plasma (NTP) to enhance combustion. PAC research involves modeling reaction mechanisms and chemical kinetics. Exergy analysis of combustion devices focuses on combustion irreversibility, including mixing, internal heat transfer, and oxidation. This novel research project merges these two branches of research.

The focus of this work is the application of exergy analysis to PAC systems, to analyze the effect introducing NTP has on trends in exergy destruction associated with oxidation during hydrogen combustion. This was accomplished by developing a plug flow reactor model using the chemical simulation tool …

Low Energy Positron Interactions With Biological Molecules, Indika Lasantha Wanniarachchi

Wayne State University Dissertations

Calculations of the positron density distribution which can be used for positrons bound to midsize and larger molecules have been tested for smaller molecules and subsequently applied to investigate the most likely e+e- annihilation sites for positrons interacting with biological molecules containing C, H, O, and N. In order to allow consideration of positrons bound to extended molecules with regions of different character and no particular symmetry, atom-centered positron basis sets of Gaussian-type functions were developed for positrons bound to molecules containing O, N, C, H, Li, Na, and Be. Testing shows that there is no need to scale the …

Towards Personalized Medicine Using Systems Biology And Machine Learning, Calin Voichita

Wayne State University Dissertations

The rate of acquiring biological data has greatly surpassed our ability to interpret it. At the same time, we have started to understand that evolution of many diseases such as cancer, are the results of the interplay between the disease itself and the immune system of the host. It is now well accepted that cancer is not a single disease, but a “complex collection of distinct genetic diseases united by common hallmarks”. Understanding the differences between such disease subtypes is key not only in providing adequate treatments for known subtypes but also identifying new ones. These unforeseen disease subtypes are …

Mission Aware Energy Saving Strategies For Army Ground Vehicles, Macam Dattathreya

Wayne State University Dissertations

Fuel energy is a basic necessity for this planet and the modern technology to perform many activities on earth. On the other hand, quadrupled automotive vehicle usage by the commercial industry and military has increased fuel consumption. Military readiness of Army ground vehicles is very important for a country to protect its people and resources. Fuel energy is a major requirement for Army ground vehicles. According to a report, a department of defense has spent nearly $13.6 billion on fuel and electricity to conduct ground missions. On the contrary, energy availability on this plant is slowly decreasing. Therefore, saving energy …

Structure Borne Noise Analysis Using Helmholtz Equation Least Squares Based Forced Vibro Acoustic Components, Logesh Kumar Natarajan

Wayne State University Dissertations

This dissertation presents a structure-borne noise analysis technology that is focused on providing a cost-effective noise reduction strategy. Structure-borne sound is generated or transmitted through structural vibration; however, only a small portion of the vibration can effectively produce sound and radiate it to the far-field. Therefore, cost-effective noise reduction is reliant on identifying and suppressing the critical vibration components that are directly responsible for an undesired sound. However, current technologies cannot successfully identify these critical vibration components from the point of view of direct contribution to sound radiation and hence cannot guarantee the best cost-effective noise reduction.

The technology developed …

Development Of Peptide Inhibitors Targeting Clostridium Difficile Toxins A/B And Characterizing The Regulatory Role Of A Putative Negative Regulator Tcdc In Clostridium Difficile Toxin Gene Expression, Sanofar Jainul Abdeen

Wayne State University Dissertations

Clostridium difficile infections cause one of the most common and vital hospitalacquired

diseases often associated with broad-spectrum antibiotic usage. TcdA and TcdB

are the key virulence factors involved in major patho-physiology. While standard

antibiotics provide some respite, due to the high relapse rates and the emergence of more

severe disease presentations, antibiotics alone have often proven to be suboptimal.

Therefore there is a desperate need to develop an effective non-antimicrobial

therapeutics. Part of this work focuses on identification and further characterization of

peptide therapeutic that target the major virulence factor TcdA/TcdB. Towards

development of mechanistic-based anti-toxin agent, phage display was …

Ionization In Diesel Combustion For On-Board Diagnostics And Engine Control, Tamer Hassan Badawy

Wayne State University Dissertations

Diesel engines have been known for their high thermal efficiency and specific power output, but there is concern about engine-out NOx and particulate matter emissions. To meet the current emission standards, advanced diesel engines are fitted with electronically controlled fuel injection systems and sophisticated and expensive after-treatment devices. Further improvements are still needed to meet future goals in better fuel economy and the more stringent emission standards. In order to meet these goals, there is a need for the control of the combustion process to reduce engine-out emissions in real-time and reduce the demand on the after-treatment devices. This requires …

1. Chromium(0)- Promoted Higher Order Cycloaddition Reactions: Studies Toward The Total Synthesis Of The Cyclocitrinols And Echinopines A And B 2. Total Synthesis Of (±)-Debromoflustramine B Via [4+1] Cyclization Of An Indole Isocyanate And A Bis(Alkylthio)Carbene, Saptarshi De

Wayne State University Dissertations

A facile and short stereoselective synthesis of the functionalized tetracyclic core structure of the cyclocitrinols, a family of unusual C25 steroid isomers, has been accomplished. The key structural unit, the bicyclo[4.4.1]A/B ring system, was constructed by a regioselective Cr(0)-promoted [6π + 4π] photochemical cycloaddition reaction.

A Bronsted acid catalyzed rearrangement of the 11-trimethylsilyl-tetracyclo[8.1.0.03,7.04,11]undeca-5,8-diene ring system to the unusual homotriquinacene ring system. The trimethylsilyl substitution on the cyclopropane moiety was found to be crucial for the rapid transformation which is believed to proceed via carbocation intermediates.

A short concise formal synthesis of Echinopines A and B is reported. The key [5.5.7] …

Studies On The Physicochemical Properties Of Eu2+ Cryptates: Implications To Contrast Agents For Magnetic Resonance Imaging, Joel Garcia

Wayne State University Dissertations

Magnetic resonance imaging (MRI) is a powerful medical imaging technique that can be enhanced using metal complexes called contrast agents. Most clinically approved contrast agents contain Gd³⁺. However, the efficiency (also known as relaxivity) of these Gd³⁺-containing complexes decreases as field strength increases, and in the ultra-high field strength regime, the relaxivity of these complexes is decreased considerably. Because of the slow water-exchange rate of most Gd³⁺-containing complexes (∼;10⁶ s^-1), I used Eu²⁺ instead of Gd³⁺ and adapted the ligand modification strategies that have been used for Gd^{3+ …}

Visual Exploration And Information Analytics Of High-Dimensional Medical Images, Darshan Pai

Wayne State University Dissertations

Data visualization has transformed how we analyze increasingly large and complex data sets. Advanced visual tools logically represent data in a way that communicates the most important information inherent within it and culminate the analysis with an insightful conclusion. Automated analysis disciplines - such as data mining, machine learning, and statistics - have traditionally been the most dominant fields for data analysis. It has been complemented with a near-ubiquitous adoption of specialized hardware and software environments that handle the storage, retrieval, and pre- and postprocessing of digital data. The addition of interactive visualization tools allows an active human participant in …

Exploring Molecular Systems From Chemical Physics To Biochemistry Using Classical And Quantum Mechanics, Brian Thomas Psciuk

Wayne State University Dissertations

Six topic are considered in this dissertation. Chapter 2 is an investigation into the role of ultra-fast hydrogen dynamics in determining fragmentation products of C3H4 following exposure to intense laser fields. Classical dynamics simulations were performed starting from C3H4 isomers with 190 - 240 kcal/mol excess energy distributed randomly as nuclear momenta. Deprotonation events were seen in ca. 50 - 75 % of all trajectories. Roughly one third of all trajectories showed fragmentation involving internal isomerization prior to dissociation. Chapter 3 is a survey of currently popular density functional methods and their ability to calculate accurate excitation energies and intensities …

Development Of Kinase Catalyzed Biotinylation To Study Phosphoproteomics, Kona Arachchilage Chamara Indunil Bandara Senevirathne

Wayne State University Dissertations

Kinase-catalyzed protein phosphorylation is involved in a wide variety of cellular events. Development of methods to identify phosphoproteins in normal and diseased states is critical to fully characterize cell biology. Our lab recently discovered kinase-catalyzed biotinylation, where ATP-biotin is utilized by kinases to label phosphopeptides or phosphoproteins with a biotin tag. To explore kinase-catalyzed biotinylation, kinetic measurements were obtained with various kinases and the data indicated that kinase-catalyzed biotinylation occurs with catalytic efficiency appropriate for phosphoproteomics application. Next, the susceptibility of the biotin tag to phosphatases was characterized and found that the phosphorylbiotin group was relatively insensitive to protein phosphatases. …

Using Heavy Flavors To Study New Physics, Kristopher Jason Healey

Wayne State University Dissertations

In this doctoral dissertation I discuss the possible standard model contributions to select leptonic heavy meson decay modes. Included are calculations of soft photon contributions to a di-lepton decay of B-mesons as well as two-particle hadronic unitary contributions to the rare di-leptonic decay of the neutral D meson. Additionally, constraints are calculated for two super-WIMP dark matter models from rare heavy flavor decays.

Synthesis And Characterization Of Transition Metal Arsenide Nanocrystals And The Metastability And Magneto-Structural Phase Transition Behavior Of Mnas Nanocrystals, Yanhua Zhang

Wayne State University Dissertations

This dissertation study focuses on (1) probing the magneto-structural phase transformation in nanoscale MnAs; (2) evaluation of the size-dependent phase stability of type-B MnAs (prepared by rapid injection); and (3) developing a general synthetic method for transition metal arsenide nanoparticles.

Discrete MnAs nanoparticles that adopt different structures at room temperature (type-A, α-structure and type-B, β-structure) have been prepared by the solution-phase arrested precipitation method. Atomic pair distribution and Rietveld refinement were employed on synchrotron data to explore the structural transitions of the bulk and nanoparticle samples, and these results were compared to AC magnetic susceptibility measurements of the samples. The …

Fundamental Studies And Applications Of Strong Field Ionization, Lu Yan

Wayne State University Dissertations

In an intense laser field, atoms and molecules experience tunneling ionization directly to the continuum. We used this method to study several aspects and applications of strong field ionization (SFI) in atoms and molecules. One study used SFI to probe the photofragments produced by photodissociation using DC sliced imaging. The photodissociation mechanism of two polyatomic molecules (sulfur dioxide and nitromethane) were investigated. In a second study, we show the strong field ionization rate depends on the sign of the magnetic number distribution. We detect the signal of sequential double ionization of argon dications by a pump-probe method to investigate the …

Modeling Of Mouse Eye And Errors In Ocular Parameters Affecting Refractive State, Gurinder Bawa

Wayne State University Dissertations

ABSTRACT

MODELING OF MOUSE EYE AND ERRORS IN OCULAR PARAMETERS AFFECTING REFRACTIVE STATE

by

GURINDER BAWA

September 2013

Advisor: Dr. Ivan Avrutsky

Major: Electrical Engineering

Degree: Doctor of Philosophy

Rodents eye are particularly used to study refractive error state of an eye and development of refractive eye. Genetic organization of rodents is similar to that of humans, which makes them interesting candidates to be researched upon. From rodents family mice models are encouraged over rats because of availability of genetically engineered models. Despite of extensive work that has been performed on mice and rat models, still no one is able …

Development And Optimization Of The First High Throughput In Vitro Fret Assay To Characterize The Saccharomyces Cerevisiae Gpi-T, Sandamali Amarasingha Ekanayaka

Wayne State University Dissertations

DEVELOPMENT AND OPTIMIZATION OF AN IN VITRO FRET ASSAY TO CHARACTERIZE THE SACCHAROMYCES CEREVISIAE GPI TRANSAMIDASE

By

SANDAMALI AMARASINGHA EKANAYAKA

December 2013

Advisor: Dr. Tamara L. Hendrickson

Major: Biochemistry

Degree: Doctor of Philosophy

The enzyme glycosylphosphatidylinositol transamidase (GPI-T) mediates the attachment of a glycosylphosphatidylinositol (GPI) anchor to the C-terminus of specific proteins to produce GPI anchored proteins. This post-translational modification is essential for viability of eukaryotic organisms. However, very little is known about GPI-T and its catalytic activity. Thus, the research described in this abstract was conducted to develop an in vitro assay to monitor GPI-T. A high-throughput assay for …

Diffusion Of Gold Nanoparticles In Synthetic And Biopolymer Solutions, Indermeet Kohli

Wayne State University Dissertations

Soft matter systems of colloidal particles, polymers, amphiphiles and liquid crystals are ubiquitous in our everyday life. Food, plastics, soap and even human body is comprised of soft materials. Research conducted to understand the behavior of these soft matter systems at molecular level is essential for many interdisciplinary fields of study as well as important for many technological applications.

We used gold nanoparticles (Au NPs) to investigate the length-scale dependent dynamics in semidilute poly(ethylene glycol) (PEG)-water, bovine serum albumin (BSA)-phosphate buffer, dextran and particulate solutions. In case of PEG-water solutions, fluctuation correlation spectroscopy was used to measure the diffusion coefficients …

Striatal Dopamine Dynamics Upon Manganese Accumulation, Madiha Khalid

Wayne State University Dissertations

STRIATAL DOPAMINE DYNAMICS UPON MANGANESE ACCUMULATION

by MADIHA KHALID

August 2013

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Doctor of Philosophy

Although manganese (Mn) is fundamental for many biological processes, exposure to excess amounts leads to a neurological disorder termed manganism. Due to its symptomatic similarity to Parkinson's disease, as well its preferential accumulation in dopamine rich brain regions, alterations in the dopamine system are implicated in the onset of manganism. In my research, Mn overexposure is mimicked via subcutaneous administration of manganese chloride to C57BL/6 mice over the course of seven days using a protocol that has been …

Development Of Matrix Assisted Ionization Methods For Characterization Of Soluble And Insoluble Proteins From Native Environments By Mass Spectrometry, Ellen Dela Victoria Inutan

Wayne State University Dissertations

Matrix-assisted laser/desorption ionization (MALDI) and electrospray ionization (ESI) have made a huge impact in the analysis of biological materials. ESI has gained its popularity involving liquid based analysis, efficient fragmentation, chromatographic and electrophoretic separations but has a limitation for solubility restricted materials and surface analysis. MALDI is applicable to large biomolecule analysis and for surface methods useful for tissue imaging but is limited for structural characterization due to poor fragmentation and is ill suited for liquid based separation methods. The research presented here relates to new ionization methods that encompass the benefits of ESI and MALDI. These novel ionization methods …

Green Diesel Production Via Catalytic Hydrogenation/Decarboxylation Of Triglycerides And Fatty Acids Of Vegetable Oil And Brown Grease, Elvan Sari

Wayne State University Dissertations

Increase in the petroleum prices, projected increases in the world’s energy demand and environmental awareness have shifted the research interest to the alternative fuel technologies. In particular, green diesel, vegetable oil/animal fat/waste oil and grease derived hydrocarbons in diesel boiling range, has become an attractive alternative to biodiesel— a mixture of fatty acid methyl esters, particularly due to its superior fuel properties that are similar to petroleum diesel. Hence, green diesel can be used as a drop-in fuel in the current diesel engines. The current technology for production of green diesel– hydrodeoxygenation of triglycerides and fatty acids over conventional hydrotreating …

Qualitative Properties Of Solutions Of Fully Nonlinear Equations And Overdetermined Problems, Jiuyi Zhu

Wayne State University Dissertations

In section 2 of part I, We study the maximum principles and radial symmetry for viscosity solutions of fully nonlinear partial differential equations. We

obtain the radial symmetry and monotonicity properties for

nonnegative viscosity solutions of fully nonlinear equations under some asymptotic decay rate at infinity. Our symmetry and monotonicity results also

apply to Hamilton-Jacobi-Bellman or Isaccs equations. A new maximum

principle for viscosity solutions to fully nonlinear elliptic equations is established. In section 3, We establish Liouville-type theorems and decay estimates for viscosity solutions to a class of fully nonlinear elliptic equations or systems in half spaces without the …