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Addressing The Threat Of Multidrug Resistant Infectious Diseases By Synthesis Of Novel Aminoglycoside Antibiotics, Girish Chandra Sati

Wayne State University Dissertations

The ever-growing increase in multidrug resistant infectious diseases is one of the major cause of human mortality, and there is an inherent need for the development of new antibiotics. Since the discovery of streptomycin, AGAs have been playing a very important role in human therapy as highly potent broad-spectrum antibiotics and are listed as one of the critically important antimicrobials by WHO. AGAs act by inhibiting the bacterial protein synthesis and by targeting the A-site present in the small subunit of bacterial ribosome. The clinical use of AGAs is somewhat restricted due to their toxic effects (ototoxicity and nephrotoxicity) and …

Computational Study Of Transition Metal Complexes For Solar Energy Conversion And Molecular Interaction With Strong Laser Fields, Xuetao Shi

Wayne State University Dissertations

There are two topics in this dissertation: ground state and excited state modeling of a few series of transition metal complexes that facilitate solar energy conversion, and Born-Oppenheimer Molecular Dynamics (BOMD) simulations of molecular cations interacting with intense mid-infrared laser light.

In Chapter 2 and 3, a few series of transition metal complexes that facilitate solar energy conversion are studied computationally. Metal-to-ligand charge-transfer (MLCT) excited states of several (ruthenium) (monodentate aromatic ligand, MDA) chromophore complexes are modeled by using time-dependent density function theory (TD-DFT). The calculated MLCT states correlate closely with the heretofore unknown emission properties that were observed experimentally. …

Spectral–Timing Analysis Of Kilohertz Quasi–Periodic Oscillations In Neutron Star Low Mass X-Ray Binaries, Jon Troyer

Wayne State University Dissertations

Kilohertz quasi-periodic oscillations or kHz QPOs are X-ray intensity variations observed

in neutron star low-mass X-ray binary (LMXB) systems. In such systems, matter is transferred

from a secondary low-mass star to a neutron star via the process of accretion. kHz

QPOs occur on the timescale of the inner accretion flow and may carry signatures of the

physics of strong gravity (c2 ~GM/R) and possibly clues to constraining the neutron star

equation of state (EOS). No model to date has been able to illuminate the origin of kHz

QPOs. Spectral-timing is a set of analysis techniques useful in deriving information about …

System Support For Stream Processing In Collaborative Cloud-Edge Environment, Quan Zhang

Wayne State University Dissertations

Stream processing is a critical technique to process huge amount of data in real-time manner.

Cloud computing has been used for stream processing due to its unlimited computation

resources. At the same time, we are entering the era of Internet of Everything (IoE). The emerging

edge computing benefits low-latency applications by leveraging computation resources at

the proximity of data sources. Billions of sensors and actuators are being deployed worldwide

and huge amount of data generated by things are immersed in our daily life. It has become

essential for organizations to be able to stream and analyze data, and provide low-latency …

Tandem Mass Spectrometry And Computational Approaches To Elucidate Conformations And N-Glycosidic Bond Stabilities Of Dna And Rna Nucleosides And Mononucleotides, Yanlong Zhu

Wayne State University Dissertations

ABSTRACT

TANDEM MASS SPECTROMETRY AND COMPUTATIONAL APPROACHES TO ELUCIDATE CONFORMATIONS AND N-GLYCOSIDIC BOND STABILITIES OF DNA AND RNA NUCLEOSIDES AND MONONUCLEOTIDES

by

YANLONG ZHU

May 2018

Advisor: Dr. Mary T. Rodgers

Major: Analytical Chemistry

Degree: Doctor of Philosophy

The influence of noncovalent interactions with sodium cations on the conformations and energetics of ten DNA and RNA nucleosides as well as two adenine mononucleotides were elucidated via infrared multiple photon dissociation (IRMPD) action spectroscopy experiments and complementary electronic structure calculations. Energy-resolved collision-induced dissociation (ER-CID) experiments of protonated and metal cationized DNA and RNA nucleosides were performed using a Bruker amaZon ETD …

Drug Delivery Strategies For The Treatment Of Advanced Lung Cancer And Various Lung Metastases, Elizabeth Bielski

Wayne State University Dissertations

Lung cancer remains the leading cause of cancer-related deaths in the United States. Secondary lung tumors metastasized from other cancer sites also remains highly prevalent, in which most metastatic tumors cannot be cured with existing therapies. Chemoresistance (multi drug resistance – MDR) that develops intrinsically or acquired is one of the key factors leading to fatality in these patients. MDR develops form a variety of resistance mechanisms that can occur consecutively or concurrently, therefore, making most current treatments unsuccessful. Current therapies have known to slow tumor growth, but rarely provide a cure. Immunotherapy has seen some promise, including the use …

Deep Learning Methods For Visual Object Recognition, Zeyad Hailat

Wayne State University Dissertations

Convolutional neural networks (CNNs) attain state-of-the-art performance on various classification tasks assuming a sufficiently large number of labeled training examples. Unfortunately, curating sufficiently large labeled training dataset requires human involvement, which is expensive, time-consuming, and susceptible to noisy labels. Semi-supervised learning methods can alleviate the aforementioned problems by employing one of two techniques. First, utilizing a limited number of labeled data in conjunction with sufficiently large unlabeled data to construct a classification model. Second, exploiting sufficiently large noisy label training data to learn a classification model. In this dissertation, we proposed a few new methods to mitigate the aforementioned problems. …

Identification Of Streptococcus Pyogenes Using Raman Spectroscopy, Ehsan Majidi

Wayne State University Dissertations

Despite the attention that Raman Spectroscopy has gained recently in the area of pathogen identification, the spectra analyses techniques are not well developed. In most scenarios, they rely on expert intervention to detect and assign the peaks of the spectra to specific molecular vibration. Although some investigators have used machine-learning techniques to classify pathogens, these studies are usually limited to a specific application, and the generalization of these techniques is not clear. Also, a wide range of algorithms have been developed for classification problems, however, there is less insight to applying such methods on Raman spectra. Furthermore, analyzing the Raman …

Monotonicity Of Set-Valued Mappings And Full Stability Of General Parametrical Variational Systems, Dat Pham

Wayne State University Dissertations

The dissertation introduces and studies the notions of Lipschitzian and Holderian full stability of solutions to three-parametric variational systems described in the generalized equation formalism involving nonsmooth base mappings and partial subgradients of prox-regular functions acting in Hilbert spaces. Employing advanced tools and techniques of second-order variational analysis allows us to establish complete characterizations of, as well as directly variable sufficient conditions for, such full stability properties under mild assumptions. Furthermore, we derive exact formulas and effective quantitative estimates for the corresponding moduli.

Cation Clock Reactions For The Determination Of Relative Reaction Kinetics In Glycosylation Reactions, Philip Adero

Wayne State University Dissertations

This dissertation presents the development of cyclization reactions as clocks for the determination of the molecularity of glycosylation reactions in individual pyranoside systems and extends it to the arabinofuranoside systems. It also describes the development of selective hydrogenolytic cleavage of naphthylmethyl ethers in the presence of sulfides.

The first part of chapter one gives an overview of the significance of glycochemistry and the challenges involved. The second part describes some selected glycosylation methods and extends this to the general mechanistic studies of glycosylation. This is followed by the discussion of the general clock reactions in literature which initiates a further …

Design, Synthesis, And Reactivity Of Homo- And Heterobimetallic Complexes Bridged By A Xanthene Linker, Thilini Samangi Hollingsworth

Wayne State University Dissertations

Cooperative reactivity of bimettalics can be is observed in many different areas of chemistry and have been increasingly investigated because of the advantageous reactivity when compared to the corresponding mononuclear systems. The focus of my dissertation is on (1) investigation of the homobimetallic cooperativity in lactide polymerization catalysis; (2) investigation of the heterobimetallic cooperativity in the biomimetic studies of Mo-Cu carbon monoxide dehydrogenase (CODH) enzyme in order to make a functional model of its active site.

Three new main group bis(alkoxide) complexes Mg(OR)2(THF)2, Zn(Cl)(μ2-OR)2Li(THF) and In(OR)2(μ2-Cl)2Li(THF)2 featuring bulky alkoxide [OCtBu2Ph] were synthesized serve as metal alkoxide precursors for bimetallic lactide …

Synthesis Of Open-Chain And Macrocyclic Xanthene-Bridged Bimetallic Cobalt, Nickel, And Copper Complexes For Cooperative Catalysis, Ryan Lance Hollingsworth

Wayne State University Dissertations

Within the numerous fields of inorganic chemistry, there is a growing interest to design dinucleating ligands for transition metals. This interest derives from the expansive list of bimetallic and polymetallic centers observed in nature that employ vital small molecules for catalysis, such as carbon dioxide, dinitrogen, and water. Many research groups have attempted to harness that structural and functional metal-metal cooperativity displayed by these enzymes, in hopes of enhancing transition metal catalysis. The overall focus of my dissertation is on utilizing late first-row transition metals, bound to either iminopyridine, bis(imino)pyridine, or bis(2-pyridinylmethyl)amine chelates, tethered by a xanthene linker towards bimetallic …

Real-Time Guarantees For Wireless Networked Sensing And Control, Yu Chen

Wayne State University Dissertations

Wireless networks are increasingly being explored for mission-critical sensing and control in emerging domains such as connected and automated vehicles, Industrial 4.0, and smart city. In wireless networked sensing and control (WSC) systems, reliable and real- time delivery of sensed data plays a crucial role for the control decision since out-of-date information will often be irrelevant and even leads to negative effects to the system. Since WSC differs dramatically from the traditional real-time (RT) systems due to its wireless nature, new design objective and perspective are necessary to achieve real-time guarantees.

First, we proposed Optimal Node Activation Multiple Access (ONAMA) …

Applications Of Effective Field Theories To New Physics, Derek Edward Hazard

Wayne State University Dissertations

We apply an effective field theory approach and argue that lepton flavor violating (LFV) decays M → l1l2 of meson states M with different quantum numbers could be used to put constraints on the Wilson coefficients of effective operators describing LFV interactions at low energy scales. We note that the restricted kinematics of the two-body decay of quarkonium or a heavy quark meson allows us to select operators with particular quantum numbers, significantly reducing the reliance on the single operator dominance assumption that is prevalent in constraining parameters of the effective LFV Lagrangian. We shall also argue that studies of …

Progress Toward Controlled Disulfide Formation To Access Neuroactive Conotoxins, Thilini Kondasinghe

Wayne State University Dissertations

"Conotoxins are mini proteins isolated from marine snails of the Conus family. They have shown activity in the selective inhibition of various ion channels. Therefore, they present an opportunity as possible therapy for a myriad of neurological ailments. The synthesis of conotoxins would enable both biological studies and evaluation of these structures as lead targets for therapeutics. However, establishing a reliable method to consistently folding disulfide rich proteins, including conotoxin, into their native structure has been challenging over few decades. In this research project, it is shown the progress towards a mild, efficient, and broadly applicable methods to generate the …

Harnessing Radical Reactivity For The Construction Of Natural Product Frameworks And Transition Metal Catalyst Stability In A Modified Kochi Coupling Reaction, Mathes Hewage Hansamali Sakuntala Sirinimal

Wayne State University Dissertations

Polycyclic N-containing heterocycles play an important role in therapeutic

applications and as molecular tools in studying biological processes, making them

important synthetic targets. Current synthetic approaches are too lengthy, use toxic

reagents or are limited to accessing a particular framework and hence, their synthesis

warrant further study. We have recently developed conditions to avoid both reduction and

slow addition in aminyl radical cyclizations in our venture to access the constrained ABC

core of calyciphilline A, a Daphniphyllum alkaloid. An electron deficient enone with a

pendent internal alkyne as the neutral aminyl radical precursor was used for radical

cyclization. Based on …

Qualitative Change Detection Approach For Preventive Therapies, Cristina Mitrea

Wayne State University Dissertations

Currently, most diseases are diagnosed only after disease-associated changes have occurred. In this PhD dissertation, we propose a paradigm shift from treating the disease to maintaining the healthy state. The proposed approach is able to identify when systemic qualitative changes in biological systems happen, thus opening the possibility of therapeutic interventions before the occurrence of symptoms. The change detection method exploits knowledge from biological networks and longitudinal data using a system impact analysis approach. This approach is validated on eight datasets, for seven different model organisms and eight biological phenomena. On these data, our proposed method performs well, consistently identifying …