Physical Sciences and Mathematics Commons^™

Uncertainty In Combustion Reaction Rates And Its Effects On Combustion Simulations, Joshua Piehl

Wayne State University Theses

This work investigates the uncertainties in reaction rates of an n-dodecane model on turbulent spray combustion simulations. Six major reactions were found to significantly impact the ignition delay of the mechanism in a 0-D batch reactor model. These reactions’ rates were independently modified and placed into individual mechanisms. These newly developed mechanisms were simulated in a 3-D turbulent spray simulation and a 0-D batch reactor at a pressure of 60 bar and temperatures from 900 to 1100 K. The combustion characteristics (e.g. ignition delays, flame lift-off length, liquid and vapor penetration) of the modified mechanisms were compared to those produced …

Differential Activation Of Dead Box Rna Helicases Rhlb And Rhle By Hfq/Srnas And Their Target Mrnas, Amit Kumar

Wayne State University Theses

Number of small RNA (sRNA) gene regulators have mounted in E. coli over the years whereas the number of validated protein partners has not changed considerably. Hfq has remained the only well studied global regulatory partner of sRNAs in E. coli. However, direct or indirect involvement of other protein partners has always been speculated. Study from Blasi lab has shown that CsdA, one of the five DEAD-box RNA helicases of E. coli, is required for the DsrA mediated upregulation of rpoS under cold stress condition. Previous study from our lab has identified two other DEAD-box RNA helicases, RhlB and RhlE, …

Design, Synthesis And Analysis Of Potential Photo-Activatable Cathepsin K Inhibitors, Khalin Evania Nisbett

Wayne State University Theses

Abstract

DESIGN, SYNTHESIS AND ANALYSIS OF POTENTIAL PHOTO-ACTIVATABLE CATHEPSIN K INHIBITORS

by

KHALIN NISBETT

May 2017

Advisor: Dr. Jeremy Kodanko

Major: Chemistry

Degree: Master of Science

Tightly regulated cysteine CA proteases play a major role in maintaining the homeostasis within cells. Subsequently, when these proteases are dysregulated and mislocalized they disrupt healthy cell dynamics and contribute to many life-threatening pathologies such arteriosclerosis, osteoporosis and cancer. As such many pharmaceutical companies and research teams are highly interested in these proteases as targets. One emergent strategy is the spatiotemporal control of biological processes. In relation to this, a series of spatiotemporally controlled …

Facile Synthesis Of Tertiary Aliphatic Amine– Containing Cyclic Motif Via Neutral Aminyl Radical Cyclization, Heng Chen

Wayne State University Theses

Tertiary amine–containing cyclic motifs are prevalent in natural products and pharmaceutical lead targets. Inspired by these biological active molecules, one focus in our lab is the development of neutral aminyl radical chemistry in the synthesis of tertiary aliphatic amine–containing cyclic compounds. In this project, I investigated the mono- and tandem cyclization of aminyl radical with different types of olefins (terminal olefin, enone, and styrenyl). The effect of the hydrogen atom donor and the limitation of the reaction will be discussed.

Targeted Delivery Of Nrf2 Sirna Using Modular Polymeric Micellar Nanodelivery System For Efficient Target Gene Knockdown In Hepatocellular Carcinoma, Shaimaa Mohamed Ibrahim Yousef

Wayne State University Theses

Tumor selective drug delivery as well as chemotherapy associated multi drug resistance (MDR) pose tremendous hurdles for effective cancer therapy. In this regard, designing multifunctional nanocarriers loaded with drug/gene payloads and engineered with tumor targeting ligands can serve as a modular platform for targeted drug/gene delivery. In this study we undertook the synthesis of a self-assembling block copolymer constructed using poly(styrene-co-maleic anhydride, partial iso-octyl ester) (SMAPIE) and branched polyethylenimine (PEI) as building blocks and evaluated its micelle forming ability, siRNA complexation and siRNA delivery potentials. In addition, we engineered galactosamine decorated nanomicelles using modular “click” chemistry based approaches for evaluating …

Modified Synthesis Of Ligands For Lanthanide Ions, Lauren Elizabeth Hopper

Wayne State University Theses

Ligands of relevance to lanthanide ions have been synthesized and modified with respect to pKa and thermal conditions (both microwave and non-microwave). Microwave-assistance has been used previously to accelerate the rates of reactions of ligand syntheses, primarily as a thermal component in agreement with the Arrhenius equation. The modified syntheses of intermediates for lanthanide complexes presented in this thesis enable rapid synthesis of common intermediates—DO2A-methyl ester, DO2A-ethyl ester, and DO2A t-butyl ester—that previously required days to synthesize. Additionally, this modified synthesis can be performed with or without microwave irradiation, suggesting that the thermal component of the rate acceleration is not …

In Vitro And In Vivo Measurments Of Serotonin For Ecological And Mental Health Via Fast Scan Cyclic Voltammetry, Matthew Nicholas Jackson

Wayne State University Theses

Fast Scan Cyclic Voltammetry has been proven to be a highly valuable technique in analysis and detection of neurotransmitters. With this technique, two novel applications are being explored to protect natural water sources as well as furthering the efficacy of antidepressants. Despite setbacks, promising data has been collected to further understand the mechanisms involved in the phototactic response observed in Daphnia Magna. Electrochemical modification of carbon fiber microelectrodes has proven to be inefficient as a means to effectively differentiate between serotonin and its metabolite. As such, this unsuccessful attempt has further narrowed down the list of candidates to electrochemically differentiate …

Isomer Detection Of Radicals Produced By The Flash Pyrolysis Of Heptane And Its Structural Isomers, Steven Lingenfelter

Wayne State University Theses

Radicals can play an important role in combustion chemistry as key intermediates. As such studying them is vital in the study of combustion chemistry. Our study focused on the production of the 1 and 2-propyl radical from heptane isomers. Radicals were produced by flash pyrolysis which was achieved by restively heating a silicon carbide tube through which a molecular beam passed. Strong field ionization was utilized to discriminate between the two propyl isomers. Results indicated the expected trend however the signal intensity was quite low with significant noise. Further improvements are needed to improve the quality as well as the …

Synthesis Of Cryptands For Eu2+-Containing Complexes, Chengcheng Wang

Wayne State University Theses

Eu2+-containing complexes have considerable applications in synthetic chemistry, medical diagnosis, and materials science. However, Eu2+ is easily oxidized in solution when exposed to air. Allen and coworkers have demonstrated that Eu2+ can be stabilized by functionalized cryptands. Based on this idea, I focused my research on synthesizing cryptands. The progress towards synthesizing several modified cryptands is described in the thesis. The Eu2+-containing complexes of these cryptates have potential applications as magnetic resonance imaging contrast agents, luminescent materials, and magnetic materials.

Design And Synthesis Of Isatin-Based Caspase Inhibitors For Ruthenium Caging Applications, Kasun Chinthaka Ratnayake

Wayne State University Theses

ABSTRACT

DESIGN AND SYNTHESIS OF ISATIN BASED CASPASE INHIBITORS FOR RUTHENIUM CAGING APPLICATIONS

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KASUN CHINTHAKA RATNAYAKE

August 2015

Advisor: Jeremy J. Kodanko, Ph.D.

Major: Chemistry (Organic)

Degree: Master of Science

Apoptosis is the energy dependent programmed cell death. Improper function of apoptosis could lead to diseases such as cancers, strokes, Alziemer’s disease. Caspases are the enzymes involved in the later stage of this process. Peptidyl and non-peptidyl caspase inhibitors have been synthesized recently. These non-peptidyl compound classes which consist of pyrrolidinyl-5-sulfo isatins have showed a greater potency against executioner caspases, caspase-3 and -7. According to literature and for further …

Effects Of Statin Drugs And Tocotrienol Rich Fraction Supplementation In Chronic Hemodialysis Patients And Metabolomic Profile, Eno Latifi

Wayne State University Theses

Chronic kidney disease (CKD) is known as a heterogeneous disorder which currently is on the rise and lately has been classified as a public health issues in the United State and worldwide. CKD is an irreversible and progressive disease which can lead to kidney failure, and this is depicted by the advanced stage of the disorder when it reaches the point, that is classified as end stage of renal disease (ESRD) (Stage 5 of CKD) (eGRF <15 mL/min/ 1.73 m2 working capacity), where both organs are in a total or permanent kidney failure. End-Stage renal disease patients, on hemodialysis have been associated to experience an accelerated form of atherosclerosis, which is induced by inflammation, impairment of antioxidant system and elevated oxidative stress. Since the problem effecting ESRD patients is multifactorial, the objective of this investigation is to explore and look at the effects of supplementing with vitamin E-tocotrienol rich fraction (TRF), a micronutrient which has anti-inflammatory, antioxidant, and lipid lower capabilities into tackling these comorbid conditions experienced by this population. Therefore the aims of this investigation will be to explore changes in lipid profiles, inflammatory markers, and oxidative status, as well as look at any changes in metabolomic profiles. It was hypothesized that by supplementing with TRF a vitamin E, for 16 weeks in ESRD patients undergoing hemodialysis, it may help reverse and/or improve, oxidative status, inflammatory markers, increase antioxidants status and improve lipid profiles.

The study was double-blinded, randomized, parallel, placebo-controlled design trial, of 81 adult patients undergoing chronic hemodialysis at Great Lake Dialysis Clinic, Detroit MI, where …

Energy Transfer In A Discrete, Soluble Heterobimetallic Complex Containing Tb3+ And Eu3+, Nikhil Kumar Barua

Wayne State University Theses

A discrete, heterobimetallic Tb3+-Eu3+ -containing complex has been synthesized, and energy transfer was observed in the complex without using an antenna. This result represents a new way of observing lanthanide emission using lanthanide excitation in discrete, soluble complex. The occurrence of energy transfer in the mixed heterobimetallic Tb3+-Eu3+ complex was characterized using steady state luminescence spectroscopy and luminescence-decay studies. These findings are likely to be useful for fundamental mechanistic studies of energy transfer in lanthanide-containing systems.

Biophysical Studies Of Mutant H69 Rna Constructs, Daya Nidhi Kharel

Wayne State University Theses

The importance of helix 69 (H69) of the large ribosomal subunit is emphasized by its location in the ribosome and key contacts with protein factors and tRNAs during different steps of protein synthesis. The presence of three highly conserved pseudouridine modifications in H69 has a significant impact on modulation of the ribosome conformations. Specific nucleotides of H69 may be necessary for the function of this helix-loop RNA, as some mutations are deleterious to bacterial growth. In this study, we investigated the effects of single nucleotide mutations in a 19-nucleotide H69 construct with and without pseudouridines on the RNA stability and …

Genetic And Biochemical Studies Of Human Apobec3h Enzyme, Thisari Sachithra Aluthgama Guruge

Wayne State University Theses

The AID/APOBEC enzymes are DNA/RNA cytosine deaminases with important functions in innate and adaptive immunity. APOBEC3 enzymes play a crucial role in restricting the replication of exogenous retroviruses such HIV-1 and endogenous retrotransposition events. In particular, APOBEC3 enzymes have evolved in humans by gene duplication to compose seven members. APOBEC3H is highly diverse in its allelic sequence and the distribution is population-specific. It has evolved under strong positive selection over millions of years. To study the catalytic mechanism, structure, function and the underlying cause of its high diversity, a high resolution crystal or NMR structure is required are not yet …

Synthesis Of 4'-O-Glycopyranosyl Paromomycin Aminoglycoside Antibiotics: Influence Of The Glycoside On Antiribosomal, Antibacterial Activity And Utilization Of Electrospray Ionization Mass Spectrometry To Evaluate Reactivity Of Glycosyl Phosphate, Weiwei Chen

Wayne State University Theses

The data in this thesis is trying to address two problems. The first problem is paromomycin associated ototoxicity; the second problem is the lack of precise reactivity data of glycosyl donors in one-pot synthesis.

Paromomycin is out of the market as an antibiotic due to its ototoxicity. Previous work done by Vasella and Böttger's groups identified 4'-O position of paromomycin as a promising site of modification to reduce the side effect. A series of 4'-O-glycopyranosyl paromomycin has been synthesized and tested for their biological activity and selectivity. From the results of anti bacterial ribosomal activity, anti hybrid ribosomal activity and …

Synthesis And Characterization Of Brain Penetrant Prodrug Of Neuroprotective D264: Potential Disease Modifying Treatment Agent For Parkinson's Disease, Fahd Shamoon Dholkawala

Wayne State University Theses

Parkinson's disease (PD) is a complex neurodegenerative disorder with progressive loss of dopamanergic neurons in the substantia nigra region of the brain and accumulation of intracytoplasmic inclusions called `Lewy bodies'. PD is characterized by tremors, rigidity, slowness of movement, bradykinesia and postural imbalances. Although the etiology of PD is not well understood, it is well established that oxidative stress, mitochondrial dysfunction, alpha-synuclein aggregation play a central role in the pathogenesis of PD. Current treatment methods are based on symptomatic relief without addressing the underlying pathophysiological factors responsible for the disease. It is important to develop therapies which can address these …

Synthesis And Characterization Of Biodegradable Poly(Vinyl Esters) With Hdac Inhibitory Activity, Kyle Lawrence Horton

Wayne State University Theses

HDAC inhibitors are known to have anti-inflammatory properties. HDAC inhibitors are used in combination with Oct4 to generate induced pluripotent stem cells. I hypothesized that polyesters based on simple aliphatic HDAC inhibitors like valproic acid (VPA) and phenylbutyric acid (PBA) can serve as alternatives to existing polyester biomaterials with improved anti-inflammatory properties and as scaffolds for generation of iPSCs when used in combination with layer-by-layer thin films delivering reprogramming transcription factors. Vinyl ester of phenylbutyric acid (VEPA) and vinyl ester of valproic acid (VEVA) were synthesized from their carboxylic acid precursors using an iridium complex catalyst at yields as high …

Spliceosomal Prp24 Unwinds A Minimal U2/U6 Complex From Yeast, Chandani Manoja Warnasooriya

Wayne State University Theses

Splicing plays a major role in eukaryotic gene expression by processing pre-mRNA to form mature mRNA. Pre-mRNAs undergo splicing to remove introns, non–protein coding regions, and religate exons, protein coding regions. This process is catalyzed by the spliceosome, which consists of five small nuclear ribonucleoprotein particles (snRNPs: U1, U2, U4, U5 and U6) and numerous protein factors. Proper assembly of spliceosomal components is critical for function, and thus, defects in assembly can be lethal. Several spliceosomal proteins facilitate structural rearrangements important for spliceosomal assembly and function. Prp24 is an essential factor in U6 snRNP assembly, and it has been proposed …

Catalytic Effects Of Period Iv Transition Metal In The Oxidation Of Biodiesel, Bradley Clark

Wayne State University Theses

CATALYTIC EFFECTS OF PERIOD IV TRANSITION METALS IN THE OXIDATION OF BIODIESEL

BRADLEY R CLARK

December 2011

Advisors: Dr. Steve Salley, Dr. Simon Ng, Dr. Naiem Henien

Major: Alternative Energy Technology

Degree: Masters of Science

Transition metals have the ability to catalyze free radical autoxidation of unsaturated fatty acid methyl esters (i.e., biodiesel). The catalytic effects of the eight period IV transition metals: V, Cr, Mn, Fe, Co Ni, Cu and Zn in soybean oil and cottonseed oil-based biodiesel are investigated. All metals produced a reduction of the induction period of biodiesel, although there are considerable differences in their catalytic …

Dc Slice Imaging, Crossed Beam Reaction Of Chlorine Radical With Butane, Tarek Oussama Abdul Ghani

Wayne State University Theses

We present an investigation of the reaction dynamics of Cl radicals with

Butane using crossed molecular beams, at two collision energies: ~ 6.5 and 9 kcal/mol. The product butyl radical was ionized using a 157 nm probe laser, and detection was through a dc slice detection setup. The translational energy distributions looked similar for both collision energies. The angular distribution shows that at the high collision energy there is a sharp increase in the forward scattering. At low collision energy there is more backscattering. The results show that the different scattering angles give different translational energy distribution. The forward scattered …

Investigating The Glutamine-Trna (Glutamine) Synthesis Appartus Of The Human Pathogen Helicobacter Pylori, Nilesh Joshi

Wayne State University Theses

INVESTIGATING THE GLUTAMINE-TRNA (GLUTAMINE) SYNTHESIS APPARTUS OF THE HUMAN PATHOGEN HELICOBACTER PYLORI

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NILESH JOSHI

August 2012

Advisor: Tamara L. Hendrickson

Major: Chemistry

Degree: Master of Science

Accurate protein biosynthesis is a vital process to all cellular life. Aminoacyl-tRNAs are at the heart of this process: A correctly formed aminoacyl-tRNA is critical for protein biosynthesis. Organisms have evolved many mechanisms to repair misacylated tRNAs before they cause errors in protein biosynthesis, thus maintaining the integrity of the genetic code. The human pathogen Helicobacter pylori (H. pylori) synthesizes Glu-tRNAGln as an intermediate to producing Gln-tRNAGln. This misacylated intermediate could cause lethal …

The Spliceosomal Protein Prp8 Stabilizes A Compact Conformation Of The U2-U6 Complex, Subasinghe Appuhamilage Lemintha Imali Subasinghe

Wayne State University Theses

The spliceosome is a large, RNA-protein complex that catalyzes pre-mRNA splicing during mRNA maturation. The RNA components (small nuclear RNA; snRNAs) of the spliceosome have been well studied and are believed to be involved in the splicing catalysis. Although proteins are essential for splicing, they may not be directly involved in catalysis. Among hundreds of proteins, Prp8 is the only protein that interacts with all of the catalytically important snRNAs. Therefore, it is hypothesized that Prp8 may catalyze splicing either by directly participating in catalysis or by stabilizing the conformation of the catalytically active spliceosome. In order to test whether …

Analysis Of Gaba And Glutamate In The Mouse Dorsal Striatum, Stella Wisidagamage

Wayne State University Theses

ABSTRACT

ANALYSIS OF GABA AND GLUTAMATE IN MICE BRAIN

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STELLA WISIDAGAMA

May 2011

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Master of Science

GABA and glutamate are the predominant inhibitory and excitatory amino acid neurotransmitters in the central nervous system (CNS), respectively. However, their altered levels cause several neurological diseases including Parkinson's and Huntington's disease, schizophrenia, and epilepsy. It is important to measure their levels in the extra- and intracellular environments to better understand and develop improved therapeutics that will treat these neurological disorders. The principle aim of this study is to study the impacts of different endogenous …

The Roles Of Rhle And Hfq In Srna-Dependent Gene Regulation, Abeykoon Jayalath Iresha Sandeepanie Rathnayake

Wayne State University Theses

THE ROLES OF RHLE AND HFQ IN SRNA-DEPENDENT GENE REGULATION

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ABEYKOON JAYALATH IRESHA SANDEEPANIE RATHNAYAKE

DECEMBER 2010

Advisor: Dr. Andrew Feig

Major: Chemistry

Degree: Master of Science

Bacteria are adapted to live in diverse environmental conditions. Thus, they show excellent tolerance and response to extreme environmental conditions caused by low or high temperatures, high salinity, reactive oxygen species or high nutrient concentrations. sRNAs have been identified and characterized as cis-acting or trans-acting post-transcriptional regulators in diverse cellular processes including virulence and adaptation to environmental stress (11,12,14,15). Interactions of sRNAs and target mRNAs result in translational repression, translational activation or/and …

Synthesis Of Site Specific 1, N^2-Ethenodeoxyguanosine In A Small Oligonucleotide, Kathryn A. Carolin

Wayne State University Theses

Malondiadehyde (MDA) is a known carcinogen and mutagen produced by lipid peroxidation and prostaglandin synthesis in vivo. MDA is unique from structurally related compounds, methyl glyoxal and acrolein, because it produces frameshift mutations whereas the latter compounds induce base-pair substitutions. MDA forms several adducts with deoxyguanosine but it is not certain which one causes the frameshift mutations. Ideally, a single adduct on a replicating genome could simulate the in vivo process by which MDA mutagenesis would occur. This technique is known as site-specific mutagenesis. The approach of choice for site-specific mutagenesis experiment is the gapped heteroduplex method which requires the …

The Preparation And Chemical Properties Of Tetracyclo [3.3.0.0^2,8.0^4,6] Octan-3-One, Arnold G. Phillips

Wayne State University Theses

No abstract provided.