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The Effects Of Passive Integrated Transponder Tagging On Cortisol Release In The Gulf Killifish, Fundulus Grandis, Ariel Marcelo Hernandez

Senior Honors Theses

Due to its ease of use, low cost, and essentially limitless number of unique codes, PIT tagging has become the favored technique for tagging individuals in biological studies. However, studies employing PIT tagging generally assume that stress due to the implantation and presence of a PIT tag has no influence on the experimental results. This study investigated the effects of PIT tagging on levels of the stress hormone cortisol in the Gulf Killifish, Fundulus grandis, an estuarine fish of the Gulf of Mexico that is prone to daily or seasonal environmental stressors. Cortisol was measured non-invasively by extracting and …

Photoremovable Protecting Groups Based On Electrocyclization With Leaving Group Expulsion Via A Proposed Zwitterion, Gilbert Ndzeidze

Dissertations (1934 -)

The triplet excited state of thioxanthone produced by photolysis undergoes reversible triplet energy transfer with a trimethylene - linked benzothiophene-2-carboxanilide ring system. The ensuing electrocyclic ring closure of the anilide moiety produces a putative zwitterionic intermediate that is capable of expelling leaving groups (LG-) from the C-3 position of the benzothiophene ring. Stern-Volmer quenching studies with cyclohexadiene as quencher furnish the rate constants for the triplet excitation transfer in the forward and reverse directions, which can be expressed as an equilibrium constant K = 0.058. Overall, the rate of triplet excited state reaction becomes K x kr = 5.7 x …

Characterization Of Ambient Noise, Rachel C. Ramirez

Theses and Dissertations

An Air Force sponsor is interested in improving an acoustic detection model by providing better estimates on how to characterize the background noise of various environments. This would inform decision makers on the probability of acoustic detection of different systems of interest given different levels of noise. Data mining and statistical learning techniques are applied to a National Park Service acoustic summary data set to find overall trends over varying environments. Linear regression, conditional inference trees, and random forest techniques are discussed. Findings indicate only sixteen geospatial variables at different resolutions are necessary to characterize the first ten ⅓ octave …

Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activities of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against …

Discovery And Development Of A Three-Component Oxidopyrylium Cycloaddition And Its Application Towards Alpha-Hydroxytropolone Synthesis, Michael P. D'Erasmo

Dissertations, Theses, and Capstone Projects

Historically, natural products have provided unique research opportunities and challenges for organic synthesis, chemical biology, and medicinal chemistry due to their molecular complexity and effects on physiological systems. The total synthesis of natural products has not only produced novel reaction methods and strategies capable of efficiently generating complex structural motifs but also granted access to sufficient quantities of otherwise scarce natural product material for clinical evaluation. These synthetic efforts have facilitated the formation of a transdisciplinary partnership between chemistry, biology, and medicine that has been paramount in elucidating the chemical and pharmaceutical utility of natural products. Chapter I of this …

Parp Pet Imaging Agents, Brandon Carney

Dissertations, Theses, and Capstone Projects

The poly (adenosine-diphosphate (ADP) ribose) polymerase (PARP) family of enzymes has been of interest to researchers and clinicians for over fifty years, especially the first member of the family, PARP1. This enzyme has become a target for cancer therapeutics due the reliance of highly proliferating cells on PARP1 for genomic maintenance. In the coming age of individualized medicine, however, highly specific therapeutic agents like PARP inhibitors are in need of similarly highly specific companion diagnostic agents. These kind of agents have been made possible with the quickly progressing field of molecular imaging. Specifically, positron emission tomography (PET) has enabled the …

Graphene Nanoplatelets-Sericin Surface-Modified Gum Alloy For Improved Biological Response, Valentina Mitran, Valentina Dinca, Raluca Ion, Vasile D. Cojocaru, Patricia Neacsu, Cerasela Zoica Dinu, Laurentiu Rusen, Simona Brajnicov, Anca Bonciu, Maria Dinescu, Doina Raducanu, Ioan Dan

Faculty & Staff Scholarship

In this study a “Gum Metal” titanium-based alloy, Ti-31.7Nb-6.21Zr-1.4Fe-0.16O, was synthesized by melting and characterized in order to evaluate its potential for biomedical applications. The results showed that the newly developed alloy presents a very high strength, high plasticity and a low Young's modulus relative to titanium alloys currently used in medicine. For further bone implant applications, the newly synthesized alloy was surface modified with graphene nanoplatelets (GNP), sericin (SS) and graphene nanoplatelets/sericine (GNP–SS) composite films via Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique. The characterization of each specimen was monitored by scanning electron microscopy (SEM), atomic force microscopy (AFM), …

Synthesis And Biological Evaluation Of Small Molecular Drug Candidates For The Treatment Of Her2 Overexpressed Breast Cancer, Anran Zhao

ETD Archive

In the US breast cancer is the most common cancer after skin cancer. Currently in the US the average risk of a woman to develop breast cancer in her life is roughly 12%. About 25-30% of breast cancer patients have HER2 overexpressed tumor, and the growth of tumor cell is depend on HER2 pathway. It has been well-documented that patients with over-expressed HER2 are associated with increased disease recurrence, worse prognosis and lower survival. Currently there are two type of HER2 targeting drug. The first group is HER2 monoclonal antibody drugs such as trastuzumab approved by FDA in 1998; the …

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 …

Biological Study On Novel Coumarinyl 1,3,4-Oxadiazoles, Maja Molnar, Ana Amic, Valentina Pavic, Tihomir Kovac, Marija Kovac, Elizabeta Has-Schön

Turkish Journal of Chemistry

Coumarinyl 1,3,4-oxadiazoles were synthesized from Schiff bases and acetic anhydride. All compounds were characterized by melting points and their structures confirmed by mass and $^{1}$H and $^{13}$C NMR spectrometry. These novel coumarinyl derivatives were subjected to antibacterial, antifungal, anta atoxigenic, and antioxidant activity. Their activity varied depending on their structure, where 2-(3-acetyl-5-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)- 2,3-dihydro-1,3,4-oxadiazol-2-yl)-1,4-phenylene diacetate showed significant antioxidant and antibacterial activity on B. subtilis. 4-(3-Acetyl-5-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-2,3-dihydro-1,3,4-oxadiazol-2-yl)-1,2-phenylene diacetate was found to possess excellent antifungal and antia atoxigenic activity.

Synthesis And Evaluation Of Novel 1,3,4-Thiadiazole--Fluoroquinolone Hybrids As Antibacterial, Antituberculosis, And Anticancer Agents, Asli Demi̇rci̇, Kaan Gökçe Karayel, Esra Tatar, Si̇nem Öktem Okullu, Ni̇han Ünübol, Paki̇ze Nesli̇han Taşli, Zühtü Tanil Kocagöz, Fi̇kretti̇n Şahi̇n, İlkay Küçükgüzel

Turkish Journal of Chemistry

A series of 5-substituted-1,3,4-thiadiazole-based fluoroquinolone derivatives were designed as potential antibacterial and anticancer agents using a molecular hybridization approach. The target compounds 16-25 were synthesized by reacting the corresponding $N$-(5-substituted-1,3,4-thiadiazol-2-yl)-2-chloroacetamides with ciprofloxacin or norfloxacin. The purity and identity of the synthesized compounds were determined by the use of chromatographic and spectral techniques (NMR, IR, MS, etc.) besides elemental analysis. Antibacterial, antituberculosis, and anticancer activity of the target compounds were evaluated against selected strains and cancer cell lines. Compound 20 was appreciated as the most active agent representing antibacterial activity against Escherichia coli and Staphylococcus aureus with MIC values of 4 …

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 …

Synthesis And Application Of Photoreactive Collagen Peptides, And Antiparasitic Agents, Alfredo Ornelas

Open Access Theses & Dissertations

Since the introduction of solid phase peptide synThesis in 1963, peptides and post-translationally modified peptides can be conveniently synthesized in the chemistry laboratory. In the past decade, there has been a remarkable increase in bioactive peptide research and the therapeutic peptide market value is expected to hit $25 billion this year. Peptides can also provide structural and biological functions and have emerged as promising novel biomaterials in tissue engineering. Here we will describe three different projects, which deal with different aspects of peptide chemistry, i.e. synthetic method development, exploration of new peptide biomaterials, and the use of cell penetrating peptides …

New Developments Of Dimension Reduction, Lei Huo

Doctoral Dissertations

"Variable selection becomes more crucial than before, since high dimensional data are frequently seen in many research areas. Many model-based variable selection methods have been developed. However, the performance might be poor when the model is mis-specified. Sufficient dimension reduction (SDR, Li 1991; Cook 1998) provides a general framework for model-free variable selection methods.

In this thesis, we first propose a novel model-free variable selection method to deal with multi-population data by incorporating the grouping information. Theoretical properties of our proposed method are also presented. Simulation studies show that our new method significantly improves the selection performance compared with those …

Quantitation Without Calibration: Response Profile As An Indicator Of Target Amount, Mrittika Debnath

Graduate Research Theses & Dissertations

Quantitative assessment of biomarkers is essential in numerous contexts from decision-making in clinical situations to food quality monitoring to the interpretation of life-science research findings. However, appropriate quantitation techniques are not as widely addressed as detection methods. One of the major challenges in biomarker’s quantitation is the need to have a calibration for correlating a measured signal to a target amount. The step complicates the methodologies and makes them less sustainable. In this work, we addressed the issue via a new strategy: relying on the position of response profile rather than absolute signal for assessment of a target nucleic acid’s …

Development Of Biclustering Techniques For Gene Expression Data Modeling And Mining, Juan Xie

Electronic Theses and Dissertations

The next-generation sequencing technologies can generate large-scale biological data with higher resolution, better accuracy, and lower technical variation than the arraybased counterparts. RNA sequencing (RNA-Seq) can generate genome-scale gene expression data in biological samples at a given moment, facilitating a better understanding of cell functions at genetic and cellular levels. The abundance of gene expression datasets provides an opportunity to identify genes with similar expression patterns across multiple conditions, i.e., co-expression gene modules (CEMs). Genomescale identification of CEMs can be modeled and solved by biclustering, a twodimensional data mining technique that allows clustering of rows and columns in a gene …

The Great Potential Of Redox Active Ligands: Applications In Cancer Research And Redox Active Catalysis, Meredith Miles

Browse all Theses and Dissertations

Metal N-heterocyclic carbene (NHC) complexes have recently gained much popularity due to their tunable, steric, and electronic properties. Applications for such versatile molecules include organocatalysis, olefin metathesis, sundry cyclization reactions, and materials chemistry. Redox active NHCs are of special interest due to their ability to alter the electronic properties of the metal centers they are ligated to. In the first chapter, Au(I)-NHC complexes were synthesized and tested for biological activity in human cancer cell lines. Increasing reactive oxygen species (ROS) in cellular systems has proven to be a successful pathway for treating cancer. The redox active group in this case …

Type I General Exponential Class Of Distributions, Gholamhossein G. Hamedani, Haitham M. Yousof, Mahdi Rasekhi, Morad Alizadeh, Seyed Morteza Najibi

Mathematics, Statistics and Computer Science Faculty Research and Publications

We introduce a new family of continuous distributions and study the mathematical properties of the new family. Some useful characterizations based on the ratio of two truncated moments and hazard function are also presented. We estimate the model parameters by the maximum likelihood method and assess its performance based on biases and mean squared errors in a simulation study framework.

Statistical Algorithms And Bioinformatics Tools Development For Computational Analysis Of High-Throughput Transcriptomic Data, Adam Mcdermaid

Electronic Theses and Dissertations

Next-Generation Sequencing technologies allow for a substantial increase in the amount of data available for various biological studies. In order to effectively and efficiently analyze this data, computational approaches combining mathematics, statistics, computer science, and biology are implemented. Even with the substantial efforts devoted to development of these approaches, numerous issues and pitfalls remain. One of these issues is mapping uncertainty, in which read alignment results are biased due to the inherent difficulties associated with accurately aligning RNA-Sequencing reads. GeneQC is an alignment quality control tool that provides insight into the severity of mapping uncertainty in each annotated gene from …

Hyperthermia As A Cancer Treatment- From Theory To Practice, Graham Fullerton

CMC Senior Theses

Using iron super-paramagnetic and ferromagnetic nanoparticles composed of Fe₃O₄ molecules, scientists analyze the effectiveness and practicality of this new treatment theory, hyperthermia. The problems of magnetic particle density, isothermal barriers/cellular cooling thresholds, and nanoparticle specific targeting are addressed in this review.

Iron magnetic nanoparticles were chosen due to their relatively low biological reactivates and lack of subsequent cellular toxicity. However, there are significant heating problems associated with these magnetic nanoparticles due to their relative size and short thermal time constants or thermal half-lives. Effectively, these aforementioned issues create a phenomenon where cancerous cells, surrounded by unheated healthy …

Crystallographically Defined Silicon Macropore Membranes, Shannon C. Knight, Bret A. Unger, Kurt W. Kolasinski

Chemistry Faculty Publications

Laser ablation with nanosecond-pulsed Nd:YAG laser irradiation combined with anisotropic alkaline etching of Si wafers creates 4–20 µm macropores that extend all the way through the wafer. The walls of these macropores are crystallographically defined by the interaction of the anisotropy of the etchant with the orientation of the single-crystal silicon substrate: rectangular/octagonal on Si(001), parallelepiped on Si(110), triangular/hexagonal on Si(111). Laser ablation can create pillars with peak-tovalley heights of over 100 µm. However, with nanosecondpulsed irradiation at 532 nm, the majority of this height is created by growth above the original plane of the substrate whereas for 355 nm …

Ultra-Fast And Memory-Efficient Lookups For Cloud, Networked Systems, And Massive Data Management, Ye Yu

Theses and Dissertations--Computer Science

Systems that process big data (e.g., high-traffic networks and large-scale storage) prefer data structures and algorithms with small memory and fast processing speed. Efficient and fast algorithms play an essential role in system design, despite the improvement of hardware. This dissertation is organized around a novel algorithm called Othello Hashing. Othello Hashing supports ultra-fast and memory-efficient key-value lookup, and it fits the requirements of the core algorithms of many large-scale systems and big data applications. Using Othello hashing, combined with domain expertise in cloud, computer networks, big data, and bioinformatics, I developed the following applications that resolve several major …

Spectroscopic Study Of Excited Molecular Nitrogen Generation Due To Interactions Of Metastable Noble Gas Atoms, Laurence Scally, James Lalor, Miroslav Gulan, Patrick J. Cullen, Vladimir Milosavljevic

Articles

This work provides an insight into the generation of excited nitrogen species by allowing noble gases to interact both with one another and ambient air. He and Ar were utilized to generate the optimum selectivity process to create reactive nitrogen species. An optimum setting for the generation of excited molecular nitrogen species, based on their excited energy levels, was obtained when using a mixture of Ar-He at a ratio of 10:1. At that point, when a voltage of 27 kV is applied to the system, it reached the maximum efficiency for selectivity processes to occur which allowed for a greater …

Syntheses Of Azepinoindole Alkaloids Cimitrypazepine, Fargesine And Hyrtioreticulins C & D, Ganesh Ghimire

Graduate Theses, Dissertations, and Problem Reports (ETD)

The Watanabe-Cenini-Söderberg reductive N-heterocyclization has emerged as a powerful tool for the synthesis of a variety of functionalized indoles. Söderberg’s elaboration of this methodology has been utilized as a late-stage cyclization protocol for the synthesis of azepinoindole alkaloids, a class of natural products characterized by an azepane skeleton fused with an indole ring. Short syntheses of the naturally occurring azepino[5,4,3-cd]indole alkaloids, cimitrypazepine, fargesine, and the diastereomeric hyrtioreticulins C & D have been completed starting from commercially available tetra-substituted benzene derivatives. The key azepinoindole core in each case was assembled via an intramolecular Mizoroki-Heck reaction followed by a …

Theoretical Circular Dichroism Spectra Of The Α-Helical Protein Calexitin With The Dipole Interaction Model Including The N-Π* Transition, Akongnwi C. Jungong, Tsvetan Aleksandrov, Rahul Nori, Justin Erickson, Kathryn A. Thomasson, Igor V. Uporov, Ethan R. Austhof, Emily Holt, Felix N. Ngassa

Chemistry Faculty Publications

Circular dichroism (CD) is an important structural biology technique used to study protein dynamics, and most especially the secondary structure of peptides and proteins. Although CD is a technique that is relatively easy to introduce to undergraduate students, the high cost of obtaining a conventional CD instrument and the time required for sample preparation prevents a good number of students from having hands-on experiments demonstrating the principle of CD. Herein, theoretical circular dichroism with the dipole interaction model, DInaMo, is proposed as a tool for introducing students to CD. Using the dipole interaction model, the CD spectra of an α-helical …

Zero-Inflated Models For Rna-Seq Count Data, Morshed Alam, Naim Al Mahi, Munni Begum

Journal Articles: Biostatistics

One of the main objectives of many biological studies is to explore differential gene expression profiles between samples. Genes are referred to as differentially expressed (DE) if the read counts change across treatments or conditions systematically. Poisson and negative binomial (NB) regressions are widely used methods for non-over-dispersed (NOD) and over-dispersed (OD) count data respectively. However, in the presence of excessive number of zeros, these methods need adjustments. In this paper, we consider a zero-inflated Poisson mixed effects model (ZIPMM) and zero-inflated negative binomial mixed effects model (ZINBMM) to address excessive zero counts in the NOD and OD RNA-seq data …

Multi-Dimensional Mass Spectrometry For The Characterization Of Glycopolymers, Maria Ganios

Williams Honors College, Honors Research Projects

Several glycopolymers synthesized by Activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP), were characterized by mass spectrometry to elucidate their microstructure and architecture. Analyses were performed using Matrix Assisted Laser Desorption Ionization- Time of Flight/ Time of Flight (MALDI-ToF/ToF) and Electrospray Ionization Mass Spectrometry (ESI-MS) instruments. The linear isopropylidenated glycopolymer (P65B1) analyzed with ESI-MS also was examined with multi-stage mass spectrometry (MSⁿ) using collision induced dissociation (CID) to examine the tetramer parent ion. This glycopolymer was found to be either cyclic or linear (sans end groups) due to the data being fit for both forms …

Synthesis Of 1,4-Triazolyl Combretacoumarins As Potential Anticancer Agents, Tashrique A. Khandaker

Dissertations and Theses

Coumarins are natural compounds that have various physiological and therapeutic properties, making them pharmacologically important. Combretastatin A-4 (CA-4) is a microtubule-binding agent that has potent cytotoxic effects against human cell lines. In CA-4 the trimethoxyarene moiety plays a crucial role in its carcinopreventive effect. Thus, we decided to synthesize novel, potential anti-cancer agents called 1,4-triazolyl combretacoumarins, by coupling different coumarins and the functionally relevant group of CA-4 i.e, the trimethoxyarene moiety, via a 1,2,3-triazolyl ring using a copper-catalyzed [3 + 2] azide-alkyne cycloaddition (CuAAC) reaction, which is a very atom-economical reaction. The coupling partners, 4-azidocoumarins, required for making these …

Split Aptameric Turn-On Fluorescence Sensor For Detection Of Sequence Specific Nucleic Acid At Ambient Temperature, Nanami Kikuchi

Electronic Theses and Dissertations

Nucleic acid amplification tests (NAATs) enable sensitive detection of low density infections that microscopy and rapid diagnostic test are not capable of detecting. They enable quantitative and qualitative nucleic acid detection, genotype analysis, and single nucleotide polymorphism (SNP) detection. Current state of the art molecular probes used with NAATs includes molecular beacon (MB), Taqman and its variations. This work presents novel molecular probe designed from Spinach and Dapoxyl aptamers. The aptamers are split into two parts (split aptamer), allowing greater sensitivity and selectivity towards fully complementary nucleic acid analyte. The major advantage of split aptamer probe over state-of-the-art fluorescent probes …

Trends In Benthic Macrofaunal Populations, Seasonal Sea Ice Persistence, And Bottom Water Temperatures In The Bering Strait Region, Jacqueline M. Grebmeier, Karen E. Frey, Lee W. Cooper, Monika Kędra

Geography

Recent declines in sea ice extent and warming seawater temperatures in the Arctic have the potential to impact regional and pan-Arctic marine ecosystems. To investigate marine biological response to these key drivers and other environmental factors, we undertook a robust trend analysis of benthic macrofaunal populations and environmental drivers in the Bering Strait region. Our focus was on the waters of the northern Bering and southern Chukchi Seas, which are shallow (m) and seasonally productive, with strong pelagic-benthic coupling between water-column-derived organic matter and the seafloor. Studies indicate that both in situ production and advection of upstream phytodetritus support persistent …