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Investigation Of Early Complex Formation Of Huntingtin Protein With And Without Lipids, Alyssa R. Stonebraker

Graduate Theses, Dissertations, and Problem Reports (ETD)

Huntington’s disease (HD) is a fatal neurodegenerative disease caused by the expansion of the polyglutamine (polyQ) domain of the huntingtin protein (htt). The expansion of the polyQ domain beyond a threshold of approximately 35 repeats triggers complex toxic aggregation mechanisms and results in altered interactions between htt and lipid membranes. Many factors modulate these processes. One such modulator includes sequences flanking the polyQ domain, most notably the first 17 amino acids at the N-terminus of the protein (Nt17), and environmental factors including the presence of membranous structures. Nt17 has the propensity to form an amphipathic a-helix in the presence of …

Solid State Nmr Analysis Of Insect Wing Membranes, Samuel Eddy

Graduate Theses, Dissertations, and Problem Reports (ETD)

Solid State NMR is a powerful tool for analyzing the chemical composition of insects. Previous studies have used Solid State NMR to investigate the chemical composition and investigate the sclerotization (tanning) process of insect exoskeletons. Acquiring sufficient exoskeleton sample for analysis has been relatively simple. This is however not the case for other components of an insect’s physiology, particularly the wing membrane material. The wings of an insect only compose a small percentage of their overall body mass, and many hundreds to thousands of insects must be processed in order to achieve a few milligrams of wing membrane sample. The …

Development Of Novel Mass Spectrometry Method For The Analysis Of Complex Compounds, Jing Wang

Graduate Theses, Dissertations, and Problem Reports (ETD)

As mass spectrometry methods continue to advance, there is a growing need for innovative interfaces that can seamlessly integrate sample pretreatment, separation, and ionization, allowing for direct mass analysis while maintaining a simple and flexible system. The evolution of ambient ionization techniques has made it feasible to nebulize analyte compounds at ambient pressure. Moreover, single-cell proteomics using mass spectrometry is gaining increasing attention, necessitating the development of precise sample preparation techniques to enhance sensitivity. In this dissertation, I demonstrate the novel mass spectrometry system to couple the sample pretreatment with the direct mass spectrometry detection for the analysis of diverse …

Application Of Computational Biophysics Techniques To Characterize Cell Membrane-Associated Events, Kyle Billings

Graduate Theses, Dissertations, and Problem Reports (ETD)

Cell membranes are crowded environments which can modulate protein structure-function relationships through interaction with lipids, other proteins, carbohydrate structures and so on. This work focuses the impact of the membrane environment on two varieties of peptides: Microbial rhodopsin proteins, and cyclic peptides.

Life on Earth is dependent on the ability of plants and microbes to harness sunlight for energy production. Their ability to transform light into carbohydrates requires tailor-made machinery, and for a wealth of microorganisms, microbial rhodopsin proteins (MR) are critical for maintaining the concentration gradients used to produce the energy molecule Adenosine triphosphate (ATP). The central retinal molecule …

Investigating The Interactions Of The Iron-Sulfur Mitochondrial Protein, Mitoneet With Its Binding Partners, Ebenezer Osei Newton

Graduate Theses, Dissertations, and Problem Reports (ETD)

MitoNEET belongs to the CDGSH Iron-Sulfur Domain (CISD)-gene family of proteins and is a [2Fe-2S] cluster-containing protein found on the outer membrane of mitochondria. The specific functions of mitoNEET/CISD1 remain to be fully elucidated, but the protein is involved in regulating mitochondrial bioenergetics in several metabolic diseases. Unfortunately, drug discovery efforts targeting mitoNEET to improve metabolic disorders are hampered by the lack of ligand-binding assays for this mitochondrial protein. We have developed a protocol amenable for high-throughput screening (HTS) assay, by modifying an ATP fluorescence polarization method to facilitate drug discovery targeting mitoNEET. Based on our observation that adenosine triphosphate …

What Moves The Needle On Dfw Rates And Student Success In General Chemistry? A Quarter-Century Perspective, Vijay Vyas, Scott A. Reid

Chemistry Faculty Research and Publications

Second-term general chemistry is a key gateway course at our institution for a variety of STEM (Science, Technology, Engineering, and Mathematics) majors. Herein, we examine data on DFW% (i.e., % of D and F grades and withdrawals) in our general chemistry courses over roughly a quarter-century period, focusing on sections taught by the authors. The data are discussed in light of changes in curriculum, pedagogy, and assessments, which included introduction of recitation sections, classroom response systems (clickers), and online homework, restructuring of course content into a modular format, followed by a redesign of the course modules along an anchoring concepts …

The Design And Characterization Of Gold Nanoclusters As Elementary Building Blocks, Heather Gaebler

Theses and Dissertations (Comprehensive)

Gold nanoclusters with diameters in the quantum size regime (< ~2 nm) are promising building blocks for the design of novel nanomaterials as they exhibit unique size-dependent properties that can be altered and fine-tuned. The research outlined in this PhD thesis employs density functional theory to construct and analyze small ligand-protected cage and rod-shaped nanoclusters. Chapter 2 reports stable halide-protected gold nanocages that were engineered to have a closed-shell valence electron count of 18. This study finds that nanocages comprised of 19 and 20 gold atoms can be converted into stable magic number species containing 18 valence electrons by modifying their charged states via adsorption of halide ligands to the cage’s surface. Chapter 3 reports stable ligand-protected gold nanoclusters with a tetrahedral Au₄ core that were engineered to have a closed-shell valence electron count of 2. This study investigates the structural and electronic effects of halide and alkoxy ligands on the tetrahedral nanocluster and concludes that the results support the broader conclusion that it’s possible to fine-tune the stability and electronic properties of small gold nanoclusters using appropriate ligands. Chapter 4 reports stable gold nanorods that have diameters in the quantum regime that were constructed from elementary building blocks that contain “halide-staples”. This study presents different orientations of the “halide-staple” motifs on …

Phosphorus Release And Recovery From Simulated Ferric Wastewater Sludge, Aseel Alnimer

Theses and Dissertations (Comprehensive)

Phosphorus (P) is a fundamental element necessary for all life forms and a key component in the fertilizer industry. Meanwhile, the excessive load of P to water bodies due to human activities has the potential to promote eutrophication. Wastewater treatment plants remove P either biologically or chemically and produce P rich sludge which could be a potential renewable source for P. At present, commercial technologies exist for P recovery from biological wastewater sludge. However, P recovery from chemical sludge particularly iron(III)-phosphate (Fe-P) sludge generated in chemical P removal plants that use iron(III) salts remains a challenge.

This study explored, in …

Amphiphilic Block Copolymers And The Applications In Therapeutics Delivery, Jie Dou

Dissertations

Well-defined thermo-responsive triblock copolymers containing polyethylene oxide (PEO) and poly(N-isopropyl acrylamide) PNIPAM are synthesized by a type of living controlled polymerization, named iniferter polymerization. The polymers are amphiphilic in nature and are self-assembled into a micelle. Their properties and application are characterized and investigated in this work.

Foremost, the initiator of the polymerization (iniferter) is designed and synthesized by condensation polymerization, where PEO is incorporated into the structure to improve biocompatibility, which has great potential for biological application. Moreover, this iniferter reagent could be applied to more than 70 percent of vinyl monomers.

NIPAM, a commercial vinyl monomer, is chosen …

Non-Traditional Methods For The Green Synthesis Of Fine Chemicals, Tara Renée Mooney

Graduate Masters Theses

Herein, the advancement of microwave-assisted flow synthesis is reviewed and the green nitration of arenes is investigated. First, microwave-assisted flow systems are described, followed by their synthetic and environmental applications. Microwave-assisted flow synthesis has been applied successfully in organic, inorganic, material, and biochemical syntheses as well as environmental applications such as water desalination and the removal of volatile organic compounds from the atmosphere. In the second part of the Thesis, the methodological development of the first catalyst and solvent-free nitration of m-xylene using only nitric acid is detailed. This environmentally friendly reaction proceeds without the use of harsh Brønsted acids, …

Coconut Shell Waste Treatment Technology For A Sustainable Waste Utilization: A Case Study Of The Smes In Bohol Village, Indonesia, Wahyu Anggo Rizal, Ria Suryani, Roni Maryana, Dwi Joko Prasetyo, Diah Pratiwi, Yuli Ary Ratnawati, Dini Ariani, Andri Suwanto

ASEAN Journal of Community Engagement

This project focused on the introduction of liquid smoke and bio briquette manufacturing technology to small and medium enterprises (SMEs) located in Bohol Village, Gunungkidul, Indonesia through technology transfer, training, and mentoring. These SMEs are engaged in the food business with the main product jenang ketan, a traditional food from Gunungkidul, especially in Rongkop District, and very popular among communities around and outside Gunungkidul. The traditional preparation of jenang ketan produces several by-products in the form of waste, which is dominated by coconut shell biomass. The project’s technology transfer was carried out through the procurement of a series of pyrolysis …

Carbon-Al Interface Effect On The Performance Of Ionic Liquid-Based Supercapacitor At 3 V And 65 OC, Zhen-Zhen Ye, Shu-Ting Zhang, Xin-Qi Chen, Jin Wang, Ying Jin, Chao-Jie Cui, Lei Zhang, Lu-Ming Qian, Gang Zhang, Wei-Zhong Qian

Journal of Electrochemistry

Ionic liquid (IL) electrolyte-based supercapacitors (SCs) have advantages of high operating voltage window, high energy density and nonflammability, as compared to conventional acetonitrile-based organic electrolyte SCs, and are typically suitable for the large-scale energy storage in the era of carbon neutrality full of renewable, but unstable electricity. However, current efforts were concentrated on the study with coin-cell type of IL-SCs, and less has been reported on the pouch type of IL-SCs for a long cycling time yet. To fabricate a reliable SC for the life time test or for the accelerated aging test under high temperature, one should concern the …

Multiomics Approach Captures Hepatic Metabolic Network Altered By Chronic Ethanol Administration, Isin Tuna Sakallioglu, Bridget Tripp, Jacy Kubik, Carol A. Casey, Paul G. Thomes, Robert Powers

Department of Chemistry: Faculty Publications

Using a multiplatform and multiomics approach, we identified metabolites, lipids, proteins, and metabolic pathways that were altered in the liver after chronic ethanol administration. A functional enrichment analysis of the multiomics dataset revealed that rats treated with ethanol experienced an increase in hepatic fatty acyl content, which is consistent with an initial development of steatosis. The nuclear magnetic resonance spectroscopy (NMR) and liquid chromatography–mass spectrometry (LC-MS) metabolomics data revealed that the chronic ethanol exposure selectively modified toxic substances such as an increase in glucuronidation tyramine and benzoyl; and a depletion in cholesterol-conjugated glucuronides. Similarly, the lipidomics results revealed that ethanol …

Late-Stage Functionalization Through Click Chemistry Provides Glut5-Targeting Glycoconjugate As A Potential Pet Imaging Probe, Adelina Oronova, Marina Tanasova

Michigan Tech Publications, Part 1

The targeting of facilitative sugar transporters (GLUTs) has been utilized in the development of tools for diagnostics and therapy. The interest in this area is promoted by the phenomenon of alterations in cellular metabolic processes that are linked to multitudes of metabolic disorders and diseases. However, nonspecific targeting (e.g., glucose-transporting GLUTs) leads to a lack of disease detection efficiency. Among GLUTs, GLUT5 stands out as a prominent target for developing specific molecular tools due to its association with metabolic diseases, including cancer. This work reports a non-radiolabeled fluoride (19F) coumarin-based glycoconjugate of 2,5-anhydro-D-mannitol as a potential PET imaging probe that …

Determination Of Total Ammonia Nitrogen By Gas-Diffusion Flow Injection Analysis (Gd-Fia)-Spectrophotometry Using Minnieroot Flower (Ruellia Tuberosa) As Natural Reagent, Lani Artana Putri, Puspita Mufidah Sari, Hermin Sulistyarti, Akhmad Sabarudin, Erwin Sulistyo

Makara Journal of Science

Total ammonia nitrogen (TAN) is a pollutant agent found in water and generated from the metabolisms of living organisms and the decomposition of organic matter. This research aims to develop an efficient, low-cost, and environmentally friendly TAN analysis method. The principle of this method is based on the reaction of TAN injected in the donor stream with NaOH to form alkaline gaseous ammonia. The gaseous ammonia diffuses through a hydrophobic membrane into an acceptor stream containing Ruellia tuberosa extract. The presence of NH₃ gas in the acceptor stream changes the extract color from pinkish to green, which is monitored …

Compatibility Of Crude Oil Blends─Processing Issues Related To Asphaltene Precipitation, Methods Of Instability Prediction─A Review, Krzysztof Bambinek, Andrzej Przyjazny, Grzegorz Boczkaj

Natural Sciences Publications

Processing crude oil of variable composition, especially due to the need to process crude oil blends obtained from various sources, presents a tremendous process challenge. This is mainly due to the destabilization of the colloidal system manifested mostly by the precipitation of the asphaltene fraction. The precipitation of asphaltenes from crude oil is a serious problem during extraction, transport, and processing. In the latter case, engineers and scientists have spent a lot of time determining what mechanisms are conducive to the occurrence of this phenomenon. On the one hand, there was a scientific curiosity about the principles of the nanoworld …

A Coherence-Colored Look Inside Reverse Micelles: Advancing Magnetic Resonance Relaxometry To Characterize Internal Water Pool Dynamics, Alec Beaton

Dissertations - ALL

Traditional data acquisition methods in Nuclear Magnetic Resonance (NMR) collect a subset of the total amount of generated data and discard the rest. In this work, a modified approach toward NMR data acquisition and analysis is formalized and applied in a series of different contexts, ultimately illustrating the utility of collecting and considering this traditionally discarded data. In particular, it is shown that this approach both facilitates and improves NMR data acquisition capabilities at low field (15 MHz), enabling one to overcome challenges arising from, for example, fluctuations in the static magnetic field.With these developments in hand, the dual resonance …

Arginine Methylation Of The Pgc-1Α C‑Terminus Is Temperature- Dependent, Meryl Mendoz, Mariel Mendoza, Tiffany Lubrino, Sidney Briski, Immaculeta Osuji, Janielle Cuala, Brendan Ly, Ivan Ocegueda, Harvey Peralta, Benjamin A. Garcia, Cecilia Zurita-Lopez

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We set out to determine whether the C-terminus (amino acids 481–798) of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, UniProt Q9UBK2), a regulatory metabolic protein involved in mitochondrial biogenesis, and respiration, is an arginine methyltransferase substrate. Arginine methylation by protein arginine methyltransferases (PRMTs) alters protein function and thus contributes to various cellular processes. In addition to confirming methylation of the C-terminus by PRMT1 as described in the literature, we have identified methylation by another member of the PRMT family, PRMT7. We performed in vitro methylation reactions using recombinant mammalian PRMT7 and PRMT1 at 37, 30, 21, 18, and 4 °C. …

Effect Of Temperature And Sodium Chloride Addition On The Conductivity Of Sodium (Polystyrene Sulfonate) Aqueous Solutions, Saida Asfour, Ahmed Ayyad, Fahed Takrori

Hebron University Research Journal-A (Natural Sciences) - (مجلة جامعة الخليل للبحوث- أ (العلوم الطبيعيه

The conductivity of sodium (polystyrene sulfonate) (NaPSS) aqueous solutions as a function of NaPSS concentration 0.15 g – 2.0 g NaPSS in 100 mL of distilled water, sodium chloride concentration (NaCl) in the range of 0.1 M - 0.4 M and in temperature range of 278 K – 328 K have been studied. The study found that conductivity increases with increasing NaPSS concentration both in pure water and in salt solution. It is also found that conductivity increases with increasing either NaCl concentration or temperature. The interesting finding here is that additivity rule, that the conductivity of the polyelectrolyte kps …

Post-Translational Modifications Of Cyclophilin D Fine-Tune Its Conformational Dynamics And Activity: Implications For Its Mitochondrial Function, Jacques Kumutima, Xin-Qiu Joe Yao, Donald Hamelberg

Chemistry Faculty Publications

Mitochondria are the powerhouse of a cell, whose disruption due to mitochondrial pore opening can cause cell death, leading to necrosis and many other diseases. The peptidyl-prolyl cis–trans isomerase cyclophilin D (CypD) is a key player in the regulation of the mitochondrial pore. The activity of CypD can be modulated by the post-translational modification (PTM). However, the detailed mechanism of this functional modulation is not well understood. Here, we investigate the catalytic mechanism of unmodified and modified CypD by calculating the reaction free energy profiles and characterizing the function-related conformational dynamics using molecular dynamics simulations and associated analyses. Our results …

Medicinal Bismuth: Bismuth-Organic Frameworks As Pharmaceutically Privileged Compounds, Shaila A. Shetu, Luis M. Sanchez-Palestino, Gildardo Rivera-Sanchez, Debasish Bandyopadhyay

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Historically organometallic compounds have been used to cure certain diseases with limited applications. Although bismuth belongs to the category of heavy metals, many of its derivatives have found applications in modern drug discovery research, mainly because of its low toxicity and higher bioavailability. Being an eco-friendly mild Lewis acid, compounds having bismuth as a central atom are capable of binding several proteins in humans and other species. Bismuth complexes demonstrated antibacterial potential in syphilis, diarrhea, gastritis, and colitis. Apart from antibacterial activities, bismuth compounds exhibited anticancer, antileishmanial, and some extent of antifungal and other medicinal properties. This article discusses major …

Speciated Isotope Dilution Mass Spectrometry In Combination With Thor’S Hammer Metaspike Technology For The Assessment Of Low-Level Biomarkers For Human Health Evaluation, Ashley Ebert

Electronic Theses and Dissertations

Our research team has been focused on quantifying important biological analytes in human blood samples to delineate the biochemical processes underlying certain states of dysfunction and evaluate treatment efficacy. These efforts have been guided by laboratory measurements with the input of medical experts. Speciated isotope dilution mass spectrometry (SIDMS) explained in detail in EPA Method 6800 has been successfully applied in the quantification of an important biomarker analyte for immune function and detoxification processes: glutathione. Past research has proven the molecule a biomarker for autism spectrum disorder (ASD) in the form of the reduced/oxidized glutathione (GSH/GSSG) ratio, and literature has …

Quantum Computations And Molecular Dynamics Simulations: From The Fundamentals Of Antimicrobial Resistance To Neurological Diseases, Angel Tamez

Electronic Theses and Dissertations

Biophysical phenomena are modeled using a combination of quantum and classical methods to interpret and supplement three distinct and diverse problems in this dissertation. In the first project, decarboxylation reactions are ubiquitous across chemical and biological disciplines, yet the origin of non-catalytic solvent effects remains elusive. Specific solvent structure and energetics have not been well described for the monoanion of malonate, nor corrected from the gas-phase charge-assisted intramolecular hydrogen bond model known as “pseudochair”. In the aqueous phase, a low-lying energy conformer known as the “orthogonal conformation” is computed to be preferred by a three-water cluster of hydrogen bonding over …

Chemical Elements, Flavor Chemicals, And Nicotine In Unused And Used Electronic Cigarettes Aged 5–10 Years And Effects Of Ph, Monique Williams, Wentai Luo, Kevin J. Mcwhirter, Omeka Ikegbu, Prue Talbot

Chemistry Faculty Publications and Presentations

The concentrations of elements/metals, nicotine, flavor chemicals and acids were compared in the e-liquids of unused and used first-generation electronic cigarettes (ECs) that were stored for 5–10 years. Metal analysis was performed using inductively coupled plasma optical emission spectroscopy; nicotine and flavor chemical analyses were performed using gas chromatography/mass spectroscopy. Of the 22 elements analyzed, 10 (aluminum, chromium, copper, iron, lead, nickel, selenium, silicon, tin, zinc) were often found in the e-liquids. Five elements had the highest average concentrations: copper (1161.6 mg/L), zinc (295.8 mg/L), tin (287.6 mg/L), nickel (71.1 mg/L), and lead (50.3 mg/L). Nicotine concentrations were always lower …

Synthesis And Application Of Functional Unimolecular [N]Catenanes In Novel Polymeric Materials, Mark Andrew Nosiglia

Arts & Sciences Graduate Student Theses and Dissertations

Mechanically interlocked molecules (MIMs) possess unique architectures and non-traditional degrees of freedom that arise from well-defined topologies that are achieved through precise mechanical bonding. Incorporation of MIMs into materials can thus provide an avenue to discover new and emergent macroscale properties. Here, the synthesis of a phenanthroline-based [2]catenane crosslinker and its incorporation into polyacrylate organogels is described. Specifically, Cu(I) metalation and de-metalation was used as a post-gelation strategy to tune the mechanical properties of a gel by controlling the conformational motions of integrated MIMs. The organogels were prepared via thermally initiated free radical polymerization, and Cu(I) metal was added in …

Development Of Redox-Responsive Phenazine-Based Foldamers. Acylative Kinetic Resolution Of Hydroxamic Acids, Jingwei Yin

Arts & Sciences Graduate Student Theses and Dissertations

Two different research directions have been presented in this thesis. The first project is about phenazine-based foldamers as molecular actuators. Researchers have been interested in the design and synthesis of foldamers and molecular actuators for years. We began our exploration by demonstrating that phenazine-1,6-dicarboxamides can function as redox-responsive molecular switches. We then designed and synthesized two generations of phenazine-based interleafed foldamers and studied their stability and redox behaviors under chemical and electrochemical conditions. In the second project, we have developed the first acylative kinetic resolution on hydroxamic acids. Although chiral hydroxamic acids have extensive applications, synthetic methods towards them are …

Functionalized Plasmonic Nanostructures For Ultrasensitive Single Cell Analysis, Priya Rathi

Arts & Sciences Graduate Student Theses and Dissertations

Ultrasensitive detection and quantification of soluble, secreted and cell surface-bound proteins is critical for advancing our understanding of cellular systems, enabling effective drug development, novel therapies, and bio-diagnostics. However, exiting technologies are largely limited by their sensitivity, making the detection and quantification of low-abundant proteins extremely challenging. This forms a major barrier in various fields of biology and biomedical sciences. In this work, we introduce novel cellular analysis methodologies based on plasmon-enhanced fluorescence for analyzing cell structure and probing surface and secreted proteins from cells. In the first part, we introduce plasmon-enhanced expansion microscopy and demonstrate the effectiveness of employing …

Tracking Reducing Equivalents Between Cellular Compartments To Understand The Metabolic Demands Of Proliferation, Yahui Wang

Arts & Sciences Graduate Student Theses and Dissertations

Proliferating cancer cells compartmentalize metabolic reactions, many of which require reducing equivalents. This compartmentalization is functionally important, but it is challenging to study with current technologies. As a consequence, our understanding of proliferating metabolism has been limited. Here, I developed an approach to track reducing equivalents between cellular compartments. By applying this method to a panel of different cell lines under various conditions, I investigated a dysregulated metabolic phenotype in proliferating cells known as “aerobic glycolysis”. Aerobic glycolysis is characterized by an elevated rate of glucose fermentation to lactate irrespective of oxygen availability. Using the NCI-60 cell lines, I first …

The Effect Of Ionization Density In Applications Of Radiation Detection, Dosimetry, And Therapy, Daniel Mulrow

Arts & Sciences Graduate Student Theses and Dissertations

This dissertation covers a wide range of topics but is linked by the common theme of radiation interacting with materials and studying the result of those interactions. The introduction describes the fundamentals of how radiation interacts with material and how we are able to detect that radiation and the application of how we use those interactions in radiation oncology. The thesis starts with a chapter detailing the temperature dependence of the photophysics in two organic scintillators. This chapter is the foundation for a future study that will look the degree to which these scintillators can distinguish between gammas and neutrons …

Non-Canonical Beta-Lactam Antibiotics, Brett Wesley Virgin-Downey

Arts & Sciences Graduate Student Theses and Dissertations

In canonical β-Lactam antibiotics, such as penicillin, the strained nature of the β-Lactam ring leads to acylation of the catalytic serine in the active site of transpeptidases. In 2018, our lab reported a novel mechanism for monocyclic β-lactam antibiotics in the inhibition of glutamine synthetase (GS) by a natural product, tabtoxinine-β-lactam (TβL) using a 3-hydroxy-β-lactam pharmacophore. This work aims to generalize the β-lactam scaffold from TβL to act as a warhead against ATP-dependent carboxylate-amine ligase enzymes, with dihydrofolate synthetase (DHFS) as the test case. A pure 3-hydroxy-β-lactam warhead was synthesized and ligated both chemically and chemoenzymatically to different pteridine mimics. …