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Devising A Scalable Synthesis To Probe The G-Protein Cell Receptor Signaling Pathway, Matthew Robert Medcalf

Arts & Sciences Graduate Student Theses and Dissertations

The G-protein coupled cell receptor signaling pathway is amongst the largest and most diverse class of cell-surface receptors in the body. Nearly 800 different genes encode for these cell membrane receptors which are responsible for mediating a variety of hormones, neurotransmitters, and sensory stimuli through the activation of intracellular G proteins. To date, roughly 34% of pharmaceuticals on the market target GPCR’s, but despite this fact, there are still many difficulties associated with targeting this family of receptors. The vast number of GPCR’s, disease states resulting from a dysregulation of multiple GPCR signaling pathways, and difficulties crystalizing and purifying the …

Sideromycin Pathway Elucidation: Insights Into Salmycin Biosynthesis, Transport Paradigms, And Drug Release, Gerry Sann Macaraeg Rivera

Arts & Sciences Graduate Student Theses and Dissertations

Antibiotic resistance is an increasing threat in today’s society. In order to overcome resistant bacteria, it is necessary to discover new drugs with novel mechanisms of action. This work focuses on the sideromycin pathway, encompassing the biosynthetic production, mechanism of entry and hydrolysis-mediated drug release. Sideromycins are an interesting approach to combat the rise of antibiotic resistance since they provide a different avenue that overcomes problems that arise when entering the cell. The dissertation is separated into distinct sections dealing with the various areas of interest in the sideromycin pathway, particularly for the sideromycin, salmycin, produced by Streptomyces violaceus. The …

Development And Application Of Mass Spectrometry-Based Protein Footprinting In Structural Proteomics, Ming Cheng

Arts & Sciences Graduate Student Theses and Dissertations

Integral mass spectrometry (MS) has emerged as an important tool for protein structural characterization. It readouts are a broad range of structural information, including stoichiometry, interactions, conformations and conformation change, and dynamics. Protein footprinting is a pivotal component in the intergral MS toolkit.My dissertation centers around the development and application of protein footprinting to characterize protein structure. It is divided into seven chapters.Chapter 1 serves as the introduction for integral mass spectrometry in structural proteomic.In Chapter 2, we extended the fast-photochemical oxidation of proteins (FPOP) platform by adding the trifluoromethyl radical (•CF3) as a new reagent. We discovered that •CF3 …

Influence Of Biosolids Upon The Uptake Of Mn And Cd By Radish (Raphanus Sativus L.), Oluwadamilola O. Fateru

Electronic Theses and Dissertations

The influence of biosolids upon the uptake of Mn and Cd by radish (Raphanus sativus L.) was investigated through the characterization of biosolids, sequential extraction of the biosolids, and the determination of the metal content in the root, shoot and leaves of radish (Raphanus sativus L.).The biosolid samples from Nacogdoches Wastewater Sludge (NWWS), Lufkin Wastewater Sludge (LWWS), Soil Therapy Compost (STC) had pHs between 5.33 – 6.74. The elemental compositions of the biosolid samples were determined using inductively coupled plasma optical emission spectroscopy (ICP-OES) and SEM/EDX. Major elements (K, Mg, Mn, P) needed for plant growth …

Computer-Aided Drug Design For The Potential Treatment Against Mycobacterium Tuberculosis, Alyssa Daniels '20, Rebecca Ellington '19

Student Publications & Research

Tuberculosis (TB) is a disease that can infect any part of the body, but most often infects the lungs. About 9 million people are infected with TB each year, and left untreated, TB is deadly. However, even when treated, Mycobacterium Tuberculosis (MTB), the pathogenic bacteria responsible for TB, can become drug-resistant and patients will need a much more rigorous treatment. Isocitrate lyase (ICL) is an enzyme that allows tuberculosis (and other pathogens) to survive in the body. ICL is an enzyme in the glyoxylate cycle that catalyzes the cleavage of isocitrate to succinate and glyoxylate. MTB is facilitated by this …

Building Mof Nanocomposites With Oxidized Graphitic Carbon Nitride Nanospheres: The Effect Of Framework Geometry On The Structural Heterogeneity, Dimitrios A. Giannakoudakis, Teresa J. Bandosz

Publications and Research

Composite of two MOFs, copper-based Cu-BTC (HKUST-1) and zirconium-based Zr-BDC (UiO-66), with oxidized graphitic carbon nitride nanospheres were synthesized. For comparison, pure MOFs were also obtained. The surface features were analyzed using x-ray diffraction (XRD), sorption of nitrogen, thermal analysis, and scanning electron microscopy (SEM). The incorporation of oxidized g-C3N4 to the Cu-BTC framework caused the formation of a heterogeneous material of a hierarchical pores structure, but a decreased surface area when compared to that of the parent MOF. In the case of UiO-66, functionalized nanospheres were acting as seeds around which the crystals grew. Even though the MOF phases …

Coordination Of Anions By Noncovalently Bonded Σ-Hole Ligands, Steve Scheiner, Mariusz Michalczyk, Wiktor Zierkiewicz

Chemistry and Biochemistry Faculty Publications

Research on σ-hole interactions that include halogen, chalcogen, pnicogen, and tetrel bonding has been accelerating in recent years. These cousins of the H-bond have many similar properties, including geometric preferences and energetics. Most of the work to date has focused on neutral complexes, with less known about these bonds to anions. This review summarizes the current state of knowledge about the complexes of anions with ligands that engage in these sorts of noncovalent bonds. Of particular interest are comparisons with H-bonds, and how the geometry of the fully coordinated complex varies as the number of surrounding ligands increases. A specific …

Oh Chemistry Of Non-Methane Organic Gases (Nmogs) Emitted From Laboratory And Ambient Biomass Burning Smoke: Evaluating The Influence Of Furans And Oxygenated Aromatics On Ozone And Secondary Nmog Formation, Matthew M. Coggon, Christopher Y. Lim, Abigail R. Koss, Kanako Sekimoto, Bin Yuan, Jessica B. Gilman, David H. Hagan, Vanessa Selimovic, Kyle J. Zarzana, Steven S. Brown, James M Roberts, Markus Müller, Robert Yokelson, Armin Wisthaler, Jordan E. Krechmer, Jose L. Jimenez, Christopher Cappa, Jesse H. Kroll, Joost De Gouw, Carsten Warneke

Chemistry and Biochemistry Faculty Publications

Chamber oxidation experiments conducted at the Fire Sciences Laboratory in 2016 are evaluated to identify important chemical processes contributing to the hydroxy radical (OH) chemistry of biomass burning non-methane organic gases (NMOGs). Based on the decay of primary carbon measured by proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS), it is confirmed that furans and oxygenated aromatics are among the NMOGs emitted from western United States fuel types with the highest reactivities towards OH. The oxidation processes and formation of secondary NMOG masses measured by PTR-ToF-MS and iodide-clustering time-of-flight chemical ionization mass spectrometry (I-CIMS) is interpreted using a box model employing …

Total Phenolic And Flavonoid Contents Of Anacyclus Pyrethrum Link Plant Extracts And Their Antioxidant Activity, Hanane Elazzouzi, Nadia Zekri, Touriya Zair, Mohamed Alaoui El Belghiti

Karbala International Journal of Modern Science

In this study, Anacyclus pyrethrm Link (roots) is a medicinal plant from the Asteraceae family, endemic to Morocco and is widely used in traditional medicine; was investigated for their total phenolics, flavonoids contents and antioxidant activities. The quantitative estimation of total flavonoids and phenols by the colorimetric method showed that the extracts were prepared by fractionation of the crude hydromethanolic extract (ethyl acetate and n-butanol). The phenol content of various extracts, estimated by the Folin-Ciocalteu method, was between 1,44 and 12,82 mg EAG / g extract of A. pyrethrum. Moreover, it is clear that ethyl acetate was the …

Design Of Reinforced Concrete Deep Beams Using Particle Swarm Optimization Technique, Qais F. Hasan, Dler A. Al-Mamany, Omer K. Fayadh

Karbala International Journal of Modern Science

Researches available in literature interrelating neural networks to civil engineering design problems, especially for beep beams, are very rare. Therefore, an optimization algorithm is developed and verified in this study and coded using MATLAB functions to determine the optimum cost design of reinforced concrete deep beams. ACI 318-14 code method is used benefiting from iterative particle swarm optimization technique due to its efficiency and reliability. Minimizing total cost is used as the objective function in terms of four decision variables. Self-adaptive penalty function technique is used to handle constraints for each of the 300 randomly selected particles, and in each …

Artificial Bee Colony Algorithm For Solving Fuzzy Multi-Objective Bed Allocation Model, Abdulhakeem Luqman Hasan

Karbala International Journal of Modern Science

With the improvement of the medical services frameworks rivalry, hospitals face more and more challenges. In the interim, allotment of resource has a crucial influence on performing competitive benefits in a hospitals. To choose the suitable beds number is one of the most essential tasks in hospital administration. Anyway, in true condition, bed allotment choice is a multiple-side problem with weakness and haphazardness of the information available. It is so sophisticated. Therefore, the research about bed allotment difficulty is comparatively rare under considering multiple departments, nursing hours, and stochastic information about arrival and service of patients. In this paper, we …

Performance Study Of The Membrane Based Layered Double Hydroxides ‘Znal-Gh’ In The Purification Of Groundwater, Jaouad Zerhouni, Omar Qabaqous, Fouzia Rhazi Filali, Mohammed Naciri Bennani, Najib Tijani

Karbala International Journal of Modern Science

The objective of this work is focused on the preparation and characterization of plan microfiltration membrane Zn₃Al-Gh and the study of their efficiency in the treatment of ground water. This membrane was carried by using the support of the clay such as Ghassoul ‘Gh’ prepared by using dry uniaxial compaction method. The layered double hydroxides (LDH) based on Zn₃Al-CO₃with molar ratio (Zn²⁺/Al³⁺=3) was deposited on support by direct co-precipitation method.

The characterizations of the membrane LDH-Gh ‘Zn₃Al-Gh’ and deposited layer Zn₃Al-CO_3, was done by scanning …

Evaluation Of Atmospherically Gases Using Models Flaash And Quac To Hyper-Spectral Imagery, Asmaa Maher

Karbala International Journal of Modern Science

The important step is correction of the effect of atmospheric on hyper-spectral imagery of the VIS “visible”, short wave & NIR “near-infrared” spectral range. In general, the cause for limiting the use of hyperspectral images is the atmospheric effects, so, atmospheric correction is necessary for any accurate processing. In this work, two atmospheric correction techniques have been applied on Hyper-spectral image. From the raw original image and also from the FLAASH and QUAC atmospheric corrected images the spectra of vegetation, water and soil were extracted. The acquisition data for study contained Hyperion bands for year “2015” images over each of …

Editorial Board

Karbala International Journal of Modern Science

No abstract provided.

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …

The Process Of Establishing Theoretically Grounded Measures Of Science And Chemistry Identity For Use In Undergraduate Chemistry Courses, Kathryn Nicole Hosbein

Dissertations and Theses

Identity has been theorized to aid in student persistence toward science, engineering, technology, and math (STEM) degrees. However, before we can explore the impacts of learning environments on identity, and subsequently persistence, robust measures that can aid in understanding how identity is fostered need to be available. This research study aims to create measures of identity by expanding an existing physics identity framework and contextualizing it to science and chemistry identities. Development of the measures was carried out through two distinct phases that provided evidence for reliability and multiple aspects of validity.

The first phase of the study used qualitative …

Spectroscopic And Computational Comparisons Of Thiolate-Ligated Ferric Nonheme Complexes To Cysteine Dioxygenase: Second-Sphere Effects On Substrate (Analogue) Positioning, Anne A. Fischer, Joshua R. Miller, Richard J. Jodts, Danushka M. Ekanayake, Sergey V. Lindeman, Thomas C. Brunold, Adam T. Fiedler

Chemistry Faculty Research and Publications

Parallel spectroscopic and computational studies of iron(III) cysteine dioxygenase (CDO) and synthetic models are presented. The synthetic complexes utilize the ligand tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (^Ph2TIP), which mimics the facial three-histidine triad of CDO and other thiol dioxygenases. In addition to the previously reported [Fe^II(CysOEt)(^Ph2TIP)]BPh₄ (1; CysOEt is the ethyl ester of anionic l-cysteine), the formation and crystallographic characterization of [Fe^II(2-MTS)(^Ph2TIP)]BPh₄ (2) is reported, where the methyl 2-thiosalicylate anion (2-MTS) resembles the substrate of 3-mercaptopropionate dioxygenase (MDO). One-electron chemical oxidation of 1 and 2 yields ferric species …

The Antimicrobial Activity And Cellular Targets Of Plant Derived Aldehydes And Degradable Pro-Antimicrobial Networks In Pseudomonas Aeruginosa, Yetunde Adewunmi

Dissertations

Essential oils (EOs) are plant-derived products that have been long exploited for their antimicrobial activities in medicine, agriculture, and food preservation. EOs represent a promising alternative to conventional antibiotics due to the broad-range antimicrobial activity, low toxicity to human commensal bacteria, and the capacity to kill microorganisms without promoting resistance. Despite the progress in the understanding of the biological activity of EOs, many aspects of their mode of action remain inconclusive. The overarching aim of this work was to address these gaps by studying molecular interactions between antimicrobial plant aldehydes and the opportunistic human pathogen Pseudomonas aeruginosa. We initiated …

Alkalinity And Mineral Concentration Estimation In Commercial Drinking Water, Holly Mills

Honor’s College Freeman Research Journal

Several aspects of water and water quality were reviewed and investigated in this study; the effects of dehydration on human health, the role of alkalinity in drinking water, and the actual levels of alkalinity and other minerals in commercial drinking water. Hydration plays a critical role in human physical performance as well as in the prevention of chronic diseases. This experiment was conducted to determine if the level of acidity ( or alkalinity) of commercial alkaline water are truly above the normal ph levels, and to identify the salts in each type of water. Based on researches, a more alkaline …

Characterization Of The Dimerization Domains On The Mannose-6-Phosphate/Insulin-Like Growth Factor Ii Receptor, Tyler Degener

Theses/Capstones/Creative Projects

The mannose-6-phosphate/insulin-like growth factor II (M6P/IGF2) receptor is a transmembrane protein known to sequester growth factors from the extracellular matrix. This behavior suggests a mechanism of tumor suppression. Structurally, the receptor’s extracellular region is segmented into 15 homologous repeats, which are divided further into 5 triplet domains, labelled 1-3, 4-6, 7-9, 10-12, and 13-15. What is notable about the triplets is their propensity to form dimers with triplets on a second M6P/IGF2 receptor. In fact, previous studies indicate that this protein functions optimally when dimerized. Thus, the purpose of this experiment is to characterize these domain interactions. Using a urea …

Advances In Liquid Chromatography And Liquid Chromatography- Mass Spectrometry For The Chiral Analysis Of Amino Acids And Differentiation Of Isomeric Amino Acid Residues In Peptides/Proteins From Complex Matrices, Siqi Du

Chemistry & Biochemistry Dissertations - Archive

Amino acids are essential building blocks in all living organisms. Initially it was believed that only L-amino acids were relevant in higher organisms, and D-amino acids were laboratory artifacts. Today, various D-amino acids have been detected in different organisms, including humans, and some even play essential roles in biological processes. In addition, abnormal D-amino acid levels have been reported in patients with different diseases. The variations in D-amino acid levels might be of some diagnostic value. However, our knowledge of D-amino acids remains limited and most of the D-amino acids are not well investigated due to the lack of a …

Direct Functionalization Of Inert C-H And C=C Bonds Using Copper And Zinc Catalysts Supported By Fluorinated Ligands, And The Chemistry Of Fe(Co)5 And Its Analogs With Coinage Metal Ions, Tharun Teja Ponduru

Chemistry & Biochemistry Dissertations - Archive

Transition-metal catalyzed direct functionalization of inert C-H and C=C bonds through nitrene- and oxo-transfer reactions are powerful and attractive synthetic strategies for constructing C-N and C-O bonds (e.g. found in amines, aziridines, alcohols, and carbonyl compounds) directly from hydrocarbon feedstocks, and have significant synthetic potential in chemical processes leading to natural products, pharmaceuticals and biologically active molecules. Chapters 2 and 3 of this work mainly focus on nitrene- and oxo-insertion chemistry catalyzed by transition metal complexes. We employed different types of fluorinated ligands to support copper and zinc metal centers. Therefore, complexes [HB(3,5-(CF3)2Pz)3]Cu(NCMe), [H2B(3,5-(CF3)2Pz)2]Cu(NCMe), [H2B(3,5-(CF3)2-4-(NO2)Pz)2]Cu(NCMe), [{(3,5-(CF3)2Pz)ZnEt}2(μ-THF)], [{(3-(CF3),5-(t-Bu)Pz)ZnEt}2(μ-THF)], [{(3,5-(i-Pr)2Pz)ZnEt}2(μ-THF)], [N{(CF3)C(C6F5)N}2]CuNCCH3, and …

High Confidence Identification Of Cross-Linked Peptides By Mass Spectrometry Cleavable Cross-Linking Technologies, Jayanta Kishor Chakrabarty

Chemistry & Biochemistry Dissertations - Archive

Mass spectrometry (MS)-based chemical cross-linking technique is a potential tool for understanding the protein structure and protein-protein interactions. However, low abundances of cross-linked products and the data complexity are the major challenges in this field. New strategies are required to pinpoint cross-linked peptides with high confidence. Our lab designed and synthesized a novel cross-linker with two differential MS-cleavable bonds, namely DUCCT. DUCCT-cross-linked peptide generates different diagnostic fragment ions in Collision Induced Dissociation (CID) and Electron Transfer Dissociation (ETD) (tandem mass spectrometric technique) which helps in the unambiguous identification of cross-linked peptide. We demonstrate the efficiency of DUCCT technology with model …

Effects Of The Dihydrouracil Lesion On Dna Using 1h/31p 1d And 2d Solution Nmr, Benjamin M. Boyd

Graduate Theses/Dissertations

The effects of the dihydrouracil lesion in DNA were studied using two dimensional NMR spectroscopy. The sequence used was based off of the Drew-Dickerson Dodecamer, with the cytosine in the three position replaced by a dihydrouracil. All of the nonexchangeable proton chemical shifts, with the exception of the H2, H5’, and H5’’, of the lesioned DNA were identified using NOESY spectra and then compared to the chemical shift values of the Drew Dickerson Dodecamer. The largest differences in chemical shifts were observed in the nucleotides neighboring the lesion, both within the strand and on the opposite strand. The imino exchangeable …

Ribbon Α-Conotoxin Ktm Exhibits Potent Inhibition Of Nicotinic Acetylcholine Receptors, Leanna A. Marquart, Matthew W. Turner, Lisa R. Warner, Matthew D. King, James R. Groome, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

KTM is a 16 amino acid peptide with the sequence WCCSYPGCYWSSSKWC. Here, we present the nuclear magnetic resonance (NMR) structure and bioactivity of this rationally designed α-conotoxin (α-CTx) that demonstrates potent inhibition of rat α3β2-nicotinic acetylcholine receptors (rα3β2-nAChRs). Two bioassays were used to test the efficacy of KTM. First, a qualitative PC12 cell-based assay confirmed that KTM acts as a nAChR antagonist. Second, bioactivity evaluation by two-electrode voltage clamp electrophysiology was used to measure the inhibition of rα3β2-nAChRs by KTM (IC₅₀ = 0.19 ± 0.02 nM), and inhibition of the same nAChR isoform by α-CTx MII (IC₅₀ = …

Qualitative Assay To Detect Dopamine Release By Ligand Action On Nicotinic Acetylcholine Receptors, Leanna A. Marquart, Matthew W. Turner, Owen M. Mcdougal

Chemistry and Biochemistry Faculty Publications and Presentations

A pheochromocytoma of the rat adrenal medulla derived (a.k.a. PC12) cell-based assay for dopamine measurement by luminescence detection was customized for the qualitative evaluation of agonists and antagonists of nicotinic acetylcholine receptors (nAChRs). The assay mechanism begins with ligand binding to transmembrane nAChRs, altering ion flow into the cell and inducing dopamine release from the cell. Following release, dopamine is oxidized by monoamine oxidase generating hydrogen peroxide that catalyzes a chemiluminescence reaction involving luminol and horseradish peroxidase, thus producing a detectable response. Results are presented for the action of nAChR agonists (acetylcholine, nicotine, and cytisine), and antagonists (α-conotoxins (α-CTxs) MII, …

Development, Evaluation, And Application Of Chromatographic Resolution Enhancement Strategies, Garrett Hellinghausen

Chemistry & Biochemistry Dissertations - Archive

With the emergence of advanced separation technologies, like high-efficiency stationary phases bonded with superficially porous particles, or sub-2 μm fully porous particles, faster and more effective methodologies are possible for liquid chromatographic analyses. Such advanced approaches can be easily applied to achiral separations but require more extensive optimization for chiral separations. Chiral molecules are subjected to extensive characterization of their enantiomeric pharmacological properties due to requirements of the Food and Drug Administration. Herein, fundamental chiral method development strategies are thoroughly discussed for hundreds of small molecules using conventional and newly synthesized chiral selectors bonded to high-efficiency supports. In these strategies …

Towards The Synthesis Of An Artificial Fluorescent Siderophore, Ashley Burns

Honors Theses

Siderophores are molecules capable of binding ferric ions with high affinity (Ka = 1052). This thesis outlines our attempts to synthesize an artificial siderophore, which incorporates a signaling group to help monitor the uptake of ferric ions. The artificial siderophore is a tripodal molecular receptor synthesized in a five-step procedure with a proposed final sixth step. Rhodamine 6G azide (95.0% yield) was formed from rhodamine 6G and the synthesis of 2-azidoethanamine was modified from the literature. The tripodal arm portion of the sensor was successfully synthesized by protecting the catechol of 2,3-dihydroxybenzaldehyde to form 3-formyl-1,2-phenylene dimethanesulfonate (98.8% yield). The reduction …

Rotational Tuning Of Transmembrane Helix Properties Based On The Precise Placements Of Aromatic And Charged Residues, Matthew J. Mckay

Graduate Theses and Dissertations

Designed model transmembrane peptides and oriented 2H and 15N solid-state nuclear magnetic resonance (NMR) spectroscopy were used to analyze how simple sequence modifications can influence peptide structure, behavior and dynamics as well as for determining the pKa of glutamic acid at the membrane interface. The GW5,19ALP23 (acetyl-GGALW(LA)6LWLAGA-amide) peptide framework adopts a well-defined tilted orientation in lipid bilayers (DLPC, DMPC and DOPC) and undergoes low amounts of dynamic motion. The sequence was initially modified by moving the Trp residues outwards to positions 4 and 20. This new sequence GW4,20ALP23 (acetyl-GGAW(AL)7AWAGA-amide) displays high amounts of signal averaging of NMR observables caused by …

Probing Of Carbohydrate-Protein Interactions Using Galactonoamidine Inhibitors, Jessica B. Pickens

Graduate Theses and Dissertations

Glycoside hydrolases are ubiquitous and one of the most catalytically proficient enzymes known, and thus understanding their mechanisms are crucial. Most research has focused on the interaction of the glycon of substrates and their inhibitors within the active site of glycoside hydrolases. The inhibitors employed to probe these interactions generally had small aglycons (i.e. a hydrogen atom, amidines, small aliphatic groups, or benzyl groups). Here, the interactions of the aglycon with glycoside hydrolases are examined by probing the active sites with a library of 25 galactonoamidines. The studies described in this dissertation aim to increase the understanding of stabilization of …