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Novel Protein Disulfide Isomerase Inhibitor With Anticancer Activity In Multiple Myeloma, Sergei Vatolin, James G. Phillips, Babal K. Jha, Shravya Govindgari, Jennifer Hu, Dale Grabowski, Yvonne Parker, Daniel J. Lindner, Fei Zhong, Clark W. Distelhorst, Mitchell R. Smith, Claudiu Cotta, Yan Xu, Sujatha Chilakala, Rebecca R. Kuang, Samantha Tall, Frederic J. Reu Jun 2016

Novel Protein Disulfide Isomerase Inhibitor With Anticancer Activity In Multiple Myeloma, Sergei Vatolin, James G. Phillips, Babal K. Jha, Shravya Govindgari, Jennifer Hu, Dale Grabowski, Yvonne Parker, Daniel J. Lindner, Fei Zhong, Clark W. Distelhorst, Mitchell R. Smith, Claudiu Cotta, Yan Xu, Sujatha Chilakala, Rebecca R. Kuang, Samantha Tall, Frederic J. Reu

Chemistry Faculty Publications

Multiple myeloma cells secrete more disulfide bond–rich proteins than any other mammalian cell. Thus, inhibition of protein disulfide isomerases (PDI) required for protein folding in the endoplasmic reticulum (ER) should increase ER stress beyond repair in this incurable cancer. Here, we report the mechanistically unbiased discovery of a novel PDI-inhibiting compound with antimyeloma activity. We screened a 30,355 small-molecule library using a multilayered multiple myeloma cell–based cytotoxicity assay that modeled disease niche, normal liver, kidney, and bone marrow. CCF642, a bone marrow–sparing compound, exhibited a submicromolar IC50 in 10 of 10 multiple myeloma cell lines. An active biotinylated analog …


Criteria For Selecting Pegylation Sites On Proteins For Higher Thermodynamic Stability, Paul B. Lawrence Jun 2016

Criteria For Selecting Pegylation Sites On Proteins For Higher Thermodynamic Stability, Paul B. Lawrence

Theses and Dissertations

PEGylation of protein side-chains has been used for more than 30 years to enhance the pharmacokinetic properties of protein drugs, and has been enabled by the recent development of many chemoselective reactions for protein side-chain modification. However, there are no structure- or sequence-based guidelines for selecting sites that provide optimal PEG-based pharmacokinetic enhancement with minimal loss to biological activity. Chapter 1 is a brief introduction to protein PEGylation. In chapter 2 we use the WW domain of the human protein Pin 1 (WW) as a model system to probe the impact of PEG on protein conformational stability. Using a combination …


N-Terminal Domains Of Copper Atpases In Plasmodium Falciparum, Dictyostelium Dicsoideum, Human Atp7b And A Chimera Of Atox1 With Metal Binding Domain Four Of Atp7b, Javan Kilango Kisaka Jun 2016

N-Terminal Domains Of Copper Atpases In Plasmodium Falciparum, Dictyostelium Dicsoideum, Human Atp7b And A Chimera Of Atox1 With Metal Binding Domain Four Of Atp7b, Javan Kilango Kisaka

Dissertations

Copper transporting ATPases (Cu-ATPases) are essential for mediating copper uptake, maintaining cellular copper levels and prevention of accumulation of toxic copper. The most studied copper ATPases are the Menkes and Wilson proteins in eukaryotes, CopA and CopB found in bacteria. The precise interaction of the metal binding domains with their copper donor, the association of each metal binding domain within the N-terminal portion of the protein, how they communicate with each other, and the eventual metal ion translocation across the membrane, is little known. The variation in number of the cytosolic metal binding domains may also offer clues on the …


Glutamic Acid Resorcinarene-Based Molecules And Their Application In Developing New Stationary Phases In Ion Chromatography, Tayyebeh Panahi Jun 2016

Glutamic Acid Resorcinarene-Based Molecules And Their Application In Developing New Stationary Phases In Ion Chromatography, Tayyebeh Panahi

Theses and Dissertations

Resorcinarenes can be functionalized at their upper and lower rims. In this work, the upper rim of a resorcinarene was functionalized with glutamic acids and the lower rim was functionalized with either methyl or undecyl alkyl groups. The cavitands were characterized by nuclear magnetic resonance (NMR), mass spectrometry (MS), UV-vis spectroscopy, dynamic light scattering (DLS) and electron microscopy. The binding of resorcinarene with amine guests was studied in DMSO by UV-vis titration. The obtained binding constants (K values) were in the range of 12,000-136000 M-1. The resorcinarenes were shown to form aggregates in a variety of solvents. The aggregates were …


Analyses Of Mrna Cleavage By Rele And The Role Of Trna Methyltransferase Trmd Using Bacterial Ribosome Profiling, Jae Yeon Hwang Jun 2016

Analyses Of Mrna Cleavage By Rele And The Role Of Trna Methyltransferase Trmd Using Bacterial Ribosome Profiling, Jae Yeon Hwang

Theses and Dissertations

Protein synthesis is a fundamental and ultimate process in living cells. Cells possess sophisticated machineries and continuously carry out complex processes. Monitoring protein synthesis in living cells not only inform us about the mechanism of translation but also deepen our insights about all aspects of life. Understanding the structure and mechanism of the ribosome and its associated factors helped us enlarge our knowledge on protein synthesis. Recently, with the dramatic advances of high-throughput sequencing and bioinformatics, a new technique called ribosome profiling emerged. By retrieving mRNA fragments protected by translating ribosomes, ribosome profiling reveals global ribosome occupancy along mRNAs in …


Carbon Nanotubes Affect The Toxicity Of Cuo Nanoparticles To Denitrification In Marine Sediments By Altering Cellular Internalization Of Nanoparticle, Xiong Zheng, Yinglong Su, Yinguang Chen, Rui Wan, Mu Li, Haining Huang, Xu Li Jun 2016

Carbon Nanotubes Affect The Toxicity Of Cuo Nanoparticles To Denitrification In Marine Sediments By Altering Cellular Internalization Of Nanoparticle, Xiong Zheng, Yinglong Su, Yinguang Chen, Rui Wan, Mu Li, Haining Huang, Xu Li

Department of Civil and Environmental Engineering: Faculty Publications

Denitrification is an important pathway for nitrate transformation in marine sediments, and this process has been observed to be negatively affected by engineered nanomaterials. However, previous studies only focused on the potential effect of a certain type of nanomaterial on microbial denitrification. Here we show that the toxicity of CuO nanoparticles (NPs) to denitrification in marine sediments is highly affected by the presence of carbon nanotubes (CNTs). It was found that the removal efficiency of total NOX−-N (NO3−-N and NO2−-N) in the presence of CuO NPs was only 62.3%, but it …


Harmful And Beneficial Role Of Ros, Sergio Di Meo, Tanea Reed, Paola Venditti, Victor M. Victor Jun 2016

Harmful And Beneficial Role Of Ros, Sergio Di Meo, Tanea Reed, Paola Venditti, Victor M. Victor

EKU Faculty and Staff Scholarship

Reactive oxygen species (ROS) are an unavoidable byproduct of oxygen metabolism and their cellular concentrations are determined by the balance between their rates of production and their rates of clearance by various antioxidant compounds and enzymes. For a long time ROS were thought to cause exclusively toxic effects which were associated with various pathologies, including carcinogenesis, neurodegeneration, atherosclerosis, diabetes, and aging. However, to date, it is known that while prolonged exposure to high ROS concentrations may lead to various disorders, low ROS concentrations exert beneficial effects regulating cell signaling cascades.


Mononuclear Iron-(Hydro/Semi)Quinonate Complexes Featuring Neutral And Charged Scorpionates: Synthetic Models Of Intermediates In The Hydroquinone Dioxygenase Mechanism, Amanda E. Baum, Sergey V. Lindeman, Adam T. Fiedler Jun 2016

Mononuclear Iron-(Hydro/Semi)Quinonate Complexes Featuring Neutral And Charged Scorpionates: Synthetic Models Of Intermediates In The Hydroquinone Dioxygenase Mechanism, Amanda E. Baum, Sergey V. Lindeman, Adam T. Fiedler

Chemistry Faculty Research and Publications

Neutral and anionic scorpionate ligands have been employed to generate active-site models of hydroquinone dioxygenases (HQDOs). While the nonheme Fe center in nearly all HQDOs is coordinated to one Asp (or Glu) and two His residues, 1,2-gentisate dioxygenase (GDO) is unique in featuring a three His triad instead. A synthetic GDO model was therefore prepared with the neutral tris(4,5-diphenyl-1-methylimidazol-2-yl)phosphine (Ph2TIP) ligand. The gentisate substrate was mimicked with the bidentate ligand 2-(1-methylbenzimidazol-2-yl)hydroquinonate (BIHQ). X-ray diffraction analysis of the resulting complex, [Fe(Ph2TIP)(BIHQ)]OTf (1a), revealed a distorted square-pyramidal geometry. Structural and electrochemical data collected for 1a were compared to …


Screening The Low Molecular Weight Fraction Of Human Serum Using Atr-Ir Spectroscopy, Franck Bonnier, Matthew J. Baker, Hugh Byrne Jun 2016

Screening The Low Molecular Weight Fraction Of Human Serum Using Atr-Ir Spectroscopy, Franck Bonnier, Matthew J. Baker, Hugh Byrne

Articles

Vibrational spectroscopic techniques can detect small variations in molecular content, linked with disease, showing promise for screening and early diagnosis. Biological fluids, particularly blood serum, are potentially valuable for diagnosis purposes. The so-called Low Molecular Weight Fraction (LMWF) contains the associated peptidome and metabolome and has been identified as potentially the most relevant molecular population for disease-associated biomarker research. Although vibrational spectroscopy can deliver a specific chemical fingerprint of the samples, the High Molecular Weight Fraction (HMWF), composed of the most abundant serum proteins, strongly dominates the response and ultimately makes the detection of minor spectral variations a challenging task. …


Water Quality In Selected Small Drinking Water Systems Of Missouri Rural Communities, Bin Hua, Ruipu Mu, Honglan Shi, Enos Inniss, John Yang Jun 2016

Water Quality In Selected Small Drinking Water Systems Of Missouri Rural Communities, Bin Hua, Ruipu Mu, Honglan Shi, Enos Inniss, John Yang

Chemistry Faculty Research & Creative Works

Small drinking water treatment systems (serving < 10,000 population) in rural communities frequently encounter multiple challenges in water quality and federal regulatory compliance, especially the disinfection byproduct (DBP) regulations, due to source water variations, limited resources, and aging infrastructures. Unlike most studies on the DBP control using synthetic water in laboratory settings, this research aimed to identify the major water quality issues confronting small systems in the state of Missouri (MO), the United States of America (USA). Three small systems were selected based on source water and geographic locations. Water samples were collected quarterly from each major treatment process during the period of May 2012 to March 2013 and analyzed to identify the treatment effectiveness and potential water quality issues in each small system. Results of water quality characterization showed that the major water quality issue in the selected small systems was the low efficiency of dissolved organic carbon (DOC) removal, especially the DOC species that are considered as the DBP precursors. Most collected water samples had a higher trihalomethane formation potential (THMFP) than the United States Environmental Protection Agency (USEPA) maximum contaminant limit (MCL) (80 µg/L). Based on the analysis of the treatment efficiency in each system, several strategies for water quality improvement were recommended, and a few of which have been implemented in the small systems, leading to improved drinking water quality and compliance with the USEPA DBP regulations. This study would provide a valuable aid to small system operators and local water authority in context of water quality improvement and the regulatory compliance.


A New Set Of Potential Energy Surfaces For Hco: Influence Of Renner-Teller Coupling On The Bound And Resonance Vibrational States, Steve Alexandre Ndengué, Richard Dawes, Hua Guo Jun 2016

A New Set Of Potential Energy Surfaces For Hco: Influence Of Renner-Teller Coupling On The Bound And Resonance Vibrational States, Steve Alexandre Ndengué, Richard Dawes, Hua Guo

Chemistry Faculty Research & Creative Works

It is commonly understood that the Renner-Teller effect can strongly influence the spectroscopy of molecules through coupling of electronic states. Here we investigate the vibrational bound states and low-lying resonances of the formyl radical treating the Renner-Teller coupled X2A' and Ã2A" states using the MultiConfiguration Time Dependent Hartree (MCTDH) method. The calculations were performed using the improved relaxation method for the bound states and a recently published extension to compute resonances. A new set of accurate global potential energy surfaces were computed at the explicitly correlated multireference configuration interaction (MRCI-F12) level and yielded remarkably close agreement with experiment in this …


Thermochemical Properties Of Fluorinated Hydrocarbons, Hydroperoxides, And Fluorinated Hydroperoxides; Thermochemistry And Kinetics On Dissociation And Association Reactions Of Oxiranyl Radical, Heng Wang May 2016

Thermochemical Properties Of Fluorinated Hydrocarbons, Hydroperoxides, And Fluorinated Hydroperoxides; Thermochemistry And Kinetics On Dissociation And Association Reactions Of Oxiranyl Radical, Heng Wang

Dissertations

Thermochemical properties on fluorinated hydrocarbons, alcohol, hydroperoxides, and alkyl hydroperoxides are determined. Reaction kinetics and modeling on the three member ring cyclic ether radical, oxiranyl radical, are studied under atmospheric and combustion environments.

Molecular geometries, vibration frequencies, internal rotor potentials, and thermo-chemical properties (ΔfHº298, S°(T) and C°p(T)) for fluorinated-hydrocarbons, thermochemical properties and bond energies, for alkyl and fluoro hydroperoxides and fluoro alcohols are determined with comparison of data from a number of different ab initio, density functional theory (DFT) and composite calculation methods, and basis sets.

Kinetic parameters for unimolecular decomposition and isomerization reactions of the oxiranyl radical are determined …


Studies On Purification And Functionalization Of Carbon Nanotubes And Their Aqueous Phase Behavior, Zheqiong Wu May 2016

Studies On Purification And Functionalization Of Carbon Nanotubes And Their Aqueous Phase Behavior, Zheqiong Wu

Dissertations

Carbon nanotubes (CNTs) are known to have unique mechanical, thermal and electrical properties which make them attractive for a wide range of applications ranging from batteries to sensors. CNTs are rolled up graphene sheets where the single-walled CNTs (SWCNTs) and multi-walled CNTs (MWCNTs) are classified according to the number of concentric rings. In this dissertation, the focus is on several different aspects of MWCNTs. These include purification, functionalization and colloidal behavior.

MWCNTs are insoluble in solvents and therefore some degree of functionalization is required prior to their real-world applications. Oxidation debris is generated during carboxylation which is usually the first …


A Tonb-Dependent Receptor Regulates Antifungal Hsaf Biosynthesis In Lysobacter, Ruping Wang, Huiyong Xu, Liangcheng Du, Shan-Ho Chou, Hongxia Liu, Youzhou Liu, Fengquan Liu, Guoliang Qian May 2016

A Tonb-Dependent Receptor Regulates Antifungal Hsaf Biosynthesis In Lysobacter, Ruping Wang, Huiyong Xu, Liangcheng Du, Shan-Ho Chou, Hongxia Liu, Youzhou Liu, Fengquan Liu, Guoliang Qian

Liangcheng Du Publications

Lysobacter species are Gram-negative bacteria that are emerging as new sources of antibiotics, including HSAF (Heat Stable Antifungal Factor), which was identified from L. enzymogenes with a new mode of action. LesR, a LuxR solo, was recently shown to regulate the HSAF biosynthesis via an unidentified mechanism in L. enzymogenes OH11. Here, we used a comparative proteomic approach to identify the LesR targets and found that LesR influenced the expression of 33 proteins belonging to 10 functional groups, with 9 proteins belonging to the TBDR (TonB-Dependent Receptor) family. The fundamental role of bacterial TBDR in nutrient uptake motivates us to …


Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi May 2016

Oleanolic Acid Inhibits High Salt-Induced Exaggeration Of Warburg-Like Metabolism In Breast Cancer Cells, Suneetha Amara, Mu Zheng, Venkataswarup Tiriveedhi

Chemistry Faculty Research

Cancer cells have a proliferative advantage by utilizing intermediates of aerobic glycolysis (Warburg effect) for their macromolecule synthesis. Although the exact causes of this Warburg effect are unclear, high osmotic stress in solid tumor microenvironment is considered one of the important factors. Oleanolic acid (OA) is known to exert anti-inflammatory and anti-cancer effect. In our current studies, using breast cancer cell lines, we determined the protective role of OA in high salt-mediated osmotic stress-induced cancer growth. Hypertonic (0.16 M NaCl) culture conditions enhanced the cancer cell growth (26 %, p < 0.05) and aerobic glycolysis as marked by increased glucose consumption (34 %, p < 0.05) and lactate production (25 %, p < 0.05) over untreated cells. This effect was associated with increased expression and activity of key rate-limiting enzymes of aerobic glycolysis, namely hexokinase, pyruvate kinase type M2, and lactate dehydrogenase A. Interestingly, this high salt-mediated enhanced expression of aerobic glycolytic enzymes was efficiently reversed by OA along with the decreased cancer cell proliferation. In cancer cells, enhanced aerobic glycolysis is associated with the decreased mitochondrial activity and mitochondrial-associated caspase activity. As expected, high salt further inhibited the mitochondrial related cytochrome oxidase and caspase-3 activity. However, OA efficiently reversed the high salt-mediated inhibition of cytochrome oxidase, caspase activity, and pro-apoptotic Bax expression, thus suggesting that OA induced mitochondrial activity and enhanced apoptosis. Taken together, our data indicate that OA efficiently reverses the enhanced Warburg-like metabolism induced by high salt-mediated osmotic stress along with potential application of OA in anti-cancer therapy.


The Study Of Drug Interactions During Separation Using Gas Chromatography – Mass Spectrometry, Leanne Mocniak May 2016

The Study Of Drug Interactions During Separation Using Gas Chromatography – Mass Spectrometry, Leanne Mocniak

Capstone Projects/Undergraduate Honors Theses

There are numerous existing techniques for forensic toxicological testing, but each one has limitations. Although there have been significant improvements in these techniques over the past 10 years, it still remains very difficult to successfully identify a wide range of drugs from one sample using a single method [12]. This difficulty arises from the major differences in molecular structure, volatility and stability in solution between these drugs. The overall goal of this study is to develop a method using gas chromatography (GC) coupled with triple quadrupole mass spectrometry (GC/MS/MS) to separate and accurately identify 10 different drugs of abuse from …


Multi-Regression Prediction Of Metal Partition Coefficients Under Various Physical/Chemical Conditions Design Of Experiments As, Cr, Cu, Ni And Zn, Eid A. Alkhatib, Danielle Grunzke, Trey Chabot May 2016

Multi-Regression Prediction Of Metal Partition Coefficients Under Various Physical/Chemical Conditions Design Of Experiments As, Cr, Cu, Ni And Zn, Eid A. Alkhatib, Danielle Grunzke, Trey Chabot

Chemistry & Physics Faculty Publications

The behavior of metals in surface water is complex and their partition coefficients can be impacted by many factors. Organic matter (OM) content in sediments, pH and salinity, are factors that may influence speciation and partitioning of metals. The difficulty in describing the impacts and relationships are that these processes are interconnected with no dominant associations among all. In this study, the partitioning of five metals (As, Cr, Cu, Ni and Zn) under different levels of salinity, pH, and OM content were investigated. A series of factorial design experiments are evaluated in which three levels of OM are tested each …


Dendrimer Modified Silica Nanoparticles As Fluorescent Chemosensors For The Detection Of Copper And Cyanide Ions, Alicia Luhrs May 2016

Dendrimer Modified Silica Nanoparticles As Fluorescent Chemosensors For The Detection Of Copper And Cyanide Ions, Alicia Luhrs

Master's Theses

A series of silica nanoparticle-based fluorescent chemosensors were synthesized for the sensitive and selective detection of Cu2+ ions in aqueous solution and subsequent CN- ion detection. Silica nanoparticles (SNP) were modified with branching polyamidoamine (PAMAM) dendrimers, which function as selective turn-off Cu2+ ion chelators and platforms for the attachment of rhodamine isothiocyanate (RITC) or fluorescein isothiocyanate (FITC) fluorescent dyes. In the presence of Cu2+ ions, the emission of the fluorescent dye is quenched by Forster resonance energy transfer (FRET) and is dependent upon dendrimer generation, pH, fluorescent dye, and surface charge. The quenching effectiveness was analyzed …


Inhibitory Effects Of Unique Sulfonamides On Leishmania Tarentolae And Potential Pathway Of Inhibition, Jade M. Katinas May 2016

Inhibitory Effects Of Unique Sulfonamides On Leishmania Tarentolae And Potential Pathway Of Inhibition, Jade M. Katinas

Theses and Dissertations

Leishmaniasis is an endemic disease caused by the protozoan parasite Leishmania. Current treatments for the parasite are limited by cost, availability, and drug resistance as the worldwide occurrence of leishmaniasis continues to be more prevalent. Sulfonamides are a class of compounds with medicinal properties that have been used to treat bacterial and parasitic diseases via various pathways. In this study, newly synthesized, unique structural analogs of sulfonamide compounds were assessed for their impact on Leishmania cell viability and potential pathways for inhibition were evaluated. Leishmania tarentolae (ATCC Strain 30143) axenic promastigote cells were grown in BHI medium and treated with …


Gamma Aapeptides As Host Defense Peptide Mimics, Yaqiong Li May 2016

Gamma Aapeptides As Host Defense Peptide Mimics, Yaqiong Li

USF Tampa Graduate Theses and Dissertations

There has been increasing concern regarding the emergence of multi-drug resistant pathogens. The resistance develops when pathogens, especially bacteria, are frequently exposed to conventional antibiotics, as they are heavily used in both human and livestock. This is due to the high target specificity of conventional antibiotics, which places pathogens in high selective pressures and eventually results in drug resistant by mutations. To address this issue, global actions and cooperation are needed. At the same time, new technologies and strategies need to be developed. Host defense peptides (HDPs) are widely found in the innate immune system. They show both direct antimicrobial …


Environmental Fullerene Chemistry: Elucidating Critical Reaction Pathways And Resulting Products In The Aqueous Phase, Jiewei Wu May 2016

Environmental Fullerene Chemistry: Elucidating Critical Reaction Pathways And Resulting Products In The Aqueous Phase, Jiewei Wu

McKelvey School of Engineering Graduate Student Theses & Dissertations

As the production of fullerenes and fullerene-based materials approaches industrial scale, there are increasing interests/concerns regarding their (potential) environmental impact(s) upon release. To date, a number of critical, aqueous-based fullerene transformation pathways under environmentally relevant conditions remain poorly understood. Comprehensive, fundamental, and quantitative understanding of the potential (major) reaction pathways and resulting products of fullerene materials, particularly in aquatic systems, is now crucial for their accurate fate, transport, life cycle, risk assessment(s), and thus ultimate material sustainability.

Herein, this dissertation is focused on identifying and elucidating aqueous transformation pathways of fullerene materials, focused on C60 as a model fullerene, under …


Cyclotron Production And Biomedical Imaging Applications Of The Pet Isotope Manganese-52, Andrew Lake Wooten May 2016

Cyclotron Production And Biomedical Imaging Applications Of The Pet Isotope Manganese-52, Andrew Lake Wooten

McKelvey School of Engineering Graduate Student Theses & Dissertations

Manganese is an important element for biomedical research because of its roles as an essential micronutrient and as a neurotoxin from chronic elevated exposure, as well as the role of manganese(II) as a paramagnetic core for contrast agents in T1-weighted magnetic resonance imaging (MRI). Using a radiotracer of manganese provides excellent sensitivity for studying these phenomena, but only 52Mn met the criteria for our experiments: (1) a half-life (t1/2=5.6 days) that was long enough to examine timepoints over several days, (2) a half-life that was short enough to emit sufficient counts for a realistic scan time, and (3) emitted radiation …


Synthesis And Evaluation Of Biological Activity Of A Potential Immunomodulatory Zwitterionic Polysaccharide, Vikram Basava May 2016

Synthesis And Evaluation Of Biological Activity Of A Potential Immunomodulatory Zwitterionic Polysaccharide, Vikram Basava

Seton Hall University Dissertations and Theses (ETDs)

The gram-negative anaerobic bacterium Bacteroides fragilis is an integral component of the normal gastrointestinal flora. The bacterium colonizes the intestinal tract of human beings as it has no reservoir other than mammals. An unprecedented proportion of the genomic DNA of B. fragilus is involved in the production of capsular polysaccharides. These capsular polysaccharides are important virulence factors in most extracellular bacterial pathogens. Eight of these polysaccharides have been identified thus far, out of which two were found to be zwitterionic polymers, PSA1 and PSA2. PSA1 was found to stimulate T-cell lineage of the immune system because of the dual charge …


Structural Analysis Of Transient Receptor Potential Vanilloid Type 1 (Trpv1) Channel Protein And Proline Mimics Using Computational Techniques, Kelly A. Raymond May 2016

Structural Analysis Of Transient Receptor Potential Vanilloid Type 1 (Trpv1) Channel Protein And Proline Mimics Using Computational Techniques, Kelly A. Raymond

Seton Hall University Dissertations and Theses (ETDs)

Chapter I

The Transient Receptor Potential (TRP) family of ion channels encompasses more than 30 members, which are expressed in many different tissues and cell types.1 Transient Receptor Potential Vanilloid Type 1 (TRPV1) is part of the TRP family gated by vanilloids, heat and protons.2 Molecular modeling will be used in order obtain structural and functional data on TRPV1 in its membrane bound environment. In particular, the transmembrane and C-terminal domain regions of TRPV1 are of particular interest. The S1-S4 region of the channel is the putative ligand-binding segment, while the C-terminal domain is suggested to respond to …


Indacenodibenzothiophenes: Synthesis, Optoelectronic Properties And Materials Applications Of Molecules With Strong Antiaromatic Character, Jonathan L. Marshall, Kazuyuki Uchida, Conerd K. Frederickson, Christian Schütt, Andrew M. Zeidell, Katelyn P. Goetz, Tristan W. Finn, Karol Jarolimek, Lev N. Zakharov, Chad Risko, Rainer Herges, Oana D. Jurchescu, Michael M. Haley May 2016

Indacenodibenzothiophenes: Synthesis, Optoelectronic Properties And Materials Applications Of Molecules With Strong Antiaromatic Character, Jonathan L. Marshall, Kazuyuki Uchida, Conerd K. Frederickson, Christian Schütt, Andrew M. Zeidell, Katelyn P. Goetz, Tristan W. Finn, Karol Jarolimek, Lev N. Zakharov, Chad Risko, Rainer Herges, Oana D. Jurchescu, Michael M. Haley

Chemistry Faculty Publications

Indeno[1,2-b]fluorenes (IFs), while containing 4n π-electrons, are best described as two aromatic benzene rings fused to a weakly paratropic s-indacene core. In this study, we find that replacement of the outer benzene rings of an IF with benzothiophenes allows the antiaromaticity of the central s-indacene to strongly reassert itself. Herein we report a combined synthetic, computational, structural, and materials study of anti- and syn-indacenodibenzothiophenes (IDBTs). We have developed an efficient and scalable synthesis for preparation of a series of aryl- and ethynyl-substituted IDBTs. NICS-XY scans and ACID calculations reveal an increasingly antiaromatic core from …


2016-01-A3dsrinp-Csc-Sta-Cmb-522-Bps-542, Raymond Pulver, Neal Buxton, Xiaodong Wang, John Lucci, Jean Yves Hervé, Lenore Martin May 2016

2016-01-A3dsrinp-Csc-Sta-Cmb-522-Bps-542, Raymond Pulver, Neal Buxton, Xiaodong Wang, John Lucci, Jean Yves Hervé, Lenore Martin

Bioinformatics Software Design Projects

Cholesterol is carried and transported through bloodstream by lipoproteins. There are two types of lipoproteins: low density lipoprotein, or LDL, and high density lipoprotein, or HDL. LDL cholesterol is considered “bad” cholesterol because it can form plaque and hard deposit leading to arteries clog and make them less flexible. Heart attack or stroke will happen if the hard deposit blocks a narrowed artery. HDL cholesterol helps to remove LDL from the artery back to the liver.

Traditionally, particle counts of LDL and HDL plays an important role to understanding and prediction of heart disease risk. But recently research suggested that …


A Pilot Study Analyzing Solvents In Electronic Cigarette “E-Liquid” Using High Performance Liquid Chromatography, Austin Matranga, Olivia Sellers, Matthew Gartner May 2016

A Pilot Study Analyzing Solvents In Electronic Cigarette “E-Liquid” Using High Performance Liquid Chromatography, Austin Matranga, Olivia Sellers, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

Introduction: Electronic cigarettes, also known as an e-cigarette, are battery-powered devices that use a heating element to convert a liquid (“e-liquid”) into an inhalable aerosol. Their advertised use is as a nicotine delivery system minus the harmful chemicals. Since “e-liquids” and the electronic cigarettes are not regulated by the Food and Drug Administration, it is not well known under what conditions, if any, carcinogenic compounds are produced. There has been little research on the toxicity of electronic cigarettes. The aim of this study was to determine if formaldehyde or acetaldehyde are formed from the e-liquid by the high heat of …


The Foundations Of Network Dynamics In An Rna Recombinase System, Jessica Anne Mellor Yeates May 2016

The Foundations Of Network Dynamics In An Rna Recombinase System, Jessica Anne Mellor Yeates

Dissertations and Theses

How life originated from physical and chemical processes is one of the great questions still unanswered today. Studies towards this effort have transitioned from the notion of a single self-replicating entity to the idea that a network of interacting molecules made this initial biological leap. In order to understand the chemical kinetic and thermodynamic mechanisms that could engender pre-life type networks we present an empirical characterization of a network of RNA recombinase molecules. We begin with 1-, 2-, and 3-molecular ensembles and provide a game theoretic analysis to describe the frequency dependent dynamics of competing and cooperating RNA genotypes. This …


Isothermal Titration Calorimetry Uncovers Substrate Promiscuity Of Bicupin Oxalate Oxidase, Hassan Ali Rana May 2016

Isothermal Titration Calorimetry Uncovers Substrate Promiscuity Of Bicupin Oxalate Oxidase, Hassan Ali Rana

Master of Science in Chemical Sciences Theses

Oxalate oxidase from Ceriporiopsis subvermispora (CsOxOx) is a manganese-dependent enzyme that catalyzes the oxygen-dependent oxidation of oxalate to form two moles of carbon dioxide and one mole of hydrogen peroxide. CsOxOx is the first oxalate oxidase reported to have a two beta barrel architecture (bicupin). The CsOxOx catalyzed oxidation of oxalate reaction can be monitored by coupling the product H2O2 to the horseradish peroxidase-catalyzed oxidation of 2,2'-azinobis-(3- ethylbenzthiazoline-6-sulphonic acid) and by membrane inlet mass spectrometry. Coupled enzyme assays often confound data interpretation. Isothermal titration calorimetry (ITC) measures heat changes that occur during a reaction. Therefore, ITC can …


Applications Of Nanoporous Gold Monoliths As Substrates For The Capture And Release Of Lectins And Glycoproteins, Allan Jonson Alla May 2016

Applications Of Nanoporous Gold Monoliths As Substrates For The Capture And Release Of Lectins And Glycoproteins, Allan Jonson Alla

Dissertations

Nanoporous gold (np-Au) monoliths are a free-standing nanostructured material with typical pore dimensions in the tens of nanometers range. The microstructure of np-Au resembles those of macroporous monolithic materials being used in chromatographic separations. The surfaces of np-Au monoliths were modified via flow methods with different ligands to develop affinity substrates for separations. A carbohydrate-modified np-Au monolith was prepared by immobilizing thiolated saccharides and further used to separate lectins. The np-Au monolith surface was also functionalized with self-assembled monolayers (SAMs) of α-lipoic acid (LA) followed by activation of carboxyl terminal groups to create amine reactive esters. Concanavalin A (Con A) …