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Case Studies Of Potential Reference Materials In Cultural Heritage Science, Heidi Kastenholz Jan 2019

Case Studies Of Potential Reference Materials In Cultural Heritage Science, Heidi Kastenholz

Undergraduate Honors Thesis Collection

The study of cultural heritage objects requires reference materials for comparison in order to determine the identity of chemical compounds in historically/culturally significant artifacts. The reference materials available today can be inaccurately labeled, can contain inauthentic compounds, or can simply be formed differently than what the labeled material should be. Utilizing the laboratory at the Indianapolis Museum of Art at Newfields, three case studies were conducted over three different potential reference materials in order to properly identify each of the three materials being focused on here. Based on the analysis, the labels for these materials often do not match ...


Near-Infrared Fluorescent Probes For Sensitive Determination Of Lysosomal & Mitochondrial Ph In Live Cells, Wafa Mazi Jan 2019

Near-Infrared Fluorescent Probes For Sensitive Determination Of Lysosomal & Mitochondrial Ph In Live Cells, Wafa Mazi

Dissertations, Master's Theses and Master's Reports

Varied intracellular pH levels are critical for various physiological processes such as enzymatic activity, cell proliferation and apoptosis, ion transport, and muscle contraction. Cellular compartments, like lysosomes, must retain an acidic environment (pH ~ 4.5) to activate hydrolytic enzymes necessary for the breakdown of large biomolecules. Another cellular organelle, the mitochondria, provides the cell with energy and must retain an alkalis environment (pH ~ 8.0) for proper function. Substantial lysosomal and mitochondrial pH deviation is associated with cellular dysfunction and disease. Therefore, the precise detection of lysosomal and mitochondrial pH is essential to provide a better understanding of cellular physiological ...


Use Of Liquid Microjunction Surface Sampling Probe Mass Spectrometry For The Development Of A Rapid Untargeted Screening Method For Veterinary Drug Residues In Animal Tissues, Laura Burns Jan 2019

Use Of Liquid Microjunction Surface Sampling Probe Mass Spectrometry For The Development Of A Rapid Untargeted Screening Method For Veterinary Drug Residues In Animal Tissues, Laura Burns

Graduate Theses and Dissertations

Veterinary diagnostic laboratories provide a variety of services to livestock producers and companion animal owners. One of these services is a general untargeted screening of animal tissues for veterinary drug residues. Results from this assay are used to determine animal cause of death or emergency treatment options in the case of toxic exposure. The established analytical methods used for this type of screening require a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) extraction and cleanup along with a liquid or gas chromatography mass spectrometry (LC/MS or GC/MS) analysis. Although these current methods are sensitive they require several ...


Crystallographic Studies Of Terpene Synthases: Important Enzymes That Synthesize Antibiotic And Biofuel Precursors, Aromatic Essential Oil Compounds And Anti-Cancer Derivatives, Patrick Neil Blank Jan 2019

Crystallographic Studies Of Terpene Synthases: Important Enzymes That Synthesize Antibiotic And Biofuel Precursors, Aromatic Essential Oil Compounds And Anti-Cancer Derivatives, Patrick Neil Blank

Publicly Accessible Penn Dissertations

Terpene synthases synthesize highly complex natural products from linear isoprenoid starting molecules. These products often have a wide variety of applications spanning multiple industries. In order to unravel the production pathway of these important compounds, macromolecular crystallography via structural biology techniques can yield enzyme crystal structures. These crystal structures provide snapshots of biocatalysis, often providing clues to support a proposed chemical mechanism when combined with computational modeling. Through studying crystal structures of geranylgeranylglyceryl phosphate synthase, epi-Isozizaene synthase, sesquisabinene synthase, and cucumene synthase, this work aims to further the mechanistic understanding of the respective natural products that have usefulness in the ...


Development Of Thioamides As Protein Probes, Daniel Miklos Szantai-Kis Jan 2019

Development Of Thioamides As Protein Probes, Daniel Miklos Szantai-Kis

Publicly Accessible Penn Dissertations

Thioamides have been used for various applications with small molecules and peptides, including as protease sensors, fluorescence quenching probes, folding probes, and handles for site-specific chemical modification. However, their use in proteins has been limited due to cumbersome incorporation through semi-synthesis, as well as their unknown effects on protein structure. In this work, I address these issues from multiple perspectives. I present improvements for the synthesis of thioamide-containing peptides, which are needed for semi-synthesis. I also investigate the effects that thioamide substitutions have on tertiary structure in a model protein and show that based on thermal denaturation experiments, the position ...


Photoassisted Synthesis Of Complex Polyheterocycles Via Esipt-Driven Dearomative Intramolecular Cycloadditions, Dmitry Kuznetsov Jan 2019

Photoassisted Synthesis Of Complex Polyheterocycles Via Esipt-Driven Dearomative Intramolecular Cycloadditions, Dmitry Kuznetsov

Electronic Theses and Dissertations

This research is focused on the development of novel photoassisted synthetic methodologies that provide straightforward access to complex and diverse libraries of polyheterocycles from modularly assembled precursors. All methods are based on the dearomative cycloadditions between two components: (i) o-azaxylylenes, generated by the excited-state intramolecular proton transfer, and (ii) tethered arene groups.

We have demonstrated the synthetic utility of four new photoinduced processes that yield complex products amenable for post-photochemical modifications:

  • [4+4] Cycloaddition of o-azaxylylenes to 1,3,4-oxadiazoles with subsequent dinitrogen extrusion. This reaction furnishes compounds outfitted with epoxide fragments, which undergo ring-openings with various nucleophiles; furthermore ...


Combination Nanovaccines Against Respiratory Pathogens, Sean Kelly Jan 2019

Combination Nanovaccines Against Respiratory Pathogens, Sean Kelly

Graduate Theses and Dissertations

Evidence of mass pandemic plagues dates back to the earliest recorded history, with the Book of Exodus describing plagues inflicted upon Egypt that devastated citizens and livestock. Since then, countless plagues have been recorded, including the Plague of Athens (430-416 BCE), Justinian’s plague (541-542 AD), and the Black Death (1346-1352 AD), which are responsible for the deaths of hundreds of millions of people throughout history.

Among the deadliest pathogens are Yersinia pestis, the causative agent of the plague, and Bacillus anthracis, the causative agent of anthrax. Y. pestis is responsible for Justinian’s plague and the Black Death and ...


Isolation And Identification Of Hsc70 Conjugates In Raw264.7 Murine Macrophage-Like Cells, Michael Arland Parsons Jan 2019

Isolation And Identification Of Hsc70 Conjugates In Raw264.7 Murine Macrophage-Like Cells, Michael Arland Parsons

Theses, Dissertations and Capstones

IL12R- β2 is a Type I cytokine receptor and contains the WXXW (WSNWS) sequence that often predicates the post-translational addition of mannose to a tryptophan residue via a carbon-carbon bond. This study will stimulate expression of IL12R- β2 in RAW 264.7 Macrophage-Like Cells by shutting down the extracellular signal kinase (ERK) pathway and introducing inflammatory agents lipopolysaccharide and CpG DNA in order to collect a concentrated sample of IL12R- β2. These samples will be analyzed for the presence of C-mannosyltryptophan residue


Metabolomics In Veterinary Medicine: Untargeted Metabolomic Analysis Of Porcine Reproductive And Respiratory Syndrome Virus And Targeted Metabolomic Analysis Of Salmonella Enteritidis, Aislinn A. Ophoff Jan 2019

Metabolomics In Veterinary Medicine: Untargeted Metabolomic Analysis Of Porcine Reproductive And Respiratory Syndrome Virus And Targeted Metabolomic Analysis Of Salmonella Enteritidis, Aislinn A. Ophoff

Graduate Theses and Dissertations

Metabolomics is an emerging diagnostic method within veterinary medicine used to examine small molecule metabolites within bodily samples. Neither targeted nor untargeted metabolomic methods have been widely used in veterinary medicine, especially in the areas of PRRSV vaccination biomarkers or targeted metabolite kits in Salmonella Enteritidis pathogenicity.

In order to evaluate the utility of untargeted metabolomics, the use of readily collectable serum and oral fluid samples were compared to characterize the metabolic changes in response to PRRSV vaccination. The samples were extracted using an RPLC method on a Thermo Fisher Dionex Ultimate 3000 UHPLC and Q Exactive Focus Quadrupole-Orbitrap mass ...


Urinalysis Screening Of Drugs In Adulterated Samples Via Direct Analysis In Real Time -- High Resolution/ Mass Spectrometry (Dart-Hr/Ms), Bianca E. Olivieri Jan 2019

Urinalysis Screening Of Drugs In Adulterated Samples Via Direct Analysis In Real Time -- High Resolution/ Mass Spectrometry (Dart-Hr/Ms), Bianca E. Olivieri

Honors Undergraduate Theses

Current screening methods for drug analysis with urine samples includes examination of the sample with an immunoassay. These methods are used to determine the concentration of drug metabolites contained within the sample prior to further confirmatory testing. Drug testing plays a crucial role in maintaining safe workplace environments and safety of individuals. However, a positive result can lead to heavy consequences for the employee including suspension or removal from the workplace. Therefore, a majority of individuals add commonly known products into the sample to evade detection by developing a false negative result. Although specimen integrity examinations are performed to identify ...


Biogeochemical Response To Vegetation And Hydrologic Change In An Alaskan Boreal Fen Ecosystem, Danielle L. Rupp Jan 2019

Biogeochemical Response To Vegetation And Hydrologic Change In An Alaskan Boreal Fen Ecosystem, Danielle L. Rupp

Dissertations, Master's Theses and Master's Reports

Boreal peatlands store approximately one third of the earth’s terrestrial carbon, locked away in currently waterlogged and frozen conditions. Peatlands of boreal and arctic ecosystems are affected increasingly by shifting hydrology caused by climate change. The consequences of these relatively rapid ecosystem changes on carbon cycling between the landscape and the atmosphere could provide an amplifying feedback to climate warming. Alternatively, the advancement of terrestrial vegetation into once waterlogged soils could uptake carbon as a sink. Previous work suggests that fens will become an increasingly dominant landscape feature in the boreal. However, studies investigating fens, their response to hydrologic ...


Effect Of Mineral Ions On The Functional Properties Of Starch Films, Aliza Sigdel Jan 2019

Effect Of Mineral Ions On The Functional Properties Of Starch Films, Aliza Sigdel

Electronic Theses and Dissertations

Essential minerals are indispensable inorganic micronutrients that modulate vital physiological functions at the molecular level. Their deficiency, though required in small amounts, impairs health significantly. Their supplementation through diet is prudent and carbohydrates standout as favorable choice. Carbohydrates, starches and polysaccharides, exhibit unique chemical structures and functionalities, and interact with mineral ions in several ways. The aim of this research is to investigate the effect of mineral ions on the physicochemical properties, tensile strength and in vitro starch digestion of starch-films. Corn starch and potato starch along with Fe2+, Mn2+, Cu2+ and Zn2+ ions have been chosen as model starch ...


Application Of Analytical Techniques In Food Product Development, Sonali R. Pandey Jan 2019

Application Of Analytical Techniques In Food Product Development, Sonali R. Pandey

Electronic Theses and Dissertations

Products are analyzed in major sectors of food industry to meet regulatory standards, food safety, quality control, and research and development. Analytical and extraction techniques have been applied for simultaneous investigation of multiple product characteristics. Food analysis faces critical challenges due to the complex composition of food, leading to matrix effects that result in loss of accuracy and reliability. The analytical techniques require an efficient sample preparation to avoid or minimize matrix effects. Solid-phase extraction has been widely used to address this issue. In this dissertation, the aim is to apply analytical techniques in food product development. To accomplish this ...


Split Probe Detection Of The Influenza A Virus For Improved Diagnostics In A Point Of Care System, Tamar Yishay Jan 2019

Split Probe Detection Of The Influenza A Virus For Improved Diagnostics In A Point Of Care System, Tamar Yishay

Honors Undergraduate Theses

A group of Influenza viruses, RNA containing viruses of the Orthomyxoviridae family, consists of Influenza virus types A-D and has been known to cause the Flu, a respiratory illness associated with numerous detrimental symptoms that can lead to death. Influenza A virus (IAV) is constantly changing and is capable of causing pandemics. Currently used diagnostic methods include virus culturing, immunoassays including rapid influenza detection tests (RIDTs), and molecular assays including those based on RT-PCR. Most of the methods can be only performed in the certified diagnostic laboratories equipped with sophisticated instrumentation and/or special biosafety facilities. The results using these ...


Investigation Of Amyloid Β Oligomer Dissociation Mechanisms By Single Molecule Fluorescence Techniques, Hope Cook Abdalla Jan 2019

Investigation Of Amyloid Β Oligomer Dissociation Mechanisms By Single Molecule Fluorescence Techniques, Hope Cook Abdalla

Theses and Dissertations--Chemistry

Alzheimer’s disease (AD) is currently considered the most prevalent neurodegenerative disease and places a large financial burden on society as healthcare resources are limited and the disease does not have a cure. Alzheimer’s disease is characterized by the presence of amyloid beta (Aβ) plaques and neurofibrillary tangles; however current literature suggests Aβ oligomers are the main aggregating species leading to AD symptoms. Therefore, the underlying cause of Alzheimer’s, accumulation of amyloid beta, is currently being studied in hopes of developing treatment options. Our research aims at determining the mechanism and kinetics of Aβ oligomer dissociation into non-toxic ...


Electrochemical Detection Of Fentanyl Using Screen-Printed Carbon Electrodes With Confirmatory Analysis Of Fentanyl And Its Analogs In Oral Fluid Using Liquid Chromatography-Tandem Mass Spectrometry, Colby E. Ott Jan 2019

Electrochemical Detection Of Fentanyl Using Screen-Printed Carbon Electrodes With Confirmatory Analysis Of Fentanyl And Its Analogs In Oral Fluid Using Liquid Chromatography-Tandem Mass Spectrometry, Colby E. Ott

Graduate Theses, Dissertations, and Problem Reports

Utilizing screen-printed carbon electrodes (SPCEs), a fast, simple, and sensitive approach toward the detection, identification, and quasi-quantitation of fentanyl was achieved both in an electrochemical cell and as a drop on the electrode surface. Electro-oxidation of fentanyl at the electrode was demonstrated using adsorptive stripping square-wave voltammetry between -0.5 V and +1.6 V with 100 mM Tris-HCl buffer at pH 8.5 as supporting electrolyte. Parameter optimization was conducted during method development to include supporting electrolyte and pH, electrochemical technique, pre-treatment and equilibration time, and various surface modifications. The simplest method utilizing an unmodified SPCE was determined to ...


Inhibition Of Hsv-1 Binding By Egcg-Stearate, Valerie Paschalis Jan 2019

Inhibition Of Hsv-1 Binding By Egcg-Stearate, Valerie Paschalis

Theses, Dissertations and Culminating Projects

Herpes simplex virus type 1 (HSV-1) is the causative agent of oral herpes, and is able to establish lifelong latent infection along with painful, recurring symptoms. Epigallocatechin-3- gallate (EGCG) is the most abundant polyphenol derived from green tea (Camellia sinensis), whose anti-inflammatory, antioxidant, anti-cancer, and antiviral properties have been widely studied. Although EGCG is not chemically stable and has poor hydrophobicity, lipophilic derivatives of EGCG have shown increased stability as well as increased antiviral efficacy against HSV. Previous studies have demonstrated that EGCG stearate (EGCG-S), a derivative of EGCG esterified at the 4’ position with stearic acid, is able to ...


Kcnq1/Kcne1 Interaction In The Cardiac Iks Channel And Its Physiological Consequences, Jiajing Xu Dec 2018

Kcnq1/Kcne1 Interaction In The Cardiac Iks Channel And Its Physiological Consequences, Jiajing Xu

Engineering and Applied Science Theses & Dissertations

Dynamic conformational changes of ion channel proteins during activation gating determine their function as carriers of current. The relationship between these molecular movements and channel function over the physiological timescale of the action potential (AP) has not been fully established due to limitations of existing techniques. We constructed a library of possible cardiac IKs protein conformations and applied a combination of protein segmentation and energy linearization to study this relationship computationally. Simulations reproduced the effects of the beta-subunit (KCNE1) on the alpha-subunit (KCNQ1) dynamics and function, observed in experiments. Mechanistically, KCNE1 increased the probability of “visiting” conducting pore conformations on ...


Assessing Biofiltration Without Ozonation For Removal Of Trihalomethane Precursors In Drinking Water At The Beaver Water District Drinking Water Treatment Plant, Sana Ajaz Dec 2018

Assessing Biofiltration Without Ozonation For Removal Of Trihalomethane Precursors In Drinking Water At The Beaver Water District Drinking Water Treatment Plant, Sana Ajaz

Theses and Dissertations

Biofiltration without pre-ozonation has the capability to remove natural organic matter (NOM) fractions that serve as precursors of disinfection byproducts (DBPs), which include the four regulated trihalomethanes (THMs) and dichloroacetonitrile (DCAN). Rapid small-scale column tests (RSSCTs) and Pilot Plant filters operated at empty-bed contact times (EBCTs) of 4, 8, and 16 minutes were used to evaluate the performance of nutrient-amended (free ammonia and phosphorus) biofiltration for THM and DCAN precursor removal, as measured using formation potential (FP) tests. NOM surrogates – which include dissolved organic carbon (DOC), specific ultraviolet absorbance (SUVA254) and fluorescence-PARAFAC components – were measured weekly throughout the 30-week study ...


Synthesis Of Dicamba Glucosides For The Study Of Environmental Dicamba Drift Effects On Soybeans, Holly Wallace Dec 2018

Synthesis Of Dicamba Glucosides For The Study Of Environmental Dicamba Drift Effects On Soybeans, Holly Wallace

Theses and Dissertations

The most popular herbicide used for weed control has been glyphosate for many years in the Midwestern United States. Plants have begun to develop a resistance to glyphosate due to over use of the herbicide. This herbicide resistance has pushed farmers to turn to alternative herbicides such as dicamba and 2,4-D. Recently agrochemical companies have developed genetically modified crops that are resistant to herbicides such as dicamba. These modified crops allow farmers to spray their fields with dicamba without fear of crop damage. Farmers of non-genetically modified crops, however, suffer damage and loss of yield from herbicide drift effects ...


Illuminating Biology With Membrane Penetrating Sulfonate Delivery Scaffolds And Near-Infrared Azasiline Fluorophores, Adam Choi Sep 2018

Illuminating Biology With Membrane Penetrating Sulfonate Delivery Scaffolds And Near-Infrared Azasiline Fluorophores, Adam Choi

GSBS Dissertations and Theses

Near-infrared (NIR) light, with wavelengths of 650 to 900 nanometers, effectively penetrates tissues. The high signal to noise ratio and low phototoxicity of NIR light makes this wavelength range ideal for deep tissue imaging. However, current NIR fluorophores are generally large hydrophobic molecules that are prone to aggregation. Sulfonation can enhance aqueous solubility, but their anionic nature prevents membrane diffusion, and thus, restricts the applications of sulfonated molecules to in vitro or fixed cells.

The repertoire of commercially available sulfonated NIR probes is mostly limited cyanines, which have low photostability. Moreover, larger cyanines require multiple sulfonates to maintain aqueous solubility ...


Fluorescent Visualization Of Cellular Proton Fluxes, Lejie Zhang Sep 2018

Fluorescent Visualization Of Cellular Proton Fluxes, Lejie Zhang

GSBS Dissertations and Theses

Proton fluxes through plasma membranes are essential for regulating intracellular and extracellular pH and mediating co-transport of metabolites and ions. Although conventional electrical measurements are highly sensitive and precise for proton current detection, they provide limited specificity and spatial information. My thesis focuses on developing optical approaches to visualize proton fluxes from ion channels and transporters.

It has been demonstrated that channel-mediated acid extrusion causes proton depletion at the inner surface of the plasma membrane. Yet, proton dynamics at the extracellular microenvironment are still unclear. In Chapter II, we developed an optical approach to directly measure pH change in this ...


Plant Stimuli-Responsive Biodegradable Polymers For The Use In Timed Release Fertilizer Coatings, Spencer Heuchan Aug 2018

Plant Stimuli-Responsive Biodegradable Polymers For The Use In Timed Release Fertilizer Coatings, Spencer Heuchan

Electronic Thesis and Dissertation Repository

The use of nitrogen-based fertilizers continues to accelerate with human population growth and increases in global food requirements. Enhanced efficiency fertilizers (EEFs) have been developed to improve the synchronization between nutrient supply and crop nutrient demand. However, many of the current controlled release fertilizers are coated with non-degradable polymers that contribute to accumulation of microplastics within ecosystems. This thesis describes research towards the development of a new class of fertilizer coatings using a self-immolative polymer known as poly (ethyl glyoxylate) (PEtG). PEtG itself does not have suitable properties to produce a viable coating but once blended with another degradable polyester ...


Building On Nature: Spectroscopic Studies Of Photosynthesis-Inspired Pigments, Fused Light Harvesting Proteins, And Bacterial Reaction Center Mutants, Kaitlyn Faries Aug 2018

Building On Nature: Spectroscopic Studies Of Photosynthesis-Inspired Pigments, Fused Light Harvesting Proteins, And Bacterial Reaction Center Mutants, Kaitlyn Faries

Arts & Sciences Electronic Theses and Dissertations

Photosynthesis is the dominant form of solar energy conversion on the planet, making it critical to understand the fundamentals of the process in order to effectively mimic and improve upon it for human energy needs. The initial stages of photosynthesis include light harvesting and chemical conversion of that harvested energy via electron transport, with both of these stages relying on pigments (or chromophores) such as chlorophyll and specific protein architectures for the processes. In this work, the fundamental underpinnings of photosynthetic light harvesting and electron transport are explored via spectroscopy of various photosynthetic systems with altered natural pigments and proteins ...


Structure And Thermodynamics Of Polyglutamine Peptides And Amyloid Fibrils Via Metadynamics And Molecular Dynamics Simulations, Riley Workman Aug 2018

Structure And Thermodynamics Of Polyglutamine Peptides And Amyloid Fibrils Via Metadynamics And Molecular Dynamics Simulations, Riley Workman

Electronic Theses and Dissertations

Aggregation of polyglutamine (polyQ)-rich polypeptides in neurons is a marker for nine neurodegenerative diseases. The molecular process responsible for the formation of polyQ fibrils is not well understood and represents a growing area of study. To enable development of treatments that could interfere with aggregation of polyQ peptides, it is crucial to understand the molecular mechanisms by which polyQ peptides aggregate into fibrils. Many experimental techniques have been employed to probe polyQ aggregation, however, observations from these studies have not lead to a unified understanding of the properties of these systems, instead yielding competing, fragmented theories of polyQ aggregation ...


Synthetic Approaches Towards Novel Isoform Selective Pi3k Inhibitors And Their Biological Activities Against Prostate Cancer Cells, Idris Wazeerud-Din Aug 2018

Synthetic Approaches Towards Novel Isoform Selective Pi3k Inhibitors And Their Biological Activities Against Prostate Cancer Cells, Idris Wazeerud-Din

Electronic Theses & Dissertations Collection for Atlanta University & Clark Atlanta University

The development of novel imidazopyridines, which includes both tetrahydroimidazo[1,5-a]pyridine (rIMP) and imidazo[1,5-a]pyridine (IMP) was investigated using conventional and microwave induced procedures that afforded compounds at high yield of 88-96%. rIMP was synthesized using a two-step procedure that involved the microwave synthesis of IMP, then the reduction of the pyridine moiety of the fused imidazopyridine rings using 10% Pd/C and hydrazine monohydrate. The microwave synthesis of imidazopyridines involved the one pot reaction of 2-benzoylpyridine, substituted benzaldehyde and ammonium formate in acetic acid under open vessel microwave conditions, which resulted in products within 40 minutes ...


Studies In Molecular Recognition: Non-Proteogenic Amino Acids For Antibiotic Studies And Chemosensors For Recognition And Reporting Of Metal-Ions, Sarah Anne Oehm Aug 2018

Studies In Molecular Recognition: Non-Proteogenic Amino Acids For Antibiotic Studies And Chemosensors For Recognition And Reporting Of Metal-Ions, Sarah Anne Oehm

Theses and Dissertations

The field of molecular recognition focuses on the selective and reversible binding of small guest molecules to larger host molecules. This dissertation describes synthesis of small molecules as binding guests for enzymatic substrates as well as molecules as host chemosensors to detect and identify metal ions. Two approaches to new antibiotic drugs have been explored, and an array of sensors for the quantitation of aqueous metals is being commercialized.

As strains of deadly bacteria emerge with evolved resistance to known antibiotics, new drugs are needed with novel mechanisms of action. Natural product antibiotics containing enduracididine, a non-canonical amino acid derived ...


Fluorescently Labeled Sirnas And Their Theranostic Applications In Cancer Gene Therapy, Stephen David Kozuch Aug 2018

Fluorescently Labeled Sirnas And Their Theranostic Applications In Cancer Gene Therapy, Stephen David Kozuch

Seton Hall University Dissertations and Theses (ETDs)

Gene therapy has emerged as a promising precision nano-medicine strategy in the treatment of numerous diseases including cancer. At the forefront of its utility are the applications of short-interfering RNA (siRNA), that silence oncogenic mRNA expression leading to cancer cell death through the RNA interference (RNAi) pathway. Despite the therapeutic potential, siRNAs are limited by poor pharmacological properties, which has hindered their translation into the clinic. Recent studies, however, have highlighted the applications of modified siRNAs, including the use of fluorescent probes and siRNA nanostructures in cancer detection and treatment. The siRNAs reported in this thesis are designed to target ...


Conformationally-Controlled Late-Stage Modifications For Sar Studies Of The C-3-Glcp Moiety Of Ipomoeassin F, Lucas Whisenhunt Aug 2018

Conformationally-Controlled Late-Stage Modifications For Sar Studies Of The C-3-Glcp Moiety Of Ipomoeassin F, Lucas Whisenhunt

Theses and Dissertations

The resin glycoside, ipomoeassin F has been shown to be extremely potent against multiple cancer lines (IC50 = 4.2-36 nM). However, the mechanism of action of this potent and complex natural product is still not fully understood. The α,β-unsaturated esters of the glucosyl moiety have been shown to be vital for the overall cytotoxicity of ipomoeassin F. Nevertheless, the importance of the tigloyl ester of the glucosyl moiety is still largely unknown. This work aimed to study the pharmacophore importance of the tigloyl ester by creating, an efficient, scalable, and flexible synthesis route for various analogs. The 18-linear step ...


Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor Aug 2018

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics ...