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Stress Granules Modulate Syk To Cause Microglial Cell Dysfunction In Alzheimer's Disease, Soumira Ghosh, Robert Geahlen Oct 2015

Stress Granules Modulate Syk To Cause Microglial Cell Dysfunction In Alzheimer's Disease, Soumira Ghosh, Robert Geahlen

Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Microglial cells in the brains of Alzheimer's patients are known to be recruited to amyloid-beta (Aβ) plaques where they exhibit an activated phenotype, but are defective for plaque removal by phagocytosis. In this study, we show that microglia stressed by exposure to sodium arsenite or Aβ(1–42) peptides or fibrils form ex- tensive stress granules (SGs) to which the tyrosine kinase, SYK, is recruited. SYK enhances the formation of SGs, is active within the resulting SGs and stimulates the production of reactive oxygen and nitrogen species that are toxic to neuronal cells. This sequestration of SYK inhibits the ability of microglial …


Analysis Of The Fabrication Conditions In Organic Field-Effect Transistors, Rachel M. Rahn, Yan Zhao, Jianguo Mei Aug 2015

Analysis Of The Fabrication Conditions In Organic Field-Effect Transistors, Rachel M. Rahn, Yan Zhao, Jianguo Mei

The Summer Undergraduate Research Fellowship (SURF) Symposium

Polymer-based organic field-effect transistors have raised substantial awareness because they enable low-cost, solution processing techniques, and have the potential to be implemented in flexible, disposable organic electronic devices. The performance of these devices is highly dependent on the processing conditions, as well as the intrinsic properties of the polymer. Processing conditions play an important role in semiconductor film formation and device performance. These factors may provide an important link between structure and performance. In this study, an empirical analysis tool, Process Scout, was applied to assess processing factors such as polymer concentration and silicon modification. This sanctioned the creation of …


Studies Of Optical And Electronic Properties Of Nanoparticles For Solar Energy Conversion, Caitlin Kruse, Libai Huang Aug 2015

Studies Of Optical And Electronic Properties Of Nanoparticles For Solar Energy Conversion, Caitlin Kruse, Libai Huang

The Summer Undergraduate Research Fellowship (SURF) Symposium

The higher energy needs for today's technological society requires sustainable and renewable energy source, such as solar energy. This study focuses on using semiconducting quantum dots and fluorescent dyes as light absorbers for solar energy conversion devices such as solar cells. Quantum dots are small nanocrystals (usually 2-10 nm in diameter) with tunable absorbing properties. The smaller the dot, the shorter the wavelength being absorbed. Quantum dots are extremely efficient light absorbers and emitters. Fluorescent dyes have a high quantum yield. In order to examine the energy conversion, cadmium selenide (CdSe) quantum dots and Rhodamine 6G (R6G) dye were spin …


Development Of A Scalable Synthesis Of Hp-Β-Cd Pluronic Polyrotaxanes, Joseph L. Skulsky, Elizabeth A. Slepko, Bradley P. Loren, David H. Thompson Aug 2015

Development Of A Scalable Synthesis Of Hp-Β-Cd Pluronic Polyrotaxanes, Joseph L. Skulsky, Elizabeth A. Slepko, Bradley P. Loren, David H. Thompson

The Summer Undergraduate Research Fellowship (SURF) Symposium

Polyrotaxanes are polymers that have macrocycles threaded onto them, analogous to beads threaded onto a string. These materials are used for a variety of different biomedical applications.1-3 The Thompson group has been developing 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) polyrotaxanes as therapeutics for the treatment of Niemann-Pick Type C (NPC) disease. NPC is a debilitating genetic disorder where cholesterol accumulates in the lysosomes of cells.4 Developing a scalable process is crucial for the advancement of these materials as NPC therapeutics. The goal of this project is to optimize the only protocol for the synthesis of HP-β-CD/Pluronic polyrotaxanes in order to develop a …


Bio-Inspired Composite Hydrogels For Osteochondral Regenerative Engineering, Grant N. Gellert, Liangju Kuang, Chunhui Jiang, Nur P. Damayanti, Joseph Irudayaraj, Meng Deng Aug 2015

Bio-Inspired Composite Hydrogels For Osteochondral Regenerative Engineering, Grant N. Gellert, Liangju Kuang, Chunhui Jiang, Nur P. Damayanti, Joseph Irudayaraj, Meng Deng

The Summer Undergraduate Research Fellowship (SURF) Symposium

Treatment of osteochondral defects encompassing injury or degeneration to both the articular cartilage as well as the underlying subchondral bone presents a significant medical challenge. Current treatment options including autografts and allografts suffer from limited availability and risk of immunogenicity, respectively. The long term goal of this work is to develop an integrated scaffold system for treatment of osteochondral defects via in situ regeneration of bone, cartilage and the bone-cartilage interface. Hydrogels composed of polymer networks swollen in water provide an attractive biomaterial platform for regeneration of cartilage. In the present study, we have developed a novel composite hydrogel consisting …


Synthesis, Characterization, And Thermoelectric Properties Of Radical Siloxanes, Arnold J. Eng, Bryan Boudouris, Edward P. Tomlinson, Martha Emily Hay Aug 2015

Synthesis, Characterization, And Thermoelectric Properties Of Radical Siloxanes, Arnold J. Eng, Bryan Boudouris, Edward P. Tomlinson, Martha Emily Hay

The Summer Undergraduate Research Fellowship (SURF) Symposium

More than half of the annual energy consumption in the United States is lost as waste heat. Polymer-based thermoelectric devices have the potential to utilize this waste heat both sustainably and cost-effectively. Although conjugated polymers currently dominate research in organic thermoelectrics, the potential of using polymers with radical pendant groups have yet to be realized. These polymers have been found to be as conductive as pristine (i.e., not doped) poly(3-hexylthiophene) (P3HT), a commonly-used charge-transporting conjugated polymer. This could yield promising avenues for thermoelectric material design as radical polymers are more synthetically tunable and are hypothesized to have a high Seebeck …


Deconstructing Cation-Pi Interactions: Understanding The Binding Energies Involved With Metal And Aromatic Amino Acid Residues, Jen E. Werner, Lyudmila V. Slipchenko, Yen Bui Aug 2015

Deconstructing Cation-Pi Interactions: Understanding The Binding Energies Involved With Metal And Aromatic Amino Acid Residues, Jen E. Werner, Lyudmila V. Slipchenko, Yen Bui

The Summer Undergraduate Research Fellowship (SURF) Symposium

The Effective Fragment Potential (EFP) method is a computationally efficient technique for describing non-covalent interactions, such as hydrogen bonding and van der Waals forces. Cation-pi interactions are a type of non-covalent interactions and are thought to be important in biological processes, such as permittivity of ion channels. The goal of our work is to establish that the EFP method reliably describes the strength, directionality, and composition of cation-pi interactions. Optimal geometries were found for a series of biologically relevant cations (K+, Li+, Na+, Ca2+, and Mg2+) and aryl moieties appearing …


Mass Spectrometric Characterization Of Peptide Radical Ions And Implication For Radical Chemistry, Lei Tan Apr 2015

Mass Spectrometric Characterization Of Peptide Radical Ions And Implication For Radical Chemistry, Lei Tan

Open Access Dissertations

Gas-phase radical ion chemistry has attracted increasing research interest from the mass spectrometry (MS) society because it provides new capabilities in bio-analysis which often complements traditional MS methods developed from even-electron ions. Fundamental studies of biomolecule related radical species are essential to broadening the scope of radical chemistry and pushing the frontiers of its analytical applications. This dissertation mainly discusses the gas-phase chemistry of peptide sulfinyl radicals (-SO·), which has been rarely studied before. In order to establish an effective research approach, a method that can generate site-specific peptide sulfinyl radical ion has been developed. This method is based on …


Effect Of Maleic Acid On The Selectivity Of Glucose And Fructose Dehydration And Degradation, Ximing Zhang Apr 2015

Effect Of Maleic Acid On The Selectivity Of Glucose And Fructose Dehydration And Degradation, Ximing Zhang

Open Access Dissertations

5-Hydroxymethyfurfural (HMF), a platform chemical can upgrade to a variety of fuels and polymers, can be manufactured from lignocellulose. This study focuses on the Lewis and Brønsted acid effect on hexose dehydration for HMF production. We report the positive effect of maleic acid, a dicarboxylic acid used as Brønsted acid, on the selectivity of hexose dehydration to 5-hydroxymethyfurfural (HMF), and subsequent hydrolysis to levulinic and formic acids. We also describe the kinetic analysis of a Lewis acid (AlCl 3) alone and in combination with HCl or maleic acid to catalyze the isomerization of glucose to fructose, dehydration of fructose …


Studies Of Arctic Halogen Chemistry From The Snowpack To The Gas Phase, Kyle D Custard Apr 2015

Studies Of Arctic Halogen Chemistry From The Snowpack To The Gas Phase, Kyle D Custard

Open Access Dissertations

The temporary depletion of both tropospheric ozone and gaseous mercury during the Arctic springtime has been a focus of active research over the past several decades. Both of these phenomena have been linked to chemical reactions with halogen radicals. In particular, bromine atoms have been shown to act as the primary driver for these chemical depletions, although both chlorine and iodine atoms also contribute. Molecular bromine, along with its oxidation products, have been well studied in the Arctic, yet chlorine has not. Chlorine is known to impact the local oxidation capacity via its high reactivity with volatile organic compounds. Despite …


Novel Methods For Manipulating Ion Types In The Solution And Gas Phases For The Structural Analysis Of Biomolecules Using Mass Spectrometry, Christine M Fisher Apr 2015

Novel Methods For Manipulating Ion Types In The Solution And Gas Phases For The Structural Analysis Of Biomolecules Using Mass Spectrometry, Christine M Fisher

Open Access Dissertations

Mass Spectrometry has become a valuable tool for the analysis of a variety of molecules, making it applicable to many fields. The advent of nanoelectrospray ionization (nESI) as a soft/low energy ionization technique has enabled the analysis of large, intact biomolecules. Most mass spectrometry experiments consist of three main steps: ionization, probe step(s), and mass analysis. The present work focuses on a variety of methods for altering ion types at various stages of the mass spectrometry experiment to affect ion fragmentation. Ion types can be manipulated in the solution/droplet phases using novel nESI emitters, generated from borosilicate theta capillaries. These …


Public Understanding Of Chemistry Research In Print News, Michael D. Hands Apr 2015

Public Understanding Of Chemistry Research In Print News, Michael D. Hands

Open Access Dissertations

Despite numerous calls for improving scientific literacy, many American adults show a lack of understanding of experiments, scientific study, and scientific inquiry. News media is one important avenue for science learning, but previous research investigating health and/or environmental science news has shown that it is inconsistent in the presentation of scientific research limitations, potentially impacting reader understanding. In the first phase of this dissertation, seventeen news articles reporting on a single chemistry research article, along with associated press releases and research articles, were analyzed using move analysis to determine the structure of each type of text. It was found that …


Polarization-Dependent Nonlinear Optical Microscopy Methods For The Analysis Of Crystals And Biological Tissues, Emma L. Kerian Apr 2015

Polarization-Dependent Nonlinear Optical Microscopy Methods For The Analysis Of Crystals And Biological Tissues, Emma L. Kerian

Open Access Dissertations

The ability to solve a high-resolution protein structure is largely dependent on the successful generation and identification of protein crystals prior to X-ray diffraction (XRD). For novel protein targets, high-throughput crystallography often involves generation of multiple targets and thousands of crystallization trials per target to generate diffraction-quality crystals. Second harmonic generation (SHG) imaging has been developed as a fast, non-destructive and sensitive method for the selective identification of protein crystals, even in highly scattering environments. Polarization-dependent SHG microscopy methods were developed to assess the presence of multidomain crystals to provide a handle on crystal quality. In addition, polarization-dependent two-photon excited …


A Bracketing Method For Proton Affinity Measurements Of Dehydro-And Didehydropyridines, Guannan Li Apr 2015

A Bracketing Method For Proton Affinity Measurements Of Dehydro-And Didehydropyridines, Guannan Li

Open Access Theses

Proton affinity (PA) is a fundamental property that is related to the structure and reactivity of a molecule. Currently, very few experimental PA values are available for organic radicals and none for biradicals. Equilibrium methods cannot be used for these measurements. The traditional bracketing method is based on monitoring reactions of different reference bases with known proton affinities with the protonated analyte for the occurrence of exothermic proton transfer to determine the upper and lower limits of proton affinity. However, the energy deposited into the precursor ions upon CAD when forming protonated radicals may cause endothermic proton transfer reactions occur …


Impact Of Biogenic Volatile Organic Compounds On Peroxyacetyl Nitrate Production In The Southeast United States, Christopher John Groff Apr 2015

Impact Of Biogenic Volatile Organic Compounds On Peroxyacetyl Nitrate Production In The Southeast United States, Christopher John Groff

Open Access Theses

Our atmosphere is arguably the fundamental entity that has made life on Earth possible. Knowledge of the delicate nature of our atmosphere continues to spread as "green" initiatives promote awareness of human influence on the environment. However, many climate scientists fear that unless immediate mitigation occurs, the reversal of human impact on our planet will be impossible, leading to unknown consequence. Perturbations to natural processes are likely to cause drastic change to the planet as we know it and ultimately result in significant health issues. It is important to push the boundaries of our understanding of atmospheric processes with intent …


Development Of Experimental And Instrumental Systems To Study Biological Systems, Amanda J Hemphill Apr 2015

Development Of Experimental And Instrumental Systems To Study Biological Systems, Amanda J Hemphill

Open Access Dissertations

Chapters 1-4 of this thesis describes the development of an experimental system to measure diffusion-limited reaction kinetics in a biological environment. About 100 years ago, the relationship between reaction rate and diffusion in homogenous solution, ie water or buffer, was described as a linear relationship by Smoluchowski. Applying this theory naively would suggest that since the diffusion coefficients drop by factors of 4-100 then the rates of reaction would drop by the same amount. However, recent theory and simulations suggest that this does not hold. Even though biological diffusion coefficients drop to 0.1-20% of that in buffer, these recent studies …


Molecular Diagnosis Of Cancer Using Ambient Ionization Mass Spectrometry, Kevin S Kerian Apr 2015

Molecular Diagnosis Of Cancer Using Ambient Ionization Mass Spectrometry, Kevin S Kerian

Open Access Dissertations

My dissertation focuses on advancing the development and application of ambient ionization mass spectrometry methodology and technology to the biomedical field. The primary ambient ionization method used in my studies is desorption electrospray ionization mass spectrometry (DESI-MS) imaging, which has been previously used to analyze and differentiate disease state (i.e. tumor and normal) and in some cases tumor subtype of human liver, kidney, bladder, testicular, prostate, and brain cancers. DESI-MS imaging is an ideal method for disease diagnosis, because it can be used to directly correlate disease state with histopathology to develop and validate MS libraries built using the molecular …


Studies Of The Interaction Of Biogenic Volatile Organic Compounds And Nox In Forest Environments, Kevin M. Mcavey Apr 2015

Studies Of The Interaction Of Biogenic Volatile Organic Compounds And Nox In Forest Environments, Kevin M. Mcavey

Open Access Dissertations

Ozone is a pollutant that causes crop damage, adverse health effects, and is a contributor to global climate change. Ozone concentrations are predicted to rise over the next half-century along with global temperature. Ozone production is controlled by the chemistry between biogenic volatile organic compounds and NOx (NO + NO2), and therefore, a greater understanding of NOx + BVOC chemistry along with their sources and sinks is needed. One large uncertainty in understanding NOx + BVOC chemistry is the production of organic nitrates (RONO2), which act as a radical termination step in the …


Spectroscopic Characterization And Photochemistry Of Nitrogen-Containing Molecules Relevant To Titan's Atmosphere, Deepali N. Mehta-Hurt Apr 2015

Spectroscopic Characterization And Photochemistry Of Nitrogen-Containing Molecules Relevant To Titan's Atmosphere, Deepali N. Mehta-Hurt

Open Access Dissertations

Titan's atmospheric chemistry has been the source of intrigue since the planetary body's discovery. Though there is a growing understanding of the atmospheric chemistry of small molecules on Titan, much less is known about larger molecule formation, and particularly about nitrile chemistry. This dissertation characterizes nitrile/isonitrile intermediates that are postulated to be important in Titan's atmosphere, adding to the necessary foundation for understanding Titan's atmospheric chemistry. The vibronic spectroscopy of para-diisocyanobenzene (pDIB, C≡N-Ph-N≡C) has been characterized as a first step towards photochemical studies that can test the transformation of the isonitrile group to other nitrogen-based functionalities.p …


Quantification Of Molecular Aggregation Equilibria Using Spectroscopic Measurements And Random Mixing Modeling, Blake M. Rankin Apr 2015

Quantification Of Molecular Aggregation Equilibria Using Spectroscopic Measurements And Random Mixing Modeling, Blake M. Rankin

Open Access Dissertations

Molecular aggregation equilibria, such as the binding of ligands to a central solute molecule, are prevalent throughout biological processes and energy storage devices. However, both the sign and magnitude of hydrophobic and ionic interactions remains a subject of theoretical debate, and has yet to be experimentally determined. Here, Raman vibrational spectroscopy is combined with multivariate curve resolution (Raman-MCR) to experimentally quantify both the number of hydrophobic contacts between alcohol molecules in water and the affinity of ions for molecular hydrophobic interfaces. Furthermore, a generalized theoretical model is developed based on random statistics in which it is assumed that the concentration …


Laboratory Studies On The Production Of Alpha-Pinene-Derived Organic Nitrates And Their Atmospheric Fate, Joel David Rindelaub Apr 2015

Laboratory Studies On The Production Of Alpha-Pinene-Derived Organic Nitrates And Their Atmospheric Fate, Joel David Rindelaub

Open Access Dissertations

Currently, the formation yields of organic nitrates from the oxidation of biogenic volatile organic compounds, such as α-pinene, is highly uncertain, negatively impacting our knowledge on tropospheric ozone production and the fate of atmospheric NOx. To lower this uncertainty, we quantified the organic nitrate yield from the OH radical oxidation of α-pinene under high NOx conditions. The α-pinene- derived nitrates created in chamber experiments readily partitioned to the aerosol phase and underwent particle phase hydrolysis, indicating that these processes are likely a sink for atmospheric NOx. The hydrolysis of organic nitrates was found to be …


Homogeneous And Heterogeneous Rhenium Catalysts For Sustainable Transformations Of Polyols, Alcohols, And Amines, Jing Yi Apr 2015

Homogeneous And Heterogeneous Rhenium Catalysts For Sustainable Transformations Of Polyols, Alcohols, And Amines, Jing Yi

Open Access Dissertations

Biomass-derived molecules, such as sugar polyols and lignin, are promising feedstock for making small and useful organics (SUO) and high value-added organics (HVO). However, the high oxygen to carbon ratio (C:O ≈ 1) prohibits the direct use of biomass-derived molecules as energy carriers and chemicals. Deoxygenation of polyols has become an important challenge in the utilization of biomass resources. Oxorhenium complexes show excellent oxophilicity to transfer oxygen and deoxygenate alcohols. Oxorhenium(VII) complexes can efficiently catalyze the transformation of glycerol to allyl alcohol, acrolein, and propanal. The volatile SUO products were easily separated from the nonvolatile residues via simple distillation. Based …


Non-Covalent Affinity Materials For Protein Structure Determination Via Single Particle Reconstruction Analysis Cryo-Electron Microscopy, Minji Ha Apr 2015

Non-Covalent Affinity Materials For Protein Structure Determination Via Single Particle Reconstruction Analysis Cryo-Electron Microscopy, Minji Ha

Open Access Theses

Single particle analysis (SPA) by cryogenic electron microscopy (Cryo-EM) is one of the powerful tools for determining biological macromolecule structure, particularly when combined with computational methods or X-ray crystallography. However, the SPA is challenged by sample processing efficiency. In this work, polyrotaxane (PRTx) was designed and synthesized such that laterally and rotationally mobile lysine nitrolicacetic acid (Lys-NTA) modified α-cyclodextrins (α-CD) were threaded onto a polyethylene glycol (PEG) core. Polyrotaxanes threaded with amine modified α-CD were also designed and synthesized for stoichiometric control of His-tagged protein capture by PRTx. For higher efficiency of single particle analysis along a single strand of …


Structure-Activity Relationships For The Water-Gas Shift Reaction Over Supported Metal Catalysts, Kaiwalya D. Sabnis Jan 2015

Structure-Activity Relationships For The Water-Gas Shift Reaction Over Supported Metal Catalysts, Kaiwalya D. Sabnis

Open Access Dissertations

The Water-Gas Shift (WGS) reaction (CO + H2O → CO2 + H2) is an important chemical process for industrial hydrogen production. The overall goal of this project is to use kinetic experiments and in situ characterization techniques in tandem, in order to derive structure-activity relationships for various catalytic systems. These relationships facilitate the rational catalyst design by identification of catalyst descriptors. In order to establish such relationships, various studies were undertaken, such as (i) effect of transition admetals on the WGS catalysis by molybdenum carbide (ii) effect of residual oxygen content on the performance of …


Instrumentation And Development Of A Mass Spectrometry System For The Study Of Gas-Phase Biomolecular Ion Reactions, Ziqing Lin Jan 2015

Instrumentation And Development Of A Mass Spectrometry System For The Study Of Gas-Phase Biomolecular Ion Reactions, Ziqing Lin

Open Access Dissertations

Gas-phase reactions of biomolecular ions are highly relevant to the understanding of structures and functions of the biomolecules. Mass spectrometry is a powerful tool in investigating gas-phase ion chemistry. Various mass spectrometers have been developed to explore ion/molecule reactions, ion/ion reactions, ion/photon reactions, ion/radical reactions etc., both at atmospheric pressure and in vacuum. In-vacuum reactions have an advantage of involving pre-selecting the ions for the reactions using a mass analyzer. Over the decades, a variety of mass analyzers have been employed in the research of ion chemistry. Hybrid configurations, such as quadrupole ion trap with a time-of-flight and or a …


The Antitumorigenic Function Of Egfr In Metastatic Breast Cancer Is Regulated By Expression Of Mig6, Michael Wendt, Whitney K. Williams, Pete E. Pascuzzi, Nikolas G. Balanis, Barbara J. Schiemann, Cathleen R. Carlin, William P. Schiemann Jan 2015

The Antitumorigenic Function Of Egfr In Metastatic Breast Cancer Is Regulated By Expression Of Mig6, Michael Wendt, Whitney K. Williams, Pete E. Pascuzzi, Nikolas G. Balanis, Barbara J. Schiemann, Cathleen R. Carlin, William P. Schiemann

Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Numerous studies by our lab and others demonstrate that epidermal growth factor receptor (EGFR) plays critical roles in primary breast cancer (BC) initiation, growth and dissemination. However, clinical trials targeting EGFR function in BC have lead to disappointing results. In the current study we sought to identify the mechanisms responsible for this disparity by investigating the function of EGFR across the continuum of the metastatic cascade. We previously established that overexpression of EGFR is sufficient for formation of in situ primary tumors by otherwise nontransformed murine mammary gland cells. Induction of epithelial-mesenchymal transition (EMT) is sufficient to drive the metastasis …