Browsing by Author "Lin He, Committee Member"

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The Development of Desorption Electrospray Ionization and Nano Flow Liquid Chromatography Mass Spectrometric Methods for Glycan Analysis: Applications for Biomarker Discovery in Epiethelial Ovarian Cancer
(2009-10-02) Bereman, Michael Seth; David Muddiman, Committee Chair; Lin He, Committee Member; Chris Gorman, Committee Member; Edmond Bowden, Committee Member
Ovarian cancer is often referred to as the Ã¢â‚¬Å“silent killerÃ¢â‚¬Â due to the deadly nature of this malignancy and its asymptomatic nature. The disease will affect an estimated 24,000 women in the United States in 2009. If the disease is caught in its early stages over 90 % of patients survive longer than 5 years; however, 7 out of 10 patients are diagnosed in the late stages, after metastasis, where 1 in 5 people meet this 5-year survival mark. Advancements in early diagnosis are critical for both early intervention as well as a more in-depth understanding of this cancer such that therapeutic targets can be elucidated. One of the major limitations for biomarker discovery research is the massive amount of time that must be allocated for preparation and analysis of large sample sets. The recent development of hybrid ionization techniques which combine ambient analysis with limited sample preparation and lead to higher sample throughput could help circumvent this current limitation. Herein, the development of a newly introduced ionization technique termed desorption electrospray ionization (DESI) is characterized for various biomarker discovery applications including proteomics and glycomics. Glycomics is an emerging field for biomarker discovery research. Herein, a method for the analysis of N-linked glycans is provided. This method is then utilized to compare the N-linked glycan profile between 48 plasma samples derived from epithelial ovarian cancer patients, 48 controls samples and 8 healthy samples. Three glycans were evaluated for their ability to differentiate between EOC and control and these results were compared to the gold standard in EOC detection, CA 125. Results indicated limited diagnostic value for three glycans in distinguishing control and EOC patients and moderate diagnostic value in differentiating EOC and healthy samples.
Development of Novel Methodologies for the Photoregulation of Biological Processes.
(2010-07-01) Georgianna, Wesleigh Edwards; Alexander Deiters, Committee Chair; Jonathan Lindsey, Committee Member; Lin He, Committee Member; David Muddiman, Committee Member; Laura Mathies, Committee Member
Experimentation in Replacement Lithography, Reductive Desorption, and Scanning Probe Imaging on Various Metal Substrates.
(2010-06-28) Williams, James Alfred; Christopher Gorman, Committee Chair; Edmond Bowden, Committee Member; Stefan Franzen, Committee Member; Lin He, Committee Member; Jack Odle, Committee Member
Exploring Fundamental Aspects of Proteomic Measurements: Increasing Mass Measurement Accuracy, Streamlining Absolute Quantification, and Increasing Electrospray Response
(2009-05-08) Williams, Dennis Keith Jr.; Kenneth W. Hanck, Committee Member; Edmond F. Bowden, Committee Member; David C. Muddiman, Committee Chair; Lin He, Committee Member
Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) offers unparalleled performance in terms of resolving power and mass measurement accuracy. In order to realize the highest achievable mass measurement accuracy for a given FT-ICR MS system, frequency shifts due to space-charge effects must be accounted for via external or internal calibration methods. Herein, a dual electrospray ionization source was coupled to a hybrid quadrupole Fourier transform ion cyclotron resonance mass spectrometer and utilized to incorporate internal calibrant to yield high mass measurement accuracy results. Frequency shifts from space-charge effects were also counteracted by accounting for total ion population and relative ion population on a MALDI-FT-ICR MS and a hybrid LTQ-FT-ICR MS equipped with automatic gain control. This was achieved through the use of multiple linear regression and artificial neural networks. These experiments resulted in mean mass measurement accuracies in the parts-per-billion range. C-reactive protein (CRP) is an important clinical marker for inflammation, atherosclerosis, and has also been observed to be upregulated in patients with epithelial ovarian cancer (EOC). This dissertation contains results from a protein cleavage isotope dilution mass spectrometry method developed for the absolute quantification of CRP from human plasma. A total of 110 human plasma samples were analyzed including 54 samples from patients with EOC. The results were compared to a CLIA certified ELISA test which showed high correlation but different absolute values, which suggested different reference ranges for different analytical techniques. In addition, a correlation was observed between the stage of diagnosis of cancer and CRP concentrations. Chemical tags have long been utilized with mass spectrometry for a multitude of purposes, extending the effectiveness of the measurements dramatically. Electrospray ionization has been shown to preferentially ionize more hydrophobic species. Four new iodoacetamide derivatives, which react with the amino acid cysteine, were reacted with three peptides to determine their ability to increase electrospray response. This resulted in increases up to 2000-fold compared to alkylation of peptides with iodoacetamide. The combination of these results will aid future studies to identify and quantify proteins and peptides which contain cysteine and can be expanded to all peptides using amine-specific chemistry.
Gold Nanocrystal Therapeutics: Treatment of Multidrug Resistant Pathogens and Disrupting Protein/Protein Interactions.
(2010-06-30) Kudgus, Rachel; Christian Melander, Committee Chair; David Shultz, Committee Member; Lin He, Committee Member; Elon Ison, Committee Member; Douglas Cullinan, Committee Member
Investigation of Helicity of Water Soluble Polycarbodiimides and Preparation of Nano Particles with Amphiphilic Polycarbodiimides.
(2006-08-04) Li, Haibo; Tatyana I. Smirnova, Committee Member; Lin He, Committee Member; Alex Deiters, Committee Member; Bruce M. Novak, Committee Chair
As a helical polymer, polycarbodiimides have been investigated for a period of time. But few water soluble polycarbodiimides had been synthesized and characterized. Since solubility of polycarbodiimides can be controlled by their side arms, achiral or chiral carbodiimides bearing hydrophilic tertiary amino group have been prepared. Single-handed sense hydrophilic polycarbodiimides were prepared from chiral monomers by achiral metal catalyst or from achiral monomers by chiral catalyst to give polycarbodiimides with predominately helical sense. The water solubility of these polycarbodiimides bearing tertiary amino groups is improved when they are methylated by methyl camphorsulfornic acid ester. Configurational and conformational predominately helical polycarbodiimides behave with different way when they are heated. For the former case, the polymers rearrange to their Thermodynamic Control Conformation (TCC) from Kinetic Control Conformation (KCC); for the later one, the polymer became racemic when annealed. The activation energies for the conformational change can be determined through Arrhenius plot analysis. Compared to the neutral polycarbodiimides bearing tertiary amino groups, the corresponding ionic polymers have higher activation energies. Helical induction of the water-soluble polycarbodiimides also has been investigated. CD spectrum was run for both the neutral and ionic polycarbodiimides and peptide mimics were found. In addition to the hydrophilic monomers, chiral or achiral hydrophobic carbodiimides were also synthesized and polymerized. Through living polymerizations, the amphiphilic polycarbodiimides were prepared from metal catalysts. Crew-cut nanoparticles have been prepared through a phase inversion method. Different conditions have been tried to achieve nano particles with different morphologies and sizes. In the nano particle preparation, water amount, acid amount and molecular weight play important roles in preparation of nano particles. TEM was used to characterize the nano particles. Amphiphilic polycarbodiimides with optical active hydrophobic blocks were synthesized and applied in the preparation of a nano-superhelix.
Materials Science and Sensing Applications of Surface Plasmon Resonance in Conducting Metal Oxides
(2008-06-15) Rhodes, Crissy Lynette; Jan Genzer, Committee Member; Stefan Franzen, Committee Chair; Lin He, Committee Member; Edmond Bowden, Committee Member
Multifunctional Heterometallic Oxide and Oxyfluoride Hybrid Solids
(2009-12-02) Lin, Haisheng; Lin He, Committee Member; Edmond F. Bowden, Committee Member; Mike H. Whangbo, Committee Member; Paul A. Maggard, Committee Chair
Heterometallic-oxide and oxyfluoride/organics are hybrids containing both organic ligands and inorganic metal-oxide/oxyfluoride components. These interesting types of materials are beginning to receive widespread attention because of their potential to express, within the same material, both the robustness and physical properties of inorganic components in conjunction with the versatility and chemical flexibility of organic ligands. My research efforts within this area have focused on the synthesis and design of new heterometallic hybrids which possess varied novel structures, and new investigations of their optical and phtocatalystic properties. Metal oxide systems were selected that contain an early transition-metal (i.e. V, Nb, Mo, W, Re) with a d0 electron configuration and a late transition-metal (i.e. Ag, Cu) with a d10 electron configuration. Organic ligands used in the reactions were chosen to possess different charges and sizes, and that would preferentially coordinate to the late transition metals that form part of the metal-oxide. The target of my work has been to investigate the hydrothermal syntheses of novel heterometallic hybrids and to explore the use of organic ligands in modifying and controlling the formation of resultant structures of metal oxides. The first section covers a new series of Ag/Cu-containing heterometallic-oxides/organics, with 0-1D, 2D layer, 3D pillar-layered or multi-fold interpenetrating structures through molecular-level interactions, and that have led to new insights regarding the range of optical bandgap absorption in compounds with d0/d10 transition metals. The latter aspect is analyzed with regard to its use in designing future photocatalytic materials. The syntheses, properties, and potential applications of these new materials are presented and analyzed herein, and especially, for the first known series of photocatalytically active silver-vanadate hybrids evaluated. The second section is focused on the synthesis and probing of the structures of new heterometallic-oxyfluoride/organics containing symmetric and/or asymmetric early transition metal (V, Nb, Mo, W) oxyfluorides anions. Their optical properties were studied as a function of small molecule absorptions. An understanding of the structure-properties relationships is used for further design and synthesis new visible-light photocatalytic materials.
Nanoparticle-based Delivery Vectors:Design, Preparation, Characterization, Cellular Internalization and Nuclear targeting
(2008-08-03) Liu, Yanli; Daniel L. Feldheim, Committee Chair; Lin He, Committee Member; Christian Melander, Committee Member; Edmond F. Bowden, Committee Member
Poly(lactic acid) Polymer Brushes as Dynamic Surfaces.
(2011-01-05) Xu, Lebo; Christopher Gorman, Committee Chair; Jan Genzer, Committee Member; Edmond Bowden, Committee Member; Stefan Franzen, Committee Member; Lin He, Committee Member
Stereochemical Effects on the Organizational and Electronic Structure of the Tartaric Acid/Ag(111) System
(2009-08-07) Santagata, Nancy Marie; Marco Buongiorno Nardelli, Committee Member; Lin He, Committee Member; Christopher Gorman, Committee Co-Chair; Thomas P. Pearl, Committee Co-Chair
This dissertation aims to develop an understanding of the forces that drive the organization of organic molecules at metallic surfaces, namely intermolecular structure, in the limit of weak molecule-surface interactions. A model system, composed of a chiral molecule, tartaric acid (C4H6O6), and a metallic surface with unique electronic properties, Ag(111), is employed. The interfacial organizational and electronic structures of the tartaric acid/Ag(111) system has been studied in detail with low energy electron diffraction (LEED), low temperature scanning tunneling microscopy (STM) and spectroscopy (STS), differential conductance (dI/dV) mapping, and density functional theory (DFT). Molecularly resolved STM images of both (R,R)- and (S,S)-tartaric acid on Ag(111) in the submonolayer coverage regime reveal the role of intermolecular hydrogen bonding in stereospecific domain formation. Global chirality is expressed upon the deposition of enantiopure tartaric acid; therefore, directional and anisotropic lateral interactions involving molecular chiral centers dictate domain organization despite a weak interaction with the underlying Ag(111) lattice. Further, these enantiopure films are characterized by adsorbates whose molecular axis lies parallel to the plane of the surface. In contrast, films deposited from a racemic mixture do not separate laterally into homochiral domains with global chirality. Molecularly resolved STM images, in combination with DFT simulations, confirm that these racemic films are composed of a unique paired (S,S)-/(R,R)-tartaric acid basis whose combined molecular axis is oriented perpendicular to the plane of the surface. The differences in adsorption geometry for enantiopure versus racemic tartaric acid films is therefore controlled by intermolecular interactions involving chiral centers, indicating that chirality can be utilized in the directed two-dimensional assembly of molecular components. This dissertation also describes the modification of the Ag(111) Shockley-type surface state as a signature of tartaric acid adsorbate structure. Shockley-type surface states exist on several metal surfaces and are characterized by electron confinement by the vacuum barrier on one side and a band gap in the bulk on the other. The proximity of the surface state to the Fermi level (-67 meV for this particular surface) amplifies its role in surface chemistry, bonding, and organization. The adsorption of both enantiopure and racemic tartaric acid in the submonolayer regime induces a positive shift of the Ag(111) surface state energy after the adsorption of both forms of tartaric acid. The magnitude of the shift differs, however, for films composed of either enantiopure (E(R,R) TA=813.9 Ã‚Â± 2.9 meV) or racemic (ÃŽâ€ EDL TA=54.5 Ã‚Â± 3.5 meV) domains. These film-dependent modifications of the Shockley-type surface state are attributed to unique the adsorbate geometries, which are controlled by intermolecular interactions involving chiral centers. In sum, the combined experimental and theoretical results presented herein indicate that internal molecular structure (chirality) can be exploited for the design of rational nanostructures that possess tailored structural and electronic properties.
The Synthesis and Characterization of Ester-Bearing Polycarbodiimides.
(2010-06-18) Clark, Joe; Bruce Novak, Committee Chair; Marian McCord, Committee Member; Tatyana Smirnova, Committee Member; Lin He, Committee Member
Theoretical and Experimental Spectroscopic studies of Conducting Metal Oxide Thin Films
(2009-08-20) Efremenko, Alina Yurievna; Stefan Franzen, Committee Chair; Lin He, Committee Member; Jon-Paul Maria, Committee Member
In order to expand on the growing field on Surface Plasmon Resonance Spectroscopy (SPRS) the application of SPRS to Conducting Metal Oxides (CMO) was studied. Through experimental and theoretical studies it was concluded that CMOÃ¢â‚¬â„¢s are capable of sustaining Surface Plasmon Polaritons (SPP) like those in noble metals. Specifically, we have used indium tin oxide (ITO) as a test case to demonstrate the interplay of experiment and theory. Theoretical studies provided an excellent basis for comparison to experimental data. Furthermore, Near Edge X-Ray Absorption Fine Structure Spectroscopy (NEXAFS) was applied in order to examine the ITO as a substrate for self assembled monolayers (SAMs). It was found that hexadecanethiol and phosphonic acid form ordered monolayers on ITO.