Thesis (Ph. D.)--Institute of Paper Chemistry, 1966. / Includes bibliographical references (p. 102-106).

Thesis (Ph. D.)--Institute of Paper Chemistry, 1964. / Includes bibliographical references (p. 52-54).

In this dissertation I describe a model system to characterize the response of an oral bacterial pathogen, Aggregatibacter actinomycetemcomitans to the metabolic byproducts of a representative member of the oral flora, Streptococcus gordonii. A. actinomycetemcomitans is a causative agent of periodontal infections in humans. To cause infection, A. actinomycetemcomitans must overcome numerous challenges, including the host immune system and toxic metabolite production from other microbes. The most numerically dominant flora in the oral cavity are oral streptococci, which are well known for their ability to produce copious amounts of lactic acid and H₂O₂. By studying the response to H₂O₂ and lactic acid in pure and co-cultures, I have demonstrated that A. actinomycetemcomitans responds to these metabolites by several novel mechanisms that both enhance its survival in the presence of the host immune system and in the presence of the model oral streptococci S. gordonii. These studies have demonstrated that metabolites produced by normal flora can impact the survival of a single species in vivo as much as previously known virulence factors have done. In addition, I present a new method for measuring metabolite production in an attached cell population. This method is a novel application of scanning electrochemical microscopy (SECM) and I used this technique to study H₂O₂ production in the three dimensional space surrounding a multispecies biofilm in real time. In a related study I present the use of SECM to discover a novel redox chemistry phenomenon in the opportunistic pathogen Pseudomonas aeruginosa. / text

The Ataxia-telangiectasia mutated (ATM) protein is regarded as the major regulator of the cellular response to DNA double Strand Breaks (DSBs). In response to DSBs, ATM dimers dissociates into active monomers in a process promoted by Mre11-Rad50-Nbs1 (MRN) complex. ATM-deficient cells exhibit signs of chronic oxidative stress, suggesting that ATM plays an important role in the regulation of reactive oxygen species (ROS). I show for the first time that ATM can be activated by oxidative stress directly in the form of exposure to H₂O₂. In vitro kinase assays with purified ATM suggest that the activation by H₂O₂ is independent of DSBs and the MRN complex. In 293T cells, H₂O₂ induces ATM autophosphorylation on serine 1981. p53 and Chk2 are also phosphorylated by ATM after H₂O₂ treatment but not histone H2AX and heterochromatin protein Kap1, indicating that ATM activation by H₂O₂ in human cells is independent of DNA damage. I also show that the cysteine residue 2991 is critical for ATM activation by H₂O₂ in vitro. / text

Recently, metal nanoparticles have attracted the attention of researchers in several fields of study due to their high surface area and other unique properties. Using metal nanoparticles as a component of an in situ chemical oxidation (ISCO) system is emerging and hence very little information is available. In this research, nano zero valent iron (nZVI) particles and iron-based bimetallic zero valent nanoparticles (BZVNs) were employed to activate some common peroxygens (hydrogen peroxide (H2O2), persulfate (S2O82-), and peroxymonosulfate (HSO5-)) to degrade hazardous organic compounds. Aqueous and soil slurry batch systems were used along with a one-dimensional physical model. The results from the aqueous batch systems showed that nZVI is a promising activator for S2O82- compared to other conventional iron activators (e.g., granular-ZVI and Fe2+). For example, the initial trichloroethylene (TCE) reaction rate by nZVI activated S2O82- was 1.11 x 10-4 M L-1 min-1 compared to an initial reaction rate of 6.25 x 10-5 M L-1 min-1, 5.18 x 10-6 M L-1 min-1, and 1.8 x 10-7 M L-1 min-1 for Fe2+ activated S2O82-, granular-ZVI activated S2O82-, and non-activated S2O82-, respectively. However, the surfaces of nZVI particles were passivated quickly following exposure to S2O82-, causing the reaction rate to reduce to a magnitude representative of an un-activated S2O82- system. An iron-sulfate (FeSO4) complex was formed on the surfaces of the nZVI particles following exposure to S2O82- compared to the iron oxyhydroxide (FeOOH) layer that was present on fresh nZVI surfaces. BZVNs showed better treatment effectiveness than nZVI particles as activators for H2O2, S2O82-, and HSO5-. For example, the TCE reaction rate constant for nano-Ag-Fe0 activated H2O2 was 9 to 18 fold higher than that for nZVI activated H2O2. Of the nine different BZVNs investigated as activators, the greatest TCE degradation was achieved by nano-Pd-Fe0 and nano-Zn-Fe0 activated S2O82- system, nano-Co-Fe0 activated HSO5- system, and nano-Ag-Fe0 activated H2O2 system. For all of these systems, an increase in the dosage of nanoparticles and peroxygens increased TCE degradation. The activated H2O2 system showed a lower TCE degradation rate compared to either the activated S2O82- or the activated HSO5- systems, suggesting that a bridged group complex is formed between the activators and H2O2. The dissolved TCE concentration remaining in the soil slurry batch systems after using the nano-Pd-Fe0 activated S2O82- system was two to three fold higher than that in an aqueous batch system. Furthermore, for five different aquifer materials used, the higher mass of aquifer materials the lower the TCE degradation, indicating that the aquifer materials compete with a target organic compound in the presence of activated S2O82-. A linear relationship was observed between the organic carbon (OC) content and the initial TCE decomposition rate. Although there is no direct evidence of the effect of OC on the treatment system, it is suggested that the OC may result in scavenging the generated free radicals or by directly consuming persulfate. In the one-dimensional physical model systems, bimetallic nanoparticles were mobile in a non-geological porous medium and relatively immobile in a geological porous medium. In the non-geological porous medium, we found that adding a second metal (e.g., Pd) to nano-Fe0 particles significantly improved their functionality and performance (e.g., mobility and suspension). For example, the results from mobility experiments using columns packed with glass beads showed that the effluent iron concentration was <6 % of the influent iron concentration for the nano-Fe0 particles, while it was ~100 % for the nano-Pd-Fe0 particles. In the geological porous medium, based on visual inspection, nano-Pd-Fe0 particles could not travel more than a few centimeters into columns packed with CFB Borden sand, and no iron was detected in the effluent. To overcome the delivery issue in porous media, nano-Pd-Fe0 particles were injected to create a zone of activation to activate S2O82- for the treatment of TCE source zone. However, we found that the TCE mass destruction was only 9 % higher in the nano-Pd-Fe0 activated S2O82- system compared to the non-activated S2O82- system as revealed by the effluent chloride concentration. In addition, the activation zone composed of nano-Pd-Fe0 particles was rapidly deactivated after exposure to persulfate as visually observed by color change, indicating that the longevity of the activation zone is limited. This research effort provides a contribution to the field of ISCO by evaluating the potential utility and applicability of a new class of activators for some common peroxygens.

Previous investigations have demonstrated that reactive oxygen species such as hydrogen peroxide (H2O2) have the ability to alter electrophysiological and mechanical properties of rat ventricular cardiac myocytes. However, despite the breadth of the literature, there is little definitive consensus on the cellular mechanisms. The purpose of this study, therefore, was to study the cellular mechanism of action of H2O2 and test whether H2O2-mediated affects were partially a result of reverse-mode Na+/Ca2+ exchanger (NCX) activity. Unloaded cell shortening, intracellular Ca2+ transients, caffeine-induced Ca2+ transients, L-type Ca2+ channel recordings, and action potential waveforms were recorded in the presence of combinations of different compounds including Cd2+, H2O2, and KB-R7943. H2O2 was found to cause significant positive inotropy by an increase in contractility of 80 ± 20 % (n=6) and an increased amplitude of Ca2+ transients by 24 ± 14 % (n=8), relative to pre-treatment values. Interestingly, H2O2 caused an increase in contractility even in the presence of Cd2+ block from 4 ± 1 % (n=9) to 15 ± 3 % (n=5) of resting cell length. Using caffeine pulse experiments to induce unloading of the sarcoplasmic reticulum (SR), we found that 100µM H2O2 did not significantly alter SR Ca2+ load. Under control conditions, H2O2 significantly increased L-type Ca2+ currents while this H2O2-induced increase was not observed in myocytes pretreated with Cd2+. Positive inotropy in the presence of H2O2 was blocked using 10µM KB-R7943, a selective reverse-mode inhibitor of the NCX. However, it was found that 10µM KB-R7943 alone altered action potential profile and suppressed normal contraction. Altogether, the major finding of this study is that H2O2 has the ability to enhance myocardial contractility, even under conditions of L-type Ca2+ channel inhibition, through a mechanism that likely involves reverse-mode of the NCX. / Thesis (Master, Physiology) -- Queen's University, 2009-03-31 14:00:34.21

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Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [78]-85).

Thesis (Ph. D.)--University of Wisconsin--Madison, 1934. / Typescript. Includes bibliographical references.