In this dissertation, I present electronic spectroscopy of a few biologically relevant species and their complexes with solvent molecules in the gas phase using a variety of techniques, including resonantly enhanced multiphoton ionization (REMPI), laser induced fluorescence (LIF), and zero kinetic energy (ZEKE) photoelectron spectroscopy. My work on several methylated uracils and thymines and thymine-water complexes alludes to a new interpretation with regard to the origin of the photostability of our genetic code. I believe that it is the water solvent that stabilizes the photophysical and photochemical behavior of these bases under UV irradiation. For systems that demonstrate vibrational resolution in the first electronically excited state (S₁) and the cationic state, I performed vibrational analysis of both states with the aid of ab initio and density functional calculations. These observations are explained in terms of the structural changes from the ground state to S₁ and further to the cation. To bridge results from the gas phase to the solution phase, I also report studies of supersonically cooled water complexes of the three isomers of aminobenzoic acid. Density functional theory calculations are carried out to identify structural minima of water complexes in the ground state. The solvation mechanism is investigated based on vibrational analysis of the S₁ state of the neutral complex and the shift of ionization thresholds with increasing water content. / Graduation date: 2005

Graduation date: 1995

Graduation date: 1994

Ultraviolet radiation (UVR) is a major risk factor for development of skin cancer. UVR-induced DNA damage and a dysfunctional p53 protein are important steps in the development of squamous cell carcinoman in human skin (SCC). The aim of the present investigation was to analyze incidence trends of SCC in Sweden, quantify the risk of second primary cancer after SCC and further analyze the effects of UVR and p53 protein in human skin in vivo and in vitro. The effect of photoprotection by sunscreens was also evaluated. We found that the age-standardized incidence rate of SCC in Sweden increased substantially in both men and women during the period 1961-1995, especially in men and at chronically sun-exposed skin sites. Patients with SCC are also at increased risk of developing new primary cancers, especially in the skin, squamous cell epithelium, hematopoietic tissues and respiratory organs. In experimental studies in vivo and in vitro in human skin we observed that repair of UV-induced DNA damage appears to be more efficient in chronically sun-exposed skin despite a less uniform p53 response. Non-sun- exposed skin is more homogeneous with respect to the epidermal p53 response. Keratinocytes in skin exposed frequently to the sun may be prone to react more easily to cytotoxic stress. Two different modalities of photoprotection significantly reduced the amount of DNA damage and the number of p53-positive cells. In addition, we demonstrated that a well-defined system for in vitro culture of explanted skin provides an excellent alternative to in vivo experiments. In conclusion, this study has increased our knowledge of SCC epidemiology in Sweden and of the effects of artificial and solar UVR and sunscreens on chronically sun-exposed and non-sun-exposed sites, respectively, of human skin.

<p>Mitochondria are the primary energy producers of the cell and play key roles in cellular signaling, apoptosis and reactive oxygen species (ROS) production. Mitochondria are the only organelles that contain their own genome which encodes for a small subset of electron transport chain (ETC) proteins as well as the necessary tRNAs and ribosomal subunits to translate these proteins. Over 300 pathogenic mitochondrial DNA (mtDNA) mutations have been shown to cause a number of mitochondrial diseases emphasizing the importance of mtDNA maintenance and integrity to human health. Additionally, mitochondrial dysfunction and mtDNA instability are linked to many wide-spread diseases associated with aging including cancer and neurodegeneration. Mitochondria lack the ability to repair certain helix-distorting lesions that are induced at high levels in mtDNA by important environmental genotoxins including polycyclic aromatic hydrocarbons, ultraviolet C radiation (UVC) and mycotoxins. These lesions are irreparable and persistent in the short term, but their long-term fate is unknown. Degradation of mitochondria and mtDNA is carried out by autophagy. Autophagy is protective against cell stress and apoptosis resulting from exposure to mitochondrial toxicants suggesting that it plays an important role in removal of unstable mitochondria that can serve as a source of ROS or initiate apoptotic cell death. Furthermore, dysfunctional mitochondria can be specifically targeted for degradation by the more specific process of mitophagy influenced in part by the processes of mitochondrial dynamics (i.e., fusion and fission). </p><p>The goals of this dissertation were to investigate the long-term fate of helix-distorting mtDNA damage and determine the significance of autophagy and mitochondrial dynamics in removal of and recovery from persistent mtDNA damage. Removal of irreparable mtDNA damage and the necessity of autophagy, mitophagy, fusion and fission genes in removal of this damage were examined using genetic approaches in adult <italic>Caenorhabditis elegans</italic>. In order to investigate the significance of autophagy, fusion and fission genes in recovery from mtDNA damage-induced mitochondrial dysfunction <italic>in vivo</italic>, an experimental method was developed to specifically induce persistent mtDNA damage and mitochondrial dysfunction without persistent nDNA damage in developing <italic>C. elegans</italic>. Additionally, the effect of persistent helix-distorting DNA damage on mitochondrial morphology, mitochondrial function and autophagy was investigated in <italic>C. elegans</italic> and in mammalian cell culture. The rate and specificity of mitochondrial degradation was further examined in cell culture using live-cell fluorescence microscopy and transmission electron microscopy. </p><p>Removal of UVC-induced mtDNA damage was detectable by 72 hours in <italic>C. elegans</italic> and mammalian cell culture, and required mitochondrial fusion, fission and autophagy, providing genetic evidence for a novel mtDNA damage removal pathway. UVC exposure induced autophagy with no detectable effect on mitochondrial morphology in both systems; mitochondrial function was inhibited in the <italic>C. elegans</italic> system but not in the cell culture system in which the degree of mtDNA damage induced was less. Furthermore, mutations in genes involved in these processes as well as pharmacological inhibition of autophagy exacerbated mtDNA damage-mediated larval arrest, illustrating the <italic>in vivo</italic> relevance of removal of persistent mtDNA damage. Mutations in genes in these pathways exist in the human population, demonstrating the potential for important gene-environment interactions affecting mitochondrial health after genotoxin exposure.</p> / Dissertation

Thesis (Ph. D.)--Lehigh University, 2002. / Includes vita. Includes bibliographical references (leaves 121-132).

The potential of hot water dipping, vapour heating or ultraviolet irradiation to eliminate the use of chemicals for control of sprouting and post-harvest diseases of the potato (Solanum tuberosum L.) was examined. The microorganisms on which these treatments were tested were the fungal dry rot (Fusarium solani) and the bacterial soft rot (Erwinia carotovora pv. carotovora), two major post-harvest pathogens of potatoes. The study focused on short-term storage (three months) at 8$ sp circ$C or 18$ sp circ$C, which are representative of storage temperatures used by producers in northern temperate and semi-arid tropical regions, respectively. / Response surface methodology was used in experimentation to facilitate analysis of data and identification of optimal operating conditions for the treatments. The following parameters were used to assess tuber quality after the treatments and 3-month storage: firmness, color and structure. / It was found possible to obtain 100% control of sprouting and diseases for the three-month storage without resorting to the use of chemicals. This was achieved without significantly altering the quality attributes of the tubers under certain conditions of hot water, ultraviolet radiation or combinations of these two with storage at 8$ sp circ$C for three months. Although 100% control was not possible for the storage at 18$ sp circ$C, treated tubers performed much better than the controls. Vapour heat (50-70$ sp circ$C) was much less effective at controlling sprouting and was therefore not tested on the pathogens. / A numerical model of the heat transfer phenomenon in the tuber was also developed. It was used to predict the transient temperature distribution in the tuber. The model was solved using the line-by-line technique and model simulations were validated against experimental data.

Ultravioletiniai spinduliai veikia daugelį polimerų, tame tarpe ir polipropileną. Darbo tikslas buvo ištirti ultravioletinės spinduliuotės (=254 nm) poveikį polipropilenui. Medžiagos cheminės sudėties pokyčiui nustatyti buvo matuojami infraraudonųjų spindulių absorbcijos spektrai, o fizinių savybių pokytis – matuojant stiprumo ribą, regimosios šviesos praleidimo faktorių, induktyvumą bei kontūro elektrinę talpą. Nustatyta, kad polipropileną veikiant 254 nm bangos ilgio šviesa medžiaga palaipsniui oksiduojasi. UV spinduliuotė generuoja peroksidinių (>CH-O-OH), karbonilinių (>C=O) ir vinilinių (-CH=CH2) grupių susidarymą anglies grandinėse ir jų koncentracija didėja ilginant švitinimo trukmę. Po 160 val. švitinimo prasideda polimero degradacija: keičiasi jo struktūra, prarandamas skaidrumas, elastingumas, didėja trapumas bei mažėja polipropileno plėvelės storis. Polipropileno paviršiuje atsiranda įtrūkimų, plėvelė pageltonuoja. Magnetinių savybių matavimai rodo, kad oksiduojantis polipropilenui didėja laisvųjų radikalų koncentracija propileno grandinėse. Mikroskopiniai tyrimai parodė plėvelės paviršiuje susidariusias destrukcijos juostas. / Wide verily of polymers undergo physicochemical changes. The aim of the paper was to study the effect of ultraviolet radiation (λ= 254 nm) on polypropylene. The chemical changes were measured by the infrared absorption spectra, and the change the physical properties – by measurement of the strength limit, visible light transmittance, polypropilene inductance and capacitance. It is determined that PP exposed to ultraviolet light undergo photo-oxidation and photo-degradation. UV radiation generates formation of peroxide (>CH-O-OH), carbonyl (>C=O) and vinyl (-CH=CH2) groups in the carbon chaines with increasing their concentrations during exposure. After 160 hours UV exposure process of PP destruction gets up: the transparency, elasticity, polypropilene film thickness and strenght is declining. Microscopic demonstrated the cracks on the surface of the films after 160 hours of exposure.

Ultraviolet (UV) radiation damages both eukaryotic and prokaryotic cells by causing the formation of free radicals which damage cell membranes and DNA. Antioxidant vitamins have been shown to protect cells from UV-induced damage by scavenging free radicals. The protection of skin and its normal flora is necessary for the health of individuals in resisting diseases caused by microorganisms and delaying the long-term damage caused by UV radiation.This research investigated the effects of the antioxidants vitamin A and ascorbic acid, as well as UV-irradiation on both prokaryotic (Staphylococcus epidermidis) cells and eukaryotic (human fibroblast skin) cells. This information is important in determining the effects of vitamin treatment on skin and its normal flora.Results indicate that ascorbic acid is rapidly (within six hours) degraded after being dissolved in water or medium. Treatment of cells with ascorbic acid must take into account this rapid degradation. S.epidermidis cells were protected from UV-induced damage by treatment with ascorbic acid but were more sensitive to UV-irradiation when treated with vitamin A. Human fibroblast cells treated with ascorbic acid did not exhibit morphological changes when compared to untreated cells. / Department of Biology

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