Pseudomonas aeruginosa is a common and important pathogen in people with cystic fibrosis (CF). Recently epidemic strains of P. aeruginosa associated with increased morbidity, have been identified. The method of transmission is not clear, but there is evidence of a potential airborne route. The aim of this study was to determine whether different strains of P. aeruginosa isolated from people with CF were able to survive within artificially generated aerosols in an aerobiological chamber. Viable P. aeruginosa could still be detected up to 45min after halting generation of the aerosols. All of the strains of P. aeruginosa expressing a non-mucoid phenotype isolated from people with CF had a reduced ability to survive within aerosols compared to an environmental strain. Expression of a mucoid phenotype by the strains of P. aeruginosa isolated from people with CF promoted survival in the aerosol model compared to strains expressing a non-mucoid phenotype.

Thesis (Ph. D.)--University of Virginia, 2008. / Includes bibliographical references. Also available online through Digital Dissertations.

Diss. (sammanfattning) Umeå : Umeå universitet, 2008. / Härtill 4 uppsatser.

Thesis--University of Oklahoma. / Bibliography: leaves 113-115.

Thesis (M.S.)--University of Tennessee Health Science Center, 2006. / The electronic version of this thesis is available at http://etd.utmem.edu/WORLD-ACCESS/2006-002-yan.pdf Includes bibliographical references (leaves 128-136).

The nucleus of epidermal keratinocytes (KCs) is a complex and highly compartmentalized organelle, whose structure is markedly changed during terminal differentiation and transition of the genome from a transcriptionally active state seen in the basal and spinous epidermal cells to a fully inactive state in the keratinized cells of the cornified layer. Here, using multicolor confocal microscopy, followed by computational image analysis and mathematical modeling, we demonstrate that in normal mouse footpad epidermis, transition of KCs from basal epidermal layer to the granular layer is accompanied by marked differences in nuclear architecture and microenvironment including the following: (i) decrease in the nuclear volume; (ii) decrease in expression of the markers of transcriptionally active chromatin; (iii) internalization and decrease in the number of nucleoli; (iv) increase in the number of pericentromeric heterochromatic clusters; and (v) increase in the frequency of associations between the pericentromeric clusters, chromosomal territory 3, and nucleoli. These data suggest a role for nucleoli and pericentromeric heterochromatin clusters as organizers of nuclear microenvironment required for proper execution of gene expression programs in differentiating KCs, and provide important background information for further analyses of alterations in the topological genome organization seen in pathological skin conditions, including disorders of epidermal differentiation and epidermal tumors.

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2005. / Typescript (photocopy).

Switches play an important regulatory role at all levels of biology, from molecular switches triggering signaling cascades to cellular switches regulating cell maturation and apoptosis. Medical therapies are often designed to toggle a system from one state to another, achieving a specified health outcome. For instance, small doses of subpathologic viruses activate the immune system’s production of antibodies. Electrical stimulation revert cardiac arrhythmias back to normal sinus rhythm. In all of these examples, a major challenge is finding the optimal stimulus waveform necessary to cause the switch to flip. This thesis develops, validates, and applies a novel model-independent stochastic algorithm, the Extrema Distortion Algorithm (EDA), towards finding the optimal stimulus. We validate the EDA’s performance for the Hodgkin-Huxley model (an empirically validated ionic model of neuronal excitability), the FitzHugh-Nagumo model (an abstract model applied to a wide range of biological systems that that exhibit an oscillatory state and a quiescent state), and the genetic toggle switch (a model of bistable gene expression). We show that the EDA is able to not only find the optimal solution, but also in some cases excel beyond the traditional analytic approaches. Finally, we have computed novel optimal stimulus waveforms for aborting epileptic seizures using the EDA in cellular and network models of epilepsy. This work represents a first step in developing a new class of adaptive algorithms and devices that flip biological switches, revealing basic mechanistic insights and therapeutic applications for a broad range of disorders.