Thesis (Ph.D.) --Murdoch University, 2004. / Thesis submitted to the Division of Science and Engineering. Includes bibliographical references.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 217-223). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves 217-223). Also available on the Internet.

Thesis (Ph. D.)--Carleton University, 1992. / Also available in electronic format on the Internet.

Thesis (M. Sc.)--Carleton University, 1993. / Includes bibliographical references. Also available in electronic format on the Internet.

Thesis (M.S.)--Villanova University, 2007. / Computer Science Dept. Includes bibliographical references.

R. Paul Wiley, Robert R. Tenney. / Bibliography: p. 34-35. / "March 1985." "24th CDC and Transactions" / "ONR/N00014-77-C-0532 (NR 041-519)" "ONR/N00014-84-K-0519 (NR 649-003)"

Este documento apresenta uma investigação sobre os relacionamentos entre os problemas de planejamento em inteligência artificial e de alcançabilidade em redes de Petri. O trabalho trata da análise de algumas maneiras de se representar um problema de planejamento como uma rede de Petri e da comparação da rede obtida com o grafo de planos. São destacadas as principais vantagens e desvantagens do uso das redes de Petri em comparação com o grafo de planos. Procura-se argumentar em favor da primeira, pois ela permite representar de maneira ao mesmo tempo precisa e econômica os mesmos relacionamentos contidos na segunda estrutura. Um dos focos da pesquisa é encontrar a melhor maneira de substituir as redundâncias presentes no grafo de planos pela dinâmica da rede de Petri. Em particular, na rede, consegue-se uma melhor representação para as relações de inconsistência e de exclusão mútua entre ações. / This thesis dissertation reports on the investigation of the relationships between the problems of planning, in the sense of Artificial Intelligence, and that of reachability, in the sense of Petri nets. The research approaches different ways to represent a planning problem as a Petri net, as well as the comparison of the given net with the plan graph. The main advantages and disadvantages in applying Petri nets compared to the plan graph method. We claim that, the use of Petri nets allows more precise and compact representation of action relationships than those obtained with the counter part method. One of the main research aims is to eliminate representational redundancies of the plan graph by projecting them against the dynamic aspects of the net. Examples of the comparative improvements are shown in the text, particularly for the relationships of inconsistency and the mutual exclusion of actions.

Neutrophils provide a rapid first response to invading pathogens and orchestrate the immune response. They are able to employ potent antipathogenic mechanisms such as phagocytosis, reactive oxygen species (ROS) generation, protease release from granules, and formation of neutrophil extracellular traps (NETs). Despite this, certain pathogens have evolved mechanisms to benefit from neutrophil effector functions. Human cytomegalovirus (HCMV) is a clinically important pathogen that infects the majority of the human population. Monocytes are considered the main vehicle of HCMV dissemination throughout the body, but little research has been done on its interaction with neutrophils. The virus encodes a range of immunomodulatory proteins including an IL-8 homologue that acts as a powerful neutrophil chemoattractant. Viral conservation of a protein that recruits neutrophils to the site of HCMV infection suggests that the interaction between neutrophils and HCMV provides an overall advantage to the virus, but little evidence exists so far to suggest this is the case. Here I report that human peripheral blood neutrophils exposed to a clinical strain of HCMV display a profound survival phenotype, as assessed by morphology, phosphatidylserine exposure, cell permeability, and caspase-3/7 activity. This occurs in the absence of viral gene production. Neutrophils also upregulated their release of inflammatory cytokines in response to HCMV, with higher concentrations of IL-6, IL-8, and MIP-1α detected in the secretomes of infected neutrophils. These secretomes induced monocyte chemotaxis and increased monocyte permissivity to HCMV infection, as well as augmented survival in healthy, uninfected neutrophils. These experiments were confirmed with clean HCMV after the discovery of contaminating Mycoplasma spp. in the viral inocula of the initial experiments. Mycoplasma-HCMV coinfection induced an autophagic phenotype in neutrophils, as assessed by Western blotting and qPCR of autophagy-related components. Inhibition of autophagy using 3-MA reversed a profound survival effect. The unintended inclusion of Mycoplasma spp. further led to the serendipitous discovery of yet another pathogenic ability to overcome neutrophil immune functions: contaminating Mycoplasma spp. as well as Mycoplasma pneumoniae profoundly degraded NETs. These extracellular chromatin structures were stimulated using PMA or pyocyanin, and their release was dependent on the generation of ROS: severely ROS-deficient murine bone marrow neutrophils were unable to generate NETs. However, small amounts of ROS were sufficient for NETs generation, as neutrophils from acute respiratory distress syndrome patients, including many that had attenuated ROS-responses, were still capable of NETs generation. The NETs-degradative properties of mycoplasma were confirmed by fluorescence confocal and scanning electron microscopy, as well as spectrophotometry and agarose gel electrophoresis. This study demonstrates that two pervasive pathogens, HCMV and M. pneumoniae, both frequently found in coinfections in clinical contexts, are able to overcome neutrophil antipathogenic mechanisms to potentially enhance pathogen dissemination. These data provide not only a novel example of manipulation of an anti-viral response in a cell not productively infected, but also a novel example of pathogenic NETs degradation. These findings may have implications on our understanding of mycoplasma and HCMV pathogenesis and provide new targets for the generation of therapies.

Many tissue-restricted diseases are linked to mutations in lamins and nuclear envelope transmembrane proteins (NETs). How these mutations in ubiquitously expressed proteins cause such defined diseases is still unknown. It is hypothesized that tissue restricted NETs that are partners of the nuclear lamins/existing linked proteins mediate tissue-specific disease pathologies. Proteomic studies have identified many tissue restricted NETs with effects on the cytoskeleton, gene positioning and regulation. This study investigates potential roles of candidate NETs in mediating tissue restricted disease pathology and their interactions with known factors such as emerin and lamins, mutations in which have been linked to a variety of tissue-specific dystrophies. This study looks into candidate tissue-specific NETs distribution in human tissues and in vitro using a solid phase binding assay to study candidate NETs interactions. I confirmed the tissue-specificity of the candidate NETs in human and mouse tissue sections but did not find clear reproducible distribution of these NETs in patient tissue biopsy. One postulate is that NETs bind WT lamin for localisation and/or function and disruption of this interaction leads to disease. Using a solid phase binding assay approach to study NETs/lamin interactions, we demonstrate that Tmem120a, an adipocyte-specific NET binds WT lamin but has a reduced Bmax when tested for binding against a lipodstrophy causing lamin mutant (R482Q and G465D). This is consistent with the hypothesis that tissue-specific NET partners might mediate tissue-specific disease pathology in lamin-linked nuclearenvelopathies.