O modelo de referência para dados de contagem é o modelo de Poisson. A principal característica do modelo de Poisson é a pressuposição de que a média e a variância são iguais. No entanto, essa relação de média-variância nem sempre ocorre em dados observacionais. Muitas vezes, a variância observada nos dados é maior do que a variância esperada, fenômeno este conhecido como superdispersão. O objetivo deste trabalho constitui-se na aplicação de modelos lineares generalizados, a fim de selecionar um modelo adequado para acomodar de forma satisfatória a superdispersão presente em dados de contagem. Os dados provêm de um experimento que objetivava avaliar e caracterizar os parâmetros envolvidos no florescimento de plantas adultas da laranjeira variedade \"x11\", enxertadas nos limoeiros das variedades \"Cravo\" e \"Swingle\". Primeiramente ajustou-se o modelo de Poisson com função de ligação canônica. Por meio da deviance, estatística X2 de Pearson e do gráfico half-normal plot observou-se forte evidência de superdispersão. Utilizou-se, então, como modelos alternativos ao Poisson, os modelos Binomial Negativo e Quase-Poisson. Verificou que o modelo Quase-Poisson foi o que melhor se ajustou aos dados, permitindo fazer inferências mais precisas e interpretações práticas para os parâmetros do modelo. / The reference model for count data is the Poisson model. The main feature of Poisson model is the assumption that mean and variance are equal. However, this mean-variance relationship rarely occurs in observational data. Often, the observed variance is greater than the expected variance, a phenomenon known as overdispersion. The aim of this work is the application of generalized linear models, in order to select an appropriated model to satisfactorily accommodate the overdispersion present in the data. The data come from an experiment that aimed to evaluate and characterize the parameters involved in the flowering of orange adult plants of the variety \"x11\" grafted on \"Cravo\" and \"Swingle\". First, the data were submitted to adjust by Poisson model with canonical link function. Using deviance, generalized Pearson chi-squared statistic and half-normal plots, it was possible to notice strong evidence of overdispersion. Thus, alternative models to Poisson were used such as the negative binomial and Quasi-Poisson models. The Quasi-Poisson model presented the best fit to the data, allowing more accurate inferences and practices interpretations for the parameters.

O modelo de referência para dados de contagem é o modelo de Poisson. A principal característica do modelo de Poisson é a pressuposição de que a média e a variância são iguais. No entanto, essa relação de média-variância nem sempre ocorre em dados observacionais. Muitas vezes, a variância observada nos dados é maior do que a variância esperada, fenômeno este conhecido como superdispersão. O objetivo deste trabalho constitui-se na aplicação de modelos lineares generalizados, a fim de selecionar um modelo adequado para acomodar de forma satisfatória a superdispersão presente em dados de contagem. Os dados provêm de um experimento que objetivava avaliar e caracterizar os parâmetros envolvidos no florescimento de plantas adultas da laranjeira variedade \"x11\", enxertadas nos limoeiros das variedades \"Cravo\" e \"Swingle\". Primeiramente ajustou-se o modelo de Poisson com função de ligação canônica. Por meio da deviance, estatística X2 de Pearson e do gráfico half-normal plot observou-se forte evidência de superdispersão. Utilizou-se, então, como modelos alternativos ao Poisson, os modelos Binomial Negativo e Quase-Poisson. Verificou que o modelo Quase-Poisson foi o que melhor se ajustou aos dados, permitindo fazer inferências mais precisas e interpretações práticas para os parâmetros do modelo. / The reference model for count data is the Poisson model. The main feature of Poisson model is the assumption that mean and variance are equal. However, this mean-variance relationship rarely occurs in observational data. Often, the observed variance is greater than the expected variance, a phenomenon known as overdispersion. The aim of this work is the application of generalized linear models, in order to select an appropriated model to satisfactorily accommodate the overdispersion present in the data. The data come from an experiment that aimed to evaluate and characterize the parameters involved in the flowering of orange adult plants of the variety \"x11\" grafted on \"Cravo\" and \"Swingle\". First, the data were submitted to adjust by Poisson model with canonical link function. Using deviance, generalized Pearson chi-squared statistic and half-normal plots, it was possible to notice strong evidence of overdispersion. Thus, alternative models to Poisson were used such as the negative binomial and Quasi-Poisson models. The Quasi-Poisson model presented the best fit to the data, allowing more accurate inferences and practices interpretations for the parameters.

Le bon fonctionnement cérébral dépend de la production et du positionnement appropriés des neurones, de la formation d’une connectivité neuronale adéquate et exige un équilibre strict de la formation de synapses excitatrice et inhibitrice. Des mutations sur des gènes qui sculptent et entretiennent normalement ces processus peuvent altérer les fonctions neuronales et conduire à divers troubles du développement neurologique chez l'homme, notamment des malformations du développement cortical (MDC). Les MDC sont des causes importantes de retard mental et représentent entre 20 et 40% des cas d'épilepsie résistante aux médicaments chez les enfants. Parmi les nombreux types de MDC, l'hétérotopie nodulaire périventriculaire (HNP) est la forme la plus répandue à l'âge adulte et elle est causée par une glie radiale défectueuse qui résulte en des nodules neuronaux ectopiques tapissant les parois des ventricules latéraux. Environ 88% des patients atteints d'HPN ont une épilepsie focale et la gravité des crises peut varier de légère à rare fréquence et de rémission sans besoin de médicaments antiépileptiques à insoluble. Plusieurs gènes ont été identifiés comme cause génétique de l'HPN chez des patients, notamment FLNA et NR2F1. Aucune corrélation entre l'étendue de l'HNP et la sévérité de l'épilepsie n'a été trouvée, ce qui suggère que des circuits aberrants dans le cortex cérébral normotopique plutôt que des nodules hétérotopiques pourrait expliquer la survenue de crises. Nous avons étudié l'impact in vivo de la perte de ces gènes lors de la dendritogénèse et de la synpatogénèse, ainsi que dans la morphologie et la maturation fonctionnelle des neurones corticaux / Proper brain function depends on the adequate production and positioning of neurons, the formation of correct neuronal connectivity, and requires a strict balance of excitatory and inhibitory synapse formation. Mutations in genes that normally carve and sustain these processes can alter neuronal functions and lead to various neurodevelopmental disorders in humans, including malformations of cortical development (MCD). MCDs are important causes of mental retardation and account for 20% - 40% of drug-resistant epilepsy cases in children. Among the many types of MCD, periventricular nodular heterotopia (PNH) is the most common form in adulthood and is caused by defective radial glia that result in ectopic neural nodules lining the walls of the lateral ventricles. About 88% of PNH patients have focal epilepsy and the severity of seizures can range from mild to rare frequency and remission without the need for antiepileptic drugs to insoluble. Several genes have been identified as a genetic cause of PNH in patients, including FLNA and NR2F1. No correlation between the extent of PNH and the severity of epilepsy was found, suggesting that aberrant circuits in the normotopic cerebral cortex rather than heterotopic nodules could explain the occurrence of seizures. We studied the in vivo impact of the loss of these genes during dendritogenesis and synpatogenesis, as well as in the morphology and functional maturation of cortical neurons.

Indiana University-Purdue University Indianapolis (IUPUI) / Haemophilus ducreyi is the causative agent of the genital ulcer disease chancroid, which has been shown to facilitate the transmission of HIV. H. ducreyi is likely exposed to multiple sources of antimicrobial peptides in vivo. APs are small, cationic molecules with both bactericidal and immunomodulatory functions. Because H. ducreyi is able to establish and maintain an infection in an environment rich with antimicrobial peptides, we hypothesized that the bacterium was resistant to the bactericidal effects of these peptides. Using a 96-well AP bactericidal assay, we examined H. ducreyi susceptibility to eight human APs likely to be encountered at the site of infection, including the α-defensins human neutrophil peptide-1, human neutrophil peptide-2, human neutrophil peptide-3, and human defensin 5, the β-defensins human β defensin-2, human beta defensin-3, and human beta defensin-4, and the human cathelicidin, LL-37. H. ducreyi survival was compared to the survival of Escherichia coli ML35, a strain known to be susceptible to several antimicrobial peptides. H. ducreyi was significantly more resistant than E. coli ML35 to the bactericidal effects of all peptides tested. Furthermore, we found that representative class I and class II strains of H. ducreyi were each resistant to APs of each functional category, indicating that resistance to antimicrobial peptides could represent a conserved method of pathogenesis for H. ducreyi as a species. The H. ducreyi genome contains a homolog for the Sap influx transporter. To study the role of the H. ducreyi Sap transporter in AP resistance, we generated an isogenic sapA mutant and used the 96-well AP bactericidal assay to compare the AP susceptibility profiles of wild-type H. ducreyi, the sapA mutant and the sapA trans-complement to α-defensins, β-defensins, and LL-37. We observed a 25% decrease in the survival of the sapA mutant when it was exposed to LL-37. These findings suggest that the H. ducreyi Sap transporter plays a role in H. ducreyi resistance to LL-37, but it is likely that other AP resistance mechanisms co-exist within the bacterium.

The objectives of the study were to identify, classify, describe and map the plant communities in the proposed Highveld National Park, including the degraded Spitskop areas. Vegetation sampling was done by means of the Braun-Blanquet method and a total of 108 stratified random relevés were sampled. A numerical classification technique (TWINSPAN) was used and the result was refined by Braun-Blanquet procedures. The final results of the classification procedure were presented in the form of phytosociological tables and twelve plant communities were described. For indirect ordination, a Detrended Correspondence Analysis (DCA) algorithm was applied to the data set to confirm the phytosociological association and to assess floristic relations between communities. For direct environmental gradient analysis the Canonical Correspondence Analysis (CCA) was applied to the data using the CANOCO software program. The plant communities were combined into six management units based on similarities regarding vegetation composition, habitat, topography and soil characteristics. Characterization of land degradation was done by grouping erosion into different classes and different degrees of severity. Degraded areas in need of rehabilitation and restoration were identified and described. Recommendations were made with regard to rehabilitation and monitoring of all degraded areas in the HNP. / Thesis (M.Sc. (Botany))--North-West University, Potchefstroom Campus, 2008.

The objectives of the study were to identify, classify, describe and map the plant communities in the proposed Highveld National Park, including the degraded Spitskop areas. Vegetation sampling was done by means of the Braun-Blanquet method and a total of 108 stratified random relevés were sampled. A numerical classification technique (TWINSPAN) was used and the result was refined by Braun-Blanquet procedures. The final results of the classification procedure were presented in the form of phytosociological tables and twelve plant communities were described. For indirect ordination, a Detrended Correspondence Analysis (DCA) algorithm was applied to the data set to confirm the phytosociological association and to assess floristic relations between communities. For direct environmental gradient analysis the Canonical Correspondence Analysis (CCA) was applied to the data using the CANOCO software program. The plant communities were combined into six management units based on similarities regarding vegetation composition, habitat, topography and soil characteristics. Characterization of land degradation was done by grouping erosion into different classes and different degrees of severity. Degraded areas in need of rehabilitation and restoration were identified and described. Recommendations were made with regard to rehabilitation and monitoring of all degraded areas in the HNP. / Thesis (M.Sc. (Botany))--North-West University, Potchefstroom Campus, 2008.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O diagnóstico da hanseníase neural pura baseia-se em dados clínicos e laboratoriais do paciente, incluindo a histopatologia de espécimes de biópsia de nervo e detecção de DNA de Mycobacterium leprae (M. leprae) pelo PCR. Como o exame histopatológico e a técnica PCR podem não ser suficientes para confirmar o diagnóstico, a imunomarcação de lipoarabinomanana (LAM) e/ou Glicolipídio fenólico 1 (PGL1) - componentes de parede celular de M. leprae foi utilizada na primeira etapa deste estudo, na tentativa de detectar qualquer presença vestigial do M. leprae em amostras de nervo sem bacilos. Além disso, sabe-se que a lesão do nervo na hanseníase pode diretamente ser induzida pelo M. leprae nos estágios iniciais da infecção, no entanto, os mecanismos imunomediados adicionam severidade ao comprometimento da função neural em períodos sintomáticos da doença. Este estudo investigou também a expressão imuno-histoquímica de marcadores envolvidos nos mecanismos de patogenicidade do dano ao nervo na hanseníase. Os imunomarcadores selecionados foram: quimiocinas CXCL10, CCL2, CD3, CD4, CD8, CD45RA, CD45RO, CD68, HLA-DR, e metaloproteinases 2 e 9. O estudo foi desenvolvido em espécimes de biópsias congeladas de nervo coletados de pacientes com HNP (n=23 / 6 BAAR+ e 17 BAAR - PCR +) e pacientes diagnosticados com outras neuropatias (n=5) utilizados como controle. Todas as amostras foram criosseccionadas e submetidas à imunoperoxidase. Os resultados iniciais demonstraram que as 6 amostras de nervos BAAR+ são LAM+/PGL1+. Já entre as 17 amostras de nervos BAAR-, 8 são LAM+ e/ou PGL1+. Nas 17 amostras de nervos BAAR-PCR+, apenas 7 tiveram resultados LAM+ e/ou PGL1+. A detecção de imunorreatividade para LAM e PGL1 nas amostras de nervo do grupo HNP contribuiu para a maior eficiência diagnóstica na ausência recursos a diagnósticos moleculares. Os resultados da segunda parte deste estudo mostraram que foram encontradas imunoreatividade para CXCL10, CCL2, MMP2 e MMP9 nos nervos da hanseníase, mas não em amostras de nervos com outras neuropatias. Além disso, essa imunomarcação foi encontrada predominantemente em células de Schwann e em macrófagos da população celular inflamatória nos nervos HNP. Os outros marcadores de ativação imunológica foram encontrados em leucócitos (linfócitos T e macrófagos) do infiltrado inflamatório encontrados nos nervos. A expressão de todos os marcadores, exceto CXCL10, apresentou associação com a fibrose, no entanto, apenas a CCL2, independentemente dos outros imunomarcadores, estava associada a esse excessivo depósito de matriz extracelular. Nenhuma diferença na frequência da imunomarcação foi detectada entre os subgrupos BAAR+ e BAAR-, exceção feita apenas às células CD68+ e HLA-DR+, que apresentaram discreta diferença entre os grupos BAAR + e BAAR- com granuloma epitelioide. A expressão de MMP9 associada com fibrose é consistente com os resultados anteriores do grupo de pesquisa. Estes resultados indicam que as quimiocinas CCL2 e CXCL10 não são determinantes para o estabelecimento das lesões com ou sem bacilos nos em nervo em estágios avançados da doença, entretanto, a CCL2 está associada com o recrutamento de macrófagos e com o desenvolvimento da fibrose do nervo na lesão neural da hanseníase. / The diagnosis of pure neural leprosy (PNL) is based on clinical and laboratory data, including the histopathology of nerve biopsy specimens and detection of M. leprae DNA by polymerase chain reaction (PCR). Given that histopathological examination and PCR methods may not be sufficient to confirm diagnosis, immunolabeling of lipoarabinomanan (LAM) and/or phenolic glycolipid 1 (PGL1) M. leprae wall components were utilized in the first step of this investigation in an attempt to detect any vestigial presence of M. leprae in AFB- nerve samples. Furthermore, its well known that nerve damage in leprosy can be directly induced by Mycobacterium leprae in the early stages of infection; however, immunomediated mechanisms add gravity to the impairment of neural function in symptomatic periods of the disease. Therefore, this study also investigated the immunohistochemical expression of immunomarkers involved in the pathogenic mechanisms of leprosy nerve damage. These markers selected were CXCL10, CCL2 chemokines and CD3, CD4, CD8, CD45RA, CD45RO, CD68, HLA-DR, metalloproteinases 2 and 9 in nerve biopsy specimens collected from leprosy (23) and nonleprosy patients (5) suffering peripheral neuropathy. Twenty-three PNL nerve samples (6 AFB+ and 17 AFB-PCR+) were cryosectioned and submitted to LAM and PGL1 immunohistochemical staining by immunoperoxidase; 5 nonleprosy nerve samples were used as controls. The 6 AFB-positive samples showed LAM/PGL1 immunoreactivity. Among the 17 AFB- samples, only 8 revealed LAM and/or PGL1 immunoreactivity. In 17 AFB-PCR+ patients, just 7 had LAM and/or PGL1-positive nerve results. In the PNL cases, the detection of immunolabeled LAM and PGL1 in the nerve samples would have contributed to enhanced diagnostic efficiency in the absence of molecular diagnostic facilities. The results of the second part of this study showed that CXCL10-, CCL2-, MMP2- and MMP9-immunoreactivities were found in the leprosy nerves but not in nonleprosy samples. Immunolabeling was predominantly found in recruited macrophages and Schwann cells composing the inflammatory cellular population in the leprosy-affected nerves. The immunohistochemical expression of all the markers, but CXCL10, was associated with fibrosis; however, only CCL2 was, independently from the other markers, associated with this excessive deposit of extracellular matrix. No difference in the frequency of the immunolabeling was detected between the AFB+ and AFB- leprosy subgroups of nerves, exception made to some statistical tendency to difference in regard to CD68+ and HLA-DR+ cells in the AFB- nerves exhibiting epithelioid granuloma. MMP9 expression associated with fibrosis is consistent with previous results of this research group. The findings conveys the idea that CCL2 and CXCL10 chemokines at least in advanced stages of leprosy nerve lesions are not determinant for the establishment of AFB+ or AFB- leprosy lesions, however, CCL2 is associated with macrophage recruitment and fibrosis.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / O diagnóstico da hanseníase neural pura baseia-se em dados clínicos e laboratoriais do paciente, incluindo a histopatologia de espécimes de biópsia de nervo e detecção de DNA de Mycobacterium leprae (M. leprae) pelo PCR. Como o exame histopatológico e a técnica PCR podem não ser suficientes para confirmar o diagnóstico, a imunomarcação de lipoarabinomanana (LAM) e/ou Glicolipídio fenólico 1 (PGL1) - componentes de parede celular de M. leprae foi utilizada na primeira etapa deste estudo, na tentativa de detectar qualquer presença vestigial do M. leprae em amostras de nervo sem bacilos. Além disso, sabe-se que a lesão do nervo na hanseníase pode diretamente ser induzida pelo M. leprae nos estágios iniciais da infecção, no entanto, os mecanismos imunomediados adicionam severidade ao comprometimento da função neural em períodos sintomáticos da doença. Este estudo investigou também a expressão imuno-histoquímica de marcadores envolvidos nos mecanismos de patogenicidade do dano ao nervo na hanseníase. Os imunomarcadores selecionados foram: quimiocinas CXCL10, CCL2, CD3, CD4, CD8, CD45RA, CD45RO, CD68, HLA-DR, e metaloproteinases 2 e 9. O estudo foi desenvolvido em espécimes de biópsias congeladas de nervo coletados de pacientes com HNP (n=23 / 6 BAAR+ e 17 BAAR - PCR +) e pacientes diagnosticados com outras neuropatias (n=5) utilizados como controle. Todas as amostras foram criosseccionadas e submetidas à imunoperoxidase. Os resultados iniciais demonstraram que as 6 amostras de nervos BAAR+ são LAM+/PGL1+. Já entre as 17 amostras de nervos BAAR-, 8 são LAM+ e/ou PGL1+. Nas 17 amostras de nervos BAAR-PCR+, apenas 7 tiveram resultados LAM+ e/ou PGL1+. A detecção de imunorreatividade para LAM e PGL1 nas amostras de nervo do grupo HNP contribuiu para a maior eficiência diagnóstica na ausência recursos a diagnósticos moleculares. Os resultados da segunda parte deste estudo mostraram que foram encontradas imunoreatividade para CXCL10, CCL2, MMP2 e MMP9 nos nervos da hanseníase, mas não em amostras de nervos com outras neuropatias. Além disso, essa imunomarcação foi encontrada predominantemente em células de Schwann e em macrófagos da população celular inflamatória nos nervos HNP. Os outros marcadores de ativação imunológica foram encontrados em leucócitos (linfócitos T e macrófagos) do infiltrado inflamatório encontrados nos nervos. A expressão de todos os marcadores, exceto CXCL10, apresentou associação com a fibrose, no entanto, apenas a CCL2, independentemente dos outros imunomarcadores, estava associada a esse excessivo depósito de matriz extracelular. Nenhuma diferença na frequência da imunomarcação foi detectada entre os subgrupos BAAR+ e BAAR-, exceção feita apenas às células CD68+ e HLA-DR+, que apresentaram discreta diferença entre os grupos BAAR + e BAAR- com granuloma epitelioide. A expressão de MMP9 associada com fibrose é consistente com os resultados anteriores do grupo de pesquisa. Estes resultados indicam que as quimiocinas CCL2 e CXCL10 não são determinantes para o estabelecimento das lesões com ou sem bacilos nos em nervo em estágios avançados da doença, entretanto, a CCL2 está associada com o recrutamento de macrófagos e com o desenvolvimento da fibrose do nervo na lesão neural da hanseníase. / The diagnosis of pure neural leprosy (PNL) is based on clinical and laboratory data, including the histopathology of nerve biopsy specimens and detection of M. leprae DNA by polymerase chain reaction (PCR). Given that histopathological examination and PCR methods may not be sufficient to confirm diagnosis, immunolabeling of lipoarabinomanan (LAM) and/or phenolic glycolipid 1 (PGL1) M. leprae wall components were utilized in the first step of this investigation in an attempt to detect any vestigial presence of M. leprae in AFB- nerve samples. Furthermore, its well known that nerve damage in leprosy can be directly induced by Mycobacterium leprae in the early stages of infection; however, immunomediated mechanisms add gravity to the impairment of neural function in symptomatic periods of the disease. Therefore, this study also investigated the immunohistochemical expression of immunomarkers involved in the pathogenic mechanisms of leprosy nerve damage. These markers selected were CXCL10, CCL2 chemokines and CD3, CD4, CD8, CD45RA, CD45RO, CD68, HLA-DR, metalloproteinases 2 and 9 in nerve biopsy specimens collected from leprosy (23) and nonleprosy patients (5) suffering peripheral neuropathy. Twenty-three PNL nerve samples (6 AFB+ and 17 AFB-PCR+) were cryosectioned and submitted to LAM and PGL1 immunohistochemical staining by immunoperoxidase; 5 nonleprosy nerve samples were used as controls. The 6 AFB-positive samples showed LAM/PGL1 immunoreactivity. Among the 17 AFB- samples, only 8 revealed LAM and/or PGL1 immunoreactivity. In 17 AFB-PCR+ patients, just 7 had LAM and/or PGL1-positive nerve results. In the PNL cases, the detection of immunolabeled LAM and PGL1 in the nerve samples would have contributed to enhanced diagnostic efficiency in the absence of molecular diagnostic facilities. The results of the second part of this study showed that CXCL10-, CCL2-, MMP2- and MMP9-immunoreactivities were found in the leprosy nerves but not in nonleprosy samples. Immunolabeling was predominantly found in recruited macrophages and Schwann cells composing the inflammatory cellular population in the leprosy-affected nerves. The immunohistochemical expression of all the markers, but CXCL10, was associated with fibrosis; however, only CCL2 was, independently from the other markers, associated with this excessive deposit of extracellular matrix. No difference in the frequency of the immunolabeling was detected between the AFB+ and AFB- leprosy subgroups of nerves, exception made to some statistical tendency to difference in regard to CD68+ and HLA-DR+ cells in the AFB- nerves exhibiting epithelioid granuloma. MMP9 expression associated with fibrosis is consistent with previous results of this research group. The findings conveys the idea that CCL2 and CXCL10 chemokines at least in advanced stages of leprosy nerve lesions are not determinant for the establishment of AFB+ or AFB- leprosy lesions, however, CCL2 is associated with macrophage recruitment and fibrosis.