Zugl.: München, Techn. Univ., Diss.

Tübingen, Univ., Diss., 2006.

Freiburg (Breisgau), University, Diss., 2003.

Universiẗat, Diss., 2004--Heidelberg.

University, Diss., 2004--Jena.

Influenza infection remains a constant threat to human health and results in huge financial loss annually. Rapid and accurate detection of influenza can aid health officials to monitor influenza activity and take measurements when necessary. In addition, influenza detection in a timely manner can help doctors make diagnosis and provide effective treatment. Additionally, novel inhibitors of influenza virus are in high demand because circulating strains have started to develop resistance to currently available anti-viral drugs. Influenza virus has two surface glycoproteins: hemagglutinin (HA) and neuraminidase (NA), which play important roles in the influenza infection. The binding of HA to sialic acid-containing carbohydrates on cell surface initiates virus internalization, while cleavage of terminal sialic acid by NA facilitates viral particle release. In this dissertation, we focus on the development of a glycan microarray that is comprised of a panel of NA resistant sialosides, and demonstrate the application of the microarray to capture influenza virus at ambient temperature without the addition of NA inhibitors. We also describe a novel electrochemical assay for the detection of influenza virus. In addition, we have developed a new class of bivalent NA inhibitors that show promising inhibitory activities against influenza viruses.

Made available in DSpace on 2018-08-01T21:35:01Z (GMT). No. of bitstreams: 1 tese_10831_122ª Ata de Defesa - Paola Fernandes Pansini.PDF: 76 bytes, checksum: e777df9eb60d248d167e2edfa6e23421 (MD5) Previous issue date: 2017-02-15 / O carcinoma epidermóide de cabeça e pescoço (CECP) é o sexto tipo de câncer mais comum em todo o mundo. Nos últimos anos, tem sido sugerida a participação da survivina na progressão tumoral em CECP. Este estudo teve como objetivo avaliar a survivina como potencial biomarcador de progressão tumoral em CECB. Foram utilizados no estudo dados clínicos e amostras biológicas de 115 indivíduos com carcinoma epidermóide da cavidade bucal. Lâminas contendo tecidos tumorais coradas pelo método hematoxilina e eosina foram usadas para as análises histopatológicas para avaliar o infiltrado linfocitário tumoral, padrão de invasão tumoral, gradação tumoral, invasão vascular, linfática e perineural. Tissue Microarrays foram construídos para realizar a análise imunohistoquímica da expressão da proteína survivina utilizando o anticorpo primário monoclonal de coelho anti-survivina. Para avaliar as associações entre as variáveis estudadas foram utilizados os testes Qui-Quadrado e o Exato de Fisher. A comparação das médias dos segmentos foi obtida pelo teste T de amostras independentes. As curvas de sobrevida foram calculadas pelo modelo de Kaplan-Meier e confirmadas pelo modelo multivariado de Cox. Nossos resultados mostraram existir correlação entre o infiltrado linfocitário tumoral alto, tamanho do tumor primário T1/T2 (p = 0,001) e estadiamento clínico I e II (p = 0,005). O padrão de invasão tumoral tipo IV foi correlacionado com o tamanho do tumor primário T3/T4 (p = 0,006) e estadiamento clínico avançado (estádio III e IV) (p = 0,028). Invasão perineural foi associada com o tamanho do tumor primário T1/T2 (p = 0,035). A expressão nuclear da survivina na porção mediana do tumor mostrou associação com a metástase em linfonodos regionais (p = 0,004) e o estadiamento clínico (p = 0,041). A análise regressiva multivariada confirmou que as variáveis tamanho do tumor primário (p = 0,004) e acometimento linfonodal (p= 0,06) são fatores prognósticos independentes para sobrevida global, enquanto o etilismo influencia na sobrevida livre de doença (p = 0,048). Com este estudo pode-se concluir que a elevada expressão da survivina está correlacionada com o comportamento tumoral mais agressivo, estadiamento clínico avançado, presença de mestástase linfonodal, podendo ser considerada como indicador de prognóstico em pacientes com CECB. A variável histopatológica padrão de invasão tumoral mostrou que sua correlação com tamanho do tumor primário e estadiamento clínico avançado podendo estar relacionada ao pior prognóstico dos pacientes em CECB.

This paper discusses about the data obtained from gene chips and methods of their analysis. Analyzes some methods for analyzing these data and focus on the method of "Random Forests". Shows dataset that is used for specific experiments. Methods are realized in R language environment. Than they are tested, and the results are presented and compared. Results with method "Random Forests" are compared with other experiments on same dataset.

Leptographium is an anamorph genus within the Ophiostomatoid group of fungi and represents a unique case for molecular applications. The genus has a near complete sequence data available for three genes across all known species. This characteristic makes it a perfect test group for investigating applications of new diagnostic techniques within ascomycetes. Probes and primers, for microarrays, are designed from phylogenetically useful gene regions and are fabricated onto a solid substrate using printing technology. The sample is prepared using PCR and is hybridised to the probes under stringent conditions. The resulting fluorescent pattern is rigorously analysed to distinguish species from each other. Diagnostic PCR uses primers that are designed in similar way to the way probes are designed for microarrays and indicate the presence of a species through positive amplification. This research methodology will be applied to Leptographium to evaluate the efficacy of microarray technology for discriminating species within that genus. The data gained from this research study will be used in applications for other genera using microarray technology. / Dissertation (MSc)--University of Pretoria, 2009. / Genetics / Unrestricted

Estrogen is thought to protect against the development of chronic kidney disease, and menopause increases the development and severity of diabetic kidney disease. In this study, we used streptozotocin (STZ) to induce diabetes in the 4-vinylcyclohexene diepoxide (VCD)-treated mouse model of menopause. DNA microarrays were used to identify gene expression changes in the diabetic kidney postmenopause. An ANOVA model, CARMA, was used to isolate the menopause effect between two groups of diabetic mice, diabetic menopausal (STZ/VCD) and diabetic cycling (STZ). In this diabetic study, 8,864 genes of the possible 15,600 genes on the array were included in the ANOVA; 99 genes were identified as demonstrating a >1.5-fold up- or downregulation between the STZ/VCD and STZ groups. We randomly selected genes for confirmation by real-time PCR; midkine (Mdk), immediate early response gene 3 (IEX-1), mitogen-inducible gene 6 (Mig6), and ubiquitin-specific protease 2 (USP2) were significantly increased in the kidneys of STZ/VCD compared with STZ mice. Western blot analysis confirmed that Mdk and IEX-1 protein abundance was significantly increased in the kidney cortex of STZ/VCD compared with STZ mice. In a separate study, DNA microarrays and CARMA analysis were used to identify the effect of menopause on the nondiabetic kidney; VCD-treated mice were compared with cycling mice. Of the possible 15,600 genes on the array, 9,142 genes were included in the ANOVA; 20 genes were identified as demonstrating a >1.5-fold up- or downregulation; histidine decarboxylase and vanin 1 were among the genes identified as differentially expressed in the postmenopausal nondiabetic kidney. These data expand our understanding of how hormone status correlates with the development of diabetic kidney disease and identify several target genes for further studies.