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Dissertations / Theses on the topic 'DNA microarrays gene expression'

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Published: 4 June 2021

Last updated: 11 February 2022

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1

Szeto, Lap Keung. "Clustering analysis of microarray gene expression data /." access full-text access abstract and table of contents, 2005. http://libweb.cityu.edu.hk/cgi-bin/ezdb/thesis.pl?mphil-it-b19885817a.pdf.

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Thesis (M.Phil.)--City University of Hong Kong, 2005.<br>"Submitted to Department of Computer Engineering and Information Technology in partial fulfillment of the requirements for the degree of Master of Philosophy" Includes bibliographical references (leaves 70-79)

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Pendleton, Carly R. "A simulation-based approach for evaluating gene expression analyses /." Diss., CLICK HERE for online access, 2007. http://contentdm.lib.byu.edu/ETD/image/etd1753.pdf.

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Alleyne, Renikko. "Tool for the identification of differentially expressed genes using a user-defined threshold /." Link to online version, 2006. https://ritdml.rit.edu/dspace/handle/1850/2363.

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Gelmi, Claudio A. "A novel probabilistic framework for microarray data analysis from fundamental probability models to experimental validation /." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 177 p, 2007. http://proquest.umi.com/pqdweb?did=1257806411&sid=6&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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Au, Siu Kie. "Gene expression profiling of non-small cell lung cancer using cDNA microarrays /." access full-text access abstract and table of contents, 2009. http://libweb.cityu.edu.hk/cgi-bin/ezdb/thesis.pl?phd-bch-b23749490f.pdf.

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Thesis (Ph.D.)--City University of Hong Kong, 2009.<br>"Submitted to Department of Biology and Chemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy." Includes bibliographical references (leaves 133-147)

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Tjaden, Brian C. "Computational methods for transcription anlysis using oligonucleotide microarrays /." Thesis, Connect to this title online; UW restricted, 2003. http://hdl.handle.net/1773/6907.

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Jiang, Ying, and 蔣穎. "Studies of gene regulation using microarray data." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B29976388.

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Srivastava, Gyan Prakash Xu Dong. "Genome scale meta analysis of microarrays for biological inferences." Diss., Columbia, Mo. : University of Missouri--Columbia, 2009. http://hdl.handle.net/10355/6841.

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Title from PDF of title page (University of Missouri--Columbia, viewed on April 5, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Dong Xu. Vita. Includes bibliographical references.

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Kirk, Michael School of Biotechnology &amp Biomolecular Science UNSW. "Bioinformatic analyses of microarray experiments on genetic control of gene expression level." Awarded by:University of New South Wales. School of Biotechnology and Biomolecular Science, 2006. http://handle.unsw.edu.au/1959.4/25986.

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The advent of microarray technology, allowing measurement of gene expression levels for thousands of genes in parallel, has made possible experiments designed to investigate the genetic control of variation in gene expression level (described in the literature as ???genetical genomics??? or ???eQTL??? experiments). Published results from these studies, in yeast and in mice, show that genetic variation is an important factor in gene regulation, and furthermore that individual polymorphisms modify the expression level of many genes. The concern of this thesis is the bioinformatic analyses of the expression level and genotype data sets that are the raw material for these studies. In particular this thesis addresses the two issues of detection of artefactual effects, and maximizing the information that can be extracted from the data. It is shown that while a polymorphism affecting the expression of many genes may be readily detected, care must be taken to determine whether the detected effect is genuinely one of genetic control of expression level, rather than the effect of correlations in measured expression level not of genetic cause. A significance test is devised to distinguish between these cases. The detection of artefactual correlation is explored further in the reanalysis of the published data from a large yeast study. A critique is given of the permutation method used to ascribe genetic control as the cause of inter gene expression level correlation. The presence of some degree of artefactual correlation is shown, and novel methods are presented for identifying such artefacts. To extend the analyses that may be applied to eQTL data, an algorithm is presented for determining secondary eQTLs for gene expression level (as opposed to a single primary QTL), along with a significance test for the putative QTL found. The technique is demonstrated on a large public data set. In addition to the use for which they are intended, the data sets generated for eQTL studies provide opportunities for additional analyses. In this thesis a method is developed for calculating a genome wide map of meiotic recombination frequency from the genotype data for multiple segregant strains. The method is demonstrated on the published genotype data generated for a large yeast eQTL study.

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Kannan, Anusha Aiyalu. "Detecting relevant changes in high throughput gene expression data /." Online version of thesis, 2008. http://hdl.handle.net/1850/10832.

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Wang, Tao. "Statistical design and analysis of microarray experiments." Connect to this title online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1117201363.

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Thesis (Ph. D.)--Ohio State University, 2005.<br>Title from first page of PDF file. Document formatted into pages; contains ix, 146 p.; also includes graphics (some col.) Includes bibliographical references (p. 145-146). Available online via OhioLINK's ETD Center

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章明明 and Ming-ming Cheung. "An examination of the regulation of gene expression using microarray and genomic resources." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B31225809.

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Cheung, Ming-ming. "An examination of the regulation of gene expression using microarray and genomic resources /." Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25205717.

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Leader, Debbie. "Methods for incorporating biological information into the statistical analysis of gene expression microarray data." Thesis, University of Auckland, 2009. http://hdl.handle.net/2292/5609.

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Microarray technology has made it possible for researchers to simultaneously measure the expression levels of tens of thousands of genes. It is believed that most human diseases and biological phenomena occur through the interaction of groups of genes that are functionally related. To investigate the feasibility of incorporating functional information and/or constraints (based on biological and technical needs) into the classification process two approaches were examined in this thesis. The first of these approaches investigated the effect of incorporating a pre-filter into the gene selection step of the classifier construction process. Both simulated and real microarray datasets were used to assess the utility of this approach. The pre-filter was based on an early method for determining if a gene had undergone a biologically relevant level of differential expression between two classes. The genes retained by the pre-filter were ranked using one of five standard statistical ranking methods and the most highly ranked were used to construct a predictive classifier. To generate the simulated data a selection of different parametric and non-parametric techniques were employed. The results from these analyses showed that when the constraints that the pre-filter contains were placed on the classification analysis, the predictive performance of the classifiers were similar to when the pre-filter was not used. The second approach explored the feasibility of incorporating sets of functionally related genes into the classification process. Three publicly available datasets obtained from studies into breast cancer were used to assess the utility of this approach. A summary of each gene-set was derived by reducing the dimensionality of each gene-set via the use of Principal Co-ordinates Analysis. The reduced gene-sets were then ranked based on their ability to distinguish between the two classes (via Hotelling’s T2) and those most highly ranked were used to construct a classifier via logistic regression. The results from the analyses undertaken for this approach showed that it was possible to incorporate function information into the classification process whilst maintaining an equivalent (if not higher) level of predictive performance, as well as improving the biological interpretability of the classifier.

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Zhao, Hongya. "Statistical analysis of gene expression data in cDNA microarray experiments." HKBU Institutional Repository, 2006. http://repository.hkbu.edu.hk/etd_ra/657.

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Rickman, Lisa. "Global regulators of gene expression in Mycobacterium tuberculosis : functional analysis using DNA microarrays." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.404827.

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Jose, Adarsh. "Gene selection by 1-D discrete wavelet transform for classifying cancer samples using DNA microarray data." Akron, OH : University of Akron, 2009. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=akron1240851642.

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Dissertation (Ph. D.)--University of Akron, Dept. of Chemical and Biomedical Engineering, 2009.<br>"May, 2009." Title from electronic dissertation title page (viewed 8/3/2009) Advisor, Dale H. Mugler; Co-advisor, Zhong-Hui Duan; Committee members, Daniel B. Sheffer; Department Chair, Daniel B. Sheffer; Dean of the College, George K. Haritos; Dean of the Graduate School, George R. Newkome. Includes bibliographical references.

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Ribeiro, Adèle Helena. "Análise de expressões gênicas com erros de medida e aplicação em dados reais." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/45/45134/tde-04082014-163616/.

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Toda medida, desde que feita por um instrumento real, tem uma imprecisão associada. Neste trabalho, abordamos a questão das imprecisões em experimentos de microarranjos de cDNA de dois canais, uma tecnologia que tem sido muito explorada nos últimos anos e que ainda é um importante auxiliar nos estudos de expressões gênicas. Dezenas de milhares de representantes de genes são impressos em uma lâmina de vidro e hibridizados simultaneamente com RNA mensageiro de duas amostras diferentes de células. Essas amostras são marcadas com corantes fluorescentes diferentes e a lâmina, após a hibridização, é digitalizada, obtendo-se duas imagens. As imagens são analisadas com programas especiais que segmentam os locais que estavam os genes e extraem estatísticas dos píxeis de cada local. Por exemplo, a média, a mediana e a variância das intensidades do conjunto de píxeis de cada local (o mesmo é feito normalmente para uma área em volta de cada local, chamada de fundo). Estimadores estatísticos como o da variância nos dão uma estimativa de quão precisa é uma certa medida. Uma vez de posse das estimativas das intensidades de cada local, para se obter a efetiva expressão de um gene, algumas transformações são feitas nos dados de forma a eliminar variabilidades sistemáticas. Neste trabalho, mostramos como podem ser feitas as análises a partir de uma medida de expressão gênica com um erro estimado. Mostramos como estimar essa imprecisão e estudamos, em termos de propagação da imprecisão, os efeitos de algumas transformações realizadas nos dados, por exemplo, a remoção do viés estimado pelo método de regressão local robusta, mais conhecido como \\textit{lowess}. Uma vez obtidas as estimativas das imprecisões propagadas, mostramos também como utilizá-las na determinação dos genes diferencialmente expressos entre as amostras estudadas. Por fim, comparamos os resultados com os obtidos por formas clássicas de análise, em que são desconsideradas as imprecisões das medidas. Concluímos que a modelagem das imprecisões das medidas pode favorecer as análises, já que os resultados obtidos em uma aplicação com dados reais de expressões gênicas foram condizentes com os que encontramos na literatura.<br>Any measurement, since it is made for a real instrument, has an uncertainty associated with it. In the present paper, we address this issue of uncertainty in two-channel cDNA Microarray experiments, a technology that has been widely used in recent years and is still an important tool for gene expression studies. Tens of thousands of gene representatives are printed onto a glass slide and hybridized simultaneously with mRNA from two different cell samples. Different fluorescent dyes are used for labeling both samples. After hybridization, the glass slide is scanned yielding two images. Image processing and analysis programs are used for spot segmentation and pixel statistics computation, for instance, the mean, median and variance of pixel intensities for each spot. The same statistics are computed for the pixel intensities in the background region. Statistical estimators such as the variance gives us an estimate of the accuracy of a measurement. Based on the intensity estimates for each spot, some data transformations are applied in order to eliminate systematic variability so we can obtain the effective gene expression. This paper shows how to analyze gene expression measurements with an estimated error. We presented an estimate of this uncertainty and we studied, in terms of error propagation, the effects of some data transformations. An example of data transformation is the correction of the bias estimated by a robust local regression method, also known as \\textit{lowess}. With the propagated errors obtained, we also showed how to use them for detecting differentially expressed genes between different conditions. Finally, we compared the results with those obtained by classical analysis methods, in which the measurement errors are disregarded. We conclude that modeling the measurements uncertainties can improve the analysis, since the results obtained in a real gene expressions data base were consistent with the literature.

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Lepikson-Neto, Jorge 1980. "Analise da expressão genica em diferentes especies de eucalipto utilizando a tecnologia de microarranjos de cDNA." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/314279.

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Orientador: Gonçalo Amarante Guimães Pereira<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-12T09:23:56Z (GMT). No. of bitstreams: 1 Lepikson-Neto_Jorge_M.pdf: 1765356 bytes, checksum: c73289c953d58c6b221c2e0927805499 (MD5) Previous issue date: 2008<br>Resumo: Com o intuito de obter informações relevantes para o melhoramento genético do eucalipto para a produção de biomassa, o presente trabalho buscou comparar a expressão dos genes relacionados com a formação e desenvolvimento da madeira em quatro diferentes espécies de eucalipto, tendo como objetivo identificar os padrões que as tornam mais aptas, bem como quais genes relacionados com determinadas características. Essa análise abre a possibilidade da identificação de genes chave que possam ser manipulados, através do melhoramento clássico ou da transgênia, para aumentar o conteúdo relativo de celulose das plantas, incrementando a sua eficiência para processos econômicos. 384 ESTs do banco de dados do Consórcio Genolyptus foram selecionadas para serem analisadas através da tecnologia de microarranjos de cDNA. Foram selecionadas ESTs de genes com funções conhecidas relacionadas com a formação da madeira, bem como de genes relacionados com o desenvolvimento do vegetal e de genes com função ainda desconhecida. Os dados obtidos foram cruzados com a biblioteca de ESTs do Consorcio Genolyptus (Northern Eletrônico), e foram feitos PCR em tempo real para os principais genes diferenciais nos microarranjos e para os genes da via de lignina e flavonóides. Os resultados mostraram que diferentes genes estão expressos nas espécies estudadas sendo um grande número deles ainda com função desconhecida no metabolismo do eucalipto. A maioria dos genes relacionados com a formação da parede celular não apresentou perfil de expressão diferencial nos microarranjos, sugerindo que as diferenças fenotípicas entre as madeiras das espécies estudadas podem estar sustentadas em vias alternativas, com fatores de elongação, cliclínas e outros genes desempenhando papel importante, bem como genes ainda não relacionados com o desenvolvimento da parede celular e ou ao desenvolvimento do vegetal. Os experimentos com PCR em tempo real mostraram que genes da via de flavonóides relacionados com a via de lignina e formação da madeira podem estar desempenhando papeis importantes no controle da formação da madeira da espécie. Esses resultados representam avanços significativos no entedimento da formação da madeira em eucalipto e servem como base para orientar futuras investigações no intuito de melhorar geneticamente esta espécie.<br>Abstract: In this work we intended to assemble relevant information for the genetic engineering of Eucalyptus for biomass production by comparing gene expression of genes related with the xylem and wood development of four different Eucalyptus species with distinct caractheristics, as a form to identify patterns and wich genes are possibly related to their differences. This analysis opens the possibilities to manipulate the specie and increase the overall celluloses content and its purpose for industrial production. 384 ESTs were selected from de Genolyptus database and analysed by microarryay cDNA experiments. Among the ESTs selected some were related to wood formation, cell wall assembly and some still had no general function known on the specie. The data from the microarray experiments were then crossed with the Genolyptus ESTs lybrary (Eletronic Northern) and Real-Time PCR were performed for the most relevant resultas as well as the genes from de lignin and flavonoid pathway. Results show that different genes are expressed among the xylem of the four species studied and most of them still have no related function to the metabolism of the plant. Most of the genes related to cell wall formation were not differentially expressed on the microarrays suggesting that the differences on the quality and structure of the wood among the four species might as well be resulted from the expression of alternative pathways and genes such as elongation factors, ciclins and others not yet related to the cell wall formation and wood development. Real-Time PCR experiments shown that genes from the flavonoid pathway related to lignin and wood formation might be playing a crucial role determining wicht pathway must be followed and therefore the type and quality of the wood on Eucalyptus. These results represent significant advances to our understanding on the formation of wood on Eucalyptus and will be valuable as a basis for future investigation aiming genetic engeneering of the specie.<br>Mestrado<br>Bioquimica<br>Mestre em Biologia Funcional e Molecular

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Tomascik-Cheeseman, Lisa Marie. "Gene expression profiling in prepubertal and adult male mice using cDNA and oligonucleotide microarrays." Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=2813.

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Thesis (Ph. D.)--West Virginia University, 2003.<br>Title from document title page. Document formatted into pages; contains xiii, 180 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 138-151).

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Xie, Dan, and 謝丹. "Application of high-throughput tissue microarray technology in cancer research." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B30283619.

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Khan, Rishi Lee. "Engineering systems neuroscience modeling of a key adaptive brain control system involved in hypertension /." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 281 p, 2007. http://proquest.umi.com/pqdweb?did=1362523091&sid=21&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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Van, Laar Ryan. "Optimisation of cDNA microarray tumour profiling and molecular analysis of epithelial ovarian cancer /." Connect to thesis, 2005. http://eprints.unimelb.edu.au/archive/00002764.

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Rysä, J. (Jaana). "Gene expression profiling in experimental models of cardiac load." Doctoral thesis, University of Oulu, 2008. http://urn.fi/urn:isbn:9789514287664.

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Abstract Cardiac hypertrophy provides an adaptive mechanism to maintain cardiac output in response to increased workload, and although initially beneficial, hypertrophy eventually leads to heart failure, a major cause of morbidity and mortality in Western countries. The hypertrophic response in cardiac myocytes is accompanied by e.g. activation of signal transduction pathways, such as mitogen-activated protein kinases (MAPKs), and complex changes in gene programming. The purpose of this study was to characterize gene expression patterns in experimental models of cardiac load by using high-throughput DNA microarray technologies. In the present study, changes in gene expression were evaluated in response to acute pressure overload and prolonged hypertension as well as during the development of left ventricular hypertrophy (LVH) and the transition to diastolic heart failure in an animal model of genetic hypertension, the spontaneously hypertensive rat (SHR). Increased expression of several immediate early genes was seen in response to acute hemodynamic overload in vivo. The transition from LVH to diastolic hypertensive heart failure was almost exclusively associated with changes in genes encoding extracellular matrix proteins and their regulatory processes showing the importance of progressive extracellular matrix remodeling. The effect of p38 MAPK activation on gene expression patterns in vivo was elucidated. Cardiac-specific overexpression of p38 MAPK resulted in upregulation of genes controlling cell division and inflammation as well as cell signaling and adhesion. Accordingly, the functional role of p38 MAPK was related to myocardial cell proliferation, inflammation and fibrosis. Finally, temporal analysis of mechanical stretch induced gene expression changes in neonatal rat cardiomyocyte cultures in vitro indicated that mechanical stretch induced complex gene expression profiles, demonstrating that both positive and negative regulators are involved in the hypertrophic process. Many novel stretch responsive genes were identified, and a subset of them may be putative downstream targets of p38 MAPK. In conclusion, in the present study a number of well-established gene expression changes of cardiac hypertrophy were observed and novel modulators associated with increased cardiac load, such as thrombospondin-4, were identified. The study provides a better understanding of molecular mechanisms associated with increased cardiac load, and may indicate potential targets for novel therapeutic interventions.

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Goh, Liang. "Computational methods for microarray gene expression analysis through integration and knowledge discovery a thesis submitted to Auckland University of Technology in partial fulfillment of the degree of Doctor of Philosophy, 2005." Full thesis. Abstract, 2005. http://puka2.aut.ac.nz/ait/theses/GohL.pdf.

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Yap, Yee-leng Daniel. "Expression profiling of Bacillus subtilis sulfur responsive genes using S-methyl-cysteine (SMeC) as sole sulfur source." Thesis, Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36602425.

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Pashalidis, Stefano. "Análise de expressão gênica de Xylella fastidiosa cultivada em diferentes concentrações de glicose pela técnica de microarrays de DNA." Universidade de São Paulo, 2005. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-21062016-142016/.

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Xylella fastidiosa (Xf) é o agente etiológico causador de doenças em uma grande variedade de cultivos de grande importância econômica, causando a c1orose variegada dos citros, uma das doenças mais danosas à indústria de citros no Brasil. Os genomas de algumas cepas deste fitopatógeno foram completamente seqüenciados promovendo assim estudos funcionais do genoma em larga escala. Neste trabalho nós nos propusemos a investigar o perfil de transcrição de Xf através da técnica microarranjos (no título da dissertação microarrays, mas a partir de agora usaremos microaarranjos) de DNA usando todo o genoma do fitopatógeno e cultivando-a sob meio definido variando a concentração de glicose. O objetivo inicial deste trabalho era observar se Xf comportava-se da mesma forma que Xac, que tem a expressão de goma aumentada devido ao aumento da concentração de glicose do meio. Nossas análises revelaram que enquanto os transcritos relacionados à goma não se mostraram afetados com a concentração de glicose, genes que codificam para análogos a Colicina-V e precursores de fimbria foram induzidos em alta concentração de glicose. Baseados nestes resultados, nós propusemos um modelo de mecanismo de produção e defesa contra a Colicina em Xf.<br>Abstract not available.

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Roberts, Kim G. "Exploration of the ErbB/Ras/MAPK signaling pathway in cancer by gene expression profiling with isoform-specific assay development and microarray technology." Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 169 p, 2007. http://proquest.umi.com/pqdweb?did=1362532051&sid=1&Fmt=2&clientId=8331&RQT=309&VName=PQD.

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Towler, James Charles. "Transcriptome activity of human cytomegalovirus (strain Merlin) in fibroblasts, epithelial cells and astrocytes." Thesis, Connect to e-thesis record to view abstract. Move to record for print version, 2007. http://theses.gla.ac.uk/42/.

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Thesis (Ph.D.) - University of Glasgow, 2007.<br>Ph.D. thesis submitted to the Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, 2007. Includes bibliographical references. Print version also available.

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Kim, Jin-Goel. "Comparative transcriptional profiling of the uterus according to stage of the estrous cycle and pregnancy status in gilts." Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/5073.

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Thesis (M.S.)--University of Missouri-Columbia, 2007.<br>The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on April 9, 2009) Vita. Includes bibliographical references.

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Baptista, Juliana Cristina 1979. "Sinalização por manose em Arabidopsis thaliana." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317158.

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Orientador: Michel Georges Albert Vincentz<br>Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-23T15:00:26Z (GMT). No. of bitstreams: 1 Baptista_JulianaCristina_D.pdf: 14259949 bytes, checksum: d33465f0d6490d2c792f6ee701daa4bd (MD5) Previous issue date: 2013<br>Resumo: O resumo poderá ser visualizado no texto completo da tese digital<br>Abstract: The abstract is available with the full electronic document<br>Doutorado<br>Genetica Vegetal e Melhoramento<br>Doutora em Genética e Biologia Molecular

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Begum, Mst Ferdouse. "Gene expression analysis of microarray data : a case study of papilllary thyroid carcinoma data." Virtual Press, 2007. http://liblink.bsu.edu/uhtbin/catkey/1371194.

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Microarray technology allows researchers to monitor the mRNA transcription levels of thousands of genes in parallel which opens the door for more advanced cancer research. This thesis focuses on a case study of papillary thyroid carcinoma data. Fourteen publicly available Affymetrix microarray data sets were used where seven samples were collected from normal thyroid tissue and the remaining seven were collected from papillary thyroid carcinoma tissue. The present study compared the results obtained from three different normalization processes: MAS5.0, RMA and GCRMA in detecting differentially expressed genes under two conditions. Internal consistencies within the methods as well as the results across three methods were compared. Statistical packages 82.5.1 and Bioconductor 2.08 are used to perform the data analysis. Each step of normalization with MAS5.0 and RMA is described. Statistical package Limma is used to fit a linear model. Finally an empirical Bayes method is used to detect the significantly differentially expressed genes. First, considering all genes a comparison is made among the three normalization methods where RMA and GCRMA showed the maximum agreement in detecting differentially expressed genes. Then using unspecified filtering process a set of genes was selected and the whole process was replicated where the top fifty differentially expressed genes did not show any overlap with each other.<br>Department of Mathematical Sciences

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Guo, Dongli. "Expression of Wnt signaling targets and their clinico-pathological significance in colorectal neoplasm a tissue microarray study /." Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B38610541.

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Roberge, Christopher (Christopher M. ). "Design, manufacture, and application of DNA microarrays to study gene expression phenotypes of lysine-producing Corynebacterium glutamicum." Thesis, Massachusetts Institute of Technology, 2005. http://hdl.handle.net/1721.1/32322.

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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2005.<br>Includes bibliographical references (leaves 197-213).<br>Corynebacterium glutamicum partial genome DNA microarrays were constructed that were capable of assaying the transcriptional profile of the genes of pathways involved in central carbon metabolism and lysine biosynthesis. It was found that to ensure arrays of high quality, protocols applying the arrays should include DNase treatment of RNA samples. additional RNA filtration purification steps, and the use of gene specific primers in the formation of labeled cDNA through reverse transcription. After implementing these procedures, the accuracy and reproducibility of the array data were validated. The microarrays were used to explore the effects of the over-expression of the key anaplerotic enzyme pyruvate carboxylase and the use of different medium carbon source compositions, both of which have been shown to influence the yields of biomass on carbon and of lysine on biomass. Three different strains of C. glutamicum that were grown on six different minimal medium formulations that varied in their balance of glucose and lactate were assayed by isolating total mRNA samples from cultures in three different phases of growth and lysine production. Genes associated with glycolysis and the pentose phosphate pathway showed decreased transcript concentrations as the available carbon source was shifted from glucose to lactate, while those associated with the TCA cycle and the glyoxylate bypass demonstrated increased transcription. As the cultures stopped generating biomass and began generating lysine, mRNA of genes associated with lysine synthesis and export was measured at elevated concentrations.<br>(cont.) Reduced gene expression trends seen for aspartokinase and aspartate semialdehyde dehydrogenase suggest that the enzymes are bottlenecks to lysine production, particularly when pyruvate carboxylase is over-expressed and lactate is the available carbon source. This over-expressing strain also had higher transcription levels of the genes of biotin synthesis. and lower transcription levels of the acyl-coA carboxylases dtsRl, dtsR2, accC, and accD. Other results implied that malic enzyme is co-expressed with pyruvate carboxylase to better allow cultures grown on lactate to produce NADPH in the absence of significant pentose phosphate pathway flux. Also, the transcriptional and flux profiles of a pair of C. glutamicum strains grown on two different medium compositions of isotopically labeled glucose and lactate were determined simultaneously from the same set of actively growing and lysine-producing cultures. Flux maps for each of the four combinations of strain and medium were constructed using calculations derived from metabolite balances and GC-MS measurements of the isotopic distributions within biomass hydrolysates of the pseudo-steady-state cultures. Comparisons of the two sets of data showed that 19 of 28 pairs of flux and transcription measurements had trends with good agreement with one another. Different pathways of the metabolic network were found to be controlled via transcription in varying degrees. On average, the Embden- Meyerhof-Parnas pathway was shown to be less likely to be regulated though transcription than the pathways of the tricarboxylic acid cycle and central carbon anaplerosis.<br>(cont.) In the split pathway available to the cells for producing lysine, the succinylation branch showed an increase in flux for only the case of a pyruvate carboxylase over-expressing strain that was grown on lactate, while the alternate dehydrogenation branch showed a complementary decrease in flux. These flux changes were matched by changes in transcription that only occurred for the same culture and growth medium. Through these findings we have demonstrated the application of C. glutamicum DNA microarrays to the determination of how the cells regulate their responses at the transcriptional level to changes in both gene over-expression and medium composition.<br>by Christopher Roberge.<br>Ph.D.

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Beaulieu, Julie. "Exploration of high-density oligoarrays as tools to assess substantial equivalence of genetically modified crops." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=97904.

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Since the early 1990s, the concept of substantial equivalence has been a guiding principle of the Canadian Food Inspection Agency and Health Canada's regulatory approach toward products of plant biotechnology destined for the food and livestock feed markets. To assess substantial equivalence in terms of chemical composition, genetically modified (GM) plants are compared to conventional counterparts at the level of macro- and micro-nutrients, allergens and toxicants. Such targeted comparative analyses are limited in their scope and their capacity to detect unintended changes in chemical composition. There is a need to develop more effective testing protocols to improve the substantial equivalence assessment of GM crops. The objective of this thesis was to explore high-density oligoarrays as tools to assess substantial equivalence of Roundup Ready(TM) soybean. Three conventional and two GM soybean varieties were selected according to the similarity of their performance in field trials. Total RNA was extracted from first trifoliate leaves harvested from soybean plants grown in a controlled environment until the V2 stage. To annotate the 37 776 soybean probesets present on the multi-organism Soybean Affymetrix GeneChip(TM), consensus sequences were aligned with TIGR Soybean Gene Index tentative consensus sequences using BLASTN. After redefining the chip description file to exclude non-soybean probesets, the effects of three different normalization methods (Robust Multichip Average (RMA), Microarray Analysis Suite (MAS 5.0) and Model-Based Expression Index) were compared and Significance Analysis of Microarrays (SAM for R-Bioconductor) was applied to detect differential gene expression between conventional and GM soybean varieties. Eleven candidate genes were selected for further studies.

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Schultz, Nikolaus. "Unraveling spermatogenesis: gene expression profiling with DNA microarrays reveals genes critical for germ cell development, fertilization and stem cell maintenance." [S.l. : s.n.], 2004. http://www.diss.fu-berlin.de/2004/178/index.html.

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Lorencini, Márcio 1981. "Avaliação global de transcritos associados ao envelhecimento da epiderme humana utilizando microarranjos de DNA = Global evaluation of transcripts associated to human epidermal aging with DNA microarrays." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/317175.

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Orientador: Nilson Ivo Tonin Zanchin<br>Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia<br>Made available in DSpace on 2018-08-24T14:29:49Z (GMT). No. of bitstreams: 1 Lorencini_Marcio_D.pdf: 16348273 bytes, checksum: 4ed299b197892b0d3297e6e6a65d947c (MD5) Previous issue date: 2014<br>Resumo: Com o aumento do tempo de vida da população humana muitas modalidades médicas, incluindo a dermatologia, deparam-se com uma revolução na forma de garantir saúde e qualidade de vida aos pacientes. Em contato com o ambiente externo, a pele representa um órgão no qual as mudanças com o envelhecimento causam danos funcionais, além de potencial impacto estético e psicossocial. A epiderme, camada mais externa da pele, constitui uma barreira seletiva com destacada capacidade de renovação e manutenção da homeostasia corporal. Entretanto, o entendimento de diversos mecanismos associados à fisiologia e envelhecimento da epiderme permanece como desafio para a comunidade científica. Com base nesse cenário, o objetivo do presente trabalho foi compreender o atual estado da arte no tema de envelhecimento da epiderme e realizar experimentos voltados para lacunas existentes, com foco na integração de aspectos clínicos, fisiológicos, morfológicos, celulares e moleculares. O capítulo de abertura descreve uma avaliação global de transcritos associados ao envelhecimento da epiderme humana, com a técnica de microarranjos de DNA e coleta não invasiva com fitas adesivas. O estudo indica características moleculares específicas do fotoenvelhecimento epidermal, com alterações relevantes e complementares a dados clínicos e morfológicos prévios, como modulação das vias de organização do citoesqueleto de actina e sinalização de cálcio, expressão gênica alterada de proteínas do envelope córneo, e avaliação de um painel segmentado por décadas de vida que sugere aspectos inéditos de regulação homeostática da epiderme, além de genes com modulação contínua ao longo das idades. O segundo capítulo compara o envelhecimento nas regiões folicular e interfolicular da epiderme. Como um sistema biológico de simples obtenção e fácil manuseio, os bulbos dos folículos pilosos representam uma fonte rica de material epidermal distinto, conforme evidencias na ampla modulação gênica diferenciada. O terceiro capítulo inclui uma avaliação in vitro do envelhecimento da epiderme, com queratinócitos de indivíduos de diferentes idades cultivados em monocamada e no modelo de pele equivalente. Os resultados evidenciam diferenças na expressão de marcadores moleculares de proliferação e diferenciação entre queratinócitos neonatais e adultos, mas não entre adultos de diferentes idades. Não houve diferença nas populações de células tronco, entretanto, observou-se aumento de células na fase proliferativa do ciclo celular em neonatos, assim como predominância de células na fase estacionária do ciclo celular em adultos mais velhos. Concluindo, os resultados obtidos no presente trabalho contribuem de forma significativa para o avanço do entendimento dos mecanismos moleculares afetados pelo avanço da idade da epiderme, possilitando a busca de novas alternativas no tratamento do envelhecimento cutâneo<br>Abstract: With the increase in lifetime of the human population many medical disciplines, including dermatology, are facing a revolution in the approaches to ensure healthcare and quality of life for patients. In contact with the external environment, the skin is an organ in which the changes of aging cause functional damage, in addition to potential aesthetic and psychosocial impact. Epidermis, the outermost skin layer, is a selective barrier with outstanding capacity for renewal and maintenance of the body homeostasis. However, the understanding of several mechanisms associated with skin physiology and aging remains a challenge for the scientific community. Considering this scenario, the objective of this work was to evaluate the state of the art knowledge on epidermal aging and to conduct experimental approaches to cover gaps that still exist on that theme, focusing on the integration of clinical, physiological, morphological, cellular and molecular aspects of epidermis aging. The opening chapter describes a study based on global transcriptional evaluation associated with aging of the human epidermis, using DNA microarrays and noninvasive tape stripping. This study reveals molecular characteristics specific of epidermal photoaging, with relevant findings complementary to previous clinical and morphological data, such as modulation of the actin cytoskeleton and calcium signaling pathways; altered gene expression of proteins of the cornified envelope; and evaluation of a segmented panel structured by decades of life, which suggests new aspects of homeostatic regulation in the epidermis and unvails genes with continuous modulation throughout different ages. The second chapter compares the gene expression patterns of the follicular and interfollicular regions of epidermis undergoing aging. As a biological system easily sampled and handled, the bulbs of plucked hair follicles represent a rich source of distinct epidermal material, as evidenced by the wide differential gene modulation that was detected. The third chapter includes an experimental in vitro evaluation of skin aging using keratinocytes isolated from individuals of different ages and cultured in monolayer and in skin equivalent models. Differences in the expression of proliferation and differentiation molecular markers between neonatal and adult keratinocytes were observed. No differences were found regarding the stem cell populations, however, neonates showed an increased percentage of cells in the proliferative phase of cell cycle, while older adults presented a predominance of cells in the stationary phase of cell cycle. The results herein presented provide novel insights on the molecular mechanisms affected by epidermal aging, enabling the search of new alternatives in the treatment of aging skin<br>Doutorado<br>Genetica Animal e Evolução<br>Doutor em Genetica e Biologia Molecular

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Hebelka, Tomáš. "Analýza dat z mikročipů pro zjišťování genové exprese." Master's thesis, Vysoké učení technické v Brně. Fakulta informačních technologií, 2010. http://www.nusl.cz/ntk/nusl-235549.

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This work concerns with data analysis of DNA microarrays by using cluster analysis. It explains biological terms - gene expression and DNA microarray. Next, it contains mathematical and informatical description of clustering methods and describes a way to apply these methods to microarrays data. Next, the work contains implementation's detail of clustering methods k-means, DBSCAN and introduces an original clustering algorithm Strom++. Then, description of implementation and application manual follow. Finally, accomplished results are evaluated.

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McWilliam, Iain Stuart. "Development of microarray techniques for the study of gene expression in the European eel (Anguilla anguilla) during silvering and migration to seawater." Thesis, St Andrews, 2008. http://hdl.handle.net/10023/502.

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Xue-Franzén, Yongtao. "DNA microarray approaches to understanding the regulation and evolution of gene expression networks." Stockholm : Huddinge : Karolinska institutet ; Södertörns högskola, 2009. http://diss.kib.ki.se/2009/978-91-7409-554-8/.

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Brandt, Regine, Robert Grützmann, Andrea Bauer, Ralf Jesenofsky, Jörg Ringel, Matthias Löhr, Christian Pilarsky, and Jörg D. Hoheisel. "DNA microarray analysis of pancreatic malignancies." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-136556.

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Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. To improve the prognosis, novel molecular markers and targets for earlier diagnosis and adjuvant and/or neoadjuvant treatment are needed. Recent advances in human genome research and high-throughput molecular technologies make it possible to cope with the molecular complexity of malignant tumors. With DNA array technology, mRNA expression levels of thousand of genes can be measured simultaneously in a single assay. As several studies using microarrays in PDAC have already been published, this review attempts to compare the published data and therefore to validate the results. In addition, the applied techniques are discussed in the context of pancreatic malignancies<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

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Guo, Dongli, and 郭冬麗. "Expression of Wnt signaling targets and their clinico-pathological significance in colorectal neoplasm: a tissuemicroarray study." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B38610541.

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Mersinias, Vassilios. "DNA microarray-based analysis of gene expression in Streptomyces coelicolor A3(2) and Streptomyces lividans." Thesis, University of Manchester, 2004. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.488026.

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Brandt, Regine, Robert Grützmann, Andrea Bauer, Ralf Jesenofsky, Jörg Ringel, Matthias Löhr, Christian Pilarsky, and Jörg D. Hoheisel. "DNA microarray analysis of pancreatic malignancies." Karger, 2004. https://tud.qucosa.de/id/qucosa%3A27711.

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Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. To improve the prognosis, novel molecular markers and targets for earlier diagnosis and adjuvant and/or neoadjuvant treatment are needed. Recent advances in human genome research and high-throughput molecular technologies make it possible to cope with the molecular complexity of malignant tumors. With DNA array technology, mRNA expression levels of thousand of genes can be measured simultaneously in a single assay. As several studies using microarrays in PDAC have already been published, this review attempts to compare the published data and therefore to validate the results. In addition, the applied techniques are discussed in the context of pancreatic malignancies.<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

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Hasegawa, Suguru. "Genome-wide analysis of gene expression in intestinal-type gastric cancers using a complementary DNA microarray representing 23,040 genes." Kyoto University, 2004. http://hdl.handle.net/2433/147563.

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Mizaku, Alda. "Biomolecular feature selection of colorectal cancer microarray data using GA-SVM hybrid and noise perturbation to address overfitting." Diss., Online access via UMI:, 2009.

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Thesis (M.S.)--State University of New York at Binghamton, Thomas J. Watson School of Engineering and Applied Science, Department of Bioengineering, Biomedical Engineering, 2009.<br>Includes bibliographical references.

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Demirkale, Cumhur Yusuf. "Classical and bayesian mixed model analysis of microarray data for detecting gene expression and DNA differences." [Ames, Iowa : Iowa State University], 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:8ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3369826.

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Peralta, Angela. "Generation of A L. Hesperus embryonic cDNA library for the isolation of genes involved in early pattern formation." Scholarly Commons, 2010. https://scholarlycommons.pacific.edu/uop_etds/755.

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While development in flies is well understood, pattem formation and the evolution thereof in arachnids have yet to be clarified. Flies and other metazoans primarily use two families of genes called Hox genes and Pax genes to regulate embryogenesis. Because of the high evolutionary conservation of Hox and Pax proteins, I hypothesize that arachnids also use this system to organize their body pattern. To enable studies of the Westem black widow spider, Latrodectus hesperus, an embryonic eDNA library and a fixation protocol were developed for L. hesperus embryos. The generation of these tools will allow comprehensive analysis of black widow spider development and give insight into whether, and how, spiders use Hox and Pax genes to organize their bodies. Finally, it will provide a more thorough understanding of how different developmental mechanisms have evolved and ultimately how changes in gene expression can lead to a change in overall body plan.

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Bednarska, Aleksandra. "Artificial systems for in vitro gene expression." Thesis, Université Paris-Saclay (ComUE), 2015. http://www.theses.fr/2015SACLN016/document.

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L’ARN polymérase dépendante d’ADN (RNAP) est une enzyme responsable de la polymérisation de ribonucleotides dans une séquence d'ARN complémentaire de l'ADN de matrice. La famille de RNAP a plusieurs membres, comme de protéines sous-unité unique (par exemple du bactériophage T7) ou multiple sous-unité (bactériennes et eucaryotes). Transcription de l'ARN - un événement crucial dans l'expression des gènes - varie en fonction de l'origine de RNAP. Bien que le processus de transcription est relativement bien caractérisée, de nombreux éléments restent mal compris, surtout par rapport à la dynamique de la reconnaissance de promoteur, d'évasion et de l'allongement dans une contexte de cellule où la densité moléculaire, les concentrations et les effets plus proches environs sont importants. L'objectif de cette thèse était la développement d’une méthode qui permettrait suivre la réaction RNAP in vitro en temps réel dans des conditions très contrôlées. Un axe majeur a été mis pour développer un biocapteur basé surface qui permettrait à la caractérisation des principales étapes de la réaction de transcription. Par conséquent, les interactions entre des molécules d'ADN immobilisés sur une surface du capteur et RNAP libre délivré par un système microfluidique de la surface ont été examinées. Changements de l'indice de réfraction, corrélés avec les changements de masse sur la surface ont été suivis en utilisant l'imagerie par résonance de plasmon de surface (SPRi). SPRi est une technique sensible dédiée à l'analyse des interactions entre deux ligands en temps réel. Les bases du mécanisme sont la détection de légères différences dans la réflexion de la lumière polarisée à un angle fixe qui est associé avec une variation de masse à l'interface. Les données obtenues à partir SPRi sont utilisées pour déterminer la cinétique des interactions. Géométrie d’ADN puces permet de suivre plusieurs échantillons simultanément, qui raccourcit considérablement le temps que de manipulation et améliore la qualité et la reproductibilité des résultats obtenus. Autres biocapteurs optofluidique: résonateur de microring et microscopie de fluorescence par réflexion totale interne (TIRF) ont été développés en parallèle. Nous avons biofunctionalisé et caractérisé des surfaces de capteur (de verre couvert de polymère pour un résonateur de microring et la microscopie TIRF et 50 nm couche mince d’or sur des prismes de SPRi) afin d'immobiliser ADN d'une manière contrôlée, par création d’une monocouche auto-assemblée (SAM). Fonctionnalisation de polymères SU-8 concernées deux méthodes: covalent immobilisation de (bio) molécules et la conjugaison non covalente sur la base de couplage hydrophobe. Pour la fonctionnalisation de surface d’or, quatre stratégies différentes d'immobilisation des molécules ont été comparés: formation de la liaison de thiol - or, la formation des liaisons amide, interactions extrAvidin - biotine et le couplage hydrophobe. Les études de la conjugaison de l'ADN à la surface d'or fonctionnalisé ont été effectuées en ce qui concerne la spécificité et la densité d'ADN immobilisées de longueurs différentes: 50, 500 et 1000 pb. Enfin, les surfaces biofunctionalized ont été utilisées pour suivre en temps réel des réactions de transcription de deux RNAP: bactériophage T7 RNAP monomère et l'holoenzyme d'Escherichia coli RNAP. Les analyses cinétiques de la formation d’un complexe nucléoprotéine et la transcription d'ARN ont été fait par report de la densité et la longueur de l'ADN immobilisé, la position de la séquence du promoteur spécifique. Transcription de l'ARN dans l'appareil SPRi a été confirmée par la collection, la détection et l'analyse des produits ARN.L'objectif final comprends une synthèse de l'ARN contrôlée qui serait une étape intermédiaire d'enquêter en temps réel la production de protéines in vitro<br>DNA-dependent RNA polymerase (RNAP) is an enzyme responsible for the polymerization of ribonucleotides into an RNA sequence complementary to the template DNA. RNAP family has several members being single subunit (e.g. T7 bacteriophage) or multi subunit (bacterial and eukaryote) proteins. RNA transcription – a crucial event in gene expression – differs depending on the RNAP origin. Although the transcription process is relatively well characterized, many elements remain poorly understood, especially with respect to the dynamics of promoter recognition, escape and elongation in a cell like context where molecular density, concentrations and nearest neighbour effects are prevalent.The goal of this thesis was to develop a robust method that would allow real time monitoring of RNAP reaction in vitro in thoroughly controlled conditions. A major axis was to develop a surface-based biosensor that would allow the characterization of the main steps of the transcription reaction. Consequently, interactions between DNA molecules immobilized on a sensor surface and free RNAP delivered through a microfluidic flow system to the surface were examined. Changes in refractive index, correlated with changes in mass at a surface were followed using surface plasmon resonance imaging (SPRi). SPRi is a sensitive technique dedicated to analysis of interactions between two ligands in real time. The mechanism bases on the detection of slight differences in the reflectivity of polarized light at a fixed angle that are associated with a mass variation at the interface. Data obtained from SPRi are used to determine the kinetics of the interactions. Microarray geometry of SPRi allows monitoring several samples simultaneously that significantly shortens manipulation time and improves a quality and reproducibility of obtained results. Other label-free optofluidic biosensors: microring resonator and total internal reflection fluorescence (TIRF) microscopy were developed in parallel.We firstly biofunctionalized and characterized sensor surfaces (polymer coated glass for microring resonator and TIRF microscopy and 50-nm thin layer gold coatings on glass prisms for SPRi) in order to immobilize DNA strands in a controlled manner, using a self-assembled monolayer (SAM). Functionalization of photoresist polymer SU-8 concerned two methods: covalent (bio)molecule grafting and non-covalent conjugation based on hydrophobic coupling. Regarding gold surface functionalization, four different strategies of antifouling (bio)molecule immobilization were compared: thiol – gold bond formation, amide bond formation, extrAvidin – biotin interactions and hydrophobic coupling. Studies of DNA conjugation to the functionalized gold surface were performed with respect to specificity and density of immobilized DNA molecules of different lengths: 50, 500 and 1000 bp.Finally, biofunctionalized surfaces were used for real time monitoring of transcription reactions using two RNAPs: monomeric bacteriophage T7 RNAP and the holoenzyme of Escherichia coli RNAP. Kinetic analyses of nucleoprotein complex formation and RNA transcription were performed as a function of immobilized DNA density, the length of the immobilized DNA, the position of the specific promoter sequence with respect to the point of immobilization and the direction of subsequent transcription. RNA transcription in the SPRi apparatus was confirmed by collection, detection and analysis of relevant products.The future development of biosensors dedicated to in vitro gene expression will include the adaptation of the methods presented above to other optofluidic systems and further development of the technique. The final goal comprises a controlled RNA synthesis that would be an intermediate step to investigate real time in vitro protein production

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Hrudíková, Radka. "Vytipování a sledování exprese genů ovlivňujících syntézu kyseliny hyaluronové ve streptococcus equi subsp. zooepidemicus pomocí technologie dna čipů a real time PCR." Doctoral thesis, Vysoké učení technické v Brně. Fakulta chemická, 2020. http://www.nusl.cz/ntk/nusl-432922.

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Hyaluronic acid (HA) is an important substance, which is mostly used in pharmaceutical and cosmetic industry. This substance is commonly found in the human body. HA is one of the factors contributing to virulence of microorganisms. Some bacterial strains produce hyaluronic acid in the form of a mucoid capsule that encapsulates the cell to protect bacteria against the immune system of the host organism. One of the main producers is the bacterial strain Streptococcus equi subsp. zooepidemicus. Contipro a.s. uses the strain CO4A to produce hyaluronic acid in large scale. The production strain was obtained by random mutagenesis by UV light. The aim of the work was to study changes in the genome, which led to a significant increase in hyaluronic acid production, using DNA microarray and real-time PCR (qPCR). The genome of the strain CO4A was sequenced and compared to reference ATCC35246 [1]. The size of the genome is 2,167,251 bp and 83 relevant variants (59 SNV and 34 indels) have been identified. Variants in coding regions were annotated and amino acid sequence changes were determined. In SNV mutations there was a change in the amino acid sequence in 45 cases. The change was identified in every case of indel mutations. The expression level of selected groups of genes was monitored in both strains by the method of DNA microarrays. A cascade of increased expression level of amino sugar metabolism genes leading to the synthesis of UDP-N-acetyl glucosamine was observed in strain CO4A (the increase in expression level of these genes compared to ATCC35246 was on average 28 %). Subsequently, the expression of selected genes was verified by qPCR. There was no significant difference in the expression level of the has operon genes of both strains. The effect of supplementation of the culture medium with N-acetylglucosamine (GlcNAc), which is one of the precursors of HA synthesis, was also studied by qPCR. A positive effect of the supplementation of the culture medium with external GlcNAc in the CO4A strain has been recorded. Also, the supplementation has positive effect on the yield of HA from the medium (increase in yield was on average by 17 %). GlcNAc has been shown to have a positive effect on the yield of HA in ATCC35246 strain as well (increase in yield was 9 % on average), but no significant changes in the expression levels were found in selected groups of genes in ATCC35246.

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