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Retinoid regulation of target gene transcription and antitumor activity of retinoid related molecules
Raška, Ivan ; Broulík, Petr (advisor) ; Kostrouch, Zdeněk (referee) ; Pokorný, Jaroslav (referee)
Nuclear Retinoic Acid (RA) Receptors (RARs) activate gene expression through dynamic interactions with coregulators in coordination with the ligand and phosphorylation processes. In the first part of this work, we showed that during RA-dependent activation of the RARq isotype, the pi 60 coactivator pCIP/ACTR/AIВ-1 /RAC-3/TRAM-1 /SRC-3 was phosphorylated by p38MAPK. SRC-3 phosphorylation was correlated to an initial facilitation of RARa-target genes activation, via the control of the dynamics of the interactions of the coactivator with RARa. Then phosphorylation inhibited transcription via promoting the degradation of SRC-3. In line with this, inhibition of p38MAPK markedly enhanced RARa-mediated transcription and RA-dependent induction of cell differentiation. SRC-3 phosphorylation and degradation occurred only within the context of RARa complexes, suggesting that the RAR isotype defined a phosphorylation code through dictating the accessibility of the coactivator to p38MAPK. We proposed a model in which RARa transcriptional activity was regulated by SRC-3 through coordinated events that are fine- tuned by RA and p38MAPK. The retinoid related molecules (RRMs), ST1926 and CD437, are promising anti-cancer agents. In the second part of this work, we compared the RAR trans-activating properties of the two RRMs...
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Cendelín, Jan ; Vožeh, František (advisor) ; Mareš, Jan (referee) ; Pokorný, Jaroslav (referee)
Lurcher mutant mice represent a model of olivocerebellar degeneration. They are heterozygots carrying a mutation in the glutamate receptor 52-subunit gene. The receptor malfunction causes excitotoxic apoptosis of Purkinje cells, extinction of which leads to secondary degeneration of cerebellar granule cells and inferior olive neurons. Lurcher mutants suffer from ataxia and deterioration of spatial learning and orientation ability. The aim of the work was to assess the effect of embryonic cerebellar tissue transplantation and enforced physical activity as well as the effect of their combination on spatial orientation ability in Lurcher mutant mice and to observe cerebellar graft survival in adult and young Lurcher and adult wild type mice. For the graft survival analysis adult wild type mice and young and adult Lurcher B6CBA mice were used. To study the effect of the transplantation and enforced activity on spatial orientation adult and young Lurchers of the same strain were used. The graft obtained from mouse embryos without the Lurcher mutation was applied into the cerebellar area of the host as solid pieces. Control mice were treated only with vehicle. Enforced activity was represented with repeated rotarod training. Spatial orientation was tested in the Morris maze 9 weeks after the surgery. Histological...
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Querying relational databases through XSLT
Mareš, Jiří ; Pokorný, Jaroslav (advisor) ; Richta, Karel (referee)
XML is becoming standard for information representing and data interchange. A question has arisen if it would be possible to combine simplicity and user friendliness of XML and its querying languages together with performance of relational databases, has arisen. There are several proposals how to carry this connection out. The aim of this thesis is to inspect one of these proposals, eventually modify it and then implement it. The inspected proposal stores XML data into relational database based on knowledge of XML DTD and subsequently queries them using XSLT. XSLT queries will be transformed to SQL queries using DTD of XML data stored in database and a way to transform data back to XML will be suggested.
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Extending Fagin's algorithm for more users.
Ondreička, Matúš ; Pokorný, Jaroslav (advisor) ; Eckhardt, Alan (referee)
We discuss the issue of searching the best K objects in more attributes for more users. Every user prefers objects in different ways. User preferences are modelled locally with a fuzzy function and globally with an aggregation function. Also, we discuss the issue of searching the best K objects without accessing all objects. We deal with the use of local preferences when computing Fagin's algorithms. We created a new model of lists for Fagin's algorithms based on B+-trees. Furthermore, we deal with the use of a multidimensional B-tree for searching the best K objects. We developed an MD-algorithm, which can effectively find the best K objects in a multidimensional B-tree in accordance with user's preferences and without accessing all the objects. Last but not least, we show results of all the tests of described algorithms. MD-algorithm achieves better results in the number of accessed objects than Fagin's algorithms.
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Quantitative analysis of networked environments to improve performance of information systems
Petříček, Václav ; Pokorný, Jaroslav (advisor) ; Cox, Ingemar J. (referee) ; Snášel, Václav (referee)
In this thesis we encounter networks in three contexts i) as the citation networks between documents in citation databases CiteSeer and DBLP, ii) as the structure of e-government websites that is navigated by users and iii) as the social network of users of a photo-sharing site Flickr and a social networking site Yahoo!360. We study the properties of networks present in real datasets, what are the effects of their structure and how this structure can be exploited. We analyze the citation networks between computer science publications and compare them to those described in Physics community. We also demonstrate the bias of citation databases collected autonomously and present mathematical models of this bias. We then analyze the link structure of three websites extracted by exhaustive crawls. We perform a user study with 134 participants on these websites in an lab. We discuss the structure of the link networks and the performance of subjects in locating information on these websites. We finally exploit the knowledge of users' social network to provide higher quality recommendations than current collaborative filtering techniques and demonstrate the performance benefit on two real datasets.
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XML Data in (Object-) Relational Databases
Mlýnková, Irena ; Pokorný, Jaroslav (advisor) ; Krátký, Michal (referee) ; Osswald, R. (referee)
As XML has become a standard for data representation, it is inevitable to propose and implement techniques for e±cient managing of XML documents. A natural alternative is to exploit features and functions of (object-)relational database management systems, i.e. to rely on their long theoretical and practical history. The main concern of such techniques is the choice of an appropriate XML-to-relational mapping strategy. In this thesis we focus on further enhancing of current most e±cient XML-to-relational storage strategies { so-called adaptive methods. Firstly, we perform a detailed analysis of existing works and especially remaining open issues. Secondly, we propose their enhancing which can be characterized as a hybrid user-driven adaptive mapping strategy, i.e. a combination of so-called user-driven and adaptive methods. In the enhancing we focus especially on deeper exploitation of user-given information, i.e. schema annotations, and we propose an approach which enables to identify new annotation candidates and thus to help users to nd a more appropriate mapping strategy. For this purpose we propose a similarity measure which focuses mainly on structural similarity of the given data and an algorithm which enables reasonable tuning of its parameters on the basis of results of statistical analysis of...
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XSLT Implementation in Relational Database Environment
Kmoch, Ondřej ; Holubová, Irena (referee) ; Pokorný, Jaroslav (advisor)
XML is widely used format for storing all kinds of data and XSLT standard represents a standardized way, how to transform a XML document to a di fferent structure. Many XSLT implementation has been introduced, but the most of them uses an in-memory representation of the transformed XML document. The implementation done in this thesis uses the relational database engine to store processed document and takes advantages of SQL to evaluate XPath expressions used by XSLT. First, importing source XML document into the generic relational mapping is described. For processing XPath expressions, the XPath to SQL convertor is introduced. Lastly, the processing of XSLT stylesheets by relational database engine is shown.
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Semantic annotation of data from web resources
Dědek, Jan ; Pokorný, Jaroslav (referee) ; Vojtáš, Peter (advisor)
This work starts with the idea of The Semantic Web. Then basic description logics is introduced with its parallel in a couple of formalisms for building of ontology. In this work, there is shown, how the ontologies are employed in the semantic annotation process and also there are described some projects that use semantic annotation in a practical way. Information extraction methods that help to automatize the semantic annotation process are mentioned. Tools for natural language processing of Czech language are described in detail. A practical experiment shows how these tools can help with extraction of information from plain text. This work also deals with the relationship of natural language processing and formal representation of knowledge in description logics.
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