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Genetic factors in lymphoproliferative malignancies Focus on CHEK2 gene in lymphomas with comparison to distinct solid tumors
Havránek, Ondřej ; Trněný, Marek (advisor) ; Papajik, Tomáš (referee) ; Veselý, Pavel (referee)
Genetic factors in lymphoproliferative malignancies. Focus on CHEK2 gene in lymphomas with comparison to distinct solid tumors. MUDr. Ondřej Havránek Summary of PhD thesis: Background: The checkpoint kinase 2 gene (CHEK2) codes for an important mediator of DNA damage response pathway that among others interacts with the p53 protein. Mutations in the CHEK2 gene increase the risk of several cancer types, however, their role in non- Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) is not clear. The most frequent TP53 gene R72P polymorphism was analyzed in several studies in NHL but not in HL. Methods: We have performed mutation analysis of the whole CHEK2 gene coding sequence in 340 NHL patients and the segment coding for CHEK2 forkhead-associated (FHA) domain in 298 HL patients and compared the results with our analyses of CHEK2 in breast, colorectal and pancreatic cancers. The TP53 R75P genotype was assessed in the same lymphoma populations. Both genes were analyzed using denaturing high-performance liquid chromatography. Results: The overall frequency of CHEK2 alterations within FHA-coding region was significantly higher in NHL and HL patients (19/340 - 5.6%; 17/298 - 5.7%, respectively) compared to non-cancer controls (19/683 - 2.8%; p = 0.03 and 0.04, respectively). These alterations were associated with...
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Online Algorithms for Packet Scheduling
Veselý, Pavel ; Sgall, Jiří (advisor) ; Stein, Clifford (referee) ; Englert, Matthias (referee)
We study online scheduling policies for buffer management models, in which packets are arriving over time to a buffer of a network switch to be sent through its single output port. However, the bandwidth of the port is limited and some packets need to be dropped, based on their weights. The goal of the scheduler is to maximize the weighted throughput, that is, the total weight of packets transmitted. Due to the natural lack of information about future, an optimal performance cannot be achieved, we thus pursue competitive analysis and its refinements to analyze online algorithms on worst-case inputs. Specifically, in the first part of the thesis, we focus on a simple online scheduling model with unit-size packets and deadlines, called Bounded-Delay Packet Scheduling. We design an optimal φ-competitive deterministic algo- rithm for the problem, where φ ≈ 1.618 is the golden ratio. It is based on a detailed understanding of an optimal schedule of pending packets, called the plan, which may be of independent interest. We also propose a semi-online setting with lookahead that allows the algorithm to see a little bit of future, namely, packets arriving in the next few steps. We provide an algorithm with lookahead for instances in which each packet can be scheduled in at most two consecutive slots and prove lower...
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Molecular basis of fluoropyrimidine toxic effect etiology with focus on palmar-plantar erythrodysesthesia and potential antidote use
Hartinger, Jan ; Veselý, Pavel (advisor) ; Květina, Jaroslav (referee) ; Brábek, Jan (referee)
(thesis): Palmar-plantar erythrodysesthesia (PPE) frequently accompanies the therapy with a continuous 5-FU infusion or peroral capecitabine (5-FU prodrug). In the most severe cases this adverse effect leads to discontinuation of a needful therapy. Local 10 % uridine ointment is used to prevent and treat the said adverse event. Nevertheless, this method is not generally accepted as an effective one because it has never been proved in a randomized controlled clinical trial. Most probably, a direct effect of a cytostatic compound on the skin of hands and foots causes PPE. The toxicity of 5-FU is mediated primarily by its incorporation into RNA and by thymidylate synthase (TS) inhibition and subsequent DNA synthesis disruption. The importance of particular 5-FU toxicity mechanisms varies in different cell types. For choosing the best PPE local antidote it is necessary to find out which molecular mechanism applies in keratinocytes. We have chosen pyrimidine nucleosides as the most suitable compounds for the local PPE therapy because the uridine ointment is already being used in several oncology centers in the Central Europe. In order to find out the 5-FU toxicity mechanism, we further tested the effect of calciumfolinate (CF) which strengthens the TS inhibition by 5-FU. We studied also uracil and...
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Web site inspector
Mansurov, Alexandr ; Mareš, Martin (advisor) ; Veselý, Pavel (referee)
Our goal is to develop a tool for automatic website checking. We created an ex- tensible system that checks the validity of links as well as HTML and CSS syntax. For that, we integrated existing tools and libraries into one application using plu- gins. Our tool looks for links in HTML and sitemaps. Also, robots.txt including crawl-delay implementation and sitemap discovery is supported. The course of inspection can be affected by configuration rules. Plugin categorization allows for customization of inspection. Not only we verify the validity of standard hypertext links but also links through other HTML tags (images, frames, cascading styles, scripts). In addition, canonical addresses and redirection, duplicates in content or usage of non-semantic tags or attributes are detected. The developed application is extensible for other types of checks. 1
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Searching trails in maps
Drahovský, Robin ; Pangrác, Ondřej (advisor) ; Veselý, Pavel (referee)
This thesis describes design and implementation of an application capable of finding the shortest paths in real world map data, while taking elevation data into account. Path finding is fast and can be adjusted to user's needs without the need for graph rebuilding, what differentiates this application from others, that only allow user to work with predefined search profiles. In addition to path finding, the application can generate highly compact graph from map data in OSM format. This allows fast access to information necessary for finding the shortest path. The application can render map data with custom rendering style and contour lines, but also can display map from OpenStreetMaps project servers.
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Molecular basis of fluoropyrimidine toxic effect etiology with focus on palmar-plantar erythrodysesthesia and potential antidote use
Hartinger, Jan ; Veselý, Pavel (advisor) ; Květina, Jaroslav (referee) ; Brábek, Jan (referee)
(thesis): Palmar-plantar erythrodysesthesia (PPE) frequently accompanies the therapy with a continuous 5-FU infusion or peroral capecitabine (5-FU prodrug). In the most severe cases this adverse effect leads to discontinuation of a needful therapy. Local 10 % uridine ointment is used to prevent and treat the said adverse event. Nevertheless, this method is not generally accepted as an effective one because it has never been proved in a randomized controlled clinical trial. Most probably, a direct effect of a cytostatic compound on the skin of hands and foots causes PPE. The toxicity of 5-FU is mediated primarily by its incorporation into RNA and by thymidylate synthase (TS) inhibition and subsequent DNA synthesis disruption. The importance of particular 5-FU toxicity mechanisms varies in different cell types. For choosing the best PPE local antidote it is necessary to find out which molecular mechanism applies in keratinocytes. We have chosen pyrimidine nucleosides as the most suitable compounds for the local PPE therapy because the uridine ointment is already being used in several oncology centers in the Central Europe. In order to find out the 5-FU toxicity mechanism, we further tested the effect of calciumfolinate (CF) which strengthens the TS inhibition by 5-FU. We studied also uracil and...
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A backup system
Setnička, Jiří ; Mareš, Martin (advisor) ; Veselý, Pavel (referee)
An overview of existing approaches to data backup and their strengths with regard to use. After considering the previous describe the resulting backup system FenixBackup as file-oriented differential backup system capable holding more historical versions. In conclusion, outlines the possible directions which the development of the system could follow. Powered by TCPDF (www.tcpdf.org)
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Artificial intelligence for Mariáš
Kaštánková, Petra ; Veselý, Pavel (advisor) ; Pangrác, Ondřej (referee)
This thesis focuses on the implementation of a card game, Mariáš, and an artificial intelligence for this game. The game is designed for three players and it can be played with either other human players, or with a computer adversary. The game is designed as a client-server application, whereby the player connects to the game using a web page. The basis of the artificial intelligence is the Minimax algorithm. To speed it up we use the Alpha-Beta pruning, hash tables for storing equivalent states of the game and various heuristics. Powered by TCPDF (www.tcpdf.org)
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Online algorithms for variants of bin packing
Veselý, Pavel ; Sgall, Jiří (advisor) ; Krčál, Marek (referee)
An online algorithm must make decisions immediately and irrevocably based only on a part of the input without any knowledge of the future part of the input. We introduce the competitive analysis of online algorithms, a standard worst-case analysis, and present main results of this analysis on the problem of online Bin Packing and on some of its variants. In Bin Packing, a sequence of items of size up to 1 arrives to be packed into the minimal number of unit capacity bins. Mainly, we focus on Colored Bin Packing in which items have also a color and we cannot pack two items of the same color adjacently in a bin. For Colored Bin Packing, we improve some previous results on the problem with two colors and present the first results for arbitrarily many colors. Most notably, in the important case when all items have size zero, we give an optimal 1.5-competitive algorithm. For items of arbitrary size we present a lower bound of 2.5 and a 3.5-competitive algorithm. Powered by TCPDF (www.tcpdf.org)
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