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Investigation of the role of the KEAP1-NRF2 antioxidant pathway in the therapy of secondary acute myeloid leukaemia
Myšáková, Michaela ; Pimková, Kristýna (advisor) ; Suttnar, Jiří (referee)
The development of therapy resistance is a long-standing problem in treating cancer, particularly in the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML), where the hypomethylating agent 5-azacytidine (AZA) is the first choice of treatment. To enhance therapeutic efficacy, AZA is often combined with other agents such as pevonedistat (Pevo), a NEDDylation inhibitor targeting the ubiquitin-proteasome system. While initial results showed a synergistic effect of the AZA and Pevo combination in treating MDS and AML, dual resistance has been described, underlining the importance of understanding the mechanisms behind the resistance development. Our previous data demonstrated an essential role of redox homeostasis and antioxidant system represented by Nuclear factor erythroid 2-related factor 2 (NRF2) in AZA resistance. The Kelch-like ECH-associated protein 1 (KEAP1)-NRF2 pathway is the master regulator of antioxidative defence in cells crucial for maintaining redox balance. However, hyperactivation of NRF2 has been implicated in therapy resistance and cancer progression. We hypothesised that NRF2 is crucial in MDS/AML therapy resistance, particularly in resistance to combined AZA and Pevo therapy. We worked with cells sensitive and resistant to AZA and Pevo and monitored...
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Genetic Algorithms Based Game in Unity
Bábek, Radomír ; Beran, Vítězslav (referee) ; Vlnas, Michal (advisor)
This thesis focuses on the areas of game development and genetic algorithms. It describes the design and implementation of the game PlantEVO, which features special fighting plants. The player's task is to understand the workings of the genetic algorithm and to use it as efficiently as possible in breeding his plants. After then the strength of his plants is tested in online battles against other players. The battles are designed in a turn-based strategy combat style. The game uses a client-server architecture. The client is programmed in the Unity game engine, the server uses the REST API architecture.
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Molecular genetic analysis of thyroid carcinomas in pediatric and adolescent patients
Bulanová, Barbora
Thyroid nodules are rare in pediatric and adolescent patients, but they are at greater risk of malignancy than adult patients. Thyroid carcinomas are the most common endocrine malignancy and their incidence is increasing. Although there are several types of thyroid carcinoma, 90% of cases in pediatric and adolescent patients are papillary thyroid carcinomas (PTCs). The aim of this study was to analyze a large cohort of PTCs from pediatric and adolescent patients, determine their genetic cause, and correlate the findings with clinical pathological data. Another aim was to characterize the most frequent findings and compare them with a cohort of adult patients with thyroid carcinoma positive for the same mutation. The final objective was to optimize a suitable methodology for detecting the most common findings in pediatric and adolescent patients for routine use. Thyroid tumor tissue samples were examined using molecular genetic methods, mostly using next-generation sequencing and real-time PCR analysis. We found that fusion genes were the most common cause of PTC in pediatric and adolescent patients, detected in 56% of patients. In total, 20 different types of fusion genes were identified, some of which have not been previously described in the literature. The fusion genes included the oncogenes...
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Genetic Algorithm Design for Distribution Network Outfits Optimalization
Ondruš, Tomáš ; Skala, Petr (referee) ; Paar, Martin (advisor)
The work deals with genetic algorithms and their potential use in application software to optimize high voltage switching elements of distribution network. Theoretical part explains the basic concepts of genetic algorithms such as a gene, population and chromosome and basic principles of the development of genetic algorithms.. The main task of the thesis is to design the algorithm that will simulate the distribution of the sectionalizers by telecontrolled section switches or reclosers and analyze how to set the the parameters affecting the convergence speed of genetic algorithm. The basic parameters affecting the convergence of breeding, mutation probability, population size or using of elitism. The second goal is finding a suitable set of input parameters for the selected population sizes without and with using elitism. The results of the work determine the most appropriate settings for each generation and determining the approximate number of generations needed to find the best solution. The genetic algorithm applocation was tested on a less extensive distribution network with six switching elements
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Evolutionary algorithms
Haupt, Daniel ; Polách, Petr (referee) ; Honzík, Petr (advisor)
The first part of this work deals with the optimization and evolutionary algorithms which are used as a tool to solve complex optimization problems. The discussed algorithms are Differential Evolution, Genetic Algorithm, Simulated Annealing and deterministic non-evolutionary algorithm Taboo Search.. Consequently the discussion is held on the issue of testing the optimization algorithms through the use of the test function gallery and comparison solution all algorithms on Travelling salesman problem. In the second part of this work all above mentioned optimization algorithms are tested on 11 test functions and on three models of placement cities in Travelling salesman problem. Firstly, the experiments are carried out with unlimited number of accesses to the fitness function and secondly with limited number of accesses to the fitness function. All the data are processed statistically and graphically.
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Evolutionary computing
Popelka, Jan ; Smékal, Zdeněk (referee) ; Karásek, Jan (advisor)
The aim of this Bachelor's Thesis was to get acquainted with the Evolutionary Optimization Techniques, mainly with the Genetic Algorithm and Genetic Programming. It was subsequently described the role of optimization problem TSP solved using Genetic Algorithms and other Chapter solving Symbolic Regression using Genetic Programming. This optimalization problems were created in the programming JAVA and there are solved practical part of the thesis.
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Comparative and phylogenetic analysis of viruses in the University Hospital Brno
Švestková, Tereza ; Sedlář, Karel (referee) ; Nykrýnová, Markéta (advisor)
This thesis is focused on the SARs-CoV-2 coronavirus associated with severe acute respiratory syndrome, which was first identified in 2019. This coronavirus caused a pandemic that affected almost the entire world. Knowledge of the genetic information is needed for vaccine development, to determine infectivity and to predict the evolution of SARs-CoV-2 variants. To obtain genetic information, RNA must be sequenced and these genomic sequences must be assembled. By comparing the assembled genomes, it is possible to find out which part of the organism has mutated. Phylogenetic analysis is performed on the basis of the concordance or divergence in the assembled genomes, which indicates the evolution of the organism and shows the evolutionary relationship with other organisms. The practical part is focused on the assembly of genomes from samples from patients in the University Hospital Brno and evaluation of the quality of the assembly. After the genomes are assembled, the next goal is to evaluate the variability and subsequent phylogenetic analysis.
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Discovery of Wireless Sensor Network Topology Using Genetic Algorithms
Dalecký, Štěpán ; Samek, Jan (referee) ; Zbořil, František (advisor)
The thesis deals with a design of the genetic algorithm that is able to discover the wireless sensor network topology using signal strength among particular sensors. At first, the thesis describes the theory of genetic algorithm and wireless sensor network. Subsequently, on the basis of this theory, the genetic algorithm serving for the wireless sensor network topology discovery has been designed. The thesis also describes important features of the algorithm implementation. In conclusion, the outcomes have been reviewed.
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