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Predicting local structural properties from antibody sequence
Beňo, Roman ; Příhoda, David (advisor) ; Hoksza, David (referee)
Predicting local structural properties of antibodies at residual level is vital for detecting the presence of post-translational modifications (PTMs), which often induce structural change in the antibody, negatively impact its shelf-life and possibly lead to the loss of the therapeutic potential. In this work, we predict relative solvent accessibility (RSA) of individual residues. This property is, alongside with the type of amino acid in question, the key indicator for presence of methionine oxidations and other types of PTMs. Due to the conservation of the antibody structure, we identified that different classes of prediction methods yield almost interchangeable results - total mean absolute error (MAE) of 5.64 RSA percentage units measured for the best performing machine learning pipeline compared to the 5.96 measured for the best performing statistical pipeline. The significant prediction quality improvement observed within comparison to the random prediction method with MAE of 35.996 may be as well attributed to the sequence conservancy. In CDR regions, RSA values are harder to predict. Although the range of methods and procedures employed throughout this work is by far not able to yield complex structure predictions, it might constitute a modular, high-throughput tool to support one's choices when...
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Enzyme optimization using sequence homology and machine learning
Neitzert, Gesa-Maret ; Příhoda, David (advisor) ; Hoksza, David (referee)
In pharmaceutical research and development, enzymes play an important role in the synthesis of drugs and drug-related molecules. For higher efficiency and increased production, it is important to optimize the yield of these enzymes, a task often addressed by protein engineering and design. This process of enzyme optimization however can become tedious with the vast options of mutations for each single protein. To improve the process of enzyme optimization, sequence homology and machine learning methods can be used. These greatly reduce the manual effort of protein redesign and can assist in finding the most fit enzyme for the given task, increasing the efficiency of the overall drug development pipeline. With this aim in mind this thesis summarizes a selection of existing methods and their possible application to enzyme optimization. Testing two predictive models with varying complexity on 4 datasets in an attempt to optimize absorption, enantioselectivity, or thermostability found only a modest correlation between actual target values and their predicted values: mean Pearson's R 0.20775 and 0.5188. Comparing probability patterns of protein sequence embeddings led to a 0.815 correlation score with the BLOSUM62 substitution matrix, confirming the language model's intuition about natural frequency of...
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Party of power in the Russian government and party system
Příhoda, David ; Mlejnek, Josef (advisor) ; Žídková, Markéta (referee)
Diploma thesis deals with parties of power in the Russian government and party system. There is supposed that the executive branch, namely president, is most significant part of the Russian government. Parties of power are established by executive with aim to reach places enough in State Duma to posses majority of seats. They are set down from above. The work is divided into three parts. The first one is focused on executive branch. Here are described power of president and government and relationships among other executive bodies. The second part deals with political parties and party system. First, there are introduced the reasons why political parties are so weak. Periodization of party system and performance of party families follow. The third part is focused on parties of power. First of all, we try to define this concept. The attantion is than turned to the parties established during Yeltsin era. Parties established during Putin era follow. Putin and Yeltsin differ in their attitude to the party of power.
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The role of the United Russia in political system of the Russian Federation
Vondráčková, Dominika ; Příhoda, David (advisor) ; Romancov, Michael (referee)
With the beginning of new millennium the political atmosphere in Russia started to change significantly. The number of political parties dramatically decreased and in 2001 was formed soon to be strongest party - the United Russia. Since then the overall centralization of the system had started - it happened to be more difficult for smaller parties to reach the Duma mandates, media are influenced more than before and NGOs with certain political opinions are forbidden to operate. In this environment exists the United Russia - the party of power - not a platform for discussion, which a political party should be, but a tool of Kremlin, which reminds more a center of elites, power and means. In the beginning of the text are described competitive and non-competitive party systems. The current party system of Russia is there acknowledged as a party system with pragmatic- hegemonic party. Further the text follows the evolution and changes of the party system in Russia, the electoral reforms and overall changes since 1999 to the present. Then the ideology of Russia in international environment is discussed as well as the ideology of the United Russia. The text shows, that even though the United Russia declares an ideology, in reality it could be found only scarcely.
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The United Russia and strengthening of the influence in the Russian Federation
Vondráčková, Dominika ; Příhoda, David (advisor) ; Romancov, Michael (referee)
This work is about the United Russia - party of power in Russian Federation. The exact aim is to define and describe main ways of strenghtening the party's power within the system. Those ways are especially: election reforms, biased medias, biased voting behavior managed through regions and youth movements. Text is divided into three chapters - theoretical, historical and practical. The first chapter talks about theory of political parties, parties of power in general, and about hegemonic party systems. This chapter provides theoretical frame and supports argumentation that hegemonic party needs to use certain activities in order to perpetuate its influence. Second chapter explores the history and tradition of political parties in Russia. Traditionally parties were very weak and often established by state, instead of being established by the civil society and its cleavages. In this part are shown longer-term factors, which are helpful in perpetuating strong Russian party of power. Last chapter shows the main spheres through which the party strengthens itself. We talk about period since 2001 when the party was established until presence (2016). Here are demonstrated concrete examples - for instance how exactly was changed the electorate system in order to advance the United Russia, how is the voting...
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The Role of the United Russia in Political System of the Russian Federation
Vondráčková, Dominika ; Příhoda, David (advisor) ; Romancov, Michael (referee)
Main focus of this text is the current party of power in Russia - the United Russia. The party was established on purpose of competing another party (and take away votes), but eventually gained quite high number of votes itself. Almost since the beginning we could have been witnessing a partnership between United Russia and Vladimir Putin. After Vladimir Putin became a president in 2000, legal changes concerning parties had occurred. The goal of my writing is to show what role does the party have and how the system influences United Russia's position in the system. In the first chapter I focus on typologies of party systems. I begin with Sartori and his classification of less competitive regimes and then I am moving towards special terms which are especially being used for Russian case. In the next chapter, I am talking mainly about changes of party system and reforms in the system which came hand in hand with Putin's presidency. Those reforms show us very clearly the tendencies within party system held by the Kremlin. At the end I talk about United Russia and its distribution of power.
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Party of power in the Russian government and party system
Příhoda, David ; Mlejnek, Josef (advisor) ; Romancov, Michael (referee)
This work deals with parties of power in the Russian government and party system. There is supposed that the executive branch, namely president, is most significant part of the Russian government. Parties of power are established by executive with aim to reach places enough in State Duma to posses majority of seats. They are set down from above. The work is divided into three parts. The first one is focused on executive branch. Here are described power of president and government and relationships among other executive bodies. The second part deals with political parties and party system. First, there are introduced the reasons why political parties are so weak. Periodization of party system and performance of party families follow. The third part is focused on parties of power. First of all, we try to define this concept. The attantion is than turned to the parties established during Yeltsin era. Parties established during Putin era follow. Putin and Yeltsin differ in their attitude to the party of power.
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Party of power in the Russian government and party system
Příhoda, David ; Mlejnek, Josef (advisor) ; Žídková, Markéta (referee)
Diploma thesis deals with parties of power in the Russian government and party system. There is supposed that the executive branch, namely president, is most significant part of the Russian government. Parties of power are established by executive with aim to reach places enough in State Duma to posses majority of seats. They are set down from above. The work is divided into three parts. The first one is focused on executive branch. Here are described power of president and government and relationships among other executive bodies. The second part deals with political parties and party system. First, there are introduced the reasons why political parties are so weak. Periodization of party system and performance of party families follow. The third part is focused on parties of power. First of all, we try to define this concept. The attantion is than turned to the parties established during Yeltsin era. Parties established during Putin era follow. Putin and Yeltsin differ in their attitude to the party of power.
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Environmental transport policy in cities
PŘÍHODA, David
This works tries to describe environmental transport policy through legislation. Specifically in selected Czech towns. Further is analysed the environmental transport policy in European state the Netherlands. With these knowledge will be created proposals to improvement of the current situation.
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