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Theoretical Study of Non-covalent Interaction from small molecules to Biomolecules
Haldar, Susanta ; Hobza, Pavel (advisor) ; Havlas, Zdeněk (referee) ; Jurečka, Petr (referee)
xv Abstract The aim of this thesis is to investigate the accurate stabilization energy and binding free energy in various non-covalent complexes spanned from small organic molecules to biomolecules. Non-covalent interactions such as H-bonds, π...π stacking and halogen bonds are mainly responsible for understanding of most biological processes, such as small molecule interactions with surface, protein-ligand binding in the cell machinery, etc. In the thesis, different non-covalent complexes such as graphene…electron donor- acceptor complexes, DNA base pair interaction with silica surface, etc, were investigated. The reference stabilization energies were calculated at ab initio level, e.g., CCSD(T)/CBS method wherever possible. On the other hand, more approximated scaled MP2 method (MP2.5/CBS/6-31G*(0.25)) is taken as reference instead of CCSD(T)/CBS due to the size of the complexes. Further, the DFT and MM energies were also tested towards the reference one. The knowledge of non- covalent interaction is required for rationalizing of any association processes in nature which requires accurate description of the free energy change. The state-of- the-art molecular dynamics simulation in full atomic scale and biased metadynamics free energy method is used for binding free energy calculations. The well tempered...
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Overseas Shipwrecks: Depictions in Spanish and Portuguese Sources from 16 th Century
Marešová, Jaroslava ; Vydrová, Hedvika (advisor) ; Housková, Anna (referee) ; Binková, Simona (referee)
Overseas Shipwrecks: Depictions in Spanish and Portuguese Sources from the 16th Century PhDr. Jaroslava Marešová Abstract This dissertation analyses Spanish and Portuguese shipwreck accounts of the 16th century. These accounts were written mainly by survivors of catastrophic shipwrecks on overseas voyages to America and India and therefore belong to the huge corpus of works written in the 16th century about exploring and conquering new territories. But unlike the most of the written sources of the period, these accounts does not celebrate the overseas enterprise, they bring a new, tragic, perspective and describe the dangers and misery of overseas voyages. Portuguese shipwrecks accounts were very popular among the readers of the 16th century and therefore they created a kind of tradition. They are often seen as a specific genre and represent an important topic of the Portuguese literature of the 16th century and are studied by many Portuguese literary scholars. In this dissertation six Portuguese accounts are analysed, five of them written by survivors. There are not as many shipwreck accounts written in Spanish. The best known of them is the account by Álvar Núñez Cabeza de Vaca. The second shipwreck account written in Spanish and analysed in this dissertation is the letter by Maestre Juan in which he...
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Assessment of foreign language writing skills in the context of the European language policy. Reliability of assessment in writing using German language Maturita writing test
Novotná Knotková, Soňa ; Starý, Karel (advisor) ; Škaloudová, Alena (referee) ; Nálepová, Jana (referee)
This dissertation deals with the assessment of open-ended test items in the Writing Part of the Maturita Exam. The influence of the European language policy on Czech curricular documents and the conception of foreign language Maturita Exam is described. Writing performance requirements in the Maturita Exam are also specified. Comparison of the holistic and analytic scoring methods follows. Based on that, analytic Maturita Exam criteria and its rater scales are introduced. The dissertation then deals with the research conducted to describe and analyse the 2009-2011 training process of German language raters for writing assessment in the Maturita Exam. Rater training is evaluated and ratings are analysed on the basis of inter-rater agreement among raters and between raters and the expert rating team. The research also explorers whether the set rating procedures and scoring principles, i.e. analytic criteria, raters and the way they use the criteria, are objective, reliable and accurate. The influence of the raters' level of German language, their age and the type of school they teach at is also addressed. The research showed that the level of intra-rater agreement tends to improve throughout the rater training and a certain level of reliability is reached. The influence of age and the type of school...
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The influence of the quality of articulation UHMWPE inserts on the lifetime of joint replacements
Fulín, Petr ; Pokorný, David (advisor) ; Koudela, Karel (referee) ; Gallo, Jiří (referee)
This thesis focuses on the introduction with the problems of high molecular weight polyethylene (UHMWPE) in orthopedics in the first part. It discusses the history, properties and processes that lead to the failure of UHMWPE joint replacement components. The experimental part validates the hypotheses expressed. It acquaints readers with the experimental verification of the effect of different types of sterilization on the oxidative stability of laboratory prepared samples and explanted UHMWPE joint replacement components using methods of infrared microscopy, electron spin resonance, mechanical tests and tests of microhardness. Other experimental measurements on a large set of explanted components of hip and knee total joint replacements validates the hypothesis that the amount of oxidative damage affects the lifespan of joint replacements. The third part of the experimental study maps the degree of oxidative damage in different places of the hip and knee joint replacements. In the final part we experimentally demonstrate the fact that the rate of oxidative damage has an effect on supramolecular structure of the UHMWPE. From the above experiments are concluded clearly defined recommendations for clinical practice, which should lead to extend the lifespan of total joints replacements in orthopaedics....
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Synthesis of biologically active compounds with quinazoline scaffold
Štěpánek, Ondřej ; Kotora, Martin (advisor) ; Hájíček, Josef (referee) ; Moravcová, Jitka (referee)
This thesis concludes my contribution to research of HIV-1 capsid assembly inhibitors. It has been shown that 2,4-disubstituted quinazoline derivatives are able to inhibit this process both, in competitive biochemical assay based on the AlphaScreen technology as well as in tissue cultures. The main objective of the work was to prepare the aforementioned quinazolines, to design and prepare new candidates with higher activity based on results of biochemical tests, and also to try to increase the solubility of otherwise poorly soluble compounds. Disubstituted quinazolines are relatively easily accessible from the commercially available anthranilic acid derivatives. These are converted to the corresponding quinazolin- 4(3H)-ones by the condensation reactions. In this work, two methods were used for the preparation of quinazolin-4(3H)-ones: reaction of acyl chlorides with aromatic anthranilamides provided 2-arylamidobenzamides whose subsequent cyclisation under basic conditions led to derivatives of 2-arylquinazolin-4(3H)-one; reaction of anthranilic acid esters with aromatic nitriles, which afforded desired quinazolin-4(3H)-one in one reaction step. Chlorination of 2-arylquinazolin-4(3H)-ones using POCl3 then led to 2-aryl-4- chloroderivatives as key intermediates. Nucleophilic substitution of...
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Vliv vybraných látek ovlivňujících centrální nervový systém na kostní metabolismus
Fekete, Soňa ; Živný, Pavel (advisor) ; Horák, Pavel (referee) ; Nobilis, Milan (referee)
The increase in life expectancy of the world population is associated with challenges regarding health issues. For instance, osteoporosis is a medical condition mostly observed in elderly people, in which the quality and quantity of the bone are severely affected. Not only for women but also for men, osteoporosis is recognized as an important public health issue. Osteoporosis is a systemic skeletal disorder and is a result of loss of skeletal mass. Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue and an increase in bone fragility and susceptibility to fracture. Osteoporotic fractures are a significant cause of morbidity and mortality. The longterm use of drugs such as antiepileptics and antidepressants could affect the onset of osteoporosis. The aim of the study was to evaluate the effect of orchidectomy, the effect of newer antiepileptic (levetiracetam, lacosamide, topiramat, lamotrigine) and antidepressive drugs (mirtazapine, venlafaxine and trazodone) on bone metabolism in healthy male Wistar rats. The first specific aim was to determine the effect of orchidectomy on bone metabolism in rats. We found that after 12 weeks post-orchidectomy there was a negative effect on bone metabolism in rats. These results established these animals as suitable models for...
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C-H activations of deazapurine heterocycles
Klečka, Martin ; Hocek, Michal (advisor) ; Hlaváč, Jan (referee) ; Rádl, Stanislav (referee)
Direct C-H borylations of 7-deazapurines (7H-pyrrolo[2,3-d]pyrimidine) were developed at position 8 using B2pin2 and Ir catalysis. The obtained boronates were efficiently applied in the Suzuki cross-couplings with aryl halides and other functional group transformations to give diverse 6-substituted 8-aryl-7-deazapurine derivatives. Furthermore, I was also interested in the synthesis of biologically relevant 8-aryl-7- deazaadenines and -7-deazahypoxanthines. As the direct C-H borylation of 7- deazaadenines was unsuccessful and the borylation/Suzuki reaction of 6-chloro-7- deazapurine gave only low yield (20%) of the desired 8-aryl derivative, I focused on the one-pot borylation/arylation of SEM-protected 6-methylsulfanyl- or 6-methoxy-7- deazapurines. The one-pot borylation/Suzuki coupling reactions were followed either by demethylation and deprotection to yield deazahypoxanthine base, or by oxidation of sulfide to sulfone, amination and deprotection to give deazaadenines. In addition, the boronate intermediates were successfully converted to 8-halo- or 8-trifluoromethyl-7- deazapurine derivatives. While the 7-deazahypoxantine analogues were almost entirely inactive, most of the 8-subtituted 6-methoxy-7-deazapurine and 7-deazaadenines bases showed significant cytostatic activities. Also a general...
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Structural and Functional Interactions of Mitochondrial ADP-Phosphorylating Apparatus
Nůsková, Hana ; Houštěk, Josef (advisor) ; Kolarov, Jordan (referee) ; Kuda, Ondřej (referee) ; Panicucci Zíková, Alena (referee)
The complexes of the oxidative phosphorylation (OXPHOS) system in the inner mitochondrial membrane are organised into structural and functional super-assemblies, so-called supercomplexes. This type of organisation enables substrate channelling and hence improves the overall OXPHOS efficiency. ATP synthase associates into dimers and higher oligomers. Within the supercomplex of ATP synthasome, it interacts with ADP/ATP translocase (ANT), which exchanges synthesised ATP for cytosolic ADP, and inorganic phosphate carrier (PiC), which imports phosphate into the mitochondrial matrix. The existence of this supercomplex is generally accepted. Experimental evidence is however still lacking. In this thesis, structural interactions between ATP synthase, ANT and PiC were studied in detail. In addition, the interdependence of their expression was examined either under physiological conditions in rat tissues or using model cell lines with ATP synthase deficiencies of different origin. Specifically, they included mutations in the nuclear genes ATP5E and TMEM70 that code for subunit ε and the ancillary factor of ATP synthase biogenesis TMEM70, respectively, and a microdeletion at the interface of genes MT-ATP6 and MT-COX3 that impairs the mitochondrial translation of both subunit a of ATP synthase and subunit Cox3...
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Pastoral care, or persuasion? The influence of church leaders and their control of clergy and believers. Research of religiosity, communication strategies of priest and their image in letters in the late 19th and early 20th Century
Pavlíček, Tomáš ; Velek, Luboš (advisor) ; Fasora, Lukáš (referee) ; Hanuš, Jiří (referee)
Pastoral care, or persuasion? The influence of church leaders and their control of clergy and believers. Research of religiosity, communication strategies of priests and their image in letters in the late 19th and early 20th century. Tomáš W. Pavlíček SUMMARY The author of the Ph.D. thesis examines the religious culture in Bohemia in the late 19th century. Contrary to the concept of secularization and the prevalent opinion about an extraordinary decline of religiosity in the Czech society, he attempts to explain the interdependence of social and religious changes in the modern times. Within the sociological concept of secularization and disenchantment of the world, the author focuses on three phenomena: the vocation of a priest, religious practices and conversion, which he treats as religious concepts and at the same time applies them in historical research. The biggest part of the thesis is devoted to the first object of the research - the attitude of a priest towards his vocation, as the clergy is the agent of religious change. The thesis contributes to the current discussions about the relationship of the church and the state and the role of clergy in the society. The main questions are: What is the role of a priest in the religious changes? In what way or under what circumstances does a person get the...
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Visceral leishmaniasis in Ethiopia: transmission and variability
Gelaglie, Aysheshm Kassahun ; Votýpka, Jan (advisor) ; Gradoni, Luigi (referee) ; ÖZBEL, Yusuf (referee)
Leishmaniasis, a protozoan infection caused by Leishmania parasites is a neglected disease affecting millions across the world. It is exhibited by diverse clinical presentations that broadly classified as visceral (VL) and cutaneous (CL) leishmaniasis. Both CL and VL are endemic to Ethiopia, which the later is generally considered as fatal, if left untreated. Leishmania donovani is the sole agent of Ethiopian human VL. In Africa, the worst VL affected regions are found in Sudan and Ethiopia. VL is considered as an endemic and at the same time emerging disease in north, northwest, south and southwest with sporadic cases in Eastern Ethiopia. The epidemiology is more or less associated with seasonal migration to endemic areas and HIV/AIDS. The transmission of CL in Ethiopia is known to involve zoonotic cycle while VL transmission isn't clearly understood despite traditional generalization of anthroponosis in East African platform. The aim of this dissertation is to determine VL transmission cycle and study variability L. donovani and P. orientalis in Ethiopia. Studies on human and non-human hosts were conducted to determine the transmission dynamics. To assess the role of symptomatic and asymptomatic L. donovani infected persons in the epidemiology of VL, a community based cohort was conducted. As the...
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