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New Optimization Algorithms for a Digital Image Reconstruction in EIT
Kříž, Tomáš ; Koňas, Petr (referee) ; Král, Bohumil (referee) ; Dědková, Jarmila (advisor)
This doctoral thesis proposes a new algorithm for the reconstruction of impedance images in monitored objects. The algorithm eliminates the spatial resolution problems present in existing reconstruction methods, and, with respect to the monitored objects, it exploits both the partial knowledge of configuration and the material composition. The discussed novel method is designed to recognize certain significant fields of interest, such as material defects or blood clots and tumors in biological images. The actual reconstruction process comprises two phases; while the former stage is focused on industry-related images, with the aim to detect defects in conductive materials, the latter one concentrates on biomedical applications. The thesis also presents a description of the numerical model used to test the algorithm. The testing procedure was centred on the resulting impedivity value, influence of the regularization parameter, initial value of the numerical model impedivity, and effect exerted by noise on the voltage electrodes upon the overall reconstruction results. Another issue analyzed herein is the possibility of reconstructing impedance images from components of the magnetic flux density measured outside the investigated object. The given magnetic field is generated by a current passing through the object. The created algorithm for the reconstruction of impedance images is modeled on the proposed algorithm for EIT-based reconstruction of impedance images from voltage. The algoritm was tested for stability, influence of the regularization parameter, and initial conductivity. From the general perspective, the thesis describes the methodology for both magnetic field measurement via NMR and processing of the obtained data.
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Optimization of method for susceptibility measurement
Jeništa, Petr ; Marcoň, Petr (referee) ; Bartušek, Karel (advisor)
The aim of this thesis is measure the specimens placed in field of MR tomograph, the measured data to evaluace the process and measurement errors. The theoretical part is focused on describing basic parameters of magnetic field, commissioning some older methods of measurement and design methods for the measurement of samples not issuing MR signal. There is performed modeling for the proposed Metod and the 1D, 2D and 3D environments using COMSOL Multiphysics. The practical part is the measurements samples in the tomograph the Institute of Scientific Instruments Academy of Science in Brno. The measured data are processed in Marevisi and Matlab programs. The MATLAB program is written for processing, analysis and data evaluation, after which it is possible to determine the value of the magnetic susceptibility of the selected samples. In conclusion of the work is the quantification accuracy of measurements.
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Study of substances transport in plants stalks
Doubek, Vladimír ; Kubásek, Radek (referee) ; Mikulka, Jan (advisor)
This thesis deals procedure nuclear magnetic resonance and next three of basic measuring technics NMR. Magnetic resonance exploit, that anyone proton and neutron have dynamics moment. Is based on monitoring response coring situated to magnetic field B0 and on interaction with HF electromagnetical wave. Measuring of response signal differ in feed RF pulse. Method spin echo (SE) is based on two pulses 90° and 180° in contrast by Inverse recovery (IR), where is it conversely.By method Hahn echo (measuring efficient relaxation time T2*) is brought 90° pulse. For all methods is final signal over stopping process captured in receiving inductor.
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Structure-assisted design of inhibitors targeting medicinally relevant enzymes
Djukic, Stefan ; Maloy Řezáčová, Pavlína (advisor) ; Kutá-Smatanová, Ivana (referee) ; Kolenko, Petr (referee)
Structure-assisted drug discovery is a powerful approach that utilizes detailed knowledge on 3D structure to design and optimize new inhibitors targeting medically relevant enzymes. X-ray crystallography is a widely used structural biology technique since it provides detailed snapshot of protein-inhibitor complex, which is used to analyze protein- inhibitor interactions. PNP plays an important role in salvage pathway of purine metabolism, it is a target in treatment of T-cell malignancies and/or parasitic infections. Our effort focused on human and M. tuberculosis PNP, and our aim was to develop new inhibitors with high selectivity and specificity. Our inhibitors are acyclic nucleoside phosphates with 9- deazahypoxanthine nucleobase that contain three moieties binding to all three regions of the active site: purine, phenyl and phosphonate moieties. The best inhibitors have IC50 values as low as 19 nM (human) and 4 nM (M. tuberculosis). The presence of short substituents at central phenyl moiety, such as methoxy and bromide group, decreases inhibitor's affinity towards human PNP, but does not affect affinity towards mycobacterial PNP. At the same time, bulky substituents, such as fluorinated phenyl ring, decrease inhibitor's affinity towards human PNP but increase affinity towards mycobacterial...
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Modification and analysis of low-molecular chitosans
Moravcová, Dagmar ; Bosáková, Zuzana (advisor) ; Strašák, Tomáš (referee)
4 Abstract Chitosan is a natural biopolymer derived from chitin, found in the exoskeletons of crustaceans and fungi. It has gained considerable attention due to its biodegradability, biocompatibility, antimicrobial properties, and potential antitumor activities. Chitosan has cationic amino groups that enable interactions with various anionic compounds. Therefore, it is an ideal candidate for conjugation with monovalent bioactive compounds to form efficient multivalent conjugates. It was found that galectins, especially Gal-1 and Gal-3, are overexpressed in tumor cells. Several monovalent inhibitors derived from the parent inhibitor thiodigalactoside, also those modified with coumaryl groups, have been synthesized, which show a high selectivity and affinity towards Gal-3. The main goal of this work was to synthesize a chitosan-based carrier and conjugate it with ligands exhibiting selectivity and inhibitory effect towards Gal-3. The first step involved the modification of chitosan using a unique effective method based on solid-phase hydrolysis, which significantly reduces the consumption of chemical materials and, in addition, excessive losses during purification. At the same time, the chitosan carrier was functionalized with pentynoic acid. Furthermore, monovalent galectin ligands,...
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Synthesis of triblock terpolymers as a tool for preparation of smart drug delivery nanosystems
Orságh, Martin ; Uchman, Mariusz Marcin (advisor) ; Fernandez Alvarez, Roberto (referee)
In this thesis, we describe the synthesis and self-assembly of new photo-responsive triblock terpolymers by RAFT polymerization. These triblock terpolymers were characterized by GPC, NMR and IR spectroscopy. The resulting nanoparticles were characterized by DLS, SAXS and Cryo-EM. To avoid problems with RAFT polymerization of the photo-responsive monomer o- nitrobenzyl acrylate, we used naphthacyl methacrylate, a new RAFT-polymerizable photo- responsive monomer. In addition, we used phenylboronic acid moieties to conjugate model drugs with our triblock terpolymers via dynamic covalent bonding and studied stimuli-triggered release of a model drug-like compound, Alizarin Red S. Our results showed that naphthacyl methacrylate is indeed polymerizable by RAFT and that such polymers retain photo-responsive properties. We were also able to bind Alizarin Red S to the polymer via boronate ester linkage and trigger its release by dopamine or fructose addition, both of which are biologically relevant compounds. Therefore, our photo- and diol-responsive nanoparticles open up opportunities for developing new drug-delivery systems.
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Numerical optimization of solid-state NMR experiments
Šmelko, Andrej ; Tošner, Zdeněk (advisor) ; Chlan, Vojtěch (referee)
Numerical optimizations of solid-state nuclear magnetic resonance experiments are one of the possible solutions to its low sensitivity. Using the Average Hamiltonian Theory, the negative effects of the radiofrequency field inhomogeneity on magnetization transfer were investigated. To overcome these effects, the Average Hamiltonian Theory was employed in the optimization of commonly used techniques such as Ramp-CP and Adiabatic-CP, optimization of pulses with arbitrarily modulated amplitude and new periodic pulses with arbitrarily modulated amplitudes and phases. Both types of shaped pulses achieved significantly higher efficiencies than Ramp- CP and Adiabatic-CP. The highest efficiency enhancement was calculated at high spinning frequencies and low dipolar coupling constants where the effect of the inhomogeneity is the strongest.
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Synthesis of polymer precursors based on isosorbide
Šichnárek, Vojtěch ; Cigánek, Martin (referee) ; Figalla, Silvestr (advisor)
The theoretical part of the thesis deals with the description of reduced hexitols, methods of isosorbide production and its application purpose in polymer materials. It includes a description of the glucose dehydration process, the influence of reaction conditions and the catalysis of the isosorbide production, the polymerization of isosorbide monomers and their properties. The experimental part of the work is focused on the optimization of isosorbide’s laboratory synthesis‘ reaction conditions, the description of its chemical modification to polymerizable isosorbide derivatives and the physical-chemical characterization of the produced molecules. The synthesis of isosorbide is monitored by LC-MS, the product is subjected to various refining methods and a detailed structural characterization. GC was chosen for the monitoring of the preparation of isosorbide dimethacrylate and structural verification of the diester was confirmed by FT-IR, MS and NMR. The physical-chemical characterization of the prepared isosorbide dimethacrylate consists of the description of its rheological properties in mixture with a commercial methacrylated oil and the study of the reactivity of the monomers by DSC. The mixture of methacrylated oil and isosorbide dimethacrylate was used to prepare polymer thermosets which were analyzed by thermo-mechanical methods such as DMA, bending and TGA. The highest isosorbide conversion achieved value of 81.9 % after 5 hours, and it reached 94,1 % for isosorbide dimethacrylate after 8 hours. According to the results, isosorbide dimethacrylate possesses the abilty to reduce the shear viscosity of polymerizable precursors and to increase the glass transition temperature and crosslinking densities of polymer thermoset.
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Characterization of protein-protein interactions between Forkhead box O (FOXO) and p53 transcription factors
Mandal, Raju ; Obšil, Tomáš (advisor) ; Hrabal, Richard (referee) ; Pavlíček, Jiří (referee)
The transcription factor p53 plays a key role in cell cycle arrest, DNA repair, apoptosis, tumor suppression, and maintaining cellular homeostasis. Under cellular stress, p53 directly interacts with the Forkhead box O (FOXO) 4 transcription factor, thereby upregulating the expression of the p21 gene, resulting in the induction of cellular senescence. However, the detailed molecular mechanism behind FOXO4-p53 interaction remains unclear due to the unavailability of structural data. Therefore, main goal of this doctoral thesis was the characterization of the interaction between FOXO4 and p53 using several biophysical techniques including sedimentation velocity analytical ultracentrifugation (SV AUC), nuclear magnetic resonance (NMR) spectroscopy and chemical cross-linking coupled to mass spectrometry. Furthermore, we also investigated the DNA binding properties of both proteins with their respective consensus DNA sequences in the presence or absence of their binding partners by fluorescence anisotropy measurements along with the comparison of p53-binding surfaces of the Forkhead domain of three different FOXO proteins by NMR spectroscopy. In addition, we also optimized small molecule compounds for the inhibition of FOXO3-DNA interaction. Our results revealed that the p53 interacts with FOXO4 through...
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