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Methods of measurement of bone density
Konvalinka, Jan ; Valášek, Jiří (referee) ; Marcián, Petr (advisor)
This bachelor's thesis focuses on methods for measuring bone density and consequences of changes in bone density on biomechanical properties of bone tissue. In first part are described methods of bone densitometry, especially radiological methods, which are currently most widely used. Second part focuses on measuring bone density from CT images (hog femur bone, healthy and damaged human femur bone and lumbar vertebra) using software ROI Analysis. Third part discusses influence of changes in bone density on strain-stress quantities of trabecular bone. For the assessment was created 2D computational model of hip using FEM.
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Stress-strain analysis of tumorous total endoprosthesis of hip joint
Vystrk, Tomáš ; Konvalinka, Jan (referee) ; Marcián, Petr (advisor)
Tumorous total endoprosthesis of hip joint is used for reconstruction of the limb affected by bone tumor and to regain its functnion. Longterm load conditions must be considered by the reconstruction and the joint mobility must be enabled. Suitability of the endoprosthesis depends on its construction considering shape, material and with this related mechanical properties. This thesis deals with creation of computational model and stress-strain analysis of tumorous total endoprosthesis of hip joint. There are two different types of endoprosthesis modeled in this thesis, each with three different length of resected bone replacement. Based on stress-strain analysis an assessment of possible limit states is made.
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Relationship of force and deformation characteristics to the energy of deformed system
Kupka, Oldřich ; Konvalinka, Jan (referee) ; Horníková, Jana (advisor)
The bachelor´s thesis deals with the description of energy in deformed systems and their use to determine the force acting on the system and displacements caused by forces. In the first part of the thesis there are described the basic types of stresses and how it is possible to determine their strain energy and displacements. After that, strain and potential energy including their complementary components are described. Next part is explanation of the principle of virtual work, Betti's theorem and Maxwell's reciprocity theorem. In the second part of thesis, the first and the second Castigliano´s theorems are derived. Castigliano´s theorems are applied to a statically determinate and indeterminate problems.
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Analysis of impact of mechanical properties of components of pathological arterial wall on its state of stress
Bartoňová, Petra ; Konvalinka, Jan (referee) ; Burša, Jiří (advisor)
The thesis deals with measurements of the atherosclerothic carotid plaques mechanical properties with wiew towards the improvements of their constitutive models and then towards the impact of application of those constitutive models in fibrous cap. The introductory part provides a brief summary of medical knowledge needed to understand atheroma formation and the risks involved. Next, there's a survey of plaque mechanical testing methods and the obtained results on tissue properties. The previously used constitutive models of atherosclerothic tissues are listed as well. Main body of the thesis describes the preparation of testing samples from obtained atheroma, methodology and course of experiments execution and subsequent processing of the experimental data to evaluate the behavior of the atheromatous tissue individual parts. Then the discussion and evaluation of our results and findings is given. Along with the evaluated mechanical properties, experimental data fitted to models are presented with respect to their predictive abilities. The final part is dedvoted to the finite element analysis of an idealized 2D model with emphasis on the effect of necrotic core and fibrous tissue properties on von Mises equivalent stress in the fibrous cap.
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Strain and stress analysis of the femur with distraction intramedullary nail
Konvalinka, Jan ; Marcián, Petr (referee) ; Florian, Zdeněk (advisor)
This master's thesis is focused on determination and analysis of stress and strain in femur with distraction intramedullary nail for treating leg length discrepancy with the method of distraction osteogenesis. Thesis is mainly focused on states after distraction when the callus consolidates. Problem of determining stress and strain is solved by computational modeling using FEM. Detailed description of modeling is included in this thesis, complicated 3D geometry of bone was acquired from segmentation of CT images. Computational model is solve with 4 different types of callus geometry and also material properties of callus are varied. The influence on stress and strain when the middle distal screw is not applied is also analyzed.
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Studies on structure and biological functions of NKR-P1 receptors
Rozbeský, Daniel ; Novák, Petr (advisor) ; Konvalinka, Jan (referee) ; Drbal, Karel (referee)
Natural killer (NK) cells play a significant role in the detection and destruction of virally infected and tumor cells. The NKR-P1 receptors regulate NK cell function by an alternative missing-self recognition system. Although the NKR-P1 receptors were among the first surface NK receptors identified on rodent NK cells more than 20 years ago, there is still very little known about their biological function and their physiological ligands. Furthermore, no three-dimensional structure of any of the NKR-P1 family receptors has been published so far. To understand the functional architecture of mouse NKR-P1 receptors, we developed a simple and efficient protocol providing large amounts of pure soluble NKR-P1 proteins. The crystal structure of mouse NKR-P1A, determined at 1.7 A resolution, is the first structure of a representative of the NKR-P1 family. Crystal structure is formed by a compact C-type lectin-like domain and an extended loop that participates in domain swapping. A potential role of the swapped loop has been suggested in natural ligand binding by in silico studies. However, chemical cross-linking and H/D exchange in combination with high resolution mass spectrometry revealed this loop in close proximity to the compact core in solution. The discrepancy between the crystal and solution structure...
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Production and characterisation of human C1 inhibitor and Plasmodium falciparum PfMSP3.1 recombinant proteins for structural studies
Čápová, Kateřina ; Konvalinka, Jan (advisor) ; Heidingsfeld, Olga (referee)
PfMSP3.1 is one of the surface proteins of the intracellular parasite Plasmodium falciparum, which causes malaria. As one of the evasion strategies of the immunity system of the human host this protein interacts with one regulator of the complement system - C1 inhibitor. Determining the exact binding site and its structural assessment would help to better understand the interaction between the parasite and the host, which is necessary for the disease progression and thus for the development of a potential therapy. In the theoretical part of the thesis, the life cycle of Plasmodium falciparum, the role of the parasite stage called merozoite, the role of its surface proteins, including merozoite surface protein 3, in the attack of red blood cells by the parasite, are described in more detail. It also briefly describes the complement system, its activation pathways and the regulation of these pathways. The experimental part includes the cloning of plasmids to produce C1 inhibitor and various forms of merozoite surface protein PfMSP3.1, transfection of S2 insect cells with these plasmids, subsequent protein expression in S2 cells and their purification. In the second half of the experimental part, we tried to create complexes of C1 inhibitor with individual PfMSP3.1 forms and an attempt to crystallize...
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Synthesis and characterization of binding ligands for the study of targeted lysosomal protein degradation
Sidej, Natan ; Konvalinka, Jan (advisor) ; Baszczyňski, Ondřej (referee)
Targeted protein degradation is a novel concept of chemical biology that has been formulated about 20 years ago. Its central postulate is based on the fact that instead of suppressing protein activity with low-molecular inhibitors, we can instead use molecular tools to hijack the host organism's own degradation pathways and force it to degrade chosen proteins by itself. This diploma thesis revolves around the preparation of biocompatible polymeric conjugates called "iBodies" that will be used to induce targeted lysosomal degradation of two model enzymes - Fibroblast activation protein α, and Glutamate carboxypeptidase II. First, a total of four low-molecular ligands were prepared and fully characterized by standard methods of organic synthesis. The first two are mannose-6-phosphonate derivatives that serve as the inducers of protein degradation via the cellular endosomal-lysosomal degradation pathway. The remaining two are known potent inhibitors of the chosen model enzymes that will serve as their targeting-ligands. The prepared compounds were then used to prepare a total of eight poly-N-(2-hydroxypropyl)methacrylamide conjugates called iBodies, after which the polymeric conjugates were fully characterized by standard means of macromolecular chemistry. Afterwards, the obtained conjugates will be...
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Functional Characterization of SCFFBXO38 Ubiquitin Ligase-dependent Protein Degradation
Dibus, Nikol ; Čermák, Lukáš (advisor) ; Konvalinka, Jan (referee) ; D´Angiolella, Vincenzo (referee)
Ubiquitin ligases are responsible for the specific recognition of proteins targeted for proteasome-dependent degradation. This project focused on the molecular and functional characterization of the SCFFBXO38 ubiquitin ligase. As with many others, its biological function has not yet been elucidated in detail, although it is the only ubiquitin ligase whose mutations lead to the onset of a distal form of muscle atrophy. In the first part of our project, we identified new substrates for this ubiquitin ligase, the nuclear proteins ZXDA and ZXDB, with insufficiently characterized functions. Using genetic and biochemical methods, we have shown that ZXDA/B proteins act as positive regulators of centromeric chromatin integrity and that experimental inactivation of the SCFFBXO38 ubiquitin ligase resulted in a ZXDA/B-dependent stabilization of CENP-A and CENP-B proteins in the centromeric regions. In the second part of the project, we focused on analyzing the mouse model deficient in the Fbxo38 gene. We demonstrated that loss of Fbxo38 leads to growth retardation affecting various organs, including the male reproductive system. A detailed histological examination revealed pathological alterations in the seminiferous tubules, accompanied by a lower number of spermatozoa and decreased fertility. We have shown...
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