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Influence of size and geometry of nanoparticles on cellular internalization pathways
Číhařová, Barbora ; Španielová, Hana (advisor) ; Lišková, Petra (referee)
Nanoparticles can be used in biomedical disciplines as carriers for transport of diagnostic as well as therapeutic substances into cells. Variety of different shapes, sizes and different compositions are used experimentally. Despite the discoveries already made in this area, the exact nature of the interaction between a nanoparticle and a cell has not been fully understood yet. The objective of this thesis is to provide the knowledge about possibilities of utilisation and aspects influencing the interaction between the cell membrane and several types of nanoparticles: liposomes, gold nanoparticles and virus-like nanoparticles. The comparison shows that generalisation of the mechanism of nanoparticle entry into the cell is problematic, although it seems that the spherical nanoparticles with the diameter of 50 nm provide the most efficient entry.
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Trafficking of purinergic P2X receptor in eukaryotic cell
Pražák, Šimon ; Tvrdoňová, Vendula (advisor) ; Kolář, David (referee)
Purinergic receptors are membrane ion channels activated by extracellular ATP. In vertebrates, seven genes encoding P2X subunits was found. These subunits are designated as P2X1 - 7. Every P2X receptor subunit consists of two transmembrane domains, extracellular domain and intracellular N- and C- termini. P2X receptors fold to homo- or heterotrimers. P2X receptors have a wide distribution in the organism, functional receptors are found in neurons, glial cells, muscle cells and also in nonexcitable tissues as epithelial, endothelial, and in hemopoietic tissue. Purinergic signalling plays an important role in pain transmission, CNS injury and immune processes. P2X receptors are synthesized on the rough endoplasmic reticulum and are transported to the plasma membrane after post-translational modifications in the Golgi apparatus. The distribution and transport of P2X receptors is subunit specific and dependent on the cell type in which they are expressed. P2X receptors can be divided into three groups according to the way they are moved in the cell, which differ in transport speed, plasma membrane accumulation rate and rate of internalization.
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The role of membrane cholesterol in delta-opioid receptor signaling Correlation with plasma membrane structure
Brejchová, Jana ; Svoboda, Petr (advisor) ; Novotný, Jiří (referee) ; Teisinger, Jan (referee)
Study of HEK293 cells stably expressing fusion protein between delta opioid receptor (δ-OR) and pertussis toxin-insensitive mutant of Gi1α protein, δ-OR-Gi1α (Cys351 -Ile351 ), provided the following results. Decrease of plasma membrane cholesterol content (cholesterol depletion) induced by cyclic oligosaccharide β-cyclodextrin did not affect binding of specific δ-OR agonist, [3 H]DADLE. Neither the maximum number of binding sites nor the affinity of [3 H]DADLE binding was changed by cholesterol depletion. However, the ability of δ-OR to activate cognate trimeric G proteins was impaired. EC50 value of agonist-stimulated [35 S]GTPγS binding was an order of magnitude higher. This effect was observed in case of both control and pertussis toxin-treated cells. It means that cholesterol depletion markedly reduced the efficiency of functional coupling of δ-OR to endogenously expressed pertussis toxin-sensitive G proteins of Gi/Go family as well as covalently bound Gi1α (Cys351 -Ile351 ) protein. Unchanged plasma membrane cholesterol content is therefore important requirement for proper δ-OR function. Detection of the effect of cholesterol depletion on the functional activity of δ-OR was supported by the analysis of changes in biophysical state of plasma membrane using fluorescent membrane probes,...
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Negative externality associated with driving under the influence of alcohol
Sladký, Jan ; Hudík, Marek (advisor) ; Šťastný, Daniel (referee)
This thesis answers the question how big is the negative externality associated with driving under the influence of alcohol in crowns per kilometer driven by the driver with alcohol in blood. The calculation includes the economic consequences of accidents, specifically, loss of production, the cost of health care, administration and social expenditures, included are also the values of lost human lives and values for heavy and light injuries. Calculation of externality is used to determine the fine that internalizes this externality.
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Impact of international production network on the configuration of the worldwide procurement organization and performance
Sahin, Turan ; Veber, Jaromír (advisor) ; Pichanič, Mikuláš (referee) ; Tomek, Gustav (referee)
Increased trends towards globalisation, optimization of the value chain, outsourcing of activities and focus on core competentencies result in increased importance of procurement's role, in that it causes high attention from top management.The focus from top management is based on the change of the cost structure, i.e. lowering internal value chain and an increase of material and purchasing costs above 50 %. The core objectives of the worldwide procurement are internationalization, strategic focus and costs reduction. There are high expectations towards procurement. First, to generate procurement savings on a global scale, to identify the best procurement markets, finding the best supplier and to determine the world class price level. The study has been targeted to analyze the configuration of worldwide procurement organizations and the impact of international production network on procurement. Furthermore, to benchmark international sourcing activities on a global scale, resulting in identification of critical success factors for improving the procurement quality and effectiveness.
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