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Development of analytical tools for quantification and screening for inhibitors of glutamate carboxypeptidases II and III
Navrátil, Václav ; Konvalinka, Jan (advisor) ; Obšil, Tomáš (referee) ; Šedo, Aleksi (referee)
Glutamate carboxypeptidase II (GCPII) usually called prostate specific membrane antigen (PSMA) is membrane bound metallopeptidase expressed mainly in prostate carcinoma (PCa). Agents targeting GCPII suitable for both imaging and treatment of PCa are in development and they show promising results in advanced clinical trials. Some studies showed that GCPII may serve also as PCa blood serum marker, but this has not been validated due to the lack of methods suitable for accurate detection of GCPII in human blood. Moreover, GCPII is also expressed in brain, where it cleaves inhibitory N-acetyl-α-L- aspartyl-L-glutamate (NAAG) to release excitatory L-glutamate and GCPII inhibition has been shown to be neuroprotective in animal models of several neuropathies. Tight binding inhibitors of GCPII have been identified by rational design, but all have poor bioavailability and thus cannot be used in clinics. Identifying new scaffolds by 'brute force' screening methods is thus essential; however, no such method for GCPII has been developed so far. Glutamate carboxypeptidase III (GCPIII) is also expressed in brain and cleaves NAAG. It is thus an important protein for understanding of GCPII function as well as GCPII targeting in medicine. Here, we focused on development of novel methods for quantification of both...
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TOWNHOUSE ON THE WATERFRONT IN PŘEROV
Superatová, Alena ; Navrátil, Václav (referee) ; Havliš, Karel (advisor)
Subject of this thesis is an urban and architectural design of buildings vacant lot at the corner intersection of streets Brabansko - A small splint near the city center of Přerov. Apartment Building Front Street closes and completes residential block. Corner is cantilevered, giving rise to leeward before. There are shops, facilities of the apartment building and garage. Above the shops are perched three floors forward of mass housing with 15 apartments. The analysis of the city has shown that in Prerov is not a retirement home and no day care. So I decided to tackle this problem. The rear wing of the house serves as a single health center. It has its own entrance, its core communications and access from the garage. Its components except surgeries and rehabilitation is the seat of nursing services. Its main role would be serving the elders who live in their homes. Nurses would be goung out for them, helping with housework, taking clothes to laundry, etc. These care services are already operating in other cities and enjoying great popularity. Residential house is inside the health center connected. Given the proximity care services are particularly suitable housing for the elders. Therefore, the flats designed to lay with disabilities. All apartments are with 2 bedrooms for one or two people. Each dwelling unit has a spacious balcony overlooking the waterfront.
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Enzyme activity of recombinant enzymes. Influence of histidine tag.
Navrátil, Václav ; Wsól, Vladimír (advisor) ; Zemanová, Lucie (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Václav Navrátil Supervisor: Prof. Ing. Vladimír Wsól, Ph.D. Title of diploma thesis: Enzymatic activity of recombinant enzymes. Evaluation of His- tag influence. AKR1B1, AKR1C1 and AKR1C3 are three representatives from 15 human enzymes of AKR superfamily, so far described. In the body they take part in a number of biochemical pathways and their substrates include both xenobiotics and endogenous compounds. Reduction of glucose to sorbitol catalyzed by AKR1B1 is associated with the development of secondary diabetic complications. AKR1B1 is also involved in cardiotoxic effect of the cytostatic drug daunorubicine. AKR1C1 is physiologically responsible for the conversion of progesterone to less efficient 20α- hydroxyprogesterone, thereby regulates progestational activity. Overexpression of AKR1C1 may be connected with resistance to certain cytostatic agents. AKR1C3 in human catalyzes a reaction in which testosterone and 5α-DHT is formed and it is also associated with development of several cancer types. Significant involvement of these enzymes in a number of pathological processes led to their closer study. The aim of this work was to evaluate influence of His-tag and chosen buffer on the...
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Design of mounting table for assembly of printing block onto hub according to micropoint
Navrátil, Václav ; Ranuša, Matúš (referee) ; Kučera, Petr (advisor)
The aim of this bachelor’s thesis is to create a draft for the design of mounting table for assembly of printig plate onto sleev according to microdot for newly designed mounting machine made by company Soma Engineering. The first part of the thesis includes the profile of the company, the principle of flexoprint and overview of other companies‘ machines. The second part focused on draft of possible versions of the solution, their pros and cons and estimated costs of individual solution. The third parst of thesis is dedicated to a chosen version and its detailed elaboration.
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TOWNHOUSE ON THE WATERFRONT IN PŘEROV
Malý, Miroslav ; Navrátil, Václav (referee) ; Havliš, Karel (advisor)
Main function of the house is living. House consists of three masses, which form the letter U, in the middle with quiscent atrium. Atrium is at the level of 2 floor, under the atrium is parking. The masses ,away from the south, rise. Southern is the lowest mass, doesnt shade the atrium. Mass in the background is the highest, overlooking the city.
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TOWNHOUSE ON THE WATERFRONT IN PŘEROV
Superatová, Alena ; Navrátil, Václav (referee) ; Havliš, Karel (advisor)
Subject of this thesis is an urban and architectural design of buildings vacant lot at the corner intersection of streets Brabansko - A small splint near the city center of Přerov. Apartment Building Front Street closes and completes residential block. There are shops, facilities of the apartment building and garage. Above the shops are perched three floors forward of mass housing with 13 apartments.
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