Estimation of the Value of the Firm

Tato diplomová práce se zabývá stanovením objektivizované hodnoty podniku Vakstav spol. s r.o. výnosovými metodami k 1. 4. 2014. Nejprve je vymezen teoretický rámec práce. Dále je provedena strategická a finanční analýza, analýza a prognóza generátorů hodnoty a sestavení finančního plánu. Samotné stanovení hodnoty podniku je provedeno na základě metody diskontovaného peněžního toku a metody ekonomické přidané hodnoty.This diploma thesis is focused on estimation of the value objectified of the Vakstav spol. s r. o. by using income-based methods at 1. 4. 2014. First is defined theoretical framework of valuation. Furthermore the strategic and financial analysis, analysis and forecast of value drivers and financial plan is done. The valuation is based on Discounted Cash flow method and Economic Value Added method.

Proteolytic systems of the blood fluke (Schistosoma mansoni).

Schistosomóza je závažné parazitární onemocnění člověka, jehož původcem jsou krevničky, krevní motolice rodu Schistosoma. Celosvětově je schistosomózou, která představuje globální světový problém, infikováno přes 200 miliónů lidí a dalších 750 miliónů je vystaveno riziku nákazy. Jediný účinný lék pro léčbu schistosomózy je chemoterapeutikum praziquantel, u kterého je riziko vzniku rezistence. Proteasy krevničky představuji nadějné cílové molekuly pro vývoj nových terapeutických strategií proti schistosomóze. Tato práce se zaměřuje na komplexní charakterizaci proteolytických systémů krevničky Schistosoma mansoni a určení jejich role v interakci s hostitelem. Za prvé byly pomocí metod funkční proteomiky popsány hlavní proteolytické aktivity sekretované jednotlivými vývojovými stádii krevničky, která parazitují v těle člověka. Tato analýza prokázala jejich komplexní a specifickou distribuci s převažujícími serinovými a cysteinovými proteasami a metaloproteasami. Za druhé byly pomocí přístupu chemické genomiky identifikovány povrchové a trávicí proteasy krevničky, konkrétně prolyloligopeptidasa a katepsiny typu B, C a D, jako vhodné cílové molekuly pro terapeutickou intervenci. Prolyloligopeptidasa byla biochemicky charakterizována na úrovni rekombinantního proteinu, byly vyvinuty její účinné...Schistosomiasis is a serious parasitic disease caused by blood flukes of the genus Schistosoma. It is a global health problem with more than 200 million people infected and 750 million people at risk. Current therapy relies on a single drug, praziquantel, for which there are concerns of emerging drug resistance. Proteases of schistosoma are promising target molecules for the development of new therapeutic strategies against schistosomiasis. This work focuses on the comprehensive characterization of proteolytic systems of Schistosoma mansoni and determination of their role in the interaction with the human host. First, the major proteolytic activities secreted by individual developmental stages of schistosoma that parasitize the human body were classified using functional proteomics. This analysis demonstrated their complex and specific distribution with predominant serine and cysteine proteases and metalloproteases. Second, tegumental and digestive proteases, namely prolyl oligopeptidase and cathepsins B, C and D, were identified by chemical genomics as suitable target molecules for therapeutic intervention. Prolyl oligopeptidase was biochemically characterized using a recombinant protein, its effective inhibitors were developed as templates for antischistosomal drugs, and a biological role of the...1. lékařská fakultaFirst Faculty of Medicin

The Proposal of Company Communication Mix

Bakalářská práce se zabývá sestavením návrhu komunikačního mixu pro spolupracující živnostníky Zdeňku Fajtovou a Helenu Šustákovou, které se zabývají výkonem biorezonanční terapie ve Východních Čechách. Práce analyzuje nynější komunikační mix, konkurenci a prostředí a navrhuje novou vhodnou kombinaci nástrojů komunikačního mixu, který zlepší postavení firmy na trhu a zlepší její konkurenceschopnost.The bachelor´s thesis deal with proposal of communication mix for cooperating self-employed person Zdeňka Fajtová and Helena Šustáková, who runs bioresonance therapy in Eastern Bohemia. The thesis analyzes the current communication mix, competition and environment, and proposes an appropriate combination of new communication mix, which improves the firm´s market position and improve its competitiveness.

SmSP2: A serine protease secreted by the blood fluke pathogen Schistosoma mansoni with anti-hemostatic properties.

BackgroundSerine proteases are important virulence factors for many pathogens. Recently, we discovered a group of trypsin-like serine proteases with domain organization unique to flatworm parasites and containing a thrombospondin type 1 repeat (TSR-1). These proteases are recognized as antigens during host infection and may prove useful as anthelminthic vaccines, however their molecular characteristics are under-studied. Here, we characterize the structural and proteolytic attributes of serine protease 2 (SmSP2) from Schistosoma mansoni, one of the major species responsible for the tropical infectious disease, schistosomiasis.Methodology/principal findingsSmSP2 comprises three domains: a histidine stretch, TSR-1 and a serine protease domain. The cleavage specificity of recombinant SmSP2 was determined using positional scanning and multiplex combinatorial libraries and the determinants of specificity were identified with 3D homology models, demonstrating a trypsin-like endopeptidase mode of action. SmSP2 displayed restricted proteolysis on protein substrates. It activated tissue plasminogen activator and plasminogen as key components of the fibrinolytic system, and released the vasoregulatory peptide, kinin, from kininogen. SmSP2 was detected in the surface tegument, esophageal glands and reproductive organs of the adult parasite by immunofluorescence microscopy, and in the excretory/secretory products by immunoblotting.Conclusions/significanceThe data suggest that SmSP2 is secreted, functions at the host-parasite interface and contributes to the survival of the parasite by manipulating host vasodilatation and fibrinolysis. SmSP2 may be, therefore, a potential target for anti-schistosomal therapy

Prolyl endopeptidase of the blood fluke Schistosoma mansoni

Prolyl endopeptidasa SmPEP z krevničky střevní (S. mansoni) nebyla dosud studována. Tento enzym je zajímavý z pohledu vyhledávání nových molekulárních cílů pro léčbu schistosomózy. SmPEP byla detekována v extraktu z dospělých červů krevničky střevní pomocí enzymové aktivity a imunoreaktivity Aktivní forma SmPEP byla připravena jako rekombinantní protein v expresním systému E. coli a byla chromatograficky izolována. Rekombinantní SmPEP vykazuje pH optimum cca 8. Analýza substrátové specifity ukázala, že SmPEP štěpí peptidové substráty v endopeptidasovém módu, ale nikoli makromolekulární proteinové substráty. Pomocí syntetických flurogenních peptidových substrátů byly určeny preference pro aminokyseliny v pozicích P3-P1'. Byla určena inhibiční specifita SmPEP a jako nejúčinnější inhibitory nalezeny Z-Ala-Pro-CMK a Z-Arg-Pro-CHO. Pro rekombinantní SmPEP byly nalezeny primární krystalizační podmínky.Prolyl endopeptidase SmPEP from the blood fluke Schistosoma mansoni is investigated here for the first time. This enzyme is potentially interesting as a drug target for the treatment of schistosomiasis. SmPEP was detected in the extract of adult worms by enzyme activity and immunoreactivity. Enzymatically active SmPEP was produced in the E. coli expression system and was chromatographically purified. The pH optimum of recombinant SmPEP was about 8. Substrate specificity analysis revealed that SmPEP cleaved peptide substrates by endopeptidase activity, however, macromolecular substrates were not fragmented. The residue preferences in the positions P3 to P1' were determined using synthetic fluorogenic peptide substrates. SmPEP was found to be highly sensitive to the inhibition by Z-Ala-Pro-CMK and Z-Arg-Pro-CHO. Primary screening of crystallization conditions for recombinant SmPEP was performed. " (In Czech)"Katedra biochemieDepartment of BiochemistryPřírodovědecká fakultaFaculty of Scienc

Recombinant procathepsin B from blood fluke Schistosoma mansoni

Department of BiochemistryKatedra biochemieFaculty of SciencePřírodovědecká fakult

Prolyl endopeptidase of the blood fluke Schistosoma mansoni

Prolyl endopeptidase SmPEP from the blood fluke Schistosoma mansoni is investigated here for the first time. This enzyme is potentially interesting as a drug target for the treatment of schistosomiasis. SmPEP was detected in the extract of adult worms by enzyme activity and immunoreactivity. Enzymatically active SmPEP was produced in the E. coli expression system and was chromatographically purified. The pH optimum of recombinant SmPEP was about 8. Substrate specificity analysis revealed that SmPEP cleaved peptide substrates by endopeptidase activity, however, macromolecular substrates were not fragmented. The residue preferences in the positions P3 to P1' were determined using synthetic fluorogenic peptide substrates. SmPEP was found to be highly sensitive to the inhibition by Z-Ala-Pro-CMK and Z-Arg-Pro-CHO. Primary screening of crystallization conditions for recombinant SmPEP was performed. " (In Czech)

The Proposal of Company Communication Mix

The bachelor´s thesis deal with proposal of communication mix for cooperating self-employed person Zdeňka Fajtová and Helena Šustáková, who runs bioresonance therapy in Eastern Bohemia. The thesis analyzes the current communication mix, competition and environment, and proposes an appropriate combination of new communication mix, which improves the firm´s market position and improve its competitiveness

Proteolytic systems of the blood fluke (Schistosoma mansoni).

Schistosomiasis is a serious parasitic disease caused by blood flukes of the genus Schistosoma. It is a global health problem with more than 200 million people infected and 750 million people at risk. Current therapy relies on a single drug, praziquantel, for which there are concerns of emerging drug resistance. Proteases of schistosoma are promising target molecules for the development of new therapeutic strategies against schistosomiasis. This work focuses on the comprehensive characterization of proteolytic systems of Schistosoma mansoni and determination of their role in the interaction with the human host. First, the major proteolytic activities secreted by individual developmental stages of schistosoma that parasitize the human body were classified using functional proteomics. This analysis demonstrated their complex and specific distribution with predominant serine and cysteine proteases and metalloproteases. Second, tegumental and digestive proteases, namely prolyl oligopeptidase and cathepsins B, C and D, were identified by chemical genomics as suitable target molecules for therapeutic intervention. Prolyl oligopeptidase was biochemically characterized using a recombinant protein, its effective inhibitors were developed as templates for antischistosomal drugs, and a biological role of the..