Data and Query Adaptation Using DaemonX

The most common applications of the today's IT world are information systems. The problems related to their design and implementation have sufficiently been solved. However, the true problems occur when an IS is already deployed and user requirements change. In this paper we introduce DaemonX - an evolution management framework which enables to manage evolution of complex applications efficiently and correctly. Using the idea of plug-ins, it enables to model almost any kind of a data format (currently XML, UML, ER, and BPMN). Since it preserves also mapping among modeled constructs of modeled formats via a common platform-independent model, it naturally supports propagation of changes to all related and affected parts

A Comparison of Two Motion Sensors for the Assessment of Free-Living Physical Activity of Adolescents

This study assessed and compared the daily step counts recorded by two different motion sensors in order to estimate the free-living physical activity of 135 adolescent girls. Each girl concurrently wore a Yamax pedometer and an ActiGraph accelerometer (criterion measure) every day for seven consecutive days. The convergent validity of the pedometer can be considered intermediate when used to measure the step counts in free-living physical activity; but should be considered with caution when used to classify participants’ step counts into corresponding physical activity categories because of a likelihood of ‘erroneous’ classification in comparison with the accelerometer

Společnost vlastníků příspěvek k řešení dělnické otázky

Katedra sociologie (1966-1971)Filozofická fakult

Petr Parléř a mistři gmündští

monografi

Hydrolytically degradable polymer micelles for drug delivery: A SAXS/SANS kinetic study

We report kinetic studies of therapeutically highly potent polymer–drug conjugates consisting of amphiphilic N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers bearing the anticancer drug doxorubicin (Dox). Highly hydrophobic cholesterol moieties as well as the drug were attached to the polymer backbone by a pH-sensitive hydrazone bond. Moreover, the structure of the spacer between the polymer carrier and the cholesterol moiety differed in order to influence the release rate of the hydrophobic moiety, and thus the disintegration of the high-molecular-weight micellar nanoparticle structure. We performed time-dependent SAXS/SANS measurements after changing pH from a typical blood value (pH 7.2) to that of tumor cells (pH 5.0) to characterize the drug release and changes in particle size and shape. Nanoparticles composed of the conjugates containing Dox were generally larger than the drug-free ones. For most conjugates, nanoparticle growth or decay was observed in the time range of several hours. It was established that the growth/decay rate and the steady-state size of nanoparticles depend on the spacer structure. From analytical fitting, we conclude that the most probable structure of the nanoparticles was a core–shell or a core with attached Gaussian chains. We concluded that the spacer structure determined the fate of a cholesterol derivative after the pH jump. Fitting results for 5α-cholestan-3-onecholestan-3-one and cholesteryl-4-oxopentanoate (Lev-chol) implied that cholesterol moieties continuously escape from the core of the nanoparticle core and concentrate in the hydrophilic shell. In contrast, cholest-4-en-3-one spacer prevent cholesterol escaping. Dox moiety release was only observed after a change in pH. Such findings justify the model proposed in our previous paper. Lastly, the cholesteryl 4-(2-oxopropyl)benzoate (Opb-Chol) was a different case where after the release of hydrophobic Opb-Chol moieties, the core becomes more compact. The physicochemical mechanisms responsible for the scenarios of the different spacers are discussed

Pronounced Cellular Uptake of Pirarubicin versus That of Other Anthracyclines: Comparison of HPMA Copolymer Conjugates of Pirarubicin and Doxorubicin

Many conjugates of water-soluble polymers with biologically active molecules were developed during the last two decades. Although, therapeutic effects of these conjugates are affected by the properties of carriers, the properties of the attached drugs appear more important than the same carrier polymer in this case. Pirarubicin (THP), a tetrahydropyranyl derivative of doxorubicin (DOX), demonstrated more rapid cellular internalization and potent cytotoxicity than DOX. Here, we conjugated the THP or DOX to <i>N</i>-(2-hydroxypropyl)­methacrylamide copolymer via a hydrazone bond. The polymeric prodrug conjugates, P-THP and P-DOX, respectively, had comparable hydrodynamic sizes and drug loading. Compared with P-DOX, P-THP showed approximately 10 times greater cellular uptake during a 240 min incubation and a cytotoxicity that was more than 10 times higher during a 72-h incubation. A marginal difference was seen in P-THP and P-DOX accumulation in the liver and kidney at 6 h after drug administration, but no significant difference occurred in the tumor drug concentration during 6–24 h after drug administration. Antitumor activity against xenograft human pancreatic tumor (SUIT2) in mice was greater for P-THP than for P-DOX. To sum up, the present study compared the biological behavior of two different drugs, each attached to an <i>N</i>-(2-hydroxypropyl)­methacrylamide copolymer carrier, with regard to their uptake by tumor cells, body distribution, accumulation in tumors, cytotoxicity, and antitumor activity <i>in vitro</i> and <i>in vivo</i>. No differences in the tumor cell uptake of the polymer–drug conjugates, P-THP and P-DOX, were observed. In contrast, the intracellular uptake of free THP liberated from the P-THP was 25–30 times higher than that of DOX liberated from P-DOX. This finding indicates that proper selection of the carrier, and especially conjugated <i>active pharmaceutical ingredient</i> (API) are most critical for anticancer activity of the polymer−drug conjugates. THP, in this respect, was found to be a more preferable API for polymer conjugation than DOX. Hence the treatment based on enhanced permeability and retention (EPR) effect that targets more selectively to solid tumors can be best achieved with THP, although both polymer conjugates of DOX and THP exhibited the EPR effects and drug release profiles in acidic pH similarly