The Interaction of the Calcium Sensitiser Levosimendan with Cardiac Troponin C

Cardiac failure is one of the leading causes of mortality in developed countries. As life expectancies of the populations of these countries grow, the number of patients suffering from cardiac insufficiency also increase. Effective treatments including the use of calcium sensitisers are being sought. They cause a positive inodilatory effect on cardio-myocytes without deleterious effects (arrhythmias) resulting from increases in intracellular calcium concentration. Levosimendan is a novel calcium sensitiser that hasbeen proved to be a welltolerated and effective treatment for patients with severe decompensated heart failure. Cardiac troponin C (cTnC) is its target protein. However, there have been controversies about the interactions between levosimendan and cTnC. Some of these controversies have been addressed in this dissertation. Furthermore, studies on the calcium sensitising mechanism based on the interactions between levosimendan and cTnC as followed by nuclear magnetic resonance(NMR) are presented and discussed. Levosimendan was found to interact with bothdomains of the calcium-saturated cTnC in the absence of cardiac troponin I (cTnI). In the presence of cTnI, the C-domain binding site was blocked and levosimendan interacted only with the regulatory domain of cTnC. This interaction may have caused the observed calcium sensitising effect by priming the N-domain for cTnI binding thereby extending the lifetime of that complex. It is suggested that this is achieved by shifting the equilibrium between open and closed conformations.

Investigation of interaction between native and impurity defects in ZnSe

Zinc selenide is a prospective material for optoelectronics. The fabrication of ZnSe­based light-emitting diodes is hindered by complexity of p-type doping of the component materials. The interaction between native and impurity defects, the tendency of doping impurity to form associative centres with native defects and the tendency to self-compensation are the main factors impeding effective control of the value and type of conductivity. The thesis is devoted to the study of the processes of interaction between native and impurity defects in zinc selenide. It is established that the Au impurity has the most prominent amphoteric properties in ZnSe among Cu, Ag and Au impurities, as it forms a great number of both Au; donors and Auz„ acceptors. Electrical measurements show that Ag and Au ions introduced into vacant sites of the Zn sublattice form simple single-charged Agz„+ and Auzn+ states with d1° electron configuration, while Cu ions can form both single-charged Cuz„ (d1) and double-charged Cuzr`+ (d`o) centres. Amphoteric properties of Ag and Au transition metals stimulated by time are found for the first time from both electrical and luminescent measurements. A model that explains the changes in electrical and luminescent parameters by displacement of Ag ions into interstitial sites due to lattice deformation forces is proposed. Formation of an Ag;-donor impurity band in ZnSe samples doped with Ag and stored at room temperature is also studied. Thus, the properties of the doped samples are modified due to large lattice relaxation during aging. This fact should be taken into account in optoelectronic applications of doped ZnSe and related compounds.

Building a usable and accessible semantic web interaction platform

Semantic Web applications take off is being slower than expected, at least with respect to “real-world” applications and users. One of the main reasons for this lack of adoption is that most Semantic Web user interfaces are still immature from the usability and accessibility points of view. This is due to the novelty of these technologies, but this also motivates the exploration of alternative interaction paradigms, different from the “traditional” Web or Desktop applications ones. Our proposal is realized in the Rhizomer platform, which explores the possibilities of the object–action interaction paradigm at the Web scale. This paradigm is well suited for heterogeneous resource spaces such as those common in the Semantic Web. Resources, described by metadata, correspond to the objects in the paradigm. Semantic web services, which are dynamically associated to these objects, correspond to the actions. The platform is being put into practice in the context of a research project in order to build an open application for media distribution based on Semantic Web technologies. Moreover, its usability and accessibility have been evaluated in this real setting and compared to similar systems.