Src kinase plays a crucial role in a multitude of fundamental cellular processes. Src is an essential component of signalling pathways controlling cellular proliferation, motility or differentiation, and is often found deregulated in tumours. Src activity is therefore maintained under stringent and complex regulation mediated by SH3 and SH2 domains and the phosphorylation state of tyrosines 416 and 527. Active Src adopts an open conformation whereas inactive state of the kinase is characterised by a compact structure stabilised by inhibitory intramolecular interactions. We identified phosphorylation of tyrosine 90 within binding surface of SH3 domain as a new regulatory switch controlling Src kinase activation. Using substitutions mimicking phosphorylation state of the residue we demonstrated that tyrosine 90 phosphorylation controls Src catalytic activity, conformation and interactions mediated by the SH3 domain, representing a positive regulatory mechanism leading to elevated activation of mitogenic pathways and increased invasive potential of cells. Based on correlation between compactness of Src structure and its catalytic activity, we constructed a FRET-based sensor of Src conformation enabling to measure the dynamics of Src activation in cells with spatio-temporal resolution. We found that...

Introduction: Actually 0.7-1 percent of all deliveries can be followed by secondary uterine bleeding. There is a residual trophoblastic tissue diagnosed in most of these cases and it is often managed by repeat intrauterine interventions. These operations are connected with high risk of formation of intrauterine adhesions and their early diagnosis and management can be important for next fertility. Material and methods: There were generally 188 patients included into the study. All patients underwent ultrasound examination in 6 weeks after delivery and ambulant hysteroscopy after next 2 months without anesthesia. Described intrauterine pathologies (residual tissue and adhesions) were managed in one step. Results: In cases with suspect ultrasound finding, the retained trophoblastic tissue was diagnosed by hysteroscopy in 66 percent vs. in 96 percent with sensitivity 85 percent and specificity 85 percent. Patients with intrauterine adhesions had normal ultrasound finding in 74 percent and it did not recognized patients with severe adhesions in 94 percent. Clinical signs had generally 72 percent of patients with diagnosed left residual tissue. Number of severe residual tissue is increasing with delay of instrumental evacuation from delivery (10 vs. 30 percent). When is necessary to repeat the operation...

The ERK signalling cascade comprised of protein kinases Raf, MEK and ERK is an evolutionarily conserved member of MAPK family that is activated in response to wide range of extracellular stimuli. The ERK pathway controls fundamental cellular functions including cell proliferation, differentiation, apoptosis or cell motility. To control such a diverse cellular responses by a single pathway cells have evolved regulatory mechanisms that channel the extracellular signals towards the specific biological response. Crucial to this control are non- enzymatic proteins termed scaffolds that associate with and enhance functional interaction of the components of MAPK pathways and can regulate amplitude, timing, specificity and location of signals. Scaffold protein RACK1 associates with several components of cell migration machinery including integrins, FAK, Src and the ERK pathway core protein kinases. RACK1 regulates distinct steps of cell migration such as establishment of cell polarity and focal adhesion turnover, however, the molecular mechanism by which RACK1 regulates these processes remains largely unknown. The main aim of this study was to investigate the functional role of RACK1 in cell motility, in particular to identify new effector proteins utilized by the ERK pathway and RACK1 in the regulation of...

The work is divided into two parts – theoretical and practical. The first, theoretical part is focused on introduction with the problematics, describing the concept of translation motion and brake physics, defining terms adhesion and friction, skid, driving resistances, calculation formulas etc. After the mechanics chapter follows the chapter about tire and its composition and properties, and a brake system chapter, describing Anti-lock brake system (ABS) and some other important brake-support systems. Second part of this thesis is focused on practical side, which contains acceleration measuring and skid marks creation, followed by evaluation of measured data in form of calculations and graphs.

The adhesion in the wheel-rail contact can be effectively controlled by using the friction modifier. Adhesion control can reduce excessive wear of the contact bodies or noise. The essence of this diploma thesis is to determine the optimal amount of friction modifier in wheel-rail contact depending on the climatic and operating conditions. For experimental study of the behavior of the friction modifier, the twin-disc device is used. Twin-disc simulates and controls the most important operating parameters such as speed, slip, attack angle or contact pressure. On the basis of these findings, the off-board top-of-rail lubricator system was designed. This system controls the amount of friction modifier according to current climatic and operating conditions.

Předložená disertační práce se zabývá experimentálním studiem modifikátorů tření a maziv pro temeno kolejnice, které jsou aplikovány do kontaktu kola a kolejnice za účelem optimalizace adheze a redukce hluku. Hlavním cílem práce bylo objasnit vliv aplikovaného množství a složení těchto látek na adhezi v kontaktu. Hlavní pozornost byla věnována zejména potencionálním hrozbám souvisejících s kriticky nízkou adhezí, která může nastat po aplikaci těchto látek. Experimentální studium probíhalo v laboratorních i reálných podmínkách, konkrétně v tramvajovém provozu. V případě laboratorních experimentů byl využit komerční tribometr a dvoudiskové zařízení umožňující simulovat průjezd vozidla traťovým obloukem. Kromě samotné adheze bylo při experimentech sledováno také opotřebení a míra hluku. Výsledky ukázaly, že maziva pro temeno kolejnice jsou schopna poskytovat požadované třecí vlastnosti, nicméně jejich chování je silně závislé na aplikovaném množství. V případě předávkování kontaktu dochází ke kriticky nízkým hodnotám adheze, které vedou k výraznému prodloužení brzdné dráhy. V případě modifikátorů tření bylo ukázáno, že chování těchto látek je výrazně ovlivněno odpařováním základního média. Výsledky také ukázaly, že nadměrné množství částic pro modifikaci tření může způsobit kriticky nízké hodnoty adheze. U obou výše zmíněných typů produktů byl prokázán pozitivní vliv na míru opotřebení a míru poškození povrchu, zatímco významná redukce hluku byla dosažena pouze v případech, kdy došlo ke značnému poklesu adheze. V závěru této práce jsou uvedena doporučení pro další výzkumné aktivity v této oblasti.

This master´s thesis is focused on chosen dynamic parameters of a sport vehicle represented by student formula Dragon 7 and comparison of these parameters with conventional vehicles represented by two exemplars of ŠKODA Superb III. Driving tests used for the comparison are simulating the real driving situations from the roads in order to possibly use those for the road accident analysis in the future. All the measurements were taken under lower adhesion conditions which might help solving of the road accidents under such conditions in the future. There is also a description of vehicle driving systems and components which have an influence on the vehicle´s driving dynamics incorporated in the thesis.

This diploma thesis deals with the analysis of selected properties of horizontal road marking (HRM). In terms of anti-skid properties measurements are made to determine the longitudinal friction coefficient, the coefficient of adhesion under different conditions and skid resistance of HRM. Measurements of anti-skid properties are supplemented by measurement of retroreflection of HRM. The theoretical part describes the current state of the issue, general characteristics of horizontal road marking and quantities measured in this thesis (friction and adhesion). The practical part consists of description of used measuring devices, custom solution and results analysis. The solution consists of the description of the measured samples, their preparation, subsequent measurement and a detailed description of the method of measured data evaluation. Data analysis is based on comparison of results obtained from individual sample groups and on comparison of measured values among themselves. The thesis is supplemented with photo documentation and video footage.

Hlavním cílem této práce je studium aktuálního problému adheze mezi kompozitními materiály, a určení vlivu složení mezivrstvy v pevnosti adhezivního spoje mezi vláknové (FRC) a částicové (PFC) kompozity, používané ve stomatologii. FRC tyčinky byly vytvořené na bázi komerční dimetakrylatové pryskyřice a skleněných S vláken. PFC byl vytvořen ze směsi pryskyřic (bis-GMA a PEGDMA), plněných drceným barnatým sklem. Celkově bylo připraveno a vyzkoušeno 84 vzorků. Vzorky byly rozdělené do pěti hlavních skupin. První skupina byla vytvořena ze série vzorků bez mezivrstvy. Zbylé čtyři skupiny byly rozděleny dle složení mezivrstvy (tloušťky a druhu pryskyřic). Částicové kompozity vzorků se lišily obsahem plniva (0, 10, 40 hm %). FRC tyčinky byly stejné pro všechny vzorky. Univerzální testovací přístroj ZWICK Z010 byl použit k zjištění smykové pevnosti adhezivního spoje všech vzorků. Rastrovací elektronový mikroskop byl použít k pozorování místa porušení. Ze získaných výsledků vyplívá, že s přidáváním mezivrstvy mezi vláknovým a částicovým narůstá smyková pevnost spoje. Důležitost těchto výsledků je způsobená tím, že v posledních letech použití těchto materiálů ve stomatologii narůstá a adheze zůstává jeden z hlavních problémů při klinické praxi.

Thesis deals with problems about areas of a non-assembling diagnostics namely resonant adhesive tester according to an EUSAMA methodology. Result of the methodology is a technical condition examination of dampers. However with regard to testing of whole suspension and damping vehicle system are results distorted by influence of testing conditons and another vehical components. Goal of thesis is analysis limits of practical use resonant adhesive tester for a quality checking of mount wheels damping. Problems are solved by a virtual simulation in a program Adams/View where is created a real model of vehical axle of Skoda Roomster TDI 1.4. In the model is consequently simulated possible functional characteristics and abrasions of single components which influence the methodology. Virtual model will be using for research activity of Institute of machine and industrial design Faculty of mechanical ingeneering Brno University of technology.