Nucleic acids have been identified as procoagulant species in plasma and in vivo animal studies. It is believed that the nucleic acids act as physiological activators of the contact system. However, in order to obtain a better understanding of the role of nucleic acids in the activation of the contact system it is important to analyze and evaluate the individual proteins of the contact system that are stimulated by nucleic acids and identify accompanying proteins required to mediate the nucleic acid-stimulated activation. Previous works suggested that nucleic acids stimulate the activation of factor XII (FXII) in the presence of prekallikrein (PK) and high molecular weight kininogen (HK). In this study we will confirm if both PK and HK are required for nucleic acid-stimulated activation of FXII. We will also study the role of nucleic acids in the activation of PK in the presence or absence of activated FXII (FXIIa) and HK. Previous works also identified that zinc (Zn2+) accelerates surface-mediated activation of FXII by PK and HK, and PK by FXIIa and HK. We will be evaluating zinc’s ability to enhance nucleic acid-stimulated activation of both FXII and PK. We have found that nucleic acids stimulate activation of FXII in the presence of PK and this furthered upon addition of HK. Nucleic acids also stimulate the activation of PK in the presence of FXIIa and this is furthered upon addition of HK. Nucleic acids have stimulated activation of FXII and PK in a dose dependent manner in the presence of the aforementioned accompanying proteins. We have showed that Zn2+ enhances activation of the contact system. Zn2+ enhances nucleic acid-stimulated, PK/HK-mediated activation of FXII. It also enhances nucleic acid-stimulated, FXIIa/HK-mediated activation of PK. These findings enrich our understanding of the role of nucleic acids and zinc in the contact system. / Thesis / Master of Science (MSc)

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Today there is an increasing clinical demand and expectation of patients for biomaterials, which underscores the importance of discovering the correlations between biomaterials and biological systems, especially blood. When an artificial material makes contact with blood, the first event is a rapid adsorption of plasma protein on the material surface, on top of which the innate immune system is triggered, with potentially detrimental consequences. The work presented in this thesis, reported in four papers, was designed to investigate complications associated with (a) biomaterial-induced immune systems, including activation mechanisms and crosstalk between cascades on the biomaterial surface, and with (b) clinical investigations. In Paper I and Paper II, a series of studies led to the development of a direct prediction of the subsequent biological events based on the pattern of initially bound proteins. A reciprocal relationship was demonstrated between activation of the contact system and the complement system when they were induced on artificial material surfaces. Based on these studies, a robust and simple method for biocompatibility testing was proposed and validated, yielding high specificity and sensitivity when compared to today’s gold standard. Paper III investigated biomaterial-induced activation of complement and leukocytes in dialysis treatment-related conditions. The results suggested that citrate is more biocompatible than the conventionally used acetate. This reduction in activation could be further enhanced with higher citrate concentrations, suggesting that dialysis fluid containing citrate is a promising alternative to acetate dialysis fluid. Paper IV investigated complement initiation mechanisms with clinical implications. An experimental system was set up to revisit the initiation of the complement alternative pathway, and correlations were found between chaotropic or nucleophilic agents and iC3 generation under physiologically relevant conditions. A clinical study of hepatic encephalopathy patients indicated a direct correlation between elevated plasma ammonia and iC3 formation, as well as with complement activation in vivo.  Taken together, these studies have provided a model for a robust biomaterial test and have investigated biomaterial-induced complications in the fluid phase in clinically related conditions; furthermore, the basic mechanisms of complement activation have been dissected in relation to disease symptoms. Keywords: Complement system, contact system, blood, biomaterials, biocompatibility, in vitro screening, iC3, dialysis

Dans la première partie de cette thèse, nous caractérisons complètement toutes les x-sorties plates et leurs lieux singuliers pour un système avec deux contrôles qui est équivalent au système chaîné. Nous appliquons aussi ce résultat au système de robot mobile avec des remorques pour calculer toutes ses x-sorties plates. Dans la deuxième partie, nous présentons un nouveau modèle pour le système à n-barres dans l'espace de dimension m+1. Nous montrons que ce système est localement équivalent au système m-chaîné et caractérisons aussi ses lieux singuliers. Ensuite, nous analysons sa propriété de platitude et donnons ses sorties plates minimales. Dans la troisième partie, nous donnons des conditions nécessaires et suffisantes pour qu'une distribution soit équivalente à la distribution de Cartan pour des surfaces. Finalement, dans la quatrième partie, nous donnons des conditions nécessaires et suffisantes vérifiables pour qu'un système multi-entrées soit linéarisable par bouclage orbital. / In the first part of the Ph.D thesis, we characterize all x-flat outputs and their singular loci of any 2-inputs driftless control system wich is equivalent to the chained system. Then we apply that result to the n-trailer system in order to calculate all its x-flats outputs. In the second part, we establish a new model of the n-bar system in (m+1)-dimensional space. With the help of this model, we show that the system is locally equivalent to the m-chained system and also describe its singular locus. Furthermore we analyse its flatness property and determine its minimal flat outputs. In the third part, we give necessary and sufficient conditions for a distribution to be lacally equivalent to the Cartan distribution for surfaces. Finally, in the fourth part, we give necessary and sufficient verifiable conditions for a multi-input affine control system to be orbital feedback linearizable.

Dans cette thèse nous présentons les résultats sur l'emploi des systèmes Hamiltoniens à port et des systèmes de contact commandés pour la modélisation et la commande de systèmes issus de la Thermodynamique Irréversible. Premièrement nous avons défini une classe de pseudo-systèmes Hamiltoniens à port, appelée systèmes Hamiltoniens à port irréversibles, qui permet de représenter simultanément le premier et le second principe de la Thermodynamique et inclut des modèles d'échangeurs thermiques ou de réacteurs chimiques. Ces systèmes ont été relevés sur l'espace des phases thermodynamiques muni d’une forme de contact, définissant ainsi une classe de systèmes de contact commandés, c'est-à-dire des systèmes commandés non-linéaires définis par des champs de contacts stricts. Deuxièmement, nous avons montré que seul un retour d'état constant préserve la forme de contact et avons alors résolu le problème d'assignation d'une forme de contact en boucle fermée. Ceci a mené à la définition de systèmes de contact entrée-sortie et l'analyse de leur équivalence par retour d'état. Troisièmement, nous avons montré que les champs de contact n'étaient en général pas stables en leur zéros et avons alors traité du problème de la stabilisation sur une sous-variété de Legendre en boucle fermée. / This doctoral thesis presents results on the use of port Hamiltonian systems (PHS) and controlled contact systems for modeling and control of irreversible thermodynamic processes. Firstly, Irreversible PHS (IPHS) has been defined as a class of pseudo-port Hamiltonian system that expresses the first and second principle of Thermodynamics and encompasses models of heat exchangers and chemical reactors. These IPHS have been lifted to the complete Thermodynamic Phase Space endowed with a natural contact structure, thereby defining a class of controlled contact systems, i.e. nonlinear control systems defined by strict contact vector fields. Secondly, it has been shown that only a constant control preserves the canonical contact structure, hence a structure preserving feedback necessarily shapes the closed-loop contact form. The conditions for state feedbacks shaping the contact form have been characterized and have lead to the definition of input-output contact systems. Thirdly, it has been shown that strict contact vector fields are in general unstable at their zeros, hence the condition for the the stability in closed-loop has been characterized as stabilization on some closed-loop invariant Legendre submanifolds

<p>Nitric oxide (NO) is expressed in inflammatory tissues. However, NO effects are controversial in inflammation; NO is described as acting in a dose dependent manner and possess both pro-inflammatory and anti-inflammatory properties. </p><p>The present thesis explored the role of NO in relation to white blood cell (WBC) and protein system activation by foreign surfaces in simulated extracorporeal circulation (SECC) using human whole blood from volunteer donors. Three doses of NO, 40 ppm, 80 ppm and 500 ppm, were administered and an array of markers of WBC and protein activation were studied. Neutrophil degranulation was detected with myeloperoxidase (MPO), human neutrophil lipocalin (HNL) and lactoferrin (LF); eosinophil degranulation with eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO); and basophil degranulation with histamine. Furthermore, whole blood and WBC capacity to produce reactive oxygen species (ROS) were studied and cytokine release was measured with IL-1 and IL-10. Complement activation was measured with C3a and C5b-9 complex and contact system activation with FXIIa-C1INH, FXIIa-AT, FXIa-C1INH and FXIa-AT.</p><p>NO increased neutrophil degranulation at all dose levels and 80 ppm NO increased basophil degranulation; whereas, NO exerted no effect on eosinophil degranulation, WBC subset counts, cytokine release or capacity to produce ROS. In addition, while increasing both specific and azurophil degranulation with 40 ppm, 80 ppm and 500 ppm, NO reversed the classical degranulation hierarchy with 500 ppm and azurophil degranulation became predominant. Furthermore, NO effect was greater with 500 ppm than with 80 ppm, indicating a dose response effect. The lack of iNOS mRNA expression in WBC and lack of L-NAME effect on degranulation and nitrite/nitrate production, together with absent increase in nitrite/nitrate in controls, excluded autocrine or paracrine regulation of degranulation. FXIIa-AT and FXIa-AT complexes increased and became predominant during early recirculation, whereas FXIIa-C1INH and FXIa-C1INH complexes were predominant at baseline but remained unaltered, suggesting contact system inhibition predominantly via AT. C3a and C5b-C9 increased. NO had no effect on either contact or complement system activation; however, 500 ppm NO shortened active clotting time.</p><p>In conclusion, the present data suggest that NO has a direct effect on neutrophil and basophil degranulation. Recognition of NO as an enhancer of degranulation may give access to new therapeutic tools for local and systemic inflammatory therapies; whereas, the identification of increased AT mediated inhibition of FXIIa and unchanged C1INH complexes presents new possibilities for therapeutic intervention in conditions such as hereditary angioedema and heart surgery.</p>

Nitric oxide (NO) is expressed in inflammatory tissues. However, NO effects are controversial in inflammation; NO is described as acting in a dose dependent manner and possess both pro-inflammatory and anti-inflammatory properties. The present thesis explored the role of NO in relation to white blood cell (WBC) and protein system activation by foreign surfaces in simulated extracorporeal circulation (SECC) using human whole blood from volunteer donors. Three doses of NO, 40 ppm, 80 ppm and 500 ppm, were administered and an array of markers of WBC and protein activation were studied. Neutrophil degranulation was detected with myeloperoxidase (MPO), human neutrophil lipocalin (HNL) and lactoferrin (LF); eosinophil degranulation with eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO); and basophil degranulation with histamine. Furthermore, whole blood and WBC capacity to produce reactive oxygen species (ROS) were studied and cytokine release was measured with IL-1 and IL-10. Complement activation was measured with C3a and C5b-9 complex and contact system activation with FXIIa-C1INH, FXIIa-AT, FXIa-C1INH and FXIa-AT. NO increased neutrophil degranulation at all dose levels and 80 ppm NO increased basophil degranulation; whereas, NO exerted no effect on eosinophil degranulation, WBC subset counts, cytokine release or capacity to produce ROS. In addition, while increasing both specific and azurophil degranulation with 40 ppm, 80 ppm and 500 ppm, NO reversed the classical degranulation hierarchy with 500 ppm and azurophil degranulation became predominant. Furthermore, NO effect was greater with 500 ppm than with 80 ppm, indicating a dose response effect. The lack of iNOS mRNA expression in WBC and lack of L-NAME effect on degranulation and nitrite/nitrate production, together with absent increase in nitrite/nitrate in controls, excluded autocrine or paracrine regulation of degranulation. FXIIa-AT and FXIa-AT complexes increased and became predominant during early recirculation, whereas FXIIa-C1INH and FXIa-C1INH complexes were predominant at baseline but remained unaltered, suggesting contact system inhibition predominantly via AT. C3a and C5b-C9 increased. NO had no effect on either contact or complement system activation; however, 500 ppm NO shortened active clotting time. In conclusion, the present data suggest that NO has a direct effect on neutrophil and basophil degranulation. Recognition of NO as an enhancer of degranulation may give access to new therapeutic tools for local and systemic inflammatory therapies; whereas, the identification of increased AT mediated inhibition of FXIIa and unchanged C1INH complexes presents new possibilities for therapeutic intervention in conditions such as hereditary angioedema and heart surgery.

This bachelor thesis is a project of new five-storey, semi basement guesthouse in Opava. This guesthouse will be used for accommodation, catering and recreation. Accommodation capacity is 21 people. In the basement is a technical background. The first floor is designed for the overall run of the guesthouse, staff, catering and sports. In the second and third floor are rooms for guests. Almost every room has a balcony. In the fourth floor is a common room with adjoining terrace. The building is brick. The vertical structures are made of ceramic blocks. Outer walls are insulated by outer contact system. The ceilings are mostly ceramic-concrete and a smaller part of the reinforced concrete. The guesthouse is roofed by single-flat roof.

Nanoparticles have been used in industry and in medicine due to their properties which give them beneficial uses. This usage of the nanoparticles has risen the question about how harmful they are to the human body, the connection between the exposure to nanoparticles, and many diseases that occur in the body. Methods This study focused on the effect of nanoparticles in a whole human blood loop model. The blood was incubated with Silica, Titanium dioxide and Palladium particles in heparinized loops without any anticoagulants added. The blood’s cell count was analyzed with a cell counter and then complement, and contact system’s markers were analyzed with ELISA to detect a presence of activations in the systems. Experiments one to five were an optimization of test settings. Results An activation of the contact system was initiated in the loops containing the aggregated titanium dioxide nanoparticles. A high platelets consumption up to 73.8 % was observed as well as two visible clots. On top of that, blood smears showed micro-clots in the blood incubated with the aggregated nanoparticles. Conclusion Nanoparticles initiated an activation in the contact system in the aggregated form in comparison with the dispersed form. Further and deeper studies should be executed to observe the importance of the single or the aggregated form in the actual effect on the immune system.

Aim of the thesis is to explain the issue of forces acting in circuit breaker caused by magnetic fields induced by short-circuit current. This thesis is focused on force affecting in concrete system of a circuit breaker. The given circuit breaker is made by OEZ Letohrad, the type Modeion BD250. In the thesis the way of creating 3-D model is shown for the purpose of creating numeric simulation by ANSYS 11. The next approach of the thesis is the description of applicating the results for DC and AC current calculations. The noted calculation is made in the programme MATLAB 6.5. The solutions are mentioned at calculations both in the graphic form and numeric specifications. Visualisation was made by using GIF graphic system animation. The individual pictures processing was done in the programme UNLEAD GIF ANIMATOR 5.