Abstract The function of the transmembrane protein FasL is to complex with the Fas receptor in a target cell and induce target cell apoptosis. Fas/FasL-mediated apoptosis plays important role in immunoregulation. FasL expression is mostly seen in activated lymphocytes. We have characterized endothelial FasL expression in different functional compartments of lymph nodes and gut-associated lymphoid tissue. Furthermore, we have explored the functional role of endothelial FasL expression by analyzing correlation with apoptosis of lymphocyte subpopulations in lymph nodes and by assessing endothelial expression under different conditions by activation of immune functions in gastrointestinal mucosa. Immunohistochemical stainings (Fas, FasL, CD3, CD20, CD19, CD23, CD56, FVIII) were performed on 20 reactive lymph node tissues (I and II), 60 pediatric endoscopy biopsy samples (III) or 60 samples from gut resections (IV). A double-staining method combining apoptosis detection with the TUNEL-method and lymphocyte classification with FasL, Fas and cell lineage markers was optimized. Patient groups included non-pathological lymph nodes, pediatric cow’s milk-sensitive enteropathy, pediatric celiac disease, appendicitis, ulcerative colitis and Crohn’s disease. Control groups included normal biopsy samples from pediatric patients and non-pathological resecate samples from the appendix, colon or ileum to correspond to patient groups. Quantitative analysis (positive vessels or cells per mm2) was performed thoroughly for each anatomical region. In a subset of patients, soluble FasL in the serum was quantified with standard enzyme-linked immunosorbent assay. In reactive lymph nodes FasL expression was predominantly present in high endothelial venules located in the paracortical area, where apoptotic T and B lymphocytes, some expressing Fas, were subsequently found. In the gut wall vascular FasL expression was seen in high endothelial vessels near lymphoid follicles. Serum FasL was elevated in children with an abundance of mucosal lymphoid follicles. In IBD, vascular FasL was upregulated in ulcers and in the submucosa of colons affected by Crohn’s disease. The results indicate that endothelial FasL is characteristically present in high endothelial venules of lymphoid tissues. Detection of apoptotic Fas expressing lymphocytes adjacent to such vessels supports the idea that endothelial FasL functions as a selective gatekeeper by inducing apoptosis of Fas+ lymphocytes entering from the blood stream. / Tiivistelmä Solukalvon läpäisevän proteiinin, FasL:n, tehtävä on sitoutua kohdesolun Fas-reseptoriin ja indusoida kohdesolun apoptoosi. Fas/FasL-välitteinen apoptoosi on merkittävä tekijä immunologisessa säätelyssä. FasL ilmentyy pääsääntöisesti aktivoituneissa lymfosyyteissä. Olemme kuvanneet tutkimuksessamme FasL:n endoteelistä ilmentymistä imukudoksen eri toiminnallisissa alueissa ja suoliston lymfaattisessa kudoksessa. Lisäksi kartoitimme endoteelin FasL:n toiminnallista merkitystä analysoimalla sen yhteyttä lymfosyyttien alaryhmien apoptoosiin imusolmukkeissa ja arvioimalla FasL:n endoteelistä ilmentymistä suoliston limakalvon immunologisesti erilaisissa sairauksissa. Teimme immunohistokemiallisia värjäyksiä (Fas, FasL, CD3, CD20, CD19, CD23, CD56 ja FVIII) 20 reaktiiviselle imusolmukkeelle (I ja II), 60 lapsen endoskooppiselle biopsianäytteelle (III) sekä 60 suoliresekaattinäytteelle (IV). Optimoimme kaksoisvärjäysmenetelmän, missä yhdistettiin apoptoosin havainnointimenetelmä TUNEL ja FasL-, Fas- tai solulinjamarkkeri. Potilasryhmiin kuului potilaita, joilla oli normaalit imusolmukkeet, sekä potilaita, jotka sairastivat lasten viivästynyttä lehmänmaitoallergiaa, lasten keliakiaa, umpilisäketulehdusta, haavaista paksusuolitulehdusta tai Crohnin tautia. Verrokkiryhmiin kuului normaaleja biopsianäytteitä lapsipotilailta sekä terveitä resekaattinäytteitä umpilisäkkeestä sekä paksu- tai sykkyräsuolesta potilasryhmien mukaisesti. Jokaiselle anatomiselle alueelle suoritimme perusteellisen määrällisen analyysin (positiivista suonta tai solua per mm2). Osalle ryhmistä suoritimme seerumin liukoisen FasL:n määrityksen entsyymivälitteisellä immunosorbenttimäärityksellä. Reaktiivisissa imusolmukkeissa FasL:n ilmentyminen näkyi pääsääntöisesti parakortikaalialueen korkeaendoteelisissä venuleissa, missä myös apoptoottiset T- ja B-lymfosyytit (joista osa ilmensi Fasia) sittemmin näkyivät. Suoliston seinämässä havaitsimme verisuoniperäistä FasL:n ilmentymistä korkeaendoteelisissä suonissa lymfaattisten itukeskusten lähettyvillä. Niillä lapsipotilailla, joilla havaitsimme limakalvon lymfaattisten itukeskuksien lisääntymistä, oli myös seerumin FasL-pitoisuus koholla. Tulehduksellisissa suolistosairauksissa verisuoniperäinen FasL oli lisääntynyt limakalvon haavaumissa sekä Crohnin tautia sairastavien potilaiden submukoosassa. Tulokset osoittavat verisuoniperäisen FasL:n tyypillisesti ilmentyvän imukudoksen korkeaendoteelisissa suonissa. Apoptoosin havaitseminen Fasia ilmentävissä lymfosyyteissä näiden suonien läheisyydessä tukee ajatusta siitä, kuinka verisuoniperäinen FasL toimii valikoivana portinvartijana ja aiheuttaa Fas-positiivisten lymfosyyttien apoptoosin estämällä niiden pääsyn verenkierrosta.

Im Mittelpunkt der 2. Tagung des Sonderforschungsbereichs Transregio 96 „Thermo-energetische Gestaltung von Werkzeugmaschinen standen erste Ergebnisse zur Modellierung und Simulation von Komponenten und Baugruppen von Werkzeugmaschinen im Mittelpunkt. An den drei Standorten Aachen, Chemnitz und Dresden werden unterschiedliche Lösungsansätze für die steuerungsintegrierte Korrektur thermischer bedingter Strukturverformungen in spanenden Werkzeugmaschinen verfolgt. Von diesen wird eine unterschiedliche Wirksamkeit bzw. Eignung für verschiedene Einsatzfälle erwartet. Bevor diese in der Praxis umgesetzt werden können, müssen Fragen zur Beschreibung der Wärmequellen und zur Wärmeübertragung beantwortet werden. Außerdem bedarf die Umsetzung der Konzepte in den CNC-Steuerungen effizienter Verfahren zur Modellierung und Simulation der thermisch bedingten Strukturverformung. Für die Entwicklung und Bewertung der Korrekturverfahren sowie zur Berechnung der notwendigen Achs-Korrekturen ist die Systemsimulation u. a. an einem prozessaktuelle Werkzeugmaschinenabbild erforderlich. Für die Bewertung ihrer Praxisrelevanz werden die Einzellösungen nach und nach in ein betriebswirtschaftlich orientiertes Gesamtmodell integriert.

Les travaux de cette thèse s’inscrivent dans le cadre du planning de traitements minimalement invasifs des lésions des artères coronaires. Le cardiologue réalise un examen coronarographique, puis dans la continuité, une angioplastie transluminale. L’angiographie rotationnelle à rayons X permet de visualiser sous différentes incidences 2D la lumière des artères coronaires sur plusieurs cycles cardiaques et aussi d’obtenir une reconstruction 3D+T des arbres coronaires. A partir de cette séquence, notre objectif est de déterminer automatiquement une incidence optimale 2D du segment sténosé compatible avec les angles du C-arm afin d’aider le cardiologue lors de l’intervention.Différentes étapes sont considérées pour calculer la position angulaire optimale du C-arm. Afin de suivre la zone de lésion durant le cycle cardiaque, une première méthode est proposée pour mettre en correspondance tous les arbres de la séquence 3D+T. Tout d’abord, un appariement deux à deux des arbres successifs est réalisé afin de construire un arbre d’union. Ces derniers sont ensuite fusionnés afin d’obtenir un arbre mosaïque représentant l’arbre le plus complet de la séquence. L’utilisation de mesures de similarités géométriques et hiérarchiques ainsi que l’insertion de nœuds artificiels permet de prendre en compte les différents mouvements non-rigides des artères coronaires subits au cours du cycle cardiaque et les variations topologiques dû à leurs extractions. Cet appariement nous permet de proposer une deuxième méthode afin d’obtenir une vue angiographique 2D optimale de la zone de lésion tout le long du cycle cardiaque. Cette incidence est proposée spécifiquement pour trois types de région d’intérêt (segment unique, segment multiple ou bifurcation) et est calculée à partir de quatre critères (raccourcissement, chevauchement interne et externe ou angle d’ouverture de bifurcation). Une vue 2D déployée du segment projeté avec le moins de superposition avec les structures vasculaires avoisinantes est obtenue. Nous donnons également la possibilité au cardiologue d’avoir une incidence optimale privilégiant soit le déploiement du stent ou soit le guidage d’outils de la racine de l’arbre à la zone sténosée. Nos différents algorithmes ont été évalués sur une séquence réelle de 10 phases segmentées à partir d’un CT et de 41 séquences simulées. / The thesis work deals with the planning of minimally invasive surgery of coronary artery lesions. The physician performs a coronarography following by a percutaneous transluminal angioplasty. The X-ray rotational angiography permits to visualize the lumen artery under different projection angles in several cardiac cycles. From these 2D projections, a 3D+T reconstruction of coronary arteries can be obtained. Our goal is to determine automatically from this 3D+T sequence, the optimal angiographic viewing angle of the stenotic segment. Several steps are proposed to compute the optimal angular position of the C-arm. Firstly, a mosaic-based tree matching algorithm of the 3D+T sequence is proposed to follow the stenotic lesion in the whole cardiac cycle. A pair-wise inexact tree matching is performed to build a tree union between successive trees. Next, these union trees are merged to obtain the mosaic tree which represents the most complete tree of the sequence. To take into account the non-rigid movement of coronary arteries during the cardiac cycle and their topology variations due to the 3D reconstruction or segmentation, similarity measures based on hierarchical and geometrical features are used. Artificial nodes are also inserted. With this global tree sequence matching, we propose secondly a new method to determine the optimal viewing angle of the stenotic lesion throughout the cardiac cycle. This 2D angiographic view which is proposed for three regions of interest (single segment, multiple segment or bifurcation) is computed from four criteria: the foreshortening, the external and internal overlap and the bifurcation opening angle rates. The optimal view shows the segment in its most extended and unobstructed dimension. This 2D view can be optimal either for the deployment of the stent or for the catheter guidance (from the root to the lesion). Our different algorithms are evaluated on real sequence (CT segmentation) and 41 simulated sequences.

Nowadays the development speed of new software products is a key to success and it is not important whether the aim is to make customer's urges satisfied or get ahead of one's competitors and fill the market gap. Because of the increase of development speed the demands on the saving process of software quality are increasing. There are two types of tools that are supporting the process of software quality assurance. Firstly, we talk about comprehensive testing tools of commercial character that usually include many functions, but their purchase is extremely expensive. On the other hand there are open-source tools that are available for free, they function on many kinds of operating systems and it is possible to modify them. Unfortunately their functions are basically focused on a certain subset of controlling the software quality assurance. Company TRASK solution a.s. has decided to change this current situation, so it asked competence centre Software Quality Assurance at the University of Economics in Prague in order to create Integrated Testing Node (ITN) that would combine the advantages of open-source tools. Moreover, it would offer broad range of functions as commercial solution. The purpose of this thesis is to describe relevant phases of the process of creating the Integrated Testing Node from the factual and methodical point of view. This aim is divided into partial aims included task analysis and the proposal of solving system, open-source products portfolio analysis, choice of the most convenient tools for following integration, choosing the method of information system building, evaluating the feedback from a client and the proposal of future development of this tool. As far as the biggest contribution of this thesis is concerned, it is the realisation of ITN project that can be used during information classes at the University of Economics in Prague. Furthermore, it can be used as the control of software quality in commercial companies.

Estudou-se o efeito do treinamento físico sobre a freqüência cardíaca (FC), a freqüência cardíaca intrínseca (FCI), o efeito vagal (EV), o tônus vagal (TV), o efeito simpático (ES) e o tônus simpático (TS), de ratos idosos em repouso volitivo, na esteira, e durante o exercício de intensidade progressiva (4 estágios de 5 min à 5; 7,5; 10 e 15 m.min-1). Verificaram-se, também, as respostas da FC à doses crescentes de agonistas ?-adrenérgico (isoproterenol) e muscarínico (metacolina). Utilizaram-se 20 ratos Wistar machos, aleatoriamente divididos em dois grupos: Treinado (T, 28+2 meses, 460+36 g), submetido a 10 semanas de treinamento físico de moderada intensidade; e Sedentário-controle (S, 28+2 meses, 461+43 g), apenas manipulado, três a cinco vezes por semana, durante nove semanas, e submetido a cinco minutos de exercício diário, na décima semana, para habituação ao pesquisador e ao ambiente experimental. Utilizaram-se duplos bloqueios farmacológicos (propranolol/atropina e atropina/propranolol) para determinação da FCI, bem como bloqueios farmacológicos autonômicos unilaterais que permitiram a medida do EV, do TV, do ES e do TS. Definições: EV = FC após atropina - FC controle, ES = FC controle - FC após propranolol, TV = FCI - FC após propranolol, TS = FC após atropina - FCI. Registros: batimento-a-batimento, 500Hz (AT/CODAS). Para comparação realizou-se análise de variância de dois caminhos para medidas repetidas, com contraste. Significância estatística, P<0,05. FC e FCI foram menores em T que S, em repouso e nos quatro estágios estudados: FC = 296+6, T vs. 325+16, S; 374+33, T vs. 420+29, S; 380+ 39, T vs. 423+29, S; 407+46, T vs. 434+25, S; 441+48, T vs. 455+30, S; e FCI = 288+28, T vs. 312+18, S; 302+27, T vs. 332+24, S; 301+30, T vs. 339+26, S; 308+30, T vs. 344+30, S; 316+31, T vs. 348+31, S. Não houve diferença na atividade vagal entre T e S, tanto considerando o EV, como o TV, em nenhuma das condições estudadas. A influência simpática para o coração se mostrou semelhante entre T e S, tanto se considerando o ES quanto o TS, em todas as condições estudadas. T e S responderam de forma semelhante aos agonistas muscarínico e adrenérgico. Tanto a FC, quanto a FCI aumentaram do repouso para o exercício, e com o aumento da intensidade do mesmo. A atividade vagal diminuiu do repouso para o exercício, mas apenas em intensidade elevada. A atividade simpática aumentou na passagem do repouso para o exercício, e com o aumento da intensidade do mesmo. Concluiu-se que, em ratos idosos: a) o treinamento físico de moderada intensidade promoveu bradicardia de repouso e atenuação da taquicardia induzida pelo exercício essencialmente à custa de redução da FCI; e b) independentemente da condição de treinamento físico, a estimulação simpática contribuiu para o aumento da FC, em resposta ao exercício, de leve à alta intensidade, enquanto a retirada vagal o fez, apenas em alta intensidade. / We studied the effect of exercise training on heart rate (HR), on intrinsic heart rate (IHR), on vagal effect (VE), on vagal tone (VT), on sympathetic effect (SE) and on sympathetic tone (ST) during both treadmill resting and exercise of progressive intensity (four 5-min stages at 5, 7.5, 10 and 15 m.min-1) in old rats. HR responses to crescent doses of ?-adrenergic (isoproterenol) and muscarinic (metacholine) agonists were also verified. We used 20 male Wistar rats randomly assigned to two groups: trained (T, 28+2 months, 460+36 g) and sedentary control (S, 28+2 months, 461+43 g) rats. T was submitted to a ten-week moderate intensity exercise training program, while S was just handled, three to five times a week, for nine weeks and submitted to five-min bouts of daily exercise during the tenth week for taming and to become accustomed to experimental environment. Double pharmacological blockades (propranolol/ methylatropine and methylatropine/propranolol) were performed in order to determine IHR. Autonomic influences on heart rate were evaluated using also unilateral autonomic pharmacological blockade, which allowed us to measure VE and VT as well as SE and ST. Definitions: VE = HR after atropine - control HR, SE = control HR - HR after propranolol, VT = IHR - HR after propranolol, ST = HR after atropine - IHR. HR was recorded on a beat-to-beat basis with a 500 Hz acquisition frequency (AT/CODAS). For statistical analysis we used two-way ANOVA for repeated measurements with contrast, considering a P<0.05 as statistically significant. T rats had lower HR as well as IHR than their sedentary counterparts both at rest and during all progressive exercise stages: HR = 296+6,T vs. 325+16,S; 374+33,T vs. 420+29,S; 380+39,T vs. 423+29,S; 407+46,T vs. 434+25,S; 441+48,T vs. 455+30,S, respectively; and IHR = 288+28,T vs. 312+18,S; 302+27,T vs. 332+24,S; 301+30,T vs. 339+26,S; 308+30,T vs. 344+30,S; 316+31,T vs. 348+31,S, respectively. Vagal activity was not significantly different between groups, either considering VE or VT. Sympathetic influence was also similar between S and T considering both SE and ST in all of the studied conditions. T and S responded similarly to both muscarinic and ?-adrenergic agonists. Both HR and IHR increased from rest to exercise and with increasing exercise intensity. Vagal activity decreased from rest to exercise but only in high intensity exercise. Sympathetic activity increased from rest to exercise and also with increasing exercise intensity. We concluded that in old rats: a) exercise training of moderate intensity led to resting bradycardia and attenuation of exercise tachycardia essentially due to the decrease in IHR; and b) independently from exercise training status, sympathetic stimulation contributed to HR increase from light to high intensity exercise while vagal withdrawal became important only at high intensity exercise

Information visualization is an important research field concerned with making sense and inferring knowledge from data collections. Graph visualizations are specific techniques for data representation relevant in diverse application domains among them biology, software-engineering, and business finance. These data visualizations benefit from the display space provided by novel interactive large display environments. However, these environments also cause new challenges and result in new requirements regarding the need for interaction beyond the desktop and according redesign of analysis tools. This thesis focuses on interactive magic lenses, specialized locally applied tools that temporarily manipulate the visualization. These may include magnification of focus regions but also more graph-specific functions such as pulling in neighboring nodes or locally reducing edge clutter. Up to now, these lenses have mostly been used as single-user, single-purpose tools operated by mouse and keyboard. This dissertation presents the extension of magic lenses both in terms of function as well as interaction for large vertical displays. In particular, this thesis contributes several natural interaction designs with magic lenses for the exploration of graph data in node-link visualizations using diverse interaction modalities. This development incorporates flexible switches between lens functions, adjustment of individual lens properties and function parameters, as well as the combination of lenses. It proposes interaction techniques for fluent multi-touch manipulation of lenses, controlling lenses using mobile devices in front of large displays, and a novel concept of body-controlled magic lenses. Functional extensions in addition to these interaction techniques convert the lenses to user-configurable, personal territories with use of alternative interaction styles. To create the foundation for this extension, the dissertation incorporates a comprehensive design space of magic lenses, their function, parameters, and interactions. Additionally, it provides a discussion on increased embodiment in tool and controller design, contributing insights into user position and movement in front of large vertical displays as a result of empirical investigations and evaluations. / Informationsvisualisierung ist ein wichtiges Forschungsfeld, das das Analysieren von Daten unterstützt. Graph-Visualisierungen sind dabei eine spezielle Variante der Datenrepräsentation, deren Nutzen in vielerlei Anwendungsfällen zum Einsatz kommt, u.a. in der Biologie, Softwareentwicklung und Finanzwirtschaft. Diese Datendarstellungen profitieren besonders von großen Displays in neuen Displayumgebungen. Jedoch bringen diese Umgebungen auch neue Herausforderungen mit sich und stellen Anforderungen an Nutzerschnittstellen jenseits der traditionellen Ansätze, die dadurch auch Anpassungen von Analysewerkzeugen erfordern. Diese Dissertation befasst sich mit interaktiven „Magischen Linsen“, spezielle lokal-angewandte Werkzeuge, die temporär die Visualisierung zur Analyse manipulieren. Dabei existieren zum Beispiel Vergrößerungslinsen, aber auch Graph-spezifische Manipulationen, wie das Anziehen von Nachbarknoten oder das Reduzieren von Kantenüberlappungen im lokalen Bereich. Bisher wurden diese Linsen vor allem als Werkzeug für einzelne Nutzer mit sehr spezialisiertem Effekt eingesetzt und per Maus und Tastatur bedient. Die vorliegende Doktorarbeit präsentiert die Erweiterung dieser magischen Linsen, sowohl in Bezug auf die Funktionalität als auch für die Interaktion an großen, vertikalen Displays. Insbesondere trägt diese Dissertation dazu bei, die Exploration von Graphen mit magischen Linsen durch natürliche Interaktion mit unterschiedlichen Modalitäten zu unterstützen. Dabei werden flexible Änderungen der Linsenfunktion, Anpassungen von individuellen Linseneigenschaften und Funktionsparametern, sowie die Kombination unterschiedlicher Linsen ermöglicht. Es werden Interaktionstechniken für die natürliche Manipulation der Linsen durch Multitouch-Interaktion, sowie das Kontrollieren von Linsen durch Mobilgeräte vor einer Displaywand vorgestellt. Außerdem wurde ein neuartiges Konzept körpergesteuerter magischer Linsen entwickelt. Funktionale Erweiterungen in Kombination mit diesen Interaktionskonzepten machen die Linse zu einem vom Nutzer einstellbaren, persönlichen Arbeitsbereich, der zudem alternative Interaktionsstile erlaubt. Als Grundlage für diese Erweiterungen stellt die Dissertation eine umfangreiche analytische Kategorisierung bisheriger Forschungsarbeiten zu magischen Linsen vor, in der Funktionen, Parameter und Interaktion mit Linsen eingeordnet werden. Zusätzlich macht die Arbeit Vor- und Nachteile körpernaher Interaktion für Werkzeuge bzw. ihre Steuerung zum Thema und diskutiert dabei Nutzerposition und -bewegung an großen Displaywänden belegt durch empirische Nutzerstudien.

This thesis deals with design of steel structure multi-storey garage. It is the five-storey steel structure of rectangular plan. The construction is designed for the city of Olomouc. Static calculation is solved by a combination of manual calculation and calculation using software Scia engineer 18. There are the following main load bearing structural elements designed and examined in the structural analysis: truss, purlin, bracing, column, composite beam, joints, foot and anchoring. Thesis includes drawing documentation

Les contractions rythmiques résultent de l’activité stimulatrice du nœud sinusal dans le cœur et des cellules interstitielles de Cajal (CICs) dans les intestins. Nous avons découvert un nouveau syndrome résultant d’une combinaison de la maladie du nœud sinusal (MNS) et de la pseudo-obstruction intestinale chronique (POIC). Ce syndrome, que nous avons nommé Chronic Atrial and Intestinal Dysrhythmia (CAID), résulte d’une mutation récessive du gène SGO1 (K23E). Cependant, les rôles connus de SGO1 n'expliquent pas l'apparition postnatale du syndrome ni la pathologie spécifique, suggérant que des rôles non canoniques de SGO1 conduisent aux manifestations cliniques observées. Cette hypothèse est supportée par la comparaison de CAID avec les autres cohésinopathies qui présentent principalement des phénotypes développementaux sans ou avec des défauts légers du cycle cellulaire. Ce projet visait à une découverte non biaisée des mécanismes non canoniques expliquant le syndrome CAID en utilisant le dogme de la biologie moléculaire (ADN→ARNm→protéine) comme ligne directrice. Pour ce faire, nous avons effectué des criblages multi-omiques sur des fibroblastes de peau de patients CAID et de contrôles sains. Les résultats des criblages ont été validés par électrophysiologie, étude des voies de signalisation pertinentes, immunohistochimie, pyroséquençage des rétrotransposons LINE-1 et quantification des marques d’histones. Nos études multi-omiques ont confirmé des changements dans la régulation du cycle cellulaire, mais aussi dans la conduction cardiaque et la fonction des muscles lisses. Plus spécifiquement, plusieurs canaux potassiques étaient sous-régulés. L’électrophysiologie a confirmé une diminution du courant potassique rectifiant entrant (IK1). L'immunohistochimie des coupes intestinales de patients CAID a confirmé l’augmentation de l’expression de SGO1 et BUB1, un régulateur de la voie de signalisation TGF-β. De plus, la voie canonique de TGF-β est augmentée et est découplée de la voie non canonique. Au niveau épigénétique, une signature unique d’hyperméthylation et de fermeture de la chromatine a été observée. Ce qui est soutenu par l’augmentation de la méthylation de H3K9me3 et de H3K27me3. En conclusion, le syndrome CAID est associé à plusieurs changements ayant possiblement un effet cumulatif plutôt que d’une seule voie de signalisation dérégulée. Nos résultats désignent la perturbation du courant IK1, la dérégulation de la signalisation TGF-β, l’hyperméthylation de l’ADN et la compaction de la chromatine comme éléments conducteurs potentiels des manifestations cliniques observées. La voie TGF-β et les changements épigénétiques peuvent être ciblées par des médicaments existants, constituant ainsi des cibles thérapeutiques prometteuses pour le traitement du syndrome CAID. / Rhythmic contractions are driven by the pacemaker activity of the cardiac sinus node and the intestinal interstitial cells of Cajal (ICC). We have discovered a new syndrome resulting from a combination of sick sinus syndrome (SSS) and chronic intestinal pseudo-obstruction (CIPO). This syndrome, which we have named Chronic Atrial and Intestinal Dysrhythmia (CAID), results from a recessive mutation in the SGO1 gene (K23E). However, the known roles of SGO1 do not explain the postnatal onset of the syndrome nor the specific pathology, suggesting that non-canonical roles of SGO1 lead to the clinical manifestations observed. This hypothesis is supported by the comparison of CAID with other cohesinopathies which mainly exhibit developmental phenotypes without or with mild cell cycle defects. This project aimed towards an unbiased discovery of noncanonical mechanisms explaining CAID using the molecular biology dogma (DNA→mRNA→protein) as a guideline. We performed multi-omic screens on skin fibroblasts from CAID patients and healthy controls. Screening results were validated by electrophysiology, study of relevant signaling pathways, immunohistochemistry, LINE-1 retrotransposon pyrosequencing, and histone marks quantification. Our multiomics analyses confirmed changes in cell cycle regulation, but also in cardiac conduction and smooth muscle function. More specifically, several potassium channels were downregulated. Electrophysiology studies confirmed a decrease in the inward rectifier potassium current (IK1). Immunohistochemistry in CAID patient’s intestinal sections confirmed overexpression of SGO1 and BUB1, a regulator of TGF-β signaling pathway. Additionally, the canonical TGF-β signaling was increased and decoupled from noncanonical signaling. At the epigenetic level, CAID patient fibroblasts have a unique signature of hypermethylation and chromatin closure. This is supported by the increased methylation of H3K9me3 and H3K27me3. In conclusion, CAID syndrome is associated with several changes that, may have a cumulative effect rather than a single deregulated signaling pathway. Our results reveal the disturbance of the IK1 current, the deregulation of TGF-β signaling, DNA hypermethylation and chromatin accessibility changes as potential conductors of intestinal and cardiac manifestations of CAID syndrome. In particular, the TGF-β pathway and epigenetic changes, may be targeted by existing drugs, thus constituting promising therapeutic targets for the treatment of CAID syndrome.

The magnetic field analysis by MKP and magnetic probe project deals with magnetic field analysis of asynchronous machine cross section. This analysis is written in detail along with the necessary theory of asynchronous machine and the ANSYS program. The magnetic field of selected machine is measured by magnetic probe and results are compared with calculation. The next part of thesis is draft of device for the magnetic field analysis.

The aim of this thesis is to create and describe the wireless system for lighting control. A part of the work is the creation of modules for switching lighting and the creation of their operating programs. The first chapter briefly describes the way how the lighting control works and contains general requirements for the intelligent home. Further, there is a description of IQRF system, which serves as a wireless platform for the system. Next part of the thesis describes individual modules in terms of hardware and software. One part of the work covers the description of the transmission protocol. The attachment includes a listing of all operating programs for this wireless control system.