This thesis has the task to bring us to the issue of the valuation of the house loaded defect perimeter walls. The first chapter focuses on the theoretical information in the issue of property valuation. The second chapter deals with possible defects and faults of real estate. The third chapter is to approach the issue of property damage. The fourth chapter provides a survey of real estate and the last, fifth, chapter focuses on a case study of the valuation of the house with impaired peripheral walls and the suggestion of possible ways how to reduce the value of the property as a result of the defect.

A general overview of the waterproofing materials. Distribution waterproofing systems according to their use in construction. Listing the possible risks of defects waterproofing systems. Remediation and prevention of defects in the insulation. General summary of the risk lifecycle isolation and analysis of defects in the insulating elements on the real structure.

The objective of this thesis is passportisation of the construction and technical condition of s of a townhouse in Havlíčkův Brod. Primarily to proof, draw and assess the condition of this townhouse suggest some appropriate solution. The next step is to aim, draw and design the building modernization while preserving its external character. The building layout and construction is part of the project. The layout places emphasis mainly on the building functionality and operation. Another aim of this project is to point out the construction and technical condition of the building and to find possible solutions to the problem. The thesis includes also a budget which puts a monetary value on the costs of the building reconstruction. The partial aim of this thesis is to propose possible modernization.

Résumé : Le métabolisme monocarboné ou métabolisme 1-C désigne l’ensemble des voies métaboliques permettant la synthèse et / ou le recyclage de molécules donneur de groupement monocarboné au cours des réactions de méthylation. L’objectif de ce travail était d’évaluer l’implication des métabolismes de la choline, de la phosphatidylcholine (PC) et de la bétaïne dans la physiopathologie des désordres impliquant le métabolisme 1-C en période prénatale et postnatale. Nous avons montré une augmentation progressive de l’expression de la majorité des gènes impliqués dans le métabolisme 1-C au cours de l’ontogénèse hépatique murine, tandis que les leur expression était plus faible avec des profils plus variable au niveau cérébral. Chez l’homme, les valeurs normales des concentrations des intermédiaires du métabolisme 1-C dans le liquide amniotique (LA) en fonction du terme gestationnel ont été déterminées pour tous les paramètres et les concentrations de S-adénosyl-homocystéine et de méthionine étaient augmentées dans les LA du groupe affecté par des défauts de fermeture du tube neural (DFTN) suggérant que certains cas de DFTN pourraient être associés à des déséquilibres du métabolisme 1-C. En post natal, nous avons montré à la fois chez l’homme et l’animal, que les hyperhomocystéinémie d’origine nutritionnelles ou génétiques induisaient une déplétion en bétaïne, épargnant uniquement le rein où elle est un osmolyte majeur. Dans un modèle murin de déficit en cystathionine–beta synthase induisant une hyperhomocystéinémie, une technique de lipidomique ciblée a montré au niveau hépatique des modifications qualitatives des phospholipides (PLs) avec une diminution des PC contenant des acides gras insaturés et des phosphatidyléthanolmines contenant de l’acide arachidonique. Ces modifications des PLs pourraient jouer un rôle dans la constitution de la stéatose hépatique observée dans l’histoire naturelle de cette maladie. En conclusion, ce travail a permis de montrer que la choline, la bétaïne et les PC sont des acteurs indissociables du métabolisme 1-C qui pourraient être impliqués dans la physiopathologie des DFTN et dans les hyperhomocystéinémies. Ils pourraient également être impliqués dans la physiopathologie des stéatoses hépatiques non alcooliques ou des déficits cognitifs, dans lesquels des désordres du métabolisme 1-C ont été observés. / Abstract: One carbon metabolism or 1C metabolism includes all metabolic pathways for the synthesis and / or recycling of molecules involved in methylation reactions. The objective of this study was to evaluate the involvement of choline, phosphatidylcholine (PC) and betaine metabolisms in the pathophysiology of diseases with impaired 1-C metabolism in prenatal and postnatal period. We showed a progressive increase of the expression of the majority of genes involved in 1-C metabolism during the mouse liver ontogeny while their gene expression was at lower levels and with more variable patterns during brain ontogeny. In humans, amniotic fluid concentrations of all intermediates of 1-C metabolism according to gestational term were determined and we observed increased concentrations of S-adenosyl-homocysteine and methionine in pregnancies affected by neural tube defects (NTD) suggesting that some NTDs cases could be associated with an imbalance in 1-C metabolism. In the postnatal period we showed that both in animal and humans and both in nutritional and genetic hyperhomocysteinemia, that betaine pools were decreased, only sparing the kidney betaine concentrations, where betaine acts as an essential osmolyte. In a mouse model of cystathionine-beta synthase deficiency inducing hyperhomocysteinemia, a technic of targeted lipidomic revealed qualitative changes in the liver phospholipids composition, in particular a decrease of PC containing unsaturated fatty acids and of phosphatidylethanolamine containing arachidonic acid and an increase of phosphatidylethanolamine containing docosohaexaenoic acid. This phospholipids remodelage may participate in the development of the steatosis observed in the natural history of this disease. In conclusion, this study has shown that choline, betaine and phosphatidylcholine are essential actors of 1-C metabolism that could be involved in the pathogenesis of NTD and hyperhomocystéinemia. They could also be involved in the pathophgysiology of non alcoholic fatty liver disease or cognitive decline, in which disorders of 1-C metabolism were observed.

Le développement des Interventions Médicales Assistées par ordinateur (CAMI) est le résultat d'évolutions convergeantes dans les domaines de la médecine, physique, biomatériaux, électronique, informatique et robotique. CAMI visent à fournir les outils qui permettent au clinicien d'utiliser des données multi-modales de manière rationnelle et quantitative pour planifier, simuler et exécuter des interventions médicales mini-invasives avec précision et sans risque. Parallèlement, les avancées technologiques dans les domaines de l’automatisation, la miniaturisation, la conception assistée par ordinateur et l'usinage ont aussi mené au développement des technologies telles que la bioimpression assistée par ordinateur permettant une impression couche par couche de biomatériaux avec une géométrie contrôlée dans l’espace. Ces résultats ouvrent la voie pour l’utilisation des technologies de bioimpression pour des Interventions Médicales Assistées par ordinateur plus précises et sans risque. Dans ce travail, nous montrons que des constructions tissulaires 3D peuvent être imprimées in vivo et in situ et adaptées à la morphologie d’un défaut. Les résultats ont montré que l'impression de cellules in situ avec une résolution à l’échelle cellulaire a tendance à orienter la réparation tissulaire. / The development of Computer-Assisted Medical Interventions (CAMI) results from converging evolutions in medicine, physics, materials, electronics, informatics and robotics. CAMI aim at providing tools that allow the clinician to use multi-modal data in a rational and quantitative way in order to plan, simulate and execute mini-invasive medical interventions accurately and safely. In parallel, technological advances in the fields of automation, miniaturization and computer aided design and machining have also led to the development of bioprinting technologies which could be defined as the computer-aided, layer-by-layer deposition, transfer and patterning of biologically relevant materials. These results pave the way of using bioprinting technologies for Computer-Assisted Medical Interventions. More precisely, we show that 3D tissue constructs can be printed in vivo and in situ in relation with defect morphology. Interestingly, we demonstrate that printing cells in situ with a cell-level resolution tends to orientate tissue repair.

Abstract Context: This study contributes to the understanding of the current state of cross-project defect prediction (CPDP) by investigating the topic in themes, with special focus on data approaches and covering search-based training data selection, by proposing data selection methods and investigating their impact. The empirical evidence for this work is collected through a formal systematic literature review method for the review, and from experiments on open source projects. Objective: We aim to understand and summarize the manner in which various data manipulation approaches are used in CPDP and their potential impacts on performance. Further, we aim at utilizing search-based methods to produce evolving training data sets to filter irrelevant instances from other projects before training. Method: Through a series of studies following the literature review of current state of CPDP, we propose a search-based method called genetic instance selection (GIS). We validate our initial findings by conducting the next study on a large set of data sets with multiple feature sets. We refine our design decisions using an exploratory study. Finally, we investigate an existing meta-learning approach, provide insights on its design and propose an alternative iterative data selection method. Results: The literature review reveals lower performances of CPDP in comparison with within project defect prediction (WPDP) models and provides a set of primary studies to be used as the basis for future research. Our proposed data selection methods make the case for search-based approaches considering their higher effectiveness and performance. We identified potential impacting factors on the effectiveness through the exploratory study and proposed methods to create better CPDP models. Conclusions: The proposal of numerous approaches in the literature over the last decade has led to progress in the area and the acquired knowledge and tools apply to many similar domains and can act as parts of academic curricula as well. Future directions of study can include searching for better validation data, better feature selection techniques, tuning the parameters of the search-based models, tuning hyper-parameters of learners, investigating the effects of multiple sources of optimization (learner, instances and features) and the impact of the class imbalance problem. / Tiivistelmä Tausta: Tämä tutkimus edistää projektienvälisten virheiden ennustamisen nykytilan ymmärtämistä (CPDP) tutkimalla aihetta teemoissa, keskittyen erityisesti tiedollisiin lähestymistapoihin ja hakuperusteisen harjoitusdatan valintaan esittelemällä datan valintamenetelmiä ja tutkimalla niiden vaikutuksia. Tämän työn empiirinen todistusaineisto on koottu muodollisella systemaattisella kirjallisuuskatsauksella ja avoimen lähdekoodin projekteissa tehdyillä kokeilla. Tavoite: Pyrimme ymmärtämään ja tiivistämään tavan, jolla erilaisia datan käsittelyn lähestymistapoja käytetään CPDP:ssa sekä niiden potentiaalisia vaikutuksia suorituskykyyn. Lisäksi, tavoitteenamme on hyödyntää hakuperusteisia menetelmiä muodostamaan kehittyviä harjoitusdata-settejä suodattamaan epäolennaisia esiintymiä muista projekteista ennen koulutusta. Menetelmä: CPDP:n nykytilan kirjallisuuskatsauksen jälkeen tehtyjen tutkimusten avulla ehdotamme hakuperusteista menetelmää, jota kutsutaan geneettisen esiintymän valinnaksi (GIS). Todistamme alustavat havaintomme suorittamalla seuraavan tutkimuksen suurella joukolla datasettejä, joilla on useita ominaisuuksia. Jalostamme suunnittelupäätöksiämme käyttäen tutkivaa tutkimusta. Lopuksi, tutkimme vallitsevaa meta-oppimisen lähestymistapaa ja tarjoamme näkemyksiä sen suunnitteluun ja ehdotamme vaihtoehtoista, toistuvaa datan valintamenetelmää. Tulokset: Kirjallisuuskatsaus paljastaa CPDP:n heikomman suorituskyvyn verrattuna projektinsisäisten virheiden ennustamisen (WPDP) malleihin ja tarjoaa joukon primaaritutkimuksia, joita voidaan käyttää perustana myöhemmälle tutkimukselle. Ehdottamamme datan valintamenetelmät puoltavat hakuperusteisten menetelmiä niiden paremman tehokkuuden ja suorituskyvyn vuoksi. Tunnistimme potentiaalisia tehokuuteen vaikuttavia tekijöitä tutkivien tutkimusten avulla ja ehdotimme metodeja parempien CPDP mallien luomiseksi. Johtopäätökset: Viime vuosikymmenten aikana kirjallisuudessa esitellyt lukuisat menetelmät ovat edistäneet alaa ja hankittu tieto ja työkalut soveltuvat monille samanlaisille alueille ja voivat toimia myös osana akateemisia opetussuunnitelmia. Tutkimuksen tulevat linjaukset voivat sisältää validointiin paremmin soveltuvan datan haun, paremmat ominaisuuksien valintatekniikat, hakuperusteisten mallien parametrien hienosäädön, oppijoiden hyper-parametrien hienosäädön, tutkimuksen useiden optimoinnin lähteiden vaikutuksista (oppija, esiintymät, ominaisuudet) ja luokan epätasapaino-ongelman vaikutuksesta.

Trotz der zunehmenden Bedeutung von freien Lappenplastiken stellen gefäßgestielte Suralis-Lappenplastiken weiterhin eine zuverlässige Methode zur Defektdeckung an der unteren Extremität dar. In der Arbeit werden 19 Fälle untersucht, bei denen eine Suralis-Lappenplastik durchgeführt wurde. Die Patientenzufriedenheit wird anhand funktioneller und ästhetischer Gesichtspunkte mittels eines standardisierten Fragebogens erfasst. Aus der ärztlichen Dokumentation werden notwendige Revisionseingriffe, stationäre und ambulante Behandlungszeiten, Nebenerkrankungen und die Erlössituation im DRG-System ausgewertet. Zudem wird im Rahmen einer anatomischen Studie an einem Leichenpräparat ein Suralis-Lappen gehoben und eine Fotodokumentation angefertigt.:1. Einleitung 2. Grundlagen 3. Material und Methoden 4. Ergebnisse 5. Diskussion 6. Zusammenfassung 7. Literaturverzeichnis 8. Anhang / Although the increasing meaning of free flaps the pedicled sural flap is a save method of covering defect wounds on lower limbs. In this report 19 cases of sural flap coverage are examined. The level of satisfaction of patients is measured by functional and aesthetic aspects using a standardised survey. Number of necessary revision operations, time of treatment, side diseases, and DRG based profit is determinded by the medical documentation. Furthermore an anatomic study is done showing the surgical raising of a sural flap.:1. Einleitung 2. Grundlagen 3. Material und Methoden 4. Ergebnisse 5. Diskussion 6. Zusammenfassung 7. Literaturverzeichnis 8. Anhang

This thesis deals with nursing care of skin defects using a wet therapy in neonatology. The first section summarizes information related to preterm infants, the development of the individual layers of the skin in the embryonic period. It lists the types of skin defects which the neonatolgy nurse may frequently encounter at the department with including a list of modern therapeutic coverage that can be used. It lists a brief history of wound healing too, focusing just on the development of the wet therapy . Furthermore is marginally discussed the evaluation and documentation of damage to the skin wound. For interest, the thesis mentions a case reportof the preterm newborn with the necrosis of the lower limb, accompanied by commentaries of the alternative treatment for this type of skin damage from my own experience. The second part is assessing the awareness of the nurses in the modern methods of the healing. The priority is the mapping of the experience in using the wet therapy through the quantitative research, which is mediated by an anonymous questionnaire. The main goal of the research is to determine the awareness of the nurses from the neonatology intensive care unit, resuscitation and intermediate care in the nursing of the skin defects using a wet therapy. For this purpose the chosen method...

The different strategies of tissue engineering for functional reconstruction of critical-size bone defects require a thorough knowledge of physiological mechanisms of bone repair. Bone healing is a complex process affected by various mediators. Several investigations have studied the gene expression 1 to 3 days after an acute or experimental fracture. Little is known about the humoral and cellular in vivo reaction in the early stages of bone healing. In contrast to other methods of molecule sampling and detection, which usually lead to the inhibition of the biological activity following complex sample preparation and quantification, microdialysis is a real-time monitoring technique which can be applied in living tissues providing a strong link between analytical methodology and biochemistry. In this study, the optimal conditions for microdialysis in a critical size rat long bone defect model for both in vivo and in vitro analyses were developed. Mediators and components of the extracellular matrix occurring in the first 24 to 48 hours of bone healing locally and systemically were monitored via microdialysis and blood sampling, respectively. Furthermore, novel proteins and their modulation were explored during this time frame. In vitro microdialysis was used to optimize the condition for protein recovery. Addition of bovine serum albumin (BSA) resulted in an enhanced recovery of interleukin (IL)-6. The maximal relative recovery (RR) was from 15.0% without BSA and 23.6% with BSA, while the maximal RR of transforming growth factor (TGF)-β1 was 11.2% with BSA and the concentration of TGF-β1 was below the detection limit of enzyme-linked immunosorbent assay (ELISA) without BSA. Using in vivo microdialysis, total protein concentrations varied between 0.20±0.12 mg/mL and 0.44±0.18 mg/mL. Among the mediators produced in the fracture hematoma within 24 h after the injury, IL-6 was secreted with the highest concentration of 309.1 pg/mL between 12 and 15 h after creation of the critical size bone defect. Meanwhile, the detectable concentrations of TGF-β1 in microdialysates ranged from 3.6 to 44.0 pg/mL and in blood plasma TGF-β1 was constantly producted ranging from 656.3 to 8398.2 pg/mL for 24 h after bone defct. Moreover, another constant producted growth factor in blood plasma was PDGF-BB and the concentration ranged from 222.1 to 589.4 pg/mL for 8 h after bone defect. Using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), 36 proteins were identified in the microdialysates over 8 h, and 884 proteins were identified on probes which were implanted into the bone defect over 24 h. Among the proteins identified in the hematoma, only a minority originated from the extracellular space. Protein analysis indicated five pathways associated with bone healing that were overrepresented after creating soft tissue and bone defects, of which FGF signaling was specific for bone defects. Furthermore, C-X-C motif ligands CXCL-1, CXCL-2, CXCL-3, CXCL-4, CXCL-5, CXCL-7, rodent bone protein (RoBo-1), insulin-like growth factor (IGF)-I, and chitinase-3-like protein 1 were detected in the fracture hematoma. These proteins are potentially associated to early bone healing. As seen by histological analysis, polymorphonuclear leukocytes (PMNs) and lymphocytes penetrated into the fracture hematoma immediately after surgery and peaked at 24 h. This study for the first time presents data from both the local and systemic acute response to bone and soft tissue injury in a small animal model. The results of mcrodialysis sampling may serve as a baseline for future investigations on different models and time frames. Several proteins and pathways have been identifeid as potentially important for early bone regeneration warranting in depth analysis in further studies.:I. Table of content II. List of abbreviations 1 Summary 2 Introduction 2.1 The process of bone healing 2.1.1 Stages of fracture healing 2.1.2 Early stage of inflammation 2.2 Clinical challenges 2.3 Microdialysis 2.3.1 The principle of Microdialysis 2.3.2 Parameters influencing the recovery 2.4 Aim of this study 3 Materials 3.1 Materials, devices and animals 3.2 Chemicals 3.3 Buffers and solutions 4 Methods 4.1 Background 4.2 In vitro microdialysis 4.2.1 Preparation of the protein solution 4.2.2 Microdialysis sampling procedure 4.3 In vivo microdialysis 4.3.1 Surgical procedure 4.3.2 Sample collection 4.4 Plasma samples 4.5 Determination of the fluid recovery 4.6 Determination of the relative recovery 4.7 Total protein measurement 4.8 Cytokine and growth factor analysis 4.8.1 IL-1β, IL-6, TNF-α and PDGF-BB ELISA 4.8.2 VEGF ELISA 4.8.3 TGF-β1 ELISA 4.8.4 BMP-2 ELISA 4.8.5 Proteome profilerTM array 4.9 Proteomic analysis 4.10 Histological analysis 4.11 Statistical analysis 5 Results 5.1 Protein selection 5.2 Determination of fluid recovery in vitro and in vivo 5.3 Determination of relative recovery (RR) in vitro 5.4 Determination of total protein concentration in vivo 5.5 Determination of cytokine and growth factor concentration in the microdialysate in vivo 5.5.1 IL-6 concentration 5.5.2 TGF-β1 concentration 5.5.3 IL-1β concentration 5.5.4 TNF-α concentration 5.5.5 PDGF-BB, BMP-2 and VEGF concentration 5.6 Determination of further cytokines and chemokines in the microdialysate in vivo 5.7 Protein determination using HPLC-MS/MS analysis 5.7.1 Proteins in the microdialysate 5.7.2 Proteins on the surface of the probe 5.8 Protein annotation 5.9 Determination of cytokines and growth factors in the blood plasma 5.9.1 Determination of IL-6 in the blood plasma 5.9.2 Determination of TGF-β1 in the blood plasma 5.9.3 Determination of PDGF-BB in the blood plasma 5.10 Histological analysis of the hematoma 6 Discussion 6.1 Fluid recovery 6.2 Influence of the crystalloid perfusate on relative recovery 6.3 Relative recovery of cytokines and growth factors in vitro 6.4 In vivo microdialysis 6.4.1 Total protein concentration 6.4.2 Annotation of proteins in hematoma identified by HPLC-MS/MS 6.4.3 Identification of cytokines and bone related proteins 6.5 The humoral inflammatory response 6.6 Cellular response 7 Conclusions 8 References 9 Appendix 9.1 Figure index 9.2 Table index III. Eidesstattliche Erklärung IV. Selbständigkeitserklärung V. Acknowledgements / Zur Entwicklung neuer Strategien der Geweberegenerierung in kritischen Knochendefekten, die sich durch Selbstheilungsprozesse nicht schließen, ist das Verständnis der beteiligten physiologischen Prozesse essentiell. Der Wiederaufbau von Gewebe, wie etwa während Knochenheilungsprozesse ist komplex reguliert und erfordert das koordinierte Zusammenspiel einer Vielzahl von Zellen und Mediatoren. Obwohl bereits in zahlreichen Studien die Veränderungen in der Genexpression in den ersten 3 Tagen nach einer akuten oder experimentell induzierten Fraktur untersucht wurden, ist noch immer wenig über die zellulären und humoralen Vorgänge in den frühen Phasen der Knochenheilung in vivo bekannt. Gebräuchliche Analysemethoden erfordern komplexe Verfahren zur Probenentnahme und Nachweisreaktionen währenddessen die biologische Aktivität der untersuchten Mediatoren häufig graduell verloren geht. Die Mikrodialyse hingegen kann in Echtzeit am lebenden Objekt und am Ort der Verletzung durchgeführt werden und bildet somit eine erfolgsversprechende Plattform um die Probengewinnung noch enger mit der anschließenden biochemischen Nachweistechnik zu verbinden. Im Rahmen dieser Arbeit wurden die optimalen Konditionen zur Mikrodialyse erstmals an einem kritischen Defektmodell eines Ratten-Röhrenknochens zur in vivo und in vitro Applikation ermittelt. Dazu wurde das Vorkommen verschiedener Komponenten der extrazellulären Matrix und ausgewählter Mediatoren während der ersten 24 bis 48 Stunden der Knochenheilung überwacht. Neben der durch Mikrodialyse gewonnenen Proben wurden auch Blutproben verarbeitet um sowohl die lokale, als auch systemische Konzentration der untersuchten Proteine zu erfassen. Durch eine Proteomanalyse konnten zudem bislang in diesem Prozess unbekannte Moleküle identifiziert und verfolgt werden. Zur Optimierung der Mikrodialyse wurden zunächst die Bedingungen hinsichtlich der Proteinrückgewinnung verbessert. Durch den Zusatz von Rinderserumalbumin (BSA) konnte die Rückgewinnung von Interleukin (IL)-6 erhöht werden. Die maximale relative Rückgewinnung (RR) konnte von 15.0% ohne BSA auf 23.6% mit BSA gesteigert werden. Noch dramatischer war dieser Effekt für den transforming growth factor (TGF)-β1 von dessen eingesetzter Menge in vitro 11.2% detektiert werden konnte, während in der BSA-freien Dialyselösung kein TGF-β1 nachgewiesen wurde. Die RR blieb stets unter der Detektionsgrenze des verwendeten enzyme-linked immunosorbent assay (ELISA). In vivo-Dialysate enthielten totale Proteinkonzentrationen zwischen 0,20±0,12 mg/mL und 0,44±0,18 mg/mL. Von den innerhalb von 24 h nach Verletzung im Frakturhämatom produzierten Mediatoren wurde IL-6 am stärksten exprimiert. Die höchsten Konzentrationen (309,1pg/mL) konnten hierfür nach 12 bis 15 Stunden nach Einführung des Defekts gemessen werden. Die Konzentrationslevel von TGF-β1 hingegegen betrug nur 3,6 bis 44,0 pg/mL.Mittels high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), konnten 36 Proteine in den über 8 Stunden gewonnenen Mikrodialysaten, und 884 Proteine von Explantaten, die 24 h im Knochendefekt integriert waren, identifiziert werden. Von den im Frakturhämatom identifizierten Proteinen war nur eine Minderheit extrazellulären Ursprungs. Durch die Proteomanalyse konnten fünf Signalwegskaskaden identifiziert werden. Von diesen trat „FGF (fibroblast growth factor) signaling“ ausschließlich in Knochendefekten, nicht jedoch in den zur Kontrolle mitgeführten reinen Weichgewebedefekten auf. Im Frakturhämatom konnten die, C-X-C motif-Liganden CXCL-1, CXCL-2,CXCL-3, CXCL-4, CXCL-5, CXCL-7, rodent bone protein (RoBo-1), insulin-like growth factor (IGF)-I, und das chitinase-3-like protein 1 nachgewiesen werden. Die identifizierten Proteine könnten von Bedeutung für die Steuerung früher Knochenheilungsprozesse sein. Histologische Untersuchungen zeigten, dass polymorphkernige Leukozyten (PMNs) und Lymphozyten sofort nach der Operation in das Frakturhämatom einwandern und ihre Anzahl nach etwa 24 h ihr Maximum erreicht. Diese Studie präsentiert erstmals Daten der lokal und systemisch ablaufenden zellulären und humoralen Vorgänge als Antwort auf einen Weichgewebs-bzw. Knochendefekt in einem Nagetier-Kleintiermodell. Die Mikrodialyse-Resultate stellen eine vielversprechende Grundlage für zukünftige Untersuchungen in anderen Modellen dar. Außerdem bilden die hier identifizierten Proteine und Signalwege eine Gruppe potenter Kandidaten für weiterführende Untersuchungen zur Knochenregeration.:I. Table of content II. List of abbreviations 1 Summary 2 Introduction 2.1 The process of bone healing 2.1.1 Stages of fracture healing 2.1.2 Early stage of inflammation 2.2 Clinical challenges 2.3 Microdialysis 2.3.1 The principle of Microdialysis 2.3.2 Parameters influencing the recovery 2.4 Aim of this study 3 Materials 3.1 Materials, devices and animals 3.2 Chemicals 3.3 Buffers and solutions 4 Methods 4.1 Background 4.2 In vitro microdialysis 4.2.1 Preparation of the protein solution 4.2.2 Microdialysis sampling procedure 4.3 In vivo microdialysis 4.3.1 Surgical procedure 4.3.2 Sample collection 4.4 Plasma samples 4.5 Determination of the fluid recovery 4.6 Determination of the relative recovery 4.7 Total protein measurement 4.8 Cytokine and growth factor analysis 4.8.1 IL-1β, IL-6, TNF-α and PDGF-BB ELISA 4.8.2 VEGF ELISA 4.8.3 TGF-β1 ELISA 4.8.4 BMP-2 ELISA 4.8.5 Proteome profilerTM array 4.9 Proteomic analysis 4.10 Histological analysis 4.11 Statistical analysis 5 Results 5.1 Protein selection 5.2 Determination of fluid recovery in vitro and in vivo 5.3 Determination of relative recovery (RR) in vitro 5.4 Determination of total protein concentration in vivo 5.5 Determination of cytokine and growth factor concentration in the microdialysate in vivo 5.5.1 IL-6 concentration 5.5.2 TGF-β1 concentration 5.5.3 IL-1β concentration 5.5.4 TNF-α concentration 5.5.5 PDGF-BB, BMP-2 and VEGF concentration 5.6 Determination of further cytokines and chemokines in the microdialysate in vivo 5.7 Protein determination using HPLC-MS/MS analysis 5.7.1 Proteins in the microdialysate 5.7.2 Proteins on the surface of the probe 5.8 Protein annotation 5.9 Determination of cytokines and growth factors in the blood plasma 5.9.1 Determination of IL-6 in the blood plasma 5.9.2 Determination of TGF-β1 in the blood plasma 5.9.3 Determination of PDGF-BB in the blood plasma 5.10 Histological analysis of the hematoma 6 Discussion 6.1 Fluid recovery 6.2 Influence of the crystalloid perfusate on relative recovery 6.3 Relative recovery of cytokines and growth factors in vitro 6.4 In vivo microdialysis 6.4.1 Total protein concentration 6.4.2 Annotation of proteins in hematoma identified by HPLC-MS/MS 6.4.3 Identification of cytokines and bone related proteins 6.5 The humoral inflammatory response 6.6 Cellular response 7 Conclusions 8 References 9 Appendix 9.1 Figure index 9.2 Table index III. Eidesstattliche Erklärung IV. Selbständigkeitserklärung V. Acknowledgements

1 Rights arising from defective performance Abstract This diploma thesis examines the institute of rights arising from defective performance. It contains not only a theoretical description of the effective legislation but also practical examples on which the theoretical background and knowledge are demonstrated. In addition to institutes of default and liability for damage, the institute of rights arising from defective performance is a key institute of ensuring the proper and timely fulfilment of the obligation. Considering how often practically one of the parties to the obligation performs defectively, it is difficult to imagine a private right of obligation without the institute of rights arising from defective performance. The factual position of the parties to the obligation is often unequal, which is the reason why the legislator strives to protect the weaker party both through general protective institutes and through special legal regulation of rights arising from defective performance. Due to the existence of several special legal regulations, and in some cases unclear relations between them, the Czech legal regulation of rights arising from defective performance is often criticized as confusing and complicated. The thesis is systematically divided into four parts. The first part provides...