L’objectif de cette thèse est d’étudier expérimentalement les deformations de microcapsules dans un écoulement confiné. Les microcapsules sont composées d’albumine du sérum humain avec des concentrations de 5 à 20 [g/100mL]. Leur taille varie de 50 à 1000 [μm]. Les capsules sont injectées dans des écoulements de Poiseuille produits dans des canaux microfluidiques présentant deux sections différentes : circulaire ou carrée.La mesure des caractéristiques géométriques de microcapsules déformées couplée à des simulations numériques mène à la détermination du module de cisaillement surfacique. Cette caractéristique mécanique augmente fortement tant avec la taille qu’avec la concentration en protéine de la capsule, et plus précisément avec le produit de ces deux paramètres.Le fluide est ensemencé avec des microparticules pour mesurer l’écoulement induit par une capsule dans un capillaire cylindrique par la méthode de la vélocimétrie par suivi de particules. Les zones de recirculation et de perturbation sont alors déduites et comparées avec la simulation numérique d’un objet rigide dans un capillaire et présentant le profil donné par les expériences. Finalement un système original de visualisation optique est consacré à l’observation simultanée de la vue de côté et de la vue de face des capsules pour obtenir sa forme entière. Ceux-ci révèlent l’existence des plis tout autour de la membrane des capsules. Le seuil de formation et l’évolution de ces plis sont étudiés en fonction de la vitesse, de la taille et du confinement, dans des canaux de section circulaire ou carrée. / The objective of this thesis is to study experimentally microcapsule deformations in confined flows. The microcapsules are made of cross-linked proteins, the human serum albumin (HSA) with concentrations from 5 to 20 [g/100mL]. Their size vary from 50 to 1000 [μm]. Capsules are injected in Poiseuille flows generated within microfluidics channels with two different cross sections geometries : circular or square.The measurement of geometrical characteristics of deformed microcapsules coupled with numerical simulations leads to the determination of the surface shear modulus. This mechanical characteristic increases strongly with both the size and the protein concentration of the capsule, and more precisely with the product of these two parameters.The flow is seeded with microparticles to measure the induced flow of a capsule in a cylindrical capillary by particle tracking velocimetry. The recirculation and perturbation zones are then deduced and compared with numerical simulation of a rigid body flowing in a capillary. Finally an original system of optical visualization is dedicated to the simultaneous observation of the side and the front view of the capsules to get its whole shape. These reveal radial wrinkles all around capsules membrane. The formation threshold and the evolution of these wrinkles are studied as function of the capsule velocity and size and the confinement within capillaries with circular or square cross–section.

Mit dem Übergang von bauwerksorientierter zu prozessorientierter Arbeitsweise erlangt die domänenübergreifende Bereitstellung von Informationen wachsende Bedeutung. Das betrifft bspw. die Erstellung von Controlling-Kennwerten, die Vorbereitung von Simulationen oder die Betrachtung neuer Aspekte wie Energieeffizienz. Aktuelle Datenformate und Erschließungsmethoden können diese Herausforderung jedoch nicht befriedigend bewältigen. Daher bedarf es einer Methode, welche interdisziplinäre Bauinformationsprozesse uneingeschränkt ermöglicht. Vorhandene Kommunikationsprozesse und Fachanwendungen sollen dabei beibehalten und weitergenutzt werden können. Mit der Multimodell-Methode wird ein Lösungsansatz für die strukturellen Probleme interdisziplinärer Bauinformationsprozesse vorgestellt. Multimodelle bündeln heterogene Fachmodelle unterschiedlicher Domänen und erlauben die Verbindung ihrer Elemente in externen, ID-basierten Linkmodellen. Da die Fachmodelle unberührt bleiben, wird auf diesem Weg eine lose und temporäre Kopplung ermöglicht. Durch den Verzicht auf ein führendes oder integrierendes Datenschema werden keine Transformationsprozesse benötigt, können etablierte und heute übliche Datenformate weitergenutzt und die verlinkten Fachmodelle neutral ausgetauscht werden. Die in Multimodellen verknüpften Daten bieten einen informationellen Mehrwert gegenüber alleinstehenden Fachmodellen. Zusammengehörende Informationen können über die persistenten Links automatisch ausgewertet werden, anstelle manuell vom Menschen immer wieder flüchtig neu zugeordnet werden zu müssen. Somit erscheint ein Multimodell gegenüber einem Benutzer wie ein einziger abgeschlossener Informationsraum. Um solche datenmodell-, datenformat- und domänenübergreifenden Informationsräume komfortabel erstellen und filtern zu können, wird die deklarative Multimodell-Abfragesprache MMQL eingeführt. Diese erlaubt einen generischen Zugriff auf die Originaldaten und bildet die Kernkonzepte der Multimodell-Erschließung - mehrwertige Linkerzeugung und strukturelle Linksemantik - ab. Ein zugehöriger Interpreter ermittelt den Lösungsweg für konkrete Anweisungen und führt diesen auf realen Daten aus. Die Umsetzung und Bereitstellung der Konzepte als IT-Komponenten auf verschiedenen Ebenen - von der Datenstruktur über Bibliotheken und Services bis hin zur alleinstehenden, universellen Multimodell-Software M2A2 - erlaubt die sofortige und direkte Anwendung der Multimodell-Methode in der Praxis. / With the transition of building-oriented to process-oriented work, the provision of cross-domain information gained growing importance - for example in the creation of controlling parameters, the preparation of simulations or when considering new aspects such as energy efficiency. However, current data formats and access methods cannot cope with this challenge satisfactory. Therefore, a method is required, that enables interdisciplinary construction information processes fully. Thereby existing communication processes and domain applications have to be retained and continued to be used as possible. With the multi-model method, an approach to structural problems of such interdisciplinary construction information processes is presented. Multi-models combine heterogeneous models of different domains and allow the connection of their elements in external ID-based link models. As the domain models remain unaffected, a loose and temporary coupling is possible in this way. By not using a leading or integrating data schema, no transformation processes are required, common established data formats can be retained and the linked domain models can be exchanged neutrally. The linked data in multi-models offer an additional value of information over single domain models. Information belonging together can be automatically evaluated by the persistent links - instead of being repeatedly reassigned by people in a volatile way. Thus, a multi-model appears to a user as a single self-contained information space. In order to create and filter such cross-format and cross-domain information spaces comfortably, the declarative multi-model query language MMQL is introduced. It allows for generic access to the original data and integrates the core concepts of the multi-model development - n-ary link generation and structural link semantics. An associated interpreter determines the approach for specific instructions and executes it on real data. The implementation and deployment of the concepts as IT components at various levels - from the data structure via libraries and services, to the universal multi-model software M2A2 - allows an immediate and direct application of the multi-model method in practice.

Cette thèse s’inscrit dans le contexte de l’ANR ISABEAU (Innovating for Structural Adhesive Bonding Evaluation and Analysis with Ultrasounds, associant des physico-chimistes et des acousticiens) et cherche à apporter des connaissances nouvelles sur l’évaluation par ultrasons du niveau d’adhésion d’un collage structural par ondes de Lamb. La première partie porte sur l’aspect cohésif et particulièrement sur l’influence du paramètre de réticulation de réseaux époxys sur les courbes de dispersion des ondes de Lamb. La deuxième partie est consacrée à la caractérisation de niveaux d’adhésion dans une structure bicouche Aluminium Epoxy en tenant compte aussi bien des aspects cohésifs qu’adhésifs. Des échantillons à niveau d’adhésion connus et maîtrisés sont réalisés avec l’aide de physico-chimistes, où l’époxy est partiellement ou totalement réticulé, et où l’interface substrat adhésif a subit différents traitements chimiques et/ou mécaniques. Les résultats expérimentaux sont confrontés à ceux issus du modèle rhéologique de Jones résolu par éléments finis. Enfin, la troisième partie porte sur l’étude d’un assemblage tricouche Aluminium/Epoxy/Aluminium et cherche à qualifier différents niveaux d’adhésion à l’aide du modèle de Jones par ondes guidées et également par l’étude des fréquences de coupure des modes verticaux de la structure. / This thesis is in the context of the ANR ISABEAU (Innovating for Structural Adhesive Bonding Evaluation and Analysis with Ultrasounds, with the association of physico-chemists and acousticians) and seeks to bring new knowledge of the ultrasonic evaluation of the level of adhesion of structural bonding using Lamb waves. The first part focuses on the cohesive aspect, in particular on the influence of the crosslinking parameter of the polymer on the Lamb waves dispersion curves. The second part is dedicated to the evaluation of the adhesion level of a bi-layer Aluminum Epoxy taking into account the both cohesive and adhesive aspects. Samples of controlled and known adhesion levels are manufactured with the help of physico-chemists, where the crosslinking of the epoxy is partial or total, and the interface substrate-adhesive have been treated chemically and/or mechanically. The experimental results are compared to those obtained from a predictive model based on the rheological model of Jones solved by finite elements method. Finally, the third part focuses on the study of tri-layers Aluminum/Epoxy/Aluminum, looking for the qualification of different levels of adhesion with the Jones model using guided waves as well as the cut-off frequencies of the structure.

Eukaryotic translation initiation is a complex and highly regulated process involving the ribosome, mRNA and proteins called eukaryotic initiation factors (eIFs). The overall aim of translation initiation is to position the ribosome at the initiation codon of the mRNA. eIF2, in its GTP-bound conformation, binds the initiator tRNA (Met-tRNAiMet) and delivers it to the 40S ribosomal subunit. When the anticodon of the tRNA is bound to the initiation codon, the GTP on eIF2 is hydrolysed to GDP. The guanine nucleotide exchange factor (GEF) eIF2B regenerates eIF2-GTP. eIF2 and eIF2B are multisubunit/multidomain protein complexes. Because information regarding the interface between each complex is limited, particularly the interface on the eIF2γ subunit, which binds the guanine-nucleotides and Met-tRNAiMet, interactions between the minimal GEF domain of eIF2Bε, εGEF, and eIF2 were mapped using mutagenesis and an in vitro cysteine cross-linking approach, with the cross-linker Mts-Atf-Biotin. Site-directed mutagenesis (SDM) was used to mutate five N-terminal and five C-terminal surface-exposed εGEF residues to cysteines. The mutant alleles were analysed in Saccharomyces cerevisiae and it was found that the gcd6-R574C allele was lethal and the gcd6-T572C was Gcd-. Further gcd6-R574 mutant alleles were also found to be lethal in yeast but expressed in vivo.εGEF-R574C has dramatically reduced GEF activity in vitro and binding assays showed that this mutant has significantly reduced affinity for eIF2. The εGEF-T572C and εGEF-S576C mutants also have severe and minor eIF2-binding defects respectively, while the C-terminal εGEF-Cys mutants have slightly reduced affinity for eIF2. The N-terminal εGEF-Cys mutants cross-link specifically to eIF2γ, while the C-terminal εGEF-Cys mutants interact predominantly with eIF2β. From the data obtained in this study, we propose a new model for eIF2B-mediated guanine-nucleotide exchange that reduces the importance of eIF2β and suggests εGEF resembles other GEFs in binding primarily to its G protein partner eIF2γ.

In our information age, it is of the highest importance that information is easy to understand by as many members of the potential target audience as possible. The present study analyses and compares the readability of 20 newspaper articles, half from the tabloid Daily Mail and the other half from the broadsheet The Daily Telegraph. The methods used to analyse the articles are mathematic readability formulas based on sentence and word length, as well as analyses of the use of the active and the passive voice, type-token ratio, number of clauses per sentence, and linking words. The results do not completely align with each other. Three of the five methods – the readability formulas, the use of the passive voice, and clauses per sentence – suggest that the Daily Mail articles are easier to understand, whereas the type-token ratios imply the opposite, and the linking words results did not show a difference in readability.

This thesis has been prepared as urban study BVV in Brno. The project deals with the revitalization of the area, streamlining usage in the long run. The area is delimited to the northeast street Hlinka, southwest Street Bauer. The territory is located near the center of Brno, near the Mendel Square. It is directly connected to the ring road. The main objectives of the project are to restore its original luster campus, thanks to which Brno became known in the world - to create an international cultural and sports science node. Open to the public year-round resort and create new areas of specific housing related to the function of the complex.

Orientador: Josimeri Hebling / Resumo: Objetivo: Investigar a citotoxicidade transdentinária da acroleína (ACR) sobre células pulpares e a resistência máxima à tração (RMT) da matriz dentinária e resistência da união (RU) resina-dentina após a biomodificação do colágeno dentinário por esse agente promotor de ligações cruzadas. Métodos: Discos de dentina (0,4 mm de espessura) foram obtidos de molares humanos hígidos e adaptados em câmaras pulpares artificiais. Células MDPC-23 foram semeadas na superfície pulpar desses discos e a superfície oclusal foi condicionada com ácido fosfórico por 15s. Sobre a dentina condicionada foi aplicado (n=9): água deionizada (controle), ACR 0,02%, 0,01%, 0,005%, glutaraldeído 5% (GD) ou peróxido de hidrogênio 3%. Após 60s, a superfície foi lavada e as câmaras foram incubadas por 24h. Foi avaliada a viabilidade das MDPC-23 (alamarBlue) aderidas na parede pulpar dos discos e os extratos foram aplicados em novas MDPC-23 e HDPCs (células da polpa dental humana) cultivadas em placas de cultura. Após 24h, essas células foram avaliadas quanto a viabilidade, atividade de fosfatase alcalina (ensaio da timolftaleína), presença de nódulos de mineralização (Alizarin red) e expressão gênica de ALPL, DSPP, MMP2, MMP9 e IL1B (PCRq). Vinte cinco molares adicionais foram seccionados para obter espécimes de dentina (n=50) que foram completamente desmineralizados com ácido fosfórico por 24h. Os espécimes de matriz dentinária foram tratados por 60s com: água, ACR 0,02%, 0,01%, 0,005% ou GD 5% e submetid... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Objective: To investigate the transdentinal cytotoxicity of acrolein (ACR) on pulp cells, as well as the ultimate tensile strength (UTS) of the dentin matrix, and the strength of resin-dentin bonds after dentin collagen biomodification with this cross-linker. Methods: Dentin disks (0.4 mm thick) were cut from sound human molars and adapted in artificial pulp chambers. MDPC-23 were seeded on the pulpal side of the disks and the occlusal surface was etched with phosphoric acid for 15s. The etched dentin was treated with (n=9): deionized water (control), 0.02%, 0.01%, 0.005% ACR, 5% glutaraldehyde (GD), or 3% hydrogen peroxide. After 60s, the surface was rinsed, and the chambers were incubated for 24h. The viability of MDPC-23 cells seeded on the disk was assessed (alamarBlue) and the extracts were applied on new MDPC-23 and HDPCs (human dental pulp cells) seeded in culture plates. After 24h, the viability of the cells was investigated as well as the activity of alkaline phosphatase, presence of mineralized nodules (Alizarin red) and ALPL, DSPP, MMP2, MMP9 and IL1b gene expression (qPCR). Additional twenty-five human molars were sectioned to obtain dentin specimens (n=50) which were completely demineralized in 10% phosphoric acid for 24h. The specimens were treated for 60s with: water, 0.02%, 0.01%, 0.005% ACR or 5% GD, and then submitted to a mechanical test to determine the UBS. Finally, flat dentin surfaces prepared in 40 human molars were etched with phosphoric acid and trea... (Complete abstract click electronic access below) / Mestre

In this master thesis we describe a method for linking named entities in a given text to a knowledge base - Named Entity Linking. Using a deep neural architecture together with BERT contextualized word embeddings we created a semi-supervised model that jointly performs Named Entity Recognition and Named Entity Disambiguation. The model outputs a Wikipedia ID for each entity detected in an input text. To compute contextualized word embeddings we used pre-trained BERT without making any changes to it (no fine-tuning). We experimented with components of our model and various versions of BERT embeddings. Moreover, we tested several different ways of using the contextual embeddings. Our model is evaluated using standard metrics and surpasses scores of models that were establishing the state of the art before the expansion of pre-trained contextualized models. The scores of our model are comparable to current state-of-the-art models.

Bacterial protein WrbA from E. coli is the founding member of a new family of FMN-dependent NAD(P)H oxidoreductases, forming a functional and structural bridge between bacterial flavodoxin and certain mammalian NAD(P)H:quinone oxidoreductase. For these reasons, protein WrbA is recently intensively studied using various analytical and computing methods. Protein WrbA participates in the protection of cells against oxidative stress, but precise function of the protein WrbA in vivo is still unknown. Protein WrbA forms multimers in solutions. In μM concentrations and at low temperature (4 řC) the protein is in the form of a dimer, with increasing temperature becomes tetrameric. Available three-dimensional crystal structure contains the information about the tetrameric form of the protein, the dimeric form has not been structurally characterized. This thesis was focused on the study of the dynamic behavior of protein WrbA in solution using methods of hydrogen-deuterium exchange and chemical cross-linking followed by mass spectrometric analysis with high resolution (FT-ICR). Behavior of the protein was monitored according to the presence of cofactor FMN. Effect of temperature and protein concentration was also studied. Hydrogen-deuterium exchange provided information about solvent accessibility and...

Transcription factors play crucial regulatory role within the cell and the entire multicellular organism. The important factor is its ability to interact with other regulatory proteins and DNA. Despite the fact that a large part of the interaction network is already documented, detailed information on the structure and dynamics of protein-protein and protein-DNA complexes is still scarce. In this thesis we focused on the possibility of studying conformational changes given by the transcription factor-DNA complex formation using the methods of structural mass spectrometry: hydrogen/deuterium exchange and chemical crosslinking. As a model, we chose a transcription factor FOXO4 which DNA binding domain is structurally well characterized both in free form and in the complex with DNA.