Philosophiae Doctor - PhD / It was postulated that each gene has three main sets of transcriptional elements: one which is gene-specific, one which is family-specific, and a third which is tissue-specific.The starting hypothesis for this project had been: “Each family of genes has a distinct set of transcriptional elements that is unique onto this family”. The primary aim of this project was therefore the identification of the family-specific set of transcriptional elements within the AMPA receptor gene family. The question then is how does one measure or identify this uniqueness within the promoters of this family of genes. The answer seemed to lie in making an assessment of the promoters of this family of genes against a background of a comprehensive set of promoter sequences and in the process,to try to find the transcriptional elements that were present in the AMPA receptor gene promoters but were not so common in the general population of gene promoters.To achieve the primary aim of this project, it was essential that a comprehensive dataset of promoter sequences was available. There are ample data freely available through the web. However, it is often not available in a form that we might want it in. Another problem that one constantly encounters is the lack of general consensus among the research community in agreeing on a standard annotation. For example, a gene can sometimes be given 2 or 3 different names by different laboratories which have successfully cloned the same gene. This, in turn, hinders the data collection process. At the start of this project, there was an existing curated database of experimentally-verified eukaryotic promoter sequences called the Eukaryotic Promoter Database (EPD) and a software called Promoter Extraction from GenBank (PEG) which, as its name implies, extracts promoter sequences available through GenBank (Cavin Périer et al., 1998;Zhang & Zhang, 2001; Praz et al., 2002; Schmid et al., 2004). However, limitations existed in both these resources. For EPD, the number of curated promoter sequences available was low and also, the length of these promoter sequences was short. For PEG,the main limitation was that the extraction from GenBank would result in extraction of sequences of variable lengths.Therefore, the 5’-end Information Extraction (FIE)system was developed for the expressed purpose of collecting promoter sequences without the limitations of PEG. This software relies on the alignment of multiple mRNA/cDNA sequences that are representative of a gene on the human genomic sequence to determine the transcription start site (TSS) of the gene and thus, with this information, extract the promoter sequence for the gene from the available human genomic sequence. This was the first promoter extraction software to work on this principle (Chong et al., 2002). This method was later supported by experimental work carried out by Coleman and colleagues (2002). Using the FIE2 software (Chong et al.,2003), some 10,000-odd human promoter sequences was extracted, starting at 1500bp uptream and ending at 1000bp downstream of the 5’-most TSS.Following the collection of the human promoter sequences, the approach developed by Bajic et al. (2004) was applied to study the promoters of the AMPA receptor genes. This approach relies on both the MATCH program to map putative transcription factor binding sites (TFBSs) to the promoter sequences and a software developed by Bajic etal. (2004) that calculates to the density for each TFBS or composite element. Having calculated the densities for the TFBSs and composite elements for both the target promoters (in this case, the AMPA receptor gene promoters) and the background promoters (the 10,000-odd human promoters), the software then calculates the degree of over-representation of each TFBS and composite element in the target promoters(measured against the background promoters) and then ranks the “singles”, “pairs” and “triplets” in the order of their degree of over-representation. Using this method, I identified the top 3 ranked “single”, “pair” and “triplet” transcriptional elements found commonly within the AMPA receptor promoters. In addition, a conventional phylogenetic footprinting study was also carried out for the human, mouse and rat GRIA1 promoter to identify key transcriptional elements within this subunit’s promoter.While the approach developed by Bajic et al. (2004) identifies key family-specific transcriptional elements, the phylogenetic footprinting study helps identify key genespecific transcriptional elements. Thus, they complement one another.The approach developed by Bajic et al. (2004) yielded an interesting result. It was found that the combination of the top 3 ranked “single”, “pair” and “triplet” transcriptional elements found in the AMPA receptor promoters were also found in 47 other genes. It was postulated that these 47 genes might, in fact, be co-regulated / co-expressed with the GRIAs and thus, explaining the existence of a shared promoter profile with the GRIA promoters. In support of this hypothesis, supporting evidence was found in published literature that 7 of these 47 genes (VAMP4, Rab3B, FKBP8, 3-OST-3A, CLSTN3,SOCS1 and IκBβ) might indeed be involved in the expression and functioning of the AMPA receptors.

Este trabalho tem por objetivo investigar as ligações viga-pilar misto preenchido, no tocante à transferência de forças de cisalhamento na região de ligação. O estudo engloba uma investigação experimental com ensaios do tipo push-out com carregamento centrado no núcleo de concreto e uma simulação numérica no pacote computacional DIANA visando obter dados de comportamento do mecanismo de transferência de forças de cisalhamento, aplicado à região de ligação viga-pilar. Foram utilizados modelos com 800 mm de altura e seção quadrada de dimensão (200 x 200 x 6,3) mm obtida a partir da composição de dois perfis U (200 x 100 x 6,3) mm. A resistência à compressão média do concreto de preenchimento foi de 50 MPa. Ao todo, foram ensaiados 3 modelos de ligação, utilizando chapas de extremidade e barras rosqueadas como mecanismo de ligação viga-pilar. Como elementos para transferência de forças entre o tubo de aço e o núcleo de concreto foram usados conectores tipo pino com cabeça ou cantoneiras. Os resultados experimentais mostraram a eficiência das barras rosqueadas e dos conectores de cisalhamento na transferência dos esforços de cisalhamento na ligação viga-pilar e na interface perfil de aço e concreto. A simulação numérica teve concordância satisfatória com os resultados experimentais obtidos. / In the design of concrete-filled steel tubular columns, the concrete and the steel tube must work together in order to achieve the overall resistance, stiffness and stability requirements. It is important that exists an adequate mechanism to transfer the forces from the steel beam to the steel tube, and then to the concrete core. This work presents a study on shear transfer in connections involving concrete-filled steel tubular columns and steel beams. The work was divided in two parts, being the first an experimental analysis with push-out tests, and the second one a numerical simulation of the tests, using the software DIANA. The tested specimens were 800 mm height , with square section (200 x 200 x 6,3mm) obtained from two welded U-shape profiles. A concrete with compressive strength of 50 MPa was used as a filling for the columns. Altogether, three connections with steel end plates and passing bars were tested. Two types of shear connectors between steel column and concrete core were used: stud-bolts and angles, and a reference specimen without connectors was also tested. The results showed the efficiency of the shear connectors in the tranference of forces.

Este trabalho tem por objetivo investigar as ligações viga-pilar misto preenchido, no tocante à transferência de forças de cisalhamento na região de ligação. O estudo engloba uma investigação experimental com ensaios do tipo push-out com carregamento centrado no núcleo de concreto e uma simulação numérica no pacote computacional DIANA visando obter dados de comportamento do mecanismo de transferência de forças de cisalhamento, aplicado à região de ligação viga-pilar. Foram utilizados modelos com 800 mm de altura e seção quadrada de dimensão (200 x 200 x 6,3) mm obtida a partir da composição de dois perfis U (200 x 100 x 6,3) mm. A resistência à compressão média do concreto de preenchimento foi de 50 MPa. Ao todo, foram ensaiados 3 modelos de ligação, utilizando chapas de extremidade e barras rosqueadas como mecanismo de ligação viga-pilar. Como elementos para transferência de forças entre o tubo de aço e o núcleo de concreto foram usados conectores tipo pino com cabeça ou cantoneiras. Os resultados experimentais mostraram a eficiência das barras rosqueadas e dos conectores de cisalhamento na transferência dos esforços de cisalhamento na ligação viga-pilar e na interface perfil de aço e concreto. A simulação numérica teve concordância satisfatória com os resultados experimentais obtidos. / In the design of concrete-filled steel tubular columns, the concrete and the steel tube must work together in order to achieve the overall resistance, stiffness and stability requirements. It is important that exists an adequate mechanism to transfer the forces from the steel beam to the steel tube, and then to the concrete core. This work presents a study on shear transfer in connections involving concrete-filled steel tubular columns and steel beams. The work was divided in two parts, being the first an experimental analysis with push-out tests, and the second one a numerical simulation of the tests, using the software DIANA. The tested specimens were 800 mm height , with square section (200 x 200 x 6,3mm) obtained from two welded U-shape profiles. A concrete with compressive strength of 50 MPa was used as a filling for the columns. Altogether, three connections with steel end plates and passing bars were tested. Two types of shear connectors between steel column and concrete core were used: stud-bolts and angles, and a reference specimen without connectors was also tested. The results showed the efficiency of the shear connectors in the tranference of forces.

Work occupies computational modelling mechanical behavior elastomers and composits with rubber matrix and their utilization for compute model of tire creation. MATADOR tire 165/65 R13 Axisymetric 2D model was created in two geometric variants. For the computational modeling is applying the Finite element method (FEM). The model was in different variants distinctive grade of modeling material. At first was done inner pressure analyst impact on deformation of each of model. Then was count influence on tire load with angular velocity meanwhile with inner pressure. The impact thickness of tire protector layer on global deformation tyre casing was verified too.

Timber-concrete composite (TCC) structures are becoming more popular in several industrial applications as an efficient method for optimizing the structural performance and the cost of construction as well as lowering the emissions of carbon dioxide. TCC floors are more sustainable than pure concrete floors and more resistant to vibrations and excessive deflections than pure wooden floors. The effectiveness of a TCC floor is dependent on the connection between the materials. The stiffness and strength of the composite element increases by having a rigid connection. An example of a rigid connection is an adhesive-bonded connection, however obtaining a connection without slip is difficult considering there will always be certain amount of slippage in the connection. In this thesis adhesive connections are investigated with two different types of adhesive, one called Sikasil SG-500 and the other Sika PS. The application of the adhesives for the test specimen differ. Since Sika PS is a more fluid glue, a different approach was necessary than for the Sikasil SG-500. Five test specimen were tested of each adhesive by performing double shear push out tests and comparing the results to a numerical model, which was performed in ABAQUS. In the numerical model, the adhesive was created as a cohesive element. Furthermore the properties of the modeled adhesive was based on the experimental results for respective adhesive. The experimental results showed that both adhesives managed the estimated shear force in the serviceability limit state and the ultimate limit state and yet remained in the elastic region. Sikasil SG-500 turned out to be more flexible while Sika PS specimen resulted in higher shear strength. The short creep tests (30 minutes of a constant load) showed that the deformation increased more for Sika PS than for Sikasil SG-500. However both adhesives had large deformations after only 30 minutes. There was also a difference in the average longitudinal shear strength, where it resulted in 1.06 MPa for Sikasil SG-500 and 2.02 MPa for Sika PS. This study indicates that Sika PS is more preferable in TCC structures than Sikasil SG-500.

The master´s thesis deals with wood-concrete composite floors constructions. The work is divided into a theoretical and a practical part. The theoretical part describes methods of construction and materials used for wood-concrete composite constructions. The practical part describes an experimental four point bend test carried out on wood-concrete composite elements and samples. Further, manual calculation was performed according to Eurocode 5 and in program Asteres three variants of test elements were modeled. Each variant had different composite stiffness according to the working diagram of composite elements. At the end, experimental, computational and numerical results were compared.

Metall-Schaumstoff-Verbundelemente werden aufgrund ihrer sehr guten Flammschutzwirkung, selbsttragenden Eigenschaften bei geringem Gewicht und der kostengünstigen Montagemöglichkeit zunehmend in der Baubranche zur effizienten Wärmedämmung eingesetzt. Die Verbundelemente bestehen aus zwei flächigen, linierten oder profilierten, außen liegenden metallischen Deckschichten geringer Dicke, in denen der Zwischenraum (Kernschicht) mit einer wärmedämmenden Hartschaumschicht aus z. B. Polyisocyanurat ausgefüllt ist. Bedingt durch den (kontinuierlichen) Fertigungsprozess entstehen im Schaumkern material- und strukturbedingte Inhomogenitäten, wodurch dessen Materialeigenschaften über der Schaumdicke variieren. Diese Inhomogenitäten können die mechanischen Eigenschaften der Verbundelemente negativ beeinflussen und zu einem frühzeitigen Versagen führen. Aus diesem Grund ist das Verständnis bzw. die Berücksichtigung der lokalen Effekte im Schaum sowohl für die Auslegung der Verbundelemente als auch zur Schöpfung möglicher Potenziale zur Verbesserung der Produktqualität essenziell. Da die Betrachtung der lokalen Einflussfaktoren experimentell und analytisch nur begrenzt isoliert möglich ist, wird in dieser Arbeit ein numerischer Multiskalen-Ansatz unter Verwendung der Finite-Elemente-Methode vorgestellt, welcher in der Lage ist, die mechanischen Eigenschaften der lokalen mesoskaligen Schaumstrukturen mittels Homogenisierung in einem makroskaligen Simulationsmodell eines kompletten Verbundelementes zu berücksichtigen. Für die Validierung und Bewertung des Modells werden kommerziell erhältliche Verbundelemente verwendet. Im ersten Schritt werden die lokalen (höhenaufgelösten) Schaumeigenschaften dieser Verbundelemente experimentell charakterisiert. Besonderes Augenmerk liegt auf der Analyse des Schaumbasismaterials und der Zellstruktur. Basierend auf den experimentellen Daten wird ein mesoskaliges Simulationsmodell eines Repräsentativen Volumenelements erstellt und validiert, welches eine Vorhersage der mechanischen Eigenschaften anisotroper Schaumstrukturen mit unterschiedlichen Aspektverhältnissen und Orientierungen der individuellen Zellen auf Basis definierter Ellipsoidpackungen und einer anisotropen Mosaik-Methode ermöglicht. Neben der Vorhersage der lokalen Schaumeigenschaften bietet das mesoskalige Modell die Möglichkeit, Auswirkungen einzelner Einflussfaktoren auf die Schaumeigenschaften isoliert zu betrachten. Ein Vergleich zwischen experimentellen und numerischen Ergebnissen aus einem zuvor definierten Bereich zeigt, dass sowohl im Experiment, als auch in der mesoskaligen Simulation die Strukturen ein stark anisotropes Verhalten aufweisen, wobei der Grad der Anisotropie in der Simulation tendenziell leicht unterschätzt wird. Trotz kleiner Abweichungen stimmen die Simulationsergebnisse gut mit den experimentellen Daten überein. Demnach ist das mesoskalige Simulationsmodell geeignet, um die lokalen, anisotropen mechanischen Schaumeigenschaften nachzubilden. Darauf aufbauend werden die lokalen Materialeigenschaften eines ausgewählten Verbundelementes numerisch bestimmt und auf das makroskopische Modell übertragen. Im Zuge dessen werden sowohl geeignete Methoden zur Implementierung der Schaumeigenschaften vorgestellt, als auch eine Sensitivitätsanalyse zum Einfluss der Auflösung der lokalen mesoskaligen Schaumstruktur auf die makroskopischen Eigenschaften der Verbundelemente durchgeführt. Die Qualität des makroskopischen Simulationsmodells wird über den Vergleich der simulativen Ergebnisse mit bauteil-typischen Messungen analysiert. Vergleichbar zur mesoskaligen Validierung können die makroskaligen Bauteileigenschaften mit kleineren Abweichungen gut wiedergegeben werden. Voraussetzung ist jedoch, dass die im Vergleich zur (nahezu) homogenen Schaum-Kernschicht äußeren, inhomogenen Randschichten separat modelliert werden. Diese Erkenntnisse lassen sich auch auf andere Verbundelemente mit unterschiedlichen Dicken übertragen, da aus den experimentellen Untersuchungen bekannt ist, dass die Verbundelemente qualitativ vergleichbare Eigenschaftsverteilungen aufweisen. Aufgrund des hohen Rechen- und Modellierungsaufwands wird abschließend bewertet, inwiefern die komplexen mesomechanischen Eigenschaften anisotroper Schaumstrukturen in zukünftigen Multiskalen-Simulationen effizienter berücksichtigt werden können. Hierzu wird ein Künstliches Neuronales Netz verwendet, wobei der Fokus aufgrund der benötigten Dauer zur Erstellung einer geeigneten Datenbasis auf der Vorhersage des orthotropen Steifigkeitstensors liegt. Die Ergebnisse zeigen, dass bei einer geeigneten Netzwerkstruktur und einer ausreichenden Datenbasis die mechanischen Eigenschaften komplexer Zellstrukturen mittels eines Neuronalen Netzes innerhalb von Sekunden sehr gut reproduziert werden können. In einer abschließenden Studie wird der Einfluss der Datenbankgröße auf die Vorhersagegenauigkeit untersucht. Es kann festgestellt werden, dass mindestens 500 Trainingsdatenpunkte erforderlich sind, um eine ausreichende Genauigkeit zu erreichen. / Metal-foam composite elements are used increasingly for efficient thermal insulation in the construction industry due to their very good flame-retardancy, self-supporting properties combined with low weight, and low-cost assembly options. The composite elements consist of two thin, flat, lined, or profiled external metallic cover layers, in which the interspace (core layer) is filled with a thermally insulating low-density layer of rigid foam, e.g. polyisocyanurate. Due to the (continuous) manufacturing process, material- and structure-related inhomogeneities occur in the foam core, causing its material properties to vary over the core thickness. These inhomogeneities can negatively affect the mechanical properties of the composite elements and lead to premature failure. For this reason, understanding and considering the local effects is essential both for the design of the composite elements and for creating possible potentials to improve the product quality. Since the consideration of local influencing factors is limited experimentally and analytically in isolation, this work presents a numerical multiscale approach using the finite element method, which can consider the mechanical properties of the local mesoscale foam structures using homogenization in a macroscale simulation model of a complete composite element. For the validation and evaluation of the model, commercially available composite elements are used. In a first step, the local (height-resolved) foam properties of these composite elements are characterized experimentally. Particular attention is paid to the analysis of foam base material, foam density, and cell structure. Based on the experimental data, a mesoscale simulation model of a representative volume element is created and validated, which allows a prediction of mechanical properties of anisotropic foam structures with different aspect ratios and orientations of the individual cells based on defined ellipsoid packings and an anisotropic tessellation method. In addition to predicting local foam properties, this mesoscale model offers the possibility to consider effects of individual influencing factors on foam performance in isolation. A comparison between experimental and numerical results from a previously defined area shows that in both the experiment and the mesoscale simulation, the structures exhibit strongly anisotropic behavior, although the degree of anisotropy tends to be slightly underestimated in the simulation. Despite small deviations, simulation results agree well with experimental data. Accordingly, this mesoscale simulation model is suitable to reproduce local anisotropic mechanical foam properties. Based on this, local material properties of a selected composite element are determined numerically and transferred to the macroscopic model. In the course of this, suitable methods for implementing foam properties are presented as well as a sensitivity analysis on the influence of resolution of the local mesoscale foam structure on macroscopic properties of composite elements. The quality of the macroscopic simulation model is again analyzed via a comparison of simulative results with component-typical measurements. Comparable to the mesoscale validation, macroscale component properties can be reproduced well with minor deviations. A prerequisite, however, is that outer, inhomogeneous layers are modeled separately compared to (nearly) homogeneous foam core layer. These findings can also be applied to other composite elements with different thicknesses since it is known from experimental investigations that composite elements exhibit qualitatively comparable property distributions. Finally, due to the high computational and modeling effort, it is evaluated to what extent the complex mesomechanical properties of anisotropic foam structures can be considered more efficiently in future multiscale simulations. For this purpose, an Artificial Neural Network is used, focusing on the prediction of orthotropic stiffness tensor due to the required duration to generate a suitable database. Results from this study show that with a suitable network structure and a sufficient database, the mechanical properties of complex foam structures can be reproduced very well via the Artificial Neural Network within seconds. In a final study, the effect of the database size on the prediction accuracy was examined. It could be observed that at least 500 training datapoints are required to obtain sufficient accuracy.