No / An extensive study of the fibre orientation structures developed in a transverse ribbed plate during injection moulding, and the use of these structures to investigate the effect of local fibre orientation state on crack initiation resistance, is reported. The fibre orientation results for the ribbed plate, measured using large area image analysis system developed at Leeds University, showed that after an initial settling down period, the central core region, where the fibres are aligned perpendicular to the flow direction, decreased in size monotonically, with an associated monotonic increase in the outer shell regions, where the fibres are aligned preferentially along the injection direction. Interestingly, the level of orientation in the two regions remained almost constant: only the proportions of the two regions were found to change with flow length. Across the plate, close to the gate, the central core region was found to have a lens-like shape, while at the other end of the plate the core was thinner and also consistent in thickness across the sample width. The transverse rib was found to cause little disturbance to the fibre orientation of the base plate. The different proportions of the shell and core regions at different locations over the ribbed plate provided an ideal case to test the proposition of Friedrich that the crack resistance of a short fibre reinforced material depends on the number of fibres that are perpendicular to the crack tip. The impact test results gathered in this way confirmed this hypothesis of Friedrich.

Le corps calleux (CC) est la principale commissure cérébrale connectant les aires corticales homologues des deux hémisphères chez les vertébrés placentaires. Les malformations du corps calleux (MCC) représentent la malformation cérébrale la plus fréquente à la naissance et sont présentes chez 5% des individus avec anomalie neuro-développementale. Une meilleure connaissance de l’ontogenèse du corps calleux et de ses causes génétiques devrait permettre d’ouvrir la voie à des corrélations cliniques pour un meilleur conseil génétique. Cet aspect constitue probablement l’enjeu de la prochaine décennie concernant les foetus avec MCC. Le travail de thèse a porté sur 138 foetus avec MCC, pour lesquels nous avons fait un examen foeto-neuropathologique et une classification en plusieurs catégories. Au total, ce travail a permis : 1/le démantèlement des causes génétiques des MCC par une triple approche de CGH array, d’exome en trio et de panels ciblés, avec une augmentation considérable des causes identifiables de MCC au sein de cette cohorte, 2/ l’identification et la caractérisation fonctionnelle d’un nouveau gène de ciliopathie dans un phénotype extrême ; 3/ l’identification de 3 nouvelles mutations de ZBTB20, récemment identifié comme responsable du syndrome de Primrose, démontrant que ce syndrome est une cause fréquente de MCC et permettant une description clinico-radiologique plus précise. 4/ L’identification de plusieurs gènes candidats en cours de validation. / Corpus callosum is the main cerebral commissure connecting homologous cortical areas in placental mammals. Malformations of corpus callosum (MCC) are the most frequent brain malformation at birth and are present in 5% of patients with neurodevelopmental delay. A good knowledge of genetics of corpus callosum development should pave the way to better clinical correlations for a more accurate genetic counselling. This is the challenge of the next decade. This thesis concerns a cohort of 138 fetuses with MCCs, well classified on neuropathological examination. It allowed 1/ to unravel the genetic causes of MCC through a triple approach combining CGH array, whole exome and NGS panels sequencing, with a considerable increase in the number of causes of MCC identified ; 2/ identification of a new gene in an extreme ciliopathy phenotype; and 3/ identification of novel ZBTB20 mutations , a gene recently identified as responsible for Primrose syndrome, showing that this syndrome is frequent among MCCs and allowing a precise clinico-radiological description of the syndrome. 4/ Several new candidate genes are under study.

Le corps calleux (CC) est la principale commissure cérébrale connectant les aires corticales homologues des deux hémisphères chez les vertébrés placentaires. Les malformations du corps calleux (MCC) représentent la malformation cérébrale la plus fréquente à la naissance et sont présentes chez 5% des individus avec anomalie neuro-développementale. Une meilleure connaissance de l’ontogenèse du corps calleux et de ses causes génétiques devrait permettre d’ouvrir la voie à des corrélations cliniques pour un meilleur conseil génétique. Cet aspect constitue probablement l’enjeu de la prochaine décennie concernant les foetus avec MCC. Le travail de thèse a porté sur 138 foetus avec MCC, pour lesquels nous avons fait un examen foeto-neuropathologique et une classification en plusieurs catégories. Au total, ce travail a permis : 1/le démantèlement des causes génétiques des MCC par une triple approche de CGH array, d’exome en trio et de panels ciblés, avec une augmentation considérable des causes identifiables de MCC au sein de cette cohorte, 2/ l’identification et la caractérisation fonctionnelle d’un nouveau gène de ciliopathie dans un phénotype extrême ; 3/ l’identification de 3 nouvelles mutations de ZBTB20, récemment identifié comme responsable du syndrome de Primrose, démontrant que ce syndrome est une cause fréquente de MCC et permettant une description clinico-radiologique plus précise. 4/ L’identification de plusieurs gènes candidats en cours de validation. / Corpus callosum is the main cerebral commissure connecting homologous cortical areas in placental mammals. Malformations of corpus callosum (MCC) are the most frequent brain malformation at birth and are present in 5% of patients with neurodevelopmental delay. A good knowledge of genetics of corpus callosum development should pave the way to better clinical correlations for a more accurate genetic counselling. This is the challenge of the next decade. This thesis concerns a cohort of 138 fetuses with MCCs, well classified on neuropathological examination. It allowed 1/ to unravel the genetic causes of MCC through a triple approach combining CGH array, whole exome and NGS panels sequencing, with a considerable increase in the number of causes of MCC identified ; 2/ identification of a new gene in an extreme ciliopathy phenotype; and 3/ identification of novel ZBTB20 mutations , a gene recently identified as responsible for Primrose syndrome, showing that this syndrome is frequent among MCCs and allowing a precise clinico-radiological description of the syndrome. 4/ Several new candidate genes are under study.

En Union Européenne les accidents frontaux font 28% des accidents routiers et sont responsables de 49% de mortalité, les fractures thoraciques étant la cause principale de décès. Les modèles en éléments finis du corps humain sont un outil important pour la simulation de chocs réels et la prédiction des risques d'endommagement. Cette thèse a permis de développer un modèle simple en éléments finis de la cage thoracique suffisamment souple d'utilisation et facilement paramétrable. Ce modèle est validé expérimentalement avant d'être utilisé pour une étude paramétrique. Cette étude a permis de caractériser l'influence de différents paramètres structurels et géométriques sur le comportement de la cage thoracique sous chargement dynamique. Le travail réalisé au cours de cette thèse est divisé en trois parties : Modélisation de la cage thoracique entière avec des éléments finis de type poutre dont les propriétés mécaniques sont déterminées à partir d'essais de flexion trois points sur des segments de côtes et complétées par des éléments de la littérature, Validation du modèle dont les résultats sont suffisamment proches des résultats des essais de chargement dynamique antéro-postérieur menés par Vezin et Berthet [Vez09], Etude paramétrique sur l'influence paramètres, géométrie des sections droites et géométrie globale de la cage thoracique (inclinaison des côtes, forme et taille globale de la cage thoracique). A partir de cette étude nous trouvons que le module d'Young et l'épaisseur du cortical ont une influence identique sur la raideur globale de la cage thoracique ainsi que sur la rotation et la déformation des côtes. Avec l'augmentation de ces deux paramètres la rigidité du thorax augmente et le taux de compression maximal diminue. D'autre part les côtes tournent plus et se déforment moins. La raideur des liaisons costo-verterbales a une influence directe sur la rotation latérale qui diminue avec l'augmentation de cette raideur alors que les déformations augmentent ; tandis que la raideur globale de la cage thoracique est légèrement modifiée. L'inclinaison des côtes est le facteur ayant la plus grande influence sur la déformation des côtes et donc sur le risque d'endommagement : plus les côtes sont proches de la direction de chargement la raideur de la cage thoracique augmente et la déformation des côtes augmente / In the European Union, 28% of road accidents are frontal impacts which provoke 49% of fatalities where the thoracic fractures are the main cause of death. The finite element models of the human body are an important tool for the simulation of real impacts and the prediction of damage. This thesis has led to develop a rib cage simplified finite element model sufficiently flexible and easily customizable. First, this model is experimentally validated and then used in a parametric study. This study allowed us to characterize the influence of different structural and geometric parameters on the behavior of the rib cage under dynamic loading. This work is divided into three parts : Modeling the rib cage using beam elements whose mechanical properties are determined by three-point bending tests on rib segments and supplemented from literature, Validating the model by simulating the anteroposterior dynamic loading tests led by Vezin and Berthet [Vez09], Performing a parametric study on the influence of the mechanical parameters (Young modulus, stiffness of costo-vertebral joints), the geometry of the rib sections and the overall geometry of the rib cage (ribs slope, shape and overall size of the rib cage). This study permitted to find that Young modulus and the thickness of the cortical have the same influence on the overall stiffness of the chest as well as on the rotation and deformation of the ribs. By increasing these parameters, the stiffness of the chest increases and the maximum compression ratio decreases. Besides, we'll find more rotation and less deformation of the ribs. The stiffness of the costoverterbal joints has a direct influence on the lateral rotation : it will decrease by increasing of the stiffness while deformation will increase. However, the overall stiffness of the chest is slightly modified by modifying the costovertebral joint stiffness. The initial inclination of the ribs accordingly to the load direction has the greatest influence on the deformation of the ribs and therefore on the damage risk. When the ribs are closer to the loading direction, the stiffness of the rib cage and the deformation of the ribs increases

INTRODUÇÃO: As reconstruções com tecidos combinados e bem vascularizados permitem a melhor reabilitação para defeitos extensos em cabeça e pescoço. O padrão-ouro tem sido as transferências microcirúrgicas de tecidos. Porém, há pacientes em que não há vasos receptores cervicais adequados para os transplantes de tecidos livres devido à múltiplas recidivas, ressecções e reconstruções; linfadenectomias cervicais; fístulas e infecções; e o tratamento com radioterapia. Com o aprimoramento do controle oncológico, pacientes nestas circunstâncias são cada vez mais frequentes e há poucas alternativas para reconstrução. OBJETIVO: Descrever a dissecação anatômica de um retalho osteomiocutâneo combinado, pediculado nos vasos torácicos internos, para reconstrução de defeitos complexos em cabeça e pescoço. MÉTODO: Retalhos osteomiocutâneos contendo 6ª e 7ª costelas e músculo reto abdominal foram dissecados bilateralmente em 35 cadáveres, 26 do sexo masculino e 9 do sexo feminino. Estudou-se a vascularização cutânea do abdome superior pelas perfurantes da artéria epigástrica superior superficial (SSEA); e os padrões de vascularização do 6º e 7º arcos costais e músculo reto abdominal a partir dos vasos torácicos internos, musculofrênicos e intercostais. O arco de rotação para segmento cefálico com ponto pivô na margem inferior da primeira costela foi avaliado. RESULTADOS: Foram dissecadas 114 perfurantes SSEA, 62 à direita e 52 à esquerda, com calibre arterial médio homogêneo de 0,68 mm. A maior frequência de perfurantes encontradas foi no grupo de 0,5 a 1,0 mm, com 60 (52,7%) ocorrências. Não houve diferença estatisticamente significativa para localização e calibre em relação ao lado. Também não houve correlação dos calibres com localização, idade, peso e altura dos cadáveres. Sessenta e dois retalhos osteomiocutâneos com pedículo nos vasos torácicos internos, 6° e 7° arcos costais e músculo reto abdominal foram divididos em 3 tipos de acordo com o padrão de vascularização do sexto arco costal. O tipo 1, em que a vascularização da sexta costela é pela artéria musculofrênica, foi o mais frequente, com 46 (74,2%) ocorrências. Dez pedículos vasculares diferentes para os componentes do retalho foram individualizados e medidos bilateralmente. Apenas quatro foram significativamente maiores nos homens e, dois, maiores à direita. Os calibres de todos os pedículos arteriais foram homogêneos em relação ao sexo e ao lado. O comprimento do pedículo para o componente ósseo do retalho variou de 18,5 a 21,6 cm, alcançando mandíbula e maxila em todos as dissecações. Já o componente miocutâneo do reto abdominal atingiu occipício em todos os casos e levou os vasos epigástricos profundos inferiores para possível anastomose vascular. Cinco pacientes foram operados em 2 anos com adequada integração dos retalhos e recuperação do contorno e função mandibulares. CONCLUSÃO: Em todas as dissecações de cadáver as perfurantes SSEA estiveram presentes bilateralmente com calibre maior que 0,3 mm; os retalhos osteomiocutâneos pediculados nos vasos torácicos internos foram constantes e alcançaram o segmento cefálico. Os pacientes operados recuperaram forma e função mandibulares. Este retalho pode ser uma alternativa para reconstruções secundárias em cabeça e pescoço / INTRODUCTION: The use of combined well-vascularized flaps offers better results and rehabilitation for complex head and neck defects. Microsurgical reconstructions are the gold standard. However, there are patients with vessel-depleted necks from multiple recurrences and resections, failed reconstructions, neck dissections, infections, fistulas and radiotherapy, which impair adequate free tissue transfers. With better oncologic therapies, these patients have become more common and lack reconstructive options. OBJECT: To describe a combined ostemyocutaneous pedicled flap based on the internal mammary artery for complex head and neck reconstructions. METHOD: Osteomyocutaneous flaps with 6th and 7th ribs and the rectus abdominis muscle were dissected bilaterally on 35 cadavers, 26 male and 9 female. We studied the upper abdominal irrigation through isolation of the superficial superior epigastric artery perforators (SSEA) and the vascular pedicles to the 6th and 7th ribs, and the rectus abdominis muscle arising from the internal mammary, the musculophrenic and the intercostal arteries. The arc of rotation of the flap to the cephalic segment was tested with the pivot point on the lower margin of the first rib. RESULTS: We dissected 114 SSEA, 62 on the right side and 52 on the left. They had an homogeneous mean arterial diameter of 0,68 mm. Sixty perforators (52,7%) were on the group that ranged from 0,5 to 1,0 mm. After statistical analysis, there were no differences in relation to the side as for location and caliber of the perforators. Neither there was any relation of the arterial calibers to the location, age, weight and height of the cadavers. Sixty-two internal mammary artery pedicled osteomyocutaneous flaps, that carried the 6th and 7th ribs and the rectus abdominis muscle, were divided in 3 types depending on the vascular pattern to the 6th costal arch. Type 1, where the pedicle to the 6th rib branches from the musculophrenic artery, was the most frequent and dissected in 46 flaps (74,2%). Ten different vascular pedicles to the components of the flap were isolated and measured bilaterally. Only four of them were significantly longer in males and, two, were longer on the right side. The arterial diameters were also homogeneous in relation to the side and sex. The pedicle length to the osseous component of the flap varied from 18,5 to 21,6 cm, which allowed to reach mandible and maxilla in all dissections. The myocutaneous component of the rectus abdominis muscle reached the occipitum in all cases and carried along the deep inferior epigastric vessels for vascular anastomosis if needed. Five patients were operated in 2 years with adequate flap integration and recovery of the mandible contour and function. CONCLUSION: In all cadaveric dissections SSEA perforators were bilaterally present with a caliber bigger than 0,3 mm; internal mammary artery osteomyocutaneous pedicled flaps were constant and reached the cephalic segment. The operated patients recovered mandibular form and function. This flap can be an alternative for secondary head and neck reconstructions

Le corps calleux (CC) est la principale commissure cérébrale connectant les aires corticales homologues des deux hémisphères chez les vertébrés placentaires. Les malformations du corps calleux (MCC) représentent la malformation cérébrale la plus fréquente à la naissance et sont présentes chez 5% des individus avec anomalie neuro-développementale. Une meilleure connaissance de l’ontogenèse du corps calleux et de ses causes génétiques devrait permettre d’ouvrir la voie à des corrélations cliniques pour un meilleur conseil génétique. Cet aspect constitue probablement l’enjeu de la prochaine décennie concernant les foetus avec MCC. Le travail de thèse a porté sur 138 foetus avec MCC, pour lesquels nous avons fait un examen foeto-neuropathologique et une classification en plusieurs catégories. Au total, ce travail a permis : 1/le démantèlement des causes génétiques des MCC par une triple approche de CGH array, d’exome en trio et de panels ciblés, avec une augmentation considérable des causes identifiables de MCC au sein de cette cohorte, 2/ l’identification et la caractérisation fonctionnelle d’un nouveau gène de ciliopathie dans un phénotype extrême ; 3/ l’identification de 3 nouvelles mutations de ZBTB20, récemment identifié comme responsable du syndrome de Primrose, démontrant que ce syndrome est une cause fréquente de MCC et permettant une description clinico-radiologique plus précise. 4/ L’identification de plusieurs gènes candidats en cours de validation. / Corpus callosum is the main cerebral commissure connecting homologous cortical areas in placental mammals. Malformations of corpus callosum (MCC) are the most frequent brain malformation at birth and are present in 5% of patients with neurodevelopmental delay. A good knowledge of genetics of corpus callosum development should pave the way to better clinical correlations for a more accurate genetic counselling. This is the challenge of the next decade. This thesis concerns a cohort of 138 fetuses with MCCs, well classified on neuropathological examination. It allowed 1/ to unravel the genetic causes of MCC through a triple approach combining CGH array, whole exome and NGS panels sequencing, with a considerable increase in the number of causes of MCC identified ; 2/ identification of a new gene in an extreme ciliopathy phenotype; and 3/ identification of novel ZBTB20 mutations , a gene recently identified as responsible for Primrose syndrome, showing that this syndrome is frequent among MCCs and allowing a precise clinico-radiological description of the syndrome. 4/ Several new candidate genes are under study.

INTRODUÇÃO: As reconstruções com tecidos combinados e bem vascularizados permitem a melhor reabilitação para defeitos extensos em cabeça e pescoço. O padrão-ouro tem sido as transferências microcirúrgicas de tecidos. Porém, há pacientes em que não há vasos receptores cervicais adequados para os transplantes de tecidos livres devido à múltiplas recidivas, ressecções e reconstruções; linfadenectomias cervicais; fístulas e infecções; e o tratamento com radioterapia. Com o aprimoramento do controle oncológico, pacientes nestas circunstâncias são cada vez mais frequentes e há poucas alternativas para reconstrução. OBJETIVO: Descrever a dissecação anatômica de um retalho osteomiocutâneo combinado, pediculado nos vasos torácicos internos, para reconstrução de defeitos complexos em cabeça e pescoço. MÉTODO: Retalhos osteomiocutâneos contendo 6ª e 7ª costelas e músculo reto abdominal foram dissecados bilateralmente em 35 cadáveres, 26 do sexo masculino e 9 do sexo feminino. Estudou-se a vascularização cutânea do abdome superior pelas perfurantes da artéria epigástrica superior superficial (SSEA); e os padrões de vascularização do 6º e 7º arcos costais e músculo reto abdominal a partir dos vasos torácicos internos, musculofrênicos e intercostais. O arco de rotação para segmento cefálico com ponto pivô na margem inferior da primeira costela foi avaliado. RESULTADOS: Foram dissecadas 114 perfurantes SSEA, 62 à direita e 52 à esquerda, com calibre arterial médio homogêneo de 0,68 mm. A maior frequência de perfurantes encontradas foi no grupo de 0,5 a 1,0 mm, com 60 (52,7%) ocorrências. Não houve diferença estatisticamente significativa para localização e calibre em relação ao lado. Também não houve correlação dos calibres com localização, idade, peso e altura dos cadáveres. Sessenta e dois retalhos osteomiocutâneos com pedículo nos vasos torácicos internos, 6° e 7° arcos costais e músculo reto abdominal foram divididos em 3 tipos de acordo com o padrão de vascularização do sexto arco costal. O tipo 1, em que a vascularização da sexta costela é pela artéria musculofrênica, foi o mais frequente, com 46 (74,2%) ocorrências. Dez pedículos vasculares diferentes para os componentes do retalho foram individualizados e medidos bilateralmente. Apenas quatro foram significativamente maiores nos homens e, dois, maiores à direita. Os calibres de todos os pedículos arteriais foram homogêneos em relação ao sexo e ao lado. O comprimento do pedículo para o componente ósseo do retalho variou de 18,5 a 21,6 cm, alcançando mandíbula e maxila em todos as dissecações. Já o componente miocutâneo do reto abdominal atingiu occipício em todos os casos e levou os vasos epigástricos profundos inferiores para possível anastomose vascular. Cinco pacientes foram operados em 2 anos com adequada integração dos retalhos e recuperação do contorno e função mandibulares. CONCLUSÃO: Em todas as dissecações de cadáver as perfurantes SSEA estiveram presentes bilateralmente com calibre maior que 0,3 mm; os retalhos osteomiocutâneos pediculados nos vasos torácicos internos foram constantes e alcançaram o segmento cefálico. Os pacientes operados recuperaram forma e função mandibulares. Este retalho pode ser uma alternativa para reconstruções secundárias em cabeça e pescoço / INTRODUCTION: The use of combined well-vascularized flaps offers better results and rehabilitation for complex head and neck defects. Microsurgical reconstructions are the gold standard. However, there are patients with vessel-depleted necks from multiple recurrences and resections, failed reconstructions, neck dissections, infections, fistulas and radiotherapy, which impair adequate free tissue transfers. With better oncologic therapies, these patients have become more common and lack reconstructive options. OBJECT: To describe a combined ostemyocutaneous pedicled flap based on the internal mammary artery for complex head and neck reconstructions. METHOD: Osteomyocutaneous flaps with 6th and 7th ribs and the rectus abdominis muscle were dissected bilaterally on 35 cadavers, 26 male and 9 female. We studied the upper abdominal irrigation through isolation of the superficial superior epigastric artery perforators (SSEA) and the vascular pedicles to the 6th and 7th ribs, and the rectus abdominis muscle arising from the internal mammary, the musculophrenic and the intercostal arteries. The arc of rotation of the flap to the cephalic segment was tested with the pivot point on the lower margin of the first rib. RESULTS: We dissected 114 SSEA, 62 on the right side and 52 on the left. They had an homogeneous mean arterial diameter of 0,68 mm. Sixty perforators (52,7%) were on the group that ranged from 0,5 to 1,0 mm. After statistical analysis, there were no differences in relation to the side as for location and caliber of the perforators. Neither there was any relation of the arterial calibers to the location, age, weight and height of the cadavers. Sixty-two internal mammary artery pedicled osteomyocutaneous flaps, that carried the 6th and 7th ribs and the rectus abdominis muscle, were divided in 3 types depending on the vascular pattern to the 6th costal arch. Type 1, where the pedicle to the 6th rib branches from the musculophrenic artery, was the most frequent and dissected in 46 flaps (74,2%). Ten different vascular pedicles to the components of the flap were isolated and measured bilaterally. Only four of them were significantly longer in males and, two, were longer on the right side. The arterial diameters were also homogeneous in relation to the side and sex. The pedicle length to the osseous component of the flap varied from 18,5 to 21,6 cm, which allowed to reach mandible and maxilla in all dissections. The myocutaneous component of the rectus abdominis muscle reached the occipitum in all cases and carried along the deep inferior epigastric vessels for vascular anastomosis if needed. Five patients were operated in 2 years with adequate flap integration and recovery of the mandible contour and function. CONCLUSION: In all cadaveric dissections SSEA perforators were bilaterally present with a caliber bigger than 0,3 mm; internal mammary artery osteomyocutaneous pedicled flaps were constant and reached the cephalic segment. The operated patients recovered mandibular form and function. This flap can be an alternative for secondary head and neck reconstructions

This is a residential house in Brno. The supporting structure is reinforced concrete. The building has one basement and six floors. Vertical load-bearing structures are made up of reinforced concrete columns and walls. Horizontal load-bearing structures are formed by slabs (bearing in both directions). The staircase is concrete slab. Foundation is on piles. Infill vertical structures are brick. In the fifth floor pool is located.

Am Anfang des Entwicklungsprozesses eines Gussbauteils für die Automobilbranche steht klassischerweise die konstruktive Ausarbeitung und die Auslegung auf Zielgrößen, wie Festigkeit, Steifigkeit bzw. die Erfüllung der Crashlasten. Im nächsten Entwicklungsschritt wird, oftmals in Zusammenarbeit mit externen Lieferanten, das Werkzeugkonzept entwickelt und die Herstellbarkeit mit Hilfe von Gießsimulationen abgesichert. Bei der Fertigung verursachen streuende Prozessgrößen, wie etwa Geschwindigkeits- oder Temperaturniveaus, Schwankungen in der Leistungsfähigkeit des Endprodukts (z. B. lokale Bruchdehnung oder Zugfestigkeit). Maßnahmen zur Erhöhung der Prozessstabilität und zur Reduktion des Verschleißes konzentrieren sich oftmals auf die erfahrungsbasierte Verbesserung des Fertigungsprozesses und Anpassungen des Anguss- und Überlaufsystems. Größere Änderungen der Bauteilgeometrie sind häufig aus zeitlichen Gründen nicht mehr möglich. Das Ziel dieser Arbeit ist es daher, optimierte modularisierte Grundgeometrien, wie Rippen oder Umlenkungen, mit Hilfe von numerischen Formoptimierungen zu entwickeln, um diese schon von Anfang an in der Bauteilentwicklung zu berücksichtigen. Als Zielfunktionen dienen strömungs- und strukturmechanische Kenngrößen, um einerseits verschleißfördernde Mechanismen und füllungsbedingte Defekte zu reduzieren und andererseits die Beanspruchbarkeit zu erhöhen. Bei den Untersuchungen wird zusätzlich die Robustheit des Ergebnisses analysiert, um Verbesserungspotenziale auch bei streuenden Randbedingungen realisieren zu können. / The virtual development process of an automotive casting part usually begins with classical design tasks and analyses of material strength, stiffness and crash load cases. In the next step, often in cooperation with external suppliers, the tooling concept is developed and casting simulations are used to ensure manufacturability. During manufacturing there is a scatter in process parameters, such as flow velocity or temperature levels, which in turn cause a scatter in the performance of the final product (e.g. local elongation at fracture or ultimate tensile strength). Means to increase process stability and yield are often limited to knowledge-based improvements of the manufacturing process parameters and adaptations of the gating and overflow system. Major changes to the part geometry are usually no longer possible due to project time constraints. Therefore it is the goal of this thesis to optimize modularized basic geometries, like ribs or bends, by using numerical shape optimizations and employ them right from the beginning of the part development process. For the objective functions of the optimizations the disciplines of fluid dynamic filling and the resulting structural behaviour are considered. In addition, the resulting shape is analyzed with regards to robustness towards scatter in manufacturing operating conditions. By using these new modularized geometries the overall robustness of the final product is expected to be increased.

Über die Ätiologie und Epidemiologie der Erkrankungen des Respirationstraktes im Frühneolithikum Mitteleuropas gibt es bislang keine umfassenden Studien. Die Häufigkeit, mögliche Geschlechts- und Altersunterschiede, Populationsunterschiede und Erkenntnisse über mögliche Ursachen und auslösende Faktoren der Atemwegserkrankungen zur Zeit der Bandkeramik sind von besonderem Interesse. Zudem soll aufgezeigt werden wie wichtig es ist, alle Strukturen zu untersuchen, die den „knöchernen Respirationstrakt“ repräsentieren. Von den ersten Ackerbauern und Viehzüchtern aus Wandersleben (Thüringen, Kreis Gotha) lagen insgesamt 112 erwachsene Individuen zur Untersuchung vor. Rippen und Schädel wurden mit paläopathologischen Methoden untersucht. Diese waren neben einer makroskopischen Begutachtung der Knochen, röntgenologische, endoskopische, lupenmikroskopische, lichtmikroskopische und rasterelektronenmikroskopische Untersuchungen, um eine verlässliche Diagnosestellung zu gewährleisten. 100 % (n = 71/71) der befundbaren Individuen zeigten Spuren chronischer Erkrankungen im Bereich der knöchernen Strukturen, die die oberen Atemwege umgeben. Bei 76,8% (n = 53/69) der Individuen mit befundbaren Rippen konnten Spuren von chronischen Erkrankungen aufgezeigt werden. Signifikante Geschlechts- oder Altersunterschiede bestehen insgesamt nicht. Bei der linearbandkeramischen Population aus Wandersleben ist davon auszugehen, dass es sich in vielen Fällen um Chronifizierungen von Erkältungskrankheiten und um die Folgen einer vergleichbar schlechten Luftqualität hauptsächlich im Haus handelt. Dazu haben die damaligen Lebensumstände, vor allem aber die sesshafte Lebensweise und Wirtschaftszweige mit Ackerbau und Viehzucht, maßgeblich beigetragen.