Ventilação mecânica (MV) com pressão positiva no final da expiração (PEEP) melhora a oxigenação sanguínea e oferta de oxigênio aos tecidos no tratamento da insuficiência respiratória aguda. No entanto, a pressão intratorácica elevada pode alterar o fluxo sanguíneo no mesentério que pode contribuir para complicações gastrointestinais durante a VM. Investigamos os efeitos da PEEP sobre as interações leucócito-endotélio durante a VM em ratos com pulmões normais e sem administração de fluido (Fase I) e os efeitos do volume corrente baixo (LTV) e pentoxifilina (PTX) sobre a microcirculação mesentérica (Fase II). O protocolo e resultados da Fase I são os seguintes: 44 ratos Wistar machos (~240g) foram anestesiados com pentobarbital (I.P., 50mg.kg-1) e com isoflurane inalatório (1.5-2%) após instrumentação, e aleatoriamente divididos em (1) INTACTO (somente anestesia), (2) PEEP0 (PEEP=0 cmH2O), (3) PEEP5 (PEEP=5 cmH2O), e (4) PEEP10 (PEEP=10 cmH2O). Os grupos PEEP foram submetidos à traqueostomia e VM com volume corrente de 10 ml.kg-1, frequência respiratória de 70 rpm e fração inspirada de oxigênio de 1. Após 2-h de VM, realizamos laparotomia mediana e avaliamos as interações leucócito-endotélio por meio de microscopia intravital e inflamação pumonar por meios histológicos. Não observamos alterações significantes na pressão sanguínea arterial média (PAM) entre os grupos ao longo do estudo. A pressão traqueal do grupo PEEP5 foi menor comparada com os grupos PEEP0 e PEEP10 (11, 15, e 16 cmH2O, respectivamente; p<0.05). Após 2-h de VM, não houve diferenças significantes entre os grupos INTACTO, PEEP0 e PEEP5 no número de leucócitos rollers (118±9, 127±14 e 147±26 células/10minutos, respectivamente), aderidos (3±1, 3±1 e 4±2 células/100m de comprimento de vênula, respectivamente), e migrados (2±1, 2±1 e 2±1 células/5,000m2, respectivamente) no mesentério. No entanto, PEEP10 aumentaram (p<0.05) o número de leucócitos rollers (188±15 células/10minutos), aderidos (8±1 células/100m de vênula) e migrados (12±1 células/5,000 m2). Observamos inflamação pulmonar nos grupos PEEP0 e PEEP10. O protocolo e resultados da Fase II são os seguintes: 57 ratos Wistar machos (~253g) foram anestesiados com pentobarbital (I.P., 50 mg.kg-1), submetidos a traqueostomia, anestesia inalatória com isoflurane (1.5-2%), VM com PEEP de 10 cmH2O, fração inspirada de oxigênio de 0,21, e aleatoriamente divididos em (1) LTV (7 ml.kg-1), (2) volume corrente elevado (HTV, 10 ml.kg-1), e (3) PTX (HTV+ PTX, 25 mg.kg-1). Nós registramos a PAM, mecânica respiratória e gases sanguíneos arteriais no basal e após 2-h de VM. Realizamos laparotomia mediana e avaliamos as interações leucócito-endotélio no mesentério, fluxo de artéria mesentérica (FAM), mecânica respiratória e inflamação pulmonar. Não observamos diferenças entre os grupos no basal e após 2-h em PAM (113±15 vs 109± 6 mmHg). Após 2-h de VM, o FAM foi similar em todos os grupos (12.4±2.6 ml.min-1). A pressão traqueal foi menor no grupo LTV (11.2±1.6 cmH2O) comparada com HTV (14.7±1.1 cmH2O) e PTX (14.1±2.4 cmH2O). Em todos os grupos a VM aumentou a elastância pulmonar (~22%, p<0.05) e diminuiu a resistência de vias aéreas (~10%, p<0.05). LTV e PTX apresentaram valores similares de leucócitos aderidos (5±2 e 6±4 células/100m de vênula, respectivamente), e migrados (1±1 e 2±1 células/5,000m2, respectivamente). Contrariamente, HTV aumentou o número de aderidos (14±4 leucócitos/100m de vênula, p<0.05) e migrados (9±3 células/5,000m2, p<0.05) no mesentério. O grupo HTV apresentou infiltrado neutrofílico e edema pulmonar. Em conclusão, nosso estudo mostrou que a pressão intratorácica elevada é prejudicial para a microcirculação mesentérica e pulmões no modelo experimental de ratos com pulmões normais e pressão sanguínea sistêmica estável, LTV previne alterações microcirculatórias e pulmonares, e a administração precoce de PTX atenua as interações leucócito-endotélio no mesentério e inflamação pulmonar durante a VM. Esses achados podem ter relevância na compreensão das complicações induzidas pela VM e prognóstico. / Mechanical ventilation (MV) with positive end expiratory pressure (PEEP) improves blood oxygenation and tissue oxygen delivery during treatment of acute respiratory failure. However, high intrathoracic pressure may alter blood flow at mesentery, which may contribute to gastrointestinal complications during MV. We investigated the effects of PEEP on mesenteric leukocyte-endothelial interactions during MV in rats with normal lungs and without fluid administration (Phase I) and the effects of low-tidal volume (LTV) and pentoxifylline (PTX) on mesenteric microcirculation (Phase II). The protocol and results of Phase I are the following: 44 male Wistar rats (~240g) were anesthetized with pentobarbital (I.P., 50mg.kg-1) and inhaled isoflurane (1.5-2%) after instrumentation, and randomly divided in (1)NAIVE (only anesthesia), (2) PEEP0 (PEEP=0 cm H2O), (3) PEEP5 (PEEP=5 cmH2O), and (4) PEEP10 (PEEP=10 cmH2O). PEEP groups were submitted to tracheostomy and MV with tidal volume of 10 ml.kg-1, respiratory rate of 70 rpm and inspired oxygen fraction of 1. After 2-hrs of MV, we performed a median laparotomy and evaluated leukocyte-endothelial interactions at the mesentery and lung inflammation by histology. We did not observe significant changes mean arterial blood pressure (MABP) among groups throughout the study. Tracheal pressure in PEEP5 was lower compared with PEEP0 and PEEP10 groups (11, 15, and 16 cmH2O, respectively; p<0.05). After 2-hrs of MV, there were no differences among NAIVE, PEEP0 e PEEP5 groups in the number of rollers (118±9, 127±14 and 147±26 cells/10 minutes, respectively), adherent leukocytes (3±1, 3±1 and 4±2 cells/100 m venule, respectively), and migrated leukocytes (2±1, 2±1 and 2±1 cells/5,000 m2, respectively) at the mesentery. However, PEEP10 increased (p<0.05) the number of rolling (188±15 cells/10min), adherent (8±1 cells/100 m) and migrated leukocytes (12±1 cells/5,000 m2). We observed lung inflammation in PEEP0 and PEEP10 groups. The protocol and results of Phase II are the following: 57 male Wistar rats (~253g) were anesthetized with pentobarbital (I.P.,50 mg.kg-1), submitted to tracheostomy, inhaled anesthesia with isoflurane (1.5-2%), MV with PEEP of 10 cmH2O, inspired oxygen fraction of 0.21, and randomly divided in (1) LTV (7 ml.kg-1), (2) High-tidal volume (HTV, 10 ml.kg-1), and (3) PTX (HTV+ PTX, 25 mg.kg-1). We registered MABP, respiratory mechanics and arterial blood gases at baseline and after 2-hrs of MV. We performed a median laparotomy and evaluated leukocyte-endothelial interactions, mesenteric artery flow (MAF), respiratory mechanics and lung inflammation. We did not observe significant differences among groups at baseline and after 2-hrs in MABP (113±15 vs 109± 6 mmHg). After 2-hrs, MAF was similar in all groups (12.4±2.6 ml.min-1). Tracheal pressure was lower in LTV (11.2±1.6 cmH2O) compared with HTV (14.7±1.1 cmH2O) and PTX (14.1±2.4 cmH2O). In all groups MV increased pulmonary elastance (22%, p<0.05) and decreased airway resistance (10%, p<0.05). LTV and PTX presented similar values of adherent (5±2 and 6±4 cells/100m venule, respectively), and migrated leukocytes (1±1 and 2±1 cells/5,000m2, respectively). On the contrary, HTV increased the number of adherent (14±4 leukocytes/100m venule, p<0.05) and migrated leukocytes (9±3 cells/5,000m2, p<0.05) in the mesentery. HTV presented lung neutrophil infiltration and edema. In conclusion, our study showed that high intrathoracic pressure is harmful to mesenteric microcirculation and lungs in the experimental model of rats with normal lungs and stable systemic blood pressure, LTV prevents microcirculatory and pulmonary alterations, and early administration of PTX attenuates leukocyte-endothelial interactions at the mesentery and lung inflammation during MV. These findings may have relevance for complications MV-induced and outcome.

O objetivo do presente trabalho foi à obtenção de aço rápido tipo AISI M2 pela técnica da conformação por “spray" e a avaliação deste, quanto ao seu desempenho quando aplicado como ferramenta de usinagem. O material obtido foi laminado a quente com razões de redução de 50 e 72%, resultando em placas a partir das quais foram confeccionadas pastilhas intercambiáveis para realização de testes de usinagem. O desempenho das pastilhas obtidas a partir do material conformado por “spray" e laminado a quente, foi confrontado com o de pastilhas confeccionadas a partir de material processado convencionalmente (lingotamento convencional), e com material processado pela técnica da metalurgia do pó (MP). As variações do material obtido por conformação por “spray", assim como também os demais materiais, foram caracterizados química, física, mecânica e microestruturalmente. Adicionalmente, foram realizados testes de usinagem para avaliação de desempenho do material quando submetido a condições reais de trabalho. Os resultados da caracterização dos materiais evidenciaram o potencial da técnica de conformação por “spray", em possibilitar a obtenção de materiais com boas características e propriedades. Para as condições de processamento, conformação mecânica e de tratamentos térmicos aplicados neste trabalho, às análises dos resultados dos testes de usinagem revelaram um comportamento muito próximo entre todos os materiais de ferramenta utilizados. Procedendo a uma análise mais refinada dos resultados dos testes de usinagem contínua, foi verificado um desempenho ligeiramente superior para o material obtido pela técnica da metalurgia do pó (MP), seguido pelo material obtido pela técnica da metalurgia convencional, o qual apresentou uma vantagem mínima em relação ao obtido pela técnica da conformação por “spray" e laminado com redução de 72%. Por fim, o desempenho inferior ficou por conta do material obtido pela técnica da conformação por “spray" e laminado com redução de 50%, o qual apresentou os maiores valores de desgaste. / The aim of the present work was the obtention of AISI M2 high-speed steel by spray forming technique and the material evaluation when used as machining tool. The obtained material was hot rolled at 50% and 72% reduction ratios, and from which it was manufactured inserts for machining tests. The performance of inserts made of the spray formed material was compared to inserts obtained from conventional and powder metallurgy (MP) processed materials. The spray formed material was chemical, physical, mechanical and microstructural characterised. For further characterisation, the materials were submitted to machining tests for performance evaluation under real work condition. The results of material characterisation highlight the potential of the spray forming technique, in the obtention of materials with good characteristics and properties. Under the current processing, hot rolling and heat treatments condition, the analysis of the results of the machining tests revealed a very similar behaviour among the tested materials. Proceeding a criterious analysis of the machining results tests, it was verified that the performance presented by the powder metallurgy material (MP) was slight superior, followed by conventional obtained material (MConv), which presented a insignificant advantage over the spray formed and hot rolled (72% reduction ratio) material. The worst result was encountered for the spray forming and hot rolled (50% reduction ratio) material that presented the highest wear values.

La durée de vie des pièces mécaniques en contact est fortement affectée par la présence d'hétérogénéités dans le matériau, comme des renforts (fibres, particules), des précipités, des porosités, ou encore des fissures. Des hétérogénéités dures et de formes complexes peuvent créer des surcontraintes locales, initiatrices de fissures par fatigue à proximité de la surface de contact. Une analyse quantitative des surcontraintes créées par les hétérogénéités est nécessaire à la compréhension des mécanismes d'endommagement. Cette étude s'applique à des roulements de ligne d'arbre qui font partie des éléments critiques de moteurs en aéronautique. Elle vise à déterminer précisément la distribution du champ de pression sur l'aire effective de contact et à prédire le profil et l'évolution des champs de contraintes/déformations à chaque passage de la charge sur un volume élémentaire représentatif prenant en compte le gradient de dureté, la présence de carbures et l'existence des contraintes initiales d'origine thermochimique. Une partie de l’étude est consacrée au développement d’un solveur du problème de contact roulant élasto-plastique avec présence d’hétérogénéité par les méthodes semi analytiques assurant un excellent gain en temps et ressources de calculs. Ensuite, un algorithme homogénéisation a été conçu pour analyser le comportement effectif d’un massif élasto-plastique hétérogène sous indentation. Enfin une partie expérimentale est dédiée à la caractérisation microstructurale des aciers étudiés dans le but de déterminer leurs propriétés. Les analyses des résultats de cette étude concourent à soutenir que bien que les inclusions de particules non métalliques soient responsables de la haute résistance de ces matériaux, certaines d’entre elles (celles de longueur dépassant les dizaines de micromètre ou celles qui forment des chaines dans une direction particulière) deviennent, au cours des cycles de fatigue, les principales sources d’endommagement depuis l’échelle locale jusqu’à la rupture globale de la structure. / The lifetime of contacting mechanical parts is strongly affected by the presence of heterogeneities in their materials, such as reinforcements (fibers, particles), precipitates, porosities, or cracks. Hard heterogeneities having complex forms can create local overstress that initiating fatigue cracks near the contact surface. The presence of heterogeneities influences the physical and mechanical properties of the material at microscopic and macroscopic scales. A quantitative analysis of the over-stresses generated by heterogeneities is necessary to the comprehension of the damage mechanisms. The present study is applied to rolling bearings which are the critical elements of the aero-engine's mainshaft. The performance required for these bearings, led SKF Aerospace to introduce a new technology of hybrid bearing with ceramic rolling elements on high-strength steels having experienced a double surface treatment (carburizing followed by nitriding). The study aims to precisely determine the pressure field distribution on the effective contact area and to predict the profile and the evolution of the stress/strain fields at each loading cycle on a representative elementary volume that takes into account the gradient of hardness, the presence of carbides and the existence of an initial compressive stress from thermochemical origin. A major part of this study is devoted to develop a heterogeneous elastic-plastic rolling contact solver, by semi-analytical methods ensuring an excellent saving of calculation time and resources. Thereafter, a homogenization algorithm was built to analyze the effective behavior of a heterogeneous elastic-plastic half-space subjected to an indentation loading. Finally, an experimental part is dedicated to the microstructure characterization of the studied steels with intent to determine their properties. A description of the carbides behavior inside the matrix during micro-tensile tests was carried out under SEM in-situ observation. In the scheme of all analyses conducted in the present work, it can be argued that, although the heterogeneities (such as carbides or nitrides) are responsible for the high resistance of the studied materials, some of them (those whose length exceeds tens of micrometer or those which form stringers in a particular direction) become, over fatigue cycles, the main sources of damage, from their local scale up to the macroscopic failure of the structure.

O ensaio de desgaste micro-abrasivo por esfera rotativa vem conquistando elevada aceitação em universidades e centros de pesquisa, sendo amplamente adotado em estudos envolvendo desgaste abrasivo de materiais. Dois modos de desgaste abrasivo podem ser observados neste tipo de ensaio: rolamento resulta quando as partículas abrasivas rolam sobre a superfície do corpo-de-prova, enquanto riscamento é observado quando as partículas abrasivas deslizam sobre o mesmo; o tipo do modo de desgaste abrasivo apresenta uma significante influência sobre o comportamento de um sistema tribológico. Diversos trabalhos envolvendo coeficiente de atrito durante ensaios de desgaste abrasivo estão disponíveis na literatura, mas somente uma pequena parcela dedicaram-se ao estudo do coeficiente de atrito desenvolvido em ensaios de desgaste micro-abrasivo conduzidos por esfera rotativa. Adicionalmente, pesquisas preliminares reportaram que os resultados são dependentes da variação de pressão, ocasionada pela condução de ensaios sob condições de força normal constante. Logo, o propósito desta Tese de Doutorado é pesquisar a relação entre coeficiente de atrito e modos de desgaste abrasivo em ensaios desgaste micro-abrasivo por esfera rotativa, em condições de força normal constante e pressão constante. Ensaios ball-cratering foram conduzidos com esferas de aço AISI 52100 e um corpo-de-prova de aço-ferramenta AISI H10. A pasta abrasiva foi preparada com partículas de carbeto de silício (SiC) preto (tamanho médio de partícula de 3 m) e água destilada. Diferentes valores de força normal constante e pressão constante foram definidos para os experimentos. As forças normal (N) e tangencial (T) foram monitoradas continuamente durante os ensaios e a relação entre T/N foi calculada para fornecer uma indicação do coeficiente de atrito atuante no sistema tribológico esfera / partículas abrasivas / corpo-de-prova. Em todos os casos, análises por Microscopia Óptica das crateras de desgaste revelaram somente a presença de desgaste abrasivo por riscamento. Entretanto, observações mais detalhadas, conduzidas por Microscopia Eletrônica de Varredura, indicaram que diferentes níveis desgaste abrasivo por rolamento atuaram ao longo dos riscos, fenômeno nomeado de micro-rolling abrasion (microrolamento). Além disso, os resultados obtidos mostraram, também, que: i) a distância de deslizamento apresenta significante influência sobre a transição entre os modos de desgaste abrasivo, ii) para os valores de força normal constante e pressão constante adotados, o coeficiente de atrito manteve-se, aproximadamente, na mesma faixa de valores e iii) o coeficiente de atrito é independente da taxa de desgaste. / The micro-scale abrasive wear test by rotative ball has gained large acceptance in universities and research centers, being widely used in studies on the abrasive wear of materials. Two wear modes are usually observed in this type of test: rolling abrasion results when the abrasive particles roll on the surface of the tested specimen, while grooving abrasion is observed when the abrasive particles slide; the type of wear mode has a significant effect on the overall behaviour of a tribological system. Several works on the friction coefficient during abrasive wear tests are available in the literature, but only a few were dedicated to the friction coefficient in micro-abrasive wear tests conducted with rotating ball. Additionally, recent works have identified that results may also be affected by the change in contact pressure that occurs when tests are conducted with constant applied force. Thus, the purpose of this work is to study the relationship between friction coefficient and abrasive wear modes in ball-cratering wear tests conducted at constant normal force and constant pressure. Micro-scale abrasive wear tests were conducted with a ball of AISI 52100 steel and a specimen of AISI H10 tool steel. The abrasive slurry was prepared with black silicon carbide (SiC) particles (average particle size of 3 m) and distilled water. Two constant normal force values and two constant pressure values were selected for the tests. The tangential and normal loads were monitored throughout the tests and their ratio was calculated to provide an indication of the friction coefficient. In all cases, optical microscopy analysis of the worn craters revelated only the presence of grooving abrasion. However, a more detailed analysis conducted by SEM has indicated that different degrees of rolling abrasion have also occurred along the grooves. The results have also shown that: i) the sliding distance presents an important role on the wear mode transition, ii) for the selected values of constant normal force and constant pressure, the friction coefficient presented, approximately, the same range of values and ii) the friction coefficient was independent of the wear rate.

L'apparition récente de nouveaux matériaux dans les structures de chaussée associée à une diminution de l'épaisseur des couches de surface et une augmentation du chargement des poids lourds et de leur fréquence de passage a entrainé de nouvelles pathologies de dégradation. Outre les problèmes d'orniérage bien connus, apparaissent désormais des fissures descendantes (top down cracking) ainsi que des problèmes de décohésion aux interfaces. Ces nouvelles pathologies entrainent des dépenses considérables sur l'ensemble du réseau (environ 15 milliards d'euros par an), particulièrement en zones urbanisées plus sujettes aux dégradations de surface et ne permettent pas d'estimer convenablement les durées de vie de la chaussée, le plus souvent surestimée dans les méthodes de dimensionnement actuelles. Ce travail de doctorat propose une nouvelle approche du contact pneu-chaussée permettant de mieux appréhender les contraintes principales et résiduelles dans une structure de chaussée bitumineuse. A l'aide d'un outil numérique rapide de calcul basé sur une approche semi-analytique (« Semi-Analytical Methods » (SAM)), la géométrie précise du pneumatique est intégrée afin d'obtenir une répartition de pression de contact ainsi qu'un cisaillement surfacique réelle sur la chaussée. Dans un premier temps, un modèle de contact roulant tractif élastique est implémenté pour des cas théoriques simples et validé par des résultats analytiques et numériques de la littérature. Ensuite, ce modèle est étendu pour prendre en compte le comportement élasto-plastique des corps en contact. Ce dernier est comparé à un résultat numérique basé sur la méthode des éléments finis issu de la littérature. Les résultats, pour une application contact pneu-chaussée, montrent une répartition non homogène des contraintes dans la structure et principalement dans les premiers centimètres sous la surface avec des niveaux beaucoup plus importants que peuvent le prédire les modèles actuels qui utilisent une charge uniformément répartie. La pression de contact est comparée aux mesures effectuées par un système nommé TekScan et les champs mécaniques en sous couches sont comparés à ceux d'Alizé-LCPC dans le cas d'une structure simple. Les cisaillements surfaciques sont déterminés dans le cas du roulement tractif. Une application est effectuée sur la modélisation des dégradations des chaussées en surface. Dans un premier temps, des analyses sur le comportement de la chaussée en surface sont effectuées pour une couche de béton bitumineux semi grenu (BBSG) semi-infinie supposée élastique, homogène sous conditions d'accélération, de freinage et de virage. Pour des études sur le top down cracking, des déformations et directions principales sont déterminées et analysées. Ensuite, le modèle de contact élasto-plastique est appliqué sur une couche semi-infinie de grave bitume GB3. Des déformations et contraintes résiduelles générées dans la structure sont déterminées en vue d'une analyse sur les ornières d'instabilité. Une fois validés, ces résultats permettront d'estimer plus fidèlement la durée de vie résiduelle des chaussées mais également de comprendre et d'éviter les mécanismes de dégradation en surface ou proche de la surface. / The recent appearance of new materials in road structures associated with surface layers thickness decreasing and the increasing of trucks loading and their passage frequency has led to new pathologies of degradation. In addition to the well-known rutting problems, top down cracking is now appearing as well as problems of decohesion at the interfaces. These new pathologies led to considerable expenditure on the entire network (around 15 billion euros per year), particularly in urbanized areas that are more prone to surface damage and do not make it possible to adequately estimate the lifetimes of the roadway, most often overestimated in current design methods. This doctoral work proposes a new approach of the tire-road contact allowing for better apprehend of the main and residual stresses in a bituminous pavement structure. Using a fast numerical tool based on a semi-analytical approach ("Semi-Analytical Methods" (SAM)), the precise geometry of the tire is integrated in order to obtain a real contact pressure distribution as well as surface shear on the pavement surface. Initially, an elastic tractive rolling contact model is implemented for simple theoretical cases and validated by analytical and numerical results from the literature.Then, this model is extended to take into account the elastoplastic behavior of the bodies in contact. This is compared to a numerical result based on the nite element method from the literature. The application for tire-pavement contact results, show a non-uniform distribution of stresses in the structure and mainly in the rst centimeters below the surface with much higher levels than can be predicted by current models that use a uniformly distributed load. The contact pressure is compared to the measurements made by a system called TekScan and the mechanical elds in sublayers are compared to those of Alizé-LCPC in the case of a simple structure. The surface shears are determined in the case of tractive rolling. An application is carried out on the modeling of surface pavement damage. Firstly, analyzes of the behavior of the surface pavement are carried out for a semi-innite semi-grit asphalt concrete layer supposed to be elastic, homogeneous under conditions of acceleration, braking and turning. For studies on top down cracking, principals deformations and directions are determined and analyzed. Then, the elastoplastic contact model is applied on a semi-innite asphalt agragate layer. Deformations and residuals stresses generated in the structure are determined for an analysis on the instability ruts. Once validated, these results will make it possible to more accurately estimate the residual life of pavements but also to understand and avoid surface or near surfacedegradation mechanisms.

Das Verhalten adhärenter Zellen hängt stark von den chemischen, topographischen und mechanischen Eigenschaften ihrer Umgebung ab. Experimentelle Untersuchungen der letzten Jahre haben gezeigt, dass adhärente Zellen aktiv die elastischen Eigenschaften ihrer Umgebung erkunden, indem sie an dieser ziehen. Der resultierende Kraftaufbau hängt von den elastischen Eigenschaften der Umgebung ab und wird an den Adhäsionskontakten in entsprechende biochemische Signale umgewandelt, die zelluläre Programme wie Wachstum, Differenzierung, programmierten Zelltod und Zellbewegung mitbestimmen. Im Allgemeinen sind Kräfte wichtige Einflussgrößen in biologischen Systemen. Weitere Beispiele dafür sind Hör- und Tastsinn, Wundheilung sowie die rollende Adhäsion von weißen Blutkörperchen auf den Wänden der Blutgefäße. In der Habilitationsschrift von Ulrich Schwarz werden mehrere theoretische Projekte vorgestellt, die die Rolle von Kräften und Elastizität in der Zelladhäsion untersuchen.<br /> (1) Es wurde eine neue Methode entwickelt, um die Kräfte auszurechnen, die Zellen an den Kontaktpunkten auf mikro-strukturierte elastische Substrate ausüben. Das Hauptergebnis ist, dass Zell-Matrix-Kontakte als Mechanosensoren funktionieren, an denen interne Kräfte in Proteinaggregation umgewandelt werden.<br /> (2) Eine Ein-Schritt-Master-Gleichung, die die stochastische Dynamik von Adhäsionsclustern als Funktion von Clustergröße, Rückbindungsrate und Kraft beschreibt, wurde sowohl analytisch als auch numerisch gelöst. Zudem wurde dieses Modell auf Zell-Matrix-Kontakte, dynamische Kraftspektroskopie sowie die rollende Adhäsion angewandt.<br /> (3) Im Rahmen der linearen Elastizitätstheorie und mit Hilfe des Konzepts der Kraftdipole wurde ein Modell formuliert und gelöst, das die Positionierung und Orientierung von Zellen in weicher Umgebung vorhersagt. Diese Vorhersagen sind in guter Übereinstimmung mit zahlreichen experimentellen Beobachtungen für Fibroblasten auf elastischen Substraten und in Kollagen-Gelen. / The behaviour of an adhering cell is strongly influenced by the chemical, topographical and mechanical properties of the surface it attaches to. During recent years, it has been found experimentally that adhering cells actively sense the elastic properties of their environment by pulling on it through numerous sites of adhesion. The resulting build-up of force at sites of adhesion depends on the elastic properties of the environment and is converted into corresponding biochemical signals, which can trigger cellular programmes like growth, differentiation, apoptosis, and migration. In general, force is an important regulator of biological systems, for example in hearing and touch, in wound healing, and in rolling adhesion of leukocytes on vessel walls. In the habilitation thesis by Ulrich Schwarz, several theoretical projects are presented which address the role of forces and elasticity in cell adhesion.<br /> (1) A new method has been developed for calculating cellular forces exerted at sites of focal adhesion on micro-patterned elastic substrates. The main result is that cell-matrix contacts function as mechanosensors, converting internal force into protein aggregation.<br /> (2) A one-step master equation for the stochastic dynamics of adhesion clusters as a function of cluster size, rebinding rate and force has been solved both analytically and numerically. Moreover this model has been applied to the regulation of cell-matrix contacts, to dynamic force spectroscopy, and to rolling adhesion.<br /> (3) Using linear elasticity theory and the concept of force dipoles, a model has been introduced and solved which predicts the positioning and orientation of mechanically active cells in soft material, in good agreement with experimental observations for fibroblasts on elastic substrates and in collagen gels.

The aim of this thesis was to investigate roller ski characteristics; classical and freestyle roller skis’ rolling resistance coefficients (μR) and classical style roller skis’ static friction coefficients (μS), and to study the influence of different μR and μS on cross-country skiers’ performance and both physiological and biomechanical indices. The aim was also to study differences in skiing economy and efficiency between recreational skiers, female and male junior and senior elite cross-country skiers.The experiments showed that during a time period of 30 minutes of rolling on a treadmill (warm-up), μR decreased significantly (p&lt;0.05) to about 60-65 % and 70-75 % of its initial value for freestyle and classical roller skis respectively. Also, there was a significant influence of normal force on μR, while different velocities and inclinations of the treadmill only resulted in small changes in μR.The study of the influence on physiological variables of a ~50 % change in μR showed that during submaximal steady rate exercise, external power, oxygen uptake, heart rate and blood lactate were significantly changed, while there were non-significant or only small changes to cycle rate, cycle length and ratings of perceived exertion. Incremental maximal tests showed that time to exhaustion was significantly changed and this occurred without a change in maximal power, maximal oxygen uptake, maximal heart rate and blood lactate, and that the influence on ratings of perceived exertion was non-significant or small.The study of classical style roller skis μS showed values that were five to eight times more than the values of μS reported from on-snow skiing with grip-waxed cross-country skis.The subsequent physiological and biomechanical experiments with different μS showed a significantly lower skiing economy (~14 % higher v̇O2), higher heart rate, lower propulsive forces coming from the legs and shorter time to exhaustion (~30 %) when using a different type of roller ski with a μS similar to on-snow skiing, while there was no difference between tests when using different pairs of roller skis with a (similar) higher μS.The part of the thesis which focused on skiing economy and efficiency as a function of skill, age and gender, showed that the elite cross-country skiers had better skiing economy and higher gross efficiency (5-18 %) compared with the recreational skiers, and the senior elite had better economy and higher efficiency (4-5 %) than their junior counterparts, while no differences could be found between the genders. / Syftet med denna avhandling var att undersöka fristils- och klassiska rullskidors rullmotståndskoefficienter (μR) och klassiska rullskidors statiska friktionskoefficienter (μS) samt effekter av olika μR och μS på längdskidåkares prestation vid rullskidåkning på rullande band. Syftet var även att undersöka s.k. åkekonomi och mekanisk verkningsgrad mellan motionärer och kvinnliga och manliga junior- och seniorlängdskidåkare på elitnivå.Experimenten visade att under en period av 30 minuters kontinuerligt rullande, på rullande band, så sjönk μR signifikant (p&lt;0.05) till 60-65 % och 70-75 % av initiala värden, för fristils- respektive klassiska rullskidor. Undersökandet av olika normalkrafter, hastigheter och lutningars påverkan på μR resulterade i en signifikant, negativ korrelation för μR som funktion av normalkraft, medan olika hastigheter och lutningar endast medförde små förändringar av μR.Studien som undersökte fysiologiska effekter av olika μR visade, vid submaximala konstanta arbetsbelastningar, att yttre effekt, syreupptagning, hjärtfrekvens och blodlaktat förändrades signifikant vid ~50 % förändring av μR. Försökspersonernas frekvens och sträcka per frekvens samt skattning av upplevd ansträngning resulterade dock i mestadels icke signifikanta eller små förändringar. Protokollen med successivt ökande arbetsbelastning (maxtest) resulterade i signifikant förändrad tid till utmattning, vid ~50 % förändring av μR. Detta inträffade utan signifikant skillnad i maximal syreupptagning, hjärtfrekvens och blodlaktat, vilket även mestadels gällde för skattning av upplevd ansträngning.Experimenten som undersökte klassiska rullskidors μS visade att dessa erhöll värden som är fem till åtta gånger högre än vad som rapporterats från studier av μS på snö med fästvallade skidor.Den efterföljande studien som undersökte fysiologiska och biomekaniska influenser av olika μS visade, vid submaximala konstanta arbetsbelastningar, att åkekonomin försämrades (~14 % högre syreförbrukning), hjärtfrekvensen ökade, den framåtdrivande kraften från benen på rullskidorna minskade samt att det blev kortare tid till utmattning (~30 %), vid maxtest, när skidåkarna använde rullskidor med en μS i likhet med vad som rapporterats för skidåkning på snö. För arbetsförsöken med olika rullskidor av olika fabrikat med en högre, och likartad, μS förelåg ingen skillnad i de undersökta variablerna.Studien som undersökte åkekonomi och mekanisk verkningsgrad som funktion av prestationsnivå, ålder och kön, visade att elitskidåkarna hade bättre åkekonomi och verkningsgrad (5-18 %) i jämförelse med motionärerna, att seniorerna hade bättre åkekonomi och verkningsgrad (4-5 %) än juniorerna och att ingen skillnad kunde konstateras mellan könen.

In 2001 the human proteome organization (HUPO) was created with the ambition to identify and characterize all proteins encoded in the human genome according to several criteria; their expression levels in different tissues and under different conditions; the sub-cellular localization; post-translational modifications; interactions, and if possible also the relationship between their structure and function.When the knowledge of different proteins and their potential interactions increases, so does the need for methods able to unravel the nature of molecular processes in cells and organized tissues, and ultimately for clinical use in samples obtained from patients. The in situ proximity ligation assay (in situ PLA) was developed to provide localized detection of proteins, post-translational modifications and protein-protein interactions in fixed cells and tissues. Dual recognition of the target or interacting targets is a prerequisite for the creation of a circular reporter DNA molecule, which subsequently is locally amplified for visualization of individual protein molecules in single cells. These features offer the high sensitivity and selectivity required for detection of even rare target molecules. Herein in situ PLA was first established and then employed as a tool for detection of both interactions and post-translational modifications in cultured cells and tissue samples. In situ PLA was also adapted to high content screening (HCS) for therapeutic effects, where it was applied for cell-based drug screening of inhibitors influencing post-translational modifications. This was performed using primary cells, paving the way for evaluation of drug effects on cells from patient as a diagnostic tool in personalized medicine. In conclusion, this thesis describes the development and applications of in situ PLA as a tool to study proteins, post-translational modifications and protein-protein interactions in genetically unmodified cells and tissues, and for clinical interactomics.

Gegenstand dieser Arbeit ist die Bereitstellung eines geeigneten Simulationswerkzeuges für die numerische Untersuchung der beim Rollkontakt zwischen Rad und Schiene auftretenden Phänomene. Hierbei liegt das Hauptaugenmerk auf der kontinuumsmechanischen Formulierung des mechanischen Feldproblems kontaktierender Körper sowie dessen numerischer Lösung mittels der Finite-Element-Methode. Zur Reduzierung des bei der Simulation von Rollkontakt aus der notwendigen sehr feinen Diskretisierung der Kontaktgebiete resultierenden numerischen Aufwandes wird eine relativkinematische Beschreibung herangezogen. Diese gemischte LAGRANGE-EULER-Betrachtungsweise beruht auf der Zerlegung der Bewegung in einen Starrkörperanteil und eine dazu relative Deformation. Die Herleitung der Bewegungsgleichung für das Kontaktproblem erfordert die relativkinematische Formulierung der kontinuumsmechanischen Grundgleichungen, d.h. der Bilanzgleichungen sowie der konstitutiven Beziehungen. Eine geeignete Kontaktmechanik einschließlich der Berücksichtigung des Kontakts rauer Oberflächen und veränderlicher Kontaktrandbedingungen ist ebenfalls notwendig. Die physikalische Einbindung der Körper in die Umgebung erfolgt über NEUMANNsche und DIRICHLETsche Randbedingungen. Auf dieser Basis können die Bewegungsgleichungen der Elastomechanik hergeleitet werden, welche sich jedoch einer analytischen Lösung verschließen. Somit werden sie in ihrer schwachen Form im integralen Mittel formuliert, was der Anwendung des Prinzips der virtuellen Verschiebungen als Ausgangspunkt für die numerische Lösung entspricht. Die rechentechnische Umsetzung erfordert die inkrementelle und diskrete Formulierung der Bewegungsgleichungen unter besonderer Beachtung der Trägheits-und Kontaktterme, wobei auf die Unterscheidung zwischen Haften und Gleiten beim Tangentialkontakt besonderes Augenmerk gelegt wird. Die numerische Lösung des Finite-Element-Gleichungssystems liefert den aktuellen Beanspruchungszustand zweier Körper im Rollkontakt. Die Funktionsfähigkeit der entwickelten Algorithmen wird abschließend anhand aussagekräftiger Beispielrechnungen zum statischen Kontakt und zum stationären Rollkontakt demonstriert, deren Ergebnisse gute Übereinstimmung mit analytischen Vergleichslösungen, soweit verfügbar, aufweisen. / Scope of this work is the preparation of a suitable simulation tool for the numerical investigation of rolling contact phenomena. The main focus lies on the continuum–mechanical formulation of the mechanical field problem of contacting bodies and its numerical solution within the framework of the Finite Element Method. For reducing the numerical effort in rolling contact simulation, induced by the necessity of a very fine discretization within the expected contact area, a relative–kinematical description is utilized. This arbitrary LAGRANGian–EULERian approach is based upon the decomposition of the total motion into a rigid body motion and a superimposed deformation. The derivation of the equation of motion for the contact problem requires the relative–kinematical formulation of the continuum–mechanical fundamental equations, i. e. the balance equations and the constitutive relations. A suitable contact model including the contact of rough surfaces and varying contact boundary conditions is also necessary. The physical embedding into the environment is accomplished by NEUMANN and DIRICHLET boundary conditions. Based upon that foundation the elastomechanics’ equations of motion are derived, which however can not be solved analytically in general. Hence, the equations of motion are transferred into their weak form by the application of the principle of virtual displacements serving for the numerical solution. The implementation of the problem demands for an incremental and discrete formulation of the equations, especially regarding the terms of inertia and the contact terms. Thereby, special attention has to be paid to the distinction between sticking and sliding within the framework of the tangential contact analysis. The numerical solution of the finite elements’ system of equations provides the state of stress, displacement and contact of two bodies in rolling contact. The reliability of the developed algorithms is finally verified by means of meaningful numerical examples for both static contact and for stationary rolling contact, whereby the numerical results coincide well with available analytical reference solutions.

Development of electric vehicles is motivated by global concerns over the need for environmental protection. In addition to its zero-emission characteristics, an electric propulsion system enables high performance torque control that may be used to maximize vehicle performance obtained from energy-efficient, low rolling resistance tires typically associated with degraded road-holding ability. A simultaneous plant/controller optimization is performed on an electric vehicle traction control system with respect to conflicting energy use and performance objectives. Due to system nonlinearities, an iterative simulation-based optimization approach is proposed using a system model and a genetic algorithm (GA) to guide search space exploration. The system model consists of: a drive cycle with a constant driver torque request and a step change in coefficient of friction, a single-wheel longitudinal vehicle model, a tire model described using the Magic Formula and a constant rolling resistance, and an adhesion gradient fuzzy logic traction controller. Optimization is defined in terms of the all at once variable selection of: either a performance oriented or low rolling resistance tire, the shape of a fuzzy logic controller membership function, and a set of fuzzy logic controller rule base conclusions. A mixed encoding, multi-chromosomal GA is implemented to represent the variables, respectively, as a binary string, a real-valued number, and a novel rule base encoding based on the definition of a partially ordered set (poset) by delta inclusion. Simultaneous optimization results indicate that, under straight-line acceleration and unless energy concerns are completely neglected, low rolling resistance tires should be incorporated in a traction control system design since the energy saving benefits outweigh the associated degradation in road-holding ability. The results also indicate that the proposed novel encoding enables the efficient representation of a fix-sized fuzzy logic rule base within a GA.