Cellular senescence is a permanent cell cycle arrest that is induced as a response to cellular stress. Replicative senescence is a well-described mechanism that limits the replicative capacity of cells and must be overcome by cancer cells. Oncogene-induced senescence (OIS) is a form of premature senescence and a potent tumor suppressor mechanism. OIS is induced in normal cells as a result of deregulated oncogene or tumor suppressor gene expression. An exciting area of research is the identification of novel targets that induce senescence in cancer cells as a therapeutic approach. In this study, a novel mechanism is described where the inhibition of Hsp90 in small cell lung cancer (SCLC) cells induced premature senescence rather than cell death. The senescence induced following Hsp90 inhibition was p21-dependent and the loss of p21 allowed SCLC cells to bypass the induction of senescence. Additionally, we identified a novel mechanism where the depletion of PKCι induced senescence in glioblastoma multiforme (GBM) cells. PKCι depletion-induced senescence did not activate the DNA-damage response pathway and was p21-dependent. Further perturbations of mitosis, using an aurora kinase inhibitor, increased the number of senescent cells when combined with PKCι depletion. This suggests that PKCι depletion-induced senescence involves defects in mitotic progression. Senescent glioblastoma cells at a basal level of senescence in culture, induced by p21 overexpression, and induced after PKCι depletion had aberrant centrosomes. Mitotic slippage is an early exit from mitosis without cell division that occurs when the spindle assembly checkpoint (SAC) is not satisfied. Senescent glioblastoma cells had multiple markers of mitotic slippage. Therefore, PKCι depletion-induced senescence involves mitotic slippage and results in aberrant centrosomes. A U87MG cell line with a doxycycline-inducible shRNA targeting PKCι was developed to deplete PKCι in established xenografts. PKCι was depleted in established glioblastoma xenografts in mice and resulted in decreased cell proliferation, delayed tumor growth and improved survival. This study has demonstrated that both Hsp90 and PKCι are novel targets to induce senescence in cancer cells as a potential therapeutic approach.

Žemės ūkio paskirties traktorių pagrindinis tikslas yra atlikti tempimo darbus esant įvairioms sąlygoms ir skirtingiems kelio paviršiams. Traukos jėga priklauso nuo traktoriaus eksploatacinių rodiklių, tokių kaip: ratų sukibimas su paviršiumi ir jų buksavimo dydis, traktoriaus išvystoma traukos galia ir t.t. Visi šie rodikliai kinta kintant traktoriaus bendrajai masei tuo pačiu ir vertikaliosioms apkrovoms veikiančioms kiekvieną iš traktoriaus ratų. Todėl atliekant įvairius žemės ūkio darbus, reikia tinkamai įvertinti traktorių veikiančias statines bei dinamines apkrovas. Magistrinio darbo tema – išanalizuoti traktoriaus ratus veikiančias reakcijos jėgas, esant skirtingiems agregato prikabinimo aukščiams ir kampams. Atlikus tyrimus, gautos priklausomybės rodo, jog didinant traukos jėgą priešinga kryptimi negu traktorius juda, apkrovos, veikiančios traktoriaus galinius ratus didėja, o priekinius – mažėja. Veikiant traukos jėga nukreipta horizontaliu kampu (imituojant posūkį į kairę pusę) kairės pusės traktoriaus ratus veikiančios apkrovos kito intensyviau negu dešinės pusės ratų. / The main purpose for agricultural tractor is to make pulling actions in various conditions and on various surfaces. Tractor pulling force depends on tractor performances such as: wheel grip with surface and their slippage value, tractor traction force etc. These performances depends on tractor weight and on its vertical wheel loads. Seeking for the best tractor efficiency while doing agricultural work it is necessary to sum up static and dynamic loads effecting tractor. Chosen Master thesis is designed to investigate tractor wheel static load, when simulating implement pull with different hitching heights and angles. After the research it can be stated that the increasing pulling force with the direction opposite tractor movement, rear wheel loads increase, while front wheel loads decrease. While pulling force with horizontal angle is increased (turning to the left is simulated), left side wheel loads varies with greater values than loads of the right side wheel.

Ce travail de thèse porte sur l'étude du comportement rhéologique de deux mélanges élastomères chargés en noir de carbone dans une gamme de températures rencontrée en extrusion (90°C à 40°C) et sur la modélisation du procédé d'extrusion. La caractérisation rhéologique des deux matériaux de l'étude a mis en évidence leur comportement rhéologique différent. En effet, le SBR et ses mélanges chargés avec différentes teneurs en noir de carbone montrent une courbe d'écoulement en deux branches stables (branche I et branche II) séparées par un plateau. La présence d'un glissement, faible en branche I et important en branche II, a été mis en évidence. Le second matériau, le NR (pur et chargé), montre, quant à lui, un comportement en deux parties distinctes : une partie sans rhéodurcissement et une autre avec rhéodurcissement dû à la mise en place d'une cristallisation sous contrainte de cisaillement. L'existence d'un temps caractéristique de cristallisation, diminué par la vitesse de cisaillement, a pu être mise en évidence. Les lois de comportement pour chacun des matériaux ont été déterminées. La réalisation d'une superposition temps/taux de charge a permis de définir une loi de comportement générale ; dans la gamme de température de 40°C à 90°C pour les mélanges SBR/noir de carbone et dans la gamme de température de 50°C à 90°C pour le NR. La loi rhéologique déterminée pour le mélange SBR chargé à 33% en masse en noir de carbone a été implémentée dans un modèle 1D et 3D. Les résultats numériques ont alors été comparés aux résultats expérimentaux, obtenus suite à des essais sur une extrudeuse instrumentée. Le modèle 1D s'est avéré insuffisant pour rendre compte des phénomènes se déroulant lors du procédé d'extrusion. L'implémentation d'un modèle 3D a été effectuée afin de prendre en compte des phénomènes tels que les effets de bords et les gradients de températures. L'importance de prendre en compte le phénomène de glissement dans le modèle 3D a été démontrée. / The present work deals with the characterization of the rheological behaviour of two rubbers filled with carbon black in a range of temperature encountered in extrusion (90°C to 40°C) and the modelling of the single screw extrusion process. The rheological characterization of the two rubbers shows behaviour totally different. The synthetic SBR rubber and SBR compounds filled with carbon black (with different amounts, from 16 to 33 wt%) showed a flow curve that can be divided in two stable parts (branch I and branch II) separated by a plateau. The occurrence of wall slip, low in branch I and important in branch II has been highlighted. The second rubber of the study, natural rubber, showed a different behaviour with a strain hardening due to the occurrence of a strain induced crystallization. The flow curve can be thus divided in two different parts: the first part without strain hardening and the second part with this phenomenon. The existence of a characteristic crystallization time, reduced by the shear rate, has been evidenced. By analysing data respectively on branch I for SBR and without strain hardening for NR, viscosity curves for all tested materials have been defined. General viscosity law have been proposed: for the SBR compound filled with carbon black valid in the range of temperature from 40°C to 90°C and for NR in the range of temperature from 50°C to 90°C. The rheological law defined for the SBR compound filled 33%wt with carbon black has been implemented in two different models: 1 D and 3D. Numerical results have been compared to experimental results obtained after experimentations on instrumented single screw extruder. The 1D approach was not sufficient to take into account all phenomena occurring during extrusion process. Then a 3D approach has been developed in order to take into account some effects as side effects and temperature gradients. The presence of the slip phenomenon in the modeling has been proved.

Darbo tikslas: ištirti transporto priemonės sudarytos iš traktoriaus ir priekabos su varančiaisiais ratais kinematinį suderinamumą, dinaminius bei ekonominius rodiklius ir nustatyti racionalios eksploatacijos sąlygas. Darbe nagrinėjami transporto priemonės sudarytos iš traktoriaus ir priekabos su varančiaisiais ratais kinematinis suderinamumas, dinaminiai bei ekonominiai rodikliai, esant išjungtiems priekabos varantiesiems tiltams bei įjungtiems vienam ir dviem priekabos varantiesiems tiltams. Nustatyta, kad transporto priemonei, važiuojant suartu lauku, kurio drėgnis 5 cm gylyje - 19,8 %, kietis - 0.85 MPa, o kietis 15 cm gylyje - 1,08 MPa, racionalu įjungti tik vieną priekabos varantįjį tiltą (kartu su traktoriaus užpakaliniu varančiuoju tiltu). Čia vieno priekabos varančiojo tilto įjungimas duoda teigiamus rezultatus važiuojant tiek su 4500 kg kroviniu, tiek ir be krovinio. Važiuojant vėžėmis per suarta dirvą be krovinio yra racionalu abu priekabos varančiuosius tiltus išjungti, o vežant krovinį įjungti vieną priekabos varantįjį tiltą. / Work aim: To investigate a vehicle consisting of a tractor-trailer-wheel drive with the compatibility of kinematic, dynamic and economic indicators and the rational exploitation conditions. The work deals with a vehicle consisting of a tractor and trailer with wheel drive . Kinematic compatibility, dynamic and economic indicators ,when the trailer driwing axles is off and on. It was found that a motor vehicle while driving convergence field, the moisture content at a depth of 5 cm - 19.8%, hardness - 0.85 MPa, and hardness at a depth of 15 cm - 1.08 MPa, it is reasonable to activate only one trailer driving axle the drive (with drive to the rear axle). This single drive axle trailers activation produce positive results in driving the 4500 kg load or without load. Going through the tracks plowed soil without load is reasonable to both drive axles off the trailer and cargo transport trailers for the drive to activate a axle.

Submitted by Lucienne Costa (lucienneferreira@ufcg.edu.br) on 2018-04-13T18:16:49Z No. of bitstreams: 1 MAURO HENRIQUE ALVES NASCIMENTO – DISSERTAÇÃO (PPGECA) 2017.pdf: 22942682 bytes, checksum: d52bbbcac224ea9695c0dd3c9ffc12d1 (MD5) / Made available in DSpace on 2018-04-13T18:16:49Z (GMT). No. of bitstreams: 1 MAURO HENRIQUE ALVES NASCIMENTO – DISSERTAÇÃO (PPGECA) 2017.pdf: 22942682 bytes, checksum: d52bbbcac224ea9695c0dd3c9ffc12d1 (MD5) Previous issue date: 2017-06-09 / Com a finalidade de sanar as degradações do pavimento, devem-se realizar estudos avaliativos das condições estruturais, objetivando identificar as possíveis causas dos defeitos e sobretudo fornecer subsídios, sobre quais medidas corretivas devem ser adotadas para a restauração das condições adequadas e aceitáveis do pavimento. Diante destas circunstâncias, o presente trabalho tem como objetivo identificar as possíveis causas das ocorrências dos defeitos parabólicos observados na superfície dos pavimentos flexíveis das pistas de pouso e decolagem e de taxiamento do Aeroporto Internacional de Natal. Para isso, realizou-se uma avaliação estrutural não destrutiva, por meio do levantamento deflectométrico com o Falling Weight Deflectometer (FWD), o qual foi realizado em toda a extensão das pistas e em diversas faixas de aquisição de dados. Com o FWD obteve-se as bacias de deflexões que possibilitaram por processo de retroanálise, por meio do software BAKFAA 2.0, caracterizar o comportamento resiliente in situ das camadas do pavimento. Com o software ELSYM5 realizou-se a análise empírico-mecanística, para verificar os níveis de tensões cisalhantes atuantes nas diversas profundidades das camadas do pavimento, inclusive na interface de ligação entre as camadas asfálticas. Também foram realizados ensaios laboratoriais de caracterização das propriedades mecânicas, tais como: módulo de resiliência, resistência a tração indireta e o ensaio de Leutner shear Test. Concluiu-se que os defeitos observados na superfície das pistas enquadravam-se na série de defeitos classificados de escorregamento do revestimento asfáltico, ou Slippage, e que os fatores que culminaram na ocorrência destes defeitos relacionam-se com a baixa aderência da interface de ligação e com a incompatibilidade de rigidez entre as camadas adjacentes de mistura asfálticas. / In order to remedy pavement degradation, evaluation studies of the structural conditions should be carried out to identify the possible causes of the defects and, above all, provide information on which corrective measures should be taken to restore adequat and acceptable conditions of the pavement. In view of these circumstances, the present work has the objective of identifying the possible causes of parabolic defects seen in the surface of the flexible pavements of the landing and take - off runways and taxiways of Natal International Airport runway. For this, a non-destructive structural evaluation was carried out by means of the deflectometric survey with the Falling Weight Deflectometer (FWD), which was carried out along the whole length of the tracks and in several ranges of data acquisition. With the FWD, the deflection basins were obtained, which enabled the BAKFAA 2.0 software to characterize the in situ resilient behavior of the pavement layers by means of a retro-analysis process. With the ELSYM5 software, the empirical-mechanistic analysis was performed to verify the levels of shear stresses at different depths of the pavement layers, including the interface between the asphalt layers. Furthermore, laboratory characterization of mechanical properties such as: resilience modulus, tensile strength and Leutner shear test were carried out. It is concluded that the defects observed on the runway surface fit into the series of defects classified as slippage of the asphalt coating, or Slippage, and that the factors that culminated in the occurrence of these defects are related to the low adhesion of the interface and With the incompatibility of stiffness between the adjacent layers of asphalt mixtures.

La détection tactile et la détection de glissement jouent un rôle important en permettant la manipulation robotique dextre des objets. Ainsi, le développement d'un système de capteur tactile entièrement intégré à haute résolution présente un intérêt certain. Ces travaux traitent de la conception et de la mise en place d'un système tactile intrinsèque basé sur un ensemble de capteurs MEMs de force à 3 axes et la détection du glissement avec ce système. Afin de créer un système tactile, les capteurs de force à 3 axes sont protégés par un revêtement, une étude sur le revêtement est réalisée. Deux systèmes intrinsèques différents basés sur un ensemble de capteurs de force à 3 axes sont développés, le premier est utilisé comme test de faisabilité de ce type de système. Le deuxième système intrinsèque est adapté à un doigt robotique à surface souple. Les systèmes proposés mesurent trois composants de force, le couple normal à la surface de contact et la position du centre de contact appliqué sur sa surface sensible. Les deux systèmes sont caractérisés et testés. La détection du glissement avec un système tactile intrinsèque est testée également. La détection du glissement est faite par l'application de la théorie de la surface limite et du modèle de contact viscoélastique. / Tactile sensing and slip detection plays an important role in enabling robotic dexterous object manipulation. Thus developing a high-resolution fully integrated tactile sensor system is of great interest. This work deals the design and implementation of an intrinsic tactile sensing system based on a set of 3-axis force MEMs sensors and the detection of slippage with such system. In order to create a tactile system the 3-axis force sensors are protected by a coating, a study about the coating is made. Two different intrinsic systems based on an array of 3-axis force sensors are developed, the first one is used a feasibility test of this kind of system. The second intrinsic system is adapted to a robotic finger with soft surface. The proposed systems measures three-force components, the normal torque to the contact surface, and the position of the contact centroid applied to its sensitive surface. Both systems are characterized and tested. The detection of slippage with an intrinsic tactile system is tested. The application of the limit surface theory and the viscoelastic model of contact make the detection of slippage.

No description available.

Im Mittelpunkt dieser kumulativ angefertigten Arbeit stehen fünf verschiedenartige biomechanische Untersuchungen faseriger Bindegewebe, welche in einer Gesamtschau zusammengeführt werden. Die einzelnen Beiträge setzen sich zusammen aus Untersuchungen zum Einfluss zellulärer Bestandteile auf die mechanischen Eigenschaften faseriger Bindegewebe und die Beeinflussung dieser Ergebnisse durch Messfehler, speziell am Beispiel des Materialschlupfs. Über diese beiden Beiträge wird eine Verbindung hergestellt zur rechnergestützten Simulation der Wirkung eines Beckenkompressionsgurts auf die Bänder des Beckenrings und dem Transmissionsverhalten faseriger Bindegewebe bei Zugbelastung. Im fünften Beitrag wird am Beispiel des Zusammenwirkens von Achillessehne, Fersenfettpolster und Plantarfaszie in vitro die Komplexität der Betrachtung faseriger Bindegewebe aufgezeigt. Die Zusammenführung der einzelnen Untersuchungen wird begleitet von der Frage, ob die bestehenden biomechanischen Untersuchungsansätze ausreichend sind, um ein umfassendes Verständnis zur funktionellen Bedeutung faseriger Bindegewebe aufbauen zu können.

Les problématiques de recherche abordées dans cette thèse concernent la conceptualisation, la modélisation et la commande générique des robots mobiles lors de leur évolution en milieux extérieurs et en présence de glissement pour des applications de suivi de précision. Ainsi, ce mémoire synthétise dans un premier temps les développements et résultats obtenus lors du suivi de trajectoire (localisation absolue), puis synthétise ensuite ceux obtenus lors de suivi de structure et de cible (localisation relative). Une dernière partie introduit un concept de plateforme robotique reconfigurable et sa commande associée pour adapter l’assiette et les dimensions du châssis en fonction de la topographie du terrain.Pour chaque application de suivi, ce mémoire présente un panel de lois de commande originales pour des robots différentiels, à un train et à deux trains directeurs. Chaque modalité de commande est présentée en quatre étapes : modélisation, estimation, commande et expérimentations. La première contribution majeure de la thèse concerne l’estimation du glissement. Cette dernière est adaptative et basée modèle. Elle intègre la modélisation cinématique étendue seule ou couplée à la modélisation dynamique du robot mobile pour assurer une estimation intègre quels que soient la vitesse, les phénomènes dynamiques rencontrés et la nature du sol. La seconde contribution majeure concerne le développement d’une stratégie de commande générique pour les robots mobiles. Cette stratégie est basée sur le principe de la commande en cascade (ou par backstepping) et est déclinée dans ce mémoire à travers un panel de lois de commande. Cette méthodologie de commande, lorsqu’elle est associée à l’observation du glissement précédent, permet d’obtenir des performances de suivi accrues quel que soit le contexte rencontré. L’ensemble des algorithmes ont été validés en simulation et/ou expérimentalement à l’aide de différentes plateformes robotiques en contextes réels. / This work is focused on the conceptualization, the modeling and the genericcontrol of mobile robots when moving in off-road contexts and facing slipperyterrains, especially for very accurate tracking and following applications. Thisthesis summarizes the proposed methods and the obtained results to addressthis research issue, first for path following applications (absolute localization)and then for edge and target tracking applications (relative localization). A finalsection of this thesis introduces an adaptive robotic concept and its associatedcontroller allowing the adaptation of the pose (position and orientation) of thechassis with respect to the environment topography.For each application, this thesis introduces a panel of innovative control algorithmsfor controlling skid-steering, two-wheel steering and four-wheel steeringmobile robots. Each algorithm of the panel is described, in this thesis, infour steps : modeling, estimation, control and experiments.The first main contribution of this thesis deals with the slippage estimation.The latter is adaptive and model-based. It also includes the extended kinematicmodeling only or together with the dynamic modeling of the mobile robot toensure a robust estimation of the slippage whatever the speed of the robot, encountereddynamic phenomena or even ground characteristics.The second main contribution deals with the design of a generic control approachfor mobile robots when path following and target tracking. The proposedstrategy is mostly based on a backstepping method and is illustrated inthis thesis via a panel of control laws. When combining this proposed controlapproach with the slippage estimation described above, significant improvedtracking and following performances are obtained (in term of stability, repeatability,accuracy and robustness) whatever the encountered context.All algorithms have been tested and validated through simulations and/orfull-scale experiments, indoor and off-road, with different mobile robots.

Ce manuscrit présente une description théorique des propriétés de transport exceptionnelles des liquides dans les nanotubes de carbone (CNT). La perméabilité de ces canaux dépasse largement ce qui est prévu par les équations de l'hydrodynamique et la condition limite de non-glissement. Au cours des dernières années, plusieurs groupes ont effectué des expériences d'écoulement de liquides dans des membranes de CNT. Une perméabilité très supérieure à l'attente classique a été observée. Dans ce contexte, nous avons mené une étude exhaustive du frottement liquide/solide qui apparaît pendant l'écoulement d'un fluide dans un CNT, à l'aide de simulations de dynamique moléculaire. Le coefficient de frottement a été mesuré pour différents systèmes en utilisant plusieurs méthodes indépendantes. Les simulations ont montré que le coefficient de frottement était indépendant du confinement, mais qu'il dépendait considérablement de la courbure de la paroi. Pour l'eau dans un CNT, le coefficient de frottement diminue avec le rayon du tube. Nous avons ensuite établi une expression approchée du coefficient de frottement, qui le relie à des propriétés microscopiques de l'interface entre le liquide et la paroi. Cette expression reproduit la dépendance du coefficient de frottement avec la courbure, et permet de l'expliquer à partir des trois paramètres statiques suivants : la densité surfacique de l'eau, la rugosité de la paroi et la commensurabilité entre les structures de la paroi et de la première couche d'eau à l'interface. En résumé, notre étude a permis une compréhension détaillée du frottement de l'eau dans les CNT, qui explique l'origine de sa valeur extrêmement basse. / Within the scope of this thesis, a theoretical study of liquid flow in graphitic nanopores was performed. More precisely, a combination of numerical simulations and analytic approach was used to establish the special properties of carbon nanotubes for fluid transport: Molecular dynamics flow simulations of different liquids in carbon nanotubes exhibited flow velocities that are 1-3 orders of magnitude higher than predicted from the continuum hydrodynamics framework and the no-slip boundary condition. These results support previous experiments performed by several groups reporting exceptionally high flow rates for water in carbon nanotube membranes. The reason for this important flow enhancement with respect to the expectation was so far unclear. In this work, a careful investigation of the water/graphite friction coefficient which we identified as the crucial parameter for fast liquid transport in the considered systems was carried out. In simulations, the friction coefficient was found to be very sensitive to wall curvature: friction is independent of confinement for water between at graphene walls with zero curvature, while it increases with increasing negative curvature (water at the outside of the tube), and it decreases with increasing positive curvature (water inside the tube), eventually leading to quasi frictionless flow for water in a single file configuration in the smallest tubes. A similar behaviour was moreover found with several other liquids, such as alcohol, alcane and OMCTS. urthermore, a theoretical approximate expression for the friction coefficient is presented which predicts qualitatively and semi-quantitatively its curvature dependent behavior. Moreover, a deeper analysis of the simulations according to the proposed theoretical description shed light on the physical mechanisms at the origin of the ultra low liquid/solid friction in carbon nanotubes. In fine, it is due to their perfectly ordered molecular structure and their atomically smooth surface that carbon nanotubes are quasi-perfect liquid conductors compared to other membrane pores like, for example, nanochannels in amorphous silica. The newly gained understanding constitutes an important validation that carbon nanotubes operate as fast transporters of various liquids which makes them a promising option for different applications like energy conversion or filtration on the molecular level.