Au niveau de la circulation pulmonaire, une exposition prolongée à l’hypoxie est responsable du phénomène de vasoconstriction hypoxique pulmonaire (VHP) qui favorise les échanges gazeux. Lorsque cette VHP se généralise, elle conduit au développement d'une hypertension pulmonaire de groupe 3 (HTP). Cette pathologie se caractérise par un remodelage vasculaire induisant une élévation progressive de la pression artérielle pulmonaire (> 25 mmHg au repos). Ceci conduit à une défaillance cardiaque droite et, à terme, à la mort. La VHP est responsable de l'étirement de la membrane des cellules musculaires lisses des artères pulmonaires (CMLAP) et peut ainsi activer des "Stretch-Activated Channels" tels que les TRPV (Transient Receptor Potential Vanilloid). Il a précédemment été décrit que les canaux TRPV1 et TRPV4, impliqués dans la migration et la prolifération des cellules vasculaires pulmonaires, sont surexprimés et suractivés lors de l'HTP. Cependant, ces modifications peuvent être dues à un effet direct de l’hypoxie ou indirect, conséquence d'un étirement membranaire plus important induit par la VHP. Nous avons donc étudié la contribution respective des stress hypoxique et mécanique, observés en contexte d’HTP, en utilisant des conditionnements in vitro sur des CMLAP d’animaux sains (rats et souris). Nous avons montré que l’hypoxie (1 % O2, 48 heures) induit une augmentation de la [Ca2+]i couplée à une potentialisation de la migration induite par l’activation de TRPV1 et V4. De même, un étirement cyclique (20 %, 1 Hz, 24 heures) provoque une augmentation de la [Ca2+]i et de la prolifération. Ces résultats montrent pour la première fois une action directe de l'hypoxie et du stress mécanique (étirement cyclique) sur des CMLAP. / Hypoxia exposure induces hypoxic pulmonary vasoconstriction (HPV) allowing the efficiency of gas exchanges by increasing the intraluminal pressure. Prolonged hypoxia leads to pulmonary hypertension of group 3 (PH), characterized by increased pulmonary pressure (> 25 mmHg), leading to right ventricular heart failure and ultimately death. HPV leads to stretch pulmonary artery smooth muscle cell (PASMC) membranes inside the vascular wall and thus can activate "Stretch-Activated-Channels" such as TRPV channels (Transient Receptor Potential Vanilloid). It has been previously shown that TRPV1 and TRPV4 channels, implicated in PASMC migration and proliferation, are overexpressed and overactivated in PASMC in the context of PH. But whether this feature is directly caused by hypoxia alone or is a consequence of stretch induced by the HPV is a matter of debate. We thus investigated the respective contribution of hypoxia and mechanical stresses observed in the context of PH using in vitro conditionings on PASMC from healthy animals (rats and mice). We showed that hypoxia (1 % O2, 48 hours) increases Ca2+ entry through TRPV4 channels as well as PASMC migration induced by TRPV1 and TRPV4 activation. Furthermore, cyclic stretch conditioning (20 %, 1 Hz, 24 hours) triggers Ca2+ increase and PASMC proliferation. This work shows for the first time the direct implication of both hypoxia and mechanical stress (cyclic) stretch on PASMC.

Les cellules épithéliales forment des tissus cohésifs, sous forme de monocouches que l'on retrouve dans les poumons, les reins ou la peau. Travaillant à partir d'expériences in vitro, nous avons caractérisé le comportement mécanique de monocouches cellulaires. Nous avons étudié la fermeture de blessures circulaires sur un substrat non adhésif. En comparant différents modèles, nous avons montré comment la fermeture est possible grâce à un cable contractile d'acto-myosine et aux fluctuations de la tension du tissu. La Microscopie des Forces de Traction (TFM) permet de mesurer les forces que les cellules exercent sur leur substrat. A partir de cette mesure et en utilisant l'équilibre des forces, nous avons développé une méthode qui résout ce problème sous-déterminé par inversion bayésienne et permet d'obtenir le champ des contraintes internes au tissu. En appliquant cette méthode sur des images (BISM: Microscopie des contraintes par inversion bayésienne) et en l'adaptant à l'aide d'un filtre de Kalman sur des films (KISM: Microscopie des contraintes par inversion de Kalman), nous avons inféré le tenseur des contraintes de monocouches cellulaires sans faire aucune hypothèse sur la rhéologie du tissu. Enfin, nous avons estimé les contraintes directement depuis les déplacements du substrat, sans passer par les forces de tractions et donc en réduisant le nombre d'inversions de matrice (BISMu: Microscopie des contraintes par inversion bayésienne à partir des déplacements du substrat). / Epithelial cells are known to form cohesive monolayers, a form of tissue organization encountered in the lung, the kidney or the skin. From in vitro experiments, we have characterized the mechanical properties of cell monolayers. We have studied the closure of circular wounds over a nonadhesive substrate. Comparing different models, we have shown how closure is possible thanks to a contractile acto-myosin cable and to fluctuations of the tissue tension. Traction Force Microscopy (TFM) allows to measure the forces that cells exert on their substrate. Starting from this measurement and using the force balance equations, we have solved this underdetermined problem by Bayesian inversion and obtained the internal stress field of the tissue. Applying this method on single images (BISM: Bayesian Inversion Stress Microscopy), and adapting it with a Kalman filter for movies (KISM: Kalman Inversion Stress Microscopy) we have inferred the stress tensor of cell monolayers, without making any hypothesis on the tissue rheology. Finally, we have estimated the stresses directly from the substrate displacements, without computing the traction forces and thus reducing the number of matrix inversions (BISMu: Bayesian Inversion Stress Microscopy from substrate displacements).

INTRODUÇÃO: Evidencia experimental sugere que padrões alterados de fluxo vascular, associados às bifurcações, estão envolvidos no desenvolvimento de lesões aneurismáticas. Pesquisamos os efeitos que a sobrecarga hemodinâmica condiciona sobre a parede arterial do ápice da bifurcação aórtica de modelos murinos. MÉTODOS: Sessenta ratos Wistar, selecionados e designados mediante amostragem probabilística simples foram agrupados equitativamente em um grupo controle e três grupos experimentais. Os espécimes foram anestesiados e sob magnificação microscópica, foi realizada uma incisão abdominal média e a aorta e os vasos ilíacos abordados e isolados desde a porção infra-renal até a porção distal da bifurcação. Modificação da geometria da bifurcação aórtica foi realizada mediante tunelamento da porção distal da artéria ilíaca no músculo ílio-lombar, no nível da raiz do membro inferior nos grupos II e IV. Nefrectomia esquerda e ligação da artéria renal inferior direita foram completadas para reforçar o estresse hemodinâmico nos grupos III e IV. Os modelos mantiveram-se em condições de laboratório convencionais com dieta standard para a espécie e água ad libitum para os grupos I e II e solução de NaCl 0,9% para os grupos III e IV. Após seis meses de seguimento, a bifurcação aórtica e as artérias ilíacas foram inspecionadas e subseqüentemente removidas para sua análise histopatológica. Um espécime por cada grupo foi submetido à angiografia digital com reconstrução tridimensional da bifurcação aórtica. RESULTADOS: 1) A pressão arterial, a freqüência cardíaca e a pressão de pulso entre os grupos, com e sem nefrectomia, mostraram diferenças com significância estatística (p <0,05). Os espécimes reunidos nos grupos III e IV que receberam sobrecarga de sódio desenvolveram um padrão hemodinâmico caracterizado por incremento da freqüência cardíaca e da pressão de pulso. 2) Seis espécimes (60%) do grupo IV desenvolveram aneurismas do ápice da bifurcação aórtica. 3) A avaliação angiográfica demonstrou que a morfologia da bifurcação do grupo controle se mantém sem modificações aparentes durante o período de seguimento. Entretanto, o grupo II apresenta dados de remodelamento longitudinal com tortuosidade e alongamento do tronco e ramos que conformam a bifurcação. Já o grupo III apresenta estenose proximal e dilatação incipiente da região do ápice da bifurcação em um padrão descrito como blister-like. Finalmente, o grupo IV demonstra aneurismas e estenoses múltiplas da porção proximal e distal ao divisor de fluxo. CONCLUSÕES: Em modelos murinos, deformações da geometria arterial, introduzidas por mudanças do ângulo de bifurcação, induzem a formação de aneurismas e a associação com hipertensão arterial, pressão de pulso aumentada, freqüência cardíaca elevada e sobrecarga de sódio potencializam a dilatação sacular desses segmentos / BACKGROUND: Experimental evidence indicates that altered patterns of vascular flow associated with bifurcations are involved in the development of aneurysmatic lesions. The effects of the hemodynamic overload on the arterial wall of the aortic bifurcation in murine models were studied. METHODS: Sixty Wistar rats were selected and assigned by simple random sampling into a control group and three experimental groups. The specimens were anesthetized. Under microscopic magnification an abdominal incision was performed and the aortic and iliac vessels were isolated from the infra-renal portion until the distal bifurcation. The modification of the geometry of the aortic bifurcation was accomplished by tunneling of the distal iliac artery into ilio-lumbar muscle in groups II and IV. Left nephrectomy and ligation of inferior right renal artery were completed to enhance the hemodynamic stress in groups III and IV. The models were maintained in conventional laboratory conditions with standard diet for the species and water ad libitum for groups I and II, and NaCl 0.9% for groups III and IV. After six months of follow up, the aortic bifurcation and iliac arteries were inspected and subsequently removed to its histopathological evaluation. One specimen from each group underwent angiography with digital three-dimensional reconstruction of the aortic bifurcation prior to sacrifice. RESULTS: 1) Blood pressure, heart rate and pulse pressure between the groups with and without nephrectomy showed statistically significant differences (p <0.05). The specimens collected in groups III and IV who received sodium overload developed a hemodynamic pattern characterized by increased heart rate and pulse pressure. 2) Six specimens (60%) in group IV developed aneurysmatic dilatation of the apex of the aortic bifurcation. 3) The angiographic evaluation showed that the morphology of the bifurcation of the control group remains unchanged during the study period. However, group II presents data from longitudinal remodeling with tortuosity and lengthening of the trunk and branches that make up the fork. The Group III presents stenosis and proximal dilatation of the apex of the bifurcation in a pattern described as blister-like. Finally, Group IV shows multiple stenosis proximal and distal to the flow divider. CONCLUSIONS: In murine models, the geometry deformation introduced by changes in the angle of bifurcation, induce inflammation of the flow divider, whereas, high blood pressure, pulse pressure, heart rate and high sodium overload catalyze the aneurysmatic dilatation of these segments

Diploma thesis deals with calculation and design study of air-cooled Wankel engine and simple mechanical stress of its main parts.

This diploma thesis describes the design of a device for measuring stress in thin films – laser deflectometer, realization of its design and its experimental testing. The thesis is divided into five chapters. The first chapter deals with the stress in thin films and its influence on substrate – thin film system. The second chapter provides an overview of devices widely used for measuring stress in thin films and describes some their advantages and disadvantages. In the third chapter some design possibilities of the device are presented. The final solution of device called deflectometr is introduced in the fourth chapter. The last chapter includes the functional testing the device.

Amorphous and nano- or micro- crystalline silicon thin films are intensively studied materials for photovoltaic applications. The films are used as intrinsic layer (absorber) in p-i-n solar cells. As opposed to crystalline silicon solar cells, the thin films contain about hundred times less silicon and can be deposited at much lower temperatures (typically around 200 0 C) which saves energy needed for production and makes it possible to use various low cost (even flexible) substrates. However, these films have a complex microstructure, which makes it difficult to measure and describe the electronic transport of the photogenerated carriers. Yet, the understanding of the structure and electronic properties of the material at nanoscale is essential on the way to improve the efficiency solar cells. One of the main aims of this work is the study of the structure and mechanical properties of the mixed phase silicon thin films of various thicknesses and structures. The key parameter of microcrystalline silicon is the crystallinity, i.e., the microcrys- talline volume fraction. It determines internal structure of the films which, in turn, decides about many other properties, including charge transport and mechanical sta- bility. Raman microspectroscopy is a fast and non-destructive method for probing the...

Age-related macular degeneration (AMD) is a major cause of blindness in adults. Abnormal growth of blood vessels in the eye during the course of AMD causes damage to the retina, resulting in irreversible blindness. The goal of this research was to determine whether physical pressure on retinal cells can contribute to the increased blood vessel formation. To replicate the tears in the cell layers, a micropatterning method was used as a means of detaching cells from each other. Two new devices were also developed to mimic slow and fast increases in mechanical pressure on cell layers of the eye. After detaching cells from each other and adding mechanical stress to cells, the levels of angiogenic proteins secreted by retinal cells were measured. The results showed that both cell-cell detachment and mechanical stress can increase the secretion of angiogenic proteins. After adding mechanical stress, we also added the secreted proteins to blood vessel cells and observed an increase in blood vessel formation, indicating that mechanical stress can independently induce angiogenesis. These results suggest that physical stimuli in the eye can contribute to the aberrant blood vessel formation in AMD.

Aminoethoxyvinyl glycine (AVG) and silver thiosulfate, antagonists of ethylene biosynthesis and action in plants, both delayed onset of leaf epinasty in Xanthium strumarium L. (cocklebur) plants rotated on horizontal clinostats. Xanthium plants mechanically stressed by continuous horizontal or vertical shaking, or continuous twisting back and forth, did not develop any significant epinasty, while plants inverted every 20 minutes (upside down half the time) did develop epinasty. From this it appears that clinostat-induced epinasty is a result of gravity compensation rather than mechanical stress. Treatment of Xanthium, Lycopersicon esculentum Mill. (tomato), and Ricinus communis L. (castor bean) plants with inhibitors of ethylene biosynthesis, AVG and cobaltous ion, and inhibitors of ethylene action, silver ion and carbon dioxide, significantly delayed stem gravitropic response times. AVG and silver were dependably effective in delaying gravitropism, while carbon dioxide and cobalt were less effective. Unilateral application of ethephon solution (1%) to the upper 10 centimeters of tomato stems, caused stems to deflect up to 80° toward the side of application after 24 hours on a clinostat, while unilateral application of indole-3-acetic acid in lanolin paste (1%) to tomato and cocklebur stems caused up to 250° and 200° bending respectively, away from the side of application after 24 hours on a clinostat. Cocklebur stems that are restricted from bending after placing them horizontally store bending energy as seen from the springing upward that occurs when the stems are released (up to an average of 150° after 40 hours of restriction). Most of these stems also showed a stored stimulus of gravitropic bending, continuing to bend for several hours after release and being placed upright, before straightening.

yes / Despite the rising interest in pharmaceutical cocrystals in the past decade, there is a lack of research in the solid processing of cocrystals downstream to crystallization. Mechanical stress induced by unit operations such as milling could affect the integrity of the material. The purpose of this study is to investigate the effect of milling on pharmaceutical cocrystal and compare the performance of ball mill and jet mill, using caffeine-glutaric acid (1:1) cocrystal as the model compound. Our results show that ball milling induced polymorphic transformation from the stable Form II to the metastable Form I; whereas Form II remained intact after jet milling. Jet milling was found to be effective in reducing particle size but ball milling was unable to reduce the particle beyond certain limit even with increasing milling intensity. Heating effect during ball milling was proposed as a possible explanation for the difference in the performance of the two types of mill. The local increase in temperature beyond the polymorphic transformation temperature may lead to the conversion from stable to metastable form. At longer ball milling duration, the local temperature could exceed the melting point of Form I, leading to surface melting and subsequent recrystallization of Form I from the melt and agglomeration of the crystals. The findings in this study have broader implications on the selection of mill and interpretation of milling results for not only pharmaceutical cocrystals but pharmaceutical compounds in general.

An analytic treatment of stresses and temperatures generated during grinding is presented from an elasticity approach. A two-dimensional heat conduction model employs an energy partition scheme in the grinding zone to produce realistic temperature profiles. By using the basic equations of thermoelasticity, the temperature profiles yield thermal stresses. An extension of the Hertzian contact theory yields mechanical stresses, which are then superimposed on the thermal stresses. Approximate plasticity corrections are used to approximate the deformation as the grinding wheel passes over the workpiece. Subsurface results are qualitatively consistent with those found experimentally. However, they still do not agree with near-surface experimental results. Possible explanations and areas of further research are discussed. / Master of Science