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Previous studies show that membrane-damaging activity of cardiotoxins (CTXs) is associated with their binding with anionic phospholipids on membrane. In order to examine this proposition, studies on the interaction between Taiwan cobra CTXs and zwitterionic phospholipids were conducted in the present study. Although membrane-damaging activity of CTX2 and CTX4 was affected by phospholipid compositions, CTX2 and CTX4 were able to induce membrane permeability of zwitterionic phospholipid vesicles. CTX2 showed a higher membrane-damaging activity toward egg yolk phosphatidylcholine (EYPC), EYPC/egg yolk phosphatidylethanolamine (EYPE) or EYPC/egg yolk phosphatidylglycerol (EYPG) than CTX4 did. Moreover, CTX2- and CTX4-induced membrane permeability of EYPC and EYPC/EYPE vesicles was higher than that of EYPC/EYPG vesicles. CTX2 and CTX4 displayed different membrane-bound mode in binding with EYPC, EYPC/EYPE and EYPC/EYPG vesicles as revealed by N-( fluorescein - 5 - thiocarbamoyl) - 1, 2 - dihexadecanoyl-phosphatidyl ethanolamine fluorescence enhancement, color transformation of phospholipids/polydiacetylene membrane assay and rhodamine-self quenching assay. CTX2 and CTX4 showed a similar binding affinity with phospholipid vesicles, but the reversibility in binding with phospholipid vesicles differed between CTX2 and CTX4. Compared with that of CTX4, membrane-damaging activity of CTX2 was markedly inhibited by anti-CTX antibodies. Taken together with the finding that gross conformation of CTX2 and CTX4 differs, our data suggest that membrane-damaging activity of CTX2 and CTX4 critically depends on their membrane-bound mode and is affected by phospholipid composition. Moreover, the ability of CTX to induce membrane permeability is not exclusively attributed to the binding with anionic phospholipids.

Naja naja atra Cardiotoxins (CTXs), basic polypeptides of 60 amino acid residues adopt a three-fingered loop-folding topology and show cytotoxicity for human tissues in targeting cell membrane. Despite having highly similar sequence, the six CTX isoforms also display different cytotoxic potencies and hemolytic activities. The goal of these studies is to explore the mechanical processes that involved in membrane-damaging activities of CTXs on vesicles composed of different cell membrane components, and to delineate the events that lead to different biological activities of CTXs. The studies were performed by estimating the color transformation of phospholipid/polydiacetylene vesicles and the fluorescence enhancement of fluorescein-labeled phospholipid/protein or fluorescein released from vesicles. It was found that vesicles consisted of unsaturated phospholipids improve membrane-damaging activity of CTXs and adopt a vital membrane-bound conformation of CTXs. In contract, the characteristic of vesicles consisted of saturated phospholipids was against CTXs adopting an essential membrane-damaging structure. It was also found that not only electrostatic force but also hydrophobic force were involved in the interaction between CTXs and membrane. Comparing with phosphatidylcholine-only vesicles, CTXs displayed higher membrane-damaging activity for the sphingomyelin-containing vesicles, and the loop2 region of CTXs play a crucial role for the membrane-damaging activity of sphingomyelin-containing vesicles. Besides, the CTX3 and CTX5 would interact with the H-antigen of blood group O red blood cells, but only the binding of CTX3 with H-antigen reduce its membrane-damaging activity for red blood cells membrane. Moreover, the fusogenicity of CTXs is responsible for the membrane-damaging activity of CTXs toward bacterial membrane-mimicking vesicles. The cardiolipin have the potency to improve the fusogenicity of CTX3, which induced the bactericidal activity toward the cardiolipin-containing bacterium.

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Un des plus grands défis de la Physique aujourd’hui est de créer une source d’énergie propre, durable et efficace qui puisse satisfaire les besoins de la société actuelle et future avec le minimum d’impact sur l’environnement. Dans ce cadre, un grand effort de recherche internationale est dévoué à l’étude de nouveaux systèmes de production d’énergie ; réacteurs de fission de Génération IV et réacteurs de fusion nucléaire sont en particulier en train d’être développés. Les matériaux utilisés dans ces réacteurs seront soumis à des hauts niveaux de radiation, ce qui rend nécessaire l’étude de leur comportement sous irradiation pour permette le succès du développement de ces nouvelles technologies. Dans cette thèse, deux matériaux ont été étudiés : la silice amorphe (a-SiO₂) et l’oxyde de magnésium (MgO). Ces deux matériaux sont des oxydes isolants avec des applications dans l’industrie de l’énergie nucléaire. Des irradiations avec des ions de haute énergie ont été réalisées sur différentes plateformes d’accélérateurs d’ions pour induire l’endommagement de ces deux matériaux par irradiation ; ensuite, les mécanismes d’endommagement ont été caractérisés en utilisant, principalement, des techniques d’analyse par faisceau d’ions (techniques IBA).Un des objectifs de cette thèse était de développer la technique d’ionoluminescence (qui est une technique IBA très peu connue) et de l’appliquer à l’étude des mécanismes d’endommagement par irradiation des matériaux, démontrant alors le potentiel de cette technique. L’ionoluminescence de trois types différents de silice (avec des différentes teneurs en OH) a ainsi été étudiée en détail et utilisée pour décrire la création et l’évolution des défauts ponctuels sous irradiation. Dans le cas de MgO, l’endommagement produit par irradiation avec des ions Au⁺ à 1.2 MeV a été caractérisé en utilisant la technique de spectrométrie de rétrodiffusion Rutherford en configuration de canalisation et la diffraction des rayons X. Finalement, l’ionoluminescence de MgO sous différentes conditions d’irradiation a aussi été étudiée. Les résultats obtenus dans cette thèse aident à comprendre les processus d’endommagement par irradiation dans les matériaux, ce qui est indispensable pour le développement de nouvelles sources d’énergie nucléaire. / One of the most important challenges in Physics today is the development of a clean, sustainable, and efficient energy source that can satisfy the needs of the actual and future society producing the minimum impact on the environment. For this purpose, a huge international research effort is being devoted to the study of new systems of energy production; in particular, Generation IV fission reactors and nuclear fusion reactors are being developed. The materials used in these reactors will be subjected to high levels of radiation, making necessary the study of their behavior under irradiation to achieve a successful development of these new technologies. In this thesis two materials have been studied: amorphous silica (a-SiO₂) and magnesium oxide (MgO). Both materials are insulating oxides with applications in the nuclear energy industry. High-energy ion irradiations have been carried out at different accelerator facilities to induce the irradiation damage in these two materials; then, the mechanisms of damage have been characterized using principally Ion Beam Analysis (IBA) techniques. One of the challenges of this thesis was to develop the Ion Beam Induced Luminescence or ionoluminescence (which is not a widely known IBA technique) and to apply it to the study of the mechanisms of irradiation damage in materials, proving the power of this technique. For this purpose, the ionoluminescence of three different types of silica (containing different amounts of OH groups) has been studied in detail and used to describe the creation and evolution of point defects under irradiation. In the case of MgO, the damage produced under 1.2 MeV Au⁺ irradiation has been characterized using Rutherford backscattering spectrometry in channeling configuration and X-ray diffraction. Finally, the ionoluminescence of MgO under different irradiation conditions has also been studied.The results obtained in this thesis help to understand the irradiation-damage processes in materials, which is essential for the development of new nuclear energy sources.

Borderline Personality Disorder (BPD) is an enduring personality disorder marked by severe self-damaging behaviors such as self-harm, substance use, and disordered eating behaviors. This study examined the emotional antecedents and consequences of self-damaging behavior (self-harm, binge drinking, substance use, and disordered eating behavior) among individualls who report features of BPD to assess the function of these behaviors. Additionally, this study examined whether self-reported difficulties in emotion regulation mediated the relationship between features of BPD and the presence of self-damaging behavior. Results from this study found support for the use of self-harm, drugs use, and disordered eating behavior to regulate emotional experiences and all forms of self-damaging behavior were found to significantly increase the presence of pleasant emotional experiences. The function of self-damaging behavior remains stable, regardless of whether the behavior occurs in isolation or co-occurs with other self-damaging behaviors. In addition, higher rates of polysubstance use were found for individuals with features of BPD compared to those without. Higher rates of difficulties in emotion regulation were found to be associated with features of BPD and the presence of self-damaging behavior was found to partially mediate the relationship between the two constructs. Findings from this study have substantial implications for the conceptualization and treatment of self-damaging behavior in individuals with BPD. / Psychology

Bioassay-guided fractionation of the ethyl acetate extract of Virola sp. (Myristicaceae) using the Sc7 yeast strain resulted in the isolation of the weakly cytotoxic biochanin A (an isoflavone compound). The bioassay of three mutant yeast strains (1138, 1104, and 1353) directed the isolation of DNA-damaging alkaloids from Solanum hostmannii. These alkaloids were identified as verazine and (20R) epimer verazine. In addition, three oxoaporphine alkaloids were isolated from the bark of Papualthia sp. (Annonaceae). Oxocrebanine and atherospermidine showed DNA-damaging activity whereas liriodenine had cytotoxic activity. / Master of Science

Ce travail de thèse consiste à caractériser l’endommagement subi par une mèche de carbone au cours des procédés de transformation textile, et plus particulièrement au cours du tissage des préformes pour les matériaux composites. Un protocole de caractérisation mécanique sur mèche sèche, ainsi qu’une méthode non-destructive d’analyse d’images, ont été mis au point pour quantifier cet endommagement. / This aim of this work is to characterize the damage suffered by a carbon tow in textile processing methods, and more particularly during preforms weaving for composites materials. A mechanical characterization protocol on dry tow tensile test and a non-destructive method of image analysis, have been developed to quantify this damage.

Le système pelvien féminin est un système complexe jouant un rôle primordial dans la miction, la défécation et la reproduction. Il comprend de nombreux organes, muscles et ligaments tous interconnectés. Malheureusement le système pelvien peut subir de nombreuses pathologies l’une d’entre elle étant le prolapsus, ou la descente d’organe, se définissant comme déplacement anormal d’un ou plusieurs organes génitaux. Le prolapsus est une pathologie très répandue au sein de la population féminine. 1 femme sur 3 serait concernée, 1 sur 10 subissant un traitement chirurgical au cours de sa vie. Cette pathologie a d’importantes conséquences sur la qualité de vie des patientes. Son traitement se fait principalement par voie chirurgicale, mais de gros progrès doivent être faits dans ce domaine. En effet, les taux de récidive post-traitement peuvent atteindre des valeurs de 60% dans la littérature.Malgré la nécessité d’une amélioration des techniques chirurgicales celle-ci ne pourra avoir lieu sans une meilleure compréhension du comportement mécanique global de cette région très complexe et encore assez mal connue. Une connaissance approfondie de la mobilité du système pelvien sain par rapport au pathologique permettrait le développement de nouvelles techniques plus à même de soigner efficacement les patientes.Malgré de nombreuses études, un manque de compréhension mécanique est à noter. En effet très peu de données provenant de patientes jeunes et saines sont disponibles. De plus la plupart des tests réalisés sont des tests de tractions uniaxiales, qui sont par essence limités. Un manque cruel de relation entre les modèles phénoménologiques et cliniques est également à regretter.Dans ce travail nous avons donc réalisés des tests uniaxiaux sur différents tissus de cadavres jeunes (<40 ans). Cela nous a permis de prouver l’hyper-élasticité et la grande déformabilité des tissus pelviens jeunes et de mieux comprendre les phénomènes de vieillissement et d’endommagements de ces tissus en les comparants aux nombreuses données de la littérature. Nous avons ainsi pu monter que les ligaments et le vagin subissaient un vieillissement de nature différente à la vessie et au rectum. Ce vieillissement que nous avons nommé « traumatique » entraine un allongement et un raidissement non réversible des tissus à niveau en rien comparable à un vieillissement « naturel ».Notre étude mécanique s’est également élargie en testant les accolements entre organes (vésico-vaginal et recto-vaginal) en les soumettant à une contrainte de cisaillement. Ce genre de tests est, à notre connaissance, une première pour les tissus mous biologiques. Nous avons ainsi pu montrer que le comportement mécanique de ces accolements était linéaire pour les petites déformations et bien que de rigidité faible par rapport aux tissus eux même, tout de même à prendre en compte dans de prochains modèle.Suite à cette étude purement mécanique nous avons tenté de mettre nos modèles phénoménologiques, dur d’accès aux professionnels de la santé, en relation avec des modèles cliniques, histologiques dans ce cas précis. Nous avons donc réalisé un modèle histologiquement fondée du comportement mécanique des tissus pelviens, mettant en relation les taux d’élastine et de collagène d’un tissu à son comportement mécanique. A l’aide de ce modèle, inspiré de la physique des élastomères à plusieurs phases, nous avons pu corréler les taux d’élastine et de collagène d’un tissu à sa rigidité et ainsi rendre plus accessible un modèle complexe.Nous avons ensuite voulu faire le bilan de nos connaissances sur la compréhension des prolapsus et dans quelle mesure notre étude nous a permis de l’approfondir. Nous nous sommes évidemment concentrés sur les modes d’endommagements et leurs conséquences d’un point de vue mécanique et histologique. Dans un but de clarté nous avons traités d’exemples précis afin d’illustrer nos propos, comme le vieillissement, l’accouchement par voie basse ou la cystocèle. / The pelvic floor is a complex anatomical system involved in urination, defecation and reproduction. It is composed of several organs, muscles and ligaments, all interconnected. Unfortunately the pelvic floor can suffer from several pathologies like prolapses. Prolapses are defined as an abnormal displacement of one or more pelvic organs. Prolapses are widespread in the woman population. One woman out of three would be affected, one out of ten undergoing a surgical treatment in her life. This pathology has tremendous consequences on the patient quality of life. Its treatment is mainly surgical, but big improvements are needed. Indeed, the recurrence rate could reach up to 60% in the literature.The improvement of surgical technics will only be possible with a better global mechanical understanding of the pelvic floor. A deep understanding of the healthy pelvic floor mobility compared to the pathological would allow for the development of technics to better treat patients.Even though several studies have been done, a lack of mechanical understanding is to be noted. Indeed very few data coming from healthy young patients are available. Moreover most tests are uniaxial testing, which are by essence quite limited. A lack of relationship between phenomenological and clinical models is also to be noted.Within our study we have then realized uniaxial testing of different tissues from young cadavers (<40 years old). That allowed us to prove the hyper-elasticity and the great deformability of young pelvic tissues. It also helped us to better understand the ageing and damaging processes of those tissues by comparing them to data available in the literature. We could should that the ligaments and the vagina undergo a different ageing process than the rectum and the bladder. That ageing that we defined as “traumatic” induces much stronger non-reversible stretching and stiffening of the tissues than a “natural” ageing.Our mechanical study broadened up by looking at bindings between organs (vesico-vaginal and recto-vaginal). Those bindings have been, for the first time to our knowledge, under shear conditions. We could then show that those binding have a linear mechanical behavior for small displacements and that their stiffness even though limited should be taken into account in numerical models.Following that purely mechanical study we tried to accommodate our models to a public of medical professionals, by linking our phenomenological models to clinical ones, histological in that case. We then realized a histologically based model of the mechanical behavior of pelvic tissues, linking the rate of collagen and elastin of a tissue to its mechanical behavior. Thanks to that model, inspired by the physics of polymers we could correlate the collagen and elastin rates of a tissue to its rigidity and therefore make a complex model more accessible.We then gathered our knowledge on the understanding of prolapses and observed how our study could deepen it. We focused on the ageing and damaging processes and their consequences from a mechanical and histological point of view. To help the understanding we looked at precise examples like ageing, vaginal delivery or cystocele.