Lipid bilayers and lipid-associated proteins play crucial roles in biology. As in vivo studies and manipulation are inherently difficult, membrane-mimetic systems are useful for the investigation of lipidic phases, lipid–protein interactions, membrane protein function and membrane structure in vitro. This dissertation describes a route to leverage the programmability of DNA nanotechnology to create DNA-encircled bilayers (DEBs), a novel nano-scaled membrane-mimetic system. DEBs are made of multiple copies of an alkylated oligonucleotide hybridized to a single-stranded minicircle, in which up to two alkyl chains per helical turn point to the inside of the toroidal DNA ring. When phospholipids are added, a bilayer is observed to self-assemble within the ring such that the alkyl chains of the oligonucleotides stabilize the hydrophobic rim of the bilayer to prevent formation of vesicles and support thermotropic lipid phase transitions. This straight-forward and robust route enables the rational design of DEBs so that their size, shape or functionalization can be adapted to the specific needs of biophysical investigations of lipidic phases and the properties of membrane proteins. Next, we optimized the DEB system to provide proper anchoring of a large variety of lipids by creating an improved DNA scaffold. This scaffold, called DNA double-decker, consists of two interconnected DNA minicircles stacked on top of each other. In comparison to the DNA minicircle in DEB system, this scaffold is two times thicker and contains two times more hydrophobic strands, which should increase the stability of the lipid bilayer rim. Finally, we explored the option of using DEBs in studies of GPCRs using CCR5 as a model protein. The CCR5 was labeled with DNA strands, purified and characterized. The strands on CCR5 are complementary to the protruding strands on the DNA minicircle in DEBs. This can allow the reconstitution of GPCRs inside DEBs with controlled orientation of the receptor.

No description available.

Mixed association of calix[4]resorcinarene with ethyl sulfonate groups on the lower rim and dimethylaminomethyl groups on the upper rim (CR) and cationic surfactant 4-aza-1-hexadecyl-azoniabicyclo[2.2.2]octane bromide (DABCO-16) is studied by methods of tensiometry, conductometry, potentiometry and NMR spectroscopy at fixed CR concentration and varied surfactant concentration. Beyond ca. 0.4 mM of DABCO-16, mixed aggregates enriched by CR are proved to be formed due to electrostatic forces, while beyond ca. 5 mM, aggregates enriched by surfactant occur due to the hydrophobic effect. Spectrophotometry monitoring of the solubilization of a hydrophobic dye, Orange OT, demonstrated that only the second type of mixed aggregate enriched by DABCO-16 is capable of binding the organic probe, while the mixed system where the surfactant is a minor component shows no binding capacity towards Orange OT. This finding can be used for the design of nanocontainers with controllable binding/release properties. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Cette thèse présente une nouvelle classe de schémas de discrétisation spatiale sur maillages polyédriques, nommée Compatible Discrete Operator (CDO) et en étudie l'application aux équations elliptiques et de Stokes. La préservation au niveau discret des caractéristiques essentielles du système continu sert de fil conducteur à la construction des opérateurs. Les opérateurs de de Rham définissent les degrés de liberté en accord avec la nature physique des champs à discrétiser. Les équations sont décomposées de manière à différencier les relations topologiques (lois de conservation) des relations constitutives (lois de fermeture).Les relations topologiques sont associées à des opérateurs différentiels discrets et les relations constitutives à des opérateurs de Hodge discrets. Une particularité de l'approche CDO est l'utilisation explicite d'un second maillage, dit dual, pour bâtir l'opérateur de Hodge discret. Deux familles de schémas CDO sont ainsi considérées : les schémas vertex-based lorsque le potentiel est discrétisé aux sommets du maillage (primal), et les schémas cell-based lorsque le potentiel est discrétisé aux sommets du maillage dual (les sommets duaux étant en bijection avec les cellules primales).Les schémas CDO associés à ces deux familles sont présentés et leur convergence est analysée. Une première analyse s'appuie sur une définition algébrique de l'opérateur de Hodge discret et permet d'identifier trois propriétés clés : symétrie, stabilité et $mathbb{P}_0$-consistance. Une seconde analyse s'appuie sur une définition de l'opérateur de Hodge discret à l'aide d'opérateurs de reconstruction pour lesquels sont identifiées les propriétés à satisfaire. Par ailleurs, les schémas CDO fournissent une vision unifiée d'une large gamme de schémas de la littérature (éléments finis, volumes finis, schémas mimétiques…).Enfin, la validité et l'efficacité de l'approche CDO sont illustrées sur divers cas tests et plusieurs maillages polyédriques / This thesis presents a new class of spatial discretization schemes on polyhedral meshes, called Compatible Discrete Operator (CDO) schemes and their application to elliptic and Stokes equations. In CDO schemes, preserving the structural properties of the continuous equations is the leading principle to design the discrete operators. De Rham maps define the degrees of freedom according to the physical nature of fields to discretize. CDO schemes operate a clear separation between topological relations (balance equations) and constitutive relations (closure laws).Topological relations are related to discrete differential operators, and constitutive relations to discrete Hodge operators. A feature of CDO schemes is the explicit use of a second mesh, called dual mesh, to build the discrete Hodge operator. Two families of CDO schemes are considered: vertex-based schemes where the potential is located at (primal) mesh vertices, and cell-based schemes where the potential is located at dual mesh vertices (dual vertices being in one-to-one correspondence with primal cells).The CDO schemes related to these two families are presented and their convergence is analyzed. A first analysis hinges on an algebraic definition of the discrete Hodge operator and allows one to identify three key properties: symmetry, stability, and $mathbb{P}_0$-consistency. A second analysis hinges on a definition of the discrete Hodge operator using reconstruction operators, and the requirements on these reconstruction operators are identified. In addition, CDO schemes provide a unified vision on a broad class of schemes proposed in the literature (finite element, finite element, mimetic schemes...).Finally, the reliability and the efficiency of CDO schemes are assessed on various test cases and several polyhedral meshes

O presente estudo intenciona, fundamentalmente, mostrar que a produção ficcional de Camilo Castelo Branco constitui-se enquanto um legado romanesco que ultrapassa, em muito, a mera veiculação de histórias de amor. Assim sendo, alguns aspectos e temas caros à literatura do escritor de São Miguel de Seide são tomados como pilares desta análise, tais como a presença de um Portugal imerso em relações capitalistas, próprias do período oitocentista; um ambiente propício para o interesse financeiro e o desejo de base mimética, mas infecundo a afeições abnegadas; e a marcante atuação do narrador camiliano, uma instância que não se priva de desvelar, a todo o momento, os motores vis que, consoante sua opinião, impulsionam tanto a engrenagem desta materialista sociedade portuguesa quanto as atitudes das personagens que nela estão inseridas. Por fim, vale ressaltar que o corpus selecionado para esta apreciação da obra camiliana é composto pelos romances Onde está a Felicidade? e Um Homem de Brios, ambos de 1856. / The present study intends, primarily, to show that Camilo Castelo Brancos fictional production consists in a Romanesque legacy that passes much beyond the mere transmission of love stories. Thus, some important aspects and themes of the writer of São Miguel de Seides literature are taken as pillars of this analysis, such as the presence of a Portugal immersed in capitalist relations, typical of the 19th century, a proper ambience to the financial interest and the desire of mimetic basis, but barren to unselfish affections, and the camilian narrators remarkable performance, an instance that not abstains from unveiling, every time, the vile engines that, according to his opinion, stimulate as much the gear of this materialist Portuguese society as the characters attitudes inserted in it. Finally, it is pertinent to emphasize that the selected corpus for this camilian works appreciation is composed by the novels Onde está a Felicidade? and Um Homem de Brios, both from 1856.

Ce travail de thèse se présente comme une relecture du conflit israélo-arabe depuis ses origines (Palestine ottomane) à travers une analyse des transformations militaires mises en oeuvre par les acteurs, parties au conflit. Ces transformations sont motivées par des effets de rivalités mimétiques. Au fil des affrontements, chaque adversaire adapte son système de défense en fonction de celui de son ennemi et inversement. Ainsi, sur le temps long du conflit on peut repérer des formes de continuité entre les différents acteurs armés en dépit des différences idéologiques et des circonstances historico-politiques. Ces transformations, parce qu’elles visent le plus souvent à re-symétriser le différentiel de puissance avec l’adversaire, privilégient les stratégies alternatives ou dissymétriques. Elles impliquent des innovations qui touchent l’ensemble de la société, suggérant l’existence de mécanismes guerriers travaillant les sociétés dans la guerre et pour la guerre. De ces mécanismes découle le caractère hautement polémique des sociétés de la région et la survivance en leur sein de différentes formes de combattants irréguliers. A partir de ces formes on peut proposer une typologie des figures contemporaines du partisan, de l’Etat islamique aux groupes armés palestiniens et libanais, en passant par la question de la violence des colons religieux-nationalistes des Territoires occupés. Cette pluralité de figures de la guerre du partisan moderne fournit des clés pour analyser les évolutions des formes de violence dans la région (crises en chaîne, délitement des Etats-nations, soulèvements révolutionnaires, etc.). / This thesis consists in a re-reading of the Arab-Israeli conflict since its origins (in the Ottoman Palestine) through an analysis of the military transformations conducted by actors involved in this conflict. These changes are driven by mimetic rivalries processes. Over the clashes, each opponent adapts its defense system according to his enemy’s one and vice versa. Thus, forms of continuity between the different armed groups are perceptible on the long-time conflict in spite of the ideological differences and historical-political circumstances. These Transformations favor alternative or di-symmetrical strategies, because they aim mostly to symmetrically re-balance the differential of power with the opponent. They involve innovations impacting the whole society, suggesting the existence of war mechanisms which affect societies for and through the war. The highly polemic nature of the region’s societies ensues from these mechanisms as well as the survival of different forms of irregular combatants within them. Based on these forms, it could be proposed a typology of the partisan’s contemporary figures, including the Islamic State, the Palestinian and Lebanese armed groups, as well as the issue of the religious-nationalist settlers’ violence in the Palestinian Occupied Territories. This plurality of the modern partisan warfare patterns provides tools for analyzing the evolutions of violence forms in the region (chain crisis, disintegration of nation states, revolutionary uprisings, etc.).

O presente estudo intenciona, fundamentalmente, mostrar que a produção ficcional de Camilo Castelo Branco constitui-se enquanto um legado romanesco que ultrapassa, em muito, a mera veiculação de histórias de amor. Assim sendo, alguns aspectos e temas caros à literatura do escritor de São Miguel de Seide são tomados como pilares desta análise, tais como a presença de um Portugal imerso em relações capitalistas, próprias do período oitocentista; um ambiente propício para o interesse financeiro e o desejo de base mimética, mas infecundo a afeições abnegadas; e a marcante atuação do narrador camiliano, uma instância que não se priva de desvelar, a todo o momento, os motores vis que, consoante sua opinião, impulsionam tanto a engrenagem desta materialista sociedade portuguesa quanto as atitudes das personagens que nela estão inseridas. Por fim, vale ressaltar que o corpus selecionado para esta apreciação da obra camiliana é composto pelos romances Onde está a Felicidade? e Um Homem de Brios, ambos de 1856. / The present study intends, primarily, to show that Camilo Castelo Brancos fictional production consists in a Romanesque legacy that passes much beyond the mere transmission of love stories. Thus, some important aspects and themes of the writer of São Miguel de Seides literature are taken as pillars of this analysis, such as the presence of a Portugal immersed in capitalist relations, typical of the 19th century, a proper ambience to the financial interest and the desire of mimetic basis, but barren to unselfish affections, and the camilian narrators remarkable performance, an instance that not abstains from unveiling, every time, the vile engines that, according to his opinion, stimulate as much the gear of this materialist Portuguese society as the characters attitudes inserted in it. Finally, it is pertinent to emphasize that the selected corpus for this camilian works appreciation is composed by the novels Onde está a Felicidade? and Um Homem de Brios, both from 1856.

La ménopause est un facteur de risques associé au développement des maladies métaboliques. Du fait de ce déficit hormonal, les femmes ménopausées pourraient présenter des risques particuliers une fois exposées à des agents chimiques capables de perturber le système endocrinien. Pour en savoir plus, nous avons mis au point un modèle de souris ovariectomisées supplémentées ou non en œstradiol (E2), et exposées de manière chronique à un mélange de polluants (TCDD, PCB153, DEHP et BPA) ajoutés à une alimentation obésogène. Chaque polluant est utilisé à une dose équivalente à la Dose Journalière Tolérable, et l’exposition recouvre différents stades de développement, incluant ou non la période maternelle (gestation + lactation). Nos résultats indiquent qu’en condition d’obésité induite par le régime, l’ovariectomie accentue la prise de poids, l’intolérance au glucose et l’insulino-résistance chez les souris femelles adultes. Ce phénotype est associé à une diminution de la signalisation œstrogénique dans le foie et une dérégulation de l’adipogenèse et de l’inflammation dans le tissu adipeux. De manière intéressante, le mélange de polluants réduit l’impact délétère de l’ovariectomie sur le phénotype métabolique, possiblement par une amélioration de la signalisation œstrogénique dans le foie et le tissu adipeux. Nos résultats suggèrent fortement que ces effets dépendent d’une exposition maternelle. En conclusion, nous montrons que notre mélange de polluants possède une activité œstrogéno-mimétique. Ceci pourrait avoir une implication dans la compréhension du rôle des polluants environnementaux dans le développement des maladies métaboliques chez la femme en transition ménopausique / Menopause is a risk factor associated with the development of metabolic diseases. Because of estrogen deficiency, postmenopausal women may be at particular risk when exposed to chemical agents that can disrupt the endocrine system. To get more insight, we have developed a model of ovariectomized mice supplemented or not with estradiol (E2), and chronically exposed to a mixture of pollutants (TCDD, PCB153, DEHP and BPA) added to an obesogenic diet. Each pollutant was used at a dose close to the Tolerable Daily Intake dose, and the exposure had covered different stages of development, including or not the maternal period (gestation + lactation). Our results indicate that in diet-induced obesity, ovariectomy triggered weight gain, increase glucose intolerance and insulin resistance. This phenotype was associated with decreased estrogenic signaling in liver and deregulation of adipogenesis and inflammation in adipose tissues. Interestingly, the mixture of pollutants reduced the deleterious impact of ovariectomy on the metabolic phenotype, possibly through an alleviation of estrogenic signaling in both liver and adipose tissues. These data were not reproduced in mice not exposed to pollutants during the maternal life. In conclusion, the mixture of pollutants displayed some estrogeno-mimetic activity. This could have implications in understanding the role of environmental pollutants in the development of metabolic diseases in women in menopausal transition.

We connect the Mimetic Finite Difference method (MFD) with the finite-volume two-point flux scheme (TPFA) for Voronoi meshes. The main effect is reducing the saddle-point system to a much smaller symmetric-positive definite matrix. In addition, the generalization allows MFD to seamlessly integrate with existing porous media modeling technology. The generalization also imparts the monotonicity property of the TPFA method on MFD. The connection is achieved by altering the consistency condition of the velocity bilinear operator. First-order convergence theory is presented as well as numerical results that support the claims. We demonstrate a methodology for using MFD in modeling fluid flow in fractures coupled with a reservoir. The method can be used for nonplanar fractures. We use the method to demonstrate the effects of fracture curvature on single-phase and multi-phase flows. Standard benchmarks are used to demonstrate the accuracy of the method. The approach is coupled with existing reservoir simulation technology. / text

This essay investigates the feminist philosophy of Rosi Braidotti with particular focus on the alternative feminine feminist nomadic subject that she creates. I also introduce Braidotti’s theoretical inspiration from Gilles Deleuze and Luce Irigaray. I argue that Braidotti creates an alternative figuration for feminism through synthesizeing Deleuze’s concept of ”becoming” with Irigaray’s sexual difference-theory. Braidotti highlights the importance of understanding the concept of difference differently. She also argues for the difference between subjectivity and identity, for the materialistic foundation of the subject, for the fundamental asymmetry between the sexes and for the nomadic mode of thinking. Braidottis suggests that the way out of the phallogocentric system, which she means we are encapsulated in, consist in working through the images that patriarchy has produced of women, through mimetic repetitons, in order to create new representations of women. I argue that the feminist philosophy of Braidotti is both humble and subversive which makes it an interesting and useful alternative for everyone who is interested in alternative, complex and thrilling ways of theorizing female feminist subjectivity.