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Influence des liserés de carbures induits par la nitruration gazeuse sur les mécanismes de fissuration de fatigue de contacts roulants / Effect of intergranular carbides induced by gas-nitriding on rolling contact fatigueLe, Marion 17 November 2015 (has links)
La nitruration gazeuse est utilisée par les fabricants d’engrenages pour traiter la surface des dentures. En effet, l’augmentation de la dureté et l’introduction de contraintes résiduelles de compression contribuent à retarder voire inhiber l’initiation et la propagation des fissures superficielles de fatigue de contact. Cependant la majorité des aciers alliés présentent des réseaux de précipités de carbures dans la couche nitrurée. Ceux-ci ont la particularité de se retrouver aux joints de grains relativement parallèles à la surface, ce qui leurs ont attribué les surnoms de «liserés de carbures». Associés à une phase dure et fragile, ces carbures constituent des zones d’hétérogénéités. Par ailleurs, la norme pour la qualité des matériaux d’engrenages autorise une large gamme de tailles de grains, conduisant à diverses microstructures pour les couches nitrurées des aciers alliés. En effet, la morphologie des réseaux de carbures après nitruration dépend entre autres de la taille de grain de l’acier. De par le manque de travaux sur l’impact réel de ces précipités sur la fatigue de contact, la présente étude propose des analyses d’essais. Les essais consistent à reproduire de l’écaillage initié en surface sur des éprouvettes dont les couches nitrurées, issues d’un seul traitement thermochimique, présentent les mêmes propriétés mécaniques (dureté et contraintes résiduelles) mais différentes propriétés microstructurales (tailles de grains et morphologies de carbures). Les analyses ont permis de proposer des mécanismes d’initiation de micro-fissures induites en proche surface sous les conditions d’essai appliquées. Les sites d’initiation dépendent de la taille de grain de l’acier et peuvent en particulier s’établir au niveau des carbures intergranulaires. L’étude des réseaux de fissures couplée à l’analyse des contraintes résiduelles a permis d’établir des scénarii de propagation des fissures dans les couches nitrurées. Sous les conditions de contact appliquées, l’apparition de déformation plastique entraîne, par accommodation des variations de volume, la relaxation des contraintes résiduelles compressives initialement présentes dans le matériau, aux profondeurs les moins sollicitées. Ces contraintes étant moins compressives, elles libèrent les micro-fissures déjà présentes en proche surface. Dès lors, la propagation au travers des carbures qui s’apparentent à des sites privilégiés pour la croissance des fissures en cours de fatigue est possible. En particulier, ces précipités entraînent les fissures vers le cœur lorsqu’ils sont en forte densité dans les couches nitrurées, tandis que l’endommagement reste superficiel lorsque l’éloignement entre les précipités est trop important. Enfin, la continuité et la longueur des carbures augmentent localement la vitesse de propagation des fissures. Ceci se traduit par l’apparition plus rapide de l’écaillage initié en surface pour les couches nitrurées de microstructures grossières. / Gas nitriding is a thermochemical surface treatment widely used by gear manufacturers to improve the rolling contact fatigue endurance of their components. Indeed, increasing the hardness and introducing compressive residual stresses to the geartooth surfaces inhibit or delay crack initiation and propagation. However, most of the alloyed steel nitrided layers show the presence of intergranular carbide networks. The precipitation of these carbides specifically occurs at parallel grain boundaries during the treatment and, being a carbon-rich phase, they are associated to tough and fragile heterogeneities. Besides, standards for gear material quality recommend a broad range of steel grain sizes which lead to various possible microstructures on gear components after nitriding. Indeed, the intergranular carbide network morphology depends on the steel grain size. Since there is no evidence regarding the real effect of the carbides on rolling contact fatigue, this work presents experimental investigations carried out on a twin-disc machine. The tests consist in reproducing surface-initiated pitting on specimens whose nitrided layers, obtained by a unique thermochemical surface treatment, display similar mechanical properties (hardness and compressive residual stresses) but different microstructures (grain sizes and carbide network morphologies). The first analysis resulted in suggesting the micro-crack nucleation mechanisms. In this study, the test conditions were chosen to induce these micro-cracks near the disc surfaces. For a given contact stress field, nucleation sites depend on the steel grain size and can take place at intergranular carbides. Investigations of crack networks led on cross sections and 3D observations by means of high energy X-ray computed tomography, coupled with compressive residual stress evolution analysis, help the authors proposing the rolling contact fatigue crack propagation scenarios in nitrided layers. When contact shear stresses locally exceed the material micro-yield shear stress limit, micro-deformations arise and add compressive residual stresses to the treated layers. To accommodate these volume variations the compressive residual stresses, initially induced by nitriding, release at depths where contact stresses are lower. The pre-existing residual stresses being less compressive, micro-cracks near the surface can propagate through the carbides that act as preferential crack growth sites. When the nitrided layers display high carbide density, the intergranular precipitates drag the cracks toward the core, whereas rolling contact fatigue failures are limited to the near surface when the distance between the precipitates is too important. Finally, the length and the continuity of the carbides, linked to the steel grain size, locally increase the crack propagation speed. This gives rise to a lower endurance to surface-initiated pitting in coarse microstructures.
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Estudo dos grânulos de lipofucsina e das sinapses do córtex temporal durante o envelhecimento / Study of lipofuscin granules and synapses in the temporal cortex during aging.Suélen Merlo 14 April 2011 (has links)
Alterações morfológicas e funcionais ocorrem durante o envelhecimento, período da vida com maior incidência de doenças neurodegenerativas. No presente trabalho acompanhou-se a evolução dos grânulos de lipofucsina durante o envelhecimento para investigar alterações sinápticas, assim como proteínas associadas com doenças neurodegenerativas (alfa-sinucleína) e com o sistema ubiquitina-proteossoma em indivíduos de diferentes idades. No córtex temporal humano e de ratos determinou-se, nos diferentes grupos etários, seguindo a área, o número e as características dos grânulos de lipofucsina, o número de sinapses excitatórias, inibitórias e elétricas, os locais de contatos pós-sinápticos, o número de vesículas sinápticas por terminal e a expressão das proteínas alfa-sinucleína e ubiquitina. Amostras de córtex temporal humano de indivíduos com diferentes idades (20 - 28, 37 - 41 e 50 - 55 anos) foram coletadas de pacientes com epilepsia submetidos à lobectomia do lobo temporal. Amostras de ratos de 2, 6, 10 e 12 meses também foram coletadas. Foram utilizadas técnicas de microscopia de luz, eletrônica, confocal e western blots. Os dados obtidos de grânulos de lipofucsina são consistentes com outros estudos que observaram aumento dessa estrutura em mamíferos de maior idade. No entanto, os grânulos parecem crescer em volume, mas não em número, com aumento considerável da fração elétron lúcida (lipídica). Não houve diferença na expressão das proteínas alfa-sinucleína e ubiquitina entre os grupos das idades estudadas. A densidade sináptica foi similar entre os grupos experimentais, assim como o local de contato pós-sináptico. O aumento de vesículas elétron densas em sinapses inibitórias deve estar associado à demanda de neurotransmissores catecolaminérgicos. Estes resultados não expressam totalmente o processo de envelhecimento, pois as faixas etárias de humanos e ratos correspondem a uma idade ainda jovem. A coleta de material humano mais idoso foi impossibilitada pela faixa etária dos doentes submetidos à lobectomia. Os ratos do biotério da FMRP, não sobrevivem mais do que 12 meses em no nosso ambiente, incluindo manutenção dos animais isolados em racks. / Morphological and functional changes occur during the aging, period of life with increased incidence of neurodegenerative diseases. Following the evolution of the lipofuscin granules along three periods of life in humans and rats, the present work investigated synaptic changes, as well as proteins associated with neurodegenerative diseases (alpha-synuclein) and the ubiquitin-proteossoma system in individuals of different ages. The objectives of the study were to analyze the temporal cortex of humans and rats: the number of excitatory, inhibitory, and electric synapses, the site of postsynaptic contacts, the number of synaptic vesicles per terminal, and the expression of the proteins alpha-synuclein and ubiquitin following the size and features of the lipofuscin granules. Samples of temporal cortex of human subjects with different ages (20-28, 37-41 and 50-55 years) were collected from patients with epilepsy who underwent temporal lobectomy. Samples from rats of 2, 6, 10 and 12 months were also collected. Light, confocal, and electron microscopy, and western blots techniques were used as procedures. The data obtained on lipofuscin granules were coincident with other studies that observed a higher area occupied by this structure in older mammals. However, the granules seem to grow in volume, but not in number, with considerable increase of the electron lucid fraction (lipidic). There was no difference in the alpha-synuclein and ubiquitin expressions between the experimental groups. The synaptic densities were similar between the groups, as well as the postsynaptic contacts. Increase of the electron dense vesicles in inhibitory synapses, appeared to be associated with the demand of catecholamines. These results do not express totally the aging process, because the range of age used in humans, and rats belong to a young age. The human samples from older ages was difficult because, in general, of the age of the patients submitted to lobotomy. The rats of the FMRP bioterium do not survived more that 12 months in our environment, even in controlled conditions.
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Modélisation du contact entre matériaux hétérogènes : Application au contact Aube/Disque. / Modeling of the contact between heteregeneous materials : Application to blade/disc contactKoumi, Koffi Espoir 04 December 2015 (has links)
Cette thèse s'intéresse à la problématique du contact entre matériaux hétérogènes. L'industrie (automobile, aéronautique, spatiale, ...) s'intéresse de plus en plus à ces types de matériaux. Il s'agira par exemple des alliages métalliques, des matériaux poreux, matériaux composites (composites tissés, interlocks 3D, interlocks 2D), des billes céramiques contenant des impuretés (porosités/précipités),... Dans ce manuscrit, un modèle de contact basé sur les méthodes semi-analytiques a été développé. Un algorithme de gradient conjugué est utilisé afin de résoudre rapidement le problème de contact. Le modèle permet de prendre en compte la présence d'une ou de plusieurs hétérogénéités isotropes/anisotropes dans le problème de contact. Une approche inspirée de la méthode de l'inclusion équivalente proposée par Eshelby est utilisée dans le solveur de contact pour prendre en compte l'effet de ces hétérogénéités. Les méthodes de transformées de Fourier rapides (FFT) permettent d'accélérer les calculs. Une méthode numérique a été mise en œuvre afin de prendre en compte l'interaction entre plusieurs hétérogénéités. Le massif peut être élastique ou viscoélastique. L'approche développée dans la thèse peut résoudre à la fois les problèmes d'indentation, de roulement/glissement ou de fretting en présence de matériaux élastiques hétérogènes, viscoélastiques homogènes ou hétérogènes. Les solutions sont données en termes de champs de pressions, de cisaillements et de contraintes. Dans le cas des matériaux viscoélastiques le code de calcul est capable de fournir le coefficient de frottement apparent ainsi que toutes les variables de contact aussi bien en régime permanent que transitoire. Le modèle a été validé par comparaison avec la méthode des éléments finis classiques en utilisant le logiciel commercial Abaqus v6.11. Le temps de calcul ainsi que l'espace mémoire nécessaire sont considérablement réduits par rapport à la méthode éléments finis. La parallélisation a été introduite dans le code de contact afin de réduire toujours plus le temps de calcul. Il s'agit d'un code robuste, rapide et facilement utilisable en Bureau d'Etudes. Une approche expérimentale originale a été mise en place afin de mesurer les champs de déplacements à l'interface des corps en contact. De bonnes corrélations essais/calculs ont été obtenues. Enfin quelques applications industrielles ont été présentées. Un couplage entre un code éléments finis structurel et le code semi-analytique de résolution de contact a été également réalisé. / The present PhD thesis deals with contact problems between heterogeneous materials. Nowadays heterogeneous materials are extensively used in several industrial domains (automotive, aeronautics, aerospace, ...). Heterogeneous materials involve porous materials, aluminum alloys, composites materials (woven composites, interlocks 3D, interlocks 2D), metallic or ceramics materials containing impurities (porosities/precipitates). In this work, a contact model based on semi-analytical method is proposed. A conjugate gradient algorithm is used for a fast resolution of contact equations. The model can account for one or more isotropic/anisotropic inhomogeneities. An approach taking inspiration from the Eshelby equivalent inclusion method is used in the contact solver to account for the effect of inhomogeneities. 2D and 3D Fast Fourier Transforms (FFT) are used to speed up the computation. A numerical method is implemented in order to take into account interactions between many heterogeneities. The semi-infinite space/ matrix can be either elastic or visco-elastic. The model developed in the present PhD thesis can solve indentation, rolling/sliding or fretting contact problems between heterogeneous elastic materials, homogeneous or heterogeneous visco-elactic materials. In the case of visco-elastic materials, the model permits to get the solution in terms of contact pressure distribution, subsurface stresses, apparent friction coefficient, both in the transient and then steady-state regimes. The model has been validated by performing a comparison with the results of a finite element model. The CPU time and memory necessary are greatly reduced in comparison with the classical finite element method. The model developed is fast, robust and extremely easy to use. An original experimental approach was proposed in order to measure the displacement fields at interface of two contacting bodies. A good agreement between experimental results and numerical simulations is obtained. Finally, the model is applied on some industrial applications. A coupling between a finite element model and the semi-analytical code allow to take into account the effects of structure on contact problem.
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Edmondo De Amicis et la France (1870-1883) : contacts et échanges entre littérature italienne et littérature française à la fin du XIXe siècle / De Amicis and France (1870-1883) : contact and interaction between Italian and French literature at the end of the nineteenth centuryBrambilla, Alberto 13 May 2011 (has links)
Le travail s’insère dans la vaste perspective des études sur les rapports entre la culture italienne et la culture française dans la seconde moitié du XIX siècle. En particulier nous avons pris en examen la période 1870-1883, c’est-à-dire les années de la conclusion de la guerre franco-prussienne, jusqu’à la crise diplomatique de Tunis (1881) et au passage de l’Italie à l’alliance politique et militaire avec l’Autriche et l’Allemagne. (1886). Dans la vaste production littéraire de De Amicis (connu presque seulement pour la publication de son roman Cuore), la France joue un rôle non secondaire, comme le témoignent le volume Ricordi di Parigi (1879) et le recueil Ritratti letterari (1881). Le but de notre recherche a été d’abord l’analyse approfondie de ces deux livres. Ensuite nous avons fait une enquête systématique sur l’ensemble de la production de De Amicis – en examinant pour la première fois plusieurs périodiques littéraires et politiques – où nous avons retrouvé beaucoup d’autres témoignages importants. En outre, grâce à l’étude de la biographie de De Amicis, nous avons reconstruit ses voyages et ses séjours en France (1873, 1878, 1880), et nous avons retrouvé le nom d’autres intellectuels français, avec lesquels De Amicis a établi des liens d’amitié et de collaboration. Enfin, à travers l’analyse de la correspondance privée de certains protagonistes de cet échange, nous avons acquis d’autres données. Nous avons ainsi mis à jour de nombreux témoignages de la remarquable réception en France des œuvres de De Amicis. Il a été beaucoup traduit en France et la critique française l’a considéré dès sa première œuvre (La vita militare, 1868) comme un des écrivains les plus importants d’Europe. Le bilan final de nos recherches confère à De Amicis un rôle très important dans les rapports entre la France et l’Italie, aussi bien au niveau culturel que politique / My research makes a contribution to the study of relations between Italy and France in the second half of the nineteenth century. Specifically, it deals with the crucial period which extends from the Franco-Prussian War to the adherence of Italy to the Triple Alliance (with Austria and Prussia) which came in response to the French occupation of Tunisia. It is within this context that the emergence of the Italian author Edmondo De Amicis (1846-1908) is to be understood. De Amicis dedicated two of his works to France, Ricordi di Parigi (1879) and Ritratti Letterari (1881), in which can be found portraits of a number of well-known French authors such as Alphonse Daudet, Emile Zola, Emile Augier and Alexandre Dumas fils. The systematic study of De Amicis’ biography and the retrieval of many authoritative sources have greatly contributed to current knowledge on De Amicis’ relationship with France. The existing sources have now been greatly enriched by a considerable number of unpublished journalistic writings and personal letters. In addition, information has been collected with regard to the French reception of De Amicis’ works, many of which came to be highly appreciated in translation. Thus, the picture which emerges is that of an intellectual of European standing, committed to the divulgation of the literary innovations of French naturalisme and, above all, to defending the values of freedom championed by the French Revolution.
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Semi-analytical modeling of damage under contact loading : Application to heterogeneous materials / Modélisation semi-analytique des dommages sous charge de contact : Application aux matériaux hétérogènesBeyer, Thibault 28 June 2019 (has links)
Les pieds d’aubes de soufflantes de turboréacteurs étant soumis à des sollicitations de type fretting, l’introduction de matériaux composites dans la nouvelle génération de moteur d’avion a rendu nécessaire le développement d’outils permettant de modéliser le contact entre des matériaux hétérogènes. En particulier, le comportement tribologique et l’endommagement de ces matériaux est encore mal compris. La mise en place de méthodes numériques capable de prédire les endommagements dans le contact permettrait de mieux prédire la durée de vie des pièces en service et de garantir la sécurité des passagers. Cette thèse porte sur le développement de méthodes semi-analytiques pour la modélisation de l’endommagement dans des conditions de fretting et de roulement. / The blade/disk interface in turbofan is subject to fretting loading. Fan blade of the new generation of aircraft engines are made of woven composite materials. The introduction of these new kind of materials create the need for a new numerical tool able to simulate the contact between heterogeneous materials. The tribological behavior and the damage mechanism associated with these kind of material are still not well understood. The developpment of new numerical tool able to model the damage in the contact area would allow to predict the life of engines parts and to guarantee the security of passengers. This PhD is about the developpment of semi-analytical methods for modeling the damage in fretting and rolling contact conditions with some applications to heterogeneous materials.
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Protein-protein interactions: impact of solvent and effects of fluorinationSamsonov, Sergey 16 November 2009 (has links)
Proteins have an indispensable role in the cell. They carry out a wide variety of structural, catalytic and signaling functions in all known biological systems. To perform their biological functions, proteins establish interactions with other bioorganic molecules including other proteins. Therefore, protein-protein interactions is one of the central topics in molecular biology. My thesis is devoted to three different topics in the field of protein-protein interactions. The first one focuses on solvent contribution to protein interfaces as it is an important component of protein complexes. The second topic discloses the structural and functional potential of fluorine's unique properties, which are attractive for protein design and engineering not feasible within the scope of canonical amino acids. The last part of this thesis is a study of the impact of charged amino acid residues within the hydrophobic interface of a coiled-coil system, which is one of the well-established model systems for protein-protein interactions studies.
I. The majority of proteins interact in vivo in solution, thus studies of solvent impact on protein-protein interactions could be crucial for understanding many processes in the cell. However, though solvent is known to be very important for protein-protein interactions in terms of structure, dynamics and energetics, its effects are often disregarded in computational studies because a detailed solvent description requires complex and computationally demanding approaches. As a consequence, many protein residues, which establish water-mediated interactions, are neither considered in an interface definition. In the previous work carried out in our group the protein interfaces database (SCOWLP) has been developed. This database takes into account interfacial solvent and based on this classifies all interfacial protein residues of the PDB into three classes based on their interacting properties: dry (direct interaction), dual (direct and water-mediated interactions), and wet spots (residues interacting only through one water molecule). To define an interaction SCOWLP considers a donor–acceptor distance for hydrogen bonds of 3.2 Å, for salt bridges of 4 Å, and for van der Waals contacts the sum of the van der Waals radii of the interacting atoms. In previous studies of the group, statistical analysis of a non-redundant protein structure dataset showed that 40.1% of the interfacial residues participate in water-mediated interactions, and that 14.5% of the total residues in interfaces are wet spots. Moreover, wet spots have been shown to display similar characteristics to residues contacting water molecules in cores or cavities of proteins.
The goals of this part of the thesis were:
1. to characterize the impact of solvent in protein-protein interactions
2. to elucidate possible effects of solvent inclusion into the correlated mutations approach for protein contacts prediction
To study solvent impact on protein interfaces a molecular dynamics (MD) approach has been used. This part of the work is elaborated in section 2.1 of this thesis. We have characterized properties of water-mediated protein interactions at residue and solvent level. For this purpose, an MD analysis of 17 representative complexes from SH3 and immunoglobulin protein families has been performed. We have shown that the interfacial residues interacting through a single water molecule (wet spots) are energetically and dynamically very similar to other interfacial residues. At the same time, water molecules mediating protein interactions have been found to be significantly less mobile than surface solvent in terms of residence time. Calculated free energies indicate that these water molecules should significantly affect formation and stability of a protein-protein complex. The results obtained in this part of the work also suggest that water molecules in protein interfaces contribute to the conservation of protein interactions by allowing more sequence variability in the interacting partners, which has important implications for the use of the correlated mutations concept in protein interactions studies. This concept is based on the assumption that interacting protein residues co-evolve, so that a mutation in one of the interacting counterparts is compensated by a mutation in the other. The study presented in section 2.2 has been carried out to prove that an explicit introduction of solvent into the correlated mutations concept indeed yields qualitative improvement of existing approaches. For this, we have used the data on interfacial solvent obtained from the SCOWLP database (the whole PDB) to construct a “wet” similarity matrix. This matrix has been used for prediction of protein contacts together with a well-established “dry” matrix. We have analyzed two datasets containing 50 domains and 10 domain pairs, and have compared the results obtained by using several combinations of both “dry” and “wet” matrices. We have found that for predictions for both intra- and interdomain contacts the introduction of a combination of a “dry” and a “wet” similarity matrix improves the predictions in comparison to the “dry” one alone. Our analysis opens up the idea that the consideration of water may have an impact on the improvement of the contact predictions obtained by correlated mutations approaches. There are two principally novel aspects in this study in the context of the used correlated mutations methodology :
i) the first introduction of solvent explicitly into the correlated mutations approach; ii) the use of the definition of protein-protein interfaces, which is essentially different from many other works in the field because of taking into account physico-chemical properties of amino acids and not being exclusively based on distance cut-offs.
II. The second part of the thesis is focused on properties of fluorinated amino acids in protein environments. In general, non-canonical amino acids with newly designed side-chain functionalities are powerful tools that can be used to improve structural, catalytic, kinetic and thermodynamic properties of peptides and proteins, which otherwise are not feasible within the use of canonical amino acids. In this context fluorinated amino acids have increasingly gained in importance in protein chemistry because of fluorine's unique properties: high electronegativity and a small atomic size. Despite the wide use of fluorine in drug design, properties of fluorine in protein environments have not been yet extensively studied. The aims of this part of the dissertation were:
1. to analyze the basic properties of fluorinated amino acids such as electrostatic and geometric characteristics, hydrogen bonding abilities, hydration properties and conformational preferences (section 3.1)
2. to describe the behavior of fluorinated amino acids in systems emulating protein environments (section 3.2, section 3.3)
First, to characterize fluorinated amino acids side chains we have used fluorinated ethane derivatives as their simplified models and applied a quantum mechanics approach. Properties such as charge distribution, dipole moments, volumes and size of the fluoromethylated groups within the model have been characterized. Hydrogen bonding properties of these groups have been compared with the groups typically presented in natural protein environments. We have shown that hydrogen and fluorine atoms within these fluoromethylated groups are weak hydrogen bond donors and acceptors. Nevertheless they should not be disregarded for applications in protein engineering. Then, we have implemented four fluorinated L-amino acids for the AMBER force field and characterized their conformational and hydration properties at the MD level. We have found that hydrophobicity of fluorinated side chains grows with the number of fluorine atoms and could be explained in terms of high electronegativity of fluorine atoms and spacial demand of fluorinated side-chains. These data on hydration agrees with the results obtained in the experimental work performed by our collaborators.
We have rationally engineered systems that allow us to study fluorine properties and extract results that could be extrapolated to proteins. For this, we have emulated protein environments by introducing fluorinated amino acids into a parallel coiled-coil and enzyme-ligand chymotrypsin systems. The results on fluorination effect on coiled-coil dimerization and substrate affinities in the chymotrypsin active site obtained by MD, molecular docking and free energy calculations are in strong agreement with experimental data obtained by our collaborators. In particular, we have shown that fluorine content and position of fluorination can considerably change the polarity and steric properties of an amino acid side chain and, thus, can influence the properties that a fluorinated amino acid reveals within a native protein environment.
III. Coiled-coils typically consist of two to five right-handed α-helices that wrap around each other to form a left-handed superhelix. The interface of two α-helices is usually represented by hydrophobic residues. However, the analysis of protein databases revealed that in natural occurring proteins up to 20% of these positions are populated by polar and charged residues. The impact of these residues on stability of coiled-coil system is not clear. MD simulations together with free energy calculations have been utilized to estimate favourable interaction partners for uncommon amino acids within the hydrophobic core of coiled-coils (Chapter 4). Based on these data, the best hits among binding partners for one strand of a coiled-coil bearing a charged amino acid in a central hydrophobic core position have been selected. Computational data have been in agreement with the results obtained by our collaborators, who applied phage display technology and CD spectroscopy. This combination of theoretical and experimental approaches allowed to get a deeper insight into the stability of the coiled-coil system.
To conclude, this thesis widens existing concepts of protein structural biology in three areas of its current importance. We expand on the role of solvent in protein interfaces, which contributes to the knowledge of physico-chemical properties underlying protein-protein interactions. We develop a deeper insight into the understanding of the fluorine's impact upon its introduction into protein environments, which may assist in exploiting the full potential of fluorine's unique properties for applications in the field of protein engineering and drug design. Finally we investigate the mechanisms underlying coiled-coil system folding. The results presented in the thesis are of definite importance for possible applications (e.g. introduction of solvent explicitly into the scoring function) into protein folding, docking and rational design methods.
The dissertation consists of four chapters:
● Chapter 1 contains an introduction to the topic of protein-protein interactions including basic concepts and an overview of the present state of research in the field.
● Chapter 2 focuses on the studies of the role of solvent in protein interfaces.
● Chapter 3 is devoted to the work on fluorinated amino acids in protein environments.
● Chapter 4 describes the study of coiled-coils folding properties.
The experimental parts presented in Chapters 3 and 4 of this thesis have been performed by our collaborators at FU Berlin.
Sections 2.1, 2.2, 3.1, 3.2 and Chapter 4 have been submitted/published in peer-reviewed international journals. Their organization follows a standard research article structure: Abstract, Introduction, Methodology, Results and discussion, and Conclusions. Section 3.3, though not published yet, is also organized in the same way. The literature references are summed up together at the end of the thesis to avoid redundancy within different chapters.
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3D printed flexible substrate with pneumatic driven electrodes for health monitoringSchubert, Martin, Friedrich, Sabine, Wedekind, Daniel, Zaunseder, Sebastian, Malberg, Hagen, Bock, Karlheinz 11 February 2019 (has links)
Telemedical methods enable remote patient monitoring and healthcare at a distance. Besides, fitness tracker and sport watches are currently trending electronic products to generate awareness of health parameters in daily life. Especially, the long-term and continuous measurement of electrophysiological signals such as electrocardiogramm (ECG) becomes increasingly attractive for telemedical applications. Typically used disposable Ag/AgCl wet electrodes for good skin-electrode contact can potentially cause skin irritation and rashes. This paper presents a low cost, individual and flexible substrate for skin electrodes to be applied in future consumer electronic or professional applications. It enables an alternative contact method of the electrode to the skin by applying a pressure during the measurement and hence good contact. If no measurement is needed pressure can be released and the electrode loses skin contact. The 3D printed polymer module is 4 mm thick and comprises a pressure chamber, silver electrodes and insulation layer. The airtight printed membrane of flexible filament, which expands when inflating the chamber, may be printed in different thicknesses and shapes, much thinner than the present 4mm. This enables a high individuality for various applications. Pressure up to 150 kPa was applied and leads to dilatation of 1400 μm. First tests on skin when measuring electrodermal activity (EDA) show promising results for future applications.
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Niobium Ohmic Contacts for Cryogenic Indium Phosphide High-Electron-Mobility Transistors / Niob-baserade Ohmska Kontakter för Kryogena Indiumfosfid HögelektronmobilitetstransistorerBendrot, Linnéa January 2022 (has links)
Ohmic contacts are crucial components in semiconductor devices such as transistors and diodes, and lowering their contact resistance is an important factor in device performance enhancement. This is especially important for low-noise amplifiers (LNAs) where device noise temperature decreases both directly and indirectly with decreasing contact resistance. This becomes relevant in quantum computers operated at cryogenic temperatures as LNAs constitutes the 4 K quantum bit (qubit) readout signal amplification chain. The goal of this project is to investigated the superconducting element niobium (Nb) as contact material for indium phosphide (InP) high-electron-mobility transistors (HEMTs), being the active component in cryogenic high-frequency LNAs. For contact and barrier resistance determination, test structures were fabricated and utilized according to the transfer length method(TLM) and the recess TLM respectively. Measurements were performed in room temperature as well as in cryogenic temperatures below and above Nb’s bulk transition temperature of 9.25 K. The results show low-resistance Nb-based ohmic contacts for n-In0.65Ga0.35As, with the non-alloyed Nb(50 nm)/Au(100 nm) stack yielding a room temperature contact resistivity of (9.4 ± 0.5) × 10−8 Ωcm2. For all contacts the contact resistivity increased moving to cryogenic temperatures, as expected when electron occupation of high-energy states decreases. At cryogenic temperatures nosuperconducting transition was observed, attributed to the Nb layer thickness being roughly equal to its coherence length. Considering the effective barrier resistance, the Ni/Ge/Au/Nb/Au alloyed contact had the lowest room temperature resistance, reporting 143 Ω µm. In cryogenic temperatures the effective barrier resistance unexpectedly decreased in all contacts. The Nb/Au contact showed the best cryogenic performance, with a barrier resistance of 28 − 37 Ω µm. This indicates great potential for non-alloyed Nb/Au contacts in cryogenic InP HEMTs. / Alla halvledarkomponenter, som dioder och transistorer, har ohmska kontakter. Att sänka kontaktresistansen hos de ohmska kontakterna är ett sätt att höja prestandan hos en komponent. Särskilt gäller detta för lågbrusförstärkare, som har en brustemperatur som minskar både direkt och indirekt med avtagande kontaktresistans. För kvantdatorer som måste kylas till kryogena temperaturer för att fungera är detta relevant eftersom förstärkningen av utläsningssignalen från kvantbitar sker via lågbrusförstärkare vid 4 K. Målet för detta examensprojekt är att undersöka ohmska kontakter baserade på det supraledande materialet niobium (Nb) i indiumfosfidbaserade högelektronmobilitetstransistorer, som är den aktivakomponenten i kryogena högfrekvens-lågbrusförstärkare. För bestämning av kontaktoch barriärresistans producerades teststrukturer enligt Transfer Length-metoden (TLM) respektive etsad TLM. Mätningar genomfördes i rumstemperatur samt vid kryogena temperaturer både över och under niobiumets kritiska temperatur på 9.25 K. Resultatet visar låg kontaktresistans för Nb-baserade ohmska kontakter på n-In0.65Ga0.35As. Den icke-legerade Nb(50 nm)/Au(100 nm)-kontakten hade en kontaktresistivitet på (9.4 ± 0.5) × 10−8 Ωcm2 . Vid kryogena temperaturer ökade kontaktresistansen för samtliga Nb-baserade kontakter, vilket är förväntat då färre elektroner fyller högenergitillstånd. Inget supraledande tillstånd observerades vid kryogena temperaturer, vilket kan förklaras av att tjockleken på niobiumlagret var ungefär lika med dess koherenslängd. Lägst barriärresistans vid rumstemperatur hade den legerade Ni/Ge/Au/Nb/Au-kontakten, med ett värde på 143 Ω µm. Vid kryogena temperaturer skedde en oväntad minskning hos barriärsresistansen hos samtliga kontakter, där den lägst barriärsresistans uppmättes på den icke-legerade Nb/Au-kontakten, 28 − 37 Ω µm. Slutsatsen som dras är att det finns stor potential för användning av icke-legerade Nb/Au-kontakter för kryogena lågbrusförstärkare baserade på indiumfosfid.
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Les stratégies d'exploitation de l'archipel côtier du Labrador : une étude de cas du 18e siècle au site d'IkkeghasarsukFields, Martin 24 April 2018 (has links)
La fin du 18e siècle était une période dynamique au Labrador. À cette époque, le phénomène climatique nommé le Petit Âge glaciaire affectait grandement l'étendue de la banquise côtière. L'arrivée des missionnaires et des objets européens enclencha une réorganisation des rôles sociaux chez les Inuits. L'établissement hivernal d'Ikkeghasarsuk, connu sous le code Borden HdCg-23 et le nom de site officiel Koliktalik-6, est composé principalement de deux maisons semi-souterraines construites avant 1776 sur un site dorsétien. La présente étude explore les stratégies d'occupation du territoire par l'analyse des restes fauniques de ces deux maisons. Les espèces de phoques chassées et leurs niches écologiques indiquent que les occupants du site exploitaient surtout les phoques présents dans les eaux libres de glace à l'automne, les phoques annelés au sina l'hiver et les phoques annelés sur la banquise côtière au printemps. Le site d'Ikkeghasarsuk, placé sur une île dénudée et balayée par le vent, aurait permis d'avoir un accès privilégié aux ressources marines diverses, peu importe les conditions climatiques. / The late 18th century was a particularly dynamic era on the northern Labrador coast. The climatic phenomenon known as the Little Ice Age created highly variable ice conditions. Missionaries settling on the northern coast and the influx of European goods set off a reorganisation of Inuit social roles. Ikkeghasarsuk, known as HdCg-23 and Koliktalik-6, is mainly composed of two sod houses built before 1776 over a Dorset site. This study focuses on regional occupation strategies through a zooarchaeological analysis of faunal materials sampled from middens associated to the two houses. This indicates that the hunters based at Ikkeghasarsuk exploited open water seals in the fall and ringed seals at the sina in the winter and on landfast ice in the spring. The site, while located on a barren and windy island, would have allowed easy access to marine resources regardless of climatic conditions.
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Tshakapesh et moi : brève exploration à l'intérieur d'un blanc ensauvagéFortin, Georges 25 April 2018 (has links)
L'interrogation primordiale, en départ de cette thèse, sur le comment structural de la rencontre entre Amérindiens et Blancs en vallée laurentienne, au XVIIe siècle d'abord et plus tard au XIXe siècle en vallée saguenayenne et jeannoise, amène l'auteur à revisiter et les lieux, et les circonstances de cette rencontre. En prenant comme perspective initiale les travaux de Claude Lévi-Strauss, c'est donc au chapitre de l'inconscient ahistorique qu'une analyse basée sur les discours des uns et des autres permettra un redéploiement original propre à inférer de nouvelles donnes. Cette opération complexe est ainsi conçue que les lecteurs, non plus comme spectateurs, mais bien comme acteurs, auront à réévaluer, à l'interne, des structures mentales que tout semblait opposer. Or, l'argument fondamental de cette thèse est bien celui de l'illusion de la différence, celle-là n'étant que le produit d'une réflexion mal blanchie. Tel qu'il est démontré au coeur même de cet ouvrage, les protagonistes partageant la même vision du monde, mais devant, par jeu de l'hubris, la distendre et la distordre pour l'accorder aux présumées lois de l'histoire. À cet égard, la construction d'une identité sur le bras de l'altérité sera traduite par les différentes opérations d'Ensauvagement et de Blanchiment dont il sera fait état de la spécieuse opposition. Mais cette partie, toujours jouée, jamais gagnée, se veut aussi l'occasion privilégiée d'un autre questionnement : cette histoire, dont il est démontré qu'elle colle mal à la réalité, comment la refaire? Ainsi, en conclusion, seront identifiées certaines pistes propres à induire le redressement nécessaire. / Québec Université Laval, Bibliothèque 2013
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