Made available in DSpace on 2016-06-02T20:16:43Z (GMT). No. of bitstreams: 1 1994.pdf: 1761798 bytes, checksum: 183ce1c471cf1079a1302b309c923a68 (MD5) Previous issue date: 2002-04-11 / Financiadora de Estudos e Projetos / In the present work the Drude weight is calculated to study the capacity of conduction at finite temperatures in one-dimensional rings with the potencial given by the sequences of different degrees of randomness and threaded by a time independent magnetic flux. In this context, the tight-binding approximation is used to solve the Schrödinger equation,also permitting the potencials, given by substitution sequences, to be implemented in a simple way. We study four situations in which the potencial is given by periodic and random sequence. The transport properties exhibited by the system in each case are to reflect the degree of randomness presented by these potencials, although in a nontrivial manner if one considers a hierarchy of disorder based on the Fourier transform of the sequences. The role played by temperature in the capacity of conduction, as compared with the role played by the potencials, is also described. / No presente trabalho, através do cálculo do peso de Drude estudamos a capacidade de condução a temperaturas finitas, em anéis unidimensionais com potenciais dados por seqüências de diferentes graus de desordem e atravessados por fluxo magnético independente do tempo. Neste contexto, utilizamos o modelo tight-binding na resolução da equação de Schrödinger, o que permite inserir os potenciais, dados por seqüências de substituição, de maneira simples. Estudamos quatro casos em que esse potencial seja dado por seqüências não periódicas. Os resultados são comparados com os dois casos limites de organização, a saber, as seqüências periódica e desordenada. Observa-se que o grau de desordem apresentado por estes potenciais reflete-se nas propriedades de transporte exibidas pelo sistema em cada caso, embora de maneira não trivial se considerada uma hierarquia de desordem baseada na transformada de Fourier das seqüências. Descreve-se também a influência da temperatura, frente à influência dos potenciais, na capacidade de condução.

Made available in DSpace on 2015-03-03T15:16:23Z (GMT). No. of bitstreams: 1 LeonardoM.pdf: 1880413 bytes, checksum: c785ee7cbc933eb3ac782dc9ac382e6c (MD5) Previous issue date: 2009-12-18 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / We use a tight-binding formulation to investigate the transmissivity and the currentvoltage (I_V) characteristics of sequences of double-strand DNA molecules. In order to reveal the relevance of the underlying correlations in the nucleotides distribution, we compare theresults for the genomic DNA sequence with those of arti_cial sequences (the long-range correlated Fibonacci and RudinShapiro one) and a random sequence, which is a kind of prototype of a short-range correlated system. The random sequence is presented here with the same _rst neighbors pair correlations of the human DNA sequence. We found that the long-range character of the correlations is important to the transmissivity spectra, although the I_V curves seem to be mostly inuenced by the short-range correlations. We also analyze in this work the electronic and thermal properties along an _-helix sequence obtained from an _3 peptide which has the uni-dimensional sequence (Leu-Glu-Thr- Leu-Ala-Lys-Ala)3. An ab initio quantum chemical calculation procedure is used to obtain the highest occupied molecular orbital (HOMO) as well as their charge transfer integrals, when the _-helix sequence forms two di_erent variants with (the so-called 5Q variant) and without (the 7Q variant) _brous assemblies that can be observed by transmission electron microscopy. The di_erence between the two structures is that the 5Q (7Q) structure have Ala ! Gln substitution at the 5th (7th) position, respectively. We estimate theoretically the density of states as well as the electronic transmission spectra for the peptides using a tight-binding Hamiltonian model together with the Dyson's equation. Besides, we solve the time dependent Schrodinger equation to compute the spread of an initially localized wave-packet. We also compute the localization length in the _nite _-helix segment and the quantum especi_c heat. Keeping in mind that _brous protein can be associated with diseases, the important di_erences observed in the present vi electronic transport studies encourage us to suggest this method as a molecular diagnostic tool / Nesta tese, investigamos a transmissividade e as caracter?sticas de corrente como fun??o da diferen?a de potencial, no contexto da liga??o forte, em seq??ncias de dupla fita do DNA. Com o intuito de investigar a relev?ncia das correla??es subjacentes nas distribui??es dos nucleot?deos, comparamos os resultados de uma seq??ncia gen?mica do DNA com duas seq??ncias artificiais (Fibonacci e Rudin-Shapiro, que apresentam correla??o de longo alcance) e uma seq??ncia aleat?ria, prot?tipo de sistemas de correla??o de curto alcance. A seq??ncia aleat?ria utilizada apresenta a mesma correla??o de pares de primeiros vizinhos que a seq??ncia do DNA humano. Observamos que a caracter?stica de correla??o de longo alcance ? importante para o espectro de transmissividade, apesar das curvas IXV serem mais influenciadas por correla??es de curto alcance. Neste trabalho, analisamos tamb?m as propriedades t?rmicas e eletr?nicas de uma seq?encia α-h?lice, obtida de um pept?deo α3, o qual apresenta a seguinte seq??ncia unidimensional (Leu-Glu-Thr-Leu-Ala-Lys-Ala)3 (estrutura prim?ria). C?lculos ab initio qu?nticos s?o utilizados para obter as energias dos orbitais moleculares mais altos (HOMO, highest occupied molecular orbital), bem como suas integrais de transfer?ncias de cargas quando a seq??ncia α-h?lice forma uma estrutura fibrosa (variante 5Q) e n?o fibrosa (variante 7Q), as quais podem ser observadas atrav?s de microscopia eletr?nica de transmiss?o. A diferen?a entre as duas estruturas ? que a estrutura 5Q (7Q) apresenta a substitui??o Ala → Gln na 5a (7a) posi??o, respectivamente. N?s estimamos, teoricamente, a densidade de estado bem como o espectro de transmiss?o eletr?nico dos pept?deos, utilizando um Hamiltoniano no formalismo da liga??o-forte juntamente com a equa??o de Dyson. Al?m disso, n?s resolvemos a equa??o de Schr?dinger dependente do tempo para obter o espalhamento de um pacote de onda inicialmente localizado. N?s calculamos tamb?m o comprimento de localiza??o e, por fim, o calor espec?fico qu?ntico. Vale lembrar que a forma??o de prote?nas fibrosas podem estar associadas ? doen?as, de forma que as importantes diferen?as observadas no estudo das propriedades eletr?nicas de transporte nos encorajam a sugerir este m?todo como uma ferramenta de diagn?stico molecular

Carbon-based conductors like carbon nanotubes (CNTs) and graphene nanoribbons (GNRs) have many properties, which make them relevant for potential electronic applications. Among them are high conductances and tunable band gap sizes. These properties make CNTs and GNRs useful in many circumstances, e.g. as channel material in transistors or transparent electrodes in solar cells. Plenty of literature can be found on the topic of single linear CNTs/GNRs. Some applications however require a large network of these conductors. In addition, a single conductor has only a small impact on the network conductance, which reduces the need to control the properties of each individual nanotube/-ribbon. This leads to networks being easier to apply. In this work, the conductance of large networks of GNRs is calculated using the quantum-transport formalism (QT). This has not been done before in literature. In order to apply QT to such a large amount of atoms, the recursive Green's function formalism is used. For this the networks are devided into subcells, which are represented by tight-binding matrices. Similar networks are also examined using two different nodal analysis (NA) approaches, where the nanoribbons are treated as ohmic conductors. For NA with one-dimensional conductors, major discrepancies are found in regards to the QT model. However, networks consisting of two-dimensional conductors (NA-2D) have many properties similar to the QT networks. A recipe to approximate the QT results with NA-2D is presented.:1. Introduction 2. Theoretical Principles 2.1 Carbon-based Conductors 2.1.1 Structure and Properties 2.1.2 Networks 2.2 Tight-Binding Model 2.3 Quantum Transport 2.3.1 Introduction 2.3.2 Level Broadening 2.3.3 Current Flow 2.3.4 Transmission 2.4 Nodal Analysis 3. Implementation 3.1 Quantum Tranport 3.1.1 Network Generation 3.1.2 Density-Functional based Tight-Binding Method 3.1.3 Recursive Green's Function Algorithm 3.1.4 Conductance 3.2 Nodal Analysis 3.2.1 One-dimensional Conductors 3.2.2 Two-dimensional Conductors 4. Results 4.1 Quantum Transport 4.1.1 Band Structures and Fermi Energies 4.1.2 Ideal Transmission and Consistency Tests 4.1.3 Percolation 4.1.4 Transmission 4.1.5 Conductance 4.1.6 Power Law Scaling 4.1.7 Size Dependence and Confinement Effects 4.1.8 Calculation Time 4.2 Nodal Analysis 4.2.1 One-dimensional Conductors 4.2.2 Two-dimensional Conductors 4.2.3 Calculation Time 4.3 Approximating QT with NA 4.3.1 Optimal Parameters 4.3.2 Percolation 4.3.3 Conductance 4.3.4 Power Law Scaling 5. Conclusions / Graphenbasierte Leiter wie Kohlenstoff-Nanoröhrchen (engl. 'carbon nanotubes', CNTs) oder Graphen-Nanobänder (engl. 'graphene nanoribbons', GNRs) haben viele Eigenschaften, die sie für potenzielle elektronische Anwendungen interessant machen. Darunter sind hohe Leitfähigkeiten und einstellbare Bandlückengrößen. Dadurch sind CNTs und GNRs in vielen Bereichen nützlich, z.B. als Kanalmaterial in Transistoren oder als transparente Elektroden in Solarzellen. Es gibt viel Literatur über einzelne, lineare CNTs/GNRs. Einige Anwendungen benötigen jedoch ein großes Netzwerk dieser Leiter. Zusätzlich hat ein einzelner Leiter wenig Einfluss auf die Leitfähigkeit des Netzwerks, wodurch die Eigenschaften der einzelnen Nanoröhrchen/-streifen weniger streng kontrolliert werden müssen. Dies führt dazu, dass es einfacher ist Netzwerke zu nutzen. In dieser Arbeit wird die Leitfähigkeit von großen GNR-Netzwerken mittels Quantentransport (QT) berechnet. Dies wurde in der Literatur noch nicht getan. Um QT auf eine so große Menge an Atomen anzuwenden wird der rekursive Greenfunktions-Formalismus benutzt. Dazu werden die Netzwerke in Unterzellen unterteilt, die durch Tight-Binding-Matrizen dargestellt werden. Ähnliche Netzwerke werden auch mit zwei Versionen der Knotenanalyse (engl. 'nodal analysis', NA) untersucht, welche die Nanobänder wie ohmische Leiter behandelt. Die Ergebnisse der NA mit eindimensionalen Leitern weisen deutliche Unterschiede zu den mit QT erzielten Ergebnissen auf. Wenn jedoch zweidimensionale Leiter in NA verwendet werden (NA-2D) gibt es viele parallelen zu den QT Ergebnissen. Zuletzt wird ein Vorgehen präsentiert, mit dem QT Resultate durch NA-2D Rechnungen genähert werden können.:1. Introduction 2. Theoretical Principles 2.1 Carbon-based Conductors 2.1.1 Structure and Properties 2.1.2 Networks 2.2 Tight-Binding Model 2.3 Quantum Transport 2.3.1 Introduction 2.3.2 Level Broadening 2.3.3 Current Flow 2.3.4 Transmission 2.4 Nodal Analysis 3. Implementation 3.1 Quantum Tranport 3.1.1 Network Generation 3.1.2 Density-Functional based Tight-Binding Method 3.1.3 Recursive Green's Function Algorithm 3.1.4 Conductance 3.2 Nodal Analysis 3.2.1 One-dimensional Conductors 3.2.2 Two-dimensional Conductors 4. Results 4.1 Quantum Transport 4.1.1 Band Structures and Fermi Energies 4.1.2 Ideal Transmission and Consistency Tests 4.1.3 Percolation 4.1.4 Transmission 4.1.5 Conductance 4.1.6 Power Law Scaling 4.1.7 Size Dependence and Confinement Effects 4.1.8 Calculation Time 4.2 Nodal Analysis 4.2.1 One-dimensional Conductors 4.2.2 Two-dimensional Conductors 4.2.3 Calculation Time 4.3 Approximating QT with NA 4.3.1 Optimal Parameters 4.3.2 Percolation 4.3.3 Conductance 4.3.4 Power Law Scaling 5. Conclusions

Im Folgenden werden Transferprozesse in Nanohybridsystemen theoretisch untersucht. Diese Hybridsysteme sind vielversprechende Kandidaten für neue optoelektronische Anwendungen und erfahren daher ein erhebliches Forschungsinteresse. Jedoch beschränken sich Arbeiten darüber hauptsächlich auf experimentelle Untersuchungen und kaum auf die dazugehörige theoretische Beschreibung. Bei den theoretischen Betrachtungen treten entscheidende Limitierungen auf. Es werden entweder Details auf der atomaren Ebene vernachlässigt oder Systemgrößen betrachtet, die wesentlich kleiner als im Experiment sind. Diese Thesis zeigt, wie die bestehenden Theorien verbessert werden können und erweitert die bisherigen Untersuchungen durch die Betrachtung von vier neuen hoch relevanten Nanohybridsystemen. Das erste System ist eine Nanostruktur, die aus einem Au-Kern und einer CdS-Schale besteht. Beim zweiten System wurde eine ZnO/Para-Sexiphenyl Nanogrenzfläche untersucht. Die zwei anderen Systeme beinhalten jeweils einen CdSe-Nanokristall, der entweder mit einem Pheophorbide-a-Molekül oder mit einem röhrenförmigen Farbstoffaggregat wechselwirkt. In allen Systemen ist der Anregungsenergie-Transfer ein entscheidender Transfermechanismus und steht im Fokus dieser Arbeit. Die betrachteten Hybridsysteme bestehen aus zehntausenden Atomen und machen daher eine individuelle Berechnung der einzelnen Subsysteme sowie deren gegenseitiger Wechselwirkung notwendig. Die Halbleiter-Nanostrukturen werden mit der Tight-Binding-Methode und der Methode der Konfigurationswechselwirkung beschrieben. Für das molekulare System wird die Dichtefunktionaltheorie verwendet. Die dazugehörigen Rechnungen wurden von T. Plehn ausgeführt. Das metallische Nanoteilchen wird durch quantisierte Plasmon-Moden beschrieben. Die verwendeten Theorien ermöglichen eine Berechnung von Anregungsenergietransfer in Nanohybridsystemen von bisher nicht gekannter Systemgröße und Detailgrad. / In the following, transfer phenomena in nanohybrid systems are investigated theoretically. Such hybrid systems are promising candidates for novel optoelectronic devices and have attracted considerable interest. Despite a vast amount of experimental studies, only a small number of theoretical investigations exist so far. Furthermore, most of the theoretical work shows substantial limitations by either neglecting the atomistic details of the structure or drastically reducing the system size far below the typical device extension. The present thesis shows how existing theories can be improved. This thesis also expands previous theoretical investigations by developing models for four new and highly relevant nanohybrid systems. The first system is a spherical nanostructure consisting of an Au core and a CdS shell. By contrast, the second system resembles a finite nanointerface built up by a ZnO nanocrystal and a para-sexiphenyl aggregate. For the last two systems, a CdSe nanocrystal couples either to a pheophorbide-a molecule or to a tubular dye aggregate. In all of these systems, excitation energy transfer is an essential transfer mechanism and is, therefore, in the focus of this work. The considered hybrid systems consist of tens of thousands of atoms and, consequently, require an individual modeling of the constituents and their mutual coupling. For each material class, suitable methods are applied. The modeling of semiconductor nanocrystals is done by the tight-binding method, combined with a configuration interaction scheme. For the simulation of the molecular systems, the density functional theory is applied. T. Plehn performed the corresponding calculations. For the metal nanoparticle, a model based on quantized plasmon modes is utilized. As a consequence of these theories, excitation energy transfer calculations in hybrid systems are possible with unprecedented system size and complexity.

Carbon nanotubes have been envisioned to become a very important material in various applications. This is due to the unique properties of carbon nanotubes which can be exploited in applications on length scales spanning from the nano world to our macroscopic world. For example, the electronic properties of carbon nanotubes makes them utterly suitable for nano electronics while the strength of them makes them suitable for reinforcements in plastics. Both of these applications do however require... mer the ability for systematic production of carbon nanotubes with certain properties. This is called selective carbon nanotube growth and today this has not been achieved with total success. In the work presented in the thesis several different computational methods have been applied in our contribution to the systematic search for selective carbon nanotube growth. Put in a context of previous knowledge about carbon nanotube growth our results provide valuable clues to which parameters that control the carbon nanotube growth. In association with the latest results we even dare to, with all modesty, speculate about a plausible control mechanism. The studies presented in the thesis addressed different stages of carbon nanotube growth, spanning from the properties affecting the initiation of the growth to the parameters affecting the termination of the growth. In some more detail this included studies of the melting temperatures of nanoscaled metal clusters. The expected size dependence of the melting temperatures was confirmed and the melting temperatures of clusters on substrates were seen to depend both on the material and shape of the surface. As this constitute the premises prior to the carbon nanotube growth it was followed by studies of the interaction between carbon nanotubes and metal clusters of different size and constitution. This was done using different computational methods and at different temperatures. It soon became apparent that the clusters adapted to the carbon nanotube and not vice versa. This held true irrespectively of the constitution of the cluster, that is for both pure metal and metal carbide. It was also seen that there exist a minimum cluster size that prevent the carbon nanotube end from closing. Closure of the carbon nanotube end is likely to lead to the termination of the growth which lead to studies of other reasons for growth termination, e.g., Ostwald ripening of the catalyst particles. This was investigated with the result that the rate of the Ostwald ripening may depend on both the chirality and diameter of the carbon nanotubes. It is suggested that this may provide some answers to the controlled growth of carbon nanotubes. / <p>Disputationen sker fredagen den 3 december 2010, kl. 10:15, Kollektorn, Kemivägen 9</p>

Shale oil (tight oil) is oil trapped in low permeability shale or sandstone. Shale oil is a resource with great potential as it is heavily supplementing oil production in the United States (U.S. Energy Information Administration, 2013). The shale rock must be stimulated using hydraulic fracturing before the production of shale oil. When the hydrocarbons are produced from fractured systems, the resulting flow is influenced by the fracture, the stimulated rock, and the matrix rock. The production decline rates from shale oil reservoirs experience flow regimes starting with fracture linear flow (fracture dominated), then bilinear flow (fracture and stimulated rock dominated), then formation linear flow (stimulated rock dominated), and finally pseudo-radial flow (unstimulated matrix rock dominated) (Cinco-Ley 1982). In this thesis, daily production rates from a shale oil reservoir are modeled using a simple spreadsheet-based, finite difference serial flow simulator that models the single-phase flow of a slightly-compressible oil. This simulator is equivalent to flow through multiple tanks (subsequent part of the thesis will call these cells) through which flow passes serially through one tank into the other. The simulator consists of 11 tanks. The user must specify the compressibility-pore volume product of each tank and the transmissibility that governs flow from one tank to another. The calculated rate was fitted to the given data using the Solver function in Excel. The fitted matches were excellent. Although we can adjust all 22 parameters (2 per cell) to affect the simulation results, we found that adjusting only the first three cells nearest to the well was sufficient. In many cases, only two cells were enough. Adjusting 4 or more cells resulted in non-unique matches. Furthermore, the properties of the very first cells proved insensitive to the matches when using the 3 cells to match the data. The cells in the 2 cell model represent the stimulated zone and the unstimulated rock. Likewise, the cells in the 3 cell model represent the hydraulic fracture, the stimulated zone, and the unstimulated rock. The accessed pore volume and transmissibility were responsive to the injected sand mass and fluid volume up to approximately 10⁶ kg and 7000 m³ respectively; injecting more sand and fluids than this caused negligible increases in the accessed pore volume and transmissibility. This observation suggests that the sand does not migrate far into the fractures. Similarly, it was observed that the number of stages was positively correlated with cell transmissibility and pore volume up to 20 stages. These results suggest that fracture treatments were significantly over designed and injecting less sand and water in fewer stages would optimize the economics of similar projects. To our knowledge this is the first work to analyze the results of fracture treatments by matching with pore volumes and transmissibility in a simple serial cell flow. / text

The Normal Accident Theory (NAT) attempts to understand why accidents occur in systems with high-risk technologies. NAT is characterized by two attributes: complexity and coupling. The combination of these attributes results in unplanned and unintended catastrophic consequences. High-risk technology systems that are complex and tightly coupled have a high probability of experiencing system failures. The mining industry has experienced significant incidents involving haulage operations up to and including severe injuries and fatalities. Although the mining industry has dramatically reduced fatalities and lost time accidents over the last three decades or more, accidents still continue to persist. For example, for the years 1998 - 2002, haulage operations in surface mines alone have accounted for over 40% of all accidents in the mining industry. The systems thinking was applied as an approach to qualitatively and quantitatively evaluate NAT in mining haulage operations. A measurement index was developed to measure this complexity. The results from the index measurements indicated a high degree of complexity that exists in haulage transfer systems than compared to loading and unloading systems. Additionally, several lines of evidence also point to the applicability of NAT in mining systems. They include strong organizational management or safety system does not guarantee zero accidents, complexity is exhibited in mining systems, and they are interactive and tightly coupled systems. Finally, the complexity of these systems were assessed with results indicating that a large number of accidents occur when there are between 4 or 5 causal factors. These factors indicate the degree of complexity necessary before accidents begin to occur.

This thesis compares novels The War of the Worlds (1898) by Herbert George Wells, Heart of Darkness (1899) by Joseph Conrad, Lord of the Flies (1954) by William Golding and A Clockwork Orange (1962) by Anthony Burgess and their film adaptations. Two of these adaptations are conceived tightly and the other two loosely. The theoretical part of this thesis focuses on defining the terms "tight adaptation" and "loose adaptation", on adaptation theories and on choosing the right criteria by which it will be possible to judge the suitability of techniques of adaptation in each case study. The practical part applies the chosen criteria on each adaptation and evaluates the success in transferring key themes and motifs from the model book into the movie version. Key words: tight adaptation, loose adaptation, fidelity, movie version, novel version 

La thèse s’inscrit dans le contexte de sûreté nucléaire relatif à l'hydruration des gainages combustibles en Zircaloy, en modélisant, à l’échelle atomique, les phénomènes d’ordre chimique hydrogène - lacune atomique, sur le sous-réseau interstitiel tétraédrique des hydrures de zirconium CFC. Une telle démarche s’est déclinée en deux étapes : en premier lieu, le développement d’un modèle énergétique atomistique à la fois précis et peu coûteux numériquement, puis l’implémentation d’approches thermostatistiques de type Monte-Carlo à l’aide de ce modèle. En prenant pour point de départ un Hamiltonien de Liaisons Fortes (TB), la construction du modèle énergétique a reposé sur la dérivation d’interactions multiatomiques entre atomes d’hydrogène, à l’aide de la méthode des perturbations généralisée (GPM) basée sur une représentation de l’état de désordre interstitiel dans l’Approximation du Potentiel Cohérent (CPA). La démarche a permis de réduire l'énergie d'ordre à un modèle d'Ising effectif dérivé des liaisons fortes (TBIM), basé sur les interactions de paires effectives entre atomes d’hydrogène. Le TBIM a ensuite été validé, en comparant les énergies de structures ordonnées d’une part reconstruites en TBIM, et d’autre part obtenues par des calculs directs d’énergie totale effectués soit en Liaisons Fortes, soit par des méthodes ab initio (DFT). L'implémentation d'une approche Monte-Carlo canonique par le TBIM a permis de caractériser les différentes transitions ordre-désordre, et d'établir un diagramme de phase de l’ordre chimique hydrogène - lacune atomique, sur le sous-réseau interstitiel tétraédrique des hydrures de zirconium CFC. / The thesis addresses the nuclear safety issue of Zircaloy fuel cladding hydruration, by modelling, at atomistic scale, chemical ordering processes between hydrogen and atomic vacancies on tetrahedral interstitial sublattice of CFC zirconium hydrides. This has been achieved into two steps : first the development of an atomistic energetic model sufficiently precise and not too much CPU time consuming, and secondly its implementation in Monte-Carlo thermostatistical simulations. Starting from a Tight-Binding (TB) Hamiltonian, the energetic model has been derived from the calculation of multiatomic interactions between hydrogen atoms, using the Generalized Perturbation Method (GPM) applied to an interstitial disorder described within the Coherent Potential Approximation (CPA). The path allows us to reduce the ordering energy to a Tight-Binding Ising Model (TBIM), based on effective pairwise interactions between hydrogen atoms. The TBIM has been validated by comparing ordering energies of ordered structures either reconstructed using TBIM, or directly obtained from total energy calculations perfor- med both within TB and ab initio (DFT) methods.By implementing a canonical Monte-Carlo with TBIM, we obtain different order-disorder phase transitions, and a phase diagram of H-vacancy chemical ordering, on the tetrahedral interstitial sublattice of CFC zirconium hydrides.

Chez les rongeurs rendus obèses par un régime hyper-lipidique, un changement du microbiote est associé à une altération de la perméabilité intestinale, augmentant le passage d’antigènes alimentaires ou bactériens et contribuant à une inflammation chronique de bas grade et une insulinorésistance. Cependant chez l’homme, les modifications de perméabilité intestinale, son impact sur les altérations métaboliques, inflammatoires systémiques et tissulaires sont peu documentées. L’objectif de ce travail est de caractériser la perméabilité intestinale (i.e. jéjunum) et les mécanismes impliqués dans sa régulation dans l’obésité humaine sévère en conditions de jeûne (basal) et après un apport aigu de lipides selon des approches complémentaires in vivo (biomarqueurs), ex vivo (chambre de Ussing, étude des protéines de jonctions serrées en immunofluorescence) et in vitro (lignée cellulaire Caco-2/TC7). A l’état basal nous avons observé une diminution de la localisation de l’occludine et de la tricelluline dans les jonctions serrées au niveau du jéjunum et des taux circulants en zonuline et LPS binding protéine plus élevés chez les obèses. La perméabilité Jéjunale basale mesurée ex vivo en chambre de Ussing était comparable entre obèses et non obèses avec cependant des liens entre ces mesures et les paramètres de l’inflammation systémique chez les patients obèses (CRP et Haptoglobine). Une charge unique en lipides alimentaires, entrainait une augmentation rapide et significative de la perméabilité aux macromolécules (FITC-Dextran 4 kDa) in vitro et ex vivo, démontrant ainsi l’effet direct des lipides postprandiaux sur la barrière épithéliale. La perméabilité aux macromolécules après exposition aux lipides était plus élevée chez les patients obèses à fortiori diabétiques de type 2 et était associée à l’inflammation systémique (CRP) et intestinale (calprotectine fécale). Ainsi, nos résultats mettent en évidence un défaut de la barrière intestinale dans l'obésité caractérisée par une hyperperméabilité jéjunale démasquée par les lipides alimentaires et associée à l’inflammation et aux troubles métaboliques. / Intestinal barrier damage is associated with low-grade inflammation and metabolic impairment in rodent models of obesity. Whether intestinal permeability is altered in human metabolic disorders remains poorly investigated. Using a large cohort of well-characterized obese subjects and a human enterocyte model, we examined intestinal permeability in the basal state and after a challenge by a lipid load. We showed a reduction of occludin and tricellulin at jejunal tight junctions and increased serum levels of zonulin and LPS-Binding Protein in obese subjects. Jejunal permeability, directly measured in Ussing chambers in the fasting condition, was not significantly increased compared to non-obese subjects. Nevertheless, within the obese cohort, high permeability was associated with systemic inflammation (CRP and haptoglobin). A single lipid load increased permeability both in Caco-2/TC7 cells and ex vivo in human jejunum, demonstrating dietary lipids’ direct effects on the epithelial barrier. Permeability after the lipid load was significantly higher in the jejunum of obese subjects and associated with systemic and intestinal inflammation (CRP and fecal calprotectin) and type 2 diabetes. Thus, our results highlight an intestinal barrier defect in obesity, with a jejunal permeability increased by a lipid challenge and linked to inflammatory and metabolic impairments.