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Vztah morfometrických charakteristik terénu a síťových analýz v prostředí GIS / Relationship between morphometric characteristics of the terrain and network analysis in GISKufner, Jan January 2013 (has links)
The main objective of the diploma thesis is creation of methodology and automatization of calibration process of network graph based on the values of morphometric characteristics and motion vectors. The resulting morphometric values of the terrain have been detected on the basis of mathematical and cartographic methods for line course expression. The most accurate one has been used in GIS network analysis over the road network and digital terrain models, which were chosen as the most appropriate for this purpose. Relationship between morphometric values and values suitable for use in network analysis (speed, time, ...) has been studied using specific examples in appropriately selected territory with using selected vehicle, which was designated as a bicycle. The practical part for the verification of functionality of the suggested methodology has been compared with other models of accessibility, available web-map portals and route planners. The process of transport network evaluation based on selected parameters has been automated in Python programming language as a tool in ArcGIS software, which is attached to the diploma thesis. Powered by TCPDF (www.tcpdf.org)
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Konfidenční množiny v nelineární regresi / Confidence regions in nonlinear regressionMarcinko, Tomáš January 2013 (has links)
The aim of this thesis is a comprehensive description of the properties of a nonlinear least squares estimator for a nonlinear regression model with normally distributed errors and thorough development of various methods for constructing confidence regions and confidence intervals for the parameters of the nonlinear model. Due to the fact that, unlike the case of linear models, there is no easy way to construct an exact confidence region for the parameters, most of these methods are only approximate. A short simulation study comparing observed coverage of various confidence regions and confidence intervals for models with different curvatures and sample sizes is also included. In case of negligible intrinsic curvature the use of likelihood-ratio confidence regions seems the most appropriate.
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Mesures en trois dimensions des distorsions cristallines par imagerie en diffraction de Bragg : application aux cristaux de glace / 3D resolved distortion measurements by Bragg diffraction imaging : application to ice crystalsKluender, Rafael 29 September 2011 (has links)
La déformation visco-plastique de la glace est fortement anisotrope, le plan de glissement préferé étant la plan de base. Le fait que dans un polycristal chaque grain possède sa propre direction de déformation produit des incompatibilités et un champ de contrainte complexe. La déformation à été étudiée expérimentellement en mésurant la dis- tortion des plans cristallins de mono- et polycristaux de glace artificielle. Les expériences ont été réalisées à l'aide d'un faisceau synchrotron. Une nouvelle procédure éxperimental, basée sur les méthodes de l'imagerie en diffraction de Bragg, comme lumière blanche, im- agerie sur la courbe de diffraction et topographie laminaire et ponctuelle, a été dévéloppée. Les désorientations angulaires, les largeurs à mi-hauteur et les intensités intégrées ont été mésurées dans les trois dimensions spatiales de l'échantillon et avec une résolution de 50× 50 × 50µm3. Les algorithmes d'analyse de données ont été écrits pour extraire des données des résultats quantitatifs, et pour calculer les neuf composantes du tenseur de courbure ainsi que la distortion entière des plans cristallins. Les résultats ont permis d'observer les premières étappes de la déformation de la glace. Par example la polygonisation d'un grain à été observée. / The viscoplastic deformation of ice is strongly anisotropic. The preferred glide system is on the basal plane. In a polycrystal each grain exhibits its own deformation direction. As a result the deformation of polycrystalline ice is associated with strain in- compatibilities, especially at the grain boundaries and the triple junction. The deforma- tion process was experimentally investigated by measuring crystal lattice distortions of single- and polycrystalline, artificially grown ice crystals. The experiments were benefic- ing from a synchrotron X-ray beam. A new experimental method, based on Bragg diffrac- tion imaging (X-ray topography) methods, as white beam X-ray diffraction topography, rocking curve imaging, section- and pinhole X-ray topography was used. Angular mis- orientations, full-width-half-maxima and integrated Bragg diffracted intensities have been measured along the three spatial dimensions of the sample and with a spatial resolution of around 50µm × 50µm × 50µm. Data analysis algorithms were written in order to extract quantitative results from the data and to calculate all nine components of the curvature ten- sor, as well as the entire lattice distortion in the sample. The results give an insight into the early stages of plastic deformation of ice, i.e. the polygonisation of a grain was observed.
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Progression de la racine primaire d'Arabidopsis thaliana en réponse à des variations de contraintes mécaniques de son substrat / Penetration of the Arabidopsis thaliana primary root in response to variations in growth medium strengthRoué, Juliette 19 December 2018 (has links)
Le comportement mécanique d’un sol constitue un des facteurs prépondérants affectant la croissance et le développement racinaire. L’augmentation de la résistance mécanique d’un sol affecte l’architecture du système racinaire, la croissance axiale et radiale des racines, et l’orientation de la croissance. Bien que ces réponses soient décrites sur diverses espèces végétales dans la littérature, leur mise en place et les mécanismes de signalisation sous-jacents restent à ce jour méconnus. L’objectif principal de cette thèse est d’étudier la mise en place des réponses des racines primaires d’Arabidopsis thaliana à des variations de contraintes mécaniques de son substrat. La littérature fait état jusqu’ici de deux voies de signalisation mécanique possibles, l’une impliquant une mécanoperception au niveau de la coiffe racinaire, et l’autre faisant intervenir entres autres l’activation de canaux mécano-sensibles au niveau de l’apex racinaire. Pour étudier leur implication respective, nous avons caractérisé les réponses à une augmentation des contraintes mécaniques de racines primaires issues de la lignée Arabidopsis thaliana sauvage et de lignées mutantes affectées au niveau de l’organisation de la coiffe (fez-2, smb-3, brn1-1 brn2-1) ou au niveau de canaux ioniques mécanosensibles (mca1-null, mslΔ5). Nous avons développé un système expérimental original basé sur le suivi de croissance et d’orientation des racines dans des milieux de culture à base de Phytagel. Ces milieux de culture permettent de mimer d’une part une augmentation à long terme et simultanée des contraintes mécaniques axiales, radiales et des frottements et d’autre part une augmentation à court terme des contraintes mécaniques axiales. Tout d’abord, nous avons observé que la mise en place des réponses de croissance des racines primaires d’Arabidopsis thaliana à ces augmentations de contraintes mécaniques reposait sur une interaction entre des processus mécaniques (flambement) et biologiques (régulations de la zone de croissance). Ensuite, nous avons mis en évidence que la coiffe racinaire participait à la mise en place des réponses des racines d’Arabidopsis thaliana face à une augmentation des contraintes mécaniques. Nos résultats suggèrent que la coiffe pourrait constituer un siège de la mécanoperception. Par ailleurs, nos résultats sur les lignées mca1-null et mslΔ5 suggèrent que les canaux ioniques MCA1 et MSLs participeraient également à la mise en place des réponses racinaires à l’augmentation des contraintes mécaniques. / Root growth and development are highly modulated by soil mechanical properties such as texture, structure and bulk density. Increases in soil penetration resistance affect root system architecture, root cell production and elongation, root diameter, and root tip orientation. Although root responses to changes in mechanical stresses are well described in several plant species, their establishment and the signaling pathways underlying these responses remains misunderstood. The main objective of this thesis is to study the establishment of Arabidopsis thaliana primary root responses to changes in mechanical stresses. So far, studies reported two distinct putative mechanical signaling pathways involving either (i) the root cap as a main mechanosensing site or (ii) the activity of stretch-activated ion channels localized on the cell plasma membranes along the root apex. According to previous studies, we studied the implication of the root cap and of the stretch-activated channels of the MCA and MSL families in the root responses to increases in mechanical stresses. We developed an original experimental set-up based on the monitoring of growth and orientation of Arabidopsis thaliana primary roots in one-layer and two-layer Phytagel based growth media. The one-layer growth media mimicked a long-term increase in frictions and in radial and axial mechanical stresses whereas the two-layer growth media mimicked a short-term increase in axial mechanical stresses. We characterized penetration abilities, growth rate and tip orientation of Arabidopsis thaliana wild type roots (Col-0) and mutant roots showing defects in root cap organization (fez-2, smb-3, brn1-1 brn2-1) or in stretch-activated ion channels activity (mca1-null, mslΔ5) in one-layer and two-layer media. Firstly, we observed that the establishment of root growth responses to increases in mechanical stresses involved both mechanical (buckling) and biological (growth zone modulations) mechanisms. Then, our experiments demonstrated that alterations in root cap organization led to altered root growth responses to increases in mechanical stresses. Our results suggest that the root cap acts as a mechanosensing site. Moreover, the results obtained with the mca1-null and mslΔ5 Arabidopsis lines suggest that the MCA1 and MSLs ion channels also participate in the establishment of root responses to increases in mechanical stresses.
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A suavização Gaussiana como método de marcação de características de fronteira entre regiões homogêneas contrastantes / The Gaussian smoothing as a method for marking boundary features between contrasting homogeneous regionsLouro, Antonio Henrique Figueira 18 May 2016 (has links)
Este trabalho mostra que a suavização Gaussiana pode exercer outra função além da filtração. Considerando-se imagens binárias, este processo pode funcionar como uma espécie de marcador, que modifica as feições das fronteiras entre duas regiões homogêneas contrastantes. Tais feições são pontos de concavidades, de convexidades ou de bordas em linha reta. Ou seja, toda a informação necessária para se caracterizar a forma bidimensional de uma região. A quantidade de suavização realizada em cada ponto depende da configuração preto/branco que compõe a vizinhança onde este se situa. Isto significa que cada ponto sofre uma quantidade particular de modificação, a qual reflete a interface local entre o objeto e o fundo. Então, para detectar tais feições, basta quantificar a suavização em cada ponto. No entanto, a discriminação pixel a pixel exige que a distribuição Gaussiana apresente boa localização, o que só acontece em escalas muito baixas (σ≅0,5). Assim, propõe-se uma distribuição construída a partir da soma de duas Gaussianas. Uma é bem estreita para garantir a boa localização e a outra possui abertura irrestrita para representar a escala desejada. Para confirmar a propriedade de marcação dessa distribuição, são propostos três detectores de corners de contorno, os quais são aplicados à detecção de pontos dominantes. O primeiro utiliza a entropia de Shannon para quantificar a suavização em cada ponto. O segundo utiliza as probabilidades de objeto e de fundo contidos na vizinhança observada. O terceiro utiliza a diferença entre Gaussianas (DoG) para determinar a quantidade suavizada, porém com a restrição de que uma das versões da imagem tenha suavização desprezível, para garantir a boa localização. Este trabalho se fundamenta na física da luz e na visão biológica. Os ótimos resultados apresentados sugerem que a detecção de curvaturas do sistema visual pode ocorrer na retina. / This work shows that the Gaussian smoothing can have additional function to filtration. Considering the binary images, this process can operate as a kind of marker that changes the features of the boundaries between two contrasting homogeneous regions. These features are points of concavities, convexities or straight edges, which are all the necessary information to characterize the two-dimensional shape of a region. The amount of smoothing performed at each point depends on the black/white configuration that composes the neighborhood where the point is located. This means that each point suffers a particular modification, which reflects the local interface between object and background. Thus, to detect such features, one must quantify the smoothing at each point. However, pixel-wise discrimination requires that the Gaussian distribution does not suffer flattening, which occurs in very low scales (σ≅0.5), only. Thus, it is proposed a distribution built from the sum of two Gaussians. One must be very narrow to ensure good localization, and the other is free to represent the desired scale. To confirm the property of marking, three boundary based corner detectors are proposed, which are applied to the detection of dominant points. The first uses the Shannon\'s entropy to quantify the smoothing at each point. The second uses the probabilities of object and background contained in the local neighborhood. The third uses the difference of Gaussians (DoG) to determine the amount of smoothing. This Work relies on the physics of light and biological vision. The presented results are good enough to suggest that the curvature detection, in visual system, occurs in the retina.
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A correspondência AdS/CFT e o plasma de quarks e glúons / The AdS/CFT correspondece and the quark-gluon plasmaJahnke, Viktor 10 October 2016 (has links)
O objetivo desse trabalho é estudar aplicações da correspondência AdS/CFT na descrição de plasmas fortemente acoplados similares ao plasma de quarks e glúons (PQG) produzido em colisões de íons pesados no RHIC e no LHC. O projeto está articulado em duas partes. Inicialmente estudamos como alguns observáveis, como a taxa de produção de fótons e diléptons, são afetados por anisotropias espaciais presentes no plasma. Isso é importante porque o PQG produzido em experimentos do mundo real tipicamente começa em configurações de alta anisotropia, que depois evoluem para configurações isotrópicas. Para modelar a anisotropia a acoplamento forte fizemos uso de uma solução de buraco negro de supergravidade do tipo IIB encontrada recentemente em arXiv:1105.3472/hep-th. Como segunda direção de pesquisa e novamente focando em aplicações da correspondência AdS/CFT na descrição do PQG, investigamos teorias de gravidade de Lovelock, que são generalizações naturais da teoria de relatividade geral de Einstein. Essas teorias contém termos com derivadas de ordem superior ao mesmo tempo que mantém equações do movimento de segunda ordem, e por isso constituem uma arena ideal para começar a entender como termos de derivada de ordem superior afetam vários observáveis físicos do plasma. / The aim of this work is to study applications of the AdS/CFT correspondence to strongly coupled plasmas similar to the quark-gluon plasma (QGP) produced in heavy ion collisions at RHIC and LHC. The project is articulated in two parts. Initially, we will study how some observables, such as photon and dilepton production rates, are affected by spatial anisotropies present in the plasma. This is important, since the QGP produced in real world experiments generically starts in highly anisotropic configurations, which later evolve towards isotropy. To model anisotropy at strong coupling we will make use of an anisotropic black hole solution of type IIB supergravity which has been recently obtained in arXiv:1105.3472/ hep-th. As a second direction of research and again focusing on applications of the AdS/CFT correspondence to the QGP, we will investigate Lovelock theories of gravity, which are natural generalizations of Einsteins general relativity. These theories contain higher derivative terms, while maintaining the equations of motion of second order, and constitute an ideal arena where to start understanding how higher derivative corrections affect various physical observables of the plasma.
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Monitoração de modelos físicos reduzidos para investigação do comportamento de estruturas em escala real. / Monitoring reduced physical models to investigate the behavior of real structures.Ticona Melo, Ladislao Roger 04 August 2011 (has links)
Esta pesquisa apresenta a monitoração de modelos reduzidos para a investigação do comportamento de estruturas. O estudo do comportamento estrutural consistiu basicamente na medição de grandezas físicas de forma experimental, para o qual os modelos físicos reduzidos foram submetidos a múltiplos ensaios em laboratório. Posteriormente, os dados experimentais foram tratados e analisados, para então serem comparados com os resultados dos modelos teóricos, avaliando assim, sua capacidade de simulação. No total foram monitorados três modelos reduzidos, cujas grandezas físicas foram medidas utilizando-se sensores elétricos, tais como: extensômetros, LVDTs e um servoatuador hidráulico, os quais estavam ligados ao sistema de aquisição da National Instrument, controlado por um computador de comando e pelos programas LabView e DynaTester. Um dos modelos construído em alumínio foi utilizado a fim de se estudar o comportamento da ponte do rio Suaçui, assim como calibrar os modelos teóricos em função dos dados experimentais da estrutura real e do modelo reduzido e estabelecer uma relação entre eles. Os outros dois modelos construídos em microconcreto foram utilizados para estudar o comportamento de estruturas na fase não linear e em fratura, para o qual foram submetidos a carregamentos incrementais. A ponte de microconcreto foi ensaiada com o intuito de se verificar a variação da rigidez de sua seção transversal e a construção de uma relação experimental de momento-curvatura. As vigas levemente armadas foram ensaiadas a flexão em três pontos até a ruptura, com a finalidade de se verificar que seu comportamento depende de vários parâmetros tais como: taxa de armadura, tamanho da viga, forma da seção transversal e a aderência aço-concreto. O estudo experimental foi complementado com ensaios de caracterização de materiais, estudos teóricos e o desenvolvimento de aplicativos como o programa PUENFLEX para o cálculo de relações de momento-curvatura de seções e o aplicativo desenvolvido em LabView para monitoração de estruturas que permite visualizar seu comportamento em tempo real. / This research presents the monitoring of scale reduced models for investigation the behavior of structures. The study of structural behavior consisted basically in the measurement of physical quantities on an experimental basis, to which the reduced physical models were subjected to multiple laboratory tests. Then the experimental data were processed and analyzed, so at the finally the results were compared with theoretical models and thereby to evaluate their ability to simulation. In total were monitored three reduced models, whose physical quantities were measured using electrical sensors such as strain gauges, LVDT\'s and a system hydraulics load, which in the same time were connected to the system of acquisition of the National Instrument, controlled by a computer command and DynaTester and LabView programs. One of the models constructed of aluminum was used to study the behavior of Suaçuí river bridge, as well as calibrate the theoretical models on the basis of experimental data of the real structure and the reduced model and to establish a relationship between them. The other two models built in microconcrete were used to study the behavior of structures in the nonlinear phase and fracture, for which they were subjected to incremental loads. The bridge of microconcrete was tested in order to verify the variations the rigidity of their cross section and the construction of an experimental relationship for the moment-curvature. The beams with minimum flexural reinforcement were tested in three-point bending to failure, in order to verify that his behavior depends on various parameters such as reinforcement ratio, the beam size, shape of cross section and steel-concrete adherence. The experimental study was completed with material characterization tests, theoretical studies and the development of applications such as PUENFLEX program for calculating the moment-curvature relationships for cross sections and the program developed in LabView for monitoring structures to visualize their behavior in real time.
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Pilares esbeltos de concreto armado com seção variável / Concrete slender columns with variable cross sectionsMalakoski, Joice 30 July 1998 (has links)
São descritas as recomendações da Norma Brasileira NBR-6118/1978 e do Código Modelo do Comité Euro-internacional du Béton CEB-1990 para a verificação da estabilidade de pilares esbeltos de concreto armado com seção variável submetidos à flexão normal composta, empregando-se a teoria do método geral. Para a obtenção dos momentos de segunda ordem são descritos os métodos de Engesser-Vianello e da integração numérica das curvaturas das seções transversais ao longo do pilar. Para a determinação do momento fletor absorvido pelas seções em função da curvatura proveniente da flexão do pilar sob a ação de uma força normal, desenvolvem-se as expressões para seções retangulares e circulares (cheias e vazadas) com base nas relações de tensão-deformação dos materiais segundo a norma e o código supracitados. Apresenta-se também um programa para microcomputador, elaborado em linguagem PASCAL, destinado à verificação da estabilidade de pilares com opção de adoção dos critérios da NBR-6118/1978 ou do CEB-1190. Não foram abordados os efeitos decorrentes de vibrações, fazendo-se apenas a descrição dos métodos de consideração dos efeitos decorrentes da deformação lenta. / The recommendations of Brazilian Code NBR-6118/1978 and Comité Euro-Internacional du Béton Model Code CEB-1990 are described, for stability verification of concrete slender columns with variable cross sections, subjected to axial load and bending moment, using the exact method. To obtain the second order bending moments, the Engesser-Vianello method and the numeric integration of the cross section curvatures along the longitudinal axial of column method are described. To obtain of bending moment supported by the cross sections due to curvature resultant of the column flexure under axialload, expressions for rectangular and circular (full and hollow) cross sections are developed, using stress-strain relations for materials proposed by model codes above mentioned. It\'s also presented a software written in PASCAL language for microcomputer and destined to column stability verification, with option to adopt the NBR-6118/1978 or CEB-1990 model code recommendations. Effects due to vibrations were nor included. Methods to take in account creep effects were described.
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Gravidade de Lovelock e a correspondência AdS/CFT / Lovelock gravity and the AdS/CFT correspondenceMisobuchi, Anderson Seigo 08 April 2016 (has links)
A correspondência AdS/CFT é uma notável ferramenta no estudo de teorias de gauge fortemente acopladas que podem ser mapeadas em uma descrição gravitacional dual fracamente acoplada. A correspondência é melhor entendida no limite em que ambos $N$ e $\\lambda$, o rank do grupo de gauge e o acoplamento de \'t Hooft da teoria de gauge, respectivamente, são infinitos. Levar em consideração interações com termos de curvatura de ordem superior nos permite considerar correções de $\\lambda$ finito. Por exemplo, a primeira correção de acoplamento finito para supergravidade tipo IIB surge como um termo de curvatura com forma esquemática $\\alpha\'^3 R^4$. Neste trabalho investigamos correções de curvatura no contexto da gravidade de Lovelock, que é um cenário simples para investigar tais correções pois as suas equações de movimento ainda são de segunda ordem em derivadas. Esse cenário também é particularmente interessante do ponto de vista da correspondência AdS/CFT devido a sua grande classe de soluções de buracos negros assintoticamente AdS. Consideramos um sistema de gravidade AdS-axion-dilaton em cinco dimensões com um termo de Gauss-Bonnet e encontramos uma solução das equações de movimento, o que corresponde a uma black brane exibindo uma anisotropia espacial, onde a fonte da anisotropia é um campo escalar linear em uma das coordenadas espaciais. Estudamos suas propriedades termodinâmicas e realizamos a renormalização holográfica usando o método de Hamilton-Jacobi. Finalmente, usamos a solução obtida como dual gravitacional de um plasma anisotrópico fortemente acoplado com duas cargas centrais independentes, $a eq c$. Calculamos vários observáveis relevantes para o estudo do plasma, a saber, a viscosidade de cisalhamento sobre densidade de entropia, a força de arrasto, o parâmetro de jet quenching, o potencial entre um par quark-antiquark e a taxa de produção de fótons. / The AdS/CFT correspondence is a remarkable tool in the study of strongly coupled gauge theories which can be mapped to a dual, weakly coupled gravitational description. The correspondence is best understood in the limit in which both $N$ and $\\lambda$, the rank of the gauge group and the \'t Hooft coupling of the gauge theory, respectively, are infinite. Accounting for higher curvature interactions allows one to begin to consider finite $\\lambda$. For example, the leading finite coupling corrections to type IIB supergravity arise as stringy corrections with schematic form $\\alpha\'^3 R^4$. In this work we investigate higher curvature corrections in a simpler scenario, the Lovelock gravity. Lovelock gravity is a nice framework to investigate such corrections since its equations of motion are still second order in derivatives and is particularly interesting from the point of view of the AdS/CFT correspondence because a large class of asymptotically AdS black holes solutions are known. We consider five-dimensional AdS-axion-dilaton gravity with a Gauss-Bonnet term and find a solution of the equations of motion which corresponds to a black brane exhibiting a spatial anisotropy, with the source of the anisotropy being an axion field linear in one of the spatial coordinates. We study its thermodynamics and we carry out the holographic renormalization using the Hamilton-Jacobi approach. Finally, we use the solution as a gravity dual to a strongly coupled anisotropic plasma with two independent central charges, $a eq c$. We compute several observables relevant to the study of the plasma, namely, the shear viscosity over entropy density ratio, the drag force, the jet quenching parameter, the quarkonium potential and the thermal photon production.
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Membrane interaction of amyloid–beta (1–42) peptide induces membrane remodeling and benefits the conversion of non–toxic Aβ species into cytotoxic aggregateJin, Sha 07 November 2016 (has links)
Das Amyloid-beta Peptid (Ab) ist der Hauptbestandteil der extrazellulären Plaques bei der Alzheimerschen Krankheit. Das Ziel der vorliegenden Arbeit ist es, die Mechanismen der Wechselwirkungen des Ab mit der Plasmamembran und der nachfolgenden zellulären Aufnahme aufzuklären. Die Aggregation, die zelluläre Aufnahme und die Zytotoxizität von Ab42 wurden durch Verwendung von fluoreszenzmarkierten Ab42 in einem Neuroblastomzellkulturmodell untersucht. Sowohl bei Inkubation mit Monomeren als auch mit Aggregaten wurde in den Zellen Ab42 detektiert. Dabei binden Ab42 Monomere und kleine Aggregate zunächst an die Zellmembran. Allerdings erfolgt keine direkte Aufnahme von Monomeren in die Zelle. Erst nach Ausbildung von Aggregaten mit geordneter Sekundärstruktur wurde Ab42 in den endozytotischen Vesikel detektiert. Voraussetzung für den an der Membran ablaufenden Aggregationsprozess ist, dass die Monomere oberhalb einer kritischen Konzentration anwesend sind, um eine Bildung von beta-Faltblatt-Strukturen (bF) und entsprechenden Aggregaten zu ermöglichen. Ab42 Aggregate, die sich durch eine bF auszeichneten, benötigten keine kritische Schwellenkonzentration für die endozytotische Aufnahme. Eng mit der Aufnahme von Ab42 Aggregaten war die Veränderung des zellulären Metabolismus verbunden. Um die Wechselwirkung zwischen Ab und der Membrannäher zu charakterisieren, wurden Modellmembransystemen einschl. riesigen Membranvesikeln genutzt. Dabei wurde beobachtet, dass sowohl Ab42 als auch Ab40 Einstülpungen in der Membran induzieren können. Kleine Aggregate beider Isoformen, die noch keine bF aufweisen, interagierten bevorzugt mit der ungeordneten Lipidphase und induzierten dabei eine negative Membrankrümmung. Diese Beobachtungen legen den Schluss nahe, dass möglicherweise das Ab selbst den endozytotischen Prozess unterstützt oder diesen sogar einleiten könnte. Dies könnte auch auf eine mögliche physiologische Funktion von Ab Aggregaten, die nicht toxisch sind, hindeuten. / The accumulation of Amyloid beta peptide 1-42 (Ab42) in extracellular plaques is one of the pathological hallmarks of Alzheimer’s disease. Several studies have suggested that a cellular reuptake of Ab42 may be a crucial step in its cytotoxicity, but mechanisms of Ab-membrane interaction and subsequent cellular uptake are not yet understood. The first aim of the present study is to answer the question whether aggregate formation is a prerequisite or a consequence of Ab-membrane interaction and of Ab endocytosis. We visualized aggregate formation of fluorescently labeled Ab42 by Förster resonance energy transfer and tracked its internalization by human neuroblastoma cells. Both monomeric and aggregated Ab42 entered the cells, however, monomer uptake faced a concentration threshold and occurred only at concentrations and time scales that allowed beta-sheet-rich (bS) aggregates to form. By uncoupling membrane binding from internalization, we found that Ab42 monomers as well as small aggregate species bound rapidly to the plasma membrane and formed bS aggregates. These structures were subsequently taken up and accumulated in endocytic vesicles. This process correlated with inhibition of cellular metabolism activities. Our data therefore imply that the formation of bS aggregates at the cell membrane is a prerequisite for Ab42 uptake and cytotoxicity. The second aim of the study is to investigate the Ab-membrane interaction in vitro by using giant unilamellar vesicles and giant plasma membrane vesicles as model membrane systems. We found that both Ab isoforms, Ab42 and Ab40, interacted with the liquid disordered phase of model membranes. Early aggregation intermediates, which did not yet bind to the amyloiddophilic dye Thioflavin T, induced negative membrane curvature. The ability of Ab to induce membrane deformation suggests that Ab may facilitate its own endocytosis. It also hints at a possible physiological function of non-toxic Ab aggregate species.
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