Zellmembranen sind hochspezialisierte Mehrkomponentenlegierungen, welche sowohl die Zelle selbst als auch ihre Organellen umgeben. Sie spielen eine entscheidende Rolle bei vielen biologisch relevanten Prozessen wie die Signaltransduktion und die Zellbewegung. Aus diesem Grund ist eine genaue Charakterisierung ihrer Eigenschaften der Schlüssel zum Verständnis der Bausteine des Lebens sowie ihrer Erkrankungen. Besonders Krebs steht im engen Zusammenhang mit Veränderungen der biomechanischen Eigenschaften vom Gewebe, Zellen und ihren Organellen. Während Veränderungen des Zytoskeletts von Krebszellen im Fokus vieler Biophysiker stehen, ist die Bedeutung der Biomechanik von Zellmembran weitgehend unklar. Zellmembranen faszinieren Wissenschaftler jedoch nicht nur wegen ihrer biomechanischen Eigenschaften. Sie sind auch Beispiele für eine selbstorganisierte und heterogene Landschaft, in der Prozesse fernab des Gleichgewichtes, wie z.B. räumliche und zeitliche Musterbildungen, auftreten. Die vorgelegte Dissertation untersucht erstmals umfassend die zentrale Rolle der Zellmembran und ihrer molekularen Architektur für die Signalübertragung, die Biomechanik und die Zellmigration. Hierfür werden einfache Modellmembranen aber auch komplexere Vesikel und ganze Zellen mittels etablierter physikalischer Methoden analysiert. Diese reichen von Fourier- Analysen zur Charakterisierung von thermisch angeregten Membranundulationen über Massenspektrometrie und ‘Optical Stretcher’ Messungen von ganzen Zellen bis hin zur Filmwaagentechnik. Des Weiteren wird ein Modellsystem vorgestellt, welches sowohl einen experimentellen als auch einen mathematischen Zugang zum ‘ME-switch’ ermöglicht. Die vorgelegte Dissertation bietet neue Einblicke in wichtige Funktionen von Zellmembranen und zeigt neue therapeutische Perspektiven in der Membran- und Krebsforschung auf.

Made available in DSpace on 2016-04-28T18:23:20Z (GMT). No. of bitstreams: 1 Denise Lage Maggioli.pdf: 29496152 bytes, checksum: d58aba37e35ff1739460c8a9b535fa32 (MD5) Previous issue date: 2007-02-13 / This research is a result of the concerns I had as a professional in education related to the evaluation of didactic material, which nowadays include not only printed material but also material connected to technology, such as softwares and online courses. This research aims at evaluating an educational software recommended to be used at the public schools of Ensino Fundamental e Médio, considering the paradigms presented in the Parâmetros Curriculares Nacionais Língua Estrangeira. The theoretical basis for this research were the Parâmetros Curriculares Nacionais -Lingua Estrangeira (Brasil, 1998) and Parâmetros Curriculares Nacionais Ensino Médio (Brasil, 1999), used as a reference by the teacher in his or her classroom, the lines of thinking in psychology that were used as basis for the teaching and learning theories that have had most influence in the teaching and learning process of foreign language in our culture (Williams & Burden, 1997; Rego, 2004; Vygotsky, 1993,2003), the language description theories (Graddol, 1994; Hutchinson & Waters 1987; Bloor & Bloor, 1995), considerations on didactic material (Cunningsworth, 1984, 1995; Tomlinson, 1998; Graves, 2000), the definition of task according to Ellis (2003), software evaluation criteria (Squires & McDougall, 1997; Stirling, 1998; Alagumali & Anderson, 1997) and the evaluation criteria for didactic material by Ramos (1998) and Freire et al. (2004). This research has shown that, although the language description theories and the teaching and learning theories that constitute the software do not match the educational paradigms in force nowadays, according to the Parâmetros Curriculares Nacionais Língua Estrangeira (Brasil, 1998) and the Parâmetros Curriculares Nacionais Ensino Médio (Brasil, 1999), from a technological point of view the software presents resources that can help both teachers and students in the teaching and learning process of a foreign language / Esta pesquisa originou-se de uma inquietação minha como profissional da área de educação com respeito à avaliação de material didático, que hoje além de material impresso inclui também materiais ligados à área tecnológica, tais como softwares e cursos on-line. O objetivo deste trabalho é avaliar um software educacional (Tell Me More), recomendado para ser usado na rede pública de Ensino Fundamental e Médio à luz dos paradigmas educacionais apregoados nos Parâmetros Curriculares Nacionais Língua Estrangeira. As bases teóricas desta pesquisa foram os Parâmetros Curriculares Nacionais -Língua Estrangeira (Brasil, 1998) e Parâmetros Curriculares Nacionais Ensino Médio (Brasil, 1999), utilizados como referência para o trabalho do professor em sala de aula, as correntes de pensamento da psicologia que serviram de base para as teorias de ensino-aprendizagem que mais influenciaram o ensino-aprendizagem de língua estrangeira em nossa cultura (Williams & Burden, 1997; Rego, 2004; Vygotsky, 1993,2003), as teorias de linguagem (Graddol, 1994; Hutchinson & Waters 1987; Bloor & Bloor, 1995), considerações sobre material didático (Cunningsworth, 1984, 1995; Tomlinson, 1998; Graves, 2000), o conceito de tarefa segundo Ellis (2003), os critérios de avaliação de software (Squires & McDougall, 1997; Stirling, 1998; Alagumali & Anderson, 1997) e os critérios de avaliação de Ramos (1998) e Freire et al. (2004). A pesquisa revelou que, embora as teorias de linguagem e de ensino-aprendizagem que embasam o software contrariam os paradigmas educacionais vigentes segundo os Parâmetros Curriculares Nacionais Língua Estrangeira (Brasil, 1998) e os Parâmetros Curriculares Nacionais Ensino Médio (Brasil, 1999), do ponto de vista tecnológico apresenta recursos que podem auxiliar a professores e alunos no processo de ensino-aprendizagem

Submitted by Filipe dos Santos (fsantos@pucsp.br) on 2018-06-21T12:35:55Z No. of bitstreams: 1 Telma Regina Ventura.pdf: 990261 bytes, checksum: f67f9c75786c9133ffe85d9e40344651 (MD5) / Made available in DSpace on 2018-06-21T12:35:55Z (GMT). No. of bitstreams: 1 Telma Regina Ventura.pdf: 990261 bytes, checksum: f67f9c75786c9133ffe85d9e40344651 (MD5) Previous issue date: 2018-04-10 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The present research aims to investigate the deconstruction of the feminine voice silencing in the contemporary Portuguese writer Inês Pedrosa’s novel Fazes-me Falta (2002). For this purpose, it is intended to undertake an analysis of the modes in which the literary formal components are constituted in order to engender a structure distinguished as a performative narrative. In the pedrosina’s performative narrative in analysis, the convergence of the literary strategies – such as the genological hybridity, the inter-artistic dialogue, the moving writing construction – are composed simultaneously and in combination with the plot, in an inter-artistical dialogue with the Galician-Portuguese troubadour-like medieval lyric, particularly with Troubadour love songs and the Troubadour friendship ones. Considering that Art constantly constitute a political action and Inês Pedrosa, in her both journalistic activity and career as an writer, lodges an active politic attitude in the Portuguese Society, it is observed that the resumption, on Perdrosa’s literary work, of the twelfth century literary structure which excluded the women’s voice produces meanings that denotes the social situation of the contemporary Portuguese women: even achieving social and political rights, women have still been subjected to the voice silencing, as long as their social voices and claims have not been incorporated on political actions. Therefore, the investigation is outlined into three chapters. The first chapter, entitled “The Performative Realism and the writing configurations in the Comtemporary Portuguese Literature”, presents the theoretical background of Linda Hutcheon, Erik Schollhammer and Marcos Siscar, supporting the Post-modernism aesthetics in a dialogue with the new realisms in Literature, and associated with Miguel Real and Álvaro Gomes produces the characterization of the literary performative realism in Portugal. The chapter 2, “Performative narrative: contemporary quests”, embraces the concepts related to the performative narrative, as established by Graciela Ravetti, as well as defines an historical overview of performative arts, taking Renato Cohen’s studies as reference. At last, the third chapter, “The Aesthetic-critical tracing of the Portuguese feminine voice silencing in the performative narrative of Fazes-me Falta”, outlines the construction elements of the corpus examined, characterized as a performative narrative – Giles Deleuze, Lúcia Castelo Branco, Graciela Ravetti and Mário Perniolla assemble the theoretical basis, elucidating the pedrosina’s novel literary formal particularities. Segismundo Spina and Natália Correia devise the aspects of the (in)existence of both poetic and authorship feminine voices in the Galician-Portuguese troubadour-like medieval lyric / A presente pesquisa tem como proposta investigar a desconstrução do silenciamento da voz feminina na obra Fazes-me Falta (2002), da escritora portuguesa contemporânea Inês Pedrosa. Para tanto, empreender-se-á uma análise dos modos pelos quais os componentes formais se constituem a fim de engendrar uma estrutura caracterizada como uma narrativa performática. Na narrativa performática pedrosina em análise, a convergência de determinadas estratégias composicionais – o hibridismo genológico, o diálogo interartístico, a escritura movente e rizomática – compõem-se em simultâneo e, em conjunto ao enredo, dialogam interartisticamente com a Lírica Medieval Trovadoresca galego-portuguesa, em especial com as Canções de Amor e as Canções de Amigo. Sabendo-se que a Arte invariavelmente se constitui em uma ação política e que Inês Pedrosa, tanto em sua atividade jornalística quanto como escritora, possui uma postura política ativa na sociedade portuguesa, observa-se que a retomada, na escrita pedrosina, de uma estrutura literária do século XII que excluía a voz da mulher, gera sentidos que evidenciam a situação social da mulher portuguesa contemporânea: mesmo tendo adquirido o direito à voz, ainda se encontra submetida ao silenciamento, visto que, mesmo falando, não é ouvida. Assim, a pesquisa apresenta-se dividida em três capítulos. O primeiro capítulo, intitulado “O Realismo Performático e as configurações da escrita na Literatura Portuguesa Contemporânea”, traz as contribuições teóricas de Linda Hutcheon, Erik Schollhammer e Marcos Siscar, subsidiando as estéticas do Pós-modernismo em diálogo com os novos realismos na Literatura e, associados a Miguel Real e Álvaro Gomes, compõem a caracterização do Realismo Performático literário em Portugal. O capítulo II, “Narrativa Performática: Demandas contemporâneas”, abarca as conceituações relativas à narrativa performática, como estabelecida por Graciela Ravetti, delineando também o Histórico das artes performáticas, tendo como referência as pesquisas de Renato Cohen. Por fim, o terceiro capítulo, “A tessitura estético-crítica do silenciamento da voz da mulher portuguesa na narrativa performática de Fazes-me Falta”, evidencia os elementos de construção do corpus em estudo, os quais o caracterizam enquanto uma narrativa performática; para tanto, Giles Deleuze, Lúcia Castelo Branco, Graciela Ravetti e Mário Perniolla compõem a fundamentação, elucidando as especificidades formais da obra pedrosina. Na sequência, os pressupostos de Segismundo Spina e Natália Correia auxiliam a pontuar os aspectos formais das da (in)existência da voz poética e da voz autoral femininas na Lírica Medieval Galego-portuguesa

Thesis (Ph. D.)--Salve Regina University, 2006.

Submitted by Aelson Maciera (aelsoncm@terra.com.br) on 2017-08-03T19:57:54Z No. of bitstreams: 1 DissBC.pdf: 2204728 bytes, checksum: d6f6478009c1aa1b7990a8bbfc71eaa8 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-08-08T19:03:08Z (GMT) No. of bitstreams: 1 DissBC.pdf: 2204728 bytes, checksum: d6f6478009c1aa1b7990a8bbfc71eaa8 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-08-08T19:03:15Z (GMT) No. of bitstreams: 1 DissBC.pdf: 2204728 bytes, checksum: d6f6478009c1aa1b7990a8bbfc71eaa8 (MD5) / Made available in DSpace on 2017-08-08T19:08:45Z (GMT). No. of bitstreams: 1 DissBC.pdf: 2204728 bytes, checksum: d6f6478009c1aa1b7990a8bbfc71eaa8 (MD5) Previous issue date: 2016-03-08 / Não recebi financiamento / Context: Operating in different contexts and segments, embedded systems (ESs) are increasingly present in everyday society. The ESs usually operate invisibly to the user but, even so, possible software failures cease to pose risks, causing serious material and financial damage. Taking into consideration the safety of users of ESs, government entities and institutions around the world have studied and created standards development and SEs test to ensure systems that are more robust and free from defects that may cause faults that may endanger the user. However, standards are usually applied at the level of code, which increases substantially the resources to be used if there are defects in the SE. Objective: To present the UL/ME Strategy that addresses the shortcomings described in SEs certification standard, UL 1998 level modeling, more specifically, in the model of Statechart states. The purpose is to anticipate the identification of defects, to generate code that has more chance to meet the standard requirements, preventing rework and therefore improving quality. Methodology: The study was conducted in three stages: first stage identified the defects treated by the standard UL 1998, tabulating these defects, and then, link them to the SEs components. In the second stage were designed generic models for each component and also the ESs models that represents the tests required by the standard for each components, and in the third step, it was created two proposed for use UL/ME Strategy, one for ESs already implemented and other for ESs in development. These proposals were used for evaluation of the strategy using two real ESs, one already implemented and other in development. Results: According to the requirements of UL 1998 standard, the use of Strategy UL/ME helped to correct the defects of the first ES and evaluated the development of the second ES. Conclusion: the use of Strategy UL/ME assisted in the correction of an SE already implemented and modeling of an ES in development. / Contexto: Operando em diferentes contextos e segmentos, os sistemas embarcados (SEs) estão cada vez mais presentes no cotidiano da sociedade. Os SEs geralmente operam de forma invisível ao usuário mas, nem por isso, possíveis falhas de software deixam de oferecer riscos, ocasionando sérios danos materiais e financeiros. Levando em consideração a segurança dos usuários de SEs, entidades governamentais e instituições pelo mundo têm estudado e criado normas de desenvolvimento e de teste de SEs que garantam sistemas mais robustos e livres de defeitos que possam gerar falhas que ponham em risco o usuário. Contudo, as normas são habitualmente aplicadas no nível de código, o que aumenta, substancialmente, os recursos a serem empregados caso haja defeitos no SE. Objetivo: Apresentar a estratégia UL/ME que trata os defeitos descritos na norma de certificação de SEs, a UL 1998, no nível de modelagem, mais especificamente, no modelo de estados Statechart. O propósito é antecipar a identificação dos defeitos, de forma a gerar código com mais chance de atender aos requisitos da norma, evitando retrabalho e, consequentemente, melhorando a qualidade. Método: O trabalho foi realizado em três etapas: na primeira identificaram-se os defeitos tratados pela norma UL 1998, tabulando esses defeitos de forma a associá-los aos componentes de SEs; na segunda etapa foram desenhados modelos genéricos para cada componente e também os modelos de componentes de SEs que representam os testes requeridos pela norma e na terceira etapa, criaram-se duas proposta para utilização da Estratégia UL/ME, uma para SEs já implementados e outra para SEs em desenvolvimento. Essas propostas serviram para avaliação da estratégia utilizando dois SEs reais, um já implementado e outro em desenvolvimento. Resultados: De acordo com os requisitos da norma UL 1998, o uso da Estratégia UL/ME auxiliou a correção dos defeitos do primeiro SE avaliado o desenvolvimento do segundo SE. Conclusão: o uso da Estratégia UL/ME auxiliou na correção de um SE já implementado e na modelagem de um SE em desenvolvimento.

Made available in DSpace on 2014-12-17T14:36:04Z (GMT). No. of bitstreams: 1 ClaudiaSRSR_dissert.pdf: 1328426 bytes, checksum: 1e2ef332bfd6ea4bbab3040b4b1f6382 (MD5) Previous issue date: 2004-03-08 / ?Ce travail que nous venons de pr?senter apport une syst?matisation sur la viabilit? de la praxis de l??ducateur fran?ais C?lestin Freinet (1896-1996). Il s?agit d?une ?tude qualificative, recherche-action, d?velopp?e dans une ?cole coop?rative l? ?cole Freinet ? Natal/RN Br?sil, aupr?s des ?l?ves du 5?me et 8?me s?ries de l?Enseignement Fondamental. Le probl?me central que nous a amen? ? cette recherche, a ?t? le fait de v?rifier les progressions dans la production scientifique et dans les pratiques des enseignants qui ont ? la charge l??ducation Infantine et les premi?res s?ries de l?Enseignement Fondamental. Tout cela en tenant compte en concevoir l??l?ve en tant que sujet actif de son apprentissage et coresponsable ? l?organisation du travail scolaire. Toutefois, qaund-il s?agit des quatre derni?res s?ries de l?Enseignement Fondamental (5?me au 8?me s?ries), les propositions progressistes sont prises comme quelque chose pratiquement impossible d?en mettre en marche. Pour attenuer la lacune th?orique sur le sujet, nous avons offert un texte significatif pour les enseignants d?une fa?on g?n?rale, les chercheurs de l?acad?mie et pour l??colechamp de la recherch?. Tout cela par le fait de ne pas donner de priorit? ? une technique ou ? un principe, en particulier. Cette p?dagogie est discut?e autant que possible dans son contexte global et aussi sur le comment s?est manifest?e dans sa pr?xis . Nous avons mis en relief les aspects importants pour le fonctionnement de la salle de classe, aussi que les estrat?gies utilis?es pour la construction, communication et documentation des connaissances L?intervention nous a permis de construire l?objet par la r?flexion en action, ? partir des donn?es obtenues pendant les observations, les entretiens, les enterviews, les moments d??tudes et de la qu?te des textes ?crits. L?analyse a ?t? faite ? la lumi?re de la methodologie comprehensive (Kaufmann, 1996), entrelac?e au materiau empirique et ? la th?orie. Cette forme d?analyse nous a permis d?obtenir la logique dans l?ensemble comme nous crayons que doit caracteriser la recherche aux Sciences Humaines et Sociales. Les consid?rations finales mettent l?accent d?un c?t? sur l?efficacit? de la p?dagogie Freinet, pour orienter le processus de l?enseignement apprentissage, en tous les d?gres de l?enseignement et de l?autre c?t? nous montre la n?cessit? urgente de l??quipe de l??cole champ de la recherche, de qualifier sa pratique ? partir des r?f?rences th?oriques-pratiques de la p?dagogie Freinet / ?Esta disserta??o constitui-se na sistematiza??o de um estudo qualitativo, pesquisa-a??o, que realizamos na Escola Freinet, em Natal/RN - Brasil, sobre a viabilidade da pr?xis da pedagogia do educador franc?s, C?lestin Freinet (1896-1966), em turmas de 5? a 8? s?ries do ensino b?sico. O problema central que nos mobilizou ? pesquisa, foi o fato de verificarmos os avan?os na produ??o cient?fica e nas pr?ticas dos docentes que atuam na educa??o infantil e nas primeiras s?ries do ensino fundamental, na perspectiva de conceber o aluno enquanto sujeito ativo da sua aprendizagem e co-respons?vel na organiza??o do trabalho escolar. Por?m, quando se trata das quatro ?ltimas s?ries do fundamental, as propostas progressistas s?o tomadas como algo praticamente imposs?vel de materializar-se. Procuramos atenuar a lacuna te?rica sobre o tema, oferecendo um texto relevante para professores, de modo geral, pesquisadores da academia e para a escola pesquisada, sobretudo, pelo fato de n?o priorizarmos uma t?cnica ou princ?pio freinetiano, em particular. Essa pedagogia ? discutida, o mais pr?ximo poss?vel, da sua globalidade e de como se revelou naquela pr?xis. Destacamos os aspectos relevantes para o funcionamento da sala de aula, bem como as estrat?gias utilizadas para a constru??o, comunica??o e documenta??o dos conhecimentos. A interven??o permitiu que constru?ssemos o objeto pela reflex?o em a??o, a partir de dados produzidos durante as observa??es, as entrevistas, as conversas, os momentos de estudos e a consulta a materiais escritos. A an?lise se deu, ? luz da metodologia compreensiva (Kaufmann, 1996), entrela?ando-se o material emp?rico com a teoria. Esta forma de an?lise permitiu alcan?armos a l?gica do conjunto, como cremos que deve caracterizar a pesquisa nas Ci?ncias Humanas e Sociais. As considera??es finais indicam o potencial da pedagogia Freinet, para orientar os processos de ensino e aprendizagem em todas as etapas da escolaridade. Revelam, ainda, a necessidade, premente, da equipe da escola pesquisada qualificar a sua pr?xis, a partir do referencial te?rico-pr?tico da pedagogia Freinet

This Bachelor’s thesis examines the use of ancient bronze statues in the 2017 film Call me by your name by director Luca Guadagnino. Various scenes which feature ancient statues are examined individually using semiotic analysis. The scenes are examined individually, first described on a denotative level, then analyzed on a connotative level. The theoretical stand point is based on the studies of art works in film. Key theoretical concepts used are ”in between-ness” which is a state in which change in narrative is made possible through looking at art, and ”parallels”, a means of which to make art represent the characters in the film. The thesis finds the sculptures in Call me by your name to play a part in affecting the narrative of the film, mainly in regard to the love story between the two lead characters, two men named Elio and Oliver. The acts of looking, examining, and touching the statues in this film help the narrative turn in favor of the lead characters romantic relationship. The thesis argues that the nude bronze sculptures of men from ancient Greece are used in this film as signifiers of desire, timelessness and homoerotic lust.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is a complex disease with unknown cause. It affects about 0.4 percent of the population. It is a chronic disease that manifests itself in an impairment fatigue that is impaired by physical exertion. Purpose: The purpose of the study was to illustrate how people diagnosed with ME/CFS experience the primary care treatment. Method: An empirical questionnaire with mixed method was used. Most questionnaires were quantitative, and one question was qualitative. Result: ME patients may wait several years and meet several doctors before they get their diagnosis. The result showed that most respondents felt that they did not receive good treatment in primary care. Conclusion: People with ME/CFS want to be treated with respect and want primary care to listen and take them seriously. In a partnership between the primary care and healthcare personnel, they could meet more equally, and the ME sufferers would not have to wait several years to meet several doctors before receiving the assistance and support they need in their illness. Clinical significance: New research on how healthcare professionals can help people with ME/CFS is needed. Research would also be needed on how the role of nurse could be extended to be a key part of primary care for people with ME/CFS.

The aim of this essay is to discover how the protagonist constructs her identity, through her discourse, in the work I, Rigoberta Menchú: An Indian Woman in Guatemala. While the work is considered a testimony, the oral narrative has been modified by the author. Hence in this essay, the work is considered narrative literature, characterised by the narrator as the protagonist. The postcolonial theory of Edward Said is applied, as well as the description of the social structures and the dominant discourse in Latin America, and the concepts of Critical Discourse Studies by Teun Adrianus van Dijk. It has been argued that the discourse by the protagonist, reproduces the existence of the separation between “Us” and the “Others”. The protagonist constructs a discourse where she must break the rules of her own community and adapt to the cultural hegemony of the society, to be able to expand her knowledge and develop herself. In addition, the protagonist creates a discourse in which she must have a pluricultural identity, to be accepted, outside of her community. In conclusion, the protagonist must follow the norms that maintain the social structures of the society, that originate from the colonial era, to be able to attain power.

Zellmembranen sind hochspezialisierte Mehrkomponentenlegierungen, welche sowohl die Zelle selbst als auch ihre Organellen umgeben. Sie spielen eine entscheidende Rolle bei vielen biologisch relevanten Prozessen wie die Signaltransduktion und die Zellbewegung. Aus diesem Grund ist eine genaue Charakterisierung ihrer Eigenschaften der Schlüssel zum Verständnis der Bausteine des Lebens sowie ihrer Erkrankungen. Besonders Krebs steht im engen Zusammenhang mit Veränderungen der biomechanischen Eigenschaften vom Gewebe, Zellen und ihren Organellen. Während Veränderungen des Zytoskeletts von Krebszellen im Fokus vieler Biophysiker stehen, ist die Bedeutung der Biomechanik von Zellmembran weitgehend unklar. Zellmembranen faszinieren Wissenschaftler jedoch nicht nur wegen ihrer biomechanischen Eigenschaften. Sie sind auch Beispiele für eine selbstorganisierte und heterogene Landschaft, in der Prozesse fernab des Gleichgewichtes, wie z.B. räumliche und zeitliche Musterbildungen, auftreten. Die vorgelegte Dissertation untersucht erstmals umfassend die zentrale Rolle der Zellmembran und ihrer molekularen Architektur für die Signalübertragung, die Biomechanik und die Zellmigration. Hierfür werden einfache Modellmembranen aber auch komplexere Vesikel und ganze Zellen mittels etablierter physikalischer Methoden analysiert. Diese reichen von Fourier- Analysen zur Charakterisierung von thermisch angeregten Membranundulationen über Massenspektrometrie und ‘Optical Stretcher’ Messungen von ganzen Zellen bis hin zur Filmwaagentechnik. Des Weiteren wird ein Modellsystem vorgestellt, welches sowohl einen experimentellen als auch einen mathematischen Zugang zum ‘ME-switch’ ermöglicht. Die vorgelegte Dissertation bietet neue Einblicke in wichtige Funktionen von Zellmembranen und zeigt neue therapeutische Perspektiven in der Membran- und Krebsforschung auf.:1 Introduction 2 Background 2.1 The Cell Membrane 2.1.1 Lipids in Cell Membranes 2.1.2 Membrane Proteins 2.1.3 An Overview on Membrane Models 2.1.4 Lipid Rafts 2.2 Model Membranes – An Experimental Access to Cell Membranes 2.2.1 Surface Tension and Thermodynamic Equilibrium 2.2.2 Langmuir Monolayer 2.2.3 The Polymorphism of Langmuir Monolayers 2.2.4 Membrane Vesicles 2.3 Biological Membranes as Semiflexible Shells 2.3.1 Elasticity of Soft Shells 2.3.2 Helfrichs Theory About Bending Deformations 2.3.3 Membrane Undulation 2.4 Membranes in Cell Signaling 2.4.1 Signal Transduction Fundamentals 2.4.2 Phosphoinositides 2.4.3 Phosphatidylinositol Signaling Pathway 2.4.4 The Myristoyl-Electrostatic Switch 2.5 Reaction-Diffusion Systems 2.5.1 Diffusion 2.5.2 Michaelis-Menten Kinetics 2.5.3 Reaction-Diffusion Systems 3 Methods, Materials and Theory 3.1 Optical Microscopy 3.1.1 Fluorescence Microscopy 3.1.2 Phase Contrast Microscopy 3.2 Cell Culture and GPMV Formation 3.2.1 Tumor Dissociation and Cell Culturing of Primary Cells 3.2.2 Cell Lines and Cell Culturing 3.2.3 Preparation of Giant Plasma Membrane Vesicles 3.3 Optical Stretcher 3.4 Fourier Analysis of Thermally Excited Membrane Fluctuations 3.4.1 The Quasi-Spherical Model – Membrane Fluctuations 3.4.2 Determination of the Bending Rigidity 3.5 Mass Spectrometry 3.5.1 MALDI-TOF Mass Spectrometry 3.5.2 ESI Mass Spectrometry 3.6 Migration, Invasion and Cell Death Assays 3.7 Langmuir-Blodgett Technique 3.7.1 Langmuir Troughs and Film Balances 3.7.2 Experimental Setup and Monolayer Preperation 3.7.3 Phospholipids, Dyes and Buffer Solutions 4 Fluctuations in Cell Membranes 4.1 Cell Membrane Softening in Human Breast and Cervical Cancer Cells 4.1.1 Bending Rigidity of Human Beast and Cervical Cell Membranes 4.1.2 MALDI-TOF Analysis of Lipid Composition 4.1.3 Summary and Discussion 4.2 Targeting of Membrane Rigidity – Implications on Migration 4.2.1 ESI Tandem Analysis of Lipid Composition 4.2.2 Biomechanical Behavior of Whole Cells and Membranes 4.2.3 Migration and Invasion Behavior 4.2.4 Summary and Discussion 5 Oscillations in Cell Membranes 5.1 Mimicking the ME-switch 5.1.1 DPPC/PIP2 monolayers at the presence of MARCKS 5.1.2 Lateral organization of PIP2 in DPPC/PIP2 monolayers 5.1.3 Translocation of MARCKS 5.1.4 Phosphorylation of MARCKS by PKC 5.1.5 Summary and Discussion 5.2 Dynamic Membrane Structure Induces Temporal Pattern Formation 5.2.1 Mechanism of the Oscillation 5.2.2 Modeling the ME-switch 5.2.3 Time Evolution 5.2.4 Phase Diagrams and Open Systems 5.2.5 Summary and Discussion 6 Conclusion and Outlook Appendix Bibliography List of Figures List of Abbreviations Acknowledgement