Despite progress in our understanding of the molecular drivers that propagate the overall process of metastasis, the adaptation of specific organs upon these molecular interactions for metastatic entry remains poorly understood. This is particularly true for liver metastases, the liver being a common site for metastatic disease, and metastatic hepatic tumors are more prominent than primary hepatocellular or biliary tumors. Liver metastases most commonly arise from colorectal cancer than any other cancer and constitute one of the most detrimental outcomes of cancer, characterized by poor prognosis, high mortality, and no effective therapies available other than surgical interventions. Since interactions between tumour cells and the tumour microenvironment play an important part in the engraftment, survival, and progression of the metastases, the discovery of new drivers of liver metastasis with the potential to become therapeutic and preventive targets is required to advance the care of liver metastasis patients as well as cancer patients at risk of metastatic spread to the liver. The alteration of the physical structure of the tissue is extremely important in the progression of malignant diseases, such as cancer metastasis, as it directly affects the extravasation and colonization of tumour cells. The major hurdles in liver metastasis research, stem not only from our insufficient understanding of the molecular mechanisms directing and mediating metastasis particularly to the liver but also from the limited number of pre-clinical models available that mimic human disease and enable the study of the complex interactions between tumor cells and the liver microenvironment. The liver metastatic process underlies the acquisition of key adaptations by tumor-derived factors and is determined by both tumour-intrinsic properties and the crosstalk between tumour cells and stromal cells in the liver. A normal functioning and structurally intact extracellular matrix (ECM) constitute a hostile “soil” for seeding tumor cells to colonize. Eventually, it is the ability of tumor cells to remodel the liver microenvironment and create a supportive niche for metastatic tumor cell survival and outgrowth that determines successful metastatic colonization. Among tumour-secreted factors, which are recognized as major contributors to the formation of pre-metastatic and metastatic niches, tumor-derived extracellular vesicles (EVs) have recently arisen as crucial players in cell-to-cell communication and in the remodeling of distant microenvironments that favor organ-specific metastasis. Therefore, we sought to determine the role of tumor-derived EVs in the modulation of the liver microenvironment and their specific contribution to supporting metastatic colonization of the liver. The preliminary step to this process was to establish a model system to identify EV-associated targets and their effect on the ECM remodelling. Immunohistochemical analyses of primary colon tumour (CRC) and secondary liver metastases (CRC liver MET) tissue samples from patients with CRC revealed higher stromal TIMP1 levels in CRC liver MET than in CRC. The elevated stromal TIMP1 signature in the invasive front was associated with poor progression-free survival in patients with CRC liver MET. Our characterisation of the CRC tumour-derived EVs showed TIMP1 enrichment in the EVs (TIMP1EV) compared to its parental cell. Using cultures of primary liver fibroblasts, we could demonstrate that TIMP1 enrichment in the CRC-EVs was associated with regulation of TIMP1 levels in the EV-conditioned liver fibroblasts. Using our optimized ex vivo 3D ECM remodelling assay, we observed that pre-conditioning the liver fibroblasts with EVs from CRC cells promotes ECM remodelling. In accordance with our cell line model, we showed that serum-derived TIMP1EV from CRC patients promotes ECM remodelling. Moreover, high serum TIMP1EV expression in CRC liver MET patients was significantly associated with poor overall survival. In addition, our data also indicated that the determination of EV-associated TIMP1 is superior for non-invasive diagnosis than the analysis of soluble TIMP1 from total serum. Finally, we showed that HSP90AA is constitutively bound to TIMP1EV and that targeting HSP90AA leads to TIMP1 downregulation and inhibits ECM-mediated remodelling. This study defining the contribution of extravesicular TIMP1 to liver metastasis brings a novel insight into the molecular mechanisms through which tumor-secreted factors packaged via EVs promote remodelling of the liver microenvironment. The clinical significance of overexpression of extravesicular TIMP1 in patients with colorectal liver metastases highlights its potential as a prognostic biomarker and therapeutic target. With further clinical studies, Heparin and HSP90 inhibitors targeting the EV mediated TIMP1 regulation could be a putative treatment strategy to treat colorectal liver metastases.:Table of Contents Abbreviations v 1. Introduction 1 1.1 Colorectal cancer 1 1.1.1. Incidence and mortality 1 1.1.1. Tumor staging 2 1.1.1. Pattern of distant metastases in colorectal cancer 5 1.2 Colorectal liver metastases 6 1.2.1 Current evaluation and treatment strategies for colorectal liver metastases 7 1.2.2 The liver metastasis cascade - a multi-step process 10 1.3 Tumor microenvironment 12 1.3.1 Tumour-stroma interactions 15 1.3.2 ECM remodelling and its role in CRC tumor progression 17 1.4 Extracellular vesicles 21 1.4.1 EV types 21 1.4.2 Biogenesis and secretion of EVs 22 1.4.3 Molecular composition of EVs 24 1.4.4 Biological functions of EVs 26 1.4.5 EVs in Tumor microenvironment 28 1.4.6 EVs in Tumor-fibroblast communication 29 1.4.7 Role of EVs in colorectal cancer 31 1.5 Tissue inhibitor of metalloproteinases (TIMP1) 35 1.5.1 TIMP1 in cancer 37 2. Background and Research Aims 39 3. Material and Methods 40 3.1 Material 40 3.1.1 Devices 40 3.1.2 Additional material and equipment 42 3.1.3 Fine chemicals 43 3.1.4 Biochemicals 45 3.1.5 Primary antibodies 46 3.1.6 Secondary antibodies 47 3.1.7 Nucleic acids 47 3.1.8 Consumables 50 3.1.9 Softwares 51 3.2 Methods 52 3.2.1 Patients 52 3.2.2 Immunohistochemistry 52 3.2.3 Hematoxylin eosin staining 54 3.2.4 Cell lines 54 3.2.5 Primary liver fibroblast cell lines 54 3.2.6 Passaging and freezing of cells 55 3.2.7 Revival of frozen cells 55 3.2.8 Cell counting 56 3.2.9 EV Isolation from CRC cell lines 56 3.2.10 Isolation of serum-derived EVs from liquid biopsies 56 3.2.11 Characterisation of EVs 57 3.2.12 Treatment of Fibroblasts with EVs 58 3.2.13 Stimulation of PFs with recombinant TIMP1 59 3.2.14 RNA isolation 59 3.2.15 cDNA synthesis 59 3.2.16 Quantitative Real-Time PCR (qRT-PCR) 60 3.2.17 Protein quantification 61 3.2.18 Immunoblotting and co-immunoprecipitation 61 3.2.19 ELISA 62 3.2.20 TIMP1 Knock-Out (KO) and Over-Expression (OE) 62 3.2.21 17 AAG and HSP90AA antibody treatment 63 3.2.22 3D ECM-remodelling assay 63 3.2.23 PKH staining 65 3.2.24 In vivo experiments 65 3.2.25 DAPI staining 66 3.2.26 Tissue explant model 66 3.2.27 Statistical analysis and reproducibility 67 4. Results 68 4.1 Identification of TIMP1 as target molecule 68 4.1.1 Identification of TIMP1 as a target through data mining 68 4.1.2 Localization pattern of TIMP1 in CRC and CRC liver MET 70 4.1.3 Invasion front-specific overexpression of TIMP1 in the stroma of patients with CRC liver MET is associated with poor progression-free survival (PFS) 72 4.2 Model system to study CRC-EV mediated ECM remodelling 73 4.2.1 Investigating the role of CRC- derived EVs in the evolution of colorectal liver metastases 73 4.2.2 Characterizsation of isolated EVs from the CRC cell lines 74 4.2.3 TIMP1 enrichment in EVs derived from CRC cell lines 75 4.2.4 CRC-derived TIMP1EV regulates TIMP1 levels in recipient fibroblasts 76 4.2.5 TIMP1EV mediated TIMP1 upregulation in the recipient fibroblast is an EV-mediated effect 79 4.2.6 Recombinant TIMP-1 induces TIMP1 levels in recipient pFs in a time- and concentration-dependent manner 81 4.2.7 Alteration of TIMP1 levels in HCT 116 cells translates into EVs but does not affect EV packaging. 83 4.2.8 TIMP1EV levels in CRC EVs determine TIMP1 levels in recipient fibroblasts 85 4.2.9 EV-mediated TIMP1 upregulation in pFs induces ECM remodelling 86 4.2.10 TIMP1 levels in the PFs influence the extent of ECM remodelling 88 4.3 Clinical significance of TIMP1EV 89 4.3.1 TIMP1 enriched in serum-derived EVs of CRC patients compared to healthy controls 89 4.3.2 Serum derived TIMP1EV from CRC patients regulate TIMP1 levels in primary liver fibroblasts 91 4.3.3 Serum derived TIMP1EV from CRC patients promote ECM remodelling 93 4.3.4 TIMP1EV exhibits superior stratification power compared to soluble TIMP1 in liquid biopsies 93 4.3.5 TIMP1EV is a non-invasive independent prognostic marker in colorectal liver metastases 94 4.4 Targeting TIMP1EV mediated ECM remodelling 97 4.4.1 TIMP1EV binds to HSP90AA 97 4.4.2 HSP90 inhibition interferes with TIMP1 protein stabilisation 99 4.4.3 17AAG attenuates TIMP1EV-mediated ECM remodelling 101 4.5 EVs derived from murine CRC cell lines regulate TIMP1 levels in recipient fibroblasts 104 4.6 Increased homing of CRC EVs to the liver compared to other organs 106 4.7 TIMPEV regulates TIMP1 levels in liver tissues 108 5. Discussion 112 5.1 TIMP1 Localization and its significance in liver metastases 112 5.2 Model system to study the role of CRC-EVs in liver metastasis 113 5.3 In-vitro model to study the pro-metastatic effects of TIMP1EV 114 5.4 Serum-derived extravesicular TIMP1 and its pro-metastatic functions underlying remodeling of the extracellular matrix 116 5.5 Clinical significance of TIMP1EV in colorectal liver metastases 117 5.6 Scope of HSP90 inhibitors in the prevention and treatment of CRC liver metastases...……………………………………………………………………………………..118 6. Future perspectives and concluding remarks 120 7. Graphical summary of the findings 122 Zusammenfassung 123 Summary 125 List of figures 127 List of Tables 129 References 130 Acknowledgements 163 Appendix 165

Molecular reprogramming of stromal microarchitecture by tumour-derived extracellular vesicles (EVs) is proposed to favour pre-metastatic niche formation. We elucidated the role of extravesicular tissue inhibitor of matrix metalloproteinase-1 (TIMP1EV) in pro-invasive extracellular matrix (ECM) remodelling of the liver microenvironment to aid tumour progression in colorectal cancer (CRC). Immunohistochemistry analysis revealed a high expression of stromal TIMP1 in the invasion front that was associated with poor progression-free survival in patients with colorectal liver metastases. Molecular analysis identified TIMP1EV enrichment in CRC-EVs as a major factor in the induction of TIMP1 upregulation in recipient fibroblasts. Mechanistically, we proved that EV-mediated TIMP1 upregulation in recipient fibroblasts induced ECM remodelling. This effect was recapitulated by human serum-derived EVs providing strong evidence that CRC release active EVs into the blood circulation of patients for the horizontal transfer of malignant traits to recipient cells. Moreover, EV-associated TIMP1 binds to HSP90AA, a heat-shock protein, and the inhibition of HSP90AA on human-derived serum EVs attenuates TIMP1EV-mediated ECM remodelling, rendering EV-associated TIMP1 a potential therapeutic target. Eventually, in accordance with REMARK guidelines, we demonstrated in three independent cohorts that EV-bound TIMP1 is a robust circulating biomarker for a non-invasive, preoperative risk stratification in patients with colorectal liver metastases.

Abiotic stresses such as salinity and phosphorous (P) deficiency are major yield-limiting factors for rice, particularly on marginal lands. Marker-aided backcrossing (MAB), enabled by advances in genomics and molecular mapping in recent years, is said to be a more precise, time-saving, and cost-effective way to develop rice varieties that can withstand these abiotic stresses than conventional breeding. The study employs the economic surplus approach to measure the benefits of MAB for salinity tolerance in rice for Bangladesh, India, Indonesia, and Philippines, and for rice with tolerance to P-deficient soils in Indonesia. At a 5% discount rate, the benefits over 15 years of planting salt-tolerant varieties amount to $226.9 million in the Philippines, $3.666 billion in Bangladesh, $4.848 billion in India, and $895.7 million in Indonesia. The gains from growing varieties that can withstand P deficient soils in Indonesia amount to $2.070 billion. The incremental benefits from completing the salt-tolerant and P-deficient tolerant breeding cycles 2 years earlier are $340.5 million in Bangladesh and $192.1 in Indonesia, respectively. In India, $227.0 million is gained even if MAB develops salt-tolerant varieties just a year earlier. The additional gains from completing the salt-tolerant rice breeding cycle 4 years earlier are $40.3 million in the Philippines and $158.9 in Indonesia. In general, the gains from saline- (Bangladesh, Indonesia, Philippines) and P-deficient (Indonesia) tolerant rice are reduced by 5%, 9%, 14%, and 18% when MAB breeding cycle is delayed by one, two, three, and four years, respectively. In India, there is 3%, 7%, 10%, and 13% loss in benefits from salt-tolerant rice for every additional year of delay in the MAB breeding cycle. / Master of Science

Textilbranschen är en global bransch som kontinuerligt producerar avfall bl.a. genom spill från tillskärningen. För att de globala hållbarhetsmålen ska kunna uppnås krävs mer studier på de olika alternativen för att minimera och eliminera avfallet. Detta är relevant även för en ekonomisk och social hållbarhet. Studien syftar till att undersöka vilka effekter det har på materialåtgången att kombinera flera modeller vid tillskärningen. Den utgår från flera modeller med samma huvudtyg som teoretiskt kan skäras i samma lägg. Det finns flertalet undersökningar på effekterna av att kombinera storlekar vid tillskärning och det är en etablerad lösning för att minimera tygåtgången inom branschen. Dock finns väldigt få undersökningar på effekterna av att kombinera modeller, därför har denna studie begränsats till enbart grundstorlekar. Med hjälp av Lectra Diamino Expert skapades 113 läggbilder, innehållande kombinationer av upp till fem modeller i vardera. Kombinationsläggbildernas längd och effektivitet jämfördes mot varandra och mot kontrolläggbilderna. Skärorderplaneringar baserade på inköpsstatistik och de upprättade läggbilderna gjordes med olika fokus för jämförelser i tygåtgång. Resultatet i studien visar på att vissa modellkombinationer genererar en minskning i tygåtgång och andra en ökning. Detta antas bero på form och relationen mellan stora och små mönsterdelar. / The textile industry is constantly producing waste, including waste from the cutting process. To reach sustainable development goals and reach economic and social sustainability more studies are needed that focus on different alternatives for minimizing and eliminating waste. The study aims to examine different effects of material usage when combining multiple models during the marker-making process. The study use multiple models with the same main fabric that theoretically could be cut in the same lay. Many studies support the positive effects of combining sizes in marker-making, and this is an established solution for minimizing material waste. Few, if any, studies exist on the effects of combining models and therefore this study focuses only on the basic sizes. Using Lectra Diamino Expert, 113 markers were made, each containing combinations of up to five models. Also lay plans based on purchase statistics was executed, this with different focus areas for comparing material usage against control-markers. The results of the study show that some model-combinations result in a decrease, and others in an increase, in material usage. This is assumed to depend on configuration and the relationship between small and large pattern pieces.

Dagens textil- och modeindustri producerar stora mängder avfall och i produktionsfasen uppstår merparten av det vid tillskärning av mönsterdelar. FN har satt upp 17 globala mål för att främja en hållbar utveckling och mål nummer 12 fokuserar på att främja hållbar konsumtion och produktion. För att uppnå det är det därav relevant att utforska alternativ för att höja utnyttjandegraden av tyg vid tillskärningsstadiet inom konfektion. Studien utförs i samarbete med ett svenskt företag och undersöker hur enklare mönsterförändringar på en jacka kan påverka effektiviteten hos plaggets läggbild. Studien dokumenterar och analyserar resultatet av olika mönsterförändringar utförda på en jacka samtidigt som plaggets design behålls snarlik och sammanställer dess effekt på läggbildseffektiviteten samt tygåtgången. Tidigare forskning har fokuserat på effektivisering av läggbilder utan mönsterförändring alternativt mönsterkonstruktion baserad på idén om zero-waste pattern cutting vilket ämnat ett eliminera materialspill men inte minska tygåtgång. Rapportens fokus ligger vid effektivisering av läggbilder med hjälp av mönsterkonstruktion utifrån studiens aktuella plagg med ambitionen att uppnå materialbesparing. Studien presenterar åtta olika mönsterförändringar, dess effekter på tygåtgång och läggbildseffektivitet samt vilka parameter som bör tas hänsyn till vid omvandling av mönster för läggbildseffektivisering. / Today's textile and fashion industry produces large amounts of waste and in the production phase most of it arises when cutting pattern pieces. Goal number 12 of the UN's 17 Global Goals for Sustainable Development stands to promote sustainable consumption and production, and in order to achieve this, it is therefore relevant to explore alternatives for increasing the degree of utilization of fabric at the cutting stage in clothing production. The study is carried out in collaboration with a Swedish company and examines how simpler pattern changes on a jacket can affect the efficiency of the garment's lay plan. The study documents and analyzes the results of various pattern changes performed on a jacket while maintaining a similar design to that of the original garment and compiling its effect on the lay plans efficiency and fabric consumption. Previous research has focused on bettering the efficiency of lay plans without pattern change or pattern design based on the idea of zero-waste pattern cutting which aims to eliminate fabric waste but not cut down on fabric consumption. Focus of the report is on how to achieve higher efficiency in lay plans using pattern construction based on the study's chosen garment with the aim of saving fabric waste. The study presents eight different pattern changes, its effects on fabric consumption and lay plan efficiency and which parameters should be considered when transforming patterns for the purpose of increasing lay plan efficiency.

Bildgesteuerte, perkutane Interventionen stellen bei vielen diagnostischen und therapeutischen Fragestellungen eine Alternative zum chirurgischen Vorgehen dar. Hierbei kommen bevorzugt die Sonographie und die Computertomographie (CT) zum Einsatz. Zu den Indikationen für eine gezielte Nutzung der Magnetresonanztomographie (MRT) zählen Befunde, die sich mit anderen Modalitäten nicht ausreichend darstellen lassen, die fehlende Strahlenexposition (CT) sowie Alleinstellungsmerkmale wie der hervorragende native Weichteilkontrast oder die Möglichkeiten zur Darstellung von Temperaturen oder Diffusionsprozessen. Zu den Nachteilen zählen die langen Messzeiten, das starke Magnetfeld sowie die räumliche Enge in den meist röhrenförmigen Geräten, die ein interventionelles Vorgehen oft erschweren. Stereotaktische Führungs- und Navigationshilfen sind kein notwendiger Bestandteil der interventionellen Ausrüstung, ermöglichen jedoch oft eine gezieltere Planung, bessere Visualisierung oder vereinfachte Durchführung, insbesondere gegenüber einer rein kognitiven Einbeziehung der MRT-Informationen. Assistenzsysteme für geschlossene MRT-Geräte sind meist rahmenbasiert und beschränken sich auf bestimmte Regionen, z. B. die Mamma, die Prostata oder das muskuloskelettale System. Diese Arbeit beschreibt hingegen eine leistungsstarke rahmenlose Assistenztechnik (Navigation), die sich praktisch in beliebigen Körperregionen einsetzen lässt. Der Operateur orientiert sich dabei anhand von hochwertigen MRT-Ansichten, die gemäß der in Echtzeit erfassten Nadellage aus einem kurz zuvor erhobenen Referenzdatensatz reformatiert werden. Ausgehend von der Implementierung an einem speziellen offenen MRT-System (0,5 T) werden interventionelle Komponenten und Methoden beschrieben, die erfolgreich auf ein herkömmliches MRT-System (1,5 T) übertragen wurden. Die Einschränkungen des geschlossenen Systems führten dabei zu einer speziellen Registrierungstechnik mit Hilfe einer kompakten, frei positionierbaren Referenzplatte mit resonanten Miniatur-Hochfrequenzspulen (semiaktiv) als MR-Positionsmarker. Im Vordergrund stand die systematische Prüfung der Marker hinsichtlich Signalverhalten und Sicherheit sowie die Zuverlässigkeit und Genauigkeit einer vollautomatischen, bildbasierten 3D-Lokalisation unter experimentellen und klinischen Randbedingungen. Gegenüber herkömmlichen, passiven (Kontrastmittel-) Markern zeichnet sich die semiaktive Technik dadurch aus, dass sie gleichzeitig, auch mehrere, beliebig über das gesamte Messvolumen verteilte Marker, praktisch unabhängig von sämtlichen anatomischen Strukturen lokalisieren kann. Sowohl die Festlegung einer Position (ein Marker) oder einer Ebene (drei Marker) wie auch die navigierte Platzierung einer Nadel zeigten im Experiment ausreichend hohe Genauigkeiten. Auf Basis einer zeitlich optimierten (Subsekunden-) Markerbildgebung konnte experimentell eine robotisch geführte Nadel direkt im MRT bildgebend verfolgt werden, was weitere Anwendungen der Lokalisationstechnik in Aussicht stellt. Navigierte Biopsien an einem Gewebephantom zeigten nach ausschließlich stereotaktischer Positionierung – ohne Kontrollbildgebung – unabhängig vom Erfahrungsgrad der medizinischen Anwender ausreichend hohe Trefferquoten. Gleichzeitig lieferte die Studie wertvolle, auch anwenderspezifische Erkenntnisse über die Bedienbarkeit sowie den Zeitbedarf für einzelne Interventionsschritte. Im Vergleich mit anderen prototypischen oder kommerziellen Systemen zeigte sich die vorgestellte Assistenztechnik – am Beispiel muskuloskelettaler Interventionen – als klinisch flexibel einsetzbar.

Burkholderia cenocepcia is one of the serious infectious agents of respiratory tract among cystic fibrosis patients. There are problems mainly with strains which are capable of epidemic spread. The known epidemic in the Czech Republic was caused by ST32 strain in the past. In this work, there was completed whole genome sequence of referential isolate 1232 of B. cenocepacia ST32 in cooperation with bioinformatics by new generation sequencing techniques and by determining the problematic areas by a combination of Sanger sequencing bioinformatics approaches and manual assembling of sequence reads localized in these areas. The final version of the genome sequence was annotated by PGAAP and at the present time it is finalized. Second part of this work is dedicated to looking for a prognostic marker of infection caused by ST32 strain in patients with cystic fibrosis. We analysed the results of ST32 trancriptomic experiment and chose genes possibly connected with the cepacia syndrome - serious, mostly fatal state of infection. By quantitative PCR we compared their expression in isolates from 4 patients from time of cepacia syndrome and month before that. We checked the possibility of direct detection of the expression of these genes in clinical material. We identified genes for type III secretion system as...

Chris Marker é um cineasta que realizou documentários políticos pouco convencionais ao longo de quase sessenta anos de carreira. Depois de uma militância ativa e inserida no coração de acontecimentos cruciais na França e na Europa, e de uma carreira literária como editor, ensaísta e romancista, natural que seus filmes, vistos isoladamente, provoquem as mais equivocadas interpretações. Esta pesquisa procura, através de um levantamento de seus filmes e escritos, dos debates que foram se travando sobre a vida nacional francesa e mundial, sempre retomando os fios dos acontecimentos decisivos do período do Front Populaire (1936), da ocupação da França pelos nazistas e das lutas de Resistência buscar uma interpretação para muitos dos aspectos aparentemente desconcertantes de sua filmografia. Ao longo dos capítulos a pesquisa aborda, a partir de documentação esparsa em textos, declarações, debates, frases de filmes, os elementos biográficos \"enigmáticos\" de que se tem conhecimento, dada a discrição do cineasta sobre a sua pessoa. Em seguida o momento crucial da entrada de Marker, com 16 anos, no liceu em Paris e turbulências do ano de 1936, na França, discorre sobre o Front Populaire. Depois foca o nascimento de uma corrente, da qual Chris Marker participa, influenciada pela filosofia personalista de Emmanuel Mounier; e depois sua passagem pela revista Esprit e posteriormente a sua integração nas lutas da Resistência. Seguindo os passos do futuro cineasta, aborda o impacto da Resistência na vida militante e a formação dos cineclubes no meio operário com a Associação Peuple et Culture. Toda esta trajetória é permeada por comentários e análises de cenas dos futuros documentários. Por fim a pesquisa, aborda a problemática do cinema militante, analisando L\'ambassade (1973), filme de solidariedade com a Unidade Popular chilena e contra o golpe de Pinochet e o curta sobre o editor François Maspero. Os últimos percalços de nosso percurso busca construir um debate sobre A. Medvedkine e V. Maiakóvsky e a profanação da arte moderna, procurando investigar como na obra de Chris Marker coincidem cinema militante, cinema experimental, cinema ensaio e cinema documentário. / Chris Marker is an intriguing filmmaker who produced unconventional political documentaries over almost sixty years. After an active militancy, and inserted in the heart of crucial events in France and Europe, and working on a literary career as an editor, essayist and novelist, it is natural that his films, viewed in isolation, could cause the most equivocal interpretations. This research seeks, through a detailed analyses of his films and writings, to work with the debates that were important on the French national and global life of his time. Always thinking about the decisive events of the Front Populaire in the period (1936), the occupation of France by the German Nazis and the participation of Marker in the struggles of the Resistance. All of this puzzeled elements seek an interpretation for many of the seemingly confusing aspects of his filmography. Throughout the chapters of this research, we seek to approach, with this documentation, texts, statements, debates, films phrases, the enigmatic biographical elements of his uncanny formation. Marker is known by the discretion about himself. Working on his years of youth and formation, we see that when aged 16, in high school in Paris and the 1936 year in France, discussing at length the Front Populaire, we seek to work about Chris Marker influence by the personalist philosophy of Emmanuel Mounier and then by Esprit and later in it\'s integration in the struggles of resistance. Following in the footsteps of the filmmaker, this work discusses the impact of this years in his militant life, including the training of workers film clubs. All this history is permeated by scenes and debates of his future documentaries. Finally, the research addresses the issue of militant cinema, analyzing L\'ambassade (1973), the solidarity with the Chilean Popular Unity and the struggle against the totalitarian latin american dictatorships, and a short film-portrait of the editor Maspero. We end our research with a debate on A. Medvedkine and V. Mayakovsky and the profanation of modern art, trying to investigate how the work of Chris Marker coincide with militant cinema, experimental cinema, film essay and documentary cinema.

Este trabalho apresenta uma técnica de diferenças finitas para resolver a equação constitutiva Fluido de Segunda Ordem para escoamentos tridimensionais com superfície livre. As equações governantes são resolvidas pelo método de diferenças finitas em uma malha deslocada 3D. A superfície livre é modelada por células marcadoras (Marker-and-Cell) e as condições de contorno a superfície livre são empregadas. O método numérico apresentado neste trabalho foi validado pela comparação entre as soluções numéricas obtidas para o escoamento em um tubo com a solução analítica correspondente para Fluidos de Segunda Ordem. Ao fazer refinamento de malha, a convergência do método numérico foi verificada. Resultados numéricos da simulação do problema do inchamento do extrudado para números de Deborah De \'< OU =\' 0:3 são apresentados / This work presents a finite difference method to simulate three-dimensional viscoelastic flow with free surfaces governed by the constitutive equation Second Order Fluid. The governing equations are solved by the finite difference method in a three-dimensional shifted mesh. The free surface of fluid is modeled by the Marker-and-Cell method which allows for the visualization and the location of the free surface of fluid. The full free surface stress conditions are employed. The numerical method developed in this work is validated by comparing the numerical and analytic solutions for the steady state flow of a Second Order Fluid in a pipe. By using mesh refinement convergence results are given. Numerical results of the simulation of the transient extrudate swell of a Second Order Fluid of the Deborah number De \'< OR =\' 0:3 are presented

Este trabalho analisa filmes do cineasta Chris Marker que indagaram sobre a Unidade Popular do Chile nos anos 1970. Entre as produções abordadas, estão duas que foram remontadas a partir de documentários chilenos feitos durante o governo de Salvador Allende: La première année (1973) e On vous parle du Chili: ce que disait Allende (1973). Além disso, mais três filmes desse realizador se dedicaram ao tema: La Spirale (1976), Lambassade (1974) e O fundo do ar é vermelho (1977). Por meio do estudo dessa filmografia, identificaram-se quais foram as estratégias narrativas utilizadas e qual foi o discurso político sobre a chamada experiência chilena que essas estratégias elaboraram. A reflexão sobre o corpus permitiu verificar que o interesse por esse processo, visto desde a França, emergiu do espaço deixado pelas frequentes desilusões diante de uma referência política anterior, igualmente vinda da América Latina e que havia motivado os debates da esquerda francesa na década de 1960: a Revolução Cubana. Assim, optou-se por incluir também na pesquisa produções markerianas que nasceram do contato entre esse realizador e o Instituto Cubano del Arte e Industria Cinematográficos (ICAIC): Cuba si (1961), La bataille des dix millions (1970), On vous parle du Brésil: tortures (1969) e On vous parle du Brésil: Carlos Marighela (1970). A análise dos filmes elencados revela que, durante os anos da UP no poder, houve uma vontade de aproximação entre Chile e França que valorizava os caminhos empregados pela via chilena ao socialismo, apontando-os como possibilidades para uma Nova Esquerda europeia. Porém, com o golpe de Estado de 1973, essa postura passou por uma revisão, e a experiência chilena serviu à elaboração de leituras que apontassem um legado e lições que poderiam ser retirados da queda da Unidade Popular. Nesse sentido, as produções de Marker fazem uma denúncia das ações da direita que derrubaram Allende, bem como constroem uma visão autocrítica que indica os erros cometidos pela própria esquerda que possibilitaram essa derrota. Essa tentativa de atribuir um legado e lições buscava responder sobretudo aos anseios de uma esquerda francesa que dispunha de um programa comum de governo fortemente inspirado naquele da UP chilena, mas que deveria ser submetido a uma revisão após o fracasso de sua referência latinoamericana. Sob essa visão, esta tese propõe um estudo voltado à circulação de ideias culturais e políticas entre América Latina e França, que delega ao continente um papel central nessa relação durante os anos 1960 e 1970 e a Chris Marker a função de um mediador cinematográfico. / This work analyses the Chris Markers films that inquired about the Popular Unity in the 1970s. Among the productions approached, two of them have been reassembled from other Chilean documentaries that had been made during the Salvador Allendes government: La première année (1973) and On vous parle du Chili: ce que disait Allende (1973). Furthermore, three other films by Chris Marker have analysed this subject: La Spirale (1976), The embassy (1974) and The grin without a cat (1977). By studying his filmography, this research could identify the narratives strategies that had been used by the director, as well as the political discourse elaborated by them. The reflections about the corpus allowed verify how the interest for this Chilean process, viewed from France, has emerged from an empty space left by the usual delusion given by an earlier reference that had motivated the French left during the 1960s, also gone from Latin-American: the Cuban Revolution. So, we chose to also include in the research the Markers productions came from the relationship between this director and the Instituto Cubano del Arte e Industria Cinematográficos (ICAIC): Cuba si (1961), La bataille des dix millions (1970), On vous parle du Brésil: tortures (1969) and On vous parle du Brésil: Carlos Marighela (1970). The analysis of the films-selected shows that, during the UPs years in the power, there was a wish to approach Chile and France by valorising the Chileans way to the socialism and pointing it as a possibility to the European New Left. However, after the coup détat in 1973, this attempt has been revised and the Chilean experience has been used to elaborate lectures that pointed a legacy and lessons from the follow of Popular Unity. In this sense, the Markers productions denounce the rights actions to overthrow Allende, as well as built a self-criticism vision to indicate the lefts mistakes that had collaborated to the defeat. This wish to show a legacy and lessons has dialogued with the expectations of a Frenchs left that had have a common government programme tightly inspired in the Chileans UP ones, but that has required a revision after the failure of its Latin-American reference. From this point of view, this thesis proposes a study based on the circulation of cultural and political ideas between Latin American and France that delegated to this continent a central role in this relationship during the 1960s and the 1970s, and assigned to Chris Marker the function of a cinematographic mediator.