L’utilisation d’oligomères d’α-amino-γ-lactame (Agl-αAA) comme vecteurs de pénétration intracellulaire est décrite dans ce manuscrit. Nous avons montré que ces oligomères structurés en ruban sont capables de traverser la membrane plasmique pour atteindre le cytosol et y délivrer un cargo biologiquement actif. A la différence des séquences peptidiques, ces oligomères ont une très bonne résistance enzymatique. Une nouvelle famille de foldamères d’α-amino-γ-lactame (Agl-βAA) obtenus à partir de séquences /β peptidiques est également décrite. La structure secondaire de ces composés a été étudiée par RMN, IR-TF, CD et DRX. Nous avons montré que ces oligomères sont capables d’adopter une structure stable en hélice 12. De façon remarquable, ces oligomères sont solubles en milieux aqueux malgré une absence totale de chaînes latérales hydrophiles. / The use of α-amino-γ-lactam oligomers (Agl-αAA) as cell penetrating vectors are described in this work. These ribbon structured oligomers are able to cross the cell membrane to reach the cytosol and deliver a biologically active cargo. Unlike peptide sequences, these oligomers display a strong enzymatic resistance. A new family of α-amino-γ-lactam oligomers (Agl-βAA) obtained from conversion of /β peptide sequences are also described. Secondary structure of these molecules have been studied by NMR, FTIR, CD and XRD. These oligomers are able to adopt a stable 12-helix structure. Unexpectedly, these oligomers are soluble in aqueous mediums without any hydrophilic side chains

Cette thèse porte sur le rapport université/entreprise au Mexique après 1990. Il s’agit d’une étude de cas sur l’Université Nationale Autonome du Mexique (UNAM), la plus grande université mexicaine et la plus importante institution productrice de connaissances scientifiques au pays. À partir de 1988, l’introduction au Mexique d’une économie du marché a été le point de départ des nombreux changements politiques et économiques qui ont modifié les conditions d’exploitation des organisations et des institutions au pays. Ainsi, depuis 1990, le nouveau contexte politique et économique du Mexique a modifié les politiques gouvernementales vers les institutions publiques y compris celles de la santé et de l’éducation. Pour ce qui est des universités publiques mexicaines, ces politiques ont réduit leur financement et leur ont demandé une participation plus active à l’économie nationale, par la production de connaissances pouvant se traduire en innovation dans le secteur de la production. Ces nouvelles conditions économiques et politiques constituent des contingences auxquelles les universitaires font face de diverses façons, y compris l’établissement des relations avec les entreprises, comme le prescrivent les politiques du gouvernement fédéral élaborées sur la base des recommandations de l’OCDE. En vue de contribuer à la connaissance des relations université/entreprise développées au Mexique, nous avons réalisé notre étude de cas fondée sur une approche méthodologique qualitative à caractère exploratoire qui a recueilli des données provenant de sources documentaires et perceptuelles. Nous avons encadré notre recherche du point de vue de l’organisation par la théorie de la contingence, et pour l’analyse de la production de la connaissance sur la base des modèles de la Triple hélice et du Mode 2. Différents documents de sources diverses, y compris l’Internet, ont été consultés pour l’encadrement des rapports université/entreprise au Mexique et à l’UNAM. Les sources perceptuelles ont été 51 entrevues semi-structurées auprès de professeurs et de chercheurs à temps plein ayant établi des rapports avec des entreprises (dans les domaines de la biomédecine, la biotechnologie, la chimie et l’ingénierie) et de personnes ayant un rôle de gestion dans les rapports des entreprises avec l’institution. Les données recueillies ont montré que la politique de l’UNAM sur les rapports université/entreprise a été aussi flottante que la structure organisationnelle soutenant sa création et formalisation. Toutes sortes d’entreprises, publiques ou privées collaborent avec les chercheurs de l’UNAM, mais ce sont les entreprises parastatales et gouvernementales qui prédominent. À cause du manque d’infrastructure scientifique et technologique de la plupart des entreprises au Mexique, les principales demandes adressées à l’UNAM sont pour des services techniques ou professionnels qui aident les entreprises à résoudre des problèmes ponctuels. Le type de production de connaissance à l’UNAM continue d’être celui du Mode 1 ou traditionnel. Néanmoins, particulièrement dans le domaine de la biotechnologie, nous avons identifié certains cas de collaboration plus étroite qui pointaient vers l’innovation non linéaire proposée par le Mode 2 et la Triple hélice. Parmi les principaux avantages découlant des rapports avec les entreprises les interviewés ont cité l’obtention de ressources additionnelles pour la recherche, y compris de l’équipement et des fonds pour les bourses d’étudiants, mais souvent ils ont observé que l’un des plus gros avantages était la connaissance qu’ils obtenaient des contacts avec les firmes et le sens du réel qu’ils pouvaient intégrer dans la formation des étudiants. Les programmes gouvernementaux du CONACYT pour la science, la technologie et l’innovation ne semblent pas réussir à renforcer les rapports entre les institutions génératrices de la connaissance et le secteur de la production du Mexique. / Since 1988, the introduction of a market economy in Mexico have changed the government policy towards public universities in the country, reducing their budget and asking them to participate more actively in the national economy, by producing knowledge that could translate into innovation in the production sector. The budgetary constraints imposed on Mexican public universities affect their functions of teaching and worsen the conditions for research. The economic and political context after 1990 has created the eventuality in which academics must implement different mechanisms, including the establishment of relations with commercial enterprises as guided by the policies of the federal government, which were developed on the basis of recommendations by the OECD. In order to contribute to the theme of university/enterprise relations developing in Mexico, we conducted a case study on the National Autonomous University of Mexico (UNAM), the largest university and which is the most advanced institution in the development of scientific knowledge in Mexico. Using a methodological approach of qualitative exploration, our case study collected data from documentary and perceptual sources to describe the characteristics of the university/enterprise relationships at the institution. From an organizational point of view, we established the framework of our research on the theory of contingency, and for the analysis of knowledge production we have taken the basis of models of the triple helix and Mode 2. The documents on various important aspects on the framework of the university/enterprise rapport in Mexico and in UNAM have been consulted and 51 semi-structured interviews conducted with persons having institutional experience of work with companies. The target population of the research was composed of two groups: 1) full-time professors (faculty and researchers) working in the fields of biomedicine, biotechnology, chemistry, and engineering, and 2) persons having a management role in the relations between firms and the institution. The institutional policy of UNAM on the university/enterprise relationship and the structure supporting their creation and formalization has varied according to the changing criteria of successive university administrations. There are all kinds of enterprises, both public and private, collaborating with researchers at UNAM, however governmental and quasi-governmental enterprises are predominant. Related to the lack of scientific and technological infrastructure of most enterprises in Mexico, the major requests addressed to UNAM are for technical or professional services to help firms to solve specific problems. Nevertheless, particularly in the field of biotechnology, we identified some cases of closer collaboration pointing to non-linear innovation, as proposed by the Mode 2 and the Triple helix. The interviewed perceived more advantages than disadvantages from these relationships. Among the main benefits the researchers cited the acquisition of additional resources for research, including funds for student scholarships and some equipment, but several of them have remarked the importance of the knowledge coming from this contacts and the sense of reality they can convey in the training of students. On the basis of the answers collected, the government programs drawn up for science, technology and innovation did not seem to succeed in strengthening the relations between the knowledge generating institutions and the productivity sector of Mexico.

The sequence of a polypeptide chain determines its structure which in turns determines its function. A protein is stabilized by multiple forces; hydrophobic interaction, electrostatic interactions and hydrogen bond formation between residues. While the above forces are non-covalent in nature the protein structure is also stabilized by disulfide bonds. Structural features such as naturally occurring cavities in proteins also affect its stability. Studying factors which affect a protein’s structural stability helps us understand complex sequence-structure-function relationships, the knowledge of which can be applied in areas such as protein engineering. The work presented in this thesis deals with various and diverse aspects of protein structure. Chapter 1 gives an overall introduction on the topics studied in this thesis. Chapter 2 focuses on a unique, non-regular, structural feature of proteins, viz. protein cavities. Cavities directly affect the packing density of the protein. It has been shown that large to small cavity creating mutations destabilize the protein with the extent of destabilization being proportional to the size of cavity created. On the other hand, small to large cavity filling mutations have been shown to increase protein stability. Tools which analyze protein cavities are thus important in studies pertaining to protein structure and stability. The chapter presents two methods which detect and calculate cavity volumes in proteins. The first method, DEPTH 2.0, focuses on accurate detection and volume calculation of cavities. The second method, ROBUSTCAVITIES, focuses on detection of biologically relevant cavities in proteins. We then study another aspect of protein structure – the disulfide bond. Disulfide bonds confer stability to the protein by decreasing the entropy of the unfolded state. Previous studies which attempted to engineer disulfides in proteins have shown mixed results. Previously, disulfide bonds in individual secondary structures were characterized. Analysis of disulfides in α-helices and antiparallel β-strands yielded important common features of such bonds. In Chapter 3 we present a review of these studies. We then use MODIP; a tool that identifies amino acid pairs which when mutated to cysteines will most likely form a disulfide bond, to analyze disulfide bonds in parallel β-strands. A direct way to analyze sequence-structure relationships is via mutating individual residues, evaluating the effect on stability and activity of the protein and inferring its effect on protein structure. Saturation mutagenesis libraries, where all possible mutations are made at every position in the protein contain a huge amount of information pertaining to the effect of mutations on structure. Making such libraries and screening them has been an extremely resource intensive process. We combine a fast inverse PCR based method to rapidly generate saturation mutagenesis libraries with the power of deep sequencing to derive phenotypes of individual mutants without any large scale screening. In Chapter 4 we present an Illumina data analysis pipeline which analyzes sequencing data from a saturation mutagenesis library, and derives individual mutant phenotypes with high confidence. In Chapter 5 we apply the insights derived from structure-function studies and apply it to the problem of protein engineering, specifically immunogen design. The Human Immunodeficiency Virus adopts various strategies to evade the host immune system. Being able to display the conserved epitopes which elicit a broadly neutralizing response is the first step towards an effective vaccine. Grafting such an epitope onto a foreign scaffold will mitigate some of the key HIV defenses. We develop a computational protocol which grafts the broadly neutralizing antibody b12 epitope on scaffolds selected from the PDB. This chapter also describes the only experimental work presented in this thesis viz. cloning, expressing and screening the epitope-scaffolds using Yeast Surface Display. Our epitope-scaffolds show modest but specific binding. In a bid to improve binding, we make random mutant libraries of the epitope-scaffolds and screen them for better binders using FACS. This work is on-going and we aim to purify our epitope-scaffolds, characterize them biophysically and eventually test their efficacy as immunogens.

The primary aim of this research was to investigate the bending behaviour of helically wound steel cables of various types (i.e. normal spiral strands, sheathed spiral strands and locked coil cables) in the presence of friction and to propose more efficient computational models for their analysis under combined tension and bending. The proposed model fully takes into account interwire contact forces both in the radial direction (point contact between wires in different layers) and hoop direction (line contact within the wires in the same layer). Extensive theoretical parametric studies have been undertaken on a variety of cable constructions covering a wide range of geometrical and material parameters. Explicit formulations have been developed for the smooth transition of the bending stiffness from no-slip to full slip regimes, as a function of cable curvature. Based on these formulations, it is now possible to calculate the relative displacements of the wires, as well as the tensile, bending and hoop stresses in the individual wires of the cable. Furthermore, bending stiffness of the cable is shown to decrease by a factor of 2 to 16, depending upon the friction coefficient between wires and the type of cable construction. Wherever possible, the theoretical results have been compared with experimental results from the available literature and are found in very good agreement with them. A simple method for the determination of the bending stiffness of large diameter multi-layered cable has been developed. The simplified method is further shown to provide estimates of the bending stiffness which are very close to those calculated by the original theory, allowing hand calculations for an easier use in industry. The proposed formulations have been extended to cater for the effects of external hydrostatic pressure on sheathed spiral strands in deep water applications. These forces are shown to have a great influence on the pattern of interwire contact forces and hence the interlayer slippage between the wires in the strand. Numerical results have been obtained and analysed for three different 127 mm diameter strands with lay angles of 12°, 18° and 24° respectively, experiencing a wide range of external hydrostatic pressures of 0 to 2,000 metres. The significant increase in normal contact force between wires is shown to suppress the slippage of wires in the cable. However, the no-slip and full slip values of the effective bending stiffness of the cable is shown to be independent of the level of hydrostatic pressure. A theoretical model is also proposed for estimating wire kinematics, pattern of interwire slippage, contact forces as well as the flexural rigidity of locked coil cables with outer layers made of shaped wires. In order to validate this model, numerical results are reported for two different locked coil cables. It is shown that the shaped wires in the outer layers of locked coil cables play an important role in the distribution of contact forces, slip initiation and cable unwinding.

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No. of bitstreams: 2 Dissertação - Geisa Muller de Campos Ribeiro - 2016.pdf: 2724443 bytes, checksum: 58e60b3cc66b5bb9542ba366d999ff97 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-05-05 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This research analyses the significant interaction of the University with two popular self-management Enterprises - cooperative societies that work with recyclable materials – located in Goiania city as part of a program named originally as Social Incubation developed by the Federal University of Goiás (UFG). It is an empirical research, in which the interactional movement between the University (Social Incubation) and the enterprises assume that there are conflicts caused by the cultural differences among the participants. These differences are represented by the non-scientific type knowledge derived from the participants’ empirical experience, from the practical and religious activities and working techniques, and by the scientific knowledge produced in the University posted as truth. It is a qualitative study. For the data collection, the participative observation constituted fundamental element. Some data were obtained from informal and semi-structured interviews, besides the documental research that was an opportunity to understand the general context of the cooperative societies and the Social Incubation. In this study, it was conceived that the relation established between the participants is not linear and permanent and it demands that the construction of the knowledge must be done in group. That’s how the knowledge among the cooperators goes through changes, significations and resignifications, caused by the dialogical practice needed. The participants’ experiences, perceptions and beliefs are inherent to the construction of knowledge and human capital. The dialogical process assumes knowledge and symbolic exchanges and it is an assumption to the communicational process among those involved. It was clear that in the process of incubation of the enterprises, there is a complexity that demands considerable efforts from the agents of the Incubator and the cooperators. There were difficulties from both parts that were broken. This way, the context of the Social Incubator enabled to think in the performance of the University through the extension, that is still an activity with little involvement and recognition by professors and students. Besides that, there is also the need to overcome capitalism in which universities are inserted into redirection of production of technology and science focusing in popular interests. This is the aspect in which the political relations are still fragile under this study’s reality. / Estudo que analisa a interação significativa entre a Universidade e dois empreendimentos populares autogestionários - cooperativas de materiais recicláveis - localizadas na cidade de Goiânia que fazem parte do programa de Incubação Social da Universidade Federal de Goiás (UFG). Trata-se de uma pesquisa empírica na qual o movimento interacional entre a Universidade (Incubadora social) e os empreendimentos incubados pressupõe que há tensionamentos causados pelas diferenças culturais entre os atores envolvidos: os conhecimentos de natureza não científica, provenientes das experiências empíricas dos cooperados, suas atividades práticas, religiosas e técnicas do trabalho, e os conhecimentos científicos produzidos na Universidade posicionados, muitas das vezes como verdade. Trata-se de um estudo qualitativo. Para a coleta de dados, a observação participante constituiu-se como um elemento fundamental. Alguns dados foram obtidos com entrevistas informais e semi-estruturadas, além da pesquisa documental que oportunizou entendimento do contexto geral das cooperativas e da incubadora social. No estudo, concebeu-se que a relação que se estabelece entre os atores não é linear e permanente e exige a construção do conhecimento em conjunto. É assim que o conhecimento depois de problematizado entre os cooperados passa por transformações, significações e resignificações, decorrentes da prática dialógica necessária. As experiências, vivências e crenças dos atores envolvidos são imanentes na construção do conhecimento e do capital humano. O processo dialógico pressupõe, trocas de saberes e trocas simbólicas e é premissa do ato comunicacional entre os envolvidos. Ficou evidente que no processo de incubação dos empreendimentos há uma complexidade que demanda esforços consideráveis dos gestores da incubadora e dos cooperados e dificuldades/resistências de ambas as partes que precisam ser rompidas. Concluindo, o contexto da incubadora social possibilitou pensar a atuação da Universidade por meio da extensão que ainda é uma atividade com pouco envolvimento e reconhecimento por parte dos docentes e discentes. Além disso, existe a necessidade de superação do capitalismo no qual as universidades estão inseridas para um redirecionamento de produção de tecnologia e ciência voltadas para interesses populares. É neste aspecto que as relações políticas ainda são frágeis para a realidade em estudo.

In spite of Sweden´s lack of formal regions, the country is evolving towards regional administrations. The regional level are to a growing extent viewed as important bases for economic growth and development. The concept of the triple helix implies that interaction between the public sector, the industry and universities is a source to economic and social development. Research has though implied that the interaction between the triple helix actors could be problematic from a multi-level governance perspective. It has been shown that since the institutional setting is horizontal and vertical fragmented, cooperation between different institutions and actors becomes difficult. In year 2005-2006 the Värmland region was one of fourteen regions in twelve countries that was included in a OECD project, that was a response to the multiplicity of initiatives across the OECD countries concerning regional development. In the report that evolved from the project actors in Värmland was recommended to improve the cooperation concerning regional development in the county. This thesis investigates the cooperation between the triple helix actors for regional growth and development in the Värmland region 1998-2008. My research questions are: Is there evidence of a lack of cooperation between the university, the public sector and the industrial actors in Värmland? And if this is the case, could these problems be related to the fragmentation of the institutional setting? The thesis is a qualitative case study, conducted through elite-interviews and document analysis. My findings implies that the cooperation between the triple helix actors in Värmland has developed dramatically the last decade. From a strive for coordination that was pervaded by institutional fragmentation to an increased closeness and mutual involvement that has come to over-bridge the institutional fragmentation on the regional level. Although, it seems like the vertical fragmentation between the regional and national level, which could impede growth and development in the region, to a great degree remains.

This thesis deals with the Kosovar agricultural economy and the introduction of new approaches. Kosova is an economy in transition with high unemployment, young population and structural problems. The privatization process promises a better future and economic growth. However, hard work and new approaches are needed. Privatization does not mean immediate growth. Hereby, clusters are considered as an appropriate approach to develop rural areas. Especially the wine sector in Kosova could be an example for cluster development as it is a promising sector. Wine has a long history in Kosova although wine consumption is not widespread. This sector is a rare example where exports are higher than imports. Climate conditions cheep working force and as stated the background make this sector attractive. Foreign agencies and investors are very interested in this sector. This thesis will show the main problems and main opportunities of this sector. It will describe the structural changes and current developments. Cluster creation is not a government function. Further, it is not a tailor-made solution. In fact, clustering involves many roles. Each participant has certain duties but the whole process needs coordination. The monitoring and supervision of the whole process, the identification of needs and permanent exchange of the participants are organized in a cluster. At the end, a win-win situation is created even if competition is raised to a high level. Competition and the functioning of free markets guarantee the success of the sector and as a results regional development. One cluster helps to create another. Starting one process means that many others could follow. By reading this thesis, the reader should recognize potentials and understand the local circumstances. This is the aim of the study. / Faton Deva "Shkodra" 14, Prishtina 10000 Kosova mob: +377(0)44122883 e-mail:faton99d@gmail.com

L’orchestration des mouvements directionnels d’architectures supramoléculaires s’avère cruciale pour la préparation de machines moléculaires artificielles. Les oligomères d’amides aromatiques (i.e. foldamères) peuvent adopter des conformations stables capables de se complexer à des tiges moléculaires pour former des (pseudo)-rotaxanes. Un contrôle fin des cinétiques d’association et de dissociation de l’hélice autour de la tige permet à l’oligomère hélicoïdal de glisser le long de celle-ci sans dissociation. Des études RMN et cristallographiques ont montré que des tiges moléculaires possédant plusieurs sites de reconnaissance pour des hélices permettaient l’élaboration d’architectures supramoléculaires hélicoïdales chirales avec une haute-fidélité. Chaque station possédant une longueur et une chiralité définie peut induire la complexation de foldamères de taille et d’hélicité concordante. Le glissement directionnel d’une double hélice le long d’une tige possédant plusieurs stations a également été investigué. Insérer un espaceur encombrant (i.e. plus large que la cavité de l’hélice) sur le chemin du foldamère le force à se déplier et se replier pour atteindre le site le plus favorable thermodynamiquement. Un oligomère asymétrique montrant de hautes affinités et de fortes sélectivités pour des tiges asymétriques a été préparé. L’enfilement de cet oligomère sur des tiges asymétriques a été étudié. Des données cinétiques (RMN) indiquent que l’enfilement de celui-ci s’effectue de façon polarisée en fonction de la nature de la tige. / The directional motion orchestration of supramolecular architectures is crucial for the construction of artificial molecular machines. Aromatic amide oligomers (i.e. foldamers) can adopt stable helical conformations able to wind around dumbbell-like guests to form (pseudo)-rotaxanes. A fine control of the association-dissociation kinetics allows the oligomers to slide along the rods without dissociation. In this thesis, based on the segregation of the kinetics of association-dissociation and sliding, helical oligomer motions were orchestrated to form complex self-assemblies and to perform directional motion. NMR and crystallographic studies showed that multistation rod guests can template the formation of well-defined multi-helical supramolecular polymers with high fidelity. Each station possessing a defined length and chirality can induce the complexation of oligomers presenting matching length and chirality. Directional sliding of a double helical oligomer along linear multistation rod guests was investigated. Placing a bulky spacer on the rod prohibits the sliding process, forcing the oligomer to dissociate and reassociate onto the thermodynamically favored station. An asymmetrical oligomer was prepared showing highly selective binding toward asymmetrical rod guests. The threading of this oligomer onto linear asymmetrical guests was investigated. Kinetic data indicated that the threading orientation of this asymmetrical oligomer was polarized by its passage along guest molecules.

No description available.

Ce travail présente la synthèse, la caractérisation et l’utilisation (transfert électronique photo-induit) de foldamères de taille nanométriques constitués d’unité quinolines. Grâce a une stratégie de synthèse de doublement de segment une grande variété d’oligomères (jusqu’à 96 unités) ont pu être préparé à partir du synthon 8 aminoquinoline-2-carboxylate.Leurs propriétés dynamiques de ces objets ont été étudiées en solution et en phase gazeuse. La spectrométrie de masse de mobilité ionique a permis de déterminer leur conformation en phase gazeuse. Les expériences de RMN DOSY et d’anisotropie de Fluorescence ont permis de déterminer leurs propriétés de diffusion (transrationnelle et rotationnelle). Ces résultats ont révélés qui ces foldamères sont rigides et que leur architecture hélicoïdale est conservée.Le transport électronique photo-induit à travers ces foldamères de taille nanométrique ont été étudié et le mécanisme de transfert ainsi que son efficacité ont été déterminé pour une série de composés de tailles variables. / Herein, synthesis, characterization and application (photoinduced electron transport) of nanosized quinoline-based foldamers have been explored. With double segment strategy, a variety of helical nanosized foldamers (up to 96 quinoline units) were successfully prepared based on 8-aminoquinoline-2-carboxylic acid monomer.The dynamic properties in gas phase and solution were investigated. Ion mobility mass spectrometry afforded access to the conformation state of foldamers ingas phase; DOSY and fluorescence anisotropy assessed the diffusion (translational and rotational, respectively) of foldamers in solution. All of these techniques revealed that quinoline-based foldamers are rigid and that helical conformation is conserved. Photoinduced electron transport through nanosized foldamer was also studied and the mechanism and the transport ratios were revealed.