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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
71

Cross-Sectoral Collaboration in Implementing the Sustainable Development Goals in Sweden

Ashraf, Aysha January 2024 (has links)
In the Sustainable Development Goal’s (SDG) decade of action, research from various disciplines focuses on the proper pattern of SDG implementation and the role of partnership to ensure balance between economic, social, and environmental dimensions. Yet, there is a lack of clarity in the empirical understanding of it. This thesis aims to unravel the potential of Triple Helix Model cooperation and the EU's Principle of Partnership in the multilevel governance system in Sweden for the proper realization of such goals. Relying on the perspectives of the Triple Helix Model and the EU's Principle of Partnership, the thesis examines potential synergies across SDGs, the pressing need for cooperation in multilevel governance systems, and meta-governance instrumental strategies for SDGs’ proper implementation. Moreover, it identifies partnership as innovative governance in SDG implementation. The study complements the existing body of knowledge and literature with relevant findings that reveal the proper functioning of implementing the SDGs. Firstly, the findings indicate interlinkages between the goals using triple helix model cooperation in the Vaxjo case. Triple Helix Model cooperation has proved to be soft governance for the SDGs' implementation. Secondly, the EU's Principle of Partnership in the multilevel governance system indicates potential challenges in harnessing synergies in implementing the SDGs. That the thesis finds these results in the case of Sweden, which is among the leading countries for SDG interaction, highlights the importance of effective cooperation at different levels of government to localize SDGs and ensure synergies. Lastly, this thesis highlights how important sub-national units are to the localization and realization of the SDGs. These findings suggest that the Triple Helix Model is a main driver of the achievement of SDGs in Sweden that may also be applicable in all countries with current triple helix model potential. However, the findings provide a new understanding of the importance of cooperation across different sectors and tiers of governance systems. The present study offers the first comprehensive assessment of cooperation in a multilevel governance system to implement SDG properly.
72

Skellefteås återkomst : En fallstudie om migrationsmönster och urbana effekter under en industriell expansion / The Return of Skellefteå : A case study of migration patterns and urban effects during an industrial expansion

Kokkalis, Elena, Adler, Rebecca January 2022 (has links)
Idag står världen inför nya typer av utmaningar för att möta hållbarhetsmål och nya behov somuppkommer. Många städer genomgår därför stora förändringar i utvecklingen där både förväntadeoch oväntade konsekvenser kommer att uppstå. Sedan Northvolt beslutade att etablera sig iSkellefteå år 2017, står staden inför den stora möjligheten att bli en pionjär stad för grön utveckling.Den nya utvecklingen har inte bara satt industrin på prov, utan även staden som helhet. Kommunensutmaning är att sprida budskapet om vad den kommande utvecklingen har att erbjuda, i hopp om attsätta fart på inflyttningen då kompetensbehovet är Skellefteås främsta utmaning idag. För att mötavisionerna kring utvecklingen behöver alla aktörer samverka för att bli en stad för grön elektrifiering.Välfungerande socialt kapital mellan offentlig sektor, industri, akademi och medborgare är enförutsättning för att skapa en framgångsrik utveckling.Arbetet utforskar hur en stad som genomgår en omfattande och snabb industriell expansionpåverkas. Genom att studera migrationsmönster ur “push and pull”-teorin undersöker arbetet hur detär möjligt att generera en ökad in-migration i olika målgrupper, som studenter eller hemvändare.Samtidigt som Skellefteå är beroende av att ha ett positiv inflyttningsnetto behöver även denuvarande invånarna bibehållas. Därför har intervjuer och en enkät genomförts för att få en tydligbild av styrkor och svagheter i utvecklingen av Skellefteå. Resultaten av enkäten och intervjuernaanalyserades och diskuterades genom en exemplifiering av de två teorierna push and pull och teorinom socialt kapital.Stora industriella expansioner av denna storlek skakar städerna till sin kärna, eftersom stadensidentitet och attribut ifrågasätts under denna typ av förändring. Vid en utveckling av denna storleksätts det sociala kapitalet på prov och beroende på dess effektivitet kan utfallen skilja sig åt. Stadentvingas väga olika faktorer mot varandra; ekonomiska, sociala och miljömässiga, då alla inte är möjligaatt upprätthålla till samma grad. Eftersom det största målet är att skapa en ökad in-migration till denexpanderande staden måste de pull-faktorer som finns och främjas ifrågasättas; Vad erbjuderegentligen Skellefteå? Arbetet identifierade sex möjliga grupper av in-migration; kontraurbanister,livsstilsmigranter, människor som flyttar för relationer/hemvändare, människor som flyttar förjobbmöjligheter, studenter och människor som flyttar för hållbarhetsskäl. Genom att lyfta fram enuppsättning av pull-faktorer specifikt för Skellefteå har staden den unika möjligheten att påverkamigrationsmönstren till deras behov och skapa en hållbar och attraktiv stad för den nuvarande ochframtida invånaren. / Today the world stands in front of the challenge of adapting to new demands, where solutions thatincrease sustainability are required. Many cities are therefore undergoing big changes indevelopments where both expected and unexpected consequences will arise. Since 2017, whenNorthvolt decided to establish in Skellefteå, the city stands in front of the opportunity to become apioneer city of green evolution. The new development has not only put the demands of the industryat test, but also the city as whole. The challenge of the municipality is how to spread the message ofwhat the upcoming development has to offer to boost the in-migration, as the need for competence isthe main challenge of Skellefteå today. To be able to fulfil and meet the visions of the transformation,all actors need to work together in becoming the green city of electrification. To create a successfuldevelopment, the overlapping collaboration between the government, industry, academia andcommunity needs to be of high quality and thus the social capital will increase.The thesis explores the effects of a city that undergoes a fast expansion. By studying migrationpatterns through push and pull theory, the thesis investigates how to generate an increasedin-migration in different target groups, such as students and returners. While Skellefteå is dependenton having a positive netto in-migration, the current residents also need to be maintained, thusinterviews and a questionnaire has allowed the thesis to obtain a clear picture of strengths andweaknesses of the development in Skellefteå. The results of the questionnaire and the interviews areanalysed and discussed through an exemplification of the two theories of push and pull and thetheory of social capital.Large industrial expansions of this size shake cities to their core, as the identity and attributes of thecity are questioned as they change. When dealing with a development of this size, the social capital isput to the test and depending on its effectiveness, the outcomes can differ. The city is forced to weighdifferent factors against each other, the benefits of accommodating economic, social andenvironmental factors are measured and prioritised as all are not possible to sustain. As the main goalis to create an increased in-migration to the expanding city, the pull factors available and promotedneed to be questioned; What is Skellefteå in fact offering? The thesis identified six possible groups ofin-migration; counterurbanists, lifestyle migrants, people moving for social ties/the returners, peoplemoving for job opportunities, students and people moving for sustainability reasons. By highlightingone set of pull factors, Skellefteå has the unique opportunity to influence the migration patterns totheir needs and create a sustainable and attractive city for the current and future residents.
73

Estratégias bem sucedidas na interação universidade e empresa: uma análise da trajetória de instituições privadas

Koste, Raquel Cecilia Jung 16 August 2010 (has links)
Submitted by William Justo Figueiro (williamjf) on 2015-07-16T21:04:12Z No. of bitstreams: 1 22c.pdf: 4652907 bytes, checksum: ab21111b63aa4aebf99649423c80f786 (MD5) / Made available in DSpace on 2015-07-16T21:04:12Z (GMT). No. of bitstreams: 1 22c.pdf: 4652907 bytes, checksum: ab21111b63aa4aebf99649423c80f786 (MD5) Previous issue date: 2010-08-16 / UNISINOS - Universidade do Vale do Rio dos Sinos / O conhecimento é o fator-chave para a criação do novo e a inovação é dependente do capital humano e da cooperação entre as pessoas e organizações. Este estudo qualitativo utiliza o método do estudo de caso e busca compreender a evolução de estratégias bem sucedidas de interação universidade e empresa e identificar os principais diferenciais que explicam os ganhos estratégicos decorrentes das parcerias. A seleção das instituições para este estudo – PUC-Rio e Fundação Dom Cabral e o relacionamento com a Petrobras – considerou o fato de serem de natureza privada, com trajetórias bem sucedidas de relacionamento com empresas e reconhecidas pela excelência no ensino e pesquisa. A trajetória destas empresas é marcada por eventos que permitem observar as implicações dos relacionamentos e da mobilização dos recursos estratégicos para a prática da inovação. O aporte teórico que embasa a análise da interação Universidade-Empresa se utiliza da abordagem da Hélice Tríplice, das Redes Interorganizacionais, da Visão Baseada em Recursos e da Visão Relacional. A análise dos dados coletados apresentou evidências de que o diferencial estratégico das instituições pesquisadas é obtido a partir de posicionamentos e ações estratégicas ao longo do tempo; da capacidade de gerar conhecimento e inovar; da capacidade de conexão com o mercado e de desenvolver novas competências organizacionais; da capacidade de mobilizar recursos internos e de estabelecer parcerias através de relacionamentos interorganizacionais; e da capacidade de atrair e reter talentos que possam contribuir para a excelência acadêmica, a sustentabilidade e a efetiva participação no desenvolvimento social. / Knowledge is the key factor for the creation of anything new and innovation is dependent on human capital and cooperation among people and organizations. This qualitative study uses the case study method and seeks to understand the evolution of successful strategies of interaction between university and industry and to identify key differences that explain the gains arising from strategic partnerships. The selection of the institutions for this study - PUC-Rio and Fundação Dom Cabral and the relationship with Petrobras - considered the fact that they are private in nature, with histories of successful relationships with companies and recognized for excellence in teaching and research. The trajectory of these companies is marked by events that allow us to observe the implications of the relationships and the mobilization of strategic resources for the practice of innovation. The theoretical bases that support the University-Industry interaction are the Triple Helix approach, the Interorganizational Network, the Resource-Based View and the Relational Vision. The data analysis presented evidence that the strategic differentiator of the institutions surveyed is derived from placements and strategic actions over time, the ability to generate knowledge and innovate, the ability to connect with the market and to develop new organizational skills, the ability to mobilize domestic resources and to establish partnerships through interorganizational relationships, and the ability to attract and retain talent that can contribute to academic excellence, sustainability and effective participation in social development.
74

Les rapports université/entreprise à l’Université Nationale Autonome du Mexique (UNAM) : la vision de professeurs ayant de l’expérience de collaboration avec des entreprises

Ortega Villalobos, Maricela 11 1900 (has links)
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.
75

O processo de incubação social da Universidade Federal de Goiás: os desafios para a interação significativa na construção do conhecimento / The process of Social Incubation in the Federal University of Goiás: the challenges to the significant interaction in the production of knowledge

Ribeiro, Geisa Müller de Campos 05 May 2016 (has links)
Submitted by Jaqueline Silva (jtas29@gmail.com) on 2016-08-30T17:20:36Z No. of bitstreams: 2 Dissertação - Geisa Muller de Campos Ribeiro - 2016.pdf: 2724443 bytes, checksum: 58e60b3cc66b5bb9542ba366d999ff97 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2016-08-30T17:21:05Z (GMT) No. of bitstreams: 2 Dissertação - Geisa Muller de Campos Ribeiro - 2016.pdf: 2724443 bytes, checksum: 58e60b3cc66b5bb9542ba366d999ff97 (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-08-30T17:21:05Z (GMT). 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.
76

Cooperation for Regional Growth and Development in the Värmland Region 1998-2008 : - With a Triple Helix Approach

Säll, Line January 2008 (has links)
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.
77

A Future Wine Cluster in Kosova?

Deva, Faton January 2007 (has links)
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
78

Les rapports université/entreprise à l’Université Nationale Autonome du Mexique (UNAM) : la vision de professeurs ayant de l’expérience de collaboration avec des entreprises

Ortega Villalobos, Maricela 11 1900 (has links)
No description available.
79

Isomerization-Locked Alkene Analogues of Xaa–Pro Dipeptides in the Proteins Collagen and Bora

Arcoria, Paul Joseph 25 July 2022 (has links)
Collagen is one of the most abundant human proteins. It exists as a right-handed superhelix called the triple helix. The triple helix consists of three left-handed polyproline type II (PPII helices) that intertwine around a common axis. Each PPII helix has the repeating peptide sequence (Gly–Xaa–Yaa)n with a high content of (2S)-proline (Pro) in the Xaa position (ca. 28%) and (2S,4R)-hydroxyproline (Hyp) in the Yaa position (ca. 38%). Unique to the prolyl amide is the ease of cis-trans isomerization. Since the triple helix necessitates that all peptide bonds be in the trans conformation, isomerization is the rate-limiting step in collagen folding. However, eliminating isomerization with a trans-locked alkene isostere destabilizes collagen-like peptides. Collagen is stabilized by electronic interactions, namely the n→π* interaction. Halo-alkene isosteres may be used to recapture these electronic interactions and stabilize a collagen-like peptide. An in-depth conformational analysis was conducted at the MP2/6-311+G(2d,p) level of theory to determine the viability of conformationally-locked halo-alkene isosteres. Fluoro-alkenes and chloro-alkenes were modeled at both the Gly–Pro and Pro–Pro (as a Pro–Hyp mimic) amide positions. Compared to the collagen crystal structure PDB ID: 1K6F, we found the fluoro-alkenes were closer geometric matches to both Gly–Pro and Pro–Pro than the corresponding chloro-alkenes. The chloro-alkene was predicted to have stronger n→π* interactions. The trans-locked proteo-alkene was also analyzed to understand why it destabilized the triple helix. We found that these models had other local minima close to the desired PPII geometry, likely leading to enhanced backbone flexibility. This deleterious flexibility was not predicted for either fluoro-alkene or chloro-alkene models. The conformationally-locked halo-alkene isostere Fmoc–Gly–Ψ[(Z)CF=C]-Pro–Hyp(tBu)–OH was designed and synthesized as a (Z)-fluoro-alkene Gly–Pro isostere. We used the chiral catalyst, L-Thr, for asymmetric aldol addition to cyclopentanone, which inadvertently enhanced the yield of the wrong enantiomer, in contrast with aldol addition to cyclohexanone. A Mg2+-promoted Horner-Wadsworth-Emmons reaction afforded the (Z)-fluoro-alkene over the (E)-fluoro-alkene in about a 2:1 ratio. The two diastereomers, Fmoc–Gly–Ψ[(Z)CF=C]-L-Pro–Hyp(tBu)–OH and Fmoc–Gly–Ψ[(Z)CF=C]-D-Pro–Hyp(tBu)–OH were separated by supercritical CO2 chromatography. The collagen-like peptides Ac–(Gly–Pro–Hyp)3–Gly–Ψ[(Z)CF=C]-L-Pro–Hyp–(Gly–Pro–Hyp)4–Gly–Gly–Tyr–NH2, Ac–(Gly–Pro–Hyp)3–Gly–Ψ[(Z)CF=C]-D-Pro–Hyp–(Gly–Pro–Hyp)4–Gly–Gly–Tyr–NH2, and the control peptide Ac–(Gly–Pro–Hyp)8–Gly–Gly–Tyr–NH2 were synthesized on solid-phase resin. The CD spectra of all three peptides showed the characteristic collagen triple-helix signature. The folding stability was determined by thermal melting (Tm). The peptide with the fluoro-alkene guest, Gly–Ψ[(Z)CF=C]-L-Pro–Hyp, was found to have a Tm value of 42.2 °C. The Tm of the control peptide was found to be 49.0 °C, a difference in stability of only ΔTm –6.8. Thus, the (Z)-fluoro-alkene as a Gly–Pro isostere forms a relatively stable triple helix. The peptide with the Gly–Ψ[(Z)CF=C]-D-Pro–Hyp guest was shown to have a linear relationship between ellipticity and temperature, indicating that a stable triple helix did not form. The enhanced stability of the (Z)-fluoro-alkene compared to the (E)-alkene Gly–Pro isostere (Tm = 28.3 °C) may be due to a stabilizing n→π* interaction, as determined by NMR deshielding of the 19F nucleus in the collagen-like peptide. In biological systems, isomerization of the prolyl amide is catalyzed by enzymes called PPIases. The PPIase Pin1 specifically catalyzes isomerization of the pSer–Pro sequence from the cis-conformation to the trans-conformation. Pin1 plays a crucial role in the G2→M transition of the cell cycle, implying the importance of cis-trans isomerization. The dipeptides H–Ser–Ψ[(Z)CH=C]-Pro–OH, H–Ser–Ψ[(E)CH=C]-Pro–OH and native H–Ser–Pro–OH were synthesized by literature methods, and activated for aminoacylation of tRNACUA for in vitro transcription-translation. Aminoacylation by chemical methods required the synthesis of a pdCpA dinucleotide. Formation of the dipeptide-dinucleotide complex was not completed because protection of the Ser side chain was problematic. On the other hand, conversion of the dipeptide into the 3,5-dinitrobenzyl ester conjugate allowed for enzymatic aminoacylation using the dFx flexizyme, an RNA enzyme. The native dipeptide was successfully coupled to tRNACUA and is ready for incorporation into a full-length Bora protein by in vitro transcription-translation. Both cis- and trans-locked alkene mimics have been converted to their respective 3,5-dinitrobenzyl ester conjugates. / Doctor of Philosophy / The proline amide (Xaa–Pro) in peptides and proteins is unique in that it allows for cis-trans isomerization. The triple-helix region of human collagen consists mostly of the repeating sequence (Gly–Pro–Hyp)n. Xaa–Pro amide-bond isomerization is rate-limiting for triple-helix formation. We eliminated isomerization at one position in a collagen-like peptide with a locked alkene mimic of Gly–Pro to attempt to stablize the triple-helix. Our computational results predicted that a fluoro-alkene Gly–Pro isostere would be a close geometric match for the native amide. Experimental results showed that a collagen-like peptide with a fluoro-alkene Gly–Pro isostere has an unfolding temperature that is 6.9 °C lower than the native control peptide. 19F NMR data of the collagen-like peptide shows a surprising deshielding of the fluorine nucleus, suggesting its participation in a stabilizing n→π* electronic interaction, similar to the native amide. Isomerization also plays a key role in proper cell division. We followed established methods to synthesize the cis- and trans-locked alkene mimics of Boc–Ser–Pro–OH and converted them into the 3,5-dinitrobenzyl ester conjugates. The 3,5-dinitrobenzyl ester is recognized by the dinitrobenzyl flexizyme (dFx) for enzymatic aminoacylation of tRNA. Once the alkene isosteres are aminoacylated, they will be incorporated into a full-length cell cycle regulatory protein called Bora to determine whether the cis- or trans-Pro state is necessary for healthy human mitosis, and which results in cancerous human mitosis.
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Managing university-industry linkage in government universities of Ethiopia : challenges and opportunities

Misganu Legesse Bareke 02 1900 (has links)
This study set-out to examine how university-industry linkage (UIL) is managed in government universities of Ethiopia to contribute to the economic development of the country. Basic questions related to the level of management of UIL, areas of linkage, benefits obtained so far from this partnership, challenges to the proper management of UIL, and the existing opportunities for promoting UIL were raised. In addition to this, strategies for strengthening UIL were also dealt with. In relation to this, the study was framed with the system theory viewpoints and human capital theory viewing universities as a system linked to its external environment like industries. As a model, interactive/balanced type of Triple Helix model was used as it integrates the activities of the government, universities and the industries. Moreover, this study reviewed global perspectives on UIL and an overview of the study context with greater emphasis on higher education reforms and proclamations. Philosophically, this study followed pragmatism research paradigm using mixed research approach. It also employed concurrent/parallel/convergent design in which both quantitative and qualitative data were collected simultaneously, interpreted separately and combined at the time of discussion for better understanding of the problem. Equal importance for both data sets was given. Data were gathered from 99 college deans and department heads, 200 instructors and 316 prospective graduates. In addition to this, 23 interviewees from UILOs, industries, MoE, and MoST took part in this study. Moreover, two focus group discussions were also conducted with the university alumni and data were gathered through survey questionnaires, semi-structured interview, FGD question guides and document reviews. The study result indicated that both quantitative and qualitative data support one another. It was found out that UIL was at its infant stage of development in government universities of Ethiopia with limited areas, dominated by students’ internship. Ethiopian government universities have a link with the industries in areas of some limited joint research projects, consultancies and capacity building. Consequently, universities benefitted by attaching their students with the industries and students got practical exposure to the real world of work. Industries also benefitted from the training provided to them, consultancies and joint research projects. On the other hand, UIL in government universities of Ethiopia was challenged by institutional bottlenecks, policy-practice gaps, contextual variation and information gaps, finance and awareness related caveats, work overload, and facility related hurdles. Moreover, lack of trust and commitment between U & I, lack of commitment and support from the leadership of both universities and industries, and the reluctance of the local industries to work with the universities remained a big rift to UIL. This study also sheds light on the expansion of universities and industries in different parts of the country as the opportunities to be tapped to promote UIL. Further, the attention of the government by designing different policies, strategies, directives and conferences was taken as the opportunity. As a major contribution, this study came up with the model that was designed to improve the practice of management of UIL in government universities of Ethiopia. To overcome the above challenges and to make use of existing opportunities, it was recommended that improving leadership and management related challenges through joint planning, organising, staffing and decision-making. Moreover, it was highly laudable to make a paradigm shift in the roles of universities from teaching dominated to research and innovation universities. Finally, bridging policy-practice gaps, increase networking, arranging various sensitising and advertising programmes and creating a further avenue for more research were commented. / Educational Leadership and Management / D. Ed. (Education Management)

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