The chromosomal translocation of t(14;18)(14q32;18q21) is a characteristic aberration of follicular lymphoma and Diffuse Large B cells lymphoma. By PCR, it was proved that the rearrangement of chromosomes 14 and 18 leads to an overexpression of BCL2, an anti-apoptotic protein, which is one of the factors responsible for the maturation of the diseases. The translocation involves the promoter region of IGH gene and the transcriptional unit of BCL2 gene. Previous studies carried out in Dr Tosi’s lab showed a looping out of the BCL2 gene from its chromosome territory in 15% of the nuclei analysed. This looping out could be possibly responsible for the transcriptional activity of the gene. A further relevant finding concerns the spatial distribution of the genes involved in the translocation in the interphase nuclei. In the Pfeiffer cell line, harbouring the t(14;18) rearrangement, the translocated BCL2 gene was positioned in the cell nuclei according to a bimodal distribution. One could speculate that the distribution in the periphery and in the centre of the nuclei could divide the Pfeiffer cell line in two different subpopulations, consequently from the transcriptional activity. These preliminary data set the ground for more experimental work to test whether genes associated with the nuclear interior were transcriptionally active as opposed to the genes positioned towards the nuclear periphery, transcriptionally inactive. The work here presented focuses on this investigation using RNA-DNA FISH (Fluorescence in situ hybridization). My work enabled the detection of IGH, BCL2 and t(14;18) genes along with their transcripts inside of the nuclei of Pfeiffer cell line. Contrary to what had been hinted by previous work, my results showed multiple nuclear positions of transcriptionally active IGH/BCL2 translocation. The result will need to be further supported by software analysis in order to define its specific nuclear position and to ensure the perfect localization of the genes inside each nucleus.

Background: Entrepreneurship plays an indispensable role in today’s society. Especially, the creation of new ventures promotes economic growth and new opportunities. Hereof, Sweden is viewed as a role-model, since it is one of the most innovative and entrepreneurial active countries in the world. Almost 6% of Sweden’s inhabitants are currently characterized as nascent entrepreneurs and thus, are engaged in early entrepreneurial activities without having started an official venture yet. Considering the fact that nascent entrepreneurs have no prior entrepreneurial experience while facing uncertain environments, they have to evaluate the attractiveness of new venture ideas and decide whether they are worth to pursue or to drop them. Purpose: The purpose of this thesis is to explore the evaluation approach of nascent entrepreneurs in the light of new venture ideas. More precisely, we want to investigate what kind of approaches they make use of when evaluating the attractiveness of those ideas and their motives behind the approaches. Method: This thesis is of qualitative nature while following an inductive approach and conducting a multiple case study with ten cases of different nascent entrepreneurs. The data is collected through semi-structured interviews, which were conducted in personal face-to-face meetings. For analysing the empirical findings, we engaged in within-case and cross-case analyses, where we identified and analysed common patterns and differences across the cases. Conclusion: All of the research respondents apply a variety of evaluation approaches, where they make use of their cognition as a means of judging and assessing the attractiveness of new venture ideas. Besides utilizing their social network, existing knowledge and future estimations, all nascent entrepreneurs are using heuristic rules-of-thumb for evaluating the idea attractiveness. Thereby, we identified Passion, Monetary Incentives, Resources and Market Potential as the most outstanding rules-of-thumb in the clear majority of the cases.

Cette recherche est consacrée à l’étude des dynamiques permettant de transformer des idées abstraites en innovations concrètes. Notre perspective stratégique vise à comprendre les mécanismes qui sont à l’œuvre lorsqu’il s’agit d’évaluer le potentiel des idées, d’organiser les ressources et de conduire le processus de passage de l’idée au projet d’innovation. Une idée abstraite devient une innovation concrète à travers un mouvement collectif de réalisation. Ce mouvement n’est possible que quand les acteurs parviennent à donner du sens à leur engagement. Ce postulat nous conduit à adopter une approche sociocognitive qui met le processus de construction de sens au cœur de l’analyse. Pour étudier un processus concret d’émergence de l’innovation, notre cadre conceptuel et méthodologique mobilise essentiellement la construction collective de sens de Weick, la sociologie de la traduction de Callon et Latour, et l’analyse processuelle de Pettigrew. Cette grille combine d’autres travaux moins répandus jusqu’à maintenant dans le management de l’innovation : la noologie de Morin, la philosophie de la technique de Simondon et l’ethnotechnologie de Gaudin. L’investigation empirique consiste en l’étude de cas d’une innovation majeure au sein de l’entreprise Air Liquide: dix ans de développement des garnissages pour la distillation cryogénique des gaz. L’étude de cas conforte la pertinence de notre approche sociocognitive. Tout particulièrement, elle permet de mettre en évidence deux dynamiques fondamentales et complémentaires dans la construction de sens : traduction et reconnaissance. Ce résultat conduit à tout à la fois remettre en cause et compléter la sociologie de la traduction en la reliant à la théorie de l’état naissant d’Alberoni à travers la « re-co-naissance » comme dynamique collective : plutôt que de se rallier par intérêt bien compris (l’intéressement / la traduction), les acteurs qui constituent le premier noyau actif, comme ceux qui se convertissent plus tard, « se reconnaissent » autour d’une idée dont ils « reconnaissent » ensemble le potentiel innovant et la capacité de transformation et de refondation de l’organisation (re-naissance / reconnaissance). Cette re-conceptualisation ouvre des perspectives théoriques et pratiques nouvelles pour la gestion des processus d’innovation. / This work is devoted to the study of sensemaking in the early stages of the development of innovative ideas. Our strategic perspective aims at understanding the dynamic mechanisms permitting to identify opportunities, to organize resources and to drive processes leading to the launch of innovation projects. We adopt a socio-cognitive view: ideas become innovations as players invest in a collective move, giving sense both to their commitment in the innovative process and to the resulting innovation. Our conceptual framework is based on Weick’s model of Organizational Sensemaking combined with Callon and Latour’s Actor-Network theory, and on Pettigrew’s Processual Analysis methodology. In addition, this conceptual construct articulates some others theories wich are less often seen in innovation management research: Morin’s works on “noology”, Simondon’s technical philosophy and Gaudin’s works on “ethno-technology”. The empirical work is a case study presenting a longitudinal analysis of a major process innovation in Air Liquide, an industrial and medical gaz producer. The main result stemming from the analysis combines two fundamental dynamics for sensemaking in innovation processes: translation and re-co-gnition. Our model thus challenges and extends the Actor-Network theory with Alberoni’s theory of Nascent state. Re-co-gnition is seen as the key mechanism operating in the ignition phase of collective movement: in contrast to transactional coalition building via a negotiated buy-in (translation), the initial players both recognize each other around the idea and recognize the innovative potential of the idea (re-cognition). These results offer a new promising approach for innovation management research and practice.

The thesis is based on data from the Global Entrepreneurship Monitor project and analyzes the link between self-efficacy of Czech nascent entrepreneurs and the disposable amount of human, social and financial capital. It also examines the link between self-efficacy and planning activities of nascent entrepreneurs. The second part of the paper analyzes the relationship between growth ambitions of nascent entrepreneurs and disposable human, social, financial capital and business planning. It also shows the relationship between entrepreneurial self-efficacy and growth aspirations of Czech nascent entrepreneurs.

Small businesses create most of the new jobs in the world, yet more than half fail before the 5th year. Small businesses contribute to the economy by originating new products and services, yet they often lack the strategies to overcome the challenges of the beginning years. When businesses fail, the community wanes from unemployment, poverty, crime, and other social dilemmas. The purpose of this single case study was to explore small business strategies for sustainability beyond Year 4, specifically in a single independent operating Ohio restaurant owner with less than 500 employees. The conceptual framework was Schumpeter's theory of the entrepreneur's role as leader of economic growth. A semistructured interview generated the data and a review of various business documents including tax returns, the business plan, an operations manual, company marketing material, and social media from the first 4 years in operation facilitated triangulation. Member checking afforded the correct meaning of various concepts and statements. This study contained 4 themes that foster business sustainability and may help nascent entrepreneurs navigate the challenges of the first 4 years: knowledge and experience, work ethic and commitment, social capital, and opportunity recognition through creative discovery. When entrepreneurs incorporate these themes into their business model, resiliency strategies materialize to expand and create jobs, launch new products or services, pay taxes, and stabilize tenuous neighborhoods. This study may also convince community stakeholders to design and reinforce training, networking, and financial opportunities to bolster entrepreneurial venture success.

Eukaryotic promoters are inherently bidirectional and allow RNA Polymerase II to transcribe both coding and noncoding RNAs. Dynamic disassembly and reassembly is a prominent feature of nucleosomes around eukaryotic promoters. While H3K56 acetylation (H3K56Ac) enhances turnover events of these promoter-proximal nucleosomes, the chromatin remodeler INO80C ensures their proper positioning. In my dissertation, I explore how chromatin dynamics regulate transcriptional homeostasis. In the first part, I investigate the role of H3K56Ac on the nascent transcriptome throughout the eukaryotic cell cycle. I find that H3K56Ac is a global, positive regulator for coding and noncoding transcription by promoting both initiation and elongation/termination. On the contrary, I find that H3K56Ac represses promiscuous transcription following replication fork passage by ensuring efficient nucleosome assembly during S-phase. In addition, I show that there is a stepwise increase in transcription in the S-G2 transition, and this response to gene dosage imbalance does not require H3K56Ac. This study clearly shows that a single histone modification, H3K56Ac can exert both positive and negative effects on transcription at different cell cycle stages. In the second part, I investigate the role of the chromatin remodeler INO80C on the nascent transcription around replication origins. I show that INO80C, together with the transcription factor Mot1, prevents cryptic transcription around yeast replication origins, and the loss of these proteins lead to an increase in DNA double strand breaks. I hypothesize that recruitment of INO80C ensures proper positioning of nucleosomes around origins and the exclusion of RNA Pol II to prevent cryptic initiation. Together these findings indicate that H3K56Ac regulates transcription globally by enhancing nucleosome turnover, and it prevents cryptic transcription and reinforces transcriptional fidelity by promoting efficient nucleosome assembly in the S-phase. In addition, INO80C maintains genome stability by preventing cryptic transcription around the origins.

Product markets have been found to be socially constructed as industry logics, product ontologies and organising visions. Information intermediaries play an important field-level role in determining the categories and ontologies of emerging products. Within shared cognitive structures, sellers and buyers come together in mutual understandings on how products are used, what features are important and what counts as value. Although market information is often legitimated through objective scientific methodologies, it can also appear as uncertain knowledge, or rumour. Contrary to the often seen conception of rumour as crowd-like behavioural contagion, it is presented here as an informal message lacking a reliable sponsor that is developed in an uncertain situation, but still may be subject to critical reasoning. This thesis investigates the ambiguity around the fuzzy front-end of product markets, as social media and blogs that trade in rumour and proposition before any official announcement by firms. Through a process of improvised news, these online collectivities, as product publics, deliberate and collectively generate expectations as meaning structures. By tracking discourse from tech blogs, I trace the emergence of meaning in the tablet device product ontology. This occurred well before product introductions by firms who eventually came to form the market.

Submitted by SBI Biblioteca Digital (sbi.bibliotecadigital@puc-campinas.edu.br) on 2017-06-28T12:49:58Z No. of bitstreams: 1 LEONARDO HENRIQUE PIACENTE.pdf: 1178258 bytes, checksum: ff6627db41d7b7353cfeec2f755778a1 (MD5) / Made available in DSpace on 2017-06-28T12:49:58Z (GMT). No. of bitstreams: 1 LEONARDO HENRIQUE PIACENTE.pdf: 1178258 bytes, checksum: ff6627db41d7b7353cfeec2f755778a1 (MD5) Previous issue date: 2016-12-14 / The encounter of nascent Christianity with classical Greco-Roman culture in the second century AD had points of confluence, dispersion and conjugation. The thought of Irenaeus of Lyons (130-208 AD) in Adversus haereses shows that the relation between Christian religion and classical culture came close to the Christian gnostic groups. These, when evangelized and adept at the good news of Jesus Christ, brought with them their cultural framework, and thus Christianity marked by Jewish customs, was gaining nuances of the diverse cultures, religions, peoples and languages present in the Roman Empire. The research was not intended to value this relation Greco-Roman culture and nascent Christianity, but rather to show the importance and the tensions present in this relation, from the first book of the Demonstration and refutation to the false gnosis. Irenaeus constructed his thought in order to make clear the thinking of the various gnostic groups, in order to refute them, and in the meantime presented a systematization of the Christian faith not yet seen in his time. Its Demonstration and Refutation of the Gnostic theses was not only a way of fighting the controversies that arose in the first centuries of the Church, but was also, as presented in this research, a means of showing the interaction between Christians, especially the thinkers, with The intellectual and cultural environment that they were inserted. As a process of conjugation, Christianity and the classical culture had mutual influences, differences and points in common, in the formation from initial Christian thought. The hermeneutics of the first book of the Adversus haereses, and classical thinking, made it possible to understand and deepen the relationship between culture and religion in the second century AD. / O encontro do cristianismo nascente com a cultura cl?ssica greco-romana, no s?culo II d.C., teve pontos de conflu?ncia, de dispers?o e de conjuga??o. O pensamento de Irineu de Li?o (130-208 d.C) na obra Adversus haereses mostra que a rela??o religi?o crist? e cultura cl?ssica teve uma aproxima??o grande em virtude dos grupos gn?sticos crist?os, que evangelizados e adeptos ? boa nova de Jesus Cristo, traziam consigo seu arcabou?o cultural, sendo assim o cristianismo marcado pelos costumes judaicos, foi ganhando matizes das diversas culturas, religi?es, povos e l?nguas presentes no Imp?rio Romano. A pesquisa n?o pretende valorar esta rela??o cultura greco-romana e cristianismo nascente, mas sim mostrar a import?ncia e as tens?es presentes nessa rela??o, a partir do primeiro livro da Demonstra??o e refuta??o ? falsa gnose. Irineu construiu seu pensamento em busca de tornar claro o pensamento dos diversos grupos gn?sticos, para assim refut?-los, e neste ?nterim apresentou uma sistematiza??o da f? crist? ainda n?o vista no seu tempo. A sua Demonstra??o e Refuta??o das teses gn?sticas, foi n?o s? um caminho de combate ?s controv?rsias, que surgiram nos primeiros s?culos da Igreja, mas tamb?m foi, como apresentado nesta pesquisa, um meio de mostrar a intera??o entre os crist?os, principalmente os pensadores, com o meio intelectual e cultural que estavam inseridos. Como um processo de conjuga??o, o cristianismo e a cultura cl?ssica tiveram influ?ncias m?tuas, diferen?as e pontos em comum, na forma??o desde pensamento crist?o inicial. A hermen?utica do primeiro livro da Adversus haereses, e do pensamento cl?ssico, possibilitou compreender e aprofundar-se na rela??o cultura e religi?o no s?culo II d.C.

Axonal protein synthesis is rapidly regulated by extrinsic cues during neural wiring but the full landscape of proteomic changes and their translational control mechanisms remain unknown. The ability to investigate the nascent proteome on subcellular compartments has been hampered by the low sensitivity of existing methodology on quantity-limited samples combined with the difficulty of obtaining sufficient amounts of pure material. By combining pulsed Stable Isotope Labelling by Amino acids in Cell culture (pSILAC) with Single-Pot Solid-Phase-enhanced Sample Preparation (SP3), I have established an approach to characterize the nascent proteome from quantity-limited somaless retinal axons (~2μg) on an unparalleled rapid time-scale (5 min). The results show that a surprisingly large number of proteins (>350) is translated constitutively in axons, many of which are linked to neurological disease. Axons stimulated by different cues (Netrin-1, BDNF, Sema3A) each show a signature set of up/down newly synthesised protein (NSP) changes (>100) within 5 min. Remarkably, conversion of Netrin-1-induced responses from repulsion to attraction triggers opposite translational regulation for 73% of a common subset corresponding to >100 NSPs. Further, I show that pharmacological increase in cAMP, known to induce chemoattractive response, also leads to rapid and wide-scale remodelling of the nascent axonal proteome (~100 NSP changes). I find that the cAMP-elicited NSP changes underlie the attractive turning but are distinct from those induced by the physiological chemoattractant Netrin-1, suggesting that the same type of chemotropic response can be mediated by different protein synthesis-dependent mechanisms. Finally, I show that Sema3A, but not Slit1, triggers a physiological and non-canonical PERK-eIF2α-eIF2B signalling pathway required in neural wiring to elicit the rapid (< 15 min) local translation control of a specific subset of NSPs. Collectively my findings lead to the general conclusion that guidance molecules rapidly induce cue-specific remodelling of the nascent axonal proteome via distinct regulatory mechanisms.

This thesis goal is to analyze the factors that are influencing the strategies and growth expectations of the Czech start-ups. The analysis is based on the data sample from the Czech GEM 2011 and unique study of the Czech start-ups performed in 2011 as well. Various statistical methods are used to determine which microeconomic factors affect (1) the strategy choice and (2) growth expectations. As for the factors influencing expected growth, the research is concluded by the creation of the regression equations explaining the expected growth in the revenues as well as expected growth in employees. The factors influencing strategy choice are: managers-owners experience, the environment, self-efficacy, gender, and innovativeness. The factors influencing expected growth in revenues are: innovativeness, self-efficacy, competitive strategy, managers-owners experience, social capital, export intention, and business planning. The factors influencing the expected growth in employment are: legal structure of company, export intention, self-efficacy, innovativeness, competitive strategy, business planning. Following variables create the regression equation explaining expected growth in revenues: financial planning, export intention, education, IPR use, and age of entrepreneur. The variables explaining expected growth in employees are: (1) export intention, product newness, and legal structure of the company, (2) product newness, differentiation inclination, and financial projections. Alongside, the Porter's generic strategies framework was proved to fit the data sample while it was showed that a portion of Czech entrepreneurs are "stuck in the middle". By these findings, this thesis provides unique empirical verification of the growth and strategy theory on the sample of the Czech entrepreneurs.