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1
Custo, Greig Luciano. „Progenitor Diversity, Lineage Commitment, and Acquisition of Cell-Type Identity in the Cerebral Cortex“. Thesis, Harvard University, 2017. http://nrs.harvard.edu/urn-3:HUL.InstRepos:32676122.
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An extraordinary variety of neuronal subtypes, each with distinct morphologies, patterns of connectivity, and electrophysiological properties, is generated during neocortical development. Elucidating programs of molecular controls that govern progressive specification of neuronal subtype identity in the cerebral cortex contributes toward our understanding its development, organization, evolution, and function. Establishing a basic framework for how and when cell fate specification decisions are made will enable more efficient manipulation of these transitions in vitro, and therefore has important practical implications for biomedical research, as it will help improve protocols for generation of specific cortical neuron subtypes for use in disease modeling, drug screening, and therapeutic transplantation.
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Fernandes, Gonçalo. „Imaging transcription in living embryos to decipher the robustness of patterning“. Electronic Thesis or Diss., Université Paris sciences et lettres, 2022. http://www.theses.fr/2022UPSLS025.
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Au cours du développement, les gradients morphogénétiques fournissent l’information positionnelle nécessaire à l’établissement des axes de polarité. Si l’importance de ces gradients est bien établie, la façon dont ils assurent la reproductibilité des patrons d’expression malgré la nature stochastique de la transcription reste énigmatique.Pour répondre à cette question, j’étudie l’établissement de l’axe antéro-postérieur (AP) de l’embryon de drosophile, sous contrôle de Bicoid (Bcd), un facteur de transcription et morphogène bien connu. Les ARNs de bcd sont exprimés maternellement et ancrés au pôle antérieur de l’ovocyte. Après la ponte, ces ARNs sont traduits en protéines, qui diffusent dans le cytoplasme pour former un gradient de concentration exponentiel avec son maximum au pôle antérieur. Un modèle simple propose que le destin de chaque cellule le long de l’axe est déterminé par la concentration de Bcd qu’elle reçoit. Toutefois, de nombreux débats ont remis en question la possibilité que les patrons d’expression induits par Bcd résultent uniquement des propriétés de diffusion et d’interaction des protéines Bcd avec leurs séquences cibles.L’objectif de ma thèse était de comprendre le rôle précis de Bcd dans l’expression de son gène cible principal, hunchback (hb). Pour cela, j’ai adapté à des gènes rapporteurs synthétiques, le système MS2-MCP, qui permet l’étiquetage fluorescent des ARN et l’analyse quantitative de la dynamique transcriptionnelle avec une forte résolution spatio-temporelle dans les embryons vivants. Dans ces rapporteurs, la séquence MS2 est contrôlée par un promoteur minimal contenant aussi les sites de fixation pour Bcd ou ses partenaires, Hb et Zelda (Zld), seul ou en combinaison. Mon but était de déterminer comment les divers rapporteurs récapitulent l’expression du promoteur d’hb et d’identifier les rôles spécifiques de chacun de ces facteurs et leurs interactions dans le mécanisme de transcription.De façon intéressante, l’expression du rapporteur avec uniquement neuf sites pour Bcd (trois de plus que dans le gène hb) récapitule l’expression du rapporteur hb-MS2, mais de façon moins rapide et avec un domaine d’expression à la bordure moins nette. Cela suggère qu’en définissant la position de la bordure mais pas sa netteté ni la rapidité de son établissement, Bcd est la source principale d’information positionnelle.En outre, la fixation des partenaires de Bcd au promoteur accélère le processus en agissant à différentes étapes : i) Hb agit en synergie avec Bcd en réduisant les fluctuations du promoteur et en augmentant le taux de démarrage de la polymérase ; ii) Zld abaisse le seuil de concentration de Bcd nécessaire à l’activation par Bcd. En collaboration avec des physiciens, nous avons développé un modèle de transcription impliquant Bcd et fournissant un contexte théorique aux données expérimentales. Ce modèle montre que l’établissement rapide de la bordure d’expression d’hb peut être expliqué par une réaction d’équilibre entre Bcd et ses sites de fixation pour l’information positionnelle nécessitant Zld et Hb pour sa dynamique temporelle.Pour confirmer que Bcd est la seule source d’information positionnelle du système, j’ai comparé la position de la bordure d’expression des gènes rapporteurs dépendant uniquement de Bcd dans des embryons exprimant une ou une demi-dose de Bcd. De manière surprenante, pour chaque rapporteur, le déplacement de la bordure est plus faible que son estimation théorique tenant compte de la constante du gradient exponentiel de concentration de Bcd. Cela indique une constante plus faible pour le gradient d’activité de Bcd et suggère l’existence de sous-populations de Bcd, avec certaines molécules moins actives que d’autres. L’amplitude du déplacement de la bordure du gène rapporteur hb-MS2 est la même que celle obtenue pour les rapporteurs dépendant uniquement de Bcd ce qui confirme que Bcd est bien la seule source d’information positionnelle pour l’expression d’hbMorphogen gradients provide concentration-dependent positional information required to establish the polarity of developmental axes. Although the critical role of these gradients is well recognized, it is unclear how they provide reproducible expression patterns. This is particularly surprising if we consider the stochastic nature of transcription.To address this question, I focus on the establishment of the anterior-posterior (AP) axis of fruit fly embryos, which is mostly defined by Bicoid (Bcd), a very well-characterized morphogen and transcription factor. bcd mRNAs are expressed maternally and anchored at the anterior tip of the oocyte. After egg laying, these mRNAs are translated into proteins, which diffuse through the cytoplasm and form a gradient with its highest concentration at the anterior. A simple model is that depending on their position along the AP axis and thus on Bcd concentration, cells will adopt different fates. However, long debates in the field have questioned the possibility that Bcd-dependent transcription patterns emerge solely from diffusive biochemical interactions between limiting amounts of Bcd molecules and the gene promoter region.The goal of my PhD was to determine how Bcd precisely regulates expression of its main target gene, hunchback (hb). For this, I adapted to synthetic reporters the MS2-MCP system, which allows the fluorescent tagging of mRNAs and provides, thus, a quantitative analysis of transcription dynamics at high spatiotemporal resolution in living embryos. In these reporters, the MS2 sequence was placed under the control of a minimal promoter also containing DNA binding sites for Bcd and/or its known partners, Hb and Zelda (Zld), either alone or in combination. My goal was to determine how the various reporters could recapitulate expression of the hb promoter (hb-MS2 reporter) and shed light on the specific roles of the different factors and their interactions in the transcription mechanism.Interestingly, expression of the reporter with only nine Bcd binding sites (three more than in the hb gene) matches almost perfectly the hb-MS2 reporter pattern, except for the very high steepness of the expression domain boundary and the speed to reach steady-state. This suggests that Bcd alone is the main source of positional information, defining the positioning of the boundary but not its steepness nor the speed of its establishment.In addition, binding of Bcd’s partners to the promoter speed-up the process by acting in different steps of the transcription mechanism: i) Hb synergizes with Bcd by reducing transcription burstiness and increasing the polymerase firing rate; ii) Zld lowers the Bcd concentration threshold required for Bcd-dependent expression. In collaboration with physicists, a biophysical model of Bcd-dependent expression was developed providing a theoretical framework for the experimental data. This model showed that the very rapid establishment of the hb expression boundary can be solely explained by an equilibrium model involving the binding of Bcd molecules to their DNA-binding sites for positional information which requires Zld and Hb for its temporal dynamics.To further confirm that Bcd is the sole source of positional information for hb expression, I compared the boundary position of the Bcd-only dependent reporters in embryos expressing one dose or half dose of Bcd. Surprisingly, the corresponding shifts of these reporters’ boundaries upon one vs half dose of Bcd were smaller than theoretically expected given the measured decay length of the Bcd protein gradient. This indicates a shorter decay length for the Bcd activity gradient and suggests the existence of different Bcd populations, with some Bcd molecules being less active than others. Importantly, the shift observed for the hb-MS2 reporter was the same as for the Bcd-only dependent reporters confirming Bcd as the sole source of positional information for hb expression
3
Jaeger, Baptiste. „Acquisition of natural killer cell effector capabilities“. Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4028.
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Les cellules Natural Killer (NK) sont des lymphocytes du système immunitaire inné capables de tuer des cellules cibles et de produire des cytokines telles que l'interféron-γ. Au cours de mon travail de thèse, j'ai utilisé des approches de génétique directe et inverse dans le but d'étudier les mécanismes impliqués dans la régulation des capacités effectrices des cellules NK. La tolérance des cellules NK au soi est en partie assurée par les récepteurs inhibiteurs de surface qui sont spécifiques des molécules du complexe majeur d'histocompatibilité de classe I (CMH-I) exprimées par les cellules du soi. Cependant, des cellules NK qui ne sont pas capables de détecter l'expression du CMH-I ne sont pas autoréactives. Dans la première partie de ce travail de thèse, nous avons cherché à déterminer, chez la souris, les mécanismes de la tolérance NK, indépendante de la reconnaissance du CMH-I, qui est associée à une hyporeactivité des cellules NK. En utilisant des techniques de spectrométrie de fluorescence par corrélation à spot variable (svFCS), nous avons montré que dans les cellules NK hyporéactives les récepteurs activateurs et inhibiteurs sont confinés à la membrane plasmique par des réseaux structurés d'actine. A l'inverse, la reconnaissance par les cellules NK du CMH-I, qui « éduque » les cellules NK pour qu'elles acquièrent leurs capacités effectrices maximales, est associée une relocalisation des récepteurs activateurs au sein de nanodomaines. Ces résultats suggèrent que ce serait le confinement particulier des récepteurs activateurs à la membrane des cellules NK qui assure la tolérance au soiNatural killer (NK) cells are bone marrow-derived innate immune lymphocytes able to kill cellular targets and secrete cytokines such as interferon-γ. During my PhD work, I used reverse and forward genetic approaches to dissect the mechanisms involved in the regulation of NK cell effector capabilities at steady state. NK cell tolerance to self is partly ensured by major histocompatibility complex class I (MHC- I)-specific inhibitory receptors on NK cells, which detect MHC-I expression on self-cells and prevent NK cell activation. However, NK cells that do not detect self MHC-I are not autoreactive. In the first part of this PhD work, we sought to determine the mechanism at the basis of this MHC-I independent NK cell tolerance. Using spot variation fluorescence correlation spectroscopy (svFCS), we showed that MHC-I-independent NK cell tolerance in mice was associated with the presence of hyporesponsive NK cells in which both activating and inhibitory receptors were confined in an actin meshwork at the plasma membrane. In contrast, the recognition of self MHC-I by inhibitory receptors "educated" NK cells to become fully reactive, and activating NK cell receptors became dynamically compartmentalized in membrane nanodomains. We thus propose that the confinement of activating receptors at the plasma membrane is essential to ensuring self-tolerance of NK cells
4
Lee, Ruey-Hua. „Cell-cell interactions during acquisition of embryogenic competence in yam (Dioscorea spp.)“. Thesis, Imperial College London, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265044.
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Jörgensen, Eskil. „Cell Acquisition and Synchronization for Unlicensed NB-IoT“. Thesis, Linköpings universitet, Kommunikationssystem, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-139862.
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Narrowband Internet-of-Things (NB-IoT) is a new wireless technology designed to support cellular networks with wide coverage for a massive number of very cheap low power user devices. Studies have been initiated for deployment of NB-IoT in unlicensed frequency bands, some of which demand the use of a frequency-hopping scheme with a short channel dwell time. In order for a device to connect to a cell, it must synchronize well within the dwell time in order to decode the frequency-hopping pattern. Due to the significant path loss, the narrow bandwidth and the device characteristics, decreasing the synchronization time is a challenge. This thesis studies different methods to decrease the synchronization time for NB-IoT without increasing the demands on the user device. The study shows how artificial fast fading can be combined with denser reference signalling in order to achieve improvements to the cell acquisition and synchronization procedure sufficient for enabling unlicensed operation of NB-IoT.Narrowband Internet-of-Things (NB-IoT) är en ny trådlös teknik som är designad för att hantera mobilnät med vidsträckt täckning för ett massivt antal mycket billiga och strömsnåla användarenheter. Studier har inletts för att operera NB-IoT i olicensierade frekvensband, varav några kräver att frekvenshoppande spridningsspektrum, med kort uppehållstid per kanal, används. För att en användarenhet ska kunna ansluta till en basstation måste den slutföra synkronisingsfasen inom uppehållstiden, så att basstationens hoppmönster kan avkodas. På grund utav den stora signalförsvagningen, den smala bandbredden och användarenhetens egenskaper är det en stor utmaning att förkorta synkroniseringstiden. Detta examensarbete studerar olika metoder för att förkorta synkroniseringstiden i NB-IoT utan att öka kraven på användarenheten. Arbetet visar att artificiell snabb-fädning kan kombineras med tätare referenssignalering för att uppnå förbättringar i synkroniseringsprocessen som är tillräckliga för att möjliggöra operation av NB-IoT i olicensierade frekvensband.
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Knapp, David Jorg Hans Fraser. „Single-cell analysis of hematopoietic stem cell identity and behaviour“. Thesis, University of British Columbia, 2015. http://hdl.handle.net/2429/55875.
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The concept of stem cell self-renewal was developed from clonal tracking of hematopoietic stem cell (HSC) divisions in vivo 50 years ago. However, protocols to expand these cells in vitro without loss of their stem cell properties have remained elusive. A number of factors contribute to this inability. Key among these is a lack of knowledge of the critical molecular characteristics that distinguish HSCs from hematopoietic progenitors as well as how the control of the fundamental biological programs of survival, division and differentiation are integrated in HSCs. Using a combination of single-cell tracking, transcriptomics, and in vivo readouts applied to highly enriched mouse HSCs, we now show that their survival, proliferation, and maintenance of stem cell properties are mechanistically dissociable. Discovery of a protocol that allows input numbers of functionally intact human HSC numbers to be maintained for 3 weeks in vitro using defined growth factors, was then leveraged to design single human HSC cell tracking and functional analyses. The results of these showed that for human HSC, as in the mouse model, survival, proliferation, and maintenance of stem cell status are mechanistically dissociable, and controlled in a combinatorial manner. We then developed a panel of mass cytometry detectors to enable >40 surface and intracellular proteins to be simultaneously measured at single cell resolution. Using this panel, we identified some of the signaling intermediates activated by growth factors that differentially control human HSC biological responses assessed in high-throughput assays. Correlation of the molecular properties, surface phenotypes and functional activities of CD34+ subsets have further revealed a surprising degree both of heterogeneity within each phenotype and overlap between phenotypes. In some cases, the results suggest a given phenotype contains distinct subsets and a broader scheme of differentiation pathways than suggested by current models of human hematopoietic cell differentiation. Finally, we identify CD33+ as a novel marker which demarcates the most potent human HSC within the current best phenotypic enrichment strategy. These results lay a foundation on which future HSC expansion strategies can be constructed, and have implications for the development of leukemia.Medicine, Faculty of
Medicine, Department of
Experimental Medicine, Division of
Graduate
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Middleton, Michael W. „Assessing the value of the Joint Rapid Acquisition Cell“. Thesis, Monterey, Calif. : Naval Postgraduate School, 2006. http://bosun.nps.edu/uhtbin/hyperion.exe/06Dec%5FMiddleton.pdf.
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Mathur, Divya Ph D. Massachusetts Institute of Technology. „Molecular control of embryonic stem cell identity“. Thesis, Massachusetts Institute of Technology, 2008. http://hdl.handle.net/1721.1/46786.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
Includes bibliographical references.
Embryonic Stem (ES) cells are the in vitro derivatives of the inner cell mass of a developing embryo, and exhibit the property of pluripotency, which is the ability of a cell to give rise to all cell lineages of an organism. Therefore, these cells hold great promise in the treatment of several degenerative diseases through patientspecific cell-based therapy. Consequently, a detailed knowledge of the factors regulating ES cell identity is required in order to exploit this therapeutic potential. In order to address this subject, genome-wide location analysis (or ChIP-chip) has been used to identify downstream genes that are bound, and potentially regulated by the key pluripotency transcription factors, Oct4 and Nanog. The data from this study have also been compared and integrated with Oct4 and Nanog DNA binding data obtained in a different study using the ChIP-PET technology. In order to gain further insight into the mechanisms by which the transcription factor Nanog regulates its downstream targets, an attempt at identifying proteins interacting with Nanog has also been described. Research on ES cells has been plagued with ethical controversies since the creation of these cells requires the destruction of embryos. Recent studies have reported the reprogramming of somatic fibroblasts into an ES cell-like induced pluripotent state (iPS) by virus-mediated transduction of four transcription factors-- Oct4, Sox2, c-Myc and Klf4, thereby circumventing the use of embryos in producing pluripotent cells.In these studies, selection for the activation of the markers Oct4 or Nanog led to completely reprogrammed cells, but selection for fbx15, a downstream target of Oct4, resulted in partially reprogrammed intermediates. An unresolved issue in the field was whether these intermediates were obtained due to early drug selection in the case of fbx15 selection, or because Fbx15 expression is not relevant to pluripotency. Drug selection for fbx15 activation at later time-points, and an examination of the methylation status of the Oct4 locus of Fbx15-iPS cells suggests that the intermediates were obtained due to early drug selection and not due to selection for fbx15. Therefore, these studies have begun to elucidate a framework that governs ES cell identity, and the mechanism by which a differentiated cell can be reprogrammed into a pluripotent state.
by Divya Mathur.
Ph.D.
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Biltcliffe, Phillippa. „A cultural geography of Victorian art collecting : identity, acquisition and display“. Thesis, Royal Holloway, University of London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491729.
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Grounded within cultural geography, this thesis focuses on the relationships between art collection and the fashioning of elite identities in the second-half of the nineteenth century. Through two detailed case studies of wealthy collectors, it investigates the ways in which the consumption of art served as a cultural medium through which collectors created distinct identities for themselves, so that collections may be seen not simply as mirrors reflecting Victorian culture, but as constitutive of that culture. Focusing on the geographical aspects of the history of art collecting, the study considers how subjectivities were crafted through negotiation of a series of sites and spaces, collecting networks and journeys. This focus on the spatiality of collections and of collecting identities enriches existing notions of class, gentility and connoisseurship. The empirical core of the thesis is a study of the collections amassed by two wealthy Victorians: Ferdinand Rothschild (1839-1898), an aristocratic and cosmopolitan connoisseur, who specialised particularly in Renaissance and eighteenth-century art objects, and Thomas Holloway (1800-1883), a millionaire businessman and philanthropist known especially for his collection of contemporary Victorian paintings. Through a close examination of the activities and collections of these two very different figures, the thesis explores how their identities and reputations were fashioned through their collections. Part 1 of the thesis provides an account of recent work on the cultures of collecting and the fashioning of class identities, with particular reference to Victorian Britain (Chapter 2). Part 2 considers the relationships between collecting, taste and the fashioning of identities, with reference to Holloway and Rothschild (Chapters 3 and 4). Part 3 examines the different means through which objects were acquired; focusing especially on the contrasting sites of acquisition, including the auction house, the private sale, the art dealer and foreign travel (Chapter 5 and 6). Part 4 focuses on display, considering how art objects were made meaningful through their location in particular places, from the public gallery to the private smoking rooms.
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Donnelly, Stephen Kevin. „Ethnic identity redefinition during acquisition of one's ancestral language (Irish) : an approach based on identity structure analysis“. Thesis, University of Ulster, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.259582.
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11
Lu, Zhixue. „DEPLOYMENT, MANAGEMENT, AND ACCESS ACQUISITION OF SMALL-CELL BASED NETWORKS“. The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1397763112.
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Botha, Elizabeth Katherine. „Discourses of language acquisition and identity in the life histories of four white South African men, fluent in isiXhosa“. Doctoral thesis, University of Cape Town, 2012. http://hdl.handle.net/11427/27735.
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A post-structuralist framework (Foucault, 1976; Weedon, 1997) is used to explore language acquisition and identity construction in the life histories of four multilingual white South African men, who became fluent in the African language of isiXhosa in the racially-divided world of Apartheid South Africa, at a time when law and policy made fluency in an African language unusual for whites. Theories used within the 'social turn' in Second Language Acquisition (Block, 2003; Norton, 2000), as well as the social learning theory of Lave and Wenger (1991), support an exploration of how the men acquired this language on the farms in the Eastern Cape where they spent their early years. The identity implications of the men's multilingualism are examined using post-colonial studies of race, 'whiteness' and hybridity (Bhabha, 1994; Frankenberg, 1993; Hall, 1992a). The study was undertaken using Life History methodology (Hatch & Wisniewsky, 1995) and biographic interviewing methods developed within the Social Sciences (Wengraf, 2001). Poststructuralist discourse analysis (Wetherell & Potter, 1992), together with aspects of narrative analysis (Brockmeier, 2000), were used to analyse the data. The study contributes to research into naturalistic language acquisition, using theories from the 'social turn', and analysing a bilingual context in which language, power, race and identity interact in unique ways. The findings endorse the importance of a post-structuralist framing for the Communities of Practice model (Wenger, 1998), and show that participation in target-language communities requires investment by learners in identities which ameliorate the inequities of power relations. The study shows that isiXhosa can become linguistic capital (Bourdieu, 1991) for white South Africans, depending on context and the isiXhosa register they use. It demonstrates that Apartheid discourse ascribes to the men an identity which is indisputably white, but that early experiences shared with isiXhosa-speakers shape their lives and form a potentially antihegemonic facet of their identities.
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Hoff, Meagan. „Ethnic Identity and Accent: Exploring Phonological Acquisition for International Students from China“. Bowling Green State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1395176320.
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14
Elstob, Philip Ronald. „Hox gene function and cell identity in Drosphila“. Thesis, University College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272353.
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Fan, Zi Peng. „Transcriptional and structural control of cell identity genes“. Thesis, Massachusetts Institute of Technology, 2015. http://hdl.handle.net/1721.1/98641.
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Thesis: Ph. D., Massachusetts Institute of Technology, Computational and Systems Biology Program, 2015.Cataloged from PDF version of thesis.
Includes bibliographical references.
Mammals contain a wide array of cell types with distinct functions, yet nearly all cell types have the same genomic DNA. How the genetic instructions in DNA are selectively interpreted by cells to specify various cellular functions is a fundamental question in biology. This thesis work describes two genome-wide studies designed to study how transcriptional control of gene expression programs defines cell identity. Recent studies suggest that a small number of transcription factors, called "master" transcription factors, dominate the control of gene expression programs. These master transcription factors and the transcriptional regulatory circuitry they produce, however, are not known for all cell types. Ectopic expression of these factors can, in principle, direct transdifferentiation of readily available cells into medically relevant cell types for applications in regenerative medicine. Limited knowledge of these factors is a roadblock to generation of many medically relevant cell types. Chapter 2 presents a study in which a novel computational approach was undertaken to generate an atlas of candidate master transcriptional factors for 100+ human tissue/cell types. The candidate master transcription factors in retinal pigment epithelial (RPE) cells were then used to guide the investigation of the regulatory circuitry of RPE cells and to reprogram human fibroblasts into functional RPE-like cells. Master transcription factors define cell-type-specific gene expression through binding to enhancer elements in the genome. These enhancer-bound transcription factors regulate genes by contacting target gene promoters via the formation of DNA loops. It is becoming increasingly clear that transcription factors operate and regulate gene expression within a larger three-dimensional (3D) chromatin architecture, but these structures and their functions are poorly understood. Chapter 3 presents a study in which Cohesin ChIA-PET data was generated to identify the local chromosomal structures at both active and repressed genes across the genome in embryonic stem cells. The results led to the discovery of functional insulated neighborhood structures that are formed by two CTCF interaction sites occupied by Cohesin. The integrity of these looped structures contributes to the transcriptional control of super-enhancer-driven active genes and repressed genes encoding lineage-specifying developmental regulators.
by Zi Peng Fan.
Ph. D.
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Codato, Roberta. „The role of the lysine Methyltransferase SMYD3 in cell differentiation and cell identity“. Thesis, Sorbonne Paris Cité, 2018. http://www.theses.fr/2018USPCC284.
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Dans les cellules eucaryotes, des changements dynamiques de la chromatine en combinaison avec des facteurs de transcription spécifiques au tissu, régulent les programmes d'expression des gènes, qui sous-tendent la différenciation cellulaire. La différenciation des muscles squelettiques est principalement orchestrée par une famille de quatre facteurs de transcription de base hélice-boucle-hélice (bHLH): MyoD, Myf5, Myogenin et Mrf4. Les technologies de cartographie à l'échelle du génome ont révélé l'étendue du remodelage épigénétique dynamique soulignant la myogenèse. Plusieurs études ont porté sur le rôle des histones Lysine Méthyltransférases (KMT) et leur rôle dans la répression (H3K9 / H3K27) ou l'activation (H3K4) transcriptionnelle, et ont mis en évidence la fonction des modifications des histones dans la myogenèse et la régulation des gènes spécifiques des muscles. Nous avons étudié le rôle de la KMT SMYD3, qui est hautement conservé, au cours de la différenciation du muscle squelettique. Les membres de la famille des protéines SMYD sont impliqués dans la myogenèse cardiaque et squelettique au cours du développement chez le poisson-zèbre, la drosophile et la souris. SMYD3 est fréquemment surexprimé dans les cancers humains et des études ont mis en évidence un rôle potentiel de SMYD3 dans le développement précoce et la différenciation des cellules musculaires. Pourtant, le rôle de SMYD3 dans ces processus est encore un sujet de débat et d'investigation. Afin d'obtenir de nouvelles informations sur la régulation de la myogenèse par la famille SMYD de KMTs, nous avons examiné le rôle de SMYD3 dans la différenciation des myoblastes en utilisant un système in vitro de myoblastes humains et murins. Nos résultats d'expériences de gain et de perte de fonction suggèrent un rôle critique pour SMYD3 dans la régulation épigénétique de l'expression génique au cours de la différenciation musculaire. En particulier, l'inhibition de l'expression de SMYD3 entraîne une altération précoce de la différenciation musculaire et la fusion des myoblastes pour former des myotubes multinucléés. D'autre part, la surexpression de SMYD3 dans les myoblastes induit l'expression de marqueurs de différenciation spécifiques et améliore globalement le processus de différenciation. En utilisant des études de séquençage haut-débit de l’ARN, nous avons montré que SMYD3 régule les gènes impliqués dans l'organisation du sarcomère et le développement musculaire lors de la différenciation. De plus, nous avons trouvé par des études ChIP que SMYD3 se lie au promoteur de la Myogenin dans les myoblastes C2C12. En conclusion, nous avons révélé un nouveau mécanisme de régulation du facteur de différenciation clé Myogenin, et identifié un nouveau rôle pour SMYD3 dans la myogenèse squelettiqueIn eukaryotic cells, dynamic changes in chromatin architecture combined with tissue-specific transcription factors regulate the gene expression programs, which underlie lineage commitment and cell differentiation. Skeletal muscle differentiation is mainly orchestrated by a family of four basic-helix-loop-helix (bHLH) transcription factors: MyoD, Myf5, Myogenin and Mrf4. Genome-wide mapping technologies revealed the extent of dynamic epigenetic remodeling underlining myogenesis. Several studies have focused on the role of Histone Lysine Methyltransferases (KMT), and their role in transcriptional repression (H3K9/H3K27) or activation (H3K4), and highlighted the function of histone modifications in myogenesis and the regulation of muscle-specific genes. We studied the role of the highly conserved KMT SMYD3 during skeletal muscle differentiation. Members of the SMYD protein family are implicated in cardiac and skeletal myogenesis during development in zebrafish, Drosophila and mice. SMYD3 is frequently upregulated in human cancers and there are evidences supporting a role of SMYD3 in early development and muscle cell differentiation. Yet, the role of SMYD3 in these processes is still a matter of debate and investigation. To gain new insights into the regulation of myogenesis by the SMYD KMT family, we examined the role of SMYD3 on myoblasts differentiation by using an in vitro system of human and mouse myoblasts. Our results of gain- and loss-of-function experiments suggest a critical role for SMYD3 in epigenetic regulation of gene expression during muscle differentiation. In particular, inhibition of SMYD3 expression leads to an impairment in early muscle differentiation, and myoblasts fusion to form multinucleated myotubes. On the other hand, SMYD3 overexpression in myoblasts induces the expression of specific differentiation markers and globally enhances the differentiation process. By using RNA-seq studies, we showed that SMYD3 regulates genes involved in sarcomere organization and muscle development upon differentiation. Moreover, we found by ChIP studies that SMYD3 binds to the Myogenin promoter in C2C12 myoblasts. In conclusion, we revealed a novel mechanism of regulation of the key differentiation factor Myogenin, and identified a novel role for SMYD3 in skeletal myogenesis
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Assarsson, Erika. „Acquisition and function of NK cell-associated molecules on T cells /“. Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-487-9/.
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Xia, Dongchun. „An automated image acquisition and analysis system for cell membrane detection“. Thesis, Georgia Institute of Technology, 1995. http://hdl.handle.net/1853/17251.
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Tervo, O. (Oskari). „Effective channel state acquisition in multi-cell multi-user MIMO system“. Master's thesis, University of Oulu, 2013. http://urn.fi/URN:NBN:fi:oulu-201306011414.
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In a cellular network with small cells, where all the communication resources are shared, the inter-cell interference becomes a limiting factor of performance. The strategies for mitigating the inter-cell interference has been quite extensively studied lately. One of the promising candidates is coordinated beamforming/scheduling, where a certain number of cells is allowed to cooperate such that the transmission from each cell takes into account the interference it would cause to the users of other cells. In this thesis, the performances of different signaling strategies which perform the weighted sum rate maximization in time division duplex multi-cell multi-user MIMO downlink system are studied. The strategies consist of iterative decentralized algorithms, aiming at reduced pilot signaling overhead and faster convergence. The required control information between the cells is provided via uplink reference signals and a backhaul. Uplink reference signals include sounding reference signals and busy bursts. Based on the earlier work, the strategies have now been extended to a larger cellular system in which the frequency selectivity and the uncertainty of the channel information are also taken into account. The ability of the strategies to handle the large network can be seen from the simulation results. It is shown that even when there is strong inter-cell interference, the strategies utilizing parallel cell-specific iterations offer practical convergence speed. It is also noticed that the joint optimization over many frequency blocks brings a minor improvement on the sum rate performance, meaning that it could also be utilized with the same order of computational complexity compared to the frequency flat case. Finally, the robustness of the centralized strategy to the imperfect channel state information is shown and the trade-off between the CSI uncertainty and multi-user diversity is statedSolukkoverkossa, jossa solujen koot ovat pieniä ja kaikki käyttävät samoja taajuuksia, solujen välinen häiriö rajoittaa verkon suorituskykyä. Viime aikoina on laajasti tutkittu strategioita, joilla häiriötä saataisiin vähennettyä. Yksi lupaavista menetelmistä tähän tarkoitukseen on koordinoitu keilanmuodostus/skedulointi, jossa tietty ryhmä soluja voi koordinoida keskenään ja näin ottaa huomioon lähetyksestä aiheutuvan häiriön toisia soluja kohtaan. Tässä diplomityössä tutkitaan erilaisten painotetun summadatanopeuden maksimoivien signalointistrategioiden suorituskykyä aikajakodupleksoidussa usean solun ja käyttäjän moniantenniverkossa, jossa dataa lähetetään tukiasemasta käyttäjille. Strategiat perustuvat iteratiivisiin hajautettuihin algoritmeihin, joiden tarkoituksena on vähentää opetussignaloinnista aiheutuvaa kuormitusta ja nopeuttaa suppenemista. Kontrolli-informaation signaloimiseen verkossa käytetään käyttäjiltä tukiasemille lähetettäviä opetussignaaleja ja taustayhteyttä tukiasemien välillä. Työ perustuu aiemmin tehtyyn tutkimukseen, josta strategiat on nyt laajenettu suurempaan solukkojärjestelmään, ottaen huomioon myös taajuusselektiivisyyden ja kanavainformaation epävarmuuden vaikutukset. Simulointitulosten perusteella voidaan sanoa, että strategiat toimivat usean käyttäjän ja solun verkossa. Tuloksista nähdään, että rinnakaisia solukohtaisia iteraatioita hyödyntävillä strategioilla voidaan saavuttaa käytännöllinen suppenemisnopeus, vaikka solujen välinen häiriö on voimakasta. Taajuusselektiivisen kanavan tuloksista huomataan, että yhteisoptimointi usean taajuuslohkon yli parantaa vähän suorituskykyä verrattuna yhden taajuuden tapaukseen. Yhteisoptimointia voitaisiin siis myös hyödyntää, koska laskennallinen monimutkaisuus on samaa suuruusluokkaa verrattuna yhden taajuuden tilanteeseen. Epävarman kanavatiedon vaikutusta tutkitaan keskitetyllä optimointimenetelmällä, joka selvästi laskee suorituskykyä verrattuna täydellisen kanavan tapaukseen, mutta antaa kuitenkin selkeän parannuksen alkuperäiseen algoritmiin verrattuna. Koska opetussignaalien teho jaetaan käyttäjien kesken, tulokset näyttävät kompromissin kanavatiedon epävarmuuden ja monikäyttäjädiversiteetin välillä
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Bottois, Hugo. „Acquisition and regulation of effector T cell functions in Crohn’s disease“. Thesis, Sorbonne Paris Cité, 2019. http://www.theses.fr/2019USPCC012.
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L’intestin représente un microenvironnement complexe notamment par la présence du microbiote intestinal nécessitant un système immunitaire spécialisé incluant les cellules CD8 T résidente (Trm). Notre but est d’étudier la différentiation et la fonction de ces Trm dans la muqueuse intestinale. Nous souhaitons également identifier l’implication des Trm dans la maladie de Crohn (MC).Des cellules T provenant de sang ont été exposées in vitro dans conditions proches de la muqueuse pour étudier leur différentiation en Trm. L’environnement intestinal est capable de convertir des T CD8 du sang en un phénotype proche de celui de la muqueuse, notamment par l’acquisition de l’intégrine CD103. L'expression mutuellement exclusive de CD103 et KLRG1 sur les CD8 Trm semble définir des sous-populations fonctionnellement distinctes.Les Trm de patients ont été restimulé pour analyser leurs fonctions. Les CD103+ Trm sont plus sensibles à une restimulation TCR, mais les KLRG1+CD8 Trm expriment le Granzyme B sont augmentés dans la muqueuse des patients. Le transcriptome des CD103+ CD8 Trm est considérablement modifié dans la MC et montre une expression de gène associés à des signaux de danger, de réparation tissulaire et de recrutement lymphocytaire comparé aux individus contrôles. En parallèle, Nous avons établi un modèle de coculture d’organoide et de cellules T autologues. Notre but est d'étudier l’interaction et l'effet des ces cellules T sur des cellules épithéliales et de tester l’efficacité des biothérapies ciblant ces interactions comme des anticorps bloquant CD103 ou NKG2D, dont le développement est en cours dans la MCThe intestine is a complex microenvironment that requires an immune system with specific features to maintain homeostasis. Tissue resident memory (Trm) CD8 T cells from the intestinal tissue participate to this regulation. We aimed to study the differentiation and function of human CD8 Trm cells in the intestinal mucosa and their impact on inflammatory disorders such as Crohn’s disease (CD). We tested in vitro the acquisition of a mucosa-associated phenotype, by exposing blood T cells to cytokines mimicking the intestinal microenvironment. This stimulation converted activated blood CD8 T cells to a mucosal-like phenotype, mainly by acquisition of the tissue resident marker, integrin CD103.Blood and mucosal CD8 T cells isolated from CD patients and controls were characterized by flow cytometry to determine the specificities of intestinal Trm cells. Interestingly, the expression of KLRG1 and CD103, both receptor of E-cadherin expressed by epithelial cells, was mutually exclusive. Restimulated Trm cells in vitro showed that CD103 CD8 Trm cells were more responsive to TCR stimulation, while KLRG1 CD8 T cells displayed higher expression of cytotoxic molecules such as granzyme B. These results suggest that these markers define distinct functional Trm subsets.We analysed the transcriptome of sorted Trm subsets from inflammatory or control tissues and showed that CD8 Trm cells expressing CD103 had increase expression of cytokines and chemokines compared to other Trm cells. Additionally, CD103 expressing Trm cells from CD patients showed major transcriptomic differences compared to controls, with increase expression of genes involved in tissue repair and recruitment of immune effector cells. Taken together, these results suggest that Trm cells in the intestine are heterogeneous, as CD103 expressing cells display functions associated with alarm signals and tissue repair, while KLRG1 positive cells exhibit cytotoxic potential. To study the interactions of these T cells with intestinal epithelial cells, we have established intestinal epithelial organoid cultures with mucosal T cells. Our aims are to examine the molecules involved in lympho-epithelial interactions and study their functional consequences. To this end we will test and study the mechanisms of action of blocking antibodies targeting CD103 and NKG2D that are two pathways tested for the treatment of CD
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Leonard, Ann Elizabeth. „Motor neuron cell fate acquisition : transcription factors and their associate proteins /“. Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2003. http://wwwlib.umi.com/cr/ucsd/fullcit?p3099545.
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Bryant, Julianne. „Language and Identity among Adolescent Heritage Spanish Students“. Diss., Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/240270.
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SpanishPh.D.
This dissertation describes the language and identity trajectories of twelve purposefully selected heritage Spanish adolescents who were currently studying in a heritage language program within an urban high school in Bethlehem, Pennsylvania. These twelve students represented six sibling groups and five different nationalities, specifically Dominican, Ecuadorian, Puerto Rican, Salvadorian, and Venezuelan,. The research questions were: 1) How do Hispanic heritage students negotiate their bicultural/bilingual identities?; 2) What is the role of the heritage language in those negotiated identities?; 3) Do these negotiated identities influence their investment to maintain the heritage language?; 4) What are the linguistic manifestations of the Spanish spoken by these bilingual students? Findings of the study revealed that 1) the study participants negotiate their bicultural/bilingual identities in a variety of ways, 2) for some of these students, the heritage language is part of their `out of school' identities, 3) the dominant language ideologies of the school system have had a significant impact on the heritage students' investment in HL practice, and 4) although each participant's identity and linguistic trajectories are distinct, they each have maintained, to a greater or lesser degree, the aspectual preterit/imperfect contrast, and, at the same time have displayed some level of incomplete acquisition of the subjunctive mood. The implications of these findings as they relate to the fields of bilingualism, languages in contact and the developing theory of Heritage Language Acquisition are addressed in the concluding remarks.
Temple University--Theses
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Tyler, Scott Robert. „Graph theory analysis of single cell transcriptomes define islet signaling networks and cell identity“. Diss., University of Iowa, 2016. https://ir.uiowa.edu/etd/2287.
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Several challenges face bioinformaticians on a regular basis. One of these is unsupervised clustering. In RNA sequencing (RNAseq), this may come in the form of blindly sequencing single cells without a priori knowledge of the cell types being sequenced. Here we create new methods to address this problem that show increased accuracy and speed compared to competing methods. We also have developed a methodology for discovering non-parametric networks which represent relationships between the variables that have been measured across samples. In the context of RNAseq, this is the expression relationships between genes (for example a positive or negative Spearman correlation). We have packaged these techniques into a software tool called PyMINEr. We show the implementation of PyMINEr here in the analysis of single cell RNAseq (scRNAseq), and integrate this dataset with others to yield novel insights to the signaling networks among within and between pancreatic islet cell types. Additionally we used this data to predict the cell type specific importance of Type 2 Diabetes (T2D) single nucleotide polymorphisms (SNPs). Lastly we have demonstrated the use of PyMINEr’s analytic techniques in discovering genetic circuitry underlying the transcriptional networks of two transcription factors (NeuroD1 and Pdx1) in beta cells. We utilized a RNA interference to modulate the expression of these transcription factors in a beta cell line (MIN6), and observe the changes in the transcriptome over time. We used this data to generate graph network models of transcription and integrated them with ChIP-seq of these transcription factors; this enabled annotation of the functional binding sites of these transcription factors. Furthermore, this approach has enabled the discovery of regulators of beta and alpha cell identity. Overall, we have developed novel informatics methods which can be applied to complex datasets to guide bench experiments towards to discovery of molecular signaling networks.
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Copland, Paul S., und n/a. „Embryonic stem cell research and the metaphysics of identity“. University of Otago. Dunedin School of Medicine, 2007. http://adt.otago.ac.nz./public/adt-NZDU20070914.141825.
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Embryonic stem cell research has the potential to revolutionise both the practice of medicine and our understanding of the human body. Although the usual technical and financial limitations of research apply, perhaps the greatest obstacle to the progress of this research at the present time is the ethical concerns surrounding the destruction of early human embryos. The established debate over the ethical significance of the early embryo has thus taken on renewed importance.
Within biology stem cell research has begun to overturn some long held assumptions about the roles of genes and cellular interaction in development. Building on recent advances in stem cell biology I develop a concept of Form that neatly captures what it is to be individuals like us in biological terms. Form not only defines a biological individual that exists across time regardless of changes in its physical constituents but also provides the biological foundation for our higher mental properties and our identity as persons.
At the heart of the embryo debate is confusion over what human individuals are and therefore when they began. Defining when we began as the ethically significant individuals that we are now is the key to the embryo debate. Our metaphysics of identity is thus crucial to understanding the moral significance of the embryo.
Compared to alternative understandings of identity within the debate surrounding the embryo Form provides compelling reasons why the very early embryo, at the stage that embryonic stem cells are derived, lacks any right to life or associated ethical significance. The derivation of embryonic stem cells is thus found to be ethically permissible.
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Saunders, Lewis O. „The relationship between cell phone use and identity theft“. Thesis, Walden University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3615824.
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The growth of mobile phone use has paralleled increased reports of identity theft. Identity theft can result in financial loss and threats to a victim's personal safety. Although trends in identity theft are well-known, less is known about individual cell phone users' attitudes toward identity theft and the extent to which they connect it to cell phone use. The purpose of this qualitative study was to determine how cell phone use is affected by attitudes toward privacy and identity theft. The study was based on social impact theory, according to which people's attitudes and behavior are affected by the strength and immediacy of others' attitudes and behavior. The research questions concerned the extent to which participants connected cell phone use with decreasing privacy and increasing cybercrime, how the use of biometrics affected cell phone users' attitudes and behavior, and what steps can be taken to reduce the misuse of private information associated with cell phone use. Data collection consisted of personal interviews with representatives from 3 groups: a private biometrics company, individual cell phone users who earn more than $55,000 a year, and individual cell phone users who earn less than $55,000 a year. Interviews were transcribed and coded for themes and patterns. Findings showed that interviewees were more likely to see identity theft as a problem among the public at large than in the industries in which they worked. Participants recommended a variety of measures to improve cell phone security and to reduce the likelihood of identity theft: passwords, security codes, voice or fingerprint recognition, and encryption. The implications for positive social change include informing government officials and individual users about the use and abuse of cell phones in order to decrease violations of privacy and identity theft while still promoting national security.
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Saunders, Lewis O. „The relationship between cell phone use and identity theft“. ScholarWorks, 2011. https://scholarworks.waldenu.edu/dissertations/1123.
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The growth of mobile phone use has paralleled increased reports of identity theft. Identity theft can result in financial loss and threats to a victim's personal safety. Although trends in identity theft are well-known, less is known about individual cell phone users' attitudes toward identity theft and the extent to which they connect it to cell phone use. The purpose of this qualitative study was to determine how cell phone use is affected by attitudes toward privacy and identity theft. The study was based on social impact theory, according to which people's attitudes and behavior are affected by the strength and immediacy of others' attitudes and behavior. The research questions concerned the extent to which participants connected cell phone use with decreasing privacy and increasing cybercrime, how the use of biometrics affected cell phone users' attitudes and behavior, and what steps can be taken to reduce the misuse of private information associated with cell phone use. Data collection consisted of personal interviews with representatives from 3 groups: a private biometrics company, individual cell phone users who earn more than {dollar}55,000 a year, and individual cell phone users who earn less than {dollar}55,000 a year. Interviews were transcribed and coded for themes and patterns. Findings showed that interviewees were more likely to see identity theft as a problem among the public at large than in the industries in which they worked. Participants recommended a variety of measures to improve cell phone security and to reduce the likelihood of identity theft: passwords, security codes, voice or fingerprint recognition, and encryption. The implications for positive social change include informing government officials and individual users about the use and abuse of cell phones in order to decrease violations of privacy and identity theft while still promoting national security.
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Cherubini, A. „MYC-DRIVEN EPIGENETIC MEMORY MAINTAINS EMBRYONIC STEM CELL IDENTITY“. Doctoral thesis, Università degli Studi di Milano, 2015. http://hdl.handle.net/2434/356044.
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Stem cells balance their self-renewal and differentiation potential by
integrating environmental signals with the Transcriptional Regulatory
Network (TRN). Moreover, the integration between extrinsic and intrinsic
signals affects the maintenance of their epigenetic state, establishing an
accurate cells identity. Although c-Myc transcription factors plays a major
role in stem cells self-renewal and pluripotency, their mechanisms of
actions and their ability to establish an epigenetic memory remains poorly
defined. We addressed this point by profiling the epigenetic pattern and
gene expression in Embryonic Stem (ES) cells, whose growth depends on
conditional c-Myc activity. Here we show that c-Myc potentiates the Wnt/β-
Catenin signaling pathway, which cooperates with the transcriptional
regulatory network in sustaining ES cells self-renewal. c-Myc activation
results in the transcriptional repression of Wnt antagonists Dkk1 and Sfrp1
through the direct recruitment of PRC2 on these targets. We found that,
through these molecular mechanisms, c-Myc promotes pluripotency and
self-renewal of ES cells by activating an alternative epigenetic program.
Finally our data suggest that the consequent potentiation of the autocrine
Wnt/β-Catenin signaling induces the transcriptional activation of the
endogenous Myc family members, which in turn activates a Myc-driven
self-reinforcing circuit. Thus, our data unravel a Myc-dependent selfpropagating
epigenetic memory in the maintenance of ES cell identity.
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Chen, Chao, und Jiayan Liu. „Brand Adapting Management in Merger and Acquisition : A Case Study of Geely/Volvo's Brand Acquisition“. Thesis, Linnéuniversitetet, Ekonomihögskolan, ELNU, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:lnu:diva-12268.
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The premise of this thesis is to conduct a research regarding the connection of brand image, brand identity, brand positioning with brand adapting management. The significant purpose of this thesis is for better understanding how a Chinese auto corporation can effectively manage and adapt an acquired foreign brand in Chinese market. In order to reach this purpose, a case study of Geely/Volvo’s acquisition has been carried out which entailed company visit (Volvo Brand Experience Center), interviews with Volvo brand specialists, Volvo dealer and Chinese market expert. The Theoretical Framework describes the general concepts of brand, brand management, company acquisition and three brand adapting concepts of brand image, brand identity and brand positioning. The Empirical Data Collection deals with the Volvo’s brand identity and value proposition, Chinese customers’ perceptions on Volvo brand image and Geely’s brand positioning strategy on Volvo. The Analysis related the theory framework with the empirical results. It discussed and analyzed how Geely can adapt Volvo in Chinese automotive market through dealing with Volvo’s core values, brand image and brand positioning. The Conclusion summarized the Chinese auto corporation needs to concern on three factors for adapting an acquired brand: value proposition of acquired brand, Chinese customers’ perceptions on acquired brand image and brand positioning strategy. Finally our recommendation presents the limitations of this study, suggestions for future research in this field, and managerial implications for the case company.
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Sacklin, Jennifer Marie. „Identity and Investment in the Community ESL Classroom“. PDXScholar, 2015. https://pdxscholar.library.pdx.edu/open_access_etds/2326.
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After Norton Peirce's (1995, Norton, 2000) groundbreaking work in conceptualizing identity as "multiple, changing, and contradictory," many researchers have explored language learners' identities. However, few studies of identity have been conducted within the "overlooked and understudied" (Mathews-Aydinli, 2008) context of adult community ESL (English as a Second Language), and even fewer studies have focused on LESLLA (low-educated second language and literacy acquisition) learners in mainstream community ESL programs.
This thesis, based on a case study of an adult LESLLA learner in a community ESL class, analyzes how this student's identity, the social context of her life, and the classroom space shaped her investment in participating in the ESL class.
Ethnographic interviews revealed that the participant's investment in language learning was linked to her identity in multiple and contradictory ways: while the participant eventually left the ESL program, her self-identification as 'no preparada' (uneducated) and therefore 'burra' (stupid) seemed to be a motivating challenge, not an insurmountable obstacle, and her sense of investment in language learning remained strong even though her in-class participation was limited.
The results have pedagogical as well as theoretical implications: there is clearly value in engaging learners' lives in the classroom as well as including learners' voices in research to have a clearer recognition of how learners see themselves and their "possible selves" (Dornyei, 2009) to be able to understand the complex factors that underlie their investments in language learning.
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Ged, Geneva. „Conscious Reconstruction: The Effects of Second Language Acquisition on Self-Perception of Gender Identity“. TopSCHOLAR®, 2013. http://digitalcommons.wku.edu/theses/1317.
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Gender interacts with other facets of English Language Learners’ social identity like race and ethnicity to guide their learning experiences, desires, and outcomes; however, much of traditional Teaching English as a Second Language (TESOL) research has focused on how motivation and language learning beliefs differ between male and female English as a Second Language/English as a Foreign Language (ESL/EFL) students with the intent to identify difference, if it exists. English Language Learners who are studying abroad or who have immigrated to the United States have already established a gender identity influenced and created by their experiences in their first language and culture. Yet, immersion in a new culture and acquiring a second language may cause these students to re-evaluate their perceptions of gender roles and influence their choice of language, as previously found by Gordon (2004) and Schmenk (2004). This thesis attempts to break from this tradition of ‘differential tendencies’ research in the creation of two pilot surveys, one of which was tested, that attempt to solicit information on English Language Learner’s perceptions of their own gendered identity and their consciousness of the catalyst for identity change that is learning a second language. In this case, an English pilot survey asked 32 ESL students to evaluate their beliefs about their own perceptions of gender identity, their conscious choice of language utilization, and their perception of their inclusion in American culture; from that survey, a second has been created but not piloted. A conclusion is drawn that incorporates research about the appropriateness of addressing developing gender identity by teachers inside of the classroom.
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Sweeney, Derina E. „Regulation of cell behaviour and identity in a branching epithelium“. Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/29388.
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Although differentiation and morphogenesis of the ureteric bud have been studied for many years, the mechanisms that control their overall pattern remain unknown. In this thesis, I have tested a specific set of hypotheses in which both differentiation and morphogenesis are controlled by a self-organization based on inhibitory interactions between tip and stalk cells. Using micro dissection and ex-vivo organ culture I show that: 1. The ureteric bud is composed of at least two distinct populations of cells, those that bind Dolichos biflorus agglutinin (DBA) and those that do not. These correspond to the stalk and tip regions respectively. DBA seems to be a marker of regions of the ureteric bud in which branching morphogenesis is inactive. 2. Using DBA to detect tip cells, I investigated the mechanisms controlling branching of the ureteric bud. Firstly, the hypothesis that branches rarely arise from the stalks of the ureteric bud because they have lost the ability to branch was tested; it seems that the stalk cells retain their ability to behave as tips when provided with an appropriate environment. Differentiation of ureteric bud cells is therefore surprisingly plastic. 3. I also tested the hypothesis that tips of the ureteric bud space out relative to each other by sensing and responding to tips in the local vicinity. There are two components to this hypothesis: (i) that tips are separated within an epithelium by a lateral inhibition mechanism that prevents new tips forming close to existing ones, and (ii) that tips of extending epithelia are repelled by the presence of nearby tips, so that they spread out to fill space optimally. I have gained supporting evidence against the first hypothesis as tips will form stalk regions whether tips are preformed or not elsewhere in the epithelium. The data presented in this thesis provide evidence both to partially support, and also to limit, the specific self-organisation hypothesis tested.
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Gogolok, Sabine Franziska. „Towards programming and reprogramming cell identity using synthetic transcription factors“. Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/25774.
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Remarkable progress has been made in our ability to design and produce synthetic DNA binding domains (TALE or Cas9-based), which can be further functionalized into synthetic transcription factors (sTFs). This technology is revolutionizing our ability to modulate expression of endogenous mammalian genes. Forced expression of cDNAs encoding transcription factors (TFs) is widely used to drive lineage conversions. However, this process is often inefficient and unreliable. Multiplex delivery of sTFs pool to activate endogenous master regulators and extinguish the expression profile of the host cell type could be a potential solution to this problem. We have developed a novel, simple TALE assembly method that enabled us to produce and screen large numbers of TAL effectors and compare their activity to dCas9-based TFs. During this process, we constructed many new functionally validated sTFs. Our ultimate goal is to test whether combining synthetic transcriptional activators and repressors can efficiently reprogram fibroblasts to NS cells or alternatively ‘program’ NS cell differentiation to neurons. We performed analyses of the transcriptome and chromatin accessibility of both fibroblasts and neural stem cells to unravel their core TF networks and their epigenetic state. This will allow us in the future the targeted design of sTFs and synthetic chromatin modifiers for specifically changing cell identity.
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Ruetz, Tyson Joel. „Smad2/3 potentiate cell identity conversions with master transcription factors“. Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/21703.
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The exogenous expression of master transcription factors (TFs) to drive cell identity changes is an exciting and powerful approach to cell and tissue engineering. Yet, the generation of desired cell types is often plagued by inefficiency and inability to produce mature cell types. Through investigations of the molecular mechanisms of induced pluripotent stem cell (iPSC) generation, I discovered that expression of constitutively active Smad2/3 (Smad2CA/3CA), together with the Yamanaka factors, could dramatically improve the efficiency of reprogramming. Mechanistically, SMAD3 interacted with both co-activators and reprogramming factors, bridging their interaction during reprogramming. Because SMAD2/3 interact with a multitude of master TFs in different cell types, I tested the conversions of B cells to macrophages, myoblasts to adipocytes, and human fibroblasts to neurons. Remarkably, each conversion system was markedly enhanced when the master TFs were co-expressed with Smad3CA. These results revealed the existence of shared molecular mechanisms underlying diverse TF-mediated cellular conversions, and demonstrated SMAD2/3 as a widely applicable cofactor that potentiates the generation of diverse cell types with profound efficiency and maturity.
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Barbosa-Sabanero, Karla Y. „Dedifferentiation and transdifferentiation: a study of the RPE cell identity“. Miami University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=miami1468660645.
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Prober, David Aaron. „Regulation of cell growth and cell identity by Ras 1 in the developing Drosophila melanogaster wing /“. Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/4988.
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Solomon, Andrew Wallace. „Transition to motherhood : the acquisition of maternal identity and its role in a mother's attachment“. Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648404.
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Scott, Camille R. „“Outside People”: Treatment, Language Acquisition, Identity, and the Foreign Student Experience in Japan“. Ohio University Honors Tutorial College / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ouhonors1400619243.
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Nicosia, Matthew. „Performing the Female Superhero: An Analysis of Identity Acquisition, Violence, and Hypersexuality in DC Comics“. Bowling Green State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=bgsu1476751594815625.
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Huang, Hsiao-Juo. „Enunciative identity in elementary English as a foreign language“. CSUSB ScholarWorks, 2005. https://scholarworks.lib.csusb.edu/etd-project/40.
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How to improve the skill of speaking English is a major challenge for English learners in Taiwan nowadays. This project focuses on issues of pronunciation as the starting point to examine the problems of learning English, and issues of identity transformation in the language-learning process. Then it addresses the concept of enunciation as a way to facilitate English learners to establish their confidence in, and ownership of, the target language. This project is designed not only for discussing issues of improving the teaching and learning of English pronunciation, but also for explicating how students can gain their own voices and define their subjectivity during their English-learning process.
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Wong, Jason Pei Wai. „Institutions, knowledge acquisition and cooperation : innovation in the emerging domestic mobile phone industry in China /“. View abstract or full-text, 2004. http://library.ust.hk/cgi/db/thesis.pl?SOSC%202004%20WONG.
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Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2004.Includes bibliographical references (leaves 71-76). Also available in electronic version. Access restricted to campus users.
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Ng, Felicia. „Genome-wide analysis of transcriptional control of haematopoietic cell type identity“. Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.709017.
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Gallizioli, Mattia. „Identity and functions of dendritic cell subsets in ischaemia-induced neuroinflammation“. Doctoral thesis, Universitat de Barcelona, 2021. http://hdl.handle.net/10803/673568.
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Cerebral ischaemia induces several inflammatory processes in the brain. Among them, the infiltration of immune cells is a hallmark of the pathology. Dendritic cells (DCs) are usually present in low numbers in the meninges and the choroid plexus, but rarely in the parenchyma. Upon ischaemia, the number of DCs increases, and the cells infiltrate the brain tissue, where they carry out different functions.
In an experimental murine model of stroke, we set out to investigate the infiltration of several subsets of DCs to the brain and their functional role. Early after stroke, we show a rapid and significant influx of DCs, especially of conventional type 2 DCs (cDC2), which are the most abundant subset at all time points analysed. Twenty- four hours after stroke, these cells were the major source of IL-23, which was able to stimulate its receptor on γδ T cells, inducing their production of IL-17. In turn, IL-17 is responsible for the stimulation of the production of Cxcl1 by astrocytes, ultimately leading to the infiltration of neutrophils to the ischaemic brain and to the exacerbation of the tissue damage. We demonstrate that the interruption of the IL- 23/IL-17 axis decreases the infarct size and improves the neurological outcome of stroke in mice, suggesting that cDC2 may play a detrimental role in the early phase of the immune response to stroke.
The analysis of the infiltration of DCs to the brain in inflammatory conditions has historically been difficult for the absence of univocal markers and for the similarity of their phenotype with other brain cells, especially microglia. The knowledge about the origin, phenotype and functions of brain DCs is therefore underdeveloped. One of the most commonly used markers for the study of DCs is CD11c, which is also expressed by a subset of microglia. The population of CD11c+ cells present in the brain increases after stroke, and we show that CD11c+ cells include proliferating microglia and infiltrating DCs. Despite their similarities, we demonstrate by RNA- Seq analysis that these two cell types exhibit a differential transcriptional profile, with interesting peculiarities in pattern recognition receptor and chemokine receptor expression. DCs extracted from the ischaemic brain outclass microglia in antigen presentation capacity, indicating a functional specialisation. We show that microglia are responsible for the production of chemokines that attract DCs to the brain, especially conventional type 1 DCs (cDC1). This specific subpopulation of DCs appears to have beneficial functions, reducing the infarct size and improving the functional outcome of ischaemic stroke.
Altogether, the studies presented in this thesis shed light on the features discriminating DCs from microglia and uncover previously unknown roles of diverse subpopulations of infiltrating DCs in the outcome of ischaemic stroke.
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Klimanova, Liudmila. „Second language identity building through participation in internet-mediated environments: a critical perspective“. Diss., University of Iowa, 2013. https://ir.uiowa.edu/etd/5001.
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Using a data-driven qualitative approach and drawing from language socialization and communities of practice theories, this dissertation study examines the second language (L2) identity-building strategies of 22 American learners of Russian who engaged in a six-week telecollaborative project with Russian native speakers in two genres of Internet-mediated communication: in one-on-one interactions with an assigned native Russian speaking keypal and in selected virtual communities populated predominantly by native Russian speakers. The investigation of L2 identity enactment in Internet-mediated environments was guided by three research questions pertaining to (1) the nature of the discourse Russian (L2) learners use in interactions with native speakers in two genres of online interactions, (2) the discursive manifestations of L2 learner and speaker identity performances in the learners' online discourse; and (3) the learners' perceptions of their online experiences in two genres of online interactions with native-speaking peers. The methods of critical discourse analysis and interpretative phenomenological analysis were employed to examine the Russian learners' online interactional discourse and offline metatalk regarding their online experiences in the two genres.
The analysis of the Russian learners' discourse revealed the complex nature of discursive L2 identity enactment as they moved into and out of the frames of language learners to complete class assignments and negotiate their competent L2 speaker positions in conversations with Russian-speaking peers. The findings indicate that the two genres of online interaction evoked distinct participation patterns and interactional practices. In both genres, L2 identity enactment involved three dimensions: the macro-level of global identity categories, the locally assigned identity positionings (e.g., heritage speaker, multilingual speaker), and interactionally negotiated stances and temporary positions that evoked self- or other-initiated L2 learner/speaker identity performances.
The author concludes that L2 identity, when enacted in Internet-mediated environments, represents a continuum of L2 learner-speaker performances that rely on the contextual factors of the online encounter, learners' global identity tokens, and the dynamics of power relations in native-nonnative speaker interaction. Performing an L2 identity online is construed as a critical experience of re-evaluating one's association with the target language and transformation into a new kind of socially oriented multilingual subject.
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Gustafsson, Joel. „What have we become? : Organizational identity in the Västerås Police Department“. Thesis, Uppsala universitet, Företagsekonomiska institutionen, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-326800.
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The organizational change of the Swedish police force has become the victim of massive criticism due to the negative results that have continued since 2015. After the organization experienced a structural change that was something between a merger and an acquisition the operational results have continued to decline. One aspect that has been left out of the discussion has been the organizational identity change of the police. Previous research on organizational identity have been very interested in structural organizational changes and have found a vast number of results in different contexts. Identity ambiguity, who are we as an organization, have been present in many cases. Weakened legitimacy claims and changed operational activities have been noticed in many as well. This is studied with a qualitative methodology and an inductive research approach. Information from nine interviews with current and former members of the Västerås police department make up the data that is analysed. What is discovered is the emergence of frustration as an organizational characteristic. This is experienced through all levels of the organization and has resulted in superfluity and resignations.
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Coates, Juliet Clare. „Armadillo homologues in Dictyostelium discoideum“. Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314303.
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Gordon-Wilson, Sianne. „The lived experiences of expectant and new mothers : an exploration of identity, role acquisition and time“. Thesis, Lancaster University, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.730636.
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Many transitions happen during an individual's adult life, which includes a woman becoming a mother. When a woman adopts her new role as a mother and she endorses the values and behavior that is attached to it, there is a significant change in her new identity, which is assisted by consumption. When her new maternal role is added to her more established non-maternal roles, she will have to find the time to fulfil all of the responsibilities associated with her abundant rotes, which has time implications. This thesis will show how women's experiences of identity, the acquisition of their new maternal role and their management of time are particularly important in understanding their consumption practices and behaviour at this life-changing stage. The methodology consisted of qualitative research, which was exploratory in nature to understand the changes in consumption practices that women encountered as they transitioned through pregnancy into motherhood. Ten mothers in the UK participated in the phenomenological interviews to address the research question: "What is expectant and new mothers' lived experience of consumption ?" This thesis found that women encountered different changes as they moved into the stage with a child after their baby was born. Certain products and services were found to help her create and maintain their maternal identity. Consumption was also found to be very significant when women transitioned into their maternal role. Additionally, numerous examples were identified to illustrate how time affected what expectant mothers and new mothers were able to do.
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Ho, Sai-Keung. „Hemisphere differences in lexical decision and in semantic priming effect: an attempt to expand ourunderstanding of the right hemisphere ability in processing theChinese language“. Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1987. http://hub.hku.hk/bib/B29782715.
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Glaros, Anastasios. „Data-driven Definition of Cell Types Based on Single-cell Gene Expression Data“. Thesis, Uppsala universitet, Institutionen för biologisk grundutbildning, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-297498.
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Kline, Leo Isaac. „Health Care Provision to Transgender Individuals; Understanding Clinician Attitudes and Knowledge Acquisition“. ScholarWorks @ UVM, 2015. http://scholarworks.uvm.edu/graddis/338.
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The Institute of Medicine report of 2011 defined Transgender Specific Health Needs as one of four priority research areas. While there is research asserting that health care providers (HCPs) do not have adequate training in providing competent care to transgender patients, there are no studies to date assessing HCPs' gender identity attitudes and their willingness to learn the Standards of Care (SOC) developed for this patient population. According to the Agency for Health Care Research and Quality, as of 2010, 52% of Nurse Practitioners (NPs) were practicing in primary care settings. As more than half of NPs practice in primary care and transgender patients often initially present their gender concerns to their primary care provider, this study focuses on the NP population.
This study describes a sample of NPs' attitudes towards gender variance, as well as their perceived need and interest in learning the SOC as published by the World Professional Association for Transgender Health. Multi-state purposive sampling of NP professional organizations was conducted. Two conservative and two progressive states' professional organizations were included in the sample. The states were randomly assigned within both geopolitical groups to intervention or control with the use of a random numbers table.
Comparisons between geopolitical groups and between control and intervention groups cannot be made due to low response rates of all states. The majority of this small sample of NPs agreed that they needed and wanted additional training in transgender health care. Future research with representative sample sizes is needed to better understand provider-sided barriers to caring for this marginalized patient population.
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Nchang, Doreen. „Language, migration and identity: exploring the motivations of selected African migrants in learning isiXhosa in Cape Town, South Africa“. Thesis, University of the Western Cape, 2014. http://hdl.handle.net/11394/4141.
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Masters of ArtThis study is an exploration of the motivations of a particular group of Cameroonian and Nigerian migrants in Cape Town for learning isiXhosa. South Africa is a multilingual and multicultural country with eleven official languages and many migrant languages, resulting from the flow of people from other countries, especially African countries, to this major economic force on the continent. Among these migrants are West African migrants who have managed to acquire some of the local languages. Forced by new trends in globalization witnessed across the globe, and by the socio-political instabilities in their respective countries, some of these West Africans from Cameroon and Nigeria have moved to South Africa for greener pastures. South Africa to these migrants is economically, socially and politically better than their countries. In the Western Cape Province, the major and official languages are isiXhosa, Afrikaans and English. These West African migrants in Cape Town find themselves in another multicultural and multilingual environment in which the use of particular languages are important for their survival in school, community and other domains. The research also seeks to find out to what extent these migrants have succeeded in acquiring isiXhosa and also to what extent has their acquisition of this language enabled them to survive in Cape Town. Is there any evidence that their identities have been changed and modified in this new space? The research paradigm followed for this study is qualitative in nature, drawing from short questionnaires followed by individual interviews and focus group interviews that were tape recorded. Data was analyzed by using thematic content analysis as well as discourse analysis. Discourse analysis since people have different identities and the creation and use of such identities can only be understood by trying to study the language that people use (Fulcher 2005). Appraisal theory (from the Systemic Functional Perspective) was used to categorize the data. The findings suggest that both the Cameroonian and Nigerian migrants have almost the same motivation for learning isiXhosa. They were both instrumentally and integratively motivated to learn the language, and most believed that they had attained a satisfactory level of proficiency. The findings also suggest that the multicultural and multilingual environment of Cape Town had affected the identities of these migrants.