Social bookmarking has gained popularity since the advent of Web 2.0. Keywords known as tags are created to annotate web content, and the resulting tag space composed of the tags, the resources, and the users arises as a new platform for web content discovery. Useful and interesting web resources can be located through searching and browsing based on tags, as well as following the user-user connections formed in the social bookmarking community. However, the effectiveness of tag-based search is limited due to the lack of explicitly represented semantics in the tag space. In addition, social connections between users are underused for web content discovery because of the inadequate social functions. In this research, we propose a comprehensive framework to reorganize the flat tag space into a hierarchical faceted model. We also studied the structure and properties of various networks emerging from the tag space for the purpose of more efficient web content discovery.The major research approach used in this research is social network analysis (SNA), together with methodologies employed in design science research. The contribution of our research includes: (i) a faceted model to categorize social bookmarking tags; (ii) a relationship ontology to represent the semantics of relationships between tags; (iii) heuristics to reorganize the flat tag space into a hierarchical faceted model using analysis of tag-tag co-occurrence networks; (iv) an implemented prototype system as proof-of-concept to validate the feasibility of the reorganization approach; (v) a set of evaluations of the social functions of the current networking features of social bookmarking and a series of recommendations as to how to improve the social functions to facilitate web content discovery.

The past few years have seen the rapid rise of all things "social" on the web from the growth of online social networks like Facebook, to user-contributed content sites like Flickr and YouTube, to social bookmarking services like Delicious, among many others. Whereas traditional approaches to organizing and accessing the web’s massive amount of information have focused on content-based and link-based approaches, these social systems offer rich opportunities for user-based and community-based exploration and analysis of the web by building on the unprecedented access to the interests and perspectives of millions of users. We focus here on the challenge of modeling and mining social bookmarking systems, in which resources are enriched by large-scale socially generated metadata (“tags”) and contextualized by the user communities that are associated with the resources. Our hypothesis is that an underlying social collective intelligence is embedded in the uncoordinated actions of users on social bookmarking services, and that this social collective intelligence can be leveraged for enhanced web-based information discovery and knowledge sharing. Concretely, we posit the existence of underlying implicit communities in these social bookmarking systems that drive the social bookmarking process which can provide a foundation for community-based organization of web resources. To that end, we make three contributions: • First, we propose a pair of novel probabilistic generative models for describing and modeling community-oriented social bookmarking. We show how these models enable effective extraction of meaningful communities over large real world social bookmarking services. • Second, we develop two frameworks for community-based web information browsing and search that are based on these community-oriented social bookmarking models. We show how both achieve improved discovery and exploration of the social web. • Third, we introduce a community evolution framework for studying and analyzing social bookmarking communities over time. We explore the temporal dimension of social bookmarking and explore the dynamics of community formation, evolution, and dissolution. By uncovering implicit communities, putting them to use in an application scenario (search and browsing), and analyzing them over time, this dissertation provides a foundation for the study of how social knowledge networks are self-organized, a deeper understanding and appreciation of the factors impacting collective intelligence, and the creation of new information access algorithms for leveraging these communities.

HNF1beta est un facteur de transcription homeobox, dont les mutations sont fréquemment rencontrées chez des patients atteints d’anomalies congénitales du rein et du tractus urinaire (Congenital Abnomalities of the Kidney and the Urogenital Tract, CAKUT). HNF1beta est également impliqué dans le diabète de type Maturity Onset Diabetes of the Young 5 (MODY5). Le laboratoire d’accueil a démontré que HNF1beta était impliqué dans un mécanisme épigénétique, le Bookmarking, nécessaire à la réexpression post-mitotique de ses gènes cibles. En particulier, des expériences de vidéo-microscopie ont montré que la partie N-terminale de HNF1beta, contenant le domaine de liaison à l’ADN, en fusion avec la GFP (HNF1beta -GFP) est liée à la chromatine pendant la mitose. L’objectif de ma thèse était de caractériser les modalités biochimiques d’interaction de HNF1beta avec la chromatine mitotique. Nous avons mis en évidence le fait que la capacité de liaison à l’ADN est indispensable à la localisation mitotique de HNF1beta. En effet, la délétion de la troisième hélice alpha de l’homéo-domaine, responsable de l’interaction avec le grand sillon de l’ADN, entraîne la dissociation de la chromatine de HNF1beta pendant la mitose. Nous avons ensuite étudié l’effet de plusieurs mutations identifiées chez des patients MODY sur la localisation mitotique de HNF1beta. Nos résultats ont montré que certaines mutations faux-sens sont capables d’empêcher la fixation de la chromatine mitotique. Parmi ces mutations, certaines manifestent un phénotype dépendant de la température. Par exemple, à une température permissive, inférieure à 30°C, les mutations P256S et C273Y présentent une localisation mitotique normale. En revanche, à 37°C pour P256S et à 39°C pour le mutant C273Y, les protéines sont complètement dissociées, alors que dans toutes ces conditions de température, l’association de la protéine sauvage avec la chromatine mitotique n’est pas affectée. A température permissive (4°C), nous avons montré par retard sur gel (Electophoresis Mobility Shift Assay EMSA) que les mutants lient l’ADN avec un Kd apparent similaire à celui de la protéine sauvage. Par contre, à température restrictive, les mutants présentent des comportements différents. En effet, P256S perd sa capacité de liaison à l’ADN (de façon réversible), tandis que C273Y continue à lier l’ADN avec une affinité similaire à celui de la protéine sauvage. Le caractère thermosensible des mutants de HNF1beta nous a permis d’étudier les modalités de son recrutement sur la chromatine mitotique. Nos résultats ont montré que l’association des protéines à la chromatine mitotique présente une nature très dynamique. En effet, nous avons observé qu’une diminution rapide de température détermine la relocalisation mitotique réversible de la protéine, dans un délai de quelques secondes. Nous avons pu montrer que la relocalisation mitotique de HNF1beta induit par la température était affectée par une déplétion d’énergie, ainsi que par l’action d’un inhibiteur spécifique de l’importine-β (importazole). Nous avons enfin mis en évidence par immuno-précipitation de chromatine (ChIP) que la liaison de HNF1beta à la chromatine mitotique est séquence-spécifique. Nos résultats suggèrent que le recrutement de HNF1beta à la chromatine mitotique est énergie-dépendante, et nécessite le bon fonctionnement du système de transport lié à l’importine-beta. Mes résultats suggèrent que des mutations trouvées chez des patients MODY3 et MODY5 inactivent ou affaiblissent la capacité de HNF1beta de remplir son activité de Bookmarking. / HNF1beta is a POU transcription factor that is frequently mutated in patients that suffer from diabetes and renal cystic dysplasia. This protein has the peculiar ability to bind mitotic chromosomes and behave as a gene bookmarking. Here we show that the capacity of HNF1beta to bind to DNA plays an essential role for mitotic binding. A close homologue, HNF1alpha, shares the ability of HNF1beta to bind to mitotic chromosomes, and several MODY mutations (e.g P256S, V265L and C273Y) affect the ability of the protein to localize to mitotic chromatin. Interestingly, the phenotype induced by these mutations is very rapidly rescued by sudden temperature shifts. Temperature-sensitivity is probably linked to a conformational change that prevents DNA binding ability of P256S and V265L mutants at 37°C. Interestingly, the mitotic relocalization of these mutants induced by temperature shift was sensitive to energy depletion and importazole, suggesting an active mechanism involving the importin-beta system. Interestingly, C273Y mutant exhibited a significantly mitotic dispersion that is not correlated with any DNA or interphase chromatin binding defect, indicating that DNA binding function is necessary but not sufficient to accomplish bookmarking.

This thesis is focused on using social applications from practical point of view in a real business environment. In fact, it is focused more on using them than dealing with hypothesis. There are two main objectives covering developing social application add-on and implementation of another type of social application in a company. The first objective is to develop social system, which provides functionality to fulfill team agenda for most of teams created within of scope on University of Economics. The second main objective is to describe important aspects of implementation Wiki system to one of departments in CSOB Company, the Bikipedia Project.

At the beginning of mitosis, chromosomes are condensed and segregated to facilitate correct alignment later in cytokinesis. Condensin is the pentameric enzyme responsible for this DNA compaction and is composed of two structural maintenance of chromosomes (SMC) subunits and three non-SMC subunits. Condensin mutations generate chromosomal abnormalities due to improper segregation, leading to genome instability and eventual malignant transformation of the cell. Cdc2 phosphorylation of the non-SMC subunits, CAP-G, CAP-D2, and CAP-H, has been demonstrated to be important for condensin supercoiling activity and function. While these subunits are thought to be phosphorylated by Cdc2, the exact sites have not yet been identified and characterized. The basis of this research was to determine the Cdc2 phosphorylation sites in the CAP-G subunit of the condensin enzyme and to characterize the functional significance of the sites in the regulation of condensin activity using site-directed mutagenesis and immunofluoresence microscopy. While DNA condensation represents a critical step early in mitosis, formation of the mitotic spindle represents a vital event leading to the division of a cell into two daughter cells in a process known as cytokinesis. Protein regulating cytokinesis 1 (PRC1) is a mitotic protein essential for cytokinesis that participates in formation of the mitotic spindle in a phosphorylation dependent manner. PRC1 possesses microtubule bundling properties. Loss of PRC1 leads to mis-segregation of chromosomes and abnormal cytokinesis. HSF2 is a transcription factor known to be important in development and differentiation. Previous research has determined that HSF2 plays a significant mechanistic role in the process of hsp70i gene bookmarking during mitosis. Bookmarking is an epigenetic phenomenon whereby certain gene promoters remain uncompacted, in contrast to the majoritiy of genomic DNA during mitosis. This lack of compaction allows quick reassembly to a transcriptionally competent in G1 of the cell cycle and ensures the ability of the cell to induce expression of the cytoprotective hsp70i protein. HSF2 and PRC1 were found to interact in a yeast-two hybrid screen. Given the importance of both of these proteins during mitosis, this study seeks to characterize the HSF2/PRC1 interaction and determine the potential role for PRC1 in hsp70i gene bookmarking.

Breast cancer arises from a series of acquired mutations that disrupt normal mammary epithelial homeostasis and create multi-potent cancer stem cells that can differentiate into clinically distinct breast cancer subtypes. Despite improved therapies and advances in early detection, breast cancer remains the leading diagnosed cancer in women. A predominant mechanism initiating invasion and migration for a variety of cancers including breast, is epithelial-to-mesenchymal transition (EMT). EMT— a trans-differentiation process through which mammary epithelial cells acquire a more aggressive mesenchymal phenotype—is a regulated process during early mammary gland development and involves many transcription factors involved in cell lineage commitment, proliferation, and growth. Despite accumulating evidence for a broad understanding of EMT regulation, the mechanism(s) by which mammary epithelial cells maintain their phenotype is unknown. Mitotic gene bookmarking, i.e., transcription factor binding to target genes during mitosis for post mitotic regulation, is a key epigenetic mechanism to convey regulatory information for cell proliferation, growth, and identity through successive cell divisions. Many phenotypic transcription factors, including the hematopoietic Runt Related Transcription Factor 1 (RUNX1/AML1), bookmark target genes during mitosis. Despite growing evidence, a role for mitotic gene bookmarking in maintaining mammary epithelial phenotype has not been investigated. RUNX1 has been recently identified to play key roles in breast cancer development and progression. Importantly, RUNX1 stabilizes the normal breast epithelial phenotype and prevents EMT through repression of EMT-initiating pathways. Findings reported in this thesis demonstrate that RUNX1 mitotically bookmarks both RNA Pol I and II transcribed genes involved in proliferation, growth, and mammary epithelial phenotype maintenance. Inhibition of RUNX1 DNA binding by a specific small molecule inhibitor led to phenotypic changes, apoptosis, differences in global protein synthesis, and differential expression of ribosomal RNA as well as protein coding genes and long non-coding RNA genes involved in cellular phenotype. Together these findings reveal a novel epigenetic regulatory role of RUNX1 in normal-like breast epithelial cells and strongly suggest that mitotic bookmarking of target genes by RUNX1 is required to maintain breast epithelial phenotype. Disruption of RUNX1 bookmarking results in initiation of epithelial to mesenchymal transition, an essential first step in the onset of breast cancer.

The canonical Wnt/β-catenin signaling pathway is essential for the proper regulation of cell-fate decisions throughout embryogenesis and in adult issues. Activation of the Wnt signaling pathway allows for nuclear localization of the cell adhesion protein β-catenin, which then interacts primarily with members of the T-Cell Factor/Lymphoid Enhancer Factor (TCF/LEF) transcription factor family to modulate gene activity. The TCF/LEF family includes TCF7, TCF7L1, TCF7L2, and LEF1. While all four family members share a common DNA binding consensus sequence, their expression throughout embryogenesis and adult stem cell populations is unique, with their misexpression commonly occurring in Wnt related cancers and correlating strongly with metastasis and poor patient outcomes. TCF/LEF exchange at target gene loci is a key feature of mediating context-specific cellular responses to Wnt signaling and can be observed to occur in a variety of populations throughout development and in adult stem cell populations. To model TCF/LEF exchange in vitro we have optimized a micropatterning fabrication and culture protocol capable of identifying and isolating discrete LEF1-only and TCF7L1-only populations during gastrulation-like processes. To characterize how complements of TCF/LEFs change during cellular divisions we have developed a novel mitotic chromatin proteomic technique. This method identifies LEF1 as the only TCF/LEF to remain associated with mitotic chromatin in Wnt-activated conditions in mouse embryonic stem cells that are transitioning out of pluripotency as a consequence of removing leukemia inhibitory factor from their culture medium. Additionally, gene targeting techniques were used to label endogenous LEF1 and TCF7L1 with different fluorescent proteins in a single mouse embryonic stem cell line, allowing us to use TCF/LEF protein expression as a reporter of Wnt/β-catenin pathway status, which we found to be capable of identifying a unique set of compounds that are undetected by traditional Wnt activity (TOP-Flash) reporter screens. By using gene editing technology, and novel applications of proteomic and cell culture techniques, we have been able to investigate the mechanisms driving TCF/LEF expression and exchange in mouse embryonic stem cells to identify potentially clinically relevant therapeutic targets for their potential use in addressing TCF/LEF dysregulation in cancer. We have identified a novel mechanism through which TCF/LEFs maintain cell fate over cellular division; presented a novel live-cell drug screening platform capable of identifying compounds missed by existing platforms; and presented an optimized cell culture technique for the isolation of TCF/LEF exchange events. Taken together, the work in this thesis provides new insights into the mechanisms through which TCF/LEFs regulate their gene targets during cell fate transitions and throughout mitosis. / Thesis / Doctor of Science (PhD) / Throughout development and adult life cells are in constant communication, using a variety of cell signaling pathways to maintain adult stem cell populations and to pattern tissues throughout the body. Communication between cells often requires one cell to release a protein molecule (called a ligand) that is recognized by a receptor molecule on the surface of another cell. These cell surface receptors, when bound by the signaling ligand become activated and often set of a cascade of internal cellular events that ultimately result in changes in gene transcription in the nucleus. These transcriptional changes are toggled by proteins known as sequence-specific transcription factors that are able to selectively regulate expression of target genes. The net effect of combinations of extracellular ligands binding cell surface receptors determines the selective recruitment of specific transcription factors that activate a cell’s transcriptional program, in turn defining its fate and function. A very important developmental signaling pathway is the Wnt signaling pathway, which employs a family of secreted Wnt molecules as ligands. The Wnt pathway is critical at all stages of organismal development and plays an essential role in tissue maintenance in mature animals. However, due to its critical role in stem cell maintenance, when mutations occur in Wnt signaling components it can have dire consequences. Wnt signaling has been found to be disrupted in more than 70-80% of all cancers. One major feature among these Wnt-related cancers is the inappropriate expression and mobilization of Wnt transcription factors. While the expression and activity of Wnt transcription factors – known as T-Cell Factor/Lymphoid Enhancer Factors (TCF/LEFs) – changes throughout development and stem cell maintenance, their inappropriate expression is frequently associated with metastasis and poor patient outcomes. We have used mouse embryonic stem cells (mESCs) as a model system with which to study the mechanisms employed by TCF/LEFs to regulate their target genes. Through a number of approaches, which include adding fluorescent tags to TCF/LEF factors to track their intercellular locations and expression levels or enzymatic tags to identify proteins that interact with individual TCF/LEFs during a snapshot of cell activity, we have gained new knowledge about how these critical transcription factors regulate Wnt-regulated transcriptional programs. We also describe a method for generating micropatterned growth surfaces for mESCs that forces clusters of cells to grow within small circular shapes with a diameter of 1 mm or less. We show that mESCs confined to circular micropatterns differentiate in a highly reproducible manner that allows us to study the cell populations undergoing differentiation with a focus on cell fate determination mechanisms.

Organizations are attempting to leverage their knowledge resources by integrating knowledge sharing systems, a key and new form of which are social computing tools. A large number of these initiatives fail, however, due to employees' reluctance to use, contribute content to, and share knowledge through such tools. Although research regarding one's motivation to share knowledge is extensive, there has been little research examining social computing systems, especially from the seeking and contributory perspectives—the two distinct, but closely interrelated facets of knowledge sharing. Motivated by such concerns, and by incorporating knowledge-seeking and knowledge- contribution perspectives in a single study, this research develops and empirically examines a theoretical model to explain what motivates employees to seek, contribute and share social tags using Enterprise Social Tagging Tools (ESTTs). Two research phases were employed to address the research objective. The goal of the first phase of the study was to explore factors affecting users’ tagging behavior in online social tagging tools. An extensive literature review was synthesized and a preliminary theoretical model emerged. A pilot study was conducted yielding 184 responses featuring eight different online social tagging tools. Mostly, the preliminary theoretical model showed positive influence on users’ tag behavior with a special focus on the newly developed concepts of information retrievability, information refindability. The goal of the study’s second phase was combining the results from the first phase with motivational theories to build and validate a belief-based and socio-organizational model that can explain employees’ tag seeking, contributing, and sharing behavior in ESTTs. The model was developed by employing theories such as Theory of Reasoned Action (TRA), Theory of Planned Behavior (TPB), Technology Acceptance Model (TAM), and social exchange theory. Through a large-scale survey (n=481) in two large Information Technology (IT) companies, the model was validated. The results speak to the importance of the three newly developed factors impacting employees’ tag seeking, contributing and sharing behavior. These factors are uniquely context-specific reflecting actual features of social tagging tools and potentially social media in general. Particularly, the results reveal that employees' tag seeking behavior is affected by their perception of the ESTTs in terms of enjoyment, information retrievability, ease of use, and managerial influence. In the context of tag contribution and sharing, the results show that employees contribute and share tags because of their perception of information refindability, ease of use, altruism, and pro-sharing norms. Differences among the seeking, contributing and sharing model have implications for future research and practice. / The thesis investigates employees' motivation to participate in enterprise social tagging tools. It describes and validates a conceputal model composed of three types of motivations: technical, social, and organizational.

Στη συγκεκριμένη Διπλωματική εργασία μελετώνται μέθοδοι κατασκευής συστήματος αναγνώρισης κακόβουλων - spammer χρηστών στο Διαδίκτυο. Συγκεκριμένα, επικεντρωνόμαστε στα Συστήματα Κοινωνικής Σελιδοσήμανσης, που αποτελούν έναν από τους βασικότερους τομείς σήμερα στο Διαδίκτυο. Οι μέθοδοι που χρησιμοποιούνται βασίζονται στο επιστημονικό πεδίο της Μηχανικής Μάθησης. Δοσμένου ενός πραγματικού συνόλου δεδομένων που περιγράφει έναν από τους πιο δημοφιλής Ιστότοπους Κοινωνικής Σελιδοσήμανσης, τον BibSonomy, εξάγονται χαρακτηριστικά σημασιολογικής φύσεως και εισάγονται σε ταξινομητές ώστε να διερευνηθεί η απόδοσή τους και να ευρεθούν οι βέλτιστες ρυθμίσεις τους στη διαδικασία ταυτοποίησης spammer και νόμιμων χρηστών. / In this Thesis are studied methods of designing a system that identifies malicious – spammer users on the Internet. In particular, we focus on Social Bookmarking Systems, which form one of the key areas on the Internet today. Methods are based on the scientific field of Machine Learning. Given a real dataset that describes one of the most popular Social Bookmarking website, BibSonomy, semantic features are extracted and introduced at classifiers in order to investigate the performance and determine the best settings in the process of identifying spammer and legitimate users.

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