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The generation and maintenance of intricate spatiotemporal patterns of gene expression in multicellular organisms requires the establishment of complex mechanisms of transcriptional regulation. Estimations that up to one million enhancers exist in the human genome accentuates the utmost importance of this type of cis-regulatory element for gene regulation. However, surprisingly little is known about the mechanisms used to temporarily or permanently activate or inactivate enhancers during cellular differentiation. The current work addresses the question how enhancer regulation can be achieved.
Using the chemokine (C-C motif) ligand gene Ccl22 as a model, the first example is based on the question how the activation of an enhancer can be prevented in a physiological context. Ccl22 is expressed by myeloid cells, such as dendritic cells, upon exposure to inflammatory stimuli. The expression in other cell types, such as fibroblasts, is prevented by the strong accumulation of H3K9me3 at the enhancer's proximal region. This accumulation is attenuated in myeloid cells through activity of the stimulus-induced demethylase Jmjd2d. To tease out which genomic fragment or fragments in the Ccl22 locus could be responsible for the maintenance of enhancer inactivity, potentially through the recruitment of H3K9 methyltransferases, the enhancer repressing capacity of 1 kb fragments of the gene locus was analysed in retroviral reporter assays. It was found that a fragment adjacent to the Ccl22 enhancer that overlaps with a member of a subfamily of long interspersed nuclear elements (LINEs) showed strong repressive potential on a model enhancer. Subsequent retroviral reporter assays with LINEs from loci of other stimulus-dependent genes identified additional LINE fragments that exhibit strong enhancer repressive capacity. These findings suggest a mechanism for enhancer silencing involving LINEs.
The second example concentrates on the inactivation of an enhancer during colorectal cancer (CRC) progression. The adenoma to carcinoma transition during CRC progression often is accompanied by a downregulation of the tumour suppressor gene EPHB2. The EMT inducing factor SNAIL1 strongly downregulated EPHB2 expression in a CRC cell model. To gain insights into the transcriptional regulation of EPHB2, potential cis-regulatory elements in the EPHB2 upstream region were analysed using reporter assays. A cell-type-specific enhancer was identified and subsequent chromatin analyses revealed a correlation between enhancer chromatin conformation and EPHB2 expression in different CRC cell lines. Additionally, the overexpression of the murine Snail1 induced chromatin changes at the EPHB2 enhancer towards a poised, transcriptionally silent chromatin conformation. Mutational analyses of the minimal enhancer region pinpointed three transcription factor binding motifs to be essential for full enhancer activity. Different binding patterns between CRC cell lines at the TCF/LEF motif were subsequently identified. Furthermore, a switch from TCF7L2 to LEF1 occupancy was found upon overexpression of Snail1 in vitro and in vivo. The generation of LS174T CRC cells overexpressing LEF1 confirmed the involvement of LEF1 in the downregulation of EPHB2 and the competitive displacement of TCF7L2. This part of the work demonstrated that the SNAIL1 induced downregulation of EPHB2 is dependent on the decommissioning of a transcriptional enhancer and led to a hypothetical model involving LEF1 and ZEB1.
In summary, this work highlighted two distinct mechanisms for enhancer regulation. One mechanism is based on enhancer repressive LINE fragments that might prevent stimulus-dependent enhancer activation. In the second, enhancer silencing was shown to be based on a competitive transcription factor binding mechanism.
Only since the turn of the 21st century have humanitarian organisations developed specific strategies that address climate change impacts as a humanitarian challenge. Taking the International Red Cross / Red Crescent Movement, being the largest humanitarian network, as an empirical case study, the article discusses the Movement’s changes in the areas 1) agenda setting, 2) organisational restructuring, 3) networking, 4) programming, and 5) advocacy. Based on the case study and a theoretical framework of organisational sociology, the article provides conclusions on internal and external factors that can explain why the Movement has been successful in being one of the first actors within the organisational field of humanitarian organisations to focus systematically on the humanitarian implications of climatic changes.
Communicating Climate Risks. A case study of the International Red Cross/Red Crescent Movement
(2015)
In education, finding the appropriate learning pace that fits to the members of a large group is a challenging task. This becomes especially evident when teaching multidisciplinary subjects such as epidemiology in medicine or computer science in most study programs, since lecturers have to face a very heterogeneous state of previous knowledge. Approaching this issue requires an individual supervision of each and every student, which is obviously bounded by the available resources. Moreover, when referring back to the second example, writing computer programs requires a complex installation and configuration of development tools. Many beginning programmers already become stuck at this entry stage. This paper introduces WHELP, a Web-based Holistic E-Learning Platform, which provides an integrated environment enabling the learning and teaching of computer science topics without the need to install any software. Moreover, WHELP includes an interactive feedback system for each programming exercise, where lecturers or tutors can supply comments, improvements, code assistance or tips helping the students to accomplish their tasks. Furthermore, WHELP offers a statistical analysis module as well as a real-time classroom polling system both promoting an overview of the state of knowledge of a course. In addition to that, WHELP enables collaborative working including code-sharing and peer-to-peer learning. This feature enables students to work on exercises simultaneously at distinct places. WHELP has been successfully deployed in the winter term 2013 at the Cologne University of Applied Sciences supporting the 120 students and 3 lecturers to learn and teach basic topics of computer science in an engineering study program.
WebSocket - WS^2 2.0
(2015)
Das Websocket-Protokoll hat sich derzeit zu einer wichtigen Technologie für die Entwicklung moderner Webanwendungen durchgesetzt. Mit der Möglichkeit eine dauerhafte bidirektionale Verbindung zwischen Client und Server aufzubauen, ergeben sich neue Anwendungsszenarien, die vorher mit dem reinen HTTP nicht realisierbar waren. Die Einsatzgebiete reichen hier von einfachen Chats bis hin zu komplexen Systemen wie das kollaborative Arbeiten an Dokumenten in Echtzeit. Mittlerweile hat sogar der Instant Messaging-Dienst WhatsApp die Vorteile der WebSocket-Technologie für sich entdeckt und erlaubt Benutzern ihre Nachrichten nun auch über den Webbrowser auszutauschen.
Dieser Workshop soll den Teilnehmern zeigen wie sie die oben genannten oder andere Echzeitwebanwendungen mit der WebSocket-Technologie implementieren können. Nach einer kurzen Einführung wird gezeigt wie es in einfachen Schritten möglich ist, mehr als nur simple Chat-Anwendungen mit den WebSocket-Protokoll zu realisieren. Zudem stellt der Workshop nach Möglichkeit auch die Verwendung von Subprotokollen vor, wodurch auch RPC- sowie Publish and Subscribe-Anwendungen mit WebSockets umgesetzt werden können.
This paper gives necessary foundations to understand the mechanism of warning processing and summarizes the state of the art in warning development. That includes a description of tools, researchers use to work in this scientific field. In detail these are models that describes the human way of processing warnings and mental models. Both are presented detailed with relevant examples. The paper tells how these tools are connected and how they are used to improve the effectiveness of warnings.
Despite the lack of standardisation for building REST-ful HTTP applications, the deployment of REST-based Web Services has attracted an increased interest. This gap causes, however, an ambiguous interpretation of REST and induces the design and implementation of REST-based systems following proprietary approaches instead of clear and agreed upon definitions. Issues arising from these shortcomings have an influence on service properties such as the loose coupling of REST-based services via a unitary service contract and the automatic generation of code. To overcome such limitations, at least two prerequisites are required: the availability of specifications for implementing REST-based services and auxiliaries for auditing the compliance of those services with such specifications. This paper introduces an approach for conformance testing of REST-based Web Services. This appears conflicting at the first glance, since there are no specifications available for implementing REST by, e.g., t he prevalent technology set HTTP/URI to test against. Still, by providing a conformance test tool and leaning it on the current practice, the exploration of service properties is enabled. Moreover, the real demand for standardisation gets explorable by such an approach. First investigations conducted with the developed conformance test system targeting major Cloud-based storage services expose inconsistencies in many respects which emphasizes the necessity for further research and standardisation.
Web of Services Security
(2015)
Dieses Buch führt Sie umfassend in die WebSocket-Technik und die damit einhergehenden neuen Entwicklungsmöglichkeiten ein. Unter den zahlreichen exemplarischen Anwendungen finden sich Beispiele auf Basis von Node.js, Vert.x, und JSR 356, als Programmiersprachen werden Java und JavaScript eingesetzt.
Appropriating Digital Fabrication Technologies — A comparative study of two 3D Printing Communities
(2015)
Digital fabrication technologies have a great potential for empowering consumers to produce their own creations. However, despite the growing availability of digital fabrication technologies in shared machine shops such as FabLabs or University Labs, they are often perceived as difficult to use, especially by users with limited technological aptitude. Hence, it is not yet clear if the potentials of the technology can be made accessible to a broader public, or if they will remain limited to some form of “maker elite”. In this paper, we study the appropriation of digital fabrication on the example of the use of 3D printers in two different communities. In doing so, we analyze how users conceptualize their use of the 3D printers, what kind of contextual understanding is necessary to work with the machines, and how users document and share their knowledge. Based on our empirical findings, we identify the potentials that the machines offer to the communities, and what kind of challenges have to be overcome in their appropriation of the technology.
3D Time-of-Flight (ToF)
(2015)
Despite the opportunities and benefits of OER, research and practice has shown how the OER repositories have a hard time in reaching an active user-base. The opportunities of experience exchange and simple feedback mechanisms of social software have been realized for improving the situation and many are basing or transforming their OER offerings towards socially powered environments. Research on social software has shown how knowledge-sharing barriers in online environments are highly culture and context-specific and require proper investigation. It is crucial to study what challenges might arise in such environments and how to overcome them, ensuring a successful uptake. A large-scale (N = 855) cross-European investigation was initiated in the school context to determine which barriers teachers and learners perceive as critical. The study highlights barriers on cultural distance, showing how those are predicted by nationality and age of the respondents. The paper concludes with recommendations for overcoming those barriers.
The aim of our research is finding measures to preserve the learners’ initial motivation in educational settings. For that we need to avoid conflicting situations that possibly could jeopardize their joy of learning.
In our thematically comprehensive Learning Culture Survey, we investigate the cultural biasing of students’ attitudes, behaviours, and expectations towards education. Particularly in times of massive international migration and growing numbers of refugees, the relevance to deeply understand cultural aspects in education increases. Just with this understanding, we can raise the awareness towards more cultural tolerance across all involved stakeholder groups and thus, foster the development of more culture-sensitive educational approaches. In this paper we focus on the most relevant aspect of motivation and comparatively discuss our study conducted in Germany and South Korea.
Mit unserer Forschung wollen wir Maßnahmen finden, die dazu beitragen, die anfängliche
Bildungsmaßnahmen zu
Motivation von Lernern bewahren. Zu diesem Zweck
in müssen Konfliktsituationen möglichst vermieden werden, wenn sie das Potential haben, ihnen die Freude am Lernen zu verderben. In unserem thematisch breitgefächerten Learning Culture Survey (Untersuchung von Lernkultur), untersuchen wir bei Lernern das Vorhandensein und den Einfluss kulturspezifischer Prägungen auf deren Verhaltensweisen, Gewohnheiten und Erwartungen bzgl. Bildung. Besonders in Zeiten massiver internationaler Migration und steigender Zahlen von Flüchtlingen wächst der Bedarf nach entsprechender Forschung stetig an. Nur wenn wir die Zusammenhänge zwischen Lernen und Kultur ausreichend verstehen, sind wir in der Lage, auf allen Ebenen die Entwicklung des erforderlichen Bewusstseins bzgl. kultursensibler Bildungsansätze zu fördern. In diesem Beitrag konzentrieren wir uns auf den sehr wichtigen Aspekt Motivation und diskutieren die Ergebnisse, die wir in unserer vergleichenden Studie in Deutschland und Südkorea erzielt haben.
With a focus on Technology Enhanced Learning, this paper investigates if and to which extent a culture shift can be expected alongside with the adoption of currently emerging Web 3.0 technologies. Instead of just offering new opportunities for the field to improve education, such a culture shift could lead to unexpected general consequences not just for Technology Enhanced Learning but the whole educational sector. Understanding the dimension of expectable changes enables us to prevent conflicts and pointedly support culture-related change processes. After an introduction of the Revised Onion Model of Culture, which, later on, serves as theoretical foundation, expectable changes in the design of learning scenarios are analysed, distinguishing the stakeholder groups “learners” and “educators”. Eventually, the found changes are analysed to which extent a general culture shift is to be expected in order to understand the transferability and limitations of future research results in the field.
Quality Management in Education: Business Process Modelling in Interdisciplinary Environments
(2015)
The Whole Is More than the Sum of Its Parts - On Culture in Education and Educational Culture
(2015)
The Learning Culture Survey investigates learners’ expectations towards and perceptions of education on international level with the aim to make culture in the context of education better understandable and support educators to prevent and solve intercultural conflicts in education. So far, we found that culture-related expectations differ between educational settings, depend on the age of the learners, and that a nationally homogenous educational culture is rather an exception than the rule. The results of our recently completed longitudinal study provided evidence that educational culture on the institutional level actually is persistent, at least over a term of four years. After a brief introduction of the general background, we will subsume the steps taken during the past seven years and achieved general insights regarding educational culture. Last, we will introduce a method for the determination of conflict potential, which bases on the understanding of culture as the level to w hich people within a society accept deviations from the usual. We close with demonstrating the method’s functionality on examples from the Learning Culture Survey.
Managing the needs of learners is crucial in order to support their motivation and keep dropout rates on a low level. With the constantly growing level of internationalization in classrooms, the variety of different context-specific requirements from learners increase; without a profound understanding of the learners’ contexts, successfully maintaining a culture-sensitive and learner-focussed education is impossible. A solution to reach this understanding is the open exchange of experiences and knowledge amongst educators of the different contexts. In this paper, we will briefly introduce the two European projects “Open Discovery Space” (ODS) and “Inspiring Science Education” (ISE), which have the aim to foster the establishment and improvement of Open Educational Practices in the context of school education. The purpose of this paper is to attract and invite potential partners to affiliate with, contribute to, and profit from the projects.
The human MPV17-related mitochondrial DNA depletion syndrome is an inherited autosomal recessive disease caused by mutations in the inner mitochondrial membrane protein MPV17. Although more than 30 MPV17 gene mutations were shown to be associated with mitochondrial DNA depletion syndrome, the function of MPV17 is still unknown. Mice deficient in Mpv17 show signs of premature aging. In the present study, we used electrophysiological measurements with recombinant MPV17 to reveal that this protein forms a non-selective channel with a pore diameter of 1.8 nm and located the channel's selectivity filter. The channel was weakly cation-selective and showed several subconductance states. Voltage-dependent gating of the channel was regulated by redox conditions and pH and was affected also in mutants mimicking a phosphorylated state. Likewise, the mitochondrial membrane potential (Δψm) and the cellular production of reactive oxygen species were higher in embryonic fibroblasts from Mpv17−/− mice. However, despite the elevated Δψm, the Mpv17-deficient mitochondria showed signs of accelerated fission. Together, these observations uncover the role of MPV17 as a Δψm-modulating channel that apparently contributes to mitochondrial homeostasis under different conditions.
Permanenz in Inkohärenz
(2015)