355 research outputs found

    E1A expression dysregulates IL-8 production and suppresses IL-6 production by lung epithelial cells

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    BACKGROUND: The adenoviral protein E1A has been proposed to play a role in the pathophysiology of COPD, in particular by increasing IL-8 gene transcription of lung epithelial cells in response to cigarette smoke-constituents such as LPS. As IL-8 production is also under tight post-transcriptional control, we planned to study whether E1A affected IL-8 production post-transcriptionally. The production of IL-6 by E1A-positive cells had not been addressed and was studied in parallel. Based on our previous work into the regulation of IL-8 and IL-6 production in airway epithelial cells, we used the lung epithelial-like cell line NCI-H292 to generate stable transfectants expressing either E1A and/or E1B, which is known to frequently co-integrate with E1A. We analyzed IL-8 and IL-6 production and the underlying regulatory processes in response to LPS and TNF-α. METHODS: Stable transfectants were generated and characterized with immunohistochemistry, western blot and flow cytometry. IL-8 and IL-6 protein production was measured by ELISA. Levels of IL-8 and IL-6 mRNA were measured using specific radiolabeled probes. EMSA was used to assess transcriptional activation of relevant transcription factors. Post-transcriptional regulation of mRNA half-life was measured by Actinomycin D chase experiments. RESULTS: Most of the sixteen E1A-expressing transfectants showed suppression of IL-6 production, indicative of biologically active E1A. Significant but no uniform effects on IL-8 production, nor on transcriptional and post-transcriptional regulation of IL-8 production, were observed in the panel of E1A-expressing transfectants. E1B expression exerted similar effects as E1A on IL-8 production. CONCLUSION: Our results indicate that integration of adenoviral DNA and expression of E1A and E1B can either increase or decrease IL-8 production. Furthermore, we conclude that expression of E1A suppresses IL-6 production. These findings question the unique role of E1A protein in the pathophysiology of COPD, but do not exclude a role for adenoviral E1A/E1B DNA in modulating inflammatory responses nor in the pathogenesis of COPD

    Studieadvies op basis van zelforganisatie: Dynamische wegwijzers in een veranderend onderwijslandschap

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    Van den Berg, B., Tattersall, C., Janssen, J., Van Es, R., & Koper, R. (2006). Studieadvies op basis van zelforganisatie: Dynamische wegwijzers in een veranderend onderwijslandschap. Unpublished manuscriptStudenten kunnen tegenwoordig kiezen uit een steeds groter aanbod van cursussen en trainingen, die vaak in de vorm van losse modules op verschillende manieren aan elkaar geschakeld kunnen worden. Dit biedt veel voordelen maar vormt ook de basis voor een keuzeprobleem: wat is de meest effectieve weg naar mijn doel? Dit artikel beschrijft de software architectuur die is ontworpen om Life-Long-Learners te ondersteunen bij het kiezen van hun leerpad in een leernetwerk. Deze architectuur sluit aan bij theorieën over zelforganisatie en indirecte sociale communicatie. De architectuur omvat de opslag, verwerking en presentatie van collectief studiegedrag en verschaft informatie over succesvolle leerpaden van medestudenten aan studenten die een vervolgkeuze voor hun studie maken. Er wordt een implementatie beschreven van een leernetwerk en verslag gedaan van de uitkomsten van een experiment met dit prototype. De resultaten leiden tot de conclusie dat er door het geven van een advies convergentie van leerpaden optreedt en dat de studenten die een studieadvies krijgen effectiever zijn

    Learners’ evaluation of a navigation support tool in distance education

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    Bolman, C., Tattersall, C., Waterink, W., Janssen, J., Van den Berg, B., Van Es, R., et al. (2007). Learner’s evaluation of a navigation support tool in distance education. Journal of Computer Assisted Learning, 23 (5), 384-392.This article investigates the usability of a navigation support tool developed to guide learners in a lifelong learning environment. The navigation support tool generates advice on the best next step to take in an e-learning course following completion of a course module, and was evaluated in a largescale experimental study based around an online Internet skills course. This article follows on from the experimental study and examines learners’ evaluation of the navigational support. It uses automatically generated logs of completion of course modules and learners’ answers to online questionnaires to give insight into learners’ evaluation, learners’ adherence to the advice and selfefficacy information. The article describes the theoretical underpinnings of the work, the experimental setup and results, and draws conclusions to refine the navigation tool and to increase adherence to the advice

    Swarm-based wayfinding support in open and distance learning

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    Please refer to the original source: Tattersall, C. Manderveld, J., Van den Berg, B., Van Es, R., Janssen, J., & Koper, R. (2005). Swarm-based wayfinding support in open and distance learning. In Alkhalifa, E.M. (Ed). Cognitively Informed Systems: Utilizing Practical Approaches to Enrich Information Presentation and Transfer. Information Science Publishing, USA. (pp. 166-183). [http://www.silvertair.com/CIS/Contents.htm] OR Tattersall, C. Manderveld, J., Van den Berg, B., Van Es, R., Janssen, J., & Koper, R. (2008). Swarm-based Wayfinding Support in Open and Distance Learning. In Sugumaran, V. (Ed). Intelligent Information Technologies: Concepts, Methodologies, Tools, and Applications. Information Science Reference, Hershey New York. (pp 846-857).Open and Distance Learning (ODL) gives learners freedom of time, place and pace of study, putting learner self-direction centre-stage. However, increased responsibility should not come at the price of over-burdening or abandonment of learners as they progress along their learning journey. This paper introduces an approach to wayfinding support for distance learners based on self-organisation theory. It describes an architecture which supports the recording, processing and presentation of collective learner behaviour designed to create a feedback loop informing learners of successful paths towards the attainment of learning goals. The approach is presented as an alternative to methods of achieving adaptation in hypermedia-based learning environments which involve learner modelling

    Swarm-based Sequencing Recommendations in E-learning

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    To be presented at the International Workshop on Recommender Agents and Adaptive Web-based Systems (RAAWS 2005) held in conjunction with the Intelligent Systems Design and Applications 2005 Conference (ISDA 2005), Wroclaw, Poland, September 8-10, 2005. Proceedings 5th International Conference on Intelligent Systems Design and Applications, (Eds) Kwasnicka, H. & Paprzycki, M., IEEE Computer Society, 2005, pp.488-493Open and distance Learning (ODL) gives learners freedom of time, place and pace of study, putting learner self-direction centre-stage. However, increased responsibility should not come at the price of over-burdening or abandonment of learners as they progress along their learning journey. This paper introduces an approach to recommending the sequencing of e-learning modules for distance learners based on self-organisation theory. It describes an architecture which supports the recording, processing and presentation of collective learner behaviour designed to create a feedback loop informing learners of successful paths towards the attainment of learning goals. The article includes initial results from a large-scale experiment designed to validate the approach

    Motor Network Degeneration in Amyotrophic Lateral Sclerosis: A Structural and Functional Connectivity Study

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    BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by motor neuron degeneration. How this disease affects the central motor network is largely unknown. Here, we combined for the first time structural and functional imaging measures on the motor network in patients with ALS and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Structural measures included whole brain cortical thickness and diffusion tensor imaging (DTI) of crucial motor tracts. These structural measures were combined with functional connectivity analysis of the motor network based on resting state fMRI. Focal cortical thinning was observed in the primary motor area in patients with ALS compared to controls and was found to correlate with disease progression. DTI revealed reduced FA values in the corpus callosum and in the rostral part of the corticospinal tract. Overall functional organisation of the motor network was unchanged in patients with ALS compared to healthy controls, however the level of functional connectedness was significantly correlated with disease progression rate. Patients with increased connectedness appear to have a more progressive disease course. CONCLUSIONS/SIGNIFICANCE: We demonstrate structural motor network deterioration in ALS with preserved functional connectivity measures. The positive correlation between functional connectedness of the motor network and disease progression rate could suggest spread of disease along functional connections of the motor network

    International Survey on Criteria for Training and Accreditation in Interventional Neuroradiology

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    Purpose With the rapid expansion of the field of interventional neuroradiology (INR) and the diverse background of aspiring neuro-interventionists, there is an ever increasing need to establish consensus criteria for training and accreditation in INR.Materials and Methods We performed a survey to explore the current state of criteria for training and accreditation in INR. The questionnaire consisting of 11 questions was emailed to the members of World Federation of Interventional and Therapeutic Neuroradiology (WFITN) worldwide. It was focused on the training charter, training program, qualifying examination, and education after training program as perceived by practitioners in each country. Results A total of 52 WFITN members in 19 countries responded to the questionnaire. There was a huge variation internationally and nationally due to the unique situation and challenges in each country and institution. Criteria for training and accreditation in INR were well established in some countries of Europe, North America, and Asia but not specified in other countries. Conclusion It is critical to establish consensus criteria for training and accreditation in INR in order to ensure safe practice and continued expansion and development of INR as a specialty
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