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While severe coronavirus infections, including Middle East respiratory syndrome coronavirus (MERS-CoV), cause lung injury with high mortality rates, protective treatment strategies are not approved for clinical use. We elucidated the molecular mechanisms by which the cyclophilin inhibitors cyclosporin A (CsA) and alisporivir (ALV) restrict MERS-CoV to validate their suitability as readily available therapy in MERS-CoV infection. Calu-3 cells and primary human alveolar epithelial cells (hAECs) were infected with MERS-CoV and treated with CsA or ALV or inhibitors targeting cyclophilin inhibitor-regulated molecules including calcineurin, nuclear factor of activated T-cells (NFATs) or mitogen-activated protein kinases. Novel CsA-induced pathways were identified by RNA sequencing and manipulated by gene knockdown or neutralising antibodies. Viral replication was quantified by quantitative real-time PCR and 50% tissue culture infective dose. Data were validated in a murine MERS-CoV infection model. Both CsA and ALV reduced MERS-CoV titres and viral RNA replication in Calu-3 cells and hAECs, improving epithelial integrity. While neither calcineurin nor NFAT inhibition reduced MERS-CoV propagation, blockade of c-Jun N-terminal kinase diminished infectious viral particle release but not RNA accumulation. Importantly, CsA induced interferon regulatory factor 1 (IRF1), a pronounced type III interferon (IFNλ) response and expression of antiviral genes. Downregulation of IRF1 or IFNλ increased MERS-CoV propagation in the presence of CsA. Importantly, oral application of CsA reduced MERS-CoV replication in vivo, correlating with elevated lung IFNλ levels and improved outcome. We provide evidence that cyclophilin inhibitors efficiently decrease MERS-CoV replication in vitro and in vivo via upregulation of inflammatory antiviral cell responses, in particular IFNλ. CsA might therefore represent a promising candidate for treating MERS-CoV infection.

In May 2017, at least 12 dogs showed signs of acute neurotoxicosis after swimming in or drinking from Lake Tegel, a mesotrophic lake in Berlin, Germany, and several of the affected dogs died shortly afterwards despite intensive veterinary treatment. Cyanobacterial blooms were not visible at the water surface or the shorelines. However, detached and floating water moss (Fontinalis antipyretica) with high amounts of Tychonema sp., a potential anatoxin-a (ATX) producing cyanobacterium, was found near the beaches where the dogs had been swimming and playing. Necropsies of two of the dogs revealed no specific lesions beside the anamnestic neurotoxicosis. ATX was detected in concentrations up to 8700 µg L−1 in the stomach contents, while other (neuro)toxic substances were not found. In the aqueous fraction of Fontinalis/Tychonema clumps sampled after the casualties, ATX was found in concentrations up to 1870 µg L−1. This is the first report of a dense population of Tychonema sp. in stands of Fontinalis resulting in high ATX contents. This case emphasizes the need for further investigation of potentially toxic, non-bloom forming cyanobacteria in less eutrophic water bodies and underlines the novel challenge of developing appropriate surveillance schemes for respective bathing sites.

In this paper I report results from recent trials in which students used mobile devices to collaboratively create, edit and share trails. These included 9- to 10-year-olds as well as adult diploma students, in the subject of horticulture in botanic gardens. Findings indicate that a narrow subject focus and a manageable amount of data capture are appropriate in most cases; trails are most effective when framed with structured tasks and a narrow focus. Structure can be introduced through the use of collaboration scripts that specify tasks, roles and groups. Findings also show that audio is an important mode for communication and interpretation, particularly when paired with photos; audio alone is effective when location data is known; but photos alone are much less effective. Audio is especially effective when used collaboratively - for example when two people have a conversation or share their impressions while in front of the object or exhibit of interest.

Doctoral training has not been studied in depth as a learning situation, and no learning environment has been designed to specifically support actors involved in the training of future researchers. The research literature on doctoral education indicates that the knowledge about doctoral training needs to be made explicit and formalized. We claim that several problems brought up in the literature on PhD Training could be reduced or solved by a doctoral training environment designed on the basis of a cognitive analysis. Doctoral training in the sciences consists essentially of research training through immersion in scientific communities and activities. Collaborative learning is built in authentic research situations, where doctoral students discover collaborative research. The model of a ‘Collaboratory' provides the foundations for the practice of collaborative research. Future researchers are expected to be competent in practicing ‘E-science' and knowledgeable about distributed research with remote access to shared instruments. The ability to practice ‘Coexperimentation' is part of the research skills. An authoring environment has been prototyped as well as an instantiation of a PhD program in the field of Cognitive Informatics One Use Case consists of two or three research distributed teams sharing observations and discussions, a research training situation involving immersion and collaborative learning. A series of tests and co-experimentations involving Inquiry Learning Environments as a topic of study in the field of Technology-Enhanced Learning was conducted. An international collaboration happened through Kaleidoscope and the coexperimentations were made possible by an optical network infrastructure providing high quality interactions in terms of sharing and telepresence.

The world is changing and changing fast. Contemporary students live in a world full of impressions, fast changing viewpoints, ubiquitous information, zapping behaviour, play and joy etc. They use facilities such as MSN, on-line gaming, and SMS. They expect a seamless access to information, mostly in a social context. At the same time we see drastic changes in learning environments, moving them to rich, multi-media, collaborative, experiential, and individualised environments. Though starting from different angles, these two developments seem to come together. Modern learning environments such as WISE (Slotta, 2004) or BioLogica (Hickey, Kindfield, Horwitz, & Christie, 2003) combine all kinds of opportunities to learn and communicate in a facilitative setting.

In a one-to-one collaborative learning classroom supported by ubiquitous computing, teachers require tools that allow them to design of learning scenarios, and to manage and monitor the activities happening in the classroom. Our project proposes an architecture for a classroom management system and a scenarios designer tool, both based on a Classroom Orchestration Modelling Language (COML), to support these requirements. We are developing and testing this with the GroupScribbles software using a set of learning scenarios for classrooms equipped with pen tablet computers.

To foster synergy between research on collaborative, mobile and inquiry learning and between different scientific and methodological perspectives (namely, educational design, psychology and computer science) and to strengthen the cohesion of the community, the Kaleidoscope network has decided to organise a “Convergence Workshop” in conjunction with the 2006 Contractors' General Assembly in Amsterdam, Dec. 4-6. The two fields of collaborative and inquiry learning have been represented in the network as Special Interest Groups from the beginning. Mobile learning was established more recently as an initiative. The three themes actually complement each other in that collaborative learning focuses on a general modality of learning which is not particularly related to a specific content or domain, whereas inquiry learning does indeed come with a specific domain focus in the areas of science, mathematics and technology. Mobile learning takes up the potential of a new generation of networked interactive and communicative devices. We though this complementarity it would be a good precondition for synergy, but of course we also hope for wider synergies, e.g. with learning at work or AI in education, in the future. In accordance with the idea of stimulating synergy in the network, workshop contributions were sought from within Kaleidoscope in the categories of full paper presentations, young researcher papers and system demos or interactive presentations. Integration of at least two of the three fields of technology enhanced learning as well as multiple methodological perspectives were required for each single paper to be accepted. This collection comprises the five papers that have been selected for publication and for presentation at the workshop in a peer reviewing process. Two of the selected papers are in full paper category (Walker and Bourdeau et al.), one is a young researcher paper (Niramitranon et al.) and two describe system demos (van Joolingen and Bollen et al.). We hope that these presentations at the Convergence Workshop will indeed promote integration and synergy between different lines of research and thus contribute to the advancement and sustainability of the Kaleidoscope network. The Convergence Workshop Task Force

The trendy notion of "mobile learning" has different connotations: On the one hand, it can be understood as "learning on the move" - often referred to as "learning any time anywhere". Of course this interpretation relies on specific kinds of technological enabling, but the definition aims at the general setting of learning activities. Particularly, it includes informal learning settings (cf. [1]). A second interpretation sees mobile learning somewhat more pragmatically as learning with mobile devices. This may include formal learning in the classroom. Here, mobile devices may enable a one-to-one orchestration with learning devices.