118 research outputs found

    From Physical to Virtual: Widening the Perspective on Multi-Agent Environments

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    The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-319-23850-0_9Since more than a decade, the environment is seen as a key element when analyzing, developing or deploying Multi-Agent Systems (MAS) applications. Especially, for the development of multi-agent platforms it has become a key concept, similarly to many application in the area of location-based, distributed systems. An emerging, prominent application area for MAS is related to Virtual Environments. The underlying technology has evolved in a way, that these applications have grown out of science fiction novels till research papers and even real applications. Even more, current technologies enable MAS to be key components of such virtual environments. In this paper, we widen the concept of the environment of a MAS to encompass new and mixed physical, virtual, simulated, etc. forms of environments. We analyze currently most interesting application domains based on three dimensions: the way different "realities" are mixed via the environment, the underlying natures of agents, the possible forms and sophistication of interactions. In addition to this characterization, we discuss how this widened concept of possible environments influences the support it can give for developing applications in the respective domains.Carrascosa Casamayor, C.; Klugl, F.; Ricci, A.; Boissier, O. (2015). From Physical to Virtual: Widening the Perspective on Multi-Agent Environments. En Agent Environments for Multi-Agent Systems IV. 4th International Workshop, E4MAS 2014 - 10 Years Later, Paris, France, May 6, 2014. 133-146. https://doi.org/10.1007/978-3-319-23850-0_9S133146Aggarwal, J.K., Ryoo, M.S.: Human activity analysis: a review. ACM Comput. 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Springer, Heidelberg (2007)Weyns, D., Omicini, A., Odell, J.: Environment as a first class abstraction in multiagent systems. Auton. Agent. Multi-Agent Syst. 14(1), 5–30 (2007)Weyns, D., Schelfthout, K., Holvoet, T., Lefever, T.: Decentralized control of e’gv transportation systems. In: Proceedings of the Fourth International Joint Conference on Autonomous Agents and Multiagent Systems, pp. 67–74. ACM (2005)Weyns, D., Schumacher, M., Ricci, A., Viroli, M., Holvoet, T.: Environments in multiagent systems. Knowl. Eng. Rev. 20(2), 127–141 (2005

    Expression of RNA interference triggers from an oncolytic herpes simplex virus results in specific silencing in tumour cells in vitro and tumours in vivo

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    <p>Abstract</p> <p>Background</p> <p>Delivery of small interfering RNA (siRNA) to tumours remains a major obstacle for the development of RNA interference (RNAi)-based therapeutics. Following the promising pre-clinical and clinical results with the oncolytic herpes simplex virus (HSV) OncoVEX<sup>GM-CSF</sup>, we aimed to express RNAi triggers from oncolytic HSV, which although has the potential to improve treatment by silencing tumour-related genes, was not considered possible due to the highly oncolytic properties of HSV.</p> <p>Methods</p> <p>To evaluate RNAi-mediated silencing from an oncolytic HSV backbone, we developed novel replicating HSV vectors expressing short-hairpin RNA (shRNA) or artificial microRNA (miRNA) against the reporter genes green fluorescent protein (eGFP) and ÎČ-galactosidase (lacZ). These vectors were tested in non-tumour cell lines <it>in vitro </it>and tumour cells that are moderately susceptible to HSV infection both <it>in vitro </it>and in mice xenografts <it>in vivo</it>. Silencing was assessed at the protein level by fluorescent microscopy, x-gal staining, enzyme activity assay, and western blotting.</p> <p>Results</p> <p>Our results demonstrate that it is possible to express shRNA and artificial miRNA from an oncolytic HSV backbone, which had not been previously investigated. Furthermore, oncolytic HSV-mediated delivery of RNAi triggers resulted in effective and specific silencing of targeted genes in tumour cells <it>in vitro </it>and tumours <it>in vivo</it>, with the viruses expressing artificial miRNA being comprehensibly more effective.</p> <p>Conclusions</p> <p>This preliminary data provide the first demonstration of oncolytic HSV-mediated expression of shRNA or artificial miRNA and silencing of targeted genes in tumour cells <it>in vitro </it>and <it>in vivo</it>. The vectors developed in this study are being adapted to silence tumour-related genes in an ongoing study that aims to improve the effectiveness of oncolytic HSV treatment in tumours that are moderately susceptible to HSV infection and thus, potentially improve response rates seen in human clinical trials.</p

    TMEM107 recruits ciliopathy proteins to subdomains of the ciliary transition zone and causes Joubert syndrome

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    The transition zone (TZ) ciliary subcompartment is thought to control cilium composition and signalling by facilitating a protein diffusion barrier at the ciliary base. TZ defects cause ciliopathies such as Meckel–Gruber syndrome (MKS), nephronophthisis (NPHP) and Joubert syndrome1 (JBTS). However, the molecular composition and mechanisms underpinning TZ organization and barrier regulation are poorly understood. To uncover candidate TZ genes, we employed bioinformatics (coexpression and co-evolution) and identified TMEM107 as a TZ protein mutated in oral–facial–digital syndrome and JBTS patients. Mechanistic studies in Caenorhabditis elegans showed that TMEM-107 controls ciliary composition and functions redundantly with NPHP-4 to regulate cilium integrity, TZ docking and assembly of membrane to microtubule Y-link connectors. Furthermore, nematode TMEM-107 occupies an intermediate layer of the TZ-localized MKS module by organizing recruitment of the ciliopathy proteins MKS-1, TMEM-231 (JBTS20) and JBTS-14 (TMEM237). Finally, MKS module membrane proteins are immobile and super-resolution microscopy in worms and mammalian cells reveals periodic localizations within the TZ. This work expands the MKS module of ciliopathy-causing TZ proteins associated with diffusion barrier formation and provides insight into TZ subdomain architecture

    Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

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    Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

    Potential Source Apportionment and Meteorological Conditions Involved in Airborne 131 I Detections in January/February 2017 in Europe

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    International audienceTraces of particulate radioactive iodine (131I) were detected in the European atmosphere in January/February 2017. Concentrations of this nuclear fission product were very low, ranging 0.1 to 10 ĂŽÂŒBq m-3 except at one location in western Russia where they reached up to several mBq m-3. Detections have been reported continuously over an 8-week period by about 30 monitoring stations. We examine possible emission source apportionments and rank them considering their expected contribution in terms of orders of magnitude from typical routine releases: radiopharmaceutical production units &gt; sewage sludge incinerators &gt; nuclear power plants &gt; spontaneous fission of uranium in soil. Inverse modeling simulations indicate that the widespread detections of 131I resulted from the combination of multiple source releases. Among them, those from radiopharmaceutical production units remain the most likely. One of them is located in Western Russia and its estimated source term complies with authorized limits. Other existing sources related to 131I use (medical purposes or sewage sludge incineration) can explain detections on a rather local scale. As an enhancing factor, the prevailing wintertime meteorological situations marked by strong temperature inversions led to poor dispersion conditions that resulted in higher concentrations exceeding usual detection limits in use within the informal Ring of Five (Ro5) monitoring network. © 2018 American Chemical Society

    Developing an Objective Framework to Evaluate Street Functions

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    Urban street networks are a vital part of urban areas and have a remarkable influence over quality of life and the use of sustainable modes. They make up about 80% of public space and shape urban activities and identity. Therefore, it is crucial to design, develop, and maintain streets in such a way as to make the most of this large and important space in a sustainable manner. Streets have three main functions: to provide access to adjoining properties, to allow transit of users on their way from their origin to their destination, and to provide space for social activities. As such, there is a need to develop indicators, methods, and tools to evaluate how streets fulfill their functions. However, most of the previously developed frameworks rely on measuring the physical environment and transportation facilities, which reflect the potential use of streets, as opposed to their actual use. To address this gap, the main objective of this paper is to propose a holistic and objective framework to evaluate streets based on their actual use by all users. The proposed framework is developed based on direct user observation to assess the various street functions (i.e., transit, access, and place) using objective indicators at a microscopic (individual) level. The developed framework and tools build on street use evaluation by diverse disciplines such as transportation engineering, urban planning, and public health. It will help transportation agencies and urban planners to manage streets and public spaces so that they fulfill their expected functions while minimizing the negative impacts
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