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- Helbig, K. L., et al.
(författare)
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De Novo Pathogenic Variants in CACNA1E Cause Developmental and Epileptic Encephalopathy with Contractures, Macrocephaly, and Dyskinesias
- 2018
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 103:5, s. 666-678
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Tidskriftsartikel (refereegranskat)abstract
- Developmental and epileptic encephalopathies (DEEs) are severe neurodevelopmental disorders often beginning in infancy or early childhood that are characterized by intractable seizures, abundant epileptiform activity on EEG, and developmental impairment or regression. CACNA1E is highly expressed in the central nervous system and encodes the alpha(1)-subunit of the voltage-gated Ca(V)2.3 channel, which conducts high voltage-activated R-type calcium currents that initiate synaptic transmission. Using next-generation sequencing techniques, we identified de novo CACNA1E variants in 30 individuals with DEE, characterized by refractory infantile-onset seizures, severe hypotonia, and profound developmental impairment, often with congenital contractures, macrocephaly, hyperkinetic movement disorders, and early death. Most of the 14, partially recurring, variants cluster within the cytoplasmic ends of all four S6 segments, which form the presumed Ca(V)2.3 channel activation gate. Functional analysis of several S6 variants revealed consistent gain-of-function effects comprising facilitated voltage-dependent activation and slowed inactivation. Another variant located in the domain II S4-S5 linker results in facilitated activation and increased current density. Five participants achieved seizure freedom on the anti-epileptic drug topiramate, which blocks R-type calcium channels. We establish pathogenic variants in CACNA1E as a cause of DEEs and suggest facilitated R-type calcium currents as a disease mechanism for human epilepsy and developmental disorders.
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| 2. |
- Amato, G., et al.
(författare)
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Robotic Ubiquitous Cognitive Ecology for Smart Homes
- 2015
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Ingår i: Journal of Intelligent and Robotic Systems. - : Springer. - 0921-0296 .- 1573-0409. ; 80, s. S57-S81
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Tidskriftsartikel (refereegranskat)abstract
- Robotic ecologies are networks of heterogeneous robotic devices pervasively embedded in everyday environments, where they cooperate to perform complex tasks. While their potential makes them increasingly popular, one fundamental problem is how to make them both autonomous and adaptive, so as to reduce the amount of preparation, pre-programming and human supervision that they require in real world applications. The project RUBICON develops learning solutions which yield cheaper, adaptive and efficient coordination of robotic ecologies. The approach we pursue builds upon a unique combination of methods from cognitive robotics, machine learning, planning and agent-based control, and wireless sensor networks. This paper illustrates the innovations advanced by RUBICON in each of these fronts before describing how the resulting techniques have been integrated and applied to a proof of concept smart home scenario. The resulting system is able to provide useful services and pro-actively assist the users in their activities. RUBICON learns through an incremental and progressive approach driven by the feedback received from its own activities and from the user, while also self-organizing the manner in which it uses available sensors, actuators and other functional components in the process. This paper summarises some of the lessons learned by adopting such an approach and outlines promising directions for future work.
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| 3. |
- Bacciu, D., et al.
(författare)
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Self-sustaining learning for robotic ecologies
- 2012
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Konferensbidrag (refereegranskat)abstract
- The most common use of wireless sensor networks (WSNs) is to collect environmental data from a specificarea, and to channel it to a central processing node for on-line or off-line analysis. The WSN technology,however, can be used for much more ambitious goals. We claim that merging the concepts and technology ofWSN with the concepts and technology of distributed robotics and multi-agent systems can open new waysto design systems able to provide intelligent services in our homes and working places. We also claim thatendowing these systems with learning capabilities can greatly increase their viability and acceptability, bysimplifying design, customization and adaptation to changing user needs. To support these claims, we illus-trate our architecture for an adaptive robotic ecology, named RUBICON, consisting of a network of sensors,effectors and mobile robots.
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