La capacité à créer des logiciels auto-diagnosticables et auto-réparables est un véritable défi pour la recherche à venir. Cet article décrit une architecture destinée à la surveillance et au diagnostic de web services. L'une des principales difficultés dans ce contexte est que les pannes se propagent d'un service à l'autre, ce qui fait du diagnostic une étape important pour réagir de manière pertinente. Notre principale contribution est d'étendre l'approche de reconnaissance de chroniques, reconnue comme efficace pour surveiller des systèmes industriels, à un contexte distribué tel que celui des chorégraphies de web services. Nous étudions deux cas, celui où les interactions entre services sont statiques et décrites au départ en WS-CDL et celui où le modèle des interactions est dynamique et doit être construit en ligne. Ce travail a été réalisé et financé dans le cadre du projet européen WS-DIAMOND. ABSTRACT. The ability to create self-healing software is a challenging task for research. This article describes an architecture dedicated to the monitoring and the diagnosis of web services. One of the main difficulties in this context is that faults may propagate from a service to another, which makes of diagnosis a crucial issue in order to react properly. Our main contribution is to extend the chronicle recognition approach to a distributed context such as choreographies of web services. Two cases are studied. In the first one, interactions between services are static and described a priori in WS-CDL; in the second one, the model of interactions is dynamic and built online. This work has been achieved and funded within the framework of the WS-DIAMOND European project.
Purpose
To characterize a novel neurodevelopmental syndrome due to loss-of-function (LoF) variants in Ankyrin 2 (ANK2), and to explore the effects on neuronal network dynamics and homeostatic plasticity in human induced pluripotent stem cell-derived neurons.
Methods
We collected clinical and molecular data of twelve individuals with heterozygous de novo LoF variants in ANK2. We generated a heterozygous LoF allele of ANK2 using CRISPR/Cas9 in human induced pluripotent stem cells (hiPSCs). HiPSCs were differentiated towards excitatory neurons of which we measured spontaneous electrophysiological responses using micro-electrode arrays (MEAs), characterized somatodendritic morphology and axon initial segment (AIS) structure and plasticity.
Results
We found a broad neurodevelopmental disorder, comprising intellectual disability, autism spectrum disorders, and early onset epilepsy. Using MEAs, we found that hiPSC-derived neurons with heterozygous LoF of ANK2 show a hyperactive and desynchronized neuronal network. ANK2 deficient neurons also showed increased somatodendritic structures and altered AIS structure of which its plasticity is impaired upon activity-dependent modulation.
Conclusions
Phenotypic characterization of patients with de novo ANK2 LoF variants define a novel NDD with early onset epilepsy. Our functional in vitro data of ANK2-deficient human neurons show a specific neuronal phenotype in which reduced ANKB expression leads to hyperactive and desynchronized neuronal network activity, increased somatodendritic complexity and AIS structure and impaired activity-dependent plasticity of the AIS.
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