The endocannabinoid system in the development of the central nervous system: Functions and importance

Το ενδοκανναβινοειδές σύστημα (ECS) αποτελείται από τους υποδοχείς κανναβινοειδών και τους συνδέτες τους, δηλαδή τα ενδογενή κανναβινοειδή (eCBs), καθώς και από τα ένζυμα που είναι υπεύθυνα για τη σύνθεση και την αποδόμηση των ενδοκανναβινοειδών. Και οι δύο υποδοχείς κανναβινοειδών CB1 και CB2 είναι υποδοχείς συζευγμένοι με πρωτεΐνη G (GPCRs), όταν ενεργοποιούνται από τα ενδοκανναβινοειδή ή εξωγενούς συνδέτες, ασκούν τις δράσεις τους μέσω της αναστολής της αδενυλικής κυκλάσης και της ρύθμισης των διαύλων ιόντων ή μέσω της ενεργοποίησης του PLC και της διέγερσης του μονοπατιού των MAP κινασών. Τα κύρια ενδοκανναβινοειδή (eCB) είναι η 2-αραχιδονυλ-γλυκερόλη (2AG) και το Ν-αραχιδονυλ-αιθανολαμίδιο (AEA, ανανδαμίδιο), ενώ οι πιο συνηθισμένοι εξωγενείς αγωνιστές περιλαμβάνουν τη Δ9-τετραϋδροκανναβινόλη (THC) και την κανναβιδιόλη (CBD), η οποίο προέρχεται από το φυτό κάνναβης, μια βοτανική κατηγορία ποικιλιών Cannabis sativa που συνταγογραφείται για την επιληψία. Οι υποδοχείς CB1 είναι οι πιο άφθονοι GPCR στο κεντρικό νευρικό σύστημα, ειδικά στον νεοφλοιό, τον ιππόκαμπο, τα βασικά γάγγλια και την παρεγκεφαλίδα. Είναι ενεργοί σε θέσεις συναπτικής δραστηριότητας, κυρίως προσυναπτικά, με υψηλή προτίμηση για τους ανασταλτικούς GABA νευρώνες έναντι των διεγερτικών γλουταμινεργικών. Ως εκ τούτου, το σύστημα σηματοδότησης ενδοκανναβινοειδών παίζει βασικό ρόλο στη ρύθμιση της απελευθέρωσης νευροδιαβιβαστών, της νευρικής διεγερσιμότητας, της μετάδοσης του νευρικού σήματος, της μακροπρόθεσμης ενίσχυσης, της νευρογένεσις, του προγραμματισμένου κυτταρικού θανάτου, της κυτταρικής διαφοροποίησης, της μετανάστευσης των κυττάρων, καθώς και στη συναπτική πλαστικότητα. Τα ευρήματα αυτά δείχνουν τον σημαντικό ρόλο των Ενδοκανναβινοειδών στην ανάπτυξη του κεντρικού νευρικού συστήματος.The endocannabinoid system (ECS) consists of the cannabinoid receptors and their ligands, that is the endogenous cannabinoids (eCBs), as well as the enzymes that are responsible for the synthesis and degradation of the endocannabinoids. Both the cannabinoid receptors CB1 and CB2 are G protein- coupled receptors (GPCRs) and, when activated by the endocannabinoids or exogenously ligands, exert their actions through inhibition of adenylyl cyclase and modulation of ion channels, or through activation of PLC and stimulation of the MAP kinases pathway. The main eCBs are 2-arachidonoyl glycerol (2AG) and N-arachidonoyl ethanolamide (AEA, anandamide), while the most common exogenous agonists include Δ9-tetrahydrocannabinol (THC), the potential intoxicating component of the cannabis sativa plant, and Cannabidiol (CBD), which derives from the hemp plant, a botanical class of Cannabis sativa cultivars, and is prescribed for epilepsy. CB1 receptors are the most abundant GPCRs in the central nervous system, especially in the neocortex, hippocampus, basal ganglia, and cerebellum, while some are also found in the peripheral nerve terminals, the spleen, the stomach, and the testis. Very interesting is the fact that CB1 receptors are highly enriched and thus active in sites of synaptic activity, primarily at presynaptic and axonal compartments, with a high preference for the inhibitory GABAergic neurons over the excitatory glutamatergic ones. Hence, the endocannabinoid (eCB) signaling system plays key roles in the regulation of neurotransmitter release, neural excitability, impulse spread, long-term potentiation, neurogenesis, programmed cell death, lineage segregation, cell migration, as well as in synaptic plasticity. These findings show the important role of endocannabinoids in the development of the central nervous system

myWebAccess: A platform for repairing, enhancing and re-distributing Web Services accessible to people with disability

International audienceWeb services are an emerging technology which has attracted much attention from both the research and the industry sectors in recent years. The exploitation of web services as components in web applications facilitates development and supports applications interoperability, regardless of the programming language and platform used. However, existing web services development standards do not take into account the fact that the provided content and the interactive functionality should be accessible to, and easily operable by, people with disabilities. This paper presents a platform named myWebAccess, which provides a mechanism for the semi-automated "repair" of web services' interaction characteristics in order to support the automatic generation of interface elements that conform to the de facto standard of the Web Content Accessibility Guidelines 2.0. myWebAccess enhances interaction quality for specific target user groups, including people with visual and motor disabilities, and supports the use of web services on diverse platforms (e.g., mobile phones equipped with a browser). The users of myWebAccess can create a personalized environment containing their favourite services, and can interact with them through interfaces appropriate to their specific individual characteristics

Interconnecting and Monitoring Heterogeneous Things in IoT Applications

International audienceInternet of Things (IoT) applications incorporate heterogeneous devices that employ different middleware protocols (MQTT, CoAP, WebSocket, etc). In this paper we present an extension of our cross-integration platform which supports the interoperability of IoT devices. In particular, we introduce the VSB Web Console which enables the development and monitoring of applications with heterogeneous IoT devices. We showcase our approach using the Fire Detection scenario

Probabilistic Event Dropping for Intermittently Connected Subscribers over Pub/Sub Systems

International audienceInternet of Things (IoT) aim to leverage data from multiple sensors, actuators and devices for improving peoples' daily life and safety. Multiple data sources must be integrated, analyzed from the corresponding application and notify interested stakeholders. To support the data exchange between data sources and stakeholders, the publish/subscribe (pub/sub) middleware is often employed. Pub/sub provides additional mechanisms such as reliable messaging, event dropping, prioritization, etc. The event dropping mechanism is often used to satisfy Quality of Service (QoS) requirements and ensure system stability. To enable event dropping, basic approaches apply finite buffers or data validity periods and more sophisticated ones are information-aware. In this paper, we introduce a pub/sub mechanism for probabilistic event dropping by considering the stakeholders' intermittent connectivity and QoS requirements. We model the pub/sub middleware as a network of queues which includes a novel ON/OFF queueing model that enables the definition of join probabilities. We validate our analytical model via simulation and compare our mechanism with existing ones. Experimental results can be used as insights for developing hybrid dropping mechanisms

Timed protocol analysis of interconnected mobile IoT devices

International audienceWith the emergence of the Internet of Things (IoT), application developers can rely on a variety of protocols and Application Programming Interfaces (APIs) to support data exchange between IoT devices. However, this may result in highly heterogeneous IoT interactions in terms of both functional and non-functional semantics. To map between heterogeneous functional semantics, middleware connectors can be utilized to interconnect IoT devices via bridging mechanisms. In this paper, we make use of the Data eXchange (DeX) connector model that enables interoperability among heterogeneous IoT devices. DeX interactions, including synchronous, asynchronous and streaming, rely on generic post and get primitives to represent IoT device behaviors with varying space/time coupling. Nevertheless, non-functional time semantics of IoT interactions such as data availability/validity, intermittent connectivity and application processing time, can severely affect response times and success rates of DeX interactions. We introduce timing parameters for time semantics to enhance the DeX API. The new DeX API enables the mapping of both functional and time semantics of DeX interactions. By precisely studying these timing parameters using timed automata models, we verify conditions for successful interactions with DeX connectors. Furthermore, we statistically analyze through simulations the effect of varying timing parameters to ensure higher probabilities of successful interactions. Simulation experiments are compared with experiments run on the DeX Mediators (DeXM) framework to evaluate the accuracy of the results. This work can provide application developers with precise design time information when setting these timing parameters in order to ensure accurate runtime behavior

Evaluating the Ease of Application Development for the Internet of Things

The Internet of Things (IoT) combines Wireless Sensor and Actuator Network (WSAN) (the challenge of large scale of systems), pervasive computing (the challenge of heterogeneity of nodes and the user's own interaction with these nodes), and the elements of the "traditional" Internet such as web and database servers. An important challenge in such a diverse and multidisciplinary field is the ease of application development for the stakeholders, who are involved in the IoT application development process. Several application development approaches have been proposed to address this challenge in the related field of WSANs and pervasive computing. However, very few approaches for IoT applications have evaluated their programming framework on factors such as expressiveness and development effort. The former guides the stakeholders to identify a suitable approach for given application requirements at hand. The latter helps the stakeholders the lines of code that need to be written to develop the IoT application, which involves large number of heterogeneous devices. In this paper, we evaluate our previously proposed model-driven approach, which supports the development of IoT applications, on two factors: expressiveness and development effort. The results of the expressiveness clearly indicate the subset of IoT application characteristics that can be suitably developed in our framework. Our evaluation results of the development effort show that (1) our approach drastically reduce development effort for developing IoT applications compared to node-level programming. (2) the reusability of specification and implementation across the same application domain, thus reducing development effort

Simulation-based Queueing Models for Performance Analysis of IoT Applications

International audienceTo facilitate the development of Internet of Things (IoT) applications, numerous middleware protocols and APIs have been introduced. Such applications built atop reliable or unreliable protocols and they expose different characteristics. Additionally, with regard to the application context (e.g., emergency response operations), several Quality of Service (QoS) requirements must be satisfied. To study QoS in IoT applications, the provision of a generic performance analysis methodology is required. Queueing network models offer a simple modeling environment, which can be used to represent IoT interactions by combining multiple queueing model types for building queueing networks. The resulting networks can be used for performance analysis through analytical or simulation models. In this paper, we present several types of queueing models that represent different QoS settings of IoT interactions, such as intermittent mobile connectivity, message drop probabilities, message availability/validity and resource constrained devices. Using MobileJINQS, we simulate our models demonstrating the significant effect on response times and message success rates when varying QoS settings

Performance Modeling of the Middleware Overlay Infrastructure of Mobile Things

International audienceInternet of Things (IoT) applications consist of diverse Things (sensors and devices) in terms of hardware resources. Furthermore, such applications are characterized by the Things' mobility and multiple interaction types, such as synchronous, asynchronous, and streaming. Middleware IoT protocols consider the above limitations and support the development of effective applications by providing several Quality of Service features. These features aim to enable application developers to tune an application by switching different levels of response times and delivery success rates. However, the profusion of the developed IoT protocols and the intermittent connectivity of mobile Things, result to a non-trivial application tuning. In this paper, we model the performance of the middleware overlay infrastructure using Queueing Network Models. To represent the mobile Thing's connections/disconnections, we model and solve analytically an ON/OFF queueing center. We apply our approach to Streaming interactions with mobile peers. Finally, we validate our model using simulations. The deviations between the performance results foreseen by the analytical model and the ones provided by the simulator are shown to be less than 5%

Timeliness Evaluation of Intermittent Mobile Connectivity over Pub/Sub Systems

International audienceSystems deployed in mobile environments are typically characterized by intermittent connectivity and asynchronous sending/reception of data. To create effective mobile systems for such environments, it is essential to guarantee acceptable levels of timeliness between sending and receiving mobile users. In order to provide QoS guarantees in different application scenarios and contexts, it is necessary to model the system performance by incorporating the intermittent connectivity. Queueing Network Models (QNMs) offer a simple modeling environment, which can be used to represent various application scenarios, and provide accurate analytical solutions for performance metrics, such as system response time. In this paper, we provide an analytical solution regarding the end-to-end response time between users sending and receiving data by modeling the intermittent connectivity of mobile users with QNMs. We utilize the publish/subscribe (pub/sub) middleware as the underlying communication infrastructure for the mobile users. To represent the user's connections/disconnections, we model and solve analytically an ON/OFF queueing system by applying a mean value approach. Finally, we validate our model using simulations with real-world workload traces. The deviations between the performance results foreseen by the analytical model and the ones provided by the simulator are shown to be less than 5% for a variety of scenarios