Inflammation leads through PGE/EP3 signaling to HDAC5/MEF2-dependent transcription in cardiac myocytes

The myocyte enhancer factor 2 (MEF2) regulates transcription in cardiac myocytes and adverse remodeling of adult hearts. Activators of G protein-coupled receptors (GPCRs) have been reported to activate MEF2, but a comprehensive analysis of GPCR activators that regulate MEF2 has to our knowledge not been performed. Here, we tested several GPCR agonists regarding their ability to activate a MEF2 reporter in neonatal rat ventricular myocytes. The inflammatory mediator prostaglandin E2 (PGE2) strongly activated MEF2. Using pharmacological and protein-based inhibitors, we demonstrated that PGE2 regulates MEF2 via the EP3 receptor, the betagamma subunit of Gi/o protein and two concomitantly activated downstream pathways. The first consists of Tiam1, Rac1, and its effector p21-activated kinase 2, the second of protein kinase D. Both pathways converge on and inactivate histone deacetylase 5 (HDAC5) and thereby de-repress MEF2. In vivo, endotoxemia in MEF2-reporter mice induced upregulation of PGE2 and MEF2 activation. Our findings provide an unexpected new link between inflammation and cardiac remodeling by de-repression of MEF2 through HDAC5 inactivation, which has potential implications for new strategies to treat inflammatory cardiomyopathies

Managing expectations: runtime negotiation of information quality requirements in event-based systems

© Springer-Verlag Berlin Heidelberg 2014.Interconnected smart devices in the Internet of Things (IoT) provide fine-granular data about real-world events, leveraged by service-based systems using the paradigm of event-based systems (EBS) for invocation. Depending on the capabilities and state of the system, the information propagated in EBS differs in content but also in properties like precision, rate and freshness. At runtime, consumers have different dynamic requirements about those properties that constitute quality of information (QoI) for them. Current approaches to support quality-related requirements in EBS are either domain-specific or limited in terms of expressiveness, flexibility and scope as they do not allow participants to adapt their behavior. We introduce the generic concept of expectations to express, negotiate and enforce arbitrary requirements about information quality in EBS at runtime. In this paper, we present the model of expectations, capabilities and feedback based on generic properties. Participants express requirements and define individual tradeoffs between them as expectations while system features are expressed as capabilities. We discuss the algorithms to (i) negotiate requirements at runtime in the middleware by matching expectations to capabilities and (ii) adapt participants as well as the middleware. We illustrate the architecture for runtime-support in industry-strength systems by describing prototypes implemented within a centralized and a decentralized EBS

Effective runtime monitoring of distributed event-based enterprise systems with ASIA

Cyber Physical Systems (CPS), interconnected smart devices in the Internet of Things (IoT) and other data sources are increasingly bridging the gap between the physical and digital world by providing fine-grained data about real-world events. Enterprise software systems are adopting the paradigm of event-based systems (EBS) to enable them to react to meaningful events in a timely manner. Smart supply chains fusing dynamic sensor data with information provided by backend-systems are one such example of event-based enterprise systems. Monitoring their global state in an effective way for runtime governance remains an open research challenge: providing the required type of information while trading off precision for costs. We previously introduced application-specific integrated aggregation (ASIA) as a means for collecting metadata in distributed event-based systems. In this paper, we show how ASIA can support IT Service Management in monitoring and governing decentralized event-based enterprise systems at runtime. We present a dashboard based on industry-strength technology as proof of concept and discuss how to integrate usage statistics provided on-the-fly by ASIA into metrics for runtime governance. We evaluate our monitoring approach in terms of performance, scalability and precision

C.: Emergence as Competitive Advantage - Engineering Tomorrow’s Enterprise Software Systems

Companies rely heavily on complex software systems and tightly integrated supply-chains to serve their customers in increasingly fast changing markets. To gain competitive advantage in such a setting, companies must adapt their processes, products and inter-organizational relationships quickly to changing environments. In the future, enterprise software systems must be explicitly designed for flexibly switching intensive interorganizational relationships and for rapidly implementing changes in requirements or context while retaining existing functionality and user acceptance. In this position paper we introduce the notion of emergence in enterprise software systems as a guiding principle. Emergent Enterprise Software Systems (EESS) will be capable of reacting to changes in the environment by adapting their behavior and exposing new functionality. The consequent challenges we face when designing, building and operating EESS are discussed