Folded Interaction Systems and Their Application to the Survivability Analysis of Unbounded Systems

Modeling the fulfillment of global properties like survivability is a challenging problem in unbounded systems such as Grids, peer-to-peer systems, or swarms. This paper proposes Folded Interaction Systems (FIS), an extension of the classic I-Systems framework, to overcome the modeling issues. FIS is applied to a case of survivability assessment in Grids and demonstrates the identification of essential capabilities, the modeling of harmful incidents, and the derivation of standard strategies to sustain the survival of a system’s mission. FIS is not restricted to survivability, it can be used for investigating the preservation of any global property

Management dynamischer Virtueller Organisationen in Grids

Seit Mitte der 1990er Jahre wird unter dem Grid-Problem allgemein das koordinierte Problemlösen und die gemeinschaftliche Nutzung von Ressourcen in dynamischen, multi-institutionellen, Virtuellen Organisationen verstanden. Das Konzept Virtueller Organisationen (VO) ist damit für Grids von zentraler Bedeutung. Intuitiv bestehen VOs aus Personen und/oder technischen Ressourcen autonomer realer Organisationen. Der für VOs typische Lebenszyklus impliziert zahlreiche, zum Teil neue, Anforderungen nicht nur an die Bereitstellung von Grid-Ressourcen, sondern insbesondere auch an das Management von VOs selbst. Fragen nach gezielter IT-Unterstützung in der Formation, dem Betrieb, und der Auflösung von VOs rücken in Grids immer mehr in den Vordergrund. Trotz der drängenden Notwendigkeit eines auch gerade VOs als managed objects umfassenden, integrierten Grid-Management-Ansatzes, sind die Fragestellungen bezüglich der hierzu erforderlichen Architekturen, Plattformen und Betriebskonzepte noch weitgehend ungeklärt. Existierende Konzepte liegen bestenfalls für einzelne Teilaspekte vor (z.B. dem Mitgliedsmanagement). Bestätigt wird dies durch eine Analyse bestehender Architekturkonzepte, deren zum Teil erhebliche Defizite auf die aktuelle betriebliche Praxis im Grid-Management und den vereinfachend getroffenen Annahmen zu Lebensdauer, Gründungsprozess oder Kooperationsstruktur von VOs zurückzuführen sind. Die Dissertation verfolgt das Ziel, eine VO-Managementarchitektur (VOMA), in der die Managementobjekte dynamische Virtuelle Organisationen sind, zu entwickeln. Im Informationsmodell der Architektur wird für alle am VO-Management beteiligten Rollen ein gemeinsames Verständnis über die auszutauschenden Managementinformationen festgelegt. Das Organisationsmodell identifiziert die am VO-Management beteiligten Rollen und ordnet ihnen entsprechende Handlungsdomänen zu. Im Kommunikationsmodell werden die spezifischen Anforderungen an die Kommunikationsmechanismen dieser Rollen spezifiziert. Im Funktionsmodell wird der Gesamtaufgabenkomplex des VO-Managements auf der Basis der anderen Teilmodelle in einzelne Funktionsbereiche gegliedert, die sich an VO-Lebenszyklen orientieren. Während VOMA zunächst Plattform-unabhängig spezifiziert wird -- und damit ein allgemeines Rahmenwerk liefert, muss die Architektur für einen realen Einsatz Plattform-spezifisch transformiert werden. Dies wird am Beispiel des Web Services Distributed Management gezeigt. Zudem wird geklärt, wie die Architektur in bestehende oder zukünftige Grid-Projekte integriert werden kann. Dazu wird VOMA um eine Infrastrukturkomponente (VOMA-I) erweitert, über die VOMA an Hand von Konfigurationsmustern in einem klassischen Manager/Agenten-Paradigma zum Einsatz gebracht werden kann. Die Tragfähigkeit des Konzeptes wird an Beispielen demonstriert. Eine Zusammenfassung der erzielten Ergebnisse und ein Ausblick auf weiterführende Forschungsthemen runden die Arbeit schließlich ab

DRIHM - An Infrastructure To Advance Hydro-Meteorological Research

One of the main challenges in hydro-meteorological research (HMR) is predicting the impact of weather and climate changes on the environment, society and economy, including local severe hazards such as floods and landslides. At the heart of this challenge lies the ability to have easy access to hydro-meteorological data and models, and facilitate the collaboration across discipline boundaries. Within the DRIHM project (Distributed Research Infrastructure for Hydro-Meteorology, www.drihm.eu, EC funded FP7 project 2011-2015) we develop a prototype e-Science environment to facilitate this collaboration and provide end-to-end HMR services (models, datasets, and post-processing tools) at the European level, with the ability to expand to global scale. The objectives of DRIHM are to lead the definition of a common long-term strategy, to foster the development of new HMR models, workflows and observational archives for the study of severe hydro-meteorological events, to promote the execution and analysis of high-end simulations, and to support the dissemination of predictive models as decision analysis tools. For this we implement a service portal to construct heterogeneous simulation workflows that can include deterministic and ensemble runs on a heterogeneous infrastructure consisting of HPC, grid and Windows cloud resources. Via another FP7 project called DRIHM2US (www.drihm2us.eu) we collaborate with the NSF funded SCIHM project (www.scihm.org) to build a wider international collaborative network. This contribution will provide a sketch of the DRIHM architecture and show some use cases such as the November 2011 Genoa flooding

Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2

Despite their central importance in mammalian development, the mechanisms that regulate the DNA methylation machinery and thereby the generation of genomic methylation patterns are still poorly understood. Here, we identify the 5mC-binding protein MeCP2 as a direct and strong interactor of DNA methyltransferase 3( DNMT3) proteins. We mapped the interaction interface to the transcriptional repression domain of MeCP2 and the ADD domain of DNMT3A and find that binding of MeCP2 strongly inhibits the activity of DNMT3A in vitro. This effect was reinforced by cellular studies where a global reduction of DNA methylation levels was observed after overexpression of MeCP2 in human cells. By engineering conformationally locked DNMT3A variants as novel tools to study the allosteric regulation of this enzyme, we show that MeCP2 stabilizes the closed, autoinhibitory conformation of DNMT3A. Interestingly, the interaction with MeCP2 and its resulting inhibition were relieved by the binding of K4 unmodified histone H3 N-terminal tail to the DNMT3A-ADD domain. Taken together, our data indicate that the localization and activity of DNMT3A are under the combined control of MeCP2 and H3 tailmodifications where, depending on the modification status of the H3 tail at the binding sites, MeCP2 can act as either a repressor or activator of DNA methylation

Towards A Grid Infrastructure For Hydro-Meteorological Research

The Distributed Research Infrastructure for Hydro-Meteorological Study (DRIHMS) is a coordinatedaction co-funded by the European Commission. DRIHMS analyzes the main issuesthat arise when designing and setting up a pan-European Grid-based e-Infrastructure for researchactivities in the hydrologic and meteorological fields. The main outcome of the projectis represented first by a set of Grid usage patterns to support innovative hydro-meteorologicalresearch activities, and second by the implications that such patterns define for a dedicatedGrid infrastructure and the respective Grid architecture

Generic pregabalin : current situation and implications for health authorities, generics and biosimilars manufacturers in the future

The manufacturer of pregabalin has a second use patent covering prescribing for neuropathic pain: its principal indication. The manufacturer has threatened legal action in the UK if generic pregabalin rather than Lyrica is prescribed for this indication. No problems exist for practitioners who prescribe pregabalin for epilepsy or generalized anxiety disorder. This has serious implications for health authorities. In Germany, however, generics could be legally prescribed for any approved indication once one indication loses its patent. We aim to establish the current situation with pregabalin among principally European countries. Personnel from 33 regional and national health authorities mainly from Europe, and nine from universities across Europe working as advisers to health authorities or with insight into their activities, were surveyed regarding four specific questions via email to shed light on the current situation with Lyrica and pregabalin in their country. The information collated from each country was subsequently checked for accuracy with each co-author by email and face-to-face contact and collated into five tables. The scenarios ranged from extending the patent life of Lyrica (e.g. France), endorsing the prescribing of Lyrica for neuropathic pain (e.g. Catalonia and South Korea), and current prescribing of pregabablin for all indications (e.g. Serbia and Germany). Little activity has taken place in European countries in which generic pregabalin is not yet reimbursed. The availability of generic pregabalin has prompted a number of different activities to be undertaken among the 33 countries and regions surveyed. The situation in Serbia and the historic situation in Germany provide examples of ways to maximize savings once a product loses its patent for at least one indication

Solid-state interconversions: Unique 100% reversible transformations between the ground and metastable states in single-crystals of a series of nickel( II) nitro complexes

The solid-state, low-temperature linkage isomerism in a series of five square planar group 10 phosphino nitro complexes have been investigated by a combination of photocrystallographic experiments, Raman spectroscopy and computer modelling. The factors influencing the reversible solid-state interconversion between the nitro and nitrito structural isomers have also been investigated, providing insight into the dynamics of this process. The cis-[Ni(dcpe)(NO2)2] (1) and cis-[Ni(dppe)(NO2)2] (2) complexes show reversible 100 % interconversion between the η1-NO2 nitro isomer and the η1-ONO nitrito form when single-crystals are irradiated with 400 nm light at 100 K. Variable temperature photocrystallographic studies for these complexes established that the metastable nitrito isomer reverted to the ground-state nitro isomer at temperatures above 180 K. By comparison, the related trans complex [Ni(PCy3)2(NO2)2] (3) showed 82 % conversion under the same experimental conditions at 100 K. The level of conversion to the metastable nitrito isomers is further reduced when the nickel centre is replaced by palladium or platinum. Prolonged irradiation of the trans-[Pd(PCy3)2(NO2)2] (4) and trans-[Pt(PCy3)2(NO2)2] (5) with 400 nm light gives reversible conversions of 44 and 27 %, respectively, consistent with the slower kinetics associated with the heavier members of group 10. The mechanism of the interconversion has been investigated by theoretical calculations based on the model complex [Ni(dmpe)Cl(NO2)]