2D QSAR and similarity studies on cruzain inhibitors aimed at improving selectivity over cathepsin L

Hologram quantitative structure-activity relationships (HQSAR) were applied to a data set of 41 cruzain inhibitors. The best HQSAR model (Q(2) = 0.77; R-2 = 0.90) employing Surflex-Sim, as training and test sets generator, was obtained using atoms, bonds, and connections as fragment distinctions and 4-7 as fragment size. This model was then used to predict the potencies of 12 test set compounds, giving satisfactory predictive R-2 value of 0,88. The contribution maps obtained from the best HQSAR model are in agreement with the biological activities of the study compounds. The Trypanosoma cruzi cruzain shares high similarity with the mammalian homolog cathepsin L. The selectivity toward cruzam was checked by a database of 123 compounds, which corresponds to the 41 cruzain inhibitors used in the HQSAR model development plus 82 cathepsin L inhibitors. We screened these compounds by ROCS (Rapid Overlay of Chemical Structures), a Gaussian-shape volume overlap filter that can rapidly identify shapes that match the query molecule. Remarkably, ROCS was able to rank the first 37 hits as being only cruzain inhibitors. In addition, the area under the curve (AUC) obtained with ROCS was 0.96, indicating that the method was very efficient to distinguishing between cruzain and cathepsin L inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

Friskfaktorer på en enhet : Identifiera & fortsatt bevara

Detta är en kvalitativ studie med syftet att inom en enhet på Stockholms Stad identifiera friskfaktorer och undersöka vad som krävs för att fortsatt bevara dessa. Vidare är syftet att undersöka vilket stöd som är nödvändigt för bevarandet samt HR-funktionens roll i detta avseende. Enheten är, sett till sjukfrånvaro, en välmående grupp som står inför förändringar inom marknaden och målsättning då de påverkas av det nyligen genomförda regeringsskiftet. Ett frågeverktyg användes för att framställa de åtta viktigaste dimensionerna av det attraktiva arbetet och en fördjupad diskussion kring dessa fördes sedan under en fokusgruppsintervju tillsammans med enhetens medarbetare. Resultatet visade att de viktigaste dimensionerna var bland annat arbetstid och relationer. Vidare påvisades att en balans mellan arbetsliv och privatliv är av stor vikt för medarbetarnas hälsa och välmående. För att fortsatt bevara det attraktiva i arbetet visade empirin att gruppens relationer och ledaren var nyckelfaktorer och att HR-funktionen, den personalstrategiska avdelningen, enbart bidrar med en administrativ och vägledande roll i frågan om stöd. Arbetets slutsatser innefattar att bevarandet av friskfaktorer kräver att tillvaron måste vara begriplig, hanterlig och meningsfull men även att medarbetarna behöver rimliga krav i relation till deras handlingsutrymme. En vidare slutsats är behovet av en förändring i ledarskapsbeteendet i kommande stadier då gruppen eventuellt kommer att hamna i en ny mognadsfas på grund förändrade omständigheter. Författarna drar även slutsatsen att friskfaktorer är till viss del individuellt beroende på livssituation men att balansen mellan arbetsliv och privatliv är betydande för de flesta. HR-funktionen, den personalstrategiska avdelningen, har en informativ och administrativ roll i frågan om stöd och författarna anser att det ligger en logik i denna roll. Sett till organisationens storlek är det lättare att vända psykosociala frågor till företagshälsovård eller en psykologgrupp och få det arbetsrättsliga stödet eller information från HR-funktionen.

Electronically Querying for the Provenance of Entities

The provenance of entities, whether electronic data or physical artefacts, is crucial information in practically all domains, including science, business and art. The increased use of software in automating activities provides the opportunity to add greatly to the amount we can know about an entityâ??s history and the process by which it came to be as it is. However, it also presents difficulties: querying for the provenance of an entity could potentially return detailed information stretching back to the beginning of time, and most of it possibly irrelevant to the querier. In this paper, we define the concept of provenance query and describe techniques that allow us to perform scoped provenance queries.

Personalised Grid Service Discovery

The authors take a broad view that ultimately Grid- or Web-services must be located via personalised, semantic-rich discovery processes. They argue that such processes must rely on the storage of arbitrary metadata about services that originates from both service providers and service users. Examples of such metadata are reliability metrics, quality of service data, or semantic service description markup. This paper presents UDDI-MT, an extension to the standard UDDI service directory approach that supports the storage of such metadata via a tunnelling technique that ties the metadata store to the original UDDI directory. They also discuss the use of a rich, graph-based RDF query language for syntactic queries on this data. Finally, they analyse the performance of each of these contributions in our implementation.

Personalised Grid Service Discovery

We take a broad view that ultimately Grid- or Web-services must be located via personalised, semantic-rich discovery processes. We argue that such processes must rely on the storage of arbitrary metadata about services that originates from both service providers and service users. Examples of such metadata are reliability metrics, quality of service data, or semantic service description markup. This paper presents UDDI-MT, an extension to the standard UDDI service directory approach that supports the storage of such metadata via a tunnelling technique that ties the metadata store to the original UDDI directory. We also discuss the use of a rich, graph-based RDF query language for syntactic queries on this data. Finally, we analyse the performance of each of these contributions in our implementation.

Chained Negotiation for Distributed Notification Services

Distributed notification services allow consumers and publishers of notifications to interact with different notification services. However, such a distributed infrastructure makes it difficult to share notifications between consumers when consumers are allowed to specify Quality of Service levels. In this paper, we present a chained negotiation engine, enabling distributed notification services to support negotiation and to reuse existing subscriptions. We demonstrate the benefit to the system as a whole by reducing load on service providers and enabling content to be shared.

Extracting Causal Graphs from an Open Provenance Data Model

The open provenance architecture (OPA) approach to the challenge was distinct in several regards. In particular, it is based on an open, well-defined data model and architecture, allowing different components of the challenge workflow to independently record documentation, and for the workflow to be executed in any environment. Another noticeable feature is that we distinguish between the data recorded about what has occurred, emphprocess documentation, and the emphprovenance of a data item, which is all that caused the data item to be as it is and is obtained as the result of a query over process documentation. This distinction allows us to tailor the system to separately best address the requirements of recording and querying documentation. Other notable features include the explicit recording of causal relationships between both events and data items, an interaction-based world model, intensional definition of data items in queries rather than relying on explicit naming mechanisms, and emphstyling of documentation to support non-functional application requirements such as reducing storage costs or ensuring privacy of data. In this paper we describe how each of these features aid us in answering the challenge provenance queries.

Leveraging new plans in AgentSpeak(PL)

In order to facilitate the development of agent-based software, several agent programming languages and architectures, have been created. Plans in these architectures are often self-contained procedures with an associated triggering event and a context condition, while any further information about the consequences of executing a plan is absent. However, agents designed using such an approach have limited flexibility at runtime, and rely on the designer’s ability to foresee all relevant situations an agent might have to handle. In order to overcome this limitation, we have created AgentSpeak(PL), an interpreter capable of performing state-space planning to generate new high-level plans. As the planning module creates new plans, the plan library is expanded, improving performance over time. However, for new plans to be useful in the long run, it is critical that the context condition associated with new plans is carefully generated. In this paper we describe a plan reuse technique aimed at improving an agent’s runtime performance by deriving optimal context conditions for new plans, allowing an agent to reuse generated plans as much as possible.

Transparent Provenance Derivation for User Decisions

It is rare for data's history to include computational processes alone. Even when software generates data, users ultimately decide to execute software procedures, choose their configuration and inputs, reconfigure, halt and restart processes, and so on. Understanding the provenance of data thus involves understanding the reasoning of users behind these decisions, but demanding that users explicitly document decisions could be intrusive if implemented naively, and impractical in some cases. In this paper, therefore, we explore an approach to transparently deriving the provenance of user decisions at query time. The user reasoning is simulated, and if the result of the simulation matches the documented decision, the simulation is taken to approximate the actual reasoning. The plausibility of this approach requires that the simulation mirror human decision -making, so we adopt an automated process explicitly modelled on human psychology. The provenance of the decision is modelled in OPM, allowing it to be queried as part of a larger provenance graph, and an OPM profile is provided to allow consistent querying of provenance across user decisions.

Automating the product derivation process of multi-agent systems product lines

Agent-oriented software engineering and software product lines are two promising software engineering techniques. Recent research work has been exploring their integration, namely multi-agent systems product lines (MAS-PLs), to promote reuse and variability management in the context of complex software systems. However, current product derivation approaches do not provide specific mechanisms to deal with MAS-PLs. This is essential because they typically encompass several concerns (e.g., trust, coordination, transaction, state persistence) that are constructed on the basis of heterogeneous technologies (e.g., object-oriented frameworks and platforms). In this paper, we propose the use of multi-level models to support the configuration knowledge specification and automatic product derivation of MAS-PLs. Our approach provides an agent-specific architecture model that uses abstractions and instantiation rules that are relevant to this application domain. In order to evaluate the feasibility and effectiveness of the proposed approach, we have implemented it as an extension of an existing product derivation tool, called GenArch. The approach has also been evaluated through the automatic instantiation of two MAS-PLs, demonstrating its potential and benefits to product derivation and configuration knowledge specification.