CTLA4-Ig inhibits optimal T helper 2 cell development but not protective immunity or memory response to Nippostrongylus brasiliensis

The B7 co-stimulatory pathway is critical to T cell activation, however its role in the generation of Th2 cells in vivo remains controversial. We have studied the role of B7 co-stimulation in the development of a Th2 immune response to the nematode parasite Nippostrongylus brasiliensis. Blockade of B7 co-stimulation with murine CTLA4-Ig (mCTLA4-Ig) resulted in decreased Th2 cell development as determined by IL-4 and IL-5 cytokine production in vitro. It also resulted in lowered Th2 cell effector function in vivo, with marked reductions in IgE production. Blood eosinophilia was variably affected by mCTLA4-Ig treatment, which resulted in both slight and very severe inhibition in different experiments. However, an effective immune response was still evident as demonstrated by the further reduction of cytokine production, IgE titers, and blood eosinophilia in mice treated with a combination of mCTLA4-Ig and anti-CD4 mAb, and by the ability of mCTLA4-Ig-treated mice to expel adult worms. In addition, mCTLA4-Ig treatment did not alter the development of a memory response following secondary infection with N. brasiliensis, with the exception of IgE production. We conclude from these results that B7 co-stimulation is required in this experimental model for optimal Th2 cell development and effector function in vivo but is not necessary for protective immunity.     

Nanoscale characterisation of ODS-Eurofer 97 steel: An atom-probe tomography study

Laser-pulsed atom-probe tomography has been used to study the nanoscale features present in an ODS-Eurofer 97 alloy. A core/shell structure was found for particles 5-10 nm in diameter. The particle cores were primarily Y and O, enriched with Mn and Si resulting in a metal (Y, Mn and Si) to oxygen ratio of M:O ∼2:3. The ∼2 nm thick outer-shell region of the particles exhibited partitioning of V, Cr, Ta, C and N together with the core elements in many cases. Detailed compositional measurements have also been made on the smallest of the yttria-based oxide clusters down to 2 nm in diameter. The 2 nm clusters were found to have a non-stoichiometric oxide composition, enriched in oxygen compared to Y₂O₃, and evidence for the existence of a shell around these smaller particles was found.     

True quadrature taps for s.a.w. delay lines

A novel technique is described in which a combination of geometrically symmetric and antisymmetric interdigital transducers may be employed to produce a constant 90° phase difference between two taps on a surface-acoustic-wave delay line. This relative phase difference is maintained at 90° over the whole transducer bandwidth.     

Discovery and Biological Characterization of the Auromomycin Chromophore as an Inhibitor of Biofilm Formation in Vibrio cholerae

Bacterial biofilms pose a significant challenge in clinical environments due to their inherent lack of susceptibility to antibiotic treatment. It is widely recognized that most pathogenic bacterial strains in the clinical setting persist in the biofilm state, and are the root cause of many recrudescent infections. The discovery and development of compounds capable of either inhibiting biofilm formation or initiating biofilm dispersal might provide new therapeutic avenues for reducing the number of hospital‐acquired, biofilm‐mediated infections. We detail here the application of our recently reported image‐based, high‐throughput screen to the discovery of microbially derived natural products with inhibitory activity against Vibrio cholerae biofilm. Examination of a prefractionated library of microbially derived marine natural products has led to the identification of a new biofilm inhibitor that is structurally unrelated to previously reported inhibitors and is one of the most potent inhibitors of V. cholerae reported to date. Combination of this compound with sub‐MIC concentrations of a number of clinically relevant antibiotics was shown to improve the inhibitory efficacy of this new compound compared to monotherapy treatments, and provides evidence for the potential therapeutic benefit of biofilm inhibitors in treating persistent biofilm‐mediated infections.     

Reusability through fine-grain inheritance

Object-oriented languages are often promoted as encouraging the production of flexible, reusable software. Unfortunately, experience suggests that although individual classes may be reusable, large class libraries seem to lack flexibility in the face of circumstances unforeseen by the designer. This paper explores the problems associated with flexibility and reuse in large libraries, and shows how fine-grain inheritance can alleviate some of these problems. A methodology for designing fine-grain inheritance graphs is proposed and a detailed case study is presented.     

The UM-MAIS Methodology for Multi-channel Adaptive Web Information Systems

Multichannel Adaptive Web Information Systems (WISs) are emerging as a new class of information systems, characterized by their powerful use of mobility and context-awareness. Different methodologies have been proposed so far for the analysis and design of Multichannel Adaptive WISs, specifically focused on the front-end layer or the back-end layer, but no methodology has aimed to cover all the lifecycle and to design all the components that characterize Multichannel Adaptive WIS. This paper fills such a gap, by presenting UM-MAIS (Unified Methodology for Multichannel Adaptive Information Systems), a new methodology that capitalizes on well-established existing methods. It supports the analysis and design of the various components of Multichannel Adaptive WISs (including the user’s experience) in a comprehensive and unified manner with special emphasis on context modeling, personalization, and adaptation.     

Compile-time and runtime analysis of active behaviors

Active rules may interact in complex and sometimes unpredictable ways, thus possibly yielding infinite rule executions by triggering each other indefinitely. This paper presents analysis techniques focused on detecting termination of rule execution. We describe an approach which combines static analysis of a rule set at compile-time and detection of endless loops during rule processing at runtime. The compile-time analysis technique is based on the distinction between mutual triggering and mutual activation of rules. This distinction motivates the introduction of two graphs defining rule interaction, called Triggering and Activation Graphs, respectively. This analysis technique allows us to identify reactive behaviors which are guaranteed to terminate and reactive behaviors which may lead to infinite rule processing. When termination cannot be guaranteed at compile-time, it is crucial to detect infinite rule executions at runtime. We propose a technique for identifying loops which is based on recognizing that a given situation has already occurred in the past and, therefore, will occur an infinite number of times in the future. This technique is potentially very expensive, therefore, we explain how it can be implemented in practice with limited computational effort. A particular use of this technique allows us to develop cycle monitors, which check that critical rule sequences, detected at compile time, do not repeat forever We bridge compile-time analysis to runtime monitoring by showing techniques, based on the result of rule analysis, for the identification of rule sets that can be independently monitored and for the optimal selection of cycle monitors     

Improving interoperability using vocabulary linked data

The concept of Linked Data has been an emerging theme within the computing and digital heritage areas in recent years. The growth and scale of Linked Data has underlined the need for greater commonality in concept referencing, to avoid local redefinition and duplication of reference resources. Achieving domain-wide agreement on common vocabularies would be an unreasonable expectation; however, datasets often already have local vocabulary resources defined, and so the prospects for large-scale interoperability can be substantially improved by creating alignment links from these local vocabularies out to common external reference resources. The ARIADNE project is undertaking large-scale integration of archaeology dataset metadata records, to create a cross-searchable research repository resource. Key to enabling this cross search will be the ‘subject’ metadata originating from multiple data providers, containing terms from multiple multilingual controlled vocabularies. This paper discusses various aspects of vocabulary mapping. Experience from the previous SENESCHAL project in the publication of controlled vocabularies as Linked Open Data is discussed, emphasizing the importance of unique URI identifiers for vocabulary concepts. There is a need to align legacy indexing data to the uniquely defined concepts and examples are discussed of SENESCHAL data alignment work. A case study for the ARIADNE project presents work on mapping between vocabularies, based on the Getty Art and Architecture Thesaurus as a central hub and employing an interactive vocabulary mapping tool developed for the project, which generates SKOS mapping relationships in JSON and other formats. The potential use of such vocabulary mappings to assist cross search over archaeological datasets from different countries is illustrated in a pilot experiment. The results demonstrate the enhanced opportunities for interoperability and cross searching that the approach offers.     

Effective scheduling of detached rules in active databases

While triggers have become a classical ingredient of relational database systems, research in active databases is aiming at extending the functionality and expressive power of active rules beyond the scope of relational triggers. One of the most important current trend concerns the support of detached active rules, i.e., of rules which are executed as separate transactions, running outside of the scope of the transaction which generates the triggering event. Detached rules have important applications in workflow management and global integrity maintenance across transactions. One of the main issues in designing the rule engine for detached rules is determining their optimal scheduling. In this paper, we study the performance of a detached rule scheduler whose objective is to minimize the interference of detached rule execution with regard to the normal transactional load. This objective is achieved by executing detached rules at given periods of time and by assigning them a fixed amount of dedicated threads; we study the performance of the scheduler relative to the two most critical design parameters, the frequency of execution of the scheduler, and the number of dedicated execution threads.