158 research outputs found

    Molecular modelling of antibody combining sites

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    Provinciality and the Art World: The Midland Group 1961- 1977

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    This paper takes as its focus the Midland Group Gallery in order to first, make a case for the consideration of the geographies of art galleries. Second, highlight the importance of galleries in the context of cultural geographies of the sixties. Third, discuss the role of provinciality in the operation of art worlds. In so doing it explicates one set of geographies surrounding the gallery – those of the local, regional and international networks that connected to produce art works and art space. It reveals how the interactions between places and practices outside of metropolitan and regional hierarchies provides a more nuanced insight into how art worlds operated during the sixties, a period of growing internationalism of art, and how contested definitions of the provincial played an integral role in this. The paper charts the operations of the Midland Group Gallery and the spaces that it occupied to demonstrate how it was representative of a post-war discourse of provincialism and a corresponding re-evaluation of regional cultural activity

    Actors and networks or agents and structures: towards a realist view of information systems

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    Actor-network theory (ANT) has achieved a measure of popularity in the analysis of information systems. This paper looks at ANT from the perspective of the social realism of Margaret Archer. It argues that the main issue with ANT from a realist perspective is its adoption of a `flat' ontology, particularly with regard to human beings. It explores the value of incorporating concepts from ANT into a social realist approach, but argues that the latter offers a more productive way of approaching information systems

    Intelligent transport systems harmonisation assessment: use case of some Spanish intelligent transport systems services

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    From the 1980s, new telematic technologies have meant a great evolution in several areas. In the transportation domain, their use has implied the development and implementation of several intelligent transport systems (ITS). However, these deployments were done in an isolated way. Traffic managers, public and private organisations, stakeholders and others have implemented ITS without much perspective, that is, without providing ITS as services for end users. In the last few years, several European Union (EU) funded projects have been dealing with the development of harmonised ITS services. For example, the EasyWay Project is involving most of the European countries (EU member states and others) to deploy harmonised ITS services taking into account the European citizen as the final target. In this study, an introduction of the EasyWay project is made, including the ITS concept services and the deployment guidelines for harmonisation. In November 2012, EasyWay presented a new version of DGs, which were approved with minor editorial changes. An overview on these DGs for the ITS services is presented and two real Spanish road traffic ITS services are analysed

    RosettaAntibody: antibody variable region homology modeling server

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    The RosettaAntibody server (http://antibody.graylab.jhu.edu) predicts the structure of an antibody variable region given the amino-acid sequences of the respective light and heavy chains. In an initial stage, the server identifies and displays the most sequence homologous template structures for the light and heavy framework regions and each of the complementarity determining region (CDR) loops. Subsequently, the most homologous templates are assembled into a side-chain optimized crude model, and the server returns a picture and coordinate file. For users requesting a high-resolution model, the server executes the full RosettaAntibody protocol which additionally models the hyper-variable CDR H3 loop. The high-resolution protocol also relieves steric clashes by optimizing the CDR backbone torsion angles and by simultaneously perturbing the relative orientation of the light and heavy chains. RosettaAntibody generates 2000 independent structures, and the server returns pictures, coordinate files, and detailed scoring information for the 10 top-scoring models. The 10 models enable users to use rational judgment in choosing the best model or to use the set as an ensemble for further studies such as docking. The high-resolution models generated by RosettaAntibody have been used for the successful prediction of antibody–antigen complex structures

    TCR cross-reactivity and allorecognition: new insights into the immunogenetics of allorecognition

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    Alloreactive T cells are core mediators of graft rejection and are a potent barrier to transplantation tolerance. It was previously unclear how T cells educated in the recipient thymus could recognize allogeneic HLA molecules. Recently it was shown that both naΓ―ve and memory CD4+ and CD8+ T cells are frequently cross-reactive against allogeneic HLA molecules and that this allorecognition exhibits exquisite peptide and HLA specificity and is dependent on both public and private specificities of the T cell receptor. In this review we highlight new insights gained into the immunogenetics of allorecognition, with particular emphasis on how viral infection and vaccination may specifically activate allo-HLA reactive T cells. We also briefly discuss the potential for virus-specific T cell infusions to produce GvHD. The progress made in understanding the molecular basis of allograft rejection will hopefully be translated into improved allograft function and/or survival, and eventually tolerance induction

    SnugDock: Paratope Structural Optimization during Antibody-Antigen Docking Compensates for Errors in Antibody Homology Models

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    High resolution structures of antibody-antigen complexes are useful for analyzing the binding interface and to make rational choices for antibody engineering. When a crystallographic structure of a complex is unavailable, the structure must be predicted using computational tools. In this work, we illustrate a novel approach, named SnugDock, to predict high-resolution antibody-antigen complex structures by simultaneously structurally optimizing the antibody-antigen rigid-body positions, the relative orientation of the antibody light and heavy chains, and the conformations of the six complementarity determining region loops. This approach is especially useful when the crystal structure of the antibody is not available, requiring allowances for inaccuracies in an antibody homology model which would otherwise frustrate rigid-backbone docking predictions. Local docking using SnugDock with the lowest-energy RosettaAntibody homology model produced more accurate predictions than standard rigid-body docking. SnugDock can be combined with ensemble docking to mimic conformer selection and induced fit resulting in increased sampling of diverse antibody conformations. The combined algorithm produced four medium (Critical Assessment of PRediction of Interactions-CAPRI rating) and seven acceptable lowest-interface-energy predictions in a test set of fifteen complexes. Structural analysis shows that diverse paratope conformations are sampled, but docked paratope backbones are not necessarily closer to the crystal structure conformations than the starting homology models. The accuracy of SnugDock predictions suggests a new genre of general docking algorithms with flexible binding interfaces targeted towards making homology models useful for further high-resolution predictions
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