148 research outputs found

    Up Rising:Rehabilitating J.G. Ballard’s High-Rise with R.D. Laing and Lauren Berlant

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    High-Rise by J.G. Ballard intriguingly contains a pivotal character named Dr. Robert Laing, surely an allusion to the then influential psychiatric writer, Dr. R.D. Laing. Re-reading Ballard's classic text through the prism of Laing’s theories, with further explication of the role of flat affect via Lauren Berlant, this article presents a new interpretation of a classic text that argues that Ballard ingeniously misdirected his readers into making identifications with precisely the wrong characters and the wrong actions. Re-focusing a subject gaze in accordance with these theoretical analyses, allows for an entirely alternative understanding of the text in which Ballard was more than a pessimistic prophet of inexorable urban breakdown, he foretold societal rehabilitation as well. High-Rise is read as a classic of psychogeography, an established genre which is argued to be of great relevance to the study of society and space. This article therefore engages in a reading of a psychogeographical text via theory implicitly alluded to by the text itself

    Analysis of leukocyte membrane protein interactions using protein microarrays

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    This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright @ 2005 Letarte et al; licensee BioMed Central Ltd.BACKGROUND: Protein microarrays represent an emerging class of proteomic tools to investigate multiple protein-protein interactions in parallel. A sufficient proportion of immobilized proteins must maintain an active conformation and an orientation that allows for the sensitive and specific detection of antibody and ligand binding. In order to establish protein array technology for the characterization of the weak interactions between leukocyte membrane proteins, we selected the human leukocyte membrane protein CD200 (OX2) and its cell surface receptor (hCD200R) as a model system. As antibody-antigen reactions are generally of higher affinity than receptor-ligand binding, we first analyzed the reactivity of monoclonal antibodies (mAb) to normal and mutant forms of immobilized CD200R. RESULTS: Fluorescently labelled mAb DX147, DX136 and OX108 were specifically reactive with immobilized recombinant hCD200R extracellular region, over a range of 0.1-40 microg ml(-1) corresponding to a limit of sensitivity of 0.01-0.05 femtomol per spot. Orientating hCD200R using capture antibodies, showed that DX147 reacts with an epitope spatially distinct from the more closely related DX136 and OX108 epitopes. A panel of soluble recombinant proteins with mutations in hCD200R domain 1 produced by transiently transfected cells, was arrayed directly without purification and screened for binding to the three mAb. Several showed decreased binding to the blocking mAb DX136 and OX108, suggesting close proximity of these epitopes to the CD200 binding site. Binding of hCD200 to directly immobilized rat, mouse, and hCD200R was achieved with multimeric ligands, in the form of biotinylated-hCD200 coupled to FITC-labelled avidin coated beads. CONCLUSION: We have achieved sensitive, specific and reproducible detection of immobilized CD200R with different antibodies and mapped antigenic epitopes for two mAb in the vicinity of the ligand binding site using protein microarrays. We also detected CD200 binding to its receptor, a low affinity interaction, using beads presenting multivalent ligands. Our results demonstrate the quantitative aspects of protein arrays and their potential use in detecting simultaneously multiple protein-protein interactions and in particular the weak interactions found between leukocyte membrane proteins.This work was supported by the Medical Research Council (UK) and the Arthritis Research Campaign (UK)

    A 'Different Class'? Homophily and Heterophily in the Social Class Networks of Britpop

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    Social network analysis is increasingly recognised as a useful way to explore music scenes. In this article we examine the individuals who were the cultural workforce that comprised the 'Britpop' music scene of the 1990s. The focus of our analysis is homophily and heterophily to determine whether the clusters of friendships and working relationships of those who were ‘best connected’ in the scene were patterned by original social class position. We find that Britpop's 'whole network' is heterophilic but its 'sub-networks' are more likely to be social class homophilic. The sub-networks that remain heterophilic are likely to be united by other common experiences that brought individuals in the network to the same social spaces. We suggest that our findings on Britpop might be generalised to the composition of other music scenes, cultural workforces and aggregations of young people. Our study differs from research on, first, British ‘indie music’ and social class which focusses upon the construction, representation and performance of social location rather than the relationships it might shape (such as Wiseman-Trowse, 2008) and second, the pioneering social network analyses of music scenes (such as Crossley 2008; 2009; 2015; Crossley et. al 2014) which currently lacks the explicit emphasis on social class

    Inequity in rehabilitation interventions after hip fracture:a systematic review

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    Objective To determine the extent to which equity factors contributed to eligibility criteria of trials of rehabilitation interventions after hip fracture. We define equity factors as those that stratify healthcare opportunities and outcomes.Design Systematic search of MEDLINE, Embase, CINHAL, PEDro, Open Grey, BASE, and ClinicalTrials.gov for randomized controlled trials of rehabilitation interventions after hip fracture published between 1st January 2008 and 30th May 2018. Trials not published in English, secondary prevention or new models of service delivery (e.g. orthogeriatric care pathway) were excluded. Duplicate screening for eligibility, risk of bias (Cochrane Risk of Bias Tool), and data extraction (Cochrane’s PROGRESS-Plus framework).Results 23 published, 8 protocol, 4 registered ongoing randomized controlled trials (4,449 participants) were identified. A total of 69 equity factors contributed to eligibility criteria of the 35 trials. For more than 50% of trials, potential participants were excluded based on residency in a nursing home, cognitive impairment, mobility/functional impairment, minimum age, and/or nonsurgical candidacy. Where reported, this equated to the exclusion of 2,383 out of 8,736 (27.3%) potential participants based on equity factors. Residency in a nursing home and cognitive impairment were the main drivers of these exclusions. Conclusion The generalizability of trial results to the underlying population of frail older adults is limited. Yet this is the evidence base underpinning current service design. Future trials should include participants with cognitive impairment and those admitted from nursing homes. For those excluded, an evidence-informed reasoning for the exclusion should be explicitly stated.PROSPERO CRD42018085930<br/

    PRIMO: an interactive homology modeling pipeline

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    The development of automated servers to predict the three-dimensional structure of proteins has seen much progress over the years. These servers make calculations simpler, but largely exclude users from the process. In this study, we present the PRotein Interactive MOdeling (PRIMO) pipeline for homology modeling of protein monomers. The pipeline eases the multi-step modeling process, and reduces the workload required by the user, while still allowing engagement from the user during every step. Default parameters are given for each step, which can either be modified or supplemented with additional external input. PRIMO has been designed for users of varying levels of experience with homology modeling. The pipeline incorporates a user-friendly interface that makes it easy to alter parameters used during modeling

    CTLA4 is expressed on mature dendritic cells derived from human monocytes and influences their maturation and antigen presentation

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    <p>Abstract</p> <p>Background</p> <p>Dendritic cells (DCs) initiate immune responses through their direct interaction with effector cells. However, the mechanism by which DC activity is regulated is not well defined. Previous studies have shown that CTLA4 on T cells regulates DCs function by "cross-talk". We investigated whether there is an intrinsic regulatory mechanism in DCs, with CTLA4 as a candidate regulator.</p> <p>Results</p> <p>We confirmed via RT-PCR and flow cytometry the natural expression of CTLA4 on mature DCs derived from human monocytes. Approximately 8% CD1a-positive cells express CTLA4 both on surface and intracellular, whereas 10% CD1a-negative cells express CTLA4 intracellularly, but little expression was observed on the cell surface. The cross-linking of CTLA4 inhibits DCs maturation and antigen presentation in vitro, but does not inhibit endocytosis.</p> <p>Conclusions</p> <p>CTLA4 is expressed by DCs and plays an inhibitory role. CTLA4-expressing DCs may represent a group of regulatory DCs. Because of its wide distribution on different cell types, CTLA4 may play a general role in regulating immune responses.</p

    CD200 Receptor Controls Sex-Specific TLR7 Responses to Viral Infection

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    Immunological checkpoints, such as the inhibitory CD200 receptor (CD200R), play a dual role in balancing the immune system during microbial infection. On the one hand these inhibitory signals prevent excessive immune mediated pathology but on the other hand they may impair clearance of the pathogen. We studied the influence of the inhibitory CD200-CD200R axis on clearance and pathology in two different virus infection models. We find that lack of CD200R signaling strongly enhances type I interferon (IFN) production and viral clearance and improves the outcome of mouse hepatitis corona virus (MHV) infection, particularly in female mice. MHV clearance is known to be dependent on Toll like receptor 7 (TLR7)-mediated type I IFN production and sex differences in TLR7 responses previously have been reported for humans. We therefore hypothesize that CD200R ligation suppresses TLR7 responses and that release of this inhibition enlarges sex differences in TLR7 signaling. This hypothesis is supported by our findings that in vivo administration of synthetic TLR7 ligand leads to enhanced type I IFN production, particularly in female Cd200−/− mice and that CD200R ligation inhibits TLR7 signaling in vitro. In influenza A virus infection we show that viral clearance is determined by sex but not by CD200R signaling. However, absence of CD200R in influenza A virus infection results in enhanced lung neutrophil influx and pathology in females. Thus, CD200-CD200R and sex are host factors that together determine the outcome of viral infection. Our data predict a sex bias in both beneficial and pathological immune responses to virus infection upon therapeutic targeting of CD200-CD200R

    Waiting for other people: a psychoanalytic interpretation of the time for action

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    Typical responses to a confrontation with failures in authority, or what Lacanians term ‘the lack in the Other’, involve attempts to shore it up. A patient undergoing psychoanalysis eventually faces the impossibility of doing this successfully; the Other will always be lacking. This creates a space through which she can reimagine how she might intervene in her suffering. Similarly, when coronavirus forces us to confront the brute fact of the lack in the Other at the socio-political level, we have the opportunity to discover a space for acting rather than continuing symptomatic behaviour that increasingly fails to work

    Towards a spatial critique of ideology: architecture as a test

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    The article presents the outline for the theory of ideological space. The ideological properties of space are reconsidered by the juxtaposition of Lefebvre’s and Bourdieu’s theories. The resultant reconciliation points towards the notion of spatial critique of ideology as well as the possibility of employing ideology for critique of space. The notion of a test (as characterized by Boltanski) is introduced to show the importance of capabilities of actors and objects in the process of critique. The article emphasizes the exceptional significance of architecture for the construction of critical positions. The architecture is described as a form of a test. In so doing, the architecture is characterized as one of the essential elements of possible social emancipation. In effect, both the social responsibilities of the architecture and its critical role are underscored
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