Remote device access in the new accelerator controls middleware

This paper presents the Remote Device Access (RDA) package developed at CERN in the framework of the joint PS/SL Controls Middleware project. The package design reflects the Accelerator Device Model in which devices, named entities in the control system, can be controlled via properties. RDA implements this model in a distributed environment with devices residing in servers that can run anywhere in the controls network. It provides a location-independent and reliable access to the devices from control programs. By invoking the device access methods, clients can read, write and subscribe to device property values. We describe the architecture and design of RDA its API, and CORBA-based implementations in Java and C++. First applications of RDA in the CERN accelerator control systems are described as well

Differential roles of CCL2 and CCR2 in host defense to coronavirus infection.

The CC chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1) is important in coordinating the immune response following microbial infection by regulating T cell polarization as well as leukocyte migration and accumulation within infected tissues. The present study examines the consequences of mouse hepatitis virus (MHV) infection in mice lacking CCL2 (CCL2(-/-)) in order to determine if signaling by this chemokine is relevant in host defense. Intracerebral infection of CCL2(-/-) mice with MHV did not result in increased morbidity or mortality as compared to either wild type or CCR2(-/-) mice and CCL2(-/-) mice cleared replicating virus from the brain. In contrast, CCR2(-/-) mice displayed an impaired ability to clear virus from the brain that was accompanied by a reduction in the numbers of antigen-specific T cells as compared to both CCL2(-/-) and wild-type mice. The paucity in T cell accumulation within the central nervous system (CNS) of MHV-infected CCR2(-/-) mice was not the result of either a deficiency in antigen-presenting cell (APC) accumulation within draining cervical lymph nodes (CLN) or the generation of virus-specific T cells within this compartment. A similar reduction in macrophage infiltration into the CNS was observed in both CCL2(-/-) and CCR2(-/-) mice when compared to wild-type mice, indicating that both CCL2 and CC chemokine receptor 2 (CCR2) contribute to macrophage migration and accumulation within the CNS following MHV infection. Together, these data demonstrate that CCR2, but not CCL2, is important in host defense following viral infection of the CNS, and CCR2 ligand(s), other than CCL2, participates in generating a protective response

The LHC Post Mortem Analysis Framework

The LHC with its unprecedented complexity and criticality of beam operation will need thorough analysis of data taken from systems such as power converters, interlocks and beam instrumentation during events like magnet quenches and beam loss. The causes of beam aborts or in the worst case equipment damage have to be revealed to improve operational procedures and protection systems. The correct functioning of the protection systems with their required redundancy has to be verified after each such event. Post mortem analysis software for the control room has been prepared with automated analysis packages in view of the large number of systems and data volume. This paper recalls the requirements for the LHC Beam Post Mortem System (PM) and the necessity for highly reliable data collection. It describes in detail the redundant architecture for data collection as well as the chosen implementation of a multi-level analysis framework, allowing for automated analysis and qualification of a beam dump event based on expert provided analysis modules. It concludes with an example of the data taken during first beam tests in September 2008 with a first version of the system

Chemotactic Activity and Receptor Binding of Neutrophil Attractant/Activation Protein‐1 (NAP‐1) and Structurally Related Host Defense Cytokines: Interaction of NAP‐2 With the NAP‐1 Receptor

Neutrophil attractant/activation protein‐1 (NAP‐1) has sequence similarity to platelet factor‐4 (PF‐4) and to NAP‐2 (a truncated form of connective tissue activating protein‐Ill [CTAP‐III(des 1–15)]. We compared chemotactic activity for neutrophils of these related proteins. We also included for comparison CTAP‐III, CTAP‐III(des 1–13), the C‐terminal dodecapeptide of PF‐4 [PF‐4(59–70)], and C5a. Chemotactic potency (EC50) was highest for NAP‐1 and C5a. Although chemotactic efficacy (peak percentage of neutrophils migrating) was comparable for C5a, NAP‐1, and NAP‐2, the NAP‐2 response occurred only at concentrations 100‐fold higher than the NAP‐1 EC50 of 10‐8 M. Data for the CTAP‐III proteins confirmed that CTAP‐III is not an attractant and that chemotactic activity appears as a result of cleavage of residues at the N‐terminus to make CTAP‐III(des 1–13) or NAP‐2 [CTAP‐III(des 1–15)]. Chemotactic activity of PF‐4 was low and variable, with no significant response by neutrophils from six of nine subjects. In contrast, PF‐4(59–70) regularly induced high chemotactic responses, although the EC50 of 1.6 × 10‐5 M was 1,000‐fold greater than that of NAP‐1. The binding of fluoresceinated NAP‐1 to neutrophils was inhibited by unlabeled NAP‐1 or NAP‐2 but not by PF‐4 or PF‐4 (59–70). This suggests that NAP‐2 interacts with the neutrophil NAP‐1 receptor. Despite the low chemotactic potency of NAP‐2, it is a potential attractant at sites of injury because of the relatively large amounts of the parent CTAP‐III released from platelets, as indicated by a serum concentration of approximately 10‐6 M.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141697/1/jlb0258.pd

CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis

BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalations of finely dispersed organic particles or low molecular weight chemicals. The disease is characterized by an alveolitis sustained by CD8(+) cytotoxic T lymphocytes, granuloma formation, and, whenever antigenic exposition continues, fibrosis. Although it is known that T-cell migration into the lungs is crucial in HP reaction, mechanisms implicated in this process remain undefined. METHODS: Using flow cytometry, immunohistochemistry, confocal microscopy analysis and chemotaxis assays we evaluated whether CXCL10 and its receptor CXCR3 regulate the trafficking of CD8(+) T cells in HP lung. RESULTS: Our data demonstrated that lymphocytes infiltrating lung biopsies are CD8 T cells which strongly stain for CXCR3. However, T cells accumulating in the BAL of HP were CXCR3(+)/IFNγ(+) Tc1 cells exhibiting a strong in vitro migratory capability in response to CXCL10. Alveolar macrophages expressed and secreted, in response to IFN-γ, definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3(+) T-cell line. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the BAL in individuals with HP. CONCLUSION: These data indicate that IFN-γ mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation

TYMSTR, a putative chemokine receptor selectively expressed in activated T cells, exhibits HIV-1 coreceptor function

AbstractBackground: Chemokines bind to specific receptors and mediate leukocyte migration to sites of inflammation. Recently, some chemokine receptors, notably CXCR4 and CCR5, have been shown to be essential fusion factors on target cells for infection by human immunodeficiency virus (HIV); the chemokines bound by these receptors have also been shown to act as potent inhibitors of HIV infection. Here, we describe the isolation of a novel, putative chemokine receptor.Results: We have isolated the cDNA for a putative human chemokine receptor, which we have termed TYMSTR (T-lymphocyte-expressed seven-transmembrane domain receptor). The TYMSTR gene is localized to human chromosome 3 and encodes a protein that has a high level of identity with chemokine receptors. TYMSTR mRNA was selectively expressed in interleukin-2-stimulated T lymphocytes but not in freshly isolated lymphocytes and leukocytes or related cell lines. The natural ligand for TYMSTR was not identified among 32 human chemokines and other potential ligands. Cells co-expressing TYMSTR and human CD4 fused with cells expressing envelope glycoproteins of macrophage (M)-tropic HIV-1 as well as T-cell line (T)-tropic HIV-1 isolates. Addition of infectious, T-tropic HIV-1 particles to TYMSTR/CD4-expressing cells resulted in viral entry and proviral DNA formation.Conclusions: Our findings demonstrate that TYMSTR, in combination with CD4, mediates HIV-1 fusion and entry. The high-level expression of TYMSTR in CD4+ T lymphocytes and the selectivity of this receptor for T-tropic and M-tropic HIV-1 strains indicates that TYMSTR might function as HIV coreceptor at both early and late stages of infection

TLR7-mediated skin inflammation remotely triggers chemokine expression and leukocyte accumulation in the brain

Background: The relationship between the brain and the immune system has become increasingly topical as, although it is immune-specialised, the CNS is not free from the influences of the immune system. Recent data indicate that peripheral immune stimulation can significantly affect the CNS. But the mechanisms underpinning this relationship remain unclear. The standard approach to understanding this relationship has relied on systemic immune activation using bacterial components, finding that immune mediators, such as cytokines, can have a significant effect on brain function and behaviour. More rarely have studies used disease models that are representative of human disorders. Methods: Here we use a well-characterised animal model of psoriasis-like skin inflammation—imiquimod—to investigate the effects of tissue-specific peripheral inflammation on the brain. We used full genome array, flow cytometry analysis of immune cell infiltration, doublecortin staining for neural precursor cells and a behavioural read-out exploiting natural burrowing behaviour. Results: We found that a number of genes are upregulated in the brain following treatment, amongst which is a subset of inflammatory chemokines (CCL3, CCL5, CCL9, CXCL10, CXCL13, CXCL16 and CCR5). Strikingly, this model induced the infiltration of a number of immune cell subsets into the brain parenchyma, including T cells, NK cells and myeloid cells, along with a reduction in neurogenesis and a suppression of burrowing activity. Conclusions: These findings demonstrate that cutaneous, peripheral immune stimulation is associated with significant leukocyte infiltration into the brain and suggest that chemokines may be amongst the key mediators driving this response