27 research outputs found

    CD74 deficiency ameliorates Pseudomonas aeruginosa-induced ocular infection

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    Eye trauma and contact lens wear are the main factors that predispose to the development of infectious keratitis. The existing therapies fail to control the inflammation-driven tissue damage that occurs during Pseudomonas aeruginosa infection. Antibiotic treatment reduces bacterial burdens, but better interventions are needed to alleviate tissue damage resulting from local inflammation. We have previously documented that inhibition of macrophage migration inhibitory factor (MIF) reduces the bacterial levels and the inflammatory damage during keratitis. Here, we report that mice deficient for CD74, the putative MIF receptor, developed milder Pseudomonas aeruginosa-induced disease, characterized by decreased proinflammatory mediators and reduced bacterial presence in the cornea. However, topical inhibition of MIF using antibodies applied to the cornea further promoted recovery from disease, suggesting that in addition to MIF-dependent signaling events, MIF-triggered CD74-independent signaling pathways regulate sensitization to P. aeruginosa-induced infection

    Inhibition of Macrophage Migration Inhibitory Factor Ameliorates Ocular Pseudomonas aeruginosa-Induced Keratitis

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    Pseudomonas aeruginosa causes severe sight-threatening corneal infections, with the inflammatory response to the pathogen being the major factor resulting in damage to the cornea that leads to loss of visual acuity. We found that mice deficient for macrophage migration inhibitory factor (MIF), a key regulator of inflammation, had significantly reduced consequences from acute P. aeruginosa keratitis. This improvement in the outcome was manifested as improved bacterial clearance, decreased neutrophil infiltration, and decreased inflammatory responses when P. aeruginosa-infected MIF knock out (KO) mice were compared to infected wild-type mice. Recombinant MIF applied to infected corneas restored the susceptibility of MIF deficient mice to P. aeruginosa-induced disease, demonstrating that MIF is necessary and sufficient to cause significant pathology at this immune privileged site. A MIF inhibitor administered during P. aeruginosa-induced infection ameliorated the disease-associated pathology. MIF regulated epithelial cell responses to infection by enhancing synthesis of proinflammatory mediators in response to P. aeruginosa infection and by promoting bacterial invasion of corneal epithelial cells, a correlate of virulence in the keratitis model. Our results uncover a host factor that elevates inflammation and propagates bacterial cellular invasion, and further suggest that inhibition of MIF during infection may have a beneficial therapeutic effect

    Long Lamai community ICT4D E‐commerce system modelling: an agent oriented role‐based approach

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    This paper presents the post‐mortem report upon completion of the Long Lamai e‐commerce development project. Some weaknesses with regards to the current software modelling approach are identified and an alternative role‐based approach is proposed. We argue that the existing software modelling technique is not suitable for modelling, making it difficult to establish a good contract between stakeholders causing delays in the project delivery. The role‐based approach is able to explicitly highlight the responsibilities among stakeholders, while also forming the contract agreement among them leading towards sustainable ICT4D

    Thermo-chemical Conversion of Biomass and Upgrading to Biofuel: The Thermo-Catalytic Reforming Process - A Review

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    Thermo‐catalytic reforming (TCR®) is a promising conversion technology for the production of liquid bio‐fuels. The process is a proven opportunity to convert biological wastes and residues into hydrogen‐rich syngas, high‐quality oil, and char without volatiles. Bio‐oil produced from TCR® has a high carbon content, low water content, low oxygen content, and a high heating value; it is therefore directly applicable as feed in boilers or as blend in dual fuel engines. A feasible opportunity for using bio‐oil in automotive combustion engines is a further upgrade step to bio‐fuel by hydrogenation. During this hydrotreatment, heterogeneous atoms like sulfur, nitrogen, and oxygen are removed or substituted with hydrogen. Fraunhofer UMSICHT already produces gasoline and diesel that comply with European fuel standards EN 228 and EN 590, using different catalysts like NiMo/Al2O3, CoMo/Al2O3, and Ru/C for hydrogenation at 643 K and a constant hydrogen pressure of 14 MPa. Various hydrocarbons and benzene derivatives are verified after hydrotreating
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