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

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

Coded Replication: A Space-Efficient Technique for Increasing File Availability

Distributed file systems offer a potential increase in file availability through replication of data. Many previous solutions have had large space requirements to achieve high availability. In this paper, we propose a method of replication that is extremely space efficient and yet provides significantly better availability than Dynamic Voting (the best of the previous methods) for reasonably reliable systems. The method employs Reed-Solomon encoding techniques, permitting each node to hold a small amount of the file, and yet allow reconstruction of the entire file given only a subset of the nodes. This increases availability at the cost of increased processing time, instead of increased disk space. The technique is shown to be flexible both in system resource demands and in the availability provided. 1 Introduction Distributing file storage over several machines can increase file availability. The most common mechanism for increasing availability is replication. Replication introduces ..

Information preserving xml schema embedding.

A fundamental concern of information integration in an XML context is the ability to embed one or more source documents in a target document so that (a) the target document conforms to a target schema and (b) the information in the source document(s) is preserved. In this paper, information preservation for XML is formally studied, and the results of this study guide the definition of a novel notion of schema embedding between two XML DTD schemas represented as graphs. Schema embedding generalizes the conventional notion of graph similarity by allowing an edge in a source DTD schema to be mapped to a path in the target DTD. Instance-level embeddings can be defined from the schema embedding in a straightforward manner, such that conformance to a target schema and information preservation are guaranteed. We show that it is NP-complete to find an embedding between two DTD schemas. We also provide efficient heuristic algorithms to find candidate embeddings, along with experimental results to evaluate and compare the algorithms. These yield the first systematic and effective approach to finding information preserving XML mappings

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