Tim J. Mitchell

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We use polyharmonic Radial Basis Functions (RBFs) to reconstruct smooth, manifold surfaces from point-cloud data and to repair incomplete meshes. An object's surface is defined implicitly as the zero set of an RBF fitted to the given surface data. Fast methods for fitting and evaluating RBFs allow us to model large data sets, consisting of millions of(More)
Streptococcus pneumoniae is one of the most important causes of microbial diseases in humans. The genomes of 44 diverse strains of S. pneumoniae were analyzed and compared with strains of non-pathogenic streptococci of the Mitis group. Despite evidence of extensive recombination, the S. pneumoniae phylogenetic tree revealed six major lineages. With the(More)
Epidemiological studies of the naturally transformable bacterial pathogen Streptococcus pneumoniae have previously been confounded by high rates of recombination. Sequencing 240 isolates of the PMEN1 (Spain(23F)-1) multidrug-resistant lineage enabled base substitutions to be distinguished from polymorphisms arising through horizontal sequence transfer. More(More)
Natural competence for genetic transformation is the best-characterized feature of the major human pathogen Streptococcus pneumoniae. Recent studies have shown the virulence of competence-deficient mutants to be attenuated, but the nature of the connection between competence and virulence remained unknown. Here we document the release, triggered by(More)
This paper shows that scattered range data can be smoothed at low cost by fitting a Radial Basis Function (RBF) to the data and convolving with a smoothing kernel (low pass filtering). The RBF exactly describes the range data and interpolates across holes and gaps. The data is smoothed during evaluation of the RBF by simply changing the basic function. The(More)
We have identified in the Streptococcus pneumoniae genome sequence a two-component system (TCS13, Blp [bacteriocin-like peptide]) which is closely related to quorum-sensing systems regulating cell density-dependent phenotypes such as the development of genetic competence or the production of antimicrobial peptides in lactic acid bacteria. In this study we(More)
From a panel of nine inbred mice strains intranasally infected with Streptococcus pneumoniae type 2 strain, BALB/c mice were resistant and CBA/Ca and SJL mice were susceptible to infection. Further investigation revealed that BALB/c mice were able to prevent proliferation of pneumococci in the lungs and blood, whereas CBA/Ca mice showed no bacterial(More)
Recent genomic-based studies have identified 13 two-component signal transduction systems (TCS) in Streptococcus pneumoniae. Bacterial TCSs are important for regulating expression of bacterial genes, including those which are important to the virulence of pathogenic bacteria. We have used virulence assays together with microarray analysis to investigate the(More)
The cholesterol-dependent cytolysins are pore-forming toxins. Pneumolysin is the cytolysin produced by Streptococcus pneumoniae and is a key virulence factor. The protein contains 471 amino acids and four structural domains. Binding to cholesterol is followed by oligomerization and membrane pore formation. Pneumolysin also activates the classical pathway of(More)
Streptococcus pneumoniae is a human commensal and pathogen able to cause a variety of diseases that annually result in over a million deaths worldwide. The S. pneumoniae(Spain23F) sequence type 81 lineage was among the first recognized pandemic clones and was responsible for almost 40% of penicillin-resistant pneumococcal infections in the United States in(More)