Structural study of the type II 3-dehydroquinate dehydratase from Actinobacillus pleuropneumoniae

9 pages, 7 figures, 2 tables.The structure of the type II dehydroquinate dehydratase (DHQase) from Actinobacillus pleuropneumoniae, the third enzyme of the shikimate pathway, has been determined. Crystals diffracting to 1.7 Å were obtained in space and on earth using the counter-diffusion technique. The structure was solved using molecular replacement and refined to high resolution. The overall structure of the dodecameric enzyme is described and compared with structures of DHQases from other bacteria. DHQases contain a flexible loop that presumably closes over the active site upon substrate binding. The enzyme can exist in an open or closed conformation. The present structure displays the open conformation, with a sulfate anion bound in the active site. The availability of this structure opens a route to structure-based antibiotics targetting this pathogenic bacterium.We thank Professor Kabsch for providing XDS free of charge. We acknowledge the support of the European Space Agency and the European Community Action to Research Infrastructure Action of the Improving Human Potential Programme to the EMBL Hamburg Outstation, contract No. HPRI-CT-1999-00017. We thank Olivier Minster (ESA) for his support of space science. The authors acknowledge the excellent work of Dr Eva ManÄ as in managing the logistics concerning the space mission. We thank Viscount Dirk Frimout for his support for space crystallization experiments.Peer reviewe

A fast Monte Carlo algorithm for site or bond percolation

We describe in detail a new and highly efficient algorithm for studying site or bond percolation on any lattice. The algorithm can measure an observable quantity in a percolation system for all values of the site or bond occupation probability from zero to one in an amount of time which scales linearly with the size of the system. We demonstrate our algorithm by using it to investigate a number of issues in percolation theory, including the position of the percolation transition for site percolation on the square lattice, the stretched exponential behavior of spanning probabilities away from the critical point, and the size of the giant component for site percolation on random graphs.Comment: 17 pages, 13 figures. Corrections and some additional material in this version. Accompanying material can be found on the web at http://www.santafe.edu/~mark/percolation

Transiting exoplanets from the CoRoT space mission. XV. CoRoT-15b: a brown dwarf transiting companion

We report the discovery by the CoRoT space mission of a transiting brown dwarf orbiting a F7V star with an orbital period of 3.06 days. CoRoT-15b has a radius of 1.12 +0.30 -0.15 Rjup, a mass of 63.3 +- 4.1 Mjup, and is thus the second transiting companion lying in the theoretical mass domain of brown dwarfs. CoRoT-15b is either very young or inflated compared to standard evolution models, a situation similar to that of M-dwarfs stars orbiting close to solar-type stars. Spectroscopic constraints and an analysis of the lightcurve favors a spin period between 2.9 and 3.1 days for the central star, compatible with a double-synchronisation of the system.Comment: 7 pages, 6 figures, accepted in A&

Value of ADC measurements for nodal staging after chemoradiation in locally advanced rectal cancer—a per lesion validation study

OBJECTIVES: To evaluate the performance of diffusion-weighted MRI (DWI) in addition to T2-weighted (T2W) MRI for nodal restaging after chemoradiation in rectal cancer. METHODS: Thirty patients underwent chemoradiation followed by MRI (1.5 T) and surgery. Imaging consisted of T2W-MRI and DWI (b0, 500, 1000). On T2W-MRI, nodes were scored as benign/malignant by two independent readers (R1, R2). Mean apparent diffusion coefficient (ADC) was measured for each node. Diagnostic performance was compared for T2W-MRI, ADC and T2W+ADC, using a per lesion histological validation. RESULTS: ADC was higher for the malignant nodes (1.43 +/- 0.38 vs 1.19 +/- 0.27 *10(-3) mm(2)/s, p < 0.001). Area under the ROC curve/sensitivity/specificity were 0.88/65%/93% (R1) and 0.95/71%/91% (R2) using T2W-MRI; 0.66/53%/82% using ADC (mean of two readers); and 0.91/56%/98% (R1) and 0.96/56%/99% (R2) using T2W+ADC. There was no significant difference between T2W-MRI and T2W+ADC. Interobserver reproducibility was good for T2W-MRI (kappa0.73) and ADC (intraclass correlation coefficient 0.77). CONCLUSIONS: After chemoradiation, ADC measurements may have potential for nodal characterisation, but DWI on its own is not reliable. Addition of DWI to T2W-MRI does not improve accuracy and T2W-MRI is already sufficiently accurate