R-Coffee: a web server for accurately aligning noncoding RNA sequences

The R-Coffee web server produces highly accurate multiple alignments of noncoding RNA (ncRNA) sequences, taking into account predicted secondary structures. R-Coffee uses a novel algorithm recently incorporated in the T-Coffee package. R-Coffee works along the same lines as T-Coffee: it uses pairwise or multiple sequence alignment (MSA) methods to compute a primary library of input alignments. The program then computes an MSA highly consistent with both the alignments contained in the library and the secondary structures associated with the sequences. The secondary structures are predicted using RNAplfold. The server provides two modes. The slow/accurate mode is restricted to small datasets (less than 5 sequences less than 150 nucleotides) and combines R-Coffee with Consan, a very accurate pairwise RNA alignment method. For larger datasets a fast method can be used (RM-Coffee mode), that uses R-Coffee to combine the output of the three packages which combines the outputs from programs found to perform best on RNA (MUSCLE, MAFFT and ProbConsRNA). Our BRAliBase benchmarks indicate that the R-Coffee/Consan combination is one of the best ncRNA alignment methods for short sequences, while the RM-Coffee gives comparable results on longer sequences. The R-Coffee web server is available at http://www.tcoffee.org

Changes in dental plaque following hospitalisation in a critical care unit: an observational study

Additional funding was provided by a grant from the Faculty of Dental Surgery, Royal College of Surgeons, England, and this work was undertaken at University College London/University College London Hospitals, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme

R-Coffee: a web server for accurately aligning noncoding RNA sequences

The R-Coffee web server produces highly accurate multiple alignments of noncoding RNA (ncRNA) sequences, taking into account predicted secondary structures. R-Coffee uses a novel algorithm recently incorporated in the T-Coffee package. R-Coffee works along the same lines as T-Coffee: it uses pairwise or multiple sequence alignment (MSA) methods to compute a primary library of input alignments. The program then computes an MSA highly consistent with both the alignments contained in the library and the secondary structures associated with the sequences. The secondary structures are predicted using RNAplfold. The server provides two modes. The slow/accurate mode is restricted to small datasets (less than 5 sequences less than 150 nucleotides) and combines R-Coffee with Consan, a very accurate pairwise RNA alignment method. For larger datasets a fast method can be used (RM-Coffee mode), that uses R-Coffee to combine the output of the three packages which combines the outputs from programs found to perform best on RNA (MUSCLE, MAFFT and ProbConsRNA). Our BRAliBase benchmarks indicate that the R-Coffee/Consan combination is one of the best ncRNA alignment methods for short sequences, while the RM-Coffee gives comparable results on longer sequences. The R-Coffee web server is available at http://www.tcoffee.org

A randomized-controlled trial of low-dose doxycycline for periodontitis in smokers

Background/Aim : Tobacco use reduces the effect of non-surgical periodontal therapy. Host-modulation with low-dose doxycycline (LDD) might favour repair and promote an improved treatment response. The aim of this study was to investigate the effect of LDD in smokers on non-surgical periodontal therapy. Material and Methods : This was a parallel arm, randomized, identical placebo-controlled trial with masking of examiner, care-giver, participant and statistician and 6 months of follow-up. Patients received non-surgical therapy and 3 months of test or control drug. Statistical analysis used both conventional methods and multilevel modelling. Results : Eighteen control and 16 test patients completed the study. The velocity of change was statistically greater for the test group for clinical attachment level −0.19 mm/month (95% CI=−0.34, 0.04; p =0.012) and probing depth 0.30 mm/month (95% CI=−0.42, −0.17; p <0.001). However, no differences were observed for absolute change in clinical or biochemical markers at 6 months. Conclusions : This study does not provide evidence of a benefit of using LDD as an adjunct to non-surgical periodontal therapy in smokers.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74791/1/j.1600-051X.2007.01058.x.pd

An optimized TOPS+ comparison method for enhanced TOPS models

This article has been made available through the Brunel Open Access Publishing Fund.Background Although methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. Previously we have discussed the basic mechanisms of our novel method for structure comparison based on our TOPS+ model (Topological descriptions of Protein Structures Enhanced with Ligand Information). In this paper we show how these results can be significantly improved using parameter optimization, and we call the resulting optimised TOPS+ method as advanced TOPS+ comparison method i.e. advTOPS+. Results We have developed a TOPS+ string model as an improvement to the TOPS [1-3] graph model by considering loops as secondary structure elements (SSEs) in addition to helices and strands, representing ligands as first class objects, and describing interactions between SSEs, and SSEs and ligands, by incoming and outgoing arcs, annotating SSEs with the interaction direction and type. Benchmarking results of an all-against-all pairwise comparison using a large dataset of 2,620 non-redundant structures from the PDB40 dataset [4] demonstrate the biological significance, in terms of SCOP classification at the superfamily level, of our TOPS+ comparison method. Conclusions Our advanced TOPS+ comparison shows better performance on the PDB40 dataset [4] compared to our basic TOPS+ method, giving 90 percent accuracy for SCOP alpha+beta; a 6 percent increase in accuracy compared to the TOPS and basic TOPS+ methods. It also outperforms the TOPS, basic TOPS+ and SSAP comparison methods on the Chew-Kedem dataset [5], achieving 98 percent accuracy. Software Availability: The TOPS+ comparison server is available at http://balabio.dcs.gla.ac.uk/mallika/WebTOPS/.This article is available through the Brunel Open Access Publishing Fun

Numerical Simulations of Void Linkage in Model Materials using a Nonlocal Ductile Damage Approximation

Experiments on the growth and linkage of 10 μm diameter holes laser drilled in high precision patterns into Al-plates were modelled with finite elements. The simulations used geometries identical to those of the experiments and incorporated ductile damage by element removal under the control of a ductile damage indicator based on the micromechanical studies of Rice and Tracey. A regularization of the problem was achieved through an integral-type nonlocal model based on the smoothing of the rate of a damage indicator D over a characteristic length L. The simulation does not predict the experimentally observed damage acceleration either in the case where no damage is included or when only a local damage model is used. However, the full three-dimensional simulations based on the nonlocal damage methodology do predict both the failure path and the failure strain at void linkage for almost all configurations studied. For the cases considered the critical parameter controlling the local deformations at void linkage was found to be the ratio between hole diameter and hole spacing

Communicating the Results of Clinical Research to Participants: Attitudes, Practices, and Future Directions

The authors discuss the available data on the effects of communicating aggregate and individual research results on participants, investigators, and the research enterprise

Association of Down's syndrome and water fluoride level: a systematic review of the evidence

BACKGROUND: A review of the safety and efficacy of drinking water fluoridation was commissioned by the UK Department of Health to investigate whether the evidence supported a beneficial effect of water fluoridation and whether there was any evidence of adverse effects. Down's syndrome was one of the adverse effects reported. The aim of this review is to examine the evidence for an association between water fluoride level and Down's syndrome. METHODS: A systematic review of research. Studies were identified through a comprehensive literature search, scanning citations and online requests for papers. Studies in all languages which investigated the incidence of Down's syndrome in areas with different levels of fluoride in their water supplies were included. Study inclusion and quality was assessed independently by 2 reviewers. A qualitative analysis was conducted. RESULTS: Six studies were included. All were ecological in design and scored poorly on the validity assessment. The estimates of the crude relative risk ranged from 0.84 to 3.0. Four studies showed no significant associations between the incidence of Down's syndrome and water fluoride level and two studies by the same author found a significant (p < 0.05) positive association (increased Down's syndrome incidence with increased water fluoride level). Only two of the studies controlled for confounding factors and only one of these presented summary outcome measures. CONCLUSIONS: The evidence of an association between water fluoride level and Down's syndrome incidence is inconclusive