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Biomedical subjects

D T Jones

Publications and source records attributed to D T Jones.

At least 37 records · Page 2Linked to original sources

Emended descriptions of Clostridium acetobutylicum and Clostridium beijerinckii, and descriptions of Clostridium saccharoperbutylacetonicum sp. nov. and Clostridium saccharobutylicum sp. nov.

On the basis of 16S rRNA gene sequencing and DNA-DNA reassociation, industrial solvent-producing clostridia have been assigned to four species. In this study, the phenotypic characteristics of Clostridium acetobutylicum, Clostridium beijerinckii, 'Clostridium saccharoperbutylacetonicum', and an unnamed Clostridium sp. represented by the strains NCP 262T and NRRL B643 are compared. In addition, a further 40 strains of solvent-producing clostridia have been classified by biotyping, DNA fingerprinting and 16S rRNA gene sequencing. These included 14 C. beijerinckii strains, two strains currently designated as 'Clostridium kaneboi' and 'Clostridium butanologenum', and 24 production strains used in the commercial acetone-butanol fermentation. All of the C. beijerinckii strains were confirmed to have been classified correctly. The 'C. kaneboi' and 'C. butanologenum' strains require reclassification as C. acetobutylicum and C. beijerinckii, respectively. The commercial production strains were found to belong either to C. beijerinckii or to the unnamed Clostridium sp. For the comparative phenotypic studies of the four species, representative strains were selected from each of the DNA-fingerprint subgroups within each species. These strains were analysed for their ability to utilize different carbohydrates, hydrolyse gelatin or aesculin, and produce indole, and were tested for the presence of catalase and urease. On the basis of these results, several phenotypic traits were found to be useful for differentiating between the four species. The descriptions of C. acetobutylicum and C. beijerinckii have been emended. The names Clostridium saccharoperbutylacetonicum sp. nov. [type strain = N1-4 (HMT) = ATCC 27021T] and Clostridium saccharobutylicum sp. nov. (type strain = DSM 13864T = ATCC BAA-117T) are proposed for the two new species.

Acetone↗

Integrated web-based viewing and secure remote access to a clinical data repository and diverse clinical systems.

The advent of the World-Wide-Web protocols and client-server technology has made it easy to build low-cost, user-friendly, platform-independent graphical user interfaces to health information systems and to integrate the presentation of data from multiple systems. The authors describe a Web interface for a clinical data repository (CDR) that was moved from concept to production status in less than six months using a rapid prototyping approach, multi-disciplinary development team, and off-the-shelf hardware and software. The system has since been expanded to provide an integrated display of clinical data from nearly 20 disparate information systems.

Computer Graphics↗

Proton relative biological effectiveness (RBE) for survival in mice after thoracic irradiation with fractionated doses.

PURPOSE: This study aims at providing relative biological effectiveness (RBE) data under reference conditions accounting for the determination of the "clinical RBE" of protons. METHODS AND MATERIALS: RBE (ref. (60)Co gamma-rays) of the 200 MeV clinical proton beam produced at the National Accelerator Centre (South Africa) was determined for lung tolerance assessed by survival after selective irradiation of the thorax in mice. Irradiations were performed in 1, 3, or 10 fractions separated by 12 h. Proton irradiations were performed at the middle of a 7-cm spread out Bragg peak (SOBP). Control gamma irradiations were randomized with proton irradiations and performed simultaneously. A total of 1008 mice was used, of which 96 were assessed for histopathology. RESULTS: RBEs derived from LD50 ratios were found not to vary significantly with fractionation (corresponding dose range, approximately 2-20 Gy). They, however, tend to increase with time and reach (mean of the RBEs for 1, 3 and 10 fractions) 1.00, 1.08, 1.14, and 1.25 for LD50 at 180, 210, 240, and 270 days, respectively (confidence interval approximately 20%). alpha/beta ratios for protons and gamma are very similar and average 2.3 (0.6-4.8) for the different endpoints. Additional irradiations in 10 fractions at the end of the SOBP were found slightly more effective ( approximately 6%) than at the middle of the SOBP. A control experiment for intestinal crypt regeneration in mice was randomized with the lung experiment and yielded an RBE of 1.14 +/- 0.03, i.e., the same value as obtained previously, which vouches for the reliability of the experimental procedure. CONCLUSION: There is no need to raise the clinical RBE of protons in consideration of the late tolerance of healthy tissues in the extent that RBE for lung tolerance was found not to vary with fractionation nor to differ significantly from those of the majority of early- and late-responding tissues.

Animals↗

Protein structure prediction in the postgenomic era.

As the number of completely sequenced genomes rapidly increases, the postgenomic problem of gene function identification becomes ever more pressing. Predicting the structures of proteins encoded by genes of interest is one possible means to glean subtle clues as to the functions of these proteins. There are limitations to this approach to gene identification and a survey of the expected reliability of different protein structure prediction techniques has been undertaken.

Animals↗

The PSIPRED protein structure prediction server.

SUMMARY: The PSIPRED protein structure prediction server allows users to submit a protein sequence, perform a prediction of their choice and receive the results of the prediction both textually via e-mail and graphically via the web. The user may select one of three prediction methods to apply to their sequence: PSIPRED, a highly accurate secondary structure prediction method; MEMSAT 2, a new version of a widely used transmembrane topology prediction method; or GenTHREADER, a sequence profile based fold recognition method. AVAILABILITY: Freely available to non-commercial users at http://globin.bio.warwick.ac.uk/psipred/

Protein Folding↗

Bacteriophage infections in the industrial acetone butanol (AB) fermentation process.

The reported incidence and effects of bacteriophage infections occurring in the industrial acetone butanol (AB) fermentation processes operated in the USA, Japan, and Puerto Rico during the earlier part of the twentieth century is reviewed. The growth characteristics and solvent-producing ability of a lysogenic strain of Clostridium madisonii isolated from a phage infection in Puerto Rico was determined in molasses fermentation medium. The host strain harbours a large lysogenic phage belonging to the Siphoviridae and the growth rate of the lysogenic strain was found to be slower than the non-lysogenic parent strain and exhibited reduced solvent production. The history of phage infections that occurred in the South African AB process is documented along with the various remedial actions that were taken to restore production. A more detailed account of the last phage infection that occurred in 1980 involving a small pseudo-lysogenic phage belonging to the Podoviridae is given. This phage infected Clostridium beijerinckii P260 and a number of closely related industrial strains. Factory-scale fermentations contaminated by this phage were compared with equivalent laboratory-scale control fermentations. The effect of the phage infection in the full-scale and laboratory-scale fermentations were monitored. Results obtained in laboratory-based studies included an assessment of the effect of the multiplicity of infection and the timing of phage infection. The general effects and symptoms of phage infections in the industrial AB fermentation are reviewed including gross changes in the fermentation and changes in cell morphology. Common techniques used for the diagnosis of phage infections and approaches for controlling phage contamination in the AB fermentation are discussed. Prevention strategies included good factory hygiene, sterilisation, decontamination and disinfection, and the use of resistant strains immunised against specific phages.

Acetone↗

Comparative fermentation studies of industrial strains belonging to four species of solvent-producing clostridia.

Industrial and culture collection strains of solvent-producing clostridia, classified as Clostridium acetobutylicum, Clostridium beijerinckii, Clostridium saccharobutylicum, and Clostridium saccharoperbutylacetonicum were utilised in a comparative study of fermentation performance in a laboratory fermentation medium, a molasses fermentation medium, and a maize fermentation medium under standardised culture conditions. At least one representative strain was selected from each of the sub-groups within the four species. Preliminary evaluations were first undertaken for the three different fermentation media to determine the most appropriate media formulations, carbohydrate concentrations, and culture conditions for comparison of the solvent-producing ability of these strains. Standardised fermentation media and culture conditions were then selected for each of the comparative fermentation studies. These included TYA medium containing 4% glucose, a supplemented molasses medium containing 6% fermentable sugars, and a supplemented maize mash medium containing 8% maize. Additional comparative fermentation studies on industrial strains belonging to two species of solvent-producing clostridia were carried out in molasses containing higher concentrations of fermentable sugars, and the sugar concentrations supporting maximum levels of solvent production were determined. Although all the strains tested grew in the maize fermentation medium and degraded starch, only a few strains produced consistently high solvent levels. Optimum starch utilisation and solvent production was obtained at a maize concentration of 80 g/l. Pretreatment of the maize by milling or saccharification decreased the buffering capacity of the medium and resulted in decreased solvent production. Decreasing the time used to gelatinise the starch had little effect. Solvent yields and concentrations obtained in this study were compared with various published data in the scientific and patent literature and appeared to closely simulate the results obtained in the industrial fermentation process. The fermentation performances of individual strains could provide useful comparative data for the selection and development of strains for use on various commercial fermentation substrates.

Biotechnology↗

Technology architecture guidelines for a health care system.

Although the demand for use of information technology within the healthcare industry is intensifying, relatively little has been written about guidelines to optimize IT investments. A technology architecture is a set of guidelines for technology integration within an enterprise. The architecture is a critical tool in the effort to control information technology (IT) operating costs by constraining the number of technologies supported. A well-designed architecture is also an important aid to integrating disparate applications, data stores and networks. The authors led the development of a thorough, carefully designed technology architecture for a large and rapidly growing health care system. The purpose and design criteria are described, as well as the process for gaining consensus and disseminating the architecture. In addition, the processes for using, maintaining, and handling exceptions are described. The technology architecture is extremely valuable to health care organizations both in controlling costs and promoting integration.

Computer Systems↗

Management reporting on the Web.

Driven by easy-to-use World Wide Web technology and new information integration concepts that have proven their worth in business and industry, online management reporting is now becoming an important strategy for improving operational performance in health care organizations. In this article, we provide an overview of these new information management concepts and describe our experience in planning and executing an enterprise-wide Web-enabled management reporting initiative. We also offer an inventory of the key organizational capacities that we found essential for developing and sustaining Web-enabled reporting services for health care managers.

Computer User Training↗

Termite assemblages, forest disturbance and greenhouse gas fluxes in Sabah, East Malaysia.

A synthesis is presented of sampling work conducted under a UK government-funded Darwin Initiative grant undertaken predominantly within the Danum Valley Conservation Area (DVCA), Sabah, East Malaysia. The project concerned the assemblage structure, gas physiology and landscape gas fluxes of termites in pristine and two ages of secondary, dipterocarp forest. The DVCA termite fauna is typical of the Sunda region, dominated by Termes-group soil-feeders and Nasutitermitinae. Selective logging appears to have relatively little effect on termite assemblages, although soil-feeding termites may be moderately affected by this level of disturbance. Species composition changes, but to a small extent when considered against the background level of compositional differences within the Sunda region. Physiologically the assemblage is very like others that have been studied, although there are some species that do not fit on the expected body size-metabolic rate curve. As elsewhere, soil-feeders and soil-wood interface-feeders tend to produce more methane. As with the termite assemblage characteristics, gross gas and energy fluxes do not differ significantly between logged and unlogged sites. Although gross methane fluxes are high, all the soils at DVCA were methane sinks, suggesting that methane oxidation by methanotrophic bacteria was a more important process than methane production by gut archaea. This implies that methane production by termites in South-East Asia is not contributing significantly to the observed increase in levels of methane production worldwide. Biomass density, species richness, clade complement and energy flow were much lower at DVCA than at a directly comparable site in southern Cameroon. This is probably due to the different biogeographical histories of the areas.

Animals↗

Protein secondary structure prediction based on position-specific scoring matrices.

A two-stage neural network has been used to predict protein secondary structure based on the position specific scoring matrices generated by PSI-BLAST. Despite the simplicity and convenience of the approach used, the results are found to be superior to those produced by other methods, including the popular PHD method according to our own benchmarking results and the results from the recent Critical Assessment of Techniques for Protein Structure Prediction experiment (CASP3), where the method was evaluated by stringent blind testing. Using a new testing set based on a set of 187 unique folds, and three-way cross-validation based on structural similarity criteria rather than sequence similarity criteria used previously (no similar folds were present in both the testing and training sets) the method presented here (PSIPRED) achieved an average Q3 score of between 76.5% to 78.3% depending on the precise definition of observed secondary structure used, which is the highest published score for any method to date. Given the success of the method in CASP3, it is reasonable to be confident that the evaluation presented here gives a fair indication of the performance of the method in general.

Algorithms↗

A systematic comparison of protein structure classifications: SCOP, CATH and FSSP.

BACKGROUND: Several methods of structural classification have been developed to introduce some order to the large amount of data present in the Protein Data Bank. Such methods facilitate structural comparisons and provide a greater understanding of structure and function. The most widely used and comprehensive databases are SCOP, CATH and FSSP, which represent three unique methods of classifying protein structures: purely manual, a combination of manual and automated, and purely automated, respectively. In order to develop reliable template libraries and benchmarks for protein-fold recognition, a systematic comparison of these databases has been carried out to determine their overall agreement in classifying protein structures. RESULTS: Approximately two-thirds of the protein chains in each database are common to all three databases. Despite employing different methods, and basing their systems on different rules of protein structure and taxonomy, SCOP, CATH and FSSP agree on the majority of their classifications. Discrepancies and inconsistencies are accounted for by a small number of explanations. Other interesting features have been identified, and various differences between manual and automatic classification methods are presented. CONCLUSIONS: Using these databases requires an understanding of the rules upon which they are based; each method offers certain advantages depending on the biological requirements and knowledge of the user. The degree of discrepancy between the systems also has an impact on reliability of prediction methods that employ these schemes as benchmarks. To generate accurate fold templates for threading, we extract information from a consensus database, encompassing agreements between SCOP, CATH and FSSP.

Databases, Factual↗

GenTHREADER: an efficient and reliable protein fold recognition method for genomic sequences.

A new protein fold recognition method is described which is both fast and reliable. The method uses a traditional sequence alignment algorithm to generate alignments which are then evaluated by a method derived from threading techniques. As a final step, each threaded model is evaluated by a neural network in order to produce a single measure of confidence in the proposed prediction. The speed of the method, along with its sensitivity and very low false-positive rate makes it ideal for automatically predicting the structure of all the proteins in a translated bacterial genome (proteome). The method has been applied to the genome of Mycoplasma genitalium, and analysis of the results shows that as many as 46 % of the proteins derived from the predicted protein coding regions have a significant relationship to a protein of known structure. In some cases, however, only one domain of the protein can be predicted, giving a total coverage of 30 % when calculated as a fraction of the number of amino acid residues in the whole proteome.

Algorithms↗

Management of distal tracheal stenosis.

OBJECTIVE: To evaluate the treatment, perioperative management, and outcome of infants who underwent repair of congenital tracheal stenosis. We hypothesized that early resection and tracheoplasty with early weaning of ventilatory support results in less mucosal injury, and thus better outcome. DESIGN: Retrospective study from 1986 to 1996. SETTING: Tertiary care children's hospital. PATIENTS: Seventeen consecutive infants with congenital tracheal stenosis, aged from birth to 16 months. Fifteen patients had complete tracheal rings, 6 of whom also had a left pulmonary artery sling. Fourteen patients underwent either tracheoplasty or resection and reanastomosis of the trachea, both facilitated by cardiopulmonary bypass. RESULTS: Six patients underwent resection and reanastomosis; 4 patients were extubated within 2 to 5 days without sequelae. There was 1 unrelated perioperative death. Two patients required reintubation. Eight patients required tracheoplasty due to severe tracheal stenosis and had variable postoperative courses. Seven of 14 patients required 0 to 1 postoperative bronchoscopies. Seven of 14 patients required 2 to 7 bronchoscopies for granulation tissue formation, cicatrix, graft collapse, and tracheitis. One patient required numerous procedures and revision tracheoplasty for cicatrix and stenosis. CONCLUSIONS: Correction of short-segment (<5 rings) tracheal stenosis by resection and reanastomosis of the trachea with the aid of cardiopulmonary bypass and early weaning of ventilatory support is recommended. Tracheoplasty using either the castellation technique or slide tracheoplasty is recommended in the treatment of infants with severe (long segment) tracheal stenosis.

Bronchoscopy↗

Successful recognition of protein folds using threading methods biased by sequence similarity and predicted secondary structure.

Analysis of our fold recognition results in the 3rd Critical Assessment in Structure Prediction (CASP3) experiment, using the programs THREADER 2 and GenTHREADER, shows an encouraging level of overall success. Of the 23 submitted predictions, 20 targets showed no clear sequence similarity to proteins of known 3D structure. These 20 targets can be divided into 22 domains, of which, 20 domains either entirely match a previously known fold, or partially match a substantial region of a known fold. Of these 20 domains, we correctly assigned the folds in 10 cases.

Algorithms↗

The NAC proton treatment planning system.

A three-dimensional proton treatment planning system called PROXELPLAN has been used at the National Accelerator Centre (NAC) since October 1994. This system is entirely based on the VOXELPLAN planning system, developed at the Deutches Krebsforschungszentrum (DKFZ), Heidelberg, Germany. The VOXELPLAN system provides the treatment planning infrastructure while the proton dose distributions are calculated using a software module that was initially developed at the Royal Marsden Hospital, UK. The proton module has been extensively modified and refined. It uses a rayline-tracing algorithm which is suitable for planning current treatments but is not sufficiently dynamic to accommodate the use of compensators. A sophisticated pencil beam algorithm is currently under development.

Algorithms↗

Nuclear data for radiotherapy: presentation of a new ICRU report and IAEA initiatives.

An ICRU report entitled "Nuclear Data for Neutron and Proton Radiotherapy and for Radiation Protection" is in preparation. The present paper presents an overview of this report, along with examples of some of the results obtained for evaluated nuclear cross sections and kerma coefficients. These cross sections are evaluated using a combination of measured data and the GNASH nuclear model code for elements of importance for biological, dosimetric, beam modification and shielding purposes. In the case of hydrogen both R-matrix and phase-shift scattering theories are used. In the report neutron cross sections and kerma coefficients will be presented up to 150 MeV and proton cross sections up to 250 MeV. An IAEA Consultants' Meeting was also convened to examine the "Status of Nuclear Data needed for Radiation Therapy and Existing Data Development Activities in Member States". Recommendations were made regarding future endeavours.

Models, Theoretical↗