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Biomedical subjects

N Goodman

Publications and source records attributed to N Goodman.

At least 19 recordsLinked to original sources

Biological data becomes computer literate: new advances in bioinformatics.

Bioinformatics is an art and science concerned with the use of computing in biological research areas such as genomics, transcriptomics, proteomics, genetics, and evolution. This review paints a broad picture of bioinformatics, drawing examples from genomic sequencing and microarray analysis. I highlight the role of bioinformatics at multiple points along the path from high-tech data generation to biological discovery.

Computational Biology↗

The effect of corona discharge on Der p 1.

BACKGROUND: Reduction of house dust mite allergens in the domestic environment can play an important part in reducing sensitization and in the amelioration of symptoms in atopic individuals. Chemical and physical methods have been tried with varied levels of success. The present paper presents a novel electrostatic way of destroying Der p 1, the major mite allergen. OBJECTIVE: To assess the efficacy of negative Trichel, negative continuous glow, positive pulse and positive continuous glow corona in destroying Der p 1. To determine whether ozone has any effect on the integrity of Der p 1 in the experimental conditions present. METHODS: A simple point-to-plane apparatus was used to irradiate samples of Der p 1 for periods of 1, 15, 30, 45, 60, 120, 180, 240 and 300 min. Controls were exposed to the atmosphere with no corona products present for the equivalent time. The effect of the corona by-product ozone was investigated alone by exposing samples of Der p 1 to molecular ozone for 60 min. Der p 1 concentration was quantified by two-site monoclonal antibody ELISA. RESULTS: High current negative glow resulted in a 67.37% reduction in Der p 1 concentration after 300 min compared with a 50.5% reduction from a low current Trichel regime. High current positive glow corona gave a reduction of 25.22% while a low current positive pulse corona caused a 13.72% reduction after 300 min. All these reductions were statistically significant (P < 0.05) compared with unexposed controls. Negative corona always gave greater percentage reductions in Der p 1 concentration for each time exposure investigated. The pattern of percentage reduction follows an exponential rise to maximum relationship in respect to time. Samples of Der p 1 were not affected by exposure to molecular ozone. CONCLUSION: These data indicate corona products to be a powerful new method of destroying Der p 1 allergen that is not dependent on the presence of the oxidizing corona product ozone.

Allergens↗

Sharp packaging.

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Accidents, Occupational↗

Long-range destruction of Der p 1 using experimental and commercially available ionizers.

BACKGROUND: To reduce the risk of sensitization and the elicitation of allergy symptoms, it is important to reduce the level of allergens in the home. It has previously been demonstrated that corona discharge, the process by which ionizers produce ions, can destroy the major house dust mite allergen Der p 1. OBJECTIVE: In this paper the denaturing efficacy of an experimental ionizer and two commercially available products are evaluated. METHODS: The first test was conducted in an electrically grounded chamber with samples of Der p 1 placed in various positions for 1, 2 and 3 weeks. The second test was conducted in situ in an unoccupied, furnished office room for 1 week. Der p 1 concentration was quantified by two-site monoclonal antibody enzyme-linked immunosorbent assay (ELISA). RESULTS: All ionizers in both tests caused significant reductions in allergen concentration (P < 0.05), reaching a maximum of 92% with the experimental ionizer in the chamber after 3 weeks. The percentage reductions observed in situ with the experimental and the larger commercial ionizer were similar, reaching a maximum of 32% at a distance of 4 m away from the experimental ionizer after 1 week of exposure. CONCLUSION: With a revised protocol for use, air ionizers may offer a simple, efficient and inexpensive way to reduce allergen levels in the domestic environment.

Air Ionization↗

Uniform integration of genome mapping data using intersection graphs.

MOTIVATION: The methods for analyzing overlap data are distinct from those for analyzing probe data, making integration of the two forms awkward. Conversion of overlap data to probe-like data elements would facilitate comparison and uniform integration of overlap data and probe data using software developed for analysis of STS data. RESULTS: We show that overlap data can be effectively converted to probe-like data elements by extracting maximal sets of mutually overlapping clones. We call these sets virtual probes, since each set determines a site in the genome corresponding to the region which is common among the clones of the set. Finding the virtual probes is equivalent to finding the maximal cliques of a graph. We modify a known maximal-clique algorithm such that it finds all virtual probes in a large dataset within minutes. We illustrate the algorithm by converting fingerprint and Alu-PCR overlap data to virtual probes. The virtual probes are then analyzed using double-linkage intersection graphs and structure graphs to show that methods designed for STS data are also applicable to overlap data represented as virtual probes. Next we show that virtual probes can produce a uniform integration of different kinds of mapping data, in particular STS probe data and fingerprint and Alu-PCR overlap data. The integrated virtual probes produce longer double-linkage contigs than STS probes alone, and in conjunction with structure graphs they facilitate the identification and elimination of anomalies. Thus, the virtual-probe technique provides: (i) a new way to examine overlap data; (ii) a basis on which to compare overlap data and probe data using the same systems and standards; and (iii) a unique and useful way to uniformly integrate overlap data with probe data.

Algorithms↗

The riddle of femininity: the interplay of primary femininity and the castration complex in analytic listening.

This study elucidates the application of an analytic attitude to questions of gender and sexuality. The paper reports on a study group's exploration of the relative heuristic use of two important organising concepts in analytic work with female analysands: primary feminity and the phallic castration complex. A tendency to cling to one position over the other skews analytic listening. Two cases are presented of women struggling to consolidate positive feminine identifications and, to that end, working through conflicting feminine identifications and defences against a resolution of the awareness of gender differences. Analytic listening requires a view of each psychic construction as a layer to be understood in its own right yet as a cloak soon to reveal the next layer--a different construction. The study includes observations on perverse fantasies in women.

Adult↗

Treatment of high-grade low-stage prostate cancer by high-dose-rate brachytherapy.

BACKGROUND AND PURPOSE: The best management of patients with low-stage, high-grade prostate cancer remains unclear. In an attempt to improve the outcomes of this high-risk group, we have offered those with Gleason > or =7 cancers removable-source high-dose-rate (HDR) brachytherapy in combination with external-beam radiation. PATIENTS AND METHODS: We reviewed the clinical histories of 61 consecutive patients with high-grade clinical stage T1-T2 lesions who received the combination radiation therapy between March 1997 and November 1998. The average Gleason score was 7.5. The HDR brachytherapy was given in three sessions with removable-source afterloaded (192)Ir to a minimum peripheral dose of 6 Gy. Conformal external-beam radiation in 25 fractions to a dose of 50 Gy was given beginning 1 week later. Patients with prostate volumes >40 cc received a luteinizing hormone-releasing hormone analog before brachytherapy. RESULTS: Among the 52 patients available for follow-up (average duration 11.8 months), there has been one death from prostate cancer. After treatment, only one patient had an initial rise in serum prostate specific antigen (PSA) concentration. In addition to the patient who died, there have been three confirmed treatment failures. Toxicity was mild, with only two patients having RTOG grade 3 or 4 effects. Neither of them required surgery. CONCLUSION: Although long-term results are not available, available data suggest that HDR brachytherapy plus external-beam radiation is at least as effective as any single therapy for high-risk, low-stage prostate cancer. The toxicity is acceptable.

Aged↗

Revealing hidden interval graph structure in STS-content data.

MOTIVATION: STS-content data for genomic mapping contain numerous errors and anomalies resulting in cross-links among distant regions of the genome. Identification of contigs within the data is an important and difficult problem. RESULTS: This paper introduces a graph algorithm which creates a simplified view of STS-content data. The shape of the resulting structure graph provides a quality check - coherent data produce a straight line, while anomalous data produce branches and loops. In the latter case, it is sometimes possible to disentangle the various paths into subsets of the data covering contiguous regions of the genome, i.e. contigs. These straight subgraphs can then be analyzed in standard ways to construct a physical map. A theoretical basis for the method is presented along with examples of its application to current STS data from human genome centers. AVAILABILITY: Freely available on request.

Algorithms↗

The LabBase system for data management in large scale biology research laboratories.

MOTIVATION: The development of laboratory information management systems (LIMSs) for large scale biology research projects can be a challenging problem. Many such projects generate complex datasets via complex procedures that undergo continuous refinement. A key software challenge is to simplify the database-development task so that databases can be built and modified quickly enough to keep pace with changing project-requirements. RESULTS: LabBase extends the facilities offered by relational database systems to simplify the task of creating databases for large scale biology research projects. LabBase provides a structural object data model, similar to ACEDB, and adds to this the concepts of Materials, Steps, and States: Materials are objects representing the identifiable things that participate in a laboratory protocol; Steps are objects reporting the results of a laboratory or analytical procedure; and States are objects denoting places in a laboratory protocol. The system provides a data definition language for succinctly defining laboratory databases, and operations for conveniently storing and retrieving data in such databases. The system also provides support for workflow management. LabBase is implemented in Perl5 and provides a natural interface for laboratory application programs written in Perl. AVAILABILITY: The software is freely available. Contact the authors. CONTACT: nat@jax.org

Computational Biology↗

A model system for studying the integration of molecular biology databases.

MOTIVATION: Integration of molecular biology databases remains limited in practice despite its practical importance and considerable research effort. The complexity of the problem is such that an experimental approach is mandatory, yet this very complexity makes it hard to design definitive experiments. This dilemma is common in science, and one tried-and-true strategy is to work with model systems. We propose a model system for this problem, namely a database of genes integrating diverse data across organisms, and describe an experiment using this model. RESULTS: We attempted to construct a database of human and mouse genes integrating data from GenBank and the human and mouse genome-databases. We discovered numerous errors in these well-respected databases: approximately 15% of genes are apparently missing from the genome-databases; links between the sequence and genome-databases are missing for another 5-10% of the cases; about a third of likely homology links are missing between the genome-databases; 10-20% of entries classified as 'genes' are apparently misclassified. By using a model system, we were able to study the problems caused by anomalous data without having to face all the hard problems of database integration. CONTACT: nat@jax.org

Animals↗

A map of 75 human ribosomal protein genes.

We mapped 75 genes that collectively encode >90% of the proteins found in human ribosomes. Because localization of ribosomal protein genes (rp genes) is complicated by the existence of processed pseudogenes, multiple strategies were devised to identify PCR-detectable sequence-tagged sites (STSs) at introns. In some cases we exploited specific, pre-existing information about the intron/exon structure of a given human rp gene or its homolog in another vertebrate. When such information was unavailable, selection of PCR primer pairs was guided by general insights gleaned from analysis of all mammalian rp genes whose intron/exon structures have been published. For many genes, PCR amplification of introns was facilitated by use of YAC pool DNAs rather than total human genomic DNA as templates. We then assigned the rp gene STSs to individual human chromosomes by typing human-rodent hybrid cell lines. The genes were placed more precisely on the physical map of the human genome by typing of radiation hybrids or screening YAC libraries. Fifty-one previously unmapped rp genes were localized, and 24 previously reported rp gene localizations were confirmed, refined, or corrected. Though functionally related and coordinately expressed, the 75 mapped genes are widely dispersed: Both sex chromosomes and at least 20 of the 22 autosomes carry one or more rp genes. Chromosome 19, known to have a high gene density, contains an unusually large number of rp genes (12). This map provides a foundation for the study of the possible roles of ribosomal protein deficiencies in chromosomal and Mendelian disorders.

Animals↗

The LabFlow system for workflow management in large scale biology research laboratories.

LabFlow is a workflow management system designed for large scale biology research laboratories. It provides a workflow model in which objects flow from task to task under programmatic control. The model supports parallelism, meaning that an object can flow down several paths simultaneously, and sub-workflows which can be invoked subroutine-style from a task. The system allocates tasks to Unix processes to achieve requisite levels of multiprocessing. The system uses the LabBase data management system to store workflow-state and laboratory results. LabFlow provides a Per15 object-oriented framework for defining workflows, and an engine for executing these. The software is freely available.

Artificial Intelligence↗

Informatics--genome and genetic databases.

Databases for biologists are becoming increasingly important. Some of these can be regarded as 'core' resources, such as the bibliographic databases, whereas others are of greater interest to specialists. As comparative genomics develops, however, even databases limited in their scope (e.g. to a single organism) are of great interest to a wider community.

Animals↗