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Biomedical subjects

G N Cohen

Publications and source records attributed to G N Cohen.

At least 19 recordsLinked to original sources
PubMed2004

Combining pattern discovery and discriminant analysis to predict gene co-regulation.

MOTIVATION: Several pattern discovery methods have been proposed to detect over-represented motifs in upstream sequences of co-regulated genes, and are for example used to predict cis-acting elements from clusters of co-expressed genes. The clusters to be analyzed are often noisy, containing a mixture of co-regulated and non-co-regulated genes. We propose a method to discriminate co-regulated from non-co-regulated genes on the basis of counts of pattern occurrences in their non-coding sequences. METHODS: String-based pattern discovery is combined with discriminant analysis to classify genes on the basis of putative regulatory motifs. RESULTS: The approach is evaluated by comparing the significance of patterns detected in annotated regulons (positive control), random gene selections (negative control) and high-throughput regulons (noisy data) from the yeast Saccharomyces cerevisiae. The classification is evaluated on the annotated regulons, and the robustness and rejection power is assessed with mixtures of co-regulated and random genes.

Algorithms↗
PubMed2003

Intraoperative dynamic dosimetry for prostate implants.

This paper describes analytic tools in support of a paradigm shift in brachytherapy treatment planning for prostate cancer--a shift from standard pre-planning to intraoperative planning using dosimetric feedback based on the actual deposited seed positions within the prostate. The method proposed is guided by several desiderata: (a) bringing both planning and evaluation in the operating room (i.e. make post-implant evaluation superfluous) therefore making rectifications--if necessary--still achievable; (b) making planning and implant evaluation consistent by using the same imaging system (ultrasound); and (c) using only equipment commonly found in a hospital operating room. The intraoperative dosimetric evaluation is based on the fusion between ultrasound images and 3D seed coordinates reconstructed from fluoroscopic projections. Automatic seed detection and registration of the fluoroscopic and ultrasound information, two of the three key ingredients needed for the intraoperative dynamic dosimetry optimization (IDDO), are explained in detail. The third one, the reconstruction of 3D coordinates from projections, was reported in a previous article. The algorithms were validated using a custom-designed phantom with non-radioactive (dummy) seeds. Also, fluoroscopic images were taken at the conclusion of an actual permanent prostate implant and compared with data on the same patient obtained from radiographic-based post-implant evaluation. To offset the effect of organ motion the comparison was performed in terms of the proximity function of the two seed distributions. The agreement between the intra- and post-operative seed distributions was excellent.

Algorithms↗
PubMed2002

Operator-free, film-based 3D seed reconstruction in brachytherapy.

In brachytherapy implants, the accuracy of dose calculation depends on the ability to localize radioactive sources correctly. If performed manually using planar images, this is a time-consuming and often error-prone process-primarily because each seed must be identified on (at least) two films. In principle, three films should allow automatic seed identification and position reconstruction; however, practical implementation of the numerous algorithms proposed so far appears to have only limited reliability. The motivation behind this work is to create a fast and reliable system for real-time implant evaluation using digital planar images obtained from radiotherapy simulators, or mobile x-ray/fluoroscopy systems. We have developed algorithms and code for 3D seed coordinate reconstruction. The input consists of projections of seed positions in each of three isocentric images taken at arbitrary angles. The method proposed here consists of a set of heuristic rules (in a sense, a learning algorithm) that attempts to minimize seed misclassifications. In the clinic, this means that the system must be impervious to errors resulting from patient motion as well as from finite tolerances accepted in equipment settings. The software program was tested with simulated data, a pelvic phantom and patient data. One hundred and twenty permanent prostate implants were examined (105 125I and 15 103Pd) with the number of seeds ranging from 35 to 138 (average 79). The mean distance between actual and reconstructed seed positions is in the range 0.03-0.11 cm. On a Pentium III computer at 600 MHz the reconstruction process takes 10-30 s. The total number of seeds is independently validated. The process is robust and able to account for errors introduced in the clinic.

Algorithms↗
PubMed2000

An independent dose-to-point calculation program for the verification of high-dose-rate brachytherapy treatment planning.

PURPOSE: We describe computer software that performs, quickly and accurately, secondary dose calculations for high-dose-rate (HDR) treatment plans, including those employed for prostate treatments. METHODS: The program takes as primary input the data file used by the HDR remote afterloader console for treatment. Dosimetric calculations are performed using the Meisberger polynomial and the anisotropy table for the HDR Iridium-192 source. For standard applicators, treatment geometry is automatically reconstructed and the dose is calculated at relevant reference point(s). Template-based treatment plans (e.g., prostate) require additional user input; the dose calculation is then performed at user-selected reference points. A total dwell time calculation for volume and planar implants using the Manchester tables was also implemented. RESULTS: For fixed-geometry HDR procedures, secondary dose calculations are within 2% of the treatment plan, and results are available for review instantly. For more general applications, the calculated and planned doses are typically within 3% at the prescription isodose line. The Manchester-based dwell time calculation is within 10% of the planned time.

Algorithms↗
PubMed1993

Directed evolution of biosynthetic pathways. Recruitment of cysteine thioethers for constructing the cell wall of Escherichia coli.

We report that expansion of thioether biosynthesis in Escherichia coli generates sulfur-containing amino acids that can replace meso-diaminopimelate, the essential amino acid used for cross-linking the cell wall. This was accomplished by jointly overexpressing the metB gene coding for L-cystathionine gamma-synthase and disrupting the metC gene, whose product, L-cystathionine beta-lyase, is responsible for the destruction of L-cystathionine and other L-cysteine thioethers. As a result, meso-lanthionine and L-allo-cystathionine were produced endogenously and incorporated in the peptidoglycan, thereby enabling E. coli strains auxotrophic for diaminopimelate to grow in its absence. Thus, current techniques of metabolic engineering can be applied to evolving the chemical constitution of living cells beyond its present state.

Alanine↗
PubMed1993

Asthma and work.

Explore the source record for details and available documents.

Asthma↗
PubMed1989

Cooperative tandem binding of met repressor of Escherichia coli.

We present biochemical and genetic data to support the hypothesis that the Escherichia coli met repressor, MetJ, binds to synthetic and natural operator sequences in tandem arrays such that repression depends not only on the affinity of the DNA-protein interaction, but also on protein-protein contacts along the tandem array. This represents a novel form of regulatory switch. Furthermore, there seems to be homology between the organization of the met and trp operators.

Apoproteins↗
PubMed1989

Pressure-induced changes in the secondary structure of the Escherichia coli methionine repressor protein.

The effect of hydrostatic pressure on the conformational properties of the E. coli methionine repressor protein in aqueous solution was investigated by infrared spectroscopy. Changes in hydrostatic pressure produce dramatic changes in the spectral region of the conformation-sensitive amide I band. As the pressure is raised up to 18 kbar, the protein undergoes a rearrangement of alpha-helical segments into beta-type structures; after the pressure is released the beta-strands reconvert into less ordered alpha-helical or random segments.

Bacterial Proteins↗
PubMed1989

Cell type-specific expression of the human transferrin gene. Role of promoter, negative, and enhancer elements.

Transferrin (Tf), the iron transport protein of vertebrate serum, is mainly synthesized in the liver. cis-Acting DNA elements required for liver-specific expression of the human Tf gene were identified by transient and stable expression assays in human hepatoma (HepG2 and Hep3B) and epithelial carcinoma (HeLa) cell lines. Deletion analysis of the 5' DNA sequences of the gene have defined four functionally different regions: (a) A cell type-specific promoter located between positions -125 and -45 which interacts with two nuclear factors and is sufficient for liver-specific expression. (b) A distal promoter region from -620 to -125 base pairs containing positive and negative cis-acting elements which regulate the promoter activity. (c) A negative-acting region between -1.0 and -0.6 kilobase pairs which down-regulates transcription from the Tf promoter. (d) An enhancer located between -4.0 and -3.3 kilobase pairs which is more active in hepatoma than in HeLa cells. Thus, Tf gene expression is modulated by a combination of multiple positive and negative cis-acting elements. The expression results are discussed with respect to our previous description of the trans-acting factors interacting with the proximal and distal promoter regions.

Base Sequence↗
PubMed1989

Interaction of DNA-binding proteins with the tissue-specific human apolipoprotein-AII enhancer.

The identification of the binding sites for liver nuclear proteins present in the enhancer that control the cell specific transcription of the human apolipoprotein AII gene is reported. Five adjacent binding sites (motifs I to V) were identified. The motifs III, IV and V can be occupied differently by liver or HeLa nuclear proteins. Two hypersensitive zones (between motifs II-III and IV-V) are present only when liver nuclear extracts were tested. A first characterization of the factors reveal that motif IV interacts with the hepatic transcription factors Tf-LF1 (29) and LF-A1 (28, 30). A CCAAT binding protein, different from CTF/NF1, appears to bind to the motif II. The different binding sites share specific DNA sequences principally with 5' regulatory regions of other apolipoprotein genes.

Apolipoprotein A-II↗