Workers' compensation aspects of noise induced hearing loss.
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Biomedical subjects
Publications and source records attributed to M S Fox.
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A stable association exists between the plasmid Flac and one of the polynucleotide strands of the bacterial chromosome. This polynucleotide strand was isolated and tested for uniqueness by DNA-DNA hybridization analysis. The association was found to involve either bacterial DNA strand.
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Ultraviolet mutagenesis of phage gamma is produced by host functions which are inducible by ultraviolet irradiation of the host cell. Induction kinetics and the half life of the inducible mutagenic DNA repair (SOS-repair) in E.coli have been determined using phage gamma assays. At 37 degrees C, both mutagenic and repair activities are maximal approximately 30 min following irradiation and decay with a half life of approximately 30 min. The presence of 100 mug/ml chloramphenicol during the first 40 min after irradiation completely abolishes induction of repair and mutagenesis. The ultraviolet induction pattern of SOS repair very much resembles that of gamma prophage in lysogenic induction (Monk and Kinross, 1975).
The role of rectification of heteroduplex heterozygotes in the formation of recombinant genotypes involving closely linked markers has been examined. Heteroduplex molecules of bacteriophage lambda DNA, heterozygous at several alleles, have been constructed and the genetic composition of phage present in infective centers derived by transfection with such molecules has been determined. Allele loss and concomitant recombinant formation is frequent, and appears to reflect marker specificity as well as specificities imposed by whether or not the transfection recipient is permissive or nonpermissive for DNA duplication of the transfecting genome. The observations support the proposal that many, perhaps most, of the events involving separation of closely linked markers occur by rectification of non-recombinant heterozygotes.
Bacteriophage crosses using density-labeled parents have been carried out under conditions restricting DNA synthesis. The parental material and genetic contributions to progeny manifesting recombination within a genetic interval sufficiently short to exhibit high negative interference have been examined. The unreplicated products of recombination isolated as phage particles appear to contain long continuous heteroduplex regions which are heterozygous for the closely linked markers. Recombination between closely linked markers seems to be the consequence of the removal of base-pair mismatches that are present within the heteroduplex regions. This localized reduction of heterozygosity within the heteroduplex regions that join the parental components of recombinant DNA molecules can account for high negative interference.
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The function responsible for discrimination among markers (point mutations) in Pneumococcus (hex) was traced back to the early strains used to demonstrate the chemical basis of transformation in the early 1940s. Those currently used laboratory strains failing to manifest this function arose from a single subline of the original strain. The function was also evident in other independently isolated strains including a number of different serological types. The hex function was not evident in transformation between heterologous pneumococcal strains probably as a result of the sensitivity of the function to saturation in the presence of deoxyribonucleic acid from closely related but nonisogenic strains.
The relative biological effectiveness (RBE) values of fast neutrons as a function of dose in the range of dose per fraction being used clinically are reported for effects on several normal mouse tissues. The specific tissues examined were: thymus, spleen, white blood cells (WBC), testes, and small intestine. The RBE values for damage to the thymus (1.2), spleen (1.2), WBC (1.0), and testes (3.0) were independent of neutron dose size. In contrast, the RBE for the small intestine varied between 2.7 and 3.4 and was dependent on the size of the neutron dose. The RBE for intestinal death (2.4) and hematopoietic death (1.1) also is reported.
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Two models designed to account for high negative interference phenomena have been examined. One proposal suggests that many recombination events are the result of insertion of a small single-stranded segment of DNA into a recipient molecule. An alternative explanation for the clustering of genetic exchanges is reduction to homozygosity of genetically heterozygous sites appearing within heteroduplex overlap regions. These proposals have been examined in phage lambda by analyzing the structure of unduplicated recombinants arising from three-factor crosses with tightly linked markers. Double recombinants are found to have received substantial contributions of DNA from both parents. In addition, their patterns of genetic heterozygosity are not readily reconcilable with a single-strand insertion hypothesis. Reconstruction experiments with artifically constructed heteroduplex heterozygotes support the reduction to homozygosity hypothesis and specify the strand polarity of the heterozygous overlap region.
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Nitrous acid-induced and hydroxylamine-induced chemical alterations in transforming DNA result in the loss of biological activity and in mutagenesis. The function responsible for the discrimination between high efficiency and low efficiency markers in pneumococcal transformation, and for the elimination of a substantial fraction of spontaneously occurring mutational events, does not appear to act on integrated DNA carrying these chemical alterations. The chemical modifications result in mutations that are evident among bacteria transformed with the treated DNA. Fusidic acid-resistant mutants isolated in this way have been shown to be predominantly of the low efficiency class. We have previously reported that most mutations of spontaneous origin occurring in this locus are of the high efficiency class, and have suggested that discrimination results from the elimination of specific classes of base pair mismatches that occur as intermediates in transformation. It would appear that the base pair mismatches most effectively eliminated in the discriminating strain of pneumococcus are those of the A:C and G:T type and that the immediate product of transformation with mutagenized DNA involves intermediates that are not recognized as A:C or G:T by the discrimination system.
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