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  • Proceedings of the National Academy of Sciences  (4)
  • 1
    Online Resource
    Online Resource
    Demographic history and rare allele sharing among human populations
    Proceedings of the National Academy of Sciences ; 2011
    In:  Proceedings of the National Academy of Sciences Vol. 108, No. 29 ( 2011-07-19), p. 11983-11988
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 108, No. 29 ( 2011-07-19), p. 11983-11988
    Abstract: High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1019276108
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2011
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy.
    Proceedings of the National Academy of Sciences ; 1977
    In:  Proceedings of the National Academy of Sciences Vol. 74, No. 5 ( 1977-05), p. 1983-1987
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 74, No. 5 ( 1977-05), p. 1983-1987
    Abstract: A therapeutic strategy for combined radiotherapy and chemotherapy of experimental solid tumors has been devised. More effective utilization of combined chemotherapy and radiotherapy may be realized clinically if comparable information is obtained in man. The overall treatment efficiency of successive courses of treatment has been determined by a method that defines tumor response quantitatively over an entire spectrum of tumor responses. The findings of this study have shown that an individual tumor that responds well to the first course of therapy will respond well to the second and third courses of combined modality therapy. Various solid tumors in different animal species have demonstrated variability of response to treatment, analogous to the many types of response found clinically.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.74.5.1983
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1977
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Solid tumor models for the assessment of different treatment modalities: I. Radiation-induced changes in growth rate characteristics of a solid tumor model.
    Proceedings of the National Academy of Sciences ; 1975
    In:  Proceedings of the National Academy of Sciences Vol. 72, No. 7 ( 1975-07), p. 2662-2666
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 72, No. 7 ( 1975-07), p. 2662-2666
    Abstract: A computer program has been developed to quantitatively evaluate changes in tumor growth rates of a solid tumor model (hepatoma 3924A) after a series of radiation doses from 375 R to 3750 R. The computer-derived growth curves are simulated from the volumes of the individual tumors rather than from the mean tumor volume at any specific time point after treatment. The ability to generate data from a family of tumor growth curves permits a more precise evaluation of therapeutic effects on tumors than can be obtained with conventional methods. The quantitative determination of equivalent amounts of radiation needed to produce comparable 5-fluorouracil-induced changes in tumor growth rate has been made. The ability to determine quantitatively radiotherapeutic and chemotherapy equivalents on these solid tumor models has direct implications in regard to our effort to improve the treatment of cancer. At present no specific solid tumor or groups of solid tumors have provided all of the necessary information for clinical utilization in therapeutic scheduling of different forms of cancer treatment. Since solid tumors comprise the majority of human cancer, one of the primary objectives of these studies has been the establishment of a solid tumor model that could serve both as a system for devising improved therapeutic scheduling and for a better understanding of solid tumors.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.72.7.2662
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1975
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
  • 4
    Online Resource
    Online Resource
    Solid tumor models for the assessment of different treatment modalities: systematics of response to radiotherapy and chemotherapy.
    Proceedings of the National Academy of Sciences ; 1976
    In:  Proceedings of the National Academy of Sciences Vol. 73, No. 3 ( 1976-03), p. 818-822
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 73, No. 3 ( 1976-03), p. 818-822
    Abstract: The change of tumor volumes (efficiency) with local tumor radiation doses from 375R to 3750R and 5-fluorouracil (5-FUra) from 50 to 250 mg/kg was assessed in rats bearing hepatoma 3924A. The data were analyzed utilizing a chi2 technique which fits the logarithmic volume response to polynomials. This provided greater flexibility in selecting different mathematical forms, and allows more accurate description of tumor changes after treatment than the least squares analysis previously used. Quantitative information can be obtained on one tumor following treatment by this method. This information is more analogous to the management of a patient with a solid tumor. The results show a continuous increase in efficiency of radiation throughout the radiation dose range from 375R to 3750R. The efficiency of 5-FUra increased slightly but did not continue to increase with doses of 5-FUra higher than 150 mg/kg. This suggests that factors such as toxicity to the host may prevent further increases of the effectiveness of 5-FUra. The time of minimum tumor volume change after radiation was approximately 6 days and for 5-FUra, 6 days. The time for maximum tumor volume change for 5-FUra was 12 days. There was a slight trend upward for maximum growth for increasing radiation doses from 18 to 22 days. The time of occurrence of both minimum and maximum tumor volume change after treatment showed little relationship to increasing doses of radiation and 5-FUra. Parallel studies have shown that the maximum rate of tumor volume change occurs shortly after the recovery of the host from the effect of 5-FUra. It is feasible, therefore, to use chemotherapy alone or in combination with radiotherapy, and optimize the scheduling of these treatment modalities with recovery of the host from previous therapy.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.73.3.818
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 1976
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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    Online Resource
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