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  • 1
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2020
    In:  Proceedings of the National Academy of Sciences Vol. 117, No. 41 ( 2020-10-13), p. 25601-25608
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 117, No. 41 ( 2020-10-13), p. 25601-25608
    Abstract: Investigations on the chronic health effects of fine particulate matter (PM 2.5 ) exposure in China are limited due to the lack of long-term exposure data. Using satellite-driven models to generate spatiotemporally resolved PM 2.5 levels, we aimed to estimate high-resolution, long-term PM 2.5 and associated mortality burden in China. The multiangle implementation of atmospheric correction (MAIAC) aerosol optical depth (AOD) at 1-km resolution was employed as a primary predictor to estimate PM 2.5 concentrations. Imputation techniques were adopted to fill in the missing AOD retrievals and provide accurate long-term AOD aggregations. Monthly PM 2.5 concentrations in China from 2000 to 2016 were estimated using machine-learning approaches and used to analyze spatiotemporal trends of adult mortality attributable to PM 2.5 exposure. Mean coverage of AOD increased from 56 to 100% over the 17-y period, with the accuracy of long-term averages enhanced after gap filling. Machine-learning models performed well with a random cross-validation R 2 of 0.93 at the monthly level. For the time period outside the model training window, prediction R 2 values were estimated to be 0.67 and 0.80 at the monthly and annual levels. Across the adult population in China, long-term PM 2.5 exposures accounted for a total number of 30.8 (95% confidence interval [CI]: 28.6, 33.2) million premature deaths over the 17-y period, with an annual burden ranging from 1.5 (95% CI: 1.3, 1.6) to 2.2 (95% CI: 2.1, 2.4) million. Our satellite-based techniques provide reliable long-term PM 2.5 estimates at a high spatial resolution, enhancing the assessment of adverse health effects and disease burden in China.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2020
    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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  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 105, No. 10 ( 2008-03-11), p. 3933-3938
    Abstract: We have designed MI-219 as a potent, highly selective and orally active small-molecule inhibitor of the MDM2–p53 interaction. MI-219 binds to human MDM2 with a K i value of 5 nM and is 10,000-fold selective for MDM2 over MDMX. It disrupts the MDM2–p53 interaction and activates the p53 pathway in cells with wild-type p53, which leads to induction of cell cycle arrest in all cells and selective apoptosis in tumor cells. MI-219 stimulates rapid but transient p53 activation in established tumor xenograft tissues, resulting in inhibition of cell proliferation, induction of apoptosis, and complete tumor growth inhibition. MI-219 activates p53 in normal tissues with minimal p53 accumulation and is not toxic to animals. MI-219 warrants clinical investigation as a new agent for cancer treatment.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2008
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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