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  • Articles  (7)
  • Oxford University Press  (3)
  • American Geophysical Union  (2)
  • Wiley  (2)
  • American Meteorological Society (AMS)
  • Paleontological Society
  • Nucleic Acids Research  (3)
  • Journal of Geophysical Research JGR - Atmospheres  (2)
  • 60967
  • 7528
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  • Articles  (7)
Publisher
  • Oxford University Press  (3)
  • American Geophysical Union  (2)
  • Wiley  (2)
  • American Meteorological Society (AMS)
  • Paleontological Society
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  • 1
    Publication Date: 2015-12-13
    Description: A 34-year (1979–2012) high-resolution (7 km grid) atmospheric hindcast over the Bohai Sea and the Yellow Sea (BYS) has been performed using COSMO-CLM (CCLM) forced by ERA-Interim reanalysis data (ERA-I). The accuracy of CCLM in surface wind reproduction and the added value of dynamical downscaling to ERA-I have been investigated through comparisons with the QuikSCAT Level2B 12.5 km version3 (L2B12v3) swath data and in situ observations. The results revealed that CCLM has a reliable ability to reproduce the regional wind characteristics over the BYS. Added value to ERA-I has been detected in the coastal areas with complex orography. CCLM wind quality had strong seasonal variability, with better performance in the summer relative to ERA-I, even in the offshore areas. CCLM was better able to represent light and moderate winds but has even more added value for strong winds relative to ERA-I. The spatial digital filter method was used to investigate the scale of the added value, and the results show that CCLM adds value to ERA-I mainly in medium scales of wind variability. Furthermore, wind climatology was investigated, and significant increasing trends in the south Yellow Sea especially in winter and spring were found for seasonal mean wind speeds.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 2
    Publication Date: 2015-03-14
    Description: The Cdk12/CycK complex promotes expression of a subset of RNA polymerase II genes, including those of the DNA damage response. CDK12 is among only nine genes with recurrent somatic mutations in high-grade serous ovarian carcinoma. However, the influence of these mutations on the Cdk12/CycK complex and their link to cancerogenesis remain ill-defined. Here, we show that most mutations prevent formation of the Cdk12/CycK complex, rendering the kinase inactive. By examining the mutations within the Cdk12/CycK structure, we find that they likely provoke structural rearrangements detrimental to Cdk12 activation. Our mRNA expression analysis of the patient samples containing the CDK12 mutations reveals coordinated downregulation of genes critical to the homologous recombination DNA repair pathway. Moreover, we establish that the Cdk12/CycK complex occupies these genes and promotes phosphorylation of RNA polymerase II at Ser2. Accordingly, we demonstrate that the mutant Cdk12 proteins fail to stimulate the faithful DNA double strand break repair via homologous recombination. Together, we provide the molecular basis of how mutated CDK12 ceases to function in ovarian carcinoma. We propose that CDK12 is a tumor suppressor of which the loss-of-function mutations may elicit defects in multiple DNA repair pathways, leading to genomic instability underlying the genesis of the cancer.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 3
    Publication Date: 2012-06-28
    Description: The Drosophila Suppressor of Hairy-wing [Su(Hw)] protein is a globally expressed, multi-zinc finger (ZnF) DNA-binding protein. Su(Hw) forms a classic insulator when bound to the gypsy retrotransposon and is essential for female germline development. These functions are genetically separable, as exemplified by Su(Hw) f that carries a defective ZnF10, causing a loss of insulator but not germline function. Here, we completed the first genome-wide analysis of Su(Hw)-binding sites (SBSs) in the ovary, showing that tissue-specific binding is not responsible for the restricted developmental requirements for Su(Hw). Mapping of ovary Su(Hw) f SBSs revealed that female fertility requires binding to only one third of the wild-type sites. We demonstrate that Su(Hw) f retention correlates with binding site affinity and partnership with Modifier of (mdg4) 67.2 protein. Finally, we identify clusters of co-regulated ovary genes flanked by Su(Hw) f bound sites and show that loss of Su(Hw) has limited effects on transcription of these genes. These data imply that the fertility function of Su(Hw) may not depend upon the demarcation of transcriptional domains. Our studies establish a framework for understanding the germline Su(Hw) function and provide insights into how chromatin occupancy is achieved by multi-ZnF proteins, the most common transcription factor class in metazoans.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 4
    Publication Date: 2017-08-12
    Description: This paper demonstrates two important aspects of regional dynamical downscaling of multi-decadal atmospheric re-analysis. First, that in this way skillful regional descriptions of multi-decadal climate variability may be constructed in regions with little or no local data. Secondly, that the concept of large-scale constraining allows global downscaling, so that global re-analyses may be completed by additions of consistent detail in all regions of the world. Global re-analyses suffer from inhomogeneities. However, their large-scale componenst are mostly homogeneous; Therefore, the concept of downscaling may be applied to homogeneously complement the large-scale state of the re-analyses with regional detail – wherever the condition of homogeneity of the description of large scales is fulfilled. Technically this can be done by dynamical downscaling using a regional or global climate model, which's large scales are constrained by spectral nudging. This approach has been developed and tested for the region of Europe, and a skillful representation of regional weather risks – in particular marine risks – was identified. We have run this system in regions with reduced or absent local data coverage, such as Central Siberia, the Bohai and Yellow Sea, Southwestern Africa and the South Atlantic. Also a global simulation was computed, which adds regional features to prescribed global dynamics. Our cases demonstrate that spatially detailed reconstructions of the climate state and its change in the recent three to six decades add useful supplementary information to existing observational data for mid-latitude and sub-tropical regions of the world.
    Print ISSN: 0148-0227
    Topics: Geosciences , Physics
    Published by Wiley on behalf of American Geophysical Union (AGU).
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  • 5
    Publication Date: 2014-07-04
    Description: The bromodomain protein Brd4 regulates the transcription of signal-inducible genes. This is achieved by recruiting the positive transcription elongation factor P-TEFb to promoters by its P-TEFb interaction domain (PID). Here we show that Brd4 stimulates the kinase activity of P-TEFb for phosphorylation of the C-terminal domain (CTD) of RNA polymerase II over basal levels. The CTD phosphorylation saturation levels, the preferences for pre-phosphorylated substrates, and the phosphorylation specificity for Ser5 of the CTD however remain unchanged. Inhibition of P-TEFb by Hexim1 is relieved by Brd4, although no mutual displacement with the Cyclin T-binding domain of Hexim1 was observed. Brd4 PID shows a surprising sequence motif similarity to the trans -activating Tat protein from HIV-1, which includes a core RxL motif, a polybasic cluster known as arginine-rich motif, and a C-terminal leucine motif. Mutation of these motifs to alanine significantly diminished the stimulatory effect of Brd4 and fully abrogated its activation potential in presence of Hexim1. Yet the protein was not found to bind Cyclin T1 as Tat, but only P-TEFb with a dissociation constant of 0.5 μM. Our data suggest a model where Brd4 acts on the kinase subunit of P-TEFb to relieve inhibition and stimulate substrate recognition.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
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  • 6
    Publication Date: 2017-08-27
    Description: This paper demonstrates two important aspects of regional dynamical downscaling of multidecadal atmospheric reanalysis. First, that in this way skillful regional descriptions of multidecadal climate variability may be constructed in regions with little or no local data. Second, that the concept of large-scale constraining allows global downscaling, so that global reanalyses may be completed by additions of consistent detail in all regions of the world. Global reanalyses suffer from inhomogeneities. However, their large-scale componenst are mostly homogeneous; Therefore, the concept of downscaling may be applied to homogeneously complement the large-scale state of the reanalyses with regional detail—wherever the condition of homogeneity of the description of large scales is fulfilled. Technically, this can be done by dynamical downscaling using a regional or global climate model, which's large scales are constrained by spectral nudging. This approach has been developed and tested for the region of Europe, and a skillful representation of regional weather risks—in particular marine risks—was identified. We have run this system in regions with reduced or absent local data coverage, such as Central Siberia, the Bohai and Yellow Sea, Southwestern Africa, and the South Atlantic. Also, a global simulation was computed, which adds regional features to prescribed global dynamics. Our cases demonstrate that spatially detailed reconstructions of the climate state and its change in the recent three to six decades add useful supplementary information to existing observational data for midlatitude and subtropical regions of the world. ©2017. American Geophysical Union. All Rights Reserved.
    Print ISSN: 2169-897X
    Electronic ISSN: 2169-8996
    Topics: Geosciences , Physics
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  • 7
    Publication Date: 2016-01-07
    Print ISSN: 2169-897X
    Electronic ISSN: 2169-8996
    Topics: Geosciences , Physics
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