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  • 1
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    Selection of code width and analysis of influencing factors in multitransient electromagnetic method (2019)
    Oxford University Press
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    Publication Date: 2019
    Description: 〈span〉〈div〉SUMMARY〈/div〉The multitransient electromagnetic method (MTEM) uses an m pseudo-random binary sequence (PRBS) as the source waveform, which requires deconvolution to recover the impulse response. To obtain high-precision impulse responses, the frequency bandwidth of a pseudo-random sequence should be consistent with the identified system. Code width is an important parameter of an m pseudo-random sequence which determines the maximum frequency bandwidth of an m pseudo-random sequence. If the code width is too wide, the signal-to-noise ratio of the high-frequency section cannot be guaranteed; if it is too narrow, it will result in wastage of transmission time and energy. Therefore, this study developed a method for selecting an appropriate code width and an empirical formula for calculating the appropriate code width on the basis of relevant numerical simulation results. Then, factors influencing the appropriate code width were investigated through formula derivations and numerical simulations. Results showed that in the uniform half-space, the code width is proportional to the conductivity and square of offset. In the 1-D model, the appropriate code width is still proportional to the conductivity, but no longer to the square of the offset.Thank you very much for your remind.I did not refer to any data bases.〈/span〉
    Print ISSN: 2051-1965
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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  • 2
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    Genome-wide association study in Chinese identifies novel loci for blood pressure and hypertension (2015)
    Oxford University Press
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    Publication Date: 2015-01-13
    Description: Hypertension is a common disorder and the leading risk factor for cardiovascular disease and premature deaths worldwide. Genome-wide association studies (GWASs) in the European population have identified multiple chromosomal regions associated with blood pressure, and the identified loci altogether explain only a small fraction of the variance for blood pressure. The differences in environmental exposures and genetic background between Chinese and European populations might suggest potential different pathways of blood pressure regulation. To identify novel genetic variants affecting blood pressure variation, we conducted a meta-analysis of GWASs of blood pressure and hypertension in 11 816 subjects followed by replication studies including 69 146 additional individuals. We identified genome-wide significant ( P 〈 5.0 x 10 –8 ) associations with blood pressure, which included variants at three new loci ( CACNA1D , CYP21A2 , and MED13L ) and a newly discovered variant near SLC4A7 . We also replicated 14 previously reported loci, 8 ( CASZ1 , MOV10 , FGF5 , CYP17A1 , SOX6 , ATP2B1 , ALDH2 , and JAG1 ) at genome-wide significance, and 6 ( FIGN , ULK4 , GUCY1A3 , HFE , TBX3-TBX5 , and TBX3 ) at a suggestive level of P = 1.81 x 10 –3 to 5.16 x 10 –8 . These findings provide new mechanistic insights into the regulation of blood pressure and potential targets for treatments.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 3
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    SUMOylation at K707 of DGCR8 controls direct function of primary microRNA (2015)
    Oxford University Press
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    Publication Date: 2015-09-19
    Description: DGCR8 (DiGeorge syndrome critical region gene 8) is essential for primary microRNA (pri-miRNA) processing in the cell nucleus. It specifically combines with Drosha, a nuclear RNase III enzyme, to form the Microprocessor complex (MC) that cleaves pri-miRNA to precursor miRNA (pre-miRNA), which is further processed to mature miRNA by Dicer, a cytoplasmic RNase III enzyme. Increasing evidences suggest that pri-/pre-miRNAs have direct functions in regulation of gene expression, however the underlying mechanism how it is fine-tuned remains unclear. Here we find that DGCR8 is modified by SUMO1 at the major site K 707 , which can be promoted by its ERK-activated phosphorylation. SUMOylation of DGCR8 enhances the protein stability by preventing the degradation via the ubiquitin proteasome pathway. More importantly, SUMOylation of DGCR8 does not alter its association with Drosha, the MC activity and miRNA biogenesis, but rather influences its affinity with pri-miRNAs. This altered affinity of DGCR8 with pri-miRNAs seems to control the direct functions of pri-miRNAs in recognition and repression of the target mRNAs, which is evidently linked to the DGCR8 function in regulation of tumorigenesis and cell migration. Collectively, our data suggest a novel mechanism that SUMOylation of DGCR8 controls direct functions of pri-miRNAs in gene silencing.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 4
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    p53 increases caspase-6 expression and activation in muscle tissue expressing mutant huntingtin (2014)
    Oxford University Press
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    Publication Date: 2014-01-11
    Description: Activation of caspase-6 in the striatum of both presymptomatic and affected persons with Huntington's disease (HD) is an early event in the disease pathogenesis. However, little is known about the role of caspase-6 outside the central nervous system (CNS) and whether caspase activation might play a role in the peripheral phenotypes, such as muscle wasting observed in HD. We assessed skeletal muscle tissue from HD patients and well-characterized mouse models of HD. Cleavage of the caspase-6 specific substrate lamin A is significantly increased in skeletal muscle obtained from HD patients as well as in muscle tissues from two different HD mouse models. p53, a transcriptional activator of caspase-6, is upregulated in neuronal cells and tissues expressing mutant huntingtin. Activation of p53 leads to a dramatic increase in levels of caspase-6 mRNA, caspase-6 activity and cleavage of lamin A. Using mouse embryonic fibroblasts (MEFs) from YAC128 mice, we show that this increase in caspase-6 activity can be mitigated by pifithrin-α (pifα), an inhibitor of p53 transcriptional activity, but not through the inhibition of p53's mitochondrial pro-apoptotic function. Remarkably, the p53-mediated increase in caspase-6 expression and activation is exacerbated in cells and tissues of both neuronal and peripheral origin expressing mutant huntingtin (Htt). These findings suggest that the presence of the mutant Htt protein enhances p53 activity and lowers the apoptotic threshold, which activates caspase-6. Furthermore, these results suggest that this pathway is activated both within and outside the CNS in HD and may contribute to both loss of CNS neurons and muscle atrophy.
    Print ISSN: 0964-6906
    Electronic ISSN: 1460-2083
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 5
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    Tumor-targeted in vivo gene silencing via systemic delivery of cRGD-conjugated siRNA (2014)
    Oxford University Press
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    Publication Date: 2014-10-10
    Description: RNAi technology is taking strong position among the key therapeutic modalities, with dozens of siRNA-based programs entering and successfully progressing through clinical stages of drug development. To further explore potentials of RNAi technology as therapeutics, we engineered and tested VEGFR2 siRNA molecules specifically targeted to tumors through covalently conjugated cyclo(Arg-Gly-Asp- d -Phe-Lys[PEG-MAL]) (cRGD) peptide, known to bind αvβ3 integrin receptors. cRGD-siRNAs were demonstrated to specifically enter and silence targeted genes in cultured αvβ3 positive human cells (HUVEC). Microinjection of zebrafish blastocysts with VEGFR2 cRGD-siRNA resulted in specific inhibition of blood vessel growth. In tumor-bearing mice, intravenously injected cRGD-siRNA molecules generated no innate immune response and bio-distributed to tumor tissues. Continuous systemic delivery of two different VEGFR2 cRGD-siRNAs resulted in down-regulation of corresponding mRNA (55 and 45%) and protein (65 and 45%) in tumors, as well as in overall reduction of tumor volume (90 and 70%). These findings demonstrate strong potential of cRGD-siRNA molecules as anti-tumor therapy.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 6
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    Phosphorothioate DNA as an antioxidant in bacteria (2012)
    Oxford University Press
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    Publication Date: 2012-10-10
    Description: Diverse bacteria contain DNA with sulfur incorporated stereo-specifically into their DNA backbone at specific sequences (phosphorothioation). We found that in vitro oxidation of phosphorothioate (PT) DNA by hydrogen peroxide (H 2 O 2 ) or peracetic acid has two possible outcomes: DNA backbone cleavage or sulfur removal resulting in restoration of normal DNA backbone. The physiological relevance of this redox reaction was investigated by challenging PT DNA hosting Salmonella enterica cells using H 2 O 2 . DNA phosphorothioation was found to correlate with increasing resistance to the growth inhibition by H 2 O 2 . Resistance to H 2 O 2 was abolished when each of the three dnd genes, required for phosphorothioation, was inactivated. In vivo , PT DNA is more resistant to the double-strand break damage caused by H 2 O 2 than PT-free DNA. Furthermore, sulfur on the modified DNA was consumed and the DNA was converted to PT-free state when the bacteria were incubated with H 2 O 2 . These findings are consistent with a hypothesis that phosphorothioation modification endows DNA with reducing chemical property, which protects the hosting bacteria against peroxide, explaining why this modification is maintained by diverse bacteria.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 7
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    In vivo imaging of protein-protein and RNA-protein interactions using novel far-red fluorescence complementation systems (2014)
    Oxford University Press
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    Publication Date: 2014-08-01
    Description: Imaging of protein–protein and RNA–protein interactions in vivo , especially in live animals, is still challenging. Here we developed far-red mNeptune-based bimolecular fluorescence complementation (BiFC) and trimolecular fluorescence complementation (TriFC) systems with excitation and emission above 600 nm in the ‘tissue optical window’ for imaging of protein–protein and RNA–protein interactions in live cells and mice. The far-red mNeptune BiFC was first built by selecting appropriate split mNeptune fragments, and then the mNeptune-TriFC system was built based on the mNeptune-BiFC system. The newly constructed mNeptune BiFC and TriFC systems were verified as useful tools for imaging protein–protein and mRNA–protein interactions, respectively, in live cells and mice. We then used the new mNeptune-TriFC system to investigate the interactions between human polypyrimidine-tract-binding protein (PTB) and HIV-1 mRNA elements as PTB may participate in HIV mRNA processing in HIV activation from latency. An interaction between PTB and the 3'long terminal repeat region of HIV-1 mRNAs was found and imaged in live cells and mice, implying a role for PTB in regulating HIV-1 mRNA processing. The study provides new tools for in vivo imaging of RNA–protein and protein–protein interactions, and adds new insight into the mechanism of HIV-1 mRNA processing.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 8
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    Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance (2013)
    Oxford University Press
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    Publication Date: 2013-02-20
    Description: DNA gyrase plays a vital role in resolving DNA topological problems and is the target of antibiotics such as fluoroquinolones. Mycobacterium fluoroquinolone resistance protein A (MfpA) from Mycobacterium smegmatis is a newly identified DNA gyrase inhibitor that is believed to confer intrinsic resistance to fluoroquinolones. However, MfpA does not prevent drug-induced inhibition of DNA gyrase in vitro , implying the involvement of other as yet unknown factors. Here, we have identified a new factor, named Mycobacterium fluoroquinolone resistance protein B (MfpB), which is involved in the protection of DNA gyrase against drugs both in vivo and in vitro . Genetic results suggest that MfpB is necessary for MfpA protection of DNA gyrase against drugs in vivo ; an mfpB knockout mutant showed greater susceptibility to ciprofloxacin than the wild-type, whereas a strain overexpressing MfpA and MfpB showed higher loss of susceptibility. Further biochemical characterization indicated that MfpB is a small GTPase and its GTP bound form interacts directly with MfpA and influences its interaction with DNA gyrase. Mutations in MfpB that decrease its GTPase activity disrupt its protective efficacy. Our studies suggest that MfpB, a small GTPase, is required for MfpA-conferred protection of DNA gyrase.
    Print ISSN: 0305-1048
    Electronic ISSN: 1362-4962
    Topics: Biology
    Published by Oxford University Press
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  • 9
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    A functional polymorphism in the promoter of ERK5 gene interacts with tobacco smoking to increase the risk of lung cancer in Chinese populations (2013)
    Oxford University Press
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    Publication Date: 2013-08-15
    Description: Mitogen/extracellular signal-regulated kinase-5 ( MEK5 )/extracellular signal-regulated protein kinase-5 ( ERK5 ) pathway plays a pro-oncogenic role in tumourigenesis by anticell apoptosis, promoting cell proliferation and differentiation in response to extracellular stimuli. As overexpressed MEK5 / ERK5 is involved in the development of lung cancer, we hypothesised that the single nucleotide polymorphisms (SNPs) in MEK5 and ERK5 genes may influence gene expression and thus be associated with lung cancer risk. Five putative functional polymorphisms (rs3743353T〉C, rs7172582C〉T and rs2278076A〉G of MEK5 and rs3866958G〉T and rs2233083C〉T of ERK5 ) were genotyped in two independent case–control studies with a total of 1559 lung cancer patients and 1679 controls in southern and eastern Chinese population. We found the rs3866958G〉T of ERK5 was significantly associated with lung cancer risk, while other SNPs were not. Compared with the rs3866958TG/TT genotypes, the GG genotype conferred an increased risk of lung cancer (odds ratio = 1.30, 95% confidence interval = 1.12–1.51, P = 5.0 x 10 –4 ), and this effect was more pronounced in smokers, accompanying with a significant interaction with smoking ( P interaction = 0.013). The GG genotype also had significant higher mRNA levels of ERK5 in lung cancer tissues than TG/TT genotypes ( P = 1.0 x 10 –4 ); the luciferase reporter with the G allele showed significant higher transcription activities than the T allele, especially after the treatment with tobacco extract in vitro . Our data indicated that the functional polymorphism rs3866958G〉T in ERK5 was associated with an increased lung cancer risk in smokers by virtue of the positive interaction with smoking on promoting the ERK5 expression, which might be a valuable indicator for predicting lung cancer risk in smokers.
    Print ISSN: 0267-8357
    Electronic ISSN: 1464-3804
    Topics: Biology , Medicine
    Published by Oxford University Press
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  • 10
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    Differential acoustic resonance spectroscopy: improved theory and application in the low frequency range (2015)
    Oxford University Press
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    Publication Date: 2015-07-26
    Description: Differential acoustic resonance spectroscopy (DARS) was developed to examine changes in the resonant frequencies of a cavity perturbed by the introduction of a centimetre-sized sample. Resonant frequency shifts, measured at different resonance modes and between empty and sample-loaded cavities, were used to infer the acoustic properties of the loaded samples in the low frequency range (0.5–2 kHz). To some extent, this laboratory-based measurement technique fills an experimental gap between the low-frequency stress–strain method (quasi-static to several kHz) and the ultrasonic transmission technique (hundreds of kHz to MHz). By means of an effective perturbation model against the DARS system, this study presents a Green's function-based theoretical derivation of an amended DARS perturbation formula under a general impedance boundary condition. Numerical and experimental results show that the amended DARS perturbation is able to reflect the DARS operation mechanism more accurately and more precisely than past efforts. In addition, inversion was performed by fitting the resonance frequencies, measured at various locations inside the DARS resonance cavity, in a least-square sense to estimate the acoustic properties of a test sample. Inversion implementation at different resonance modes makes it possible to perform direct dispersion analysis on reservoir rocks at different low-frequency bands. The results of this study show that the DARS laboratory device, in conjunction with the amended perturbation formula and the proposed inversion strategy, are useful tools for estimating the acoustic properties of centimetre-sized rock samples in the low frequency range.
    Print ISSN: 0956-540X
    Electronic ISSN: 1365-246X
    Topics: Geosciences
    Published by Oxford University Press on behalf of The Deutsche Geophysikalische Gesellschaft (DGG) and the Royal Astronomical Society (RAS).
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