128 research outputs found

    Terrane‐controlled crustal shear wave splitting in Taiwan

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    Taiwan is the result of arc‐continent collision associated with the convergence of the Philippine Sea plate with the eastern Eurasian plate continental margin. The locus of deformation is found in eastern Taiwan in the form of mountain building (Central Range) with underlying thickened lithosphere. Rapid tectonic exhumation in the Central Range has uncovered low‐to‐high‐grade metamorphic rocks marked by steep cleavage. We carried out a crustal seismic anisotropy study across Taiwan, producing a database of over 27,000 local earthquake shear wave splitting measurements. Additionally, we carried out rock physics measurements of metamorphic outcrop samples to quantify shear wave rock anisotropy. We produced a map of station‐averaged splitting measurements across Taiwan. Patterns of fast shear wave directions correlate with tectonic terranes produced by plate convergence. Deformation‐related mineral‐preferred orientation in the metamorphic rocks produces a significant amount of the crustal anisotropy in the Taiwan collision zone

    Terrane‐controlled crustal shear wave splitting in Taiwan

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    Taiwan is the result of arc‐continent collision associated with the convergence of the Philippine Sea plate with the eastern Eurasian plate continental margin. The locus of deformation is found in eastern Taiwan in the form of mountain building (Central Range) with underlying thickened lithosphere. Rapid tectonic exhumation in the Central Range has uncovered low‐to‐high‐grade metamorphic rocks marked by steep cleavage. We carried out a crustal seismic anisotropy study across Taiwan, producing a database of over 27,000 local earthquake shear wave splitting measurements. Additionally, we carried out rock physics measurements of metamorphic outcrop samples to quantify shear wave rock anisotropy. We produced a map of station‐averaged splitting measurements across Taiwan. Patterns of fast shear wave directions correlate with tectonic terranes produced by plate convergence. Deformation‐related mineral‐preferred orientation in the metamorphic rocks produces a significant amount of the crustal anisotropy in the Taiwan collision zone

    Magnetostimulated Chandges of Microhardness in Potassium Acid Phthalate Crystals

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    A decrease in microhardness along the (010) cleavage in potassium acid phthalate single crystals by 15--18% after the application of a permanent magnetic field was revealed for the first time. It is shown that the effect revealed is of the volume character. The role of interlayer water in the processes stimulated by a magnetic field is studied., Interlayer water plays does not cause the observed changes it only plays the part of an indicator of these changes in potassium acid phthalate crystals in a magnetic field. It is established that microhardness in the (100) plane of the crystal in an applied a magnetic field first increases by 12--15% and then remains constant in time within the accuracy of the experiment. The possibility of varying the crystal structure of potassium acid phthalate crystals by applying magnetic fields inducing rearrangement in the system of hydrogen bonds or in the defect structure is discussed.Comment: 6 pages, 7 figure

    Effects of Hepatocyte CD14 Upregulation during Cholestasis on Endotoxin Sensitivity

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    Cholestasis is frequently related to endotoxemia and inflammatory response. Our previous investigation revealed a significant increase in plasma endotoxin and CD14 levels during biliary atresia. We therefore propose that lipopolysacharides (LPS) may stimulate CD14 production in liver cells and promote the removal of endotoxins. The aims of this study are to test the hypothesis that CD14 is upregulated by LPS and investigate the pathophysiological role of CD14 production during cholestasis. Using Western blotting, qRT-PCR, and promoter activity assay, we demonstrated that LPS was associated with a significant increase in CD14 and MD2 protein and mRNA expression and CD14 promoter activity in C9 rat hepatocytes but not in the HSC-T6 hepatic stellate cell line in vitro. To correlate CD14 expression and endotoxin sensitivity, in vivo biliary LPS administration was performed on rats two weeks after they were subjected to bile duct ligation (BDL) or a sham operation. CD14 expression and endotoxin levels were found to significantly increase after LPS administration in BDL rats. These returned to basal levels after 24 h. In contrast, although endotoxin levels were increased in sham-operated rats given LPS, no increase in CD14 expression was observed. However, mortality within 24 h was more frequent in the BDL animals than in the sham-operated group. In conclusion, cholestasis and LPS stimulation were here found to upregulate hepatic CD14 expression, which may have led to increased endotoxin sensitivity and host proinflammatory reactions, causing organ failure and death in BDL rats

    A20 Modulates Lipid Metabolism and Energy Production to Promote Liver Regeneration

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    Background: Liver Regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κ\kappaB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR) in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice. Methodology and Principal Findings: We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20) and rAd.β\betagalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κ\kappaB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV. Conclusion: This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings support pursuit of A20-based therapies to improve patients' outcomes in the context of extreme liver injury and extensive LR for tumor treatment or donation

    Sequence-defined multifunctional polyethers via liquid-phase synthesis with molecular sieving

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    Synthetic chemists have devoted tremendous effort towards the production of precision synthetic polymers with defined sequences and specific functions. However, the creation of a general technology that enables precise control over monomer sequence, with efficient isolation of the target polymers, is highly challenging. Here, we report a robust strategy for the production of sequence-defined synthetic polymers through a combination of liquid-phase synthesis and selective molecular sieving. The polymer is assembled in solution with real-time monitoring to ensure couplings proceed to completion, on a three-armed star-shaped macromolecule to maximize efficiency during the molecular sieving process. This approach is applied to the construction of sequence-defined polyethers, with side-arms at precisely defined locations that can undergo site-selective modification after polymerization. Using this versatile strategy, we have introduced structural and functional diversity into sequence-defined polyethers, unlocking their potential for real-life applications in nanotechnology, healthcare and information storage

    Upper Crustal Structure from the Santa Monica Mountains to the Sierra Nevada, Southern California: Tomographic Results from the Los Angeles Regional Seismic Experiment, Phase II (LARSE II)

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    In 1999, the U.S. Geological Survey and the Southern California Earthquake Center (SCEC) collected refraction and low-fold reflection data along a 150-km-long corridor extending from the Santa Monica Mountains northward to the Sierra Nevada. This profile was part of the second phase of the Los Angeles Region Seismic Experiment (LARSE II). Chief imaging targets included sedimentary basins beneath the San Fernando and Santa Clarita Valleys and the deep structure of major faults along the transect, including causative faults for the 1971 M 6.7 San Fernando and 1994 M 6.7 Northridge earthquakes, the San Gabriel Fault, and the San Andreas Fault. Tomographic modeling of first arrivals using the methods of Hole (1992) and Lutter et al. (1999) produces velocity models that are similar to each other and are well resolved to depths of 5-7.5 km. These models, together with oil-test well data and independent forward modeling of LARSE II refraction data, suggest that regions of relatively low velocity and high velocity gradient in the San Fernando Valley and the northern Santa Clarita Valley (north of the San Gabriel Fault) correspond to Cenozoic sedimentary basin fill and reach maximum depths along the profile of ∼4.3 km and >3 km, respectively. The Antelope Valley, within the western Mojave Desert, is also underlain by low-velocity, high-gradient sedimentary fill to an interpreted maximum depth of ∼2.4 km. Below depths of ∼2 km, velocities of basement rocks in the Santa Monica Mountains and the central Transverse Ranges vary between 5.5 and 6.0 km/sec, but in the Mojave Desert, basement rocks vary in velocity between 5.25 and 6.25 km/sec. The San Andreas Fault separates differing velocity structures of the central Transverse Ranges and Mojave Desert. A weak low-velocity zone is centered approximately on the north-dipping aftershock zone of the 1971 San Fernando earthquake and possibly along the deep projection of the San Gabriel Fault. Modeling of gravity data, using densities inferred from the velocity model, indicates that different velocity-density relationships hold for both sedimentary and basement rocks as one crosses the San Andreas Fault. The LARSE II velocity model can now be used to improve the SCEC Community Velocity Model, which is used to calculate seismic amplitudes for large scenario earthquakes

    Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

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    MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe
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