2,043 research outputs found

    Lessons of Defeat and Success: Taiwan’s 2012 Elections in Comparative Perspective

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    In early 2011, the Kuomintang (KMT, Guomindang) government appeared to be in danger of losing power in the upcoming presidential elections. The DPP had recovered sufficiently from its disastrous electoral performance in 2008 to pose a real challenge to Ma Ying-jeou (Ma Yingjiu) and had matched the KMT’s vote share in mid-term local elections. Ma also faced the challenge of an independent presidential candidate, James Soong (Song Chuyu), who had come a close second in 2000 and now threatened to divide the pro KMT vote. Nevertheless, the KMT was able to win reduced majorities in both the presidential and legislative elections in January 2012. This article seeks to explain how the KMT was able to hold on to power by comparing the campaign with earlier national-level elections. We are interested in identifying the degree to which the Democratic Progressive Party (DPP, Minjindang) learnt from its electoral setbacks in 2008 and whether the KMT employed a similar campaign strategy to the one that had been so effective in returning it to power in 2008. Our analysis relies of an examination of campaign propaganda and campaign strategies as well as participant observation and survey data from 2012 and earlier contests

    High temperature integrated and flexible ultrasonic transducers for NDT

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    Peer reviewed: YesNRC publication: Ye

    Bioactive Cembranoids from the Dongsha Atoll Soft Coral Sarcophyton crassocaule

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    Seven new cembranoids, sarcocrassocolides F–L (1–7), have been isolated from a soft coral Sarcophyton crassocaule. Their structures were determined by extensive spectroscopic analysis. Most new compounds exhibited significant cytotoxic activity against a limited panel of cancer cell lines, and the structure–activity relationship was studied. Compounds 1–7 were found to display significant in vitro anti-inflammatory activity in LPS-stimulated RAW264.7 macrophage cells by inhibiting the expression of the iNOS protein. Compound 4 was also found to effectively reduce the level of COX-2 protein

    Quantifying sediment mass redistribution from joint time-lapse gravimetry and photogrammetry surveys

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    The accurate quantification of sediment mass redistribution is central to the study of surface processes, yet it remains a challenging task. Here we test a new combination of terrestrial gravity and drone photogrammetry methods to quantify sediment mass redistribution over a 1 km2 area. Gravity and photogrammetry are complementary methods. Indeed, gravity changes are sensitive to mass changes and to their location. Thus, by using photogrammetry data to constrain this location, the sediment mass can be properly estimated from the gravity data. We carried out three joint gravimetry–photogrammetry surveys, once a year in 2015, 2016 and 2017, over a 1 km^2 area in southern Taiwan, featuring both a wide meander of the Laonong River and a slow landslide. We first removed the gravity changes from non-sediment effects, such as tides, groundwater, surface displacements and air pressure variations. Then, we inverted the density of the sediment with an attempt to distinguish the density of the landslide from the density of the river sediments. We eventually estimate an average loss of 3.7 \ub1 0.4  7 10^9 kg of sediment from 2015 to 2017 mostly due to the slow landslide. Although the gravity devices used in this study are expensive and need week-long surveys, new instrumentation currently being developed will enable dense and continuous measurements at lower cost, making the method that has been developed and tested in this study well-suited for the estimation of erosion, sediment transfer and deposition in landscapes

    Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

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    X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model

    Interface properties and built-in potential profile of a LaCrO3_3/SrTiO3_3 superlattice determined by standing-wave excited photoemission spectroscopy

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    LaCrO3_3 (LCO) / SrTiO3_3 (STO) heterojunctions are intriguing due to a polar discontinuity along (001), two distinct and controllable interface structures [(LaO)+^+/(TiO2_2)0^0 and (SrO)0^0/(CrO2_2)^-], and interface-induced polarization. In this study, we have used soft- and hard x-ray standing-wave excited photoemission spectroscopy (SW-XPS) to generate a quantitative determination of the elemental depth profiles and interface properties, band alignments, and the depth distribution of the interface-induced built-in potentials in the two constituent oxides. We observe an alternating charged interface configuration: a positively charged (LaO)+^+/(TiO2_2)0^0 intermediate layer at the LCOtop_\textbf{top}/STObottom_\textbf{bottom} interface and a negatively charged (SrO)0^0/(CrO2_2)^- intermediate layer at the STOtop_\textbf{top}/LCObottom_\textbf{bottom} interface. Using core-level SW data, we have determined the depth distribution of species, including through the interfaces, and these results are in excellent agreement with scanning transmission electron microscopy and electron energy loss spectroscopy (STEM-EELS) mapping of local structure and composition. SW-XPS also enabled deconvolution of the LCO-contributed and STO- contributed matrix-element-weighted density of states (MEWDOSs) from the valence band (VB) spectra for the LCO/STO superlattice (SL). Monitoring the VB edges of the deconvoluted MEWDOS shifts with a change in probing profile, the alternating charge- induced built-in potentials are observed in both constituent oxides. Finally, using a two-step simulation approach involving first core-level binding energy shifts and then valence-band modeling, the built-in potential gradients across the SL are resolved in detail and represented by the depth distribution of VB edges.Comment: Main text: 29 pages, 5 figures; Supplementary Information: 20 pages, 10 figure

    Resistance to paclitaxel in a cisplatin-resistant ovarian cancer cell line is mediated by P-glycoprotein

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    The IGROVCDDP cisplatin-resistant ovarian cancer cell line is also resistant to paclitaxel and models the resistance phenotype of relapsed ovarian cancer patients after first-line platinum/taxane chemotherapy. A TaqMan low-density array (TLDA) was used to characterise the expression of 380 genes associated with chemotherapy resistance in IGROVCDDP cells. Paclitaxel resistance in IGROVCDDP is mediated by gene and protein overexpression of P-glycoprotein and the protein is functionally active. Cisplatin resistance was not reversed by elacridar, confirming that cisplatin is not a P-glycoprotein substrate. Cisplatin resistance in IGROVCDDP is multifactorial and is mediated in part by the glutathione pathway and decreased accumulation of drug. Total cellular glutathione was not increased. However, the enzyme activity of GSR and GGT1 were up-regulated. The cellular localisation of copper transporter CTR1 changed from membrane associated in IGROV-1 to cytoplasmic in IGROVCDDP. This may mediate the previously reported accumulation defect. There was decreased expression of the sodium potassium pump (ATP1A), MRP1 and FBP which all have been previously associated with platinum accumulation defects in platinum-resistant cell lines. Cellular localisation of MRP1 was also altered in IGROVCDDP shifting basolaterally, compared to IGROV-1. BRCA1 was also up-regulated at the gene and protein level. The overexpression of P-glycoprotein in a resistant model developed with cisplatin is unusual. This demonstrates that P-glycoprotein can be up-regulated as a generalised stress response rather than as a specific response to a substrate. Mechanisms characterised in IGROVCDDP cells may be applicable to relapsed ovarian cancer patients treated with frontline platinum/taxane chemotherapy

    Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways

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    The gamma-secretase complex is involved in the intramembranous proteolysis of a variety of substrates, including the amyloid precursor protein and the Notch receptor. Nicastrin (NCT) is an essential component of the gamma-secretase complex and functions as a receptor for gamma-secretase substrates. In this study, we determined that serum- and glucocorticoid-induced protein kinase 1 (SGK1) markedly reduced the protein stability of NCT. The SGK1 kinase activity was decisive for NCT degradation and endogenous SGK1 inhibited gamma-secretase activity. SGK1 downregulates NCT protein levels via proteasomal and lysosomal pathways. Furthermore, SGK1 directly bound to and phosphorylated NCT on Ser437, thereby promoting protein degradation. Collectively, our findings indicate that SGK1 is a gamma-secretase regulator presumably effective through phosphorylation and degradation of NCT
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