726 research outputs found

    Cognitive metaphor in the West and the East : A comparison of metaphors in the speeches of Barack Obama and Wen Jiabao

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    The thesis discusses the metaphors used in the speeches of US President Barack Obama and Chinese Premier Wen Jiabao. The framework is Cognitive Metaphor Theory, which introduces the idea that cognitive metaphors are conceptualizations or patterns of thought, not lingusitic phenomena, although these metaphors give rise to linguistic metaphors. The metaphorical mapping, the relations between conceptual metaphors and our experience, the differences between conceptual metaphors and poetic metaphors, as well as the functions of metaphors are also discussed. It is the purpose of the thesis to show the ubiquity of metaphor by analyzing the metaphors used in the West (represented by Obama) and the East (represented by Wen). A comparison of the similarities and differences of the conceptual metaphors used by the two politicians is made. The topics of speeches vary, from internal affairs (such as economy and domestic politics) to international affairs. The findings show that the conceptual metaphors TO PURSUE WELL-BEING IS A JOURNEY, PERSONIFICATION and POLITICS IS WAR are found to be the most dominant in both the English and the Chinese corpus, but some details or linguistic expressions in the same conceptual metaphors differ. Some specific American and Chinese metaphors are also highlighted, for instance, the American Dream and the Chinese flag. Metaphors are extensively used in both Obama and Wen’s speeches, and in fact among politicians as well, since metaphors not only have rhetoric functions, but also the power function of legitimization and delegitimization

    Down-regulation of Insulin Receptor Substrate 1 during Hyperglycemia Induces Vascular Smooth Muscle Cell Dedifferentiation

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    Diabetes is a major risk factor for the development of atherosclerosis, but the mechanism by which hyperglycemia accelerates lesion development is not well defined. Insulin and insulin-like growth factor I (IGF-I) signal through the scaffold protein insulin receptor substrate 1 (IRS-1). In diabetes, IRS-1 is down-regulated, and cells become resistant to insulin. Under these conditions, the IGF-I receptor signals through an alternate scaffold protein, SHPS-1, resulting in pathophysiologic stimulation of vascular smooth muscle cell (VSMC) migration and proliferation. These studies were undertaken to determine whether IRS-1 is functioning constitutively to maintain VSMCs in their differentiated state and, thereby, inhibit aberrant signaling. Here we show that deletion of IRS-1 expression in VSMCs in non-diabetic mice results in dedifferentiation, SHPS-1 activation, and aberrant signaling and that these changes parallel those that occur in response to hyperglycemia. The mice showed enhanced sensitivity to IGF-I stimulation of VSMC proliferation and a hyperproliferative response to vascular injury. KLF4, a transcription factor that induces VSMC dedifferentiation, was up-regulated in IRS-1−/− mice, and the differentiation inducer myocardin was undetectable. Importantly, these changes were replicated in wild-type mice during hyperglycemia. These findings illuminate a new function of IRS-1: that of maintaining cells in their normal, differentiated state. Because IRS-1 is down-regulated in states of insulin resistance that occur in response to metabolic stresses such as obesity and cytokine stimulation, the findings provide a mechanism for understanding how patients with metabolic stress and/or diabetes are predisposed to developing vascular complications

    Antitumor activity of the tea polyphenol epigallocatechin-3-gallate encapsulated in targeted vesicles after intravenous administration

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    The therapeutic potential of epigallocatechin gallate, a green tea polyphenol with anti-cancer properties, is limited by its inability to specifically reach tumors following intravenous administration. The purpose of this study is to determine whether a tumor-targeted vesicular formulation of epigallocatechin gallate would suppress the growth of A431 epidermoid carcinoma and B16-F10 melanoma in vitro and in vivo. Transferrin-bearing vesicles encapsulating epigallocatechin gallate were intravenously administered to mice bearing subcutaneous A431 and B16-F10 tumors. The intravenous administration of epigallocatechin gallate encapsulated in transferrin-bearing vesicles resulted in tumor suppression for 40% of A431 and B16-F10 tumors. Animal survival was improved by more than 20 days compared to controls. Encapsulation of epigallocatechin gallate in transferrin-bearing vesicles is a promising therapeutic strategy

    Tumor protein Tctp regulates axon development in the embryonic visual system.

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    The transcript encoding translationally controlled tumor protein (Tctp), a molecule associated with aggressive breast cancers, was identified among the most abundant in genome-wide screens of axons, suggesting that Tctp is important in neurons. Here, we tested the role of Tctp in retinal axon development in Xenopus laevis We report that Tctp deficiency results in stunted and splayed retinotectal projections that fail to innervate the optic tectum at the normal developmental time owing to impaired axon extension. Tctp-deficient axons exhibit defects associated with mitochondrial dysfunction and we show that Tctp interacts in the axonal compartment with myeloid cell leukemia 1 (Mcl1), a pro-survival member of the Bcl2 family. Mcl1 knockdown gives rise to similar axon misprojection phenotypes, and we provide evidence that the anti-apoptotic activity of Tctp is necessary for the normal development of the retinotectal projection. These findings suggest that Tctp supports the development of the retinotectal projection via its regulation of pro-survival signalling and axonal mitochondrial homeostasis, and establish a novel and fundamental role for Tctp in vertebrate neural circuitry assembly.This work was supported by Fundação para a Ciência e Tecnologia (C.G.R.; fellowship SFRH/BD/33891/2009), Sir Edward Youde Memorial Fund, Croucher Foundation, Cambridge Commonwealth–European & International Trust (H.W.), Gates Cambridge Scholarship (J.Q.L.), and a Wellcome Trust Programme Grant (C.E.H.; grant 085314/Z/08/Z).This is the final version of the article. It first appeared from The Company of Biologists via http://dx.doi.org/10.1242/dev.13106

    Young Children's Understanding of Teaching and Learning and Their Theory of Mind Development: A Causal Analysis from a Cross-Cultural Perspective

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    Children's understanding of the concepts of teaching and learning is closely associated with their theory of mind (ToM) ability and vital for school readiness. This study aimed to develop and validate a Preschool Teaching and Learning Comprehension Index (PTLCI) across cultures and examine the causal relationship between children's comprehension of teaching and learning and their mental state understanding. Two hundred and twelve children from 3 to 6 years of age from Hong Kong and the United States participated in study. The results suggested strong construct validity of the PTLCI, and its measurement and structural equivalence within and across cultures. ToM and PTLCI were significantly correlated with a medium effect size, even after controlling for age, and language ability. Hong Kong children outperformed their American counterparts in both ToM and PTLCI. Competing structural equation models suggested that children's performance on the PTLCI causally predicted their ToM across countries

    Charge density wave and superconductivity competition in Lu5_5Ir4_4Si10_{10} : a proton irradiation study

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    Real-space modulated Charge Density Waves (CDW) are an ubiquituous feature in many families of superconductors. In particular, how CDW relates to superconductivity is an active and open question that has recently gathered much interest since CDWs have been discovered in many cuprates superconductors. Here we show that disorder induced by proton irradiation is a full-fledged tuning parameter that can bring essential information to answer this question as it affects CDW and superconductivity with different and unequivocal mechanisms. Specifically, in the model CDW superconductor Lu5_5Ir4_4Si10_{10} that develops a 1D CDW below 77\,K and s-wave superconductivity below 4\,K, we show that disorder enhances the superconducting critical temperature TcT_\mathrm{c} and Hc2H_\mathrm{c2} while it suppresses the CDW. Discussing how disorder affects both superconductivity and the CDW, we make a compelling case that superconductivity and CDW are competing for electronic density of states at the Fermi level in Lu5_5Ir4_4Si10_{10}, and we reconcile the results obtained via the more common tuning parameters of pressure and doping. Owing to its prototypical, 1D, Peierls type CDW and the s-wave, weak-coupling nature of its superconductivity, this irradiation study of Lu5_5Ir4_4Si10_{10} provides the basis to understand and extend such studies to the more complex cases of density waves and superconductivity coexistence in heavy fermions, Fe-based or cuprates superconductors.Comment: 25 pages single column, 4 figures in main text + 3 figures in appendi

    Disorder raises the critical temperature of a cuprate superconductor

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    With the discovery of charge density waves (CDW) in most members of the cuprate high temperature superconductors, the interplay between superconductivity and CDW has become a key point in the debate on the origin of high temperature superconductivity. Some experiments in cuprates point toward a CDW state competing with superconductivity, but others raise the possibility of a CDW-superconductivity intertwined order, or more elusive pair-density wave (PDW). Here we have used proton irradiation to induce disorder in crystals of La1.875_{1.875}Ba0.125_{0.125}CuO4_4 and observed a striking 50% increase of TcT_\mathrm{c} accompanied by a suppression of the CDW. This is in clear contradiction with the behaviour expected of a d-wave superconductor for which both magnetic and non-magnetic defects should suppress TcT_\mathrm{c}. Our results thus make an unambiguous case for the strong detrimental effect of the CDW on bulk superconductivity in La1.875_{1.875}Ba0.125_{0.125}CuO4_4. Using tunnel diode oscillator (TDO) measurements, we find evidence for dynamic layer decoupling in PDW phase. Our results establish irradiation-induced disorder as a particularly relevant tuning parameter for the many families of superconductors with coexisting density waves, which we demonstrate on superconductors such as the dichalcogenides and Lu5_5Ir4_4Si10_{10}.Comment: 10 pages, 7 figure

    The Coordinate Cellular Response to Insulin-like Growth Factor-I (IGF-I) and Insulin-like Growth Factor-binding Protein-2 (IGFBP-2) Is Regulated through Vimentin Binding to Receptor Tyrosine Phosphatase β (RPTPβ)

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    Insulin-like growth factor-binding protein-2 (IGFBP-2) functions coordinately with IGF-I to stimulate cellular proliferation and differentiation. IGFBP-2 binds to receptor tyrosine phosphatase β (RPTPβ), and this binding in conjunction with IGF-I receptor stimulation induces RPTPβ polymerization leading to phosphatase and tensin homolog inactivation, AKT stimulation, and enhanced cell proliferation. To determine the mechanism by which RPTPβ polymerization is regulated, we analyzed the protein(s) that associated with RPTPβ in response to IGF-I and IGFBP-2 in vascular smooth muscle cells. Proteomic experiments revealed that IGF-I stimulated the intermediate filament protein vimentin to bind to RPTPβ, and knockdown of vimentin resulted in failure of IGFBP-2 and IGF-I to stimulate RPTPβ polymerization. Knockdown of IGFBP-2 or inhibition of IGF-IR tyrosine kinase disrupted vimentin/RPTPβ association. Vimentin binding to RPTPβ was mediated through vimentin serine phosphorylation. The serine threonine kinase PKCζ was recruited to vimentin in response to IGF-I and inhibition of PKCζ activation blocked these signaling events. A cell-permeable peptide that contained the vimentin phosphorylation site disrupted vimentin/RPTPβ association, and IGF-I stimulated RPTPβ polymerization and AKT activation. Integrin-linked kinase recruited PKCζ to SHPS-1-associated vimentin in response to IGF-I and inhibition of integrin-linked kinase/PKCζ association reduced vimentin serine phosphorylation. PKCζ stimulation of vimentin phosphorylation required high glucose and vimentin/RPTPβ-association occurred only during hyperglycemia. Disruption of vimetin/RPTPβ in diabetic mice inhibited RPTPβ polymerization, vimentin serine phosphorylation, and AKT activation in response to IGF-I, whereas nondiabetic mice showed no difference. The induction of vimentin phosphorylation is important for IGFBP-2-mediated enhancement of IGF-I-stimulated proliferation during hyperglycemia, and it coordinates signaling between these two receptor-linked signaling systems

    A Protocol for Single-Molecule Translation Imaging in Xenopus Retinal Ganglion Cells

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    Single-molecule translation imaging (SMTI) is a straightforward technique for the direct quantification of local protein synthesis. The protein of interest is fused to a fast-folding and fast-bleaching fluorescent protein, allowing one to monitor the appearance of individual fluorescence events after photobleaching of pre-existing proteins in the cell under investigation. The translation of individual molecules is then indicated by photon bursts of sub-second length that appear over a dark background. The method thus shares attributes with fluorescence recovery after photobleaching (FRAP) microscopy. Resulting datasets are similar to those generated by localization-based super-resolution microscopy techniques and can be used both to generate density maps of local protein production and to quantify the kinetics of local synthesis. The detailed protocol described in this chapter uses a Venus-β-actin fusion construct to visualize and measure the β-actin mRNA translational activity in Xenopus retinal ganglion cell growth cones upon Netrin-1 stimulation, which can be readily adapted for detecting translation events of other mRNAs in various cell types
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