9,138 research outputs found

    Entanglement generation outside a Schwarzschild black hole and the Hawking effect

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    We examine the Hawking effect by studying the asymptotic entanglement of two mutually independent two-level atoms placed at a fixed radial distance outside a Schwarzschild black hole in the framework of open quantum systems. We treat the two-atom system as an open quantum system in a bath of fluctuating quantized massless scalar fields in vacuum and calculate the concurrence, a measurement of entanglement, of the equilibrium state of the system at large times, for the Unruh, Hartle-Hawking and Boulware vacua respectively. We find, for all three vacuum cases, that the atoms turn out to be entangled even if they are initially in a separable state as long as the system is not placed right at the even horizon. Remarkably, only in the Unruh vacuum, will the asymptotic entanglement be affected by the backscattering of the thermal radiation off the space-time curvature. The effect of the back scatterings on the asymptotic entanglement cancels in the Hartle-Hawking vacuum case.Comment: 15 pages, no figures, Revte

    Water extract of Rheum officinale Baill. induces apoptosis in human lung adenocarcinoma A549 and human breast cancer MCF-7 cell lines

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    Author name used in this publication: De-Jian GuoAuthor name used in this publication: Peter Hoi-Fu Yu2009-2010 > Academic research: refereed > Publication in refereed journalAccepted ManuscriptPublishe

    Prediction by graph theoretic measures of structural effects in proteins arising from non-synonymous single nucleotide polymorphisms.

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    Recent analyses of human genome sequences have given rise to impressive advances in identifying non-synonymous single nucleotide polymorphisms (nsSNPs). By contrast, the annotation of nsSNPs and their links to diseases are progressing at a much slower pace. Many of the current approaches to analysing disease-associated nsSNPs use primarily sequence and evolutionary information, while structural information is relatively less exploited. In order to explore the potential of such information, we developed a structure-based approach, Bongo (Bonds ON Graph), to predict structural effects of nsSNPs. Bongo considers protein structures as residue-residue interaction networks and applies graph theoretical measures to identify the residues that are critical for maintaining structural stability by assessing the consequences on the interaction network of single point mutations. Our results show that Bongo is able to identify mutations that cause both local and global structural effects, with a remarkably low false positive rate. Application of the Bongo method to the prediction of 506 disease-associated nsSNPs resulted in a performance (positive predictive value, PPV, 78.5%) similar to that of PolyPhen (PPV, 77.2%) and PANTHER (PPV, 72.2%). As the Bongo method is solely structure-based, our results indicate that the structural changes resulting from nsSNPs are closely associated to their pathological consequences

    PI3K/mTORC2 regulates TGF-β/Activin signalling by modulating Smad2/3 activity via linker phosphorylation

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    Crosstalk between the phosphatidylinositol 3-kinase (PI3K) and the transforming growth factor-β signalling pathways play an important role in regulating many cellular functions. However, the molecular mechanisms underpinning this crosstalk remain unclear. Here, we report that PI3K signalling antagonizes the Activin-induced definitive endoderm (DE) differentiation of human embryonic stem cells by attenuating the duration of Smad2/3 activation via the mechanistic target of rapamycin complex 2 (mTORC2). Activation of mTORC2 regulates the phosphorylation of the Smad2/3-T220/T179 linker residue independent of Akt, CDK and Erk activity. This phosphorylation primes receptor-activated Smad2/3 for recruitment of the E3 ubiquitin ligase Nedd4L, which in turn leads to their degradation. Inhibition of PI3K/mTORC2 reduces this phosphorylation and increases the duration of Smad2/3 activity, promoting a more robust mesendoderm and endoderm differentiation. These findings present a new and direct crosstalk mechanism between these two pathways in which mTORC2 functions as a novel and critical mediator

    Cloning and expression analysis of two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp, Ctenopharyngodon idellus

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    BACKGROUND: Hypoxia-inducible factors (HIFs) are involved in adaptive and survival responses to hypoxic stress in mammals. In fish, very little is known about the functions of HIFs. RESULTS: We have cloned and characterized two distinct HIF-alpha cDNAs – gcHIF-1alpha and gcHIF-4alpha – from the hypoxia-tolerant grass carp. The deduced gcHIF-1alpha protein is highly similar to the HIF-1alphas (57–68%) from various vertebrate species, while gcHIF-4alpha is a novel isoform, and shows an equivalent degree of amino acid identity (41–47%) to the HIF-1alpha, HIF-2alpha and HIF-3alpha proteins so far described. Parsimony analysis indicated that gcHIF-4alpha is most closely related to the HIF-3alpha proteins. Northern blot analysis showed that mRNA levels of gcHIF-1alpha and gcHIF-4alpha differ substantially under normoxic and hypoxic conditions, while Western blot studies demonstrated that the endogenous protein levels for both gcHIF-1alpha and gcHIF-4alpha are similarly responsive to hypoxia. Our findings suggest that both gcHIF-1alpha and gcHIF-4alpha are differentially regulated at the transcriptional and translational levels. HRE-luciferase reporter assays show that both proteins function as transcription activators and play distinct roles in modulating the hypoxic response in grass carp. CONCLUSION: There are at least two distinct HIF-alpha isoforms – gcHIF-1alpha and gcHIF-4alpha – in the hypoxia-tolerant grass carp, which are differentially expressed and regulated in different fish organs in response to hypoxic stress. Overall, the results suggest that unique molecular mechanisms operate through these two HIF-alpha isoforms, which underpin the hypoxic response in the hypoxia-tolerant grass carp

    The Recombinant Profilin from Free-Living Amoebae Induced Allergic Immune Responses via TLR2

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    Mi Kyung Park,1 Hye-Kyung Park,2 Hak Sun Yu1,3 1Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea; 2Department of Internal Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea; 3Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of KoreaCorrespondence: Hye-Kyung Park; Hak Sun Yu, Tel +82+51-240-7000 ; +82+51-510-8022, Email [email protected]; [email protected]: Repeated exposure to recombinant profilin from Acanthamoeba (rAc-PF) induces allergic airway responses in vitro and in vivo. Based on the role of toll-like receptors (TLRs) in allergic airway diseases, TLRs play a central role in innate immune responses and the adaptive immune system and regulate responses against antigens through antigen-specific receptors. In this study, we attempted to determine the molecular mechanisms underlying rAc-PF-induced allergic inflammatory responses.Methods: We determined the correlation between rAc-PF and TLRs and analyzed changes in allergic immune responses after blocking multiple TLR signaling under rAc-PF treatment conditions in vitro. We also compared allergic inflammatory responses in TLR2 knockout (KO) and wild-type (WT) mice. To investigate the effect of TLR2 on antigen prototyping and T cell activation in the inflammatory response induced by rAc-PF, we assessed maturation of BMDCs and polarization of naïve T cells by rAc-PF stimulation. Additionally, we compared changes in inflammation-related gene expression by rAc-PF treatment in primary lung epithelial cells isolated from TLR2 KO and WT mice.Results: The rAc-PF treatment was increased the expression level of TLR2 and 9 in vitro. But, there were not significantly differ the others TLRs expression by rAc-PF treated group. And then, the mRNA expression levels of inflammation-related genes were reduced in the TLR2 or TLR9 antagonist-treated groups compared to those in the rAc-PF alone, were no difference the treated with the other TLRs (TLR4, 6, and 7/8) antagonist. The difference was higher in the TLR2 antagonist group. Additionally, the levels of airway inflammatory disease indicators were lower in the TLR2 KO group than in the WT group after rAc-PF treatment. Furthermore, the expression of bone marrow-derived dendritic cell (BMDC) surface molecular markers following rAc-PF stimulation was lower in TLR2 KO mice than in WT mice, and TLR2 KO in BMDCs resulted in a remarkable decline in Th2/17-related cytokine production and Th2/17 subset differentiation. In addition, the expression levels of rAc-PF-induced inflammatory genes were reduced inTLR2 KO primary lung cells compared to those in normal primary lung cells.Conclusion: These results suggest that the rAc-PF-induced airway inflammatory response is regulated by TLR2 signaling.Keywords: rAc-PF, profilin, toll-like receptors, airway inflammation, T cell activatio

    Geometric phase outside a Schwarzschild black hole and the Hawking effect

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    We study the Hawking effect in terms of the geometric phase acquired by a two-level atom as a result of coupling to vacuum fluctuations outside a Schwarzschild black hole in a gedanken experiment. We treat the atom in interaction with a bath of fluctuating quantized massless scalar fields as an open quantum system, whose dynamics is governed by a master equation obtained by tracing over the field degrees of freedom. The nonunitary effects of this system are examined by analyzing the geometric phase for the Boulware, Unruh and Hartle-Hawking vacua respectively. We find, for all the three cases, that the geometric phase of the atom turns out to be affected by the space-time curvature which backscatters the vacuum field modes. In both the Unruh and Hartle-Hawking vacua, the geometric phase exhibits similar behaviors as if there were thermal radiation at the Hawking temperature from the black hole. So, a measurement of the change of the geometric phase as opposed to that in a flat space-time can in principle reveal the existence of the Hawking radiation.Comment: 14 pages, no figures, a typo in the References corrected, version to appear in JHEP. arXiv admin note: text overlap with arXiv:1109.033

    Enabler for interdisciplinary ehealthcare: A qualitative study

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    © 2017 The authors and IOS Press. The complex relations between Health Technologies and clinical practices have been the focus of intensive research in recent years. This research represents a shift towards a holistic view where evaluation of health technologies is linked to organisational practices. In this paper, we address the gaps in existing literature regarding the holistic evaluation of e-health in clinical practice. We report the results from a qualitative study conducted to gain insight into e-health in practice within an interdisciplinary healthcare domain. Findings from this qualitative study, provides the foundation for the creation of a generic measurement model that allows for the comparative analysis of health technologies and assist in the decision-making of its stakeholders

    Hypoxia induces telomerase reverse transcriptase (TERT) gene expression in non-tumor fish tissues in vivo: the marine medaka (Oryzias melastigma) model

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    BACKGROUND: Current understanding on the relationships between hypoxia, hypoxia-inducible factor-1 (HIF-1) and telomerase reverse transcriptase (TERT) gene expression are largely based on in vitro studies in human cancer cells. Although several reports demonstrated HIF-1- mediated upregulation of the human TERT gene under hypoxia, conflicting findings have also been reported. Thus far, it remains uncertain whether these findings can be directly extrapolated to non-tumor tissues in other whole animal systems in vivo. While fish often encounter environmental hypoxia, the in vivo regulation of TERT by hypoxia in non-neoplastic tissues of fish remains virtually unknown. RESULTS: The adult marine medaka (Oryzias melastigma) was employed as a model fish in this study. We have cloned and characterized a 3261-bp full-length TERT cDNA, omTERT, which encodes a protein of 1086 amino acids. It contains all of the functional motifs that are conserved in other vertebrate TERTs. Motif E is the most highly conserved showing 90.9–100% overall identity among the fish TERTs and 63.6% overall identity among vertebrates. Analysis of the 5'-flanking sequence of the omTERT gene identified two HRE (hypoxia-responsive element; nt. – 283 and – 892) cores. Overexpression of the HIF-1α induced omTERT promoter activity as demonstrated using transient transfection assays. The omTERT gene is ubiquitously expressed in fish under normoxia, albeit at varying levels, where highest expression was observed in gonads and the lowest in liver. In vivo expression of omTERT was significantly upregulated in testis and liver in response to hypoxia (at 96 h and 48 h, respectively), where concomitant induction of the omHIF-1α and erythropoietin (omEpo) genes was also observed. In situ hybridization analysis showed that hypoxic induction of omTERT mRNA was clearly evident in hepatocytes in the caudal region of liver and in spermatogonia-containing cysts in testis. CONCLUSION: This study demonstrates for the first time, hypoxic regulation of TERT expression in vivo in a whole fish system. Our findings support the notion that hypoxia upregulates omTERT expression via omHIF-1 in non-neoplastic fish liver and testis in vivo. Overall, the structure and regulation of the TERT gene is highly conserved in vertebrates from fish to human
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