1,450 research outputs found

    Desensitization of T lymphocyte function by CXCR3 ligands in human hepatocellular carcinoma

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    Aim: Despite the presence of lymphocyte infiltration, human hepatocellular carcinoma (HCC) is typically a rapidly progressive disease. The mechanism of regulation of lymphocyte migration is poorly understood. In this study, we investigated various factors regulating T cell migration in HCC patients. We examined serum CXC chemokine levels in HCC patients and demonstrated the production of CXC chemokines by HCC cell lines. We determined the effect of both HCC patient serum and tumor cell conditioned supernatant upon lymphocyte expression of chemokine receptor CXCR3 as well as lymphocyte migration. Lastly, we examined the chemotactic responses of lymphocytes derived from HCC patients. Methods: The serum chemokines IP-10 (CXCL10) and Mig (CXCL9) levels were measured by cytometric bead array (CBA) and the tumor tissue IP-10 concentration was measured by ELISA. The surface expression of CXCR3 on lymphocytes was determined by flow cytometry. The migratory function of lymphocytes to the corresponding chemokines was assessed using an in vitro chemotactic assay. Phosphorylation of extracellular signal-regulated kinase (ERK) was determined by Western blot analysis. Results: Increased levels of IP-10 and Mig were detected in HCC patient serum and culture supernatants of HCC cell lines. The IP-10 concentration in the tumor was significantly higher than that in the non-involved adjacent liver tissues. HCC cell lines secreted functional chemokines that induced a CXCR3-specific chemotactic response of lymphocytes. Furthermore, tumor-cell-derived chemokines induced initial rapid phosphorylation of lymphocyte ERK followed by later inhibition of ERK phosphorylation. The culture of normal lymphocytes with HCC cell line supernatants or medium containing serum from HCC patients resulted in a significant reduction in the proportion of lymphocytes exhibiting surface expression of CXCR3. The reduction in T cell expression of CXCR3 resulted in reduced migration toward the ligand IP-10, and both CD4 + and CD8 + T cells from HCC patients exhibited diminished chemotactic responses to IP-10 in vitro compared to T cells from healthy control subjects. Conclusion: This study demonstrates functional desensitization of the chemokine receptor CXCR3 in lymphocytes from HCC patients by CXCR3 ligands secreted by tumor cells. This may cause lymphocyte dysfunction and subsequently impaired immune defense against the tumor. © 2005 The WJG Press and Elsevier Inc. All rights reserved.published_or_final_versio

    Urban energy consumption and CO2 emissions in Beijing: current and future

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    This paper calculates the energy consumption and CO2 emissions of Beijing over 2005–2011 in light of the Beijing’s energy balance table and the carbon emission coefficients of IPCC. Furthermore, based on a series of energy conservation planning program issued in Beijing, the Long-range Energy Alternatives Planning System (LEAP)-BJ model is developed to study the energy consumption and CO2 emissions of Beijing’s six end-use sectors and the energy conversion sector over 2012–2030 under the BAU scenario and POL scenario. Some results are found in this research: (1) During 2005–2011, the energy consumption kept increasing, while the total CO2 emissions fluctuated obviously in 2008 and 2011. The energy structure and the industrial structure have been optimized to a certain extent. (2) If the policies are completely implemented, the POL scenario is projected to save 21.36 and 35.37 % of the total energy consumption and CO2 emissions than the BAU scenario during 2012 and 2030. (3) The POL scenario presents a more optimized energy structure compared with the BAU scenario, with the decrease of coal consumption and the increase of natural gas consumption. (4) The commerce and service sector and the energy conversion sector will become the largest contributor to energy consumption and CO2 emissions, respectively. The transport sector and the industrial sector are the two most potential sectors in energy savings and carbon reduction. In terms of subscenarios, the energy conservation in transport (TEC) is the most effective one. (5) The macroparameters, such as the GDP growth rate and the industrial structure, have great influence on the urban energy consumption and carbon emissions

    Searching for sterile neutrinos in ice

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    Oscillation interpretation of the results from the LSND, MiniBooNE and some other experiments requires existence of sterile neutrino with mass 1\sim 1 eV and mixing with the active neutrinos Uμ02(0.020.04)|U_{\mu 0}|^2 \sim (0.02 - 0.04). It has been realized some time ago that existence of such a neutrino affects significantly the fluxes of atmospheric neutrinos in the TeV range which can be tested by the IceCube Neutrino Observatory. In view of the first IceCube data release we have revisited the oscillations of high energy atmospheric neutrinos in the presence of one sterile neutrino. Properties of the oscillation probabilities are studied in details for various mixing schemes both analytically and numerically. The energy spectra and angular distributions of the νμ\nu_\mu-events have been computed for the simplest νs\nu_s-mass, and νsνμ\nu_s - \nu_\mu mixing schemes and confronted with the IceCube data. An illustrative statistical analysis of the present data shows that in the νs\nu_s-mass mixing case the sterile neutrinos with parameters required by LSND/MiniBooNE can be excluded at about 3σ3\sigma level. The νsνμ\nu_s- \nu_\mu mixing scheme, however, can not be ruled out with currently available IceCube data.Comment: 41 pages, 16 figures. Accepted for publication in JHEP. Minor changes from the previous versio

    Superconductivity at the Border of Electron Localization and Itinerancy

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    The superconducting state of iron pnictides and chalcogenides exists at the border of antiferromagnetic order. Consequently, these materials could provide clues about the relationship between magnetism and unconventional superconductivity. One explanation, motivated by the so-called bad-metal behaviour of these materials, proposes that magnetism and superconductivity develop out of quasi-localized magnetic moments which are generated by strong electron-electron correlations. Another suggests that these phenomena are the result of weakly interacting electron states that lie on nested Fermi surfaces. Here we address the issue by comparing the newly discovered alkaline iron selenide superconductors, which exhibit no Fermi-surface nesting, to their iron pnictide counterparts. We show that the strong-coupling approach leads to similar pairing amplitudes in these materials, despite their different Fermi surfaces. We also find that the pairing amplitudes are largest at the boundary between electronic localization and itinerancy, suggesting that new superconductors might be found in materials with similar characteristics.Comment: Version of the published manuscript prior to final journal-editting. Main text (23 pages, 4 figures) + Supplementary Information (14 pages, 7 figures, 3 tables). Calculation on the single-layer FeSe is added. Enhancement of the pairing amplitude in the vicinity of the Mott transition is highlighted. Published version is at http://www.nature.com/ncomms/2013/131115/ncomms3783/full/ncomms3783.htm

    Stem cell differentiation increases membrane-actin adhesion regulating cell blebability, migration and mechanics

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    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/K. S. is funded by an EPSRC PhD studentship. S.T. is funded by an EU Marie Curie Intra European Fellowship (GENOMICDIFF)

    Adaptive Sliding Mode Control of Lateral Stability of Four Wheel Hub Electric Vehicles

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    Some physical parameters of a hub motor-driven four-wheel electric vehicle will change when the vehicle turns or maneuvers and the parameter change is caused by the change of the driving conditions. An adaptive sliding mode control is proposed in this paper to maintain the vehicle’s stability by compensating for the change of these parameters. The control parameter being adapted is the converging rate of the system state towards the sliding mode. As the Lyapunov method is used, so both the vehicle stability and adaptive rate convergence are guaranteed. Moreover, the hierarchical control structure is adopted for this vehicle stability control system. The above adaptive sliding model control forms the upper-layer; while the lower-layer control is to distribute the upper torque to the four wheels in an optimal way, subject to several constraints. In addition, the best feasible reference of the yaw rate and the vehicle side slip angle are obtained and used in the control system. The developed method is simulated under the CarSim/MATLAB co-simulation environment to evaluate the system performance. The simulation results are compared with the non-adaptive existing sliding mode control, and show that the proposed method is superior under different conditions. © 2020, KSAE

    Spectroscopic characterization and properties of some bioactive peroxovanadium complexes in aqueous solution

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    Four bioactive peroxovanadium (pV) complexes-bpV(ox), bpV(bipy), bpV(phen). and bpV(pic), ([VO(O-2)(2)L](n-), where ligand L = oxalic acid dianion (ox), bipyridine(bipy), 1,10-phenanthroline(phen), and pyridine-2-carboxylic acid (pic), were synthesized,and characterized by V-51 NMR, H-1 NMR, C-13 NMR, ESI-MS, IR and elemental analysis. All H-1 and C-13 peaks were,assigned by 2D H-1-H-1 peaks were assigned by 2D H-1-H-1 COSY, HMQC and HMBC. Their stereochemical structures in solution were discussed according to the NMR signals of organic ligands. The descending stability order of complexes in aqueous solution determined by V-51 NMR is bpV(phen), bpV(bipy) bpV (pic) and pV(ox). The predominant decomposition patterns of these complexes were proposed on the basis of electrospray ionization MS (ESI-MS) and V-51 NMR. This work will facilitate the studies of interactions between pV complexes and target biomolecules in solution so as:to clarify structure-function relationship of these:bioactive complexes

    Histone Acetylation-Mediated Regulation of the Hippo Pathway

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    The Hippo pathway is a signaling cascade recently found to play a key role in tumorigenesis therefore understanding the mechanisms that regulate it should open new opportunities for cancer treatment. Available data indicate that this pathway is controlled by signals from cell-cell junctions however the potential role of nuclear regulation has not yet been described. Here we set out to verify this possibility and define putative mechanism(s) by which it might occur. By using a luciferase reporter of the Hippo pathway, we measured the effects of different nuclear targeting drugs and found that chromatin-modifying agents, and to a lesser extent certain DNA damaging drugs, strongly induced activity of the reporter. This effect was not mediated by upstream core components (i.e. Mst, Lats) of the Hippo pathway, but through enhanced levels of the Hippo transducer TAZ. Investigation of the underlying mechanism led to the finding that cancer cell exposure to histone deacetylase inhibitors induced secretion of growth factors and cytokines, which in turn activate Akt and inhibit the GSK3 beta associated protein degradation complex in drug-affected as well as in their neighboring cells. Consequently, expression of EMT genes, cell migration and resistance to therapy were induced. These processes were suppressed by using pyrvinium, a recently described small molecule activator of the GSK 3 beta associated degradation complex. Overall, these findings shed light on a previously unrecognized phenomenon by which certain anti-cancer agents may paradoxically promote tumor progression by facilitating stabilization of the Hippo transducer TAZ and inducing cancer cell migration and resistance to therapy. Pharmacological targeting of the GSK3 beta associated degradation complex may thus represent a unique approach to treat cancer. © 2013 Basu et al

    Otitis Media in a New Mouse Model for CHARGE Syndrome with a Deletion in the Chd7 Gene

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    Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome
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