341 research outputs found

    Noise analysis and optimization of the gear transmission system for two-speed automatic transmission of pure electric vehicles

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    In this study, the noise of the gear transmission system for two-speed automatic transmission (2EAT) of pure electric vehicles was analyzed and optimized. Firstly, through vehicle noise tests, poor working conditions and noise contribution of each gear pair were determined with the order analysis method. Secondly, a dynamics calculation model and a simulation model of the gear transmission system were established and the poor meshing state of the main reducer gear pair under specific conditions was determined as the main cause of noise. Finally, a genetic algorithm combined the weight method was used for gear modification. After gear modifications, the fluctuation range of transmission error was reduced and the contact condition of the tooth surface was significantly improved.</p

    Robust H-infinity filtering for 2-D systems with intermittent measurements

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    This paper is concerned with the problem of robust H∞ filtering for uncertain two-dimensional (2-D) systems with intermittent measurements. The parameter uncertainty is assumed to be of polytopic type, and the measurements transmission is assumed to be imperfect, which is modeled by a stochastic variable satisfying the Bernoulli random binary distribution. Our attention is focused on the design of an H∞ filter such that the filtering error system is stochastically stable and preserves a guaranteed H∞ performance. This problem is solved in the parameter-dependent framework, which is much less conservative than the quadratic approach. By introducing some slack matrix variables, the coupling between the positive definite matrices and the system matrices is eliminated, which greatly facilitates the filter design procedure. The corresponding results are established in terms of linear matrix inequalities, which can be easily tested by using standard numerical software. An example is provided to show the effectiveness of the proposed approac

    Organophosphate esters (OPEs)in Chinese foodstuffs: Dietary intake estimation via a market basket method, and suspect screening using high-resolution mass spectrometry

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    Despite of the ubiquity of organophosphate esters (OPEs)in various environmental matrices, information regarding the dietary intakes of OPEs is currently limited. To better understand dietary exposure and intake, the present study investigated 11 OPE flame retardants (FRs)in 105 co

    FoxQ1 Overexpression Influences Poor Prognosis in Non-Small Cell Lung Cancer, Associates with the Phenomenon of EMT

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    BACKGROUND: We determined the expression of forkhead box Q1 (FoxQ1), E-cadherin (E-cad), Mucin 1 (MUC1), vimentin (VIM) and S100 calcium binding protein A4 (S100A4), all epithelial-mesenchymal transition (EMT) indicator proteins in non-small cell lung cancer (NSCLC) tissue samples. We also investigated the relationship between these five proteins expression and other clinicopathologic factors in NSCLC. Finally, we assessed the potential value of these markers as prognostic indicators of survival in NSCLC's patients. METHODS: Quantitative real-time PCR and immunohistochemistry were used to characterize the expression of the FoxQ1 mRNA and protein in NSCLC. Expression of transcripts and translated products for the other four EMT indicator proteins was assessed by immunohistochemistry in the same clinical NSCLC samples. RESULTS: FoxQ1 mRNA and protein were up-regulated in NSCLC compared with normal tissues (P = 0.015 and P<0.001, respectively). Expression of FoxQ1 in adenocarcinoma was higher than in squamous cell carcinoma (P = 0.005), and high expression of FoxQ1 correlated with loss of E-cad expression (P = 0.012), and anomalous positivity of VIM (P = 0.024) and S100A4 (P = 0.004). Additional survival analysis showed that high expression of FoxQ1 (P = 0.047) and E-cad (P = 0.021) were independent prognostic factors. CONCLUSION: FoxQ1 maybe plays a specific role in the EMT of NSCLC, and could be used as a prognostic factor for NSCLC

    Catecholamine up-regulates MMP-7 expression by activating AP-1 and STAT3 in gastric cancer

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    <p>Abstract</p> <p>Background</p> <p>Stress, anxiety and depression can cause complex physiological and neuroendocrine changes, resulting in increased level of stress related hormone catecholamine, which may constitute a primary mechanism by which physiological factors impact gene expression in tumors. In the present study, we investigated the effects of catecholamine stimulation on MMP-7 expression in gastric cancer cells and elucidated the molecular mechanisms of the up-regulation of MMP-7 level by catecholamine through an adrenergic signaling pathway.</p> <p>Results</p> <p>Increased MMP-7 expression was identified at both mRNA and protein levels in the gastric cancer cells in response to isoproterenol stimulation. Ξ²2-AR antigonist effectively abrogated isoproterenol-induced MMP-7 expression. The activation of STAT3 and AP-1 was prominently induced by isoproterenol stimulation and AP-1 displayed a greater efficacy than STAT3 in isoproterenol-induced MMP-7 expression. Mutagenesis of three STAT3 binding sites in MMP-7 promoter failed to repress the transactivation of MMP-7 promoter and silencing STAT3 expression was not effective in preventing isoproterenol-induced MMP-7 expression. However, isoproterenol-induced MMP-7 promoter activities were completely disappeared when the AP-1 site was mutated. STAT3 and c-Jun could physically interact and bind to the AP-1 site, implicating that the interplay of both transcriptional factors on the AP-1 site is responsible for isoproterenol-stimulated MMP-7 expression in gastric cancer cells. The expression of MMP-7 in gastric cancer tissues was found to be at the site where Ξ²2-AR was overexpressed and the levels of MMP-7 and Ξ²2-AR were the highest in the metastatic locus of gastric cancer.</p> <p>Conclusions</p> <p>Up-regulation of MMP-7 expression through Ξ²2-AR-mediated signaling pathway is involved in invasion and metastasis of gastric cancer.</p

    Downregulation of Integrin Ξ²4 Decreases the Ability of Airway Epithelial Cells to Present Antigens

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    Airway epithelial cells have been demonstrated to be accessory antigen presentation cells (APC) capable of activating T cells and may play an important role in the development of allergic airway inflammation of asthma. In asthmatic airways, loss of expression of the adhesion molecule integrin Ξ²4 (ITGB4) and an increase in Th2 inflammation bias has been observed in our previous study. Given that ITGB4 is engaged in multiple signaling pathways, we studied whether disruption of ITGB4-mediated cell adhesion may contribute to the adaptive immune response of epithelial cells, including their ability to present antigens, induce the activate and differentiate of T cells. We silenced ITGB4 expression in bronchial epithelial cells with an effective siRNA vector and studied the effects of ITGB4 silencing on the antigen presentation ability of airway epithelial cells. T cell proliferation and cytokine production was investigated after co-culturing with ITGB4-silenced epithelial cells. Surface expression of B7 homologs and the major histocompatibility complex (MHC) class II was also detected after ITGB4 was silenced. Our results demonstrated that silencing of ITGB4 resulted in impaired antigen presentation processes and suppressed T cell proliferation. Meanwhile, decrease in Th1 cytokine production and increase in Th17 cytokine production was induced after co-culturing with ITGB4-silenced epithelial cells. Moreover, HLA-DR was decreased and the B7 homologs expression was different after ITGB4 silencing. Overall, this study suggested that downregulation of ITGB4 expression in airway epithelial cells could impair the antigen presentation ability of these cells, which further regulate airway inflammation reaction in allergic asthma

    Genetic or pharmaceutical blockade of phosphoinositide 3-kinase p110Ξ΄ prevents chronic rejection of heart allografts.

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    Chronic rejection is the major cause of long-term heart allograft failure, characterized by tissue infiltration by recipient T cells with indirect allospecificity. Phosphoinositol-3-kinase p110Ξ΄ is a key mediator of T cell receptor signaling, regulating both T cell activation and migration of primed T cells to non-lymphoid antigen-rich tissue. We investigated the effect of genetic or pharmacologic inactivation of PI3K p110Ξ΄ on the development of chronic allograft rejection in a murine model in which HY-mismatched male hearts were transplanted into female recipients. We show that suppression of p110Ξ΄ activity significantly attenuates the development of chronic rejection of heart grafts in the absence of any additional immunosuppressive treatment by impairing the localization of antigen-specific T cells to the grafts, while not inducing specific T cell tolerance. p110Ξ΄ pharmacologic inactivation is effective when initiated after transplantation. Targeting p110Ξ΄ activity might be a viable strategy for the treatment of heart chronic rejection in humans

    NF-ΞΊB Hyper-Activation by HTLV-1 Tax Induces Cellular Senescence, but Can Be Alleviated by the Viral Anti-Sense Protein HBZ

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    Activation of I-ΞΊB kinases (IKKs) and NF-ΞΊB by the human T lymphotropic virus type 1 (HTLV-1) trans-activator/oncoprotein, Tax, is thought to promote cell proliferation and transformation. Paradoxically, expression of Tax in most cells leads to drastic up-regulation of cyclin-dependent kinase inhibitors, p21CIP1/WAF1 and p27KIP1, which cause p53-/pRb-independent cellular senescence. Here we demonstrate that p21CIP1/WAF1-/p27KIP1-mediated senescence constitutes a checkpoint against IKK/NF-ΞΊB hyper-activation. Senescence induced by Tax in HeLa cells is attenuated by mutations in Tax that reduce IKK/NF-ΞΊB activation and prevented by blocking NF-ΞΊB using a degradation-resistant mutant of I-ΞΊBΞ± despite constitutive IKK activation. Small hairpin RNA-mediated knockdown indicates that RelA induces this senescence program by acting upstream of the anaphase promoting complex and RelB to stabilize p27KIP1 protein and p21CIP1/WAF1 mRNA respectively. Finally, we show that down-regulation of NF-ΞΊB by the HTLV-1 anti-sense protein, HBZ, delay or prevent the onset of Tax-induced senescence. We propose that the balance between Tax and HBZ expression determines the outcome of HTLV-1 infection. Robust HTLV-1 replication and elevated Tax expression drive IKK/NF-ΞΊB hyper-activation and trigger senescence. HBZ, however, modulates Tax-mediated viral replication and NF-ΞΊB activation, thus allowing HTLV-1-infected cells to proliferate, persist, and evolve. Finally, inactivation of the senescence checkpoint can facilitate persistent NF-ΞΊB activation and leukemogenesis
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