We demonstrate that Mycobacterium tuberculosis recombinant leucine-responsive regulatory protein （rLrp） inhibits lipopolysaccharide （LPS）-induced tumor necrosis factor alpha （TNF-a）, interleukin-6, and interleuk...We demonstrate that Mycobacterium tuberculosis recombinant leucine-responsive regulatory protein （rLrp） inhibits lipopolysaccharide （LPS）-induced tumor necrosis factor alpha （TNF-a）, interleukin-6, and interleukin-12 production and blocks the nuclear translocation of subunits of the nuclear-receptor transcription factor NF-KB （Nuclear factor-kappa B）. Moreover, rLrp attenuated LPS-induced DNA binding and NF-κB transcriptional activity, which was accompanied by the degradation of inhibitory IκBα and a consequent decrease in the nuclear translocation of the NF-κB p65 subunit. RLrp interfered with the LPS-induced clustering of TNF receptor-associated factor 6 and with interleukin-1 receptor-associated kinase 1 binding to TAKI. Furthermore, rLrp did not attenuate proinflammatory cytokines or the expression of CD86 and major histocompatibility complex class-II induced by interferon-gamma in the macrophages of Toll-like receptor 2 deletion （TLR2-/-） mice and in protein kinase b （Akt）-depleted mouse cells, indicating that the inhibitory effects of rLrp were dependent on TLR2-mediated activation of the phosphatidylinositol 3-OH kinase （PI3K）/ Akt pathway. RLrp could also activate the PI3K/Akt pathway by stimulating the rapid phosphorylation of PI3K, Akt, and glycogen synthase kinase 3 beta in macrophages. In addition, 19 amino acid residues in the N-terminus of rLrp were determined to be important and required for the inhibitory effects mediated by TLR2. The inhibitory function of these 19 amino acids of rLrp raises the possibility that mimetic inhibitory peptides could be used to restrict innate immune responses in situations in which prolonged TLR signaling has deleterious effects. Our study offers new insight into the inhibitory mechanisms by which the TLR2-mediated PI3K/Akt pathway ensures the transient expression of potent inflammatory mediators.展开更多
针对国内外金融领域可疑交易的低检测率问题,通过对RBF(Radial Basis Function)神经网络技术的分析与研究,提出了一种基于APC-III聚类算法和RLS(Recursive Least Square)算法的面向反洗钱的RBF神经网络模型并加以实现。APC-III聚类算法...针对国内外金融领域可疑交易的低检测率问题,通过对RBF(Radial Basis Function)神经网络技术的分析与研究,提出了一种基于APC-III聚类算法和RLS(Recursive Least Square)算法的面向反洗钱的RBF神经网络模型并加以实现。APC-III聚类算法用于确定RBF神经网络隐含层的中心向量,RLS算法用来调整隐含层与输出层之间的连接权值。RBF神经网络与支持向量机(SVM)和孤立点检测相比,有更高的检测率和较低的误检率,因此,提出的模型具有重要的理论和实用价值。展开更多
文摘We demonstrate that Mycobacterium tuberculosis recombinant leucine-responsive regulatory protein （rLrp） inhibits lipopolysaccharide （LPS）-induced tumor necrosis factor alpha （TNF-a）, interleukin-6, and interleukin-12 production and blocks the nuclear translocation of subunits of the nuclear-receptor transcription factor NF-KB （Nuclear factor-kappa B）. Moreover, rLrp attenuated LPS-induced DNA binding and NF-κB transcriptional activity, which was accompanied by the degradation of inhibitory IκBα and a consequent decrease in the nuclear translocation of the NF-κB p65 subunit. RLrp interfered with the LPS-induced clustering of TNF receptor-associated factor 6 and with interleukin-1 receptor-associated kinase 1 binding to TAKI. Furthermore, rLrp did not attenuate proinflammatory cytokines or the expression of CD86 and major histocompatibility complex class-II induced by interferon-gamma in the macrophages of Toll-like receptor 2 deletion （TLR2-/-） mice and in protein kinase b （Akt）-depleted mouse cells, indicating that the inhibitory effects of rLrp were dependent on TLR2-mediated activation of the phosphatidylinositol 3-OH kinase （PI3K）/ Akt pathway. RLrp could also activate the PI3K/Akt pathway by stimulating the rapid phosphorylation of PI3K, Akt, and glycogen synthase kinase 3 beta in macrophages. In addition, 19 amino acid residues in the N-terminus of rLrp were determined to be important and required for the inhibitory effects mediated by TLR2. The inhibitory function of these 19 amino acids of rLrp raises the possibility that mimetic inhibitory peptides could be used to restrict innate immune responses in situations in which prolonged TLR signaling has deleterious effects. Our study offers new insight into the inhibitory mechanisms by which the TLR2-mediated PI3K/Akt pathway ensures the transient expression of potent inflammatory mediators.
文摘针对国内外金融领域可疑交易的低检测率问题,通过对RBF(Radial Basis Function)神经网络技术的分析与研究,提出了一种基于APC-III聚类算法和RLS(Recursive Least Square)算法的面向反洗钱的RBF神经网络模型并加以实现。APC-III聚类算法用于确定RBF神经网络隐含层的中心向量,RLS算法用来调整隐含层与输出层之间的连接权值。RBF神经网络与支持向量机(SVM)和孤立点检测相比,有更高的检测率和较低的误检率,因此,提出的模型具有重要的理论和实用价值。
