A modified method for simulating non-stationary multi-point earthquake ground motion

A spectral-representation-based algorithm is proposed to simulate non-stationary and stochastic processes with evolutionary power,according to a prescribed non-stationary cross-spectral density matrix. Non-stationary multi-point seismic ground motions at different locations on the ground surface are generated for use in engineering applications. First,a modified iterative procedure is used to generate uniformly modulated non-stationary ground motion time histories which are compatible with the prescribed power spectrum. Then,ground motion time histories are modeled as a non-stationary stochastic process with amplitude and frequency modulation. The characteristic frequency and damping ratio of the Clough-Penzien acceleration spectrum are considered as a function of time in order to study the frequency time variation. Finally,two numerical examples are presented to validate the efficiency of the proposed method,and the results show that this method can be effectively applied to the dynamic seismic analysis of long and large scale structures.

Insulin-like growth factor-binding protein-3 inhibits IGF-1-induced proliferation of human hepatocellular carcinoma cells

OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.

Experimental study about the regulating effect of Par-4 gene overexpression on the nephroblastoma sensitivity to cisplatin

Objective: To study the regulating effect of Par-4 gene overexpression on the nephroblastoma sensitivity to cisplatin. Methods: Nephroblastoma SK-NEP-1 cells were cultured and divided into four groups, control group were treated with RMPI-1640 without serum or drugs, cisplatin group were treated with serum-free RMPI-1640 containing 5 μg/mL cisplatin, Par-4 group were transfected by Par-4 overexpression plasmids with serum-free RMPI-1640, and cisplatin+ Par-4 group were transfected by Par-4 overexpression plasmid with serum-free RMPI-1640 containing 5 μg/mL cisplatin. The cell proliferation activity as well the expression of apoptosis genes, migration genes and invasion genes was measured. Results: 8 h, 16 h and 24 h after different conditions of treatment, the cell proliferation activity of cisplatin group, Par-4 group and cisplatin + Par-4 group were significantly lower than that of control group, and the cell proliferation activity of cisplatin + Par-4 group was significantly lower than that of cisplatin group and Par-4 group;24 h after different conditions of treatment, Bim, PDCD4, WT1, RGS4, Axin, KAI1, E-cadherin, PPARγ and PTEN mRNA expression in cisplatin group, Par-4 group and cisplatin + Par-4 group were greatly higher than those in control group whereas GDNF, GFRα1, TUBB3, NME1 and FGF1 mRNA expression were greatly lower than those in control group;Bim, PDCD4, WT1, RGS4, Axin, KAI1, E-cadherin, PPARγ and PTEN mRNA expression in cisplatin + Par-4 group were greatly higher than those in cisplatin group and Par-4 group whereas GDNF, GFRα1, TUBB3, NME1 and FGF1 mRNA expression were greatly significantly lower than those in cisplatin group and Par-4 group. Conclusion:Par-4 gene overexpression can increase the nephroblastoma sensitivity to cisplatin, reduce cell proliferation activity, promote apoptosis and inhibit cell migration and invasion.