AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral l...AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-lb-infected patients treated with IFN. METHODS: The C-terminal part of E2 (codons 617-711) including PKR/eIF2α phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to iFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to iFN (25.0% vs 6.9 %, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P 〈 0.0001) and sustained response to iFN (85.7% vs 2.9%, P 〈 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P 〈 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independentpredictors for small viral load, and ISDR (OR = 39.0, P 〈 0.0001) was selected as the only independent predictor for sustained response. CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.展开更多
Experimental results indicate three regimes for cracking in a ferroelectric double cantilever beam (DCB) under combined electromechanical loading. In the loading, the maximum amplitude of the applied electric field re...Experimental results indicate three regimes for cracking in a ferroelectric double cantilever beam (DCB) under combined electromechanical loading. In the loading, the maximum amplitude of the applied electric field reaches almost twice the coercive field of ferroelectrics. Thus, the model of small scale domain switching is not applicable any more, which is dictated only by the singular term of the crack tip field. In the DCB test, a large or global scale domain switching takes place instead, which is driven jointly by both the singular and non-singular terms of the crack-tip electric field. Combining a full field solution with an energy based switching criterion, we obtain the switching zone by the large scale model around the tip of a stationary impermeable crack. It is observed that the switching zone by the large scale model is significantly different from that by the small scale model. According to the large scale switching zone, the switch-induced stress intensity factor (SIF) and the transverse stress (T-stress) are evaluated numerically. Via the SIF and T-stress induced by the combined loading and corresponding criteria, we address the crack initiation and crack growth stability simultaneously. The two theoretical predictions roughly coincide with the experimental observations.展开更多
文摘AIM: To study the amino acid substitutions in the carboxy (C)-terminal part of E2 protein and in the interferon (IFN) sensitivity determining region (ISDR) and their correlation with response to IFN and viral load in 85 hepatitis C virus (HCV)-lb-infected patients treated with IFN. METHODS: The C-terminal part of E2 (codons 617-711) including PKR/eIF2α phosphorylation homology domain (PePHD) and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS: The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to iFN or with viral load. The presence of substitutions in a N-terminal variable region (codons 617-641) in the C-terminal part of E2 was significantly correlated with both small viral load (33.9% vs 13.8%, P = 0.0394) and sustained response to iFN (25.0% vs 6.9 %, P = 0.0429). Four or more substitutions in ISDR were significantly correlated with both small viral load (78.6% vs 16.2%, P 〈 0.0001) and sustained response to iFN (85.7% vs 2.9%, P 〈 0.0001). In multivariate analysis, ISDR in nonstructural (NS) 5A (OR = 0.39, P 〈 0.0001) and N-terminal variable region (OR = 0.51, P = 0.039) was selected as the independentpredictors for small viral load, and ISDR (OR = 39.0, P 〈 0.0001) was selected as the only independent predictor for sustained response. CONCLUSION: The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.
基金supported by the "Sino-German Center for Research Promotion" under a project of "Crack Growth in Ferroelectrics Driven by Cyclic Electric Loading", the National Natural Science Foundation of China (Grant No. 10702071)the China Postdoctoral Science Foundation (Grant No. 201003281)the Shanghai Postdoctoral Scientific Program (Grant No. 10R21415800)
文摘Experimental results indicate three regimes for cracking in a ferroelectric double cantilever beam (DCB) under combined electromechanical loading. In the loading, the maximum amplitude of the applied electric field reaches almost twice the coercive field of ferroelectrics. Thus, the model of small scale domain switching is not applicable any more, which is dictated only by the singular term of the crack tip field. In the DCB test, a large or global scale domain switching takes place instead, which is driven jointly by both the singular and non-singular terms of the crack-tip electric field. Combining a full field solution with an energy based switching criterion, we obtain the switching zone by the large scale model around the tip of a stationary impermeable crack. It is observed that the switching zone by the large scale model is significantly different from that by the small scale model. According to the large scale switching zone, the switch-induced stress intensity factor (SIF) and the transverse stress (T-stress) are evaluated numerically. Via the SIF and T-stress induced by the combined loading and corresponding criteria, we address the crack initiation and crack growth stability simultaneously. The two theoretical predictions roughly coincide with the experimental observations.