点的变化

给下面的字各添上一点，使它们变成新字。

New real-time-PCR method to identify single point mutations in hepatitis C virus

AIM To develop a fast, low-cost diagnostic strategy to identify single point mutations in highly variable genomes such as hepatitis C virus(HCV).METHODS In patients with HCV infection, resistance-associated amino acid substitutions within the viral quasispecies prior to therapy can confer decreased susceptibility to direct-acting antiviral agents and lead to treatment failure and virological relapse. One such naturally occurring mutation is the Q80 K substitution in the HCV-NS3 protease gene, which confers resistance to PI inhibitors, particularly simeprevir. Low-cost, highly sensitive techniques enabling routine detection of these single point mutations would be useful to identify patients at a risk of treatment failure. Light Cycler methods, based on real-time PCR with sequencespecific probe hybridization, have been implemented in most diagnostic laboratories. However, this technique cannot identify single point mutations in highly variable genetic environments, such as the HCV genome. To circumvent this problem, we developed a new method to homogenize all nucleotides present in a region except the point mutation of interest. RESULTS Using nucleotide-specific probes Q, K, and R substitutions at position 80 were clearly identified at a sensitivity of 10%(mutations present at a frequency of at least 10% were detected). The technique was successfully applied to identify the Q80 K substitution in 240 HCV G1 serum samples, with performance comparable to that of direct Sanger sequencing, the current standard procedure for this purpose. The new method was then validated in a Catalonian population of 202 HCV G1-infected individuals. Q80 K was detected in 14.6% of G1 a patients and 0% of G1 b in our setting. CONCLUSION A fast, low-cost diagnostic strategy based on real-time PCR and fluorescence resonance energy transfer probe melting curve analysis has been successfully developed to identify single point mutations in highly variable genomes such as hepatitis C virus. This technique can be adapted to detect any single point mutation in highly variable genomes.

On Variational Inequality and Fixed Point Problems

In this paper,A strong convergence theorem for a finite family of nonexpansive mappings and relaxed cocoercive mappings based on an iterative method in the framework of Hilbert spaces is established.

Changes and Characteristics of EFL Teachers' Professional Identity:The Cases of Nine University Teachers

Teacher identity has emerged as a central topic in educational research since 1990s. Professional identity among university EFL teachers is however understudied, especially those were engaged in in-service PhD study. Drawing on the interviews with nine EFL teachers in a Chinese university, this qualitative case research explored the changes of their professional identity with in-service PhD study experience. Positive changes were reported by all nine teachers, although with varied loci. Consistent with prior studies, the nine teachers demonstrated multi-leveled, achievement-oriented and discipline-focused professional identities. This research highlights the powerful influence of policy upon their identity changes. Their professional identities are shaped and reshaped in the process of negotiating and balancing between personal beliefs and rules at different levels. Teachers with non-English PhD academic background displayed conflicting professional identity, with institutional pressure being the important sources of their struggle and dilemma.

On high-dimensional change point problem

New statistics are proposed to estimate and test the structural change when the data dimension is comparable to or larger than the sample size. Consistency of the new statistic in estimating the change point position is established under the alternative hypothesis. The asymptotic distribution of the new statistic in testing the existence of a change point is obtained under the null hypothesis. Some simulation results are presented which show that the numerical performance of our method is satisfactory. The method is illustrated via the analysis of the house price index of US.