Browsing by Subject "AGGREGATION"

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • Thumbnail Image
    ItemOpen Access
    Numerical method for multi-alleles genetic drift problem
    (SIAM Journal on Numerical Analysis, 2019-01-01) Xu, S; Chen, X; Liu, C; Yue, X
    Genetic drift describes random fluctuations in the number of genes variants in a population. One of the most popular models is the Wright-Fisher model. The diffusion limit of this model is a degenerate diffusion-convection equation. Due to the degeneration and convection, Dirac singularities will always develop at the boundaries as time evolves, i.e., the fixation phenomenon occurs. Theoretical analysis has proven that the weak solution of this equation, regarded as measure, conserves total probability and expectations. In the current work, we propose a scheme for 3-alleles model with absolute stability and generalize it to N-alleles case (N > 3). Our method can conserve not only total probability and expectations, but also positivity. We also prove that the discrete solution converges to a measure as the mesh size tends to zero, which is the exact measure solution of the original problem. The simulations illustrate that the probability density decays to zero first on the inner nodes, then also on the edge nodes except at the three vertex nodes, on which the density finally concentrates. The results correctly predict the fixation probability and are consistent with theoretical ones and with direct Monte Carlo simulations.
  • Thumbnail Image
    ItemOpen Access
    Therapeutic potential of ReACp53 targeting mutant p53 protein in CRPC.
    (Prostate cancer and prostatic diseases, 2020-03) Zhang, Yaqun; Xu, Lingfan; Chang, Yan; Li, YanJing; Butler, William; Jin, Er; Wang, Aifen; Tao, Yulei; Chen, Xufeng; Liang, Chaozhao; Huang, Jiaoti
    BACKGROUNDS:p53 is a tumor suppressor that prevents cancer onset and progression, and mutations in the p53 gene cause loss of the tumor suppressor function of the protein. The mutant p53 protein in tumor cells can form aggregates which contribute to the dominant-negative effect over the wild-type p53 protein, causing loss of p53 tumor suppression or gain of novel oncogenic functions. Mutations in p53 have been implicated in the pathogenesis of primary prostate cancer (PCa), and are often detected in recurrent and metastatic disease. Thus, targeting mutant p53 may constitute an alternative therapeutic strategy for advanced PCa for which there are no other viable options. METHODS:In this study, we used immunoprecipitation, immunofluorescence, clonogenic survival, and cell proliferation assays, flow cytometric analysis and in vivo xenograft to investigate the biological effects of ReACp53, a cell-permeable peptide inhibitor of p53 aggregation, on mutant p53-carrying PCa cells. RESULTS:Our results show that ReACp53 targets amyloid aggregates of mutant p53 protein and restores the p53 nuclear function as transcriptional factor, induces mitochondrial cell death and reduces DNA synthesis of mutant p53-carrying PCa cells; ReACp53 also inhibits xenograft tumor growth in vivo. CONCLUSIONS:The data presented here suggest a therapeutic potential of targeting mutant p53 protein in advanced PCa setting, which has a clinical impact for aggressive PCa with transforming how such tumors are managed.