Search

// Cheng-Wei Li 1 , Tzu-Ying Lai 1 and Bor-Sen Chen 1 1 Laboratory of Control and Systems Biology, Department of Electrical Engineering, National Tsing Hua University, Hsinchu, Taiwan Correspondence to: Bor-Sen Chen, email: bschen@ee.nthu.edu.tw Keywords: transductivity; network robustness; transductivity sensitivity; error sensitivity; basal sensitivity Received: November 11, 2016 Accepted: April 11, 2018 Published: May 04, 2018 ABSTRACT Mutation accumulation and epigenetic alterations in genes are important for carcinogenesis. Because leukemogenesis-related signal pathways have been investigated and microarray sample data have been produced in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and normal cells, systems analysis in coupling pathways becomes possible. Based on system modeling and identification, we could construct the coupling pathways and their associated gene regulatory networks using microarray sample data. By applying system theory to the estimated system model in coupling pathways, we can then obtain transductivity sensitivity, basal sensitivity and error sensitivity of each protein to identify the potential impact of genetic mutations, epigenetic alterations and the coupling of other pathways from the perspective of energy, respectively. By comparing the results in AML, MDS and normal cells, we investigated the potential critical genetic mutations and epigenetic alterations that activate or repress specific cellular functions to promote MDS or AML leukemogenesis. We suggested that epigenetic modification of β-catenin and signal integration of CSLs, AP-2α, STATs, c-Jun and β-catenin could contribute to cell proliferation at AML and MDS. Epigenetic regulation of ERK and genetic mutation of p53 could lead to the repressed apoptosis, cell cycle arrest and DNA repair in leukemic cells. Genetic mutation of JAK, epigenetic regulation of ERK, and signal integration of C/EBPα could result in the promotion of MDS cell differentiation. According to the results, we proposed three drugs, decitabine, genistein, and monorden for preventing AML leukemogenesis, while three drugs, decitabine, thalidomide, and geldanamycin, for preventing MDS leukemogenesis.

Folic acid (FA) was coupled onto titanium dioxide nanoparticles to provide a specificity of cell targeting. Modification was confirmed by infrared absorption spectra and zeta potential that suggested a formation of linkage between carboxylic acid of FA and titanium dioxide. The surface attachment of folic acid did not cause a significantly change in particles size, but led to a reduction of photocatalytic activity of TiO 2 . The FA-modified TiO 2 nanoparticles could be internalized by cells at a much faster rate than the unmodified TiO 2 , due to the mediation of folate receptor on the cancer cells. The UV irradiation caused death of HeLa cells pretreated with FA-modified TiO 2 more effectively than that of HeLa cells treated with unmodified TiO 2 . Results suggest that to modify TiO 2 with folic acid using appropriately the FA-to-TiO 2 mass ratio of 0.2 could yield nanoparticles having higher cytotoxicity under photoexcitation. Photocatalytic TiO 2 nanoparticles could not only damage to cellular components including plasma membranes leading to cell nucrosis but also induce the programming cell death. Results from flow cytometry-based analysis indicated that the mechanism of cell death was a combination of necrosis and apoptosis.

Recently, Multi-Objective Differential Evolution (MODE), powerful and efficient population-based stochastic processing, has become an indispensable algorithm for solving numerical optimization problems widely. It is found in various benchmark functions that traditional MODE is unable to search global optima completely, falling into local optima because only using one strategy to search global optimal. This paper proposes adjustable proportional distribution (APD) mechanism to deal with this problem. The proposed APD-MODE can combine several strategies with proportional distribution to search global optima. It calculates proportions of each strategy in external archive and then uses Taguchi method to select the best proportion in evolution. In next iteration, it selects the best proportion to adjust particles size and scale factor F used in each strategy according to Taguchi method. Benchmark experiments prove that APD-MODE can improve the maximum spread of solutions in external archive and find global optima more effectively and completely.