A split-optimization approach for obtaining multiple solutions in single-objective process parameter optimization.

It can be observed from the experimental data of different processes that different process parameter combinations can lead to the same performance indicators, but during the optimization of process parameters, using current techniques, only one of these combinations can be found when a given objective function is specified. The combination of process parameters obtained after optimization may not always be applicable in actual production or may lead to undesired experimental conditions. In this paper, a split-optimization approach is proposed for obtaining multiple solutions in a single-objective process parameter optimization problem. This is accomplished by splitting the original search space into smaller sub-search spaces and using GA in each sub-search space to optimize the process parameters. Two different methods, i.e., cluster centers and hill and valley splitting strategy, were used to split the original search space, and their efficiency was measured against a method in which the original search space is split into equal smaller sub-search spaces. The proposed approach was used to obtain multiple optimal process parameter combinations for electrochemical micro-machining. The result obtained from the case study showed that the cluster centers and hill and valley splitting strategies were more efficient in splitting the original search space than the method in which the original search space is divided into smaller equal sub-search spaces.

Blockade of Notch Signalling by γ-Secretase Inhibitor in Lung T Cells of Asthmatic Mice Affects T Cell Differentiation and Pulmonary Inflammation.

Notch is a single-pass transmembrane receptor protein expressed by T cells, which contributes to the pathogenesis of asthma through regulation of the development and differentiation of T cells. γ-Secretase inhibitor (GSI) acts as an effective blocker of Notch signalling. The present study aimed to investigate the role of GSI MW167 in T cell differentiation and antigen-induced airway inflammation. An OVA-induced airway inflammation mouse model was established. Blockade of Notch signalling was achieved using MW167. The expression of IL-4, IL-5, IFN-γ, Notch1 signalling and pro-inflammatory transcription factors in activated lung T cells was evaluated. Finally, the therapeutic effect of MW167 was investigated by haematoxylin and eosin staining, real-time PCR and ELISA. The expression of IL-4 and IL-5 decreased and that of IFN-γ increased significantly, and the protein expression levels of pro-inflammatory transcription factors reduced in active lung T cells after administration of MW167, compared to the control group. MW167 treatment prevented OVA-induced airway inflammation and histological changes. The serum and bronchoalveolar lavage fluid (BALF) levels of IL-4 and IL-5 in MW167-treated mice decreased significantly, whereas those of IFN-γ increased, relative to the levels in OVA-challenged animals treated with PBS. Our findings indicate that Notch signalling plays an important role in the pathogenesis of asthma and that MW167 may be a potential therapeutic target for allergen-induced airway inflammation.

Analysis of the expression of the Notch3 receptor protein in adult lung cancer.

Abnormalities in the Notch signaling system are considered to play a role in the tumorigenesis of bronchiogenic carcinoma. The present study aimed to investigate the expression of Notch3 in adult lung cancer patients and its role in the pathogenesis of primary bronchiogenic carcinoma. The expression of the Notch3 protein in lung squamous cell carcinoma, adenocarcinoma, small cell carcinoma and corresponding non-tumor tissues was detected by immunohistochemistry. To investigate the expression of Notch3 in adenocarcinoma tissues, Notch3 mRNA and protein expression were measured with reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis, respectively. It was demonstrated that Notch3 had a stronger positive degree of expression in lung squamous cell carcinoma and adenocarcinoma compared with the corresponding non-tumor tissue (P<0.01). The expression of Notch3 in small cell carcinoma tissue was lower compared with that of the corresponding non-tumor tissue (P<0.01). The expression of Notch3 in the lung adenocarcinoma group was the highest of the three lung carcinoma groups (P<0.01). RT-PCR revealed that the expression of Notch3 mRNA in the lung adenocarcinoma group was higher than that of the normal lung group, but there was no statistically significant difference (P=0.05). The expression of Notch1 protein in the lung adenocarcinoma group was significantly higher compared with the normal lung group (P<0.01), as shown by western blot analysis. Notch3 may be involved in the pathogenesis of bronchogenic carcinoma, in particular in the promotion of the lung cancer oncogene, and a difference in its expression may exist in the various pathological types.