A multi-tier adaptive grid algorithm for the evolutionary multi-objective optimisation of complex problems

The multi-tier Covariance Matrix Adaptation Pareto Archived Evolution Strategy (m-CMA-PAES) is an evolutionary multi-objective optimisation (EMO) algorithm for real-valued optimisation problems. It combines a non-elitist adaptive grid based selection scheme with the efficient strategy parameter adaptation of the elitist Covariance Matrix Adaptation Evolution Strategy (CMA-ES). In the original CMA-PAES, a solution is selected as a parent for the next population using an elitist adaptive grid archiving (AGA) scheme derived from the Pareto Archived Evolution Strategy (PAES). In contrast, a multi-tiered AGA scheme to populate the archive using an adaptive grid for each level of non-dominated solutions in the considered candidate population is proposed. The new selection scheme improves the performance of the CMA-PAES as shown using benchmark functions from the ZDT, CEC09, and DTLZ test suite in a comparison against the (μ+λ) μ λ Multi-Objective Covariance Matrix Adaptation Evolution Strategy (MO-CMA-ES). In comparison with MO-CMA-ES, the experimental results show that the proposed algorithm offers up to a 69 % performance increase according to the Inverse Generational Distance (IGD) metric

Lipoic acid plays a role in scleroderma: insights obtained from scleroderma dermal fibroblasts

Abstract Introduction Systemic sclerosis (SSc) is a connective tissue disease characterized by fibrosis of the skin and organs. Increase in oxidative stress and platelet-derived growth factor receptor (PDGFR) activation promote type I collagen (Col I) production, leading to fibrosis in SSc. Lipoic acid (LA) and its active metabolite dihydrolipoic acid (DHLA) are naturally occurring thiols that act as cofactors and antioxidants and are produced by lipoic acid synthetase (LIAS). Our goals in this study were to examine whether LA and LIAS were deficient in SSc patients and to determine the effect of DHLA on the phenotype of SSc dermal fibroblasts. N-acetylcysteine (NAC), a commonly used thiol antioxidant, was included as a comparison. Methods Dermal fibroblasts were isolated from healthy subjects and patients with diffuse cutaneous SSc. Matrix metalloproteinase (MMPs), tissue inhibitors of MMPs (TIMP), plasminogen activator inhibitor 1 (PAI-1) and LIAS were measured by enzyme-linked immunosorbent assay. The expression of Col I was measured by immunofluorescence, hydroxyproline assay and quantitative PCR. PDGFR phosphorylation and α-smooth muscle actin (αSMA) were measured by Western blotting. Student’s t-tests were performed for statistical analysis, and P-values less than 0.05 with two-tailed analysis were considered statistically significant. Results The expression of LA and LIAS in SSc dermal fibroblasts was lower than normal fibroblasts; however, LIAS was significantly higher in SSc plasma and appeared to be released from monocytes. DHLA lowered cellular oxidative stress and decreased PDGFR phosphorylation, Col I, PAI-1 and αSMA expression in SSc dermal fibroblasts. It also restored the activities of phosphatases that inactivated the PDGFR. SSc fibroblasts produced lower levels of MMP-1 and MMP-3, and DHLA increased them. In contrast, TIMP-1 levels were higher in SSc, but DHLA had a minimal effect. Both DHLA and NAC increased MMP-1 activity when SSc cells were stimulated with PDGF. In general, DHLA showed better efficacy than NAC in most cases. Conclusions DHLA acts not only as an antioxidant but also as an antifibrotic because it has the ability to reverse the profibrotic phenotype of SSc dermal fibroblasts. Our study suggests that thiol antioxidants, including NAC, LA, or DHLA, could be beneficial for patients with SSc.http://deepblue.lib.umich.edu/bitstream/2027.42/112060/1/13075_2014_Article_411.pd