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For the design of computer experiments, column orthogonality and space-filling are two desirable properties. In this paper, we develop methods for constructing a new class of column-orthogonal designs (ODs) with two-dimensional stratifications on finer grids, including orthogonal Latin hypercube designs (OLHDs) as special cases. In addition to being column-orthogonal, these designs have good space-filling properties in two dimensions. The resulting designs achieve stratifications on s2×s or s×s2 grids, and most column pairs satisfy stratifications on s2×s2 grids. Moreover, many column pairs can achieve stratifications on s4×s2 and s2×s4 grids. Furthermore, the obtained space-filling ODs can have s6 levels, s4 levels, and mixed levels, as required for different needs.

Many studies have suggested that VSMC (vascular smooth muscle cell) apoptosis plays a key role in destabilization and rupture of atherosclerotic plaques. Therefore protection for VSMCs from apoptosis is a promising approach to stabilize 'vulnerable' lesions. However, the mechanisms as to why VSMCs in the fibrous cap often appear as profilerated in early stages, but turn apoptotic in advanced stages, are still unknown. In the present study, using RNAi (RNA interference) technology and a CaN (calcineurin) antagonist, the correlation between CaN and RANTES (regulated upon activation, normal T-cell expressed and secreted) in cultured rat apoptotic VSMCs stimulated by IFNγ (interferon γ; 20 ng/ml) and CD40L (CD40 ligand; 100 ng/ml) was investigated. RANTES released from VSMCs in each group was measured by ELISA and its mRNA in VSMCs was determined by RT (reverse transcription)-PCR. The total activity and expression of CaN in VSMCs were detected by the zymochemistry method and Western blot analysis respectively. From the results of the present study it can be hypothesized that an elevated CaN concentration in endochylema, by the CD40-CD40L signal pathway, induces VSMC apoptosis accomplished by the overexpression of RANTES. Therefore RANTES is a potential target for treating vulnerable atherosclerotic plaques owing to its crucial downstream regulating role in CaN-dependent VSMC apoptosis. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that metformin has obvious antiatherogenic properties, but the exact mechanism remains unclear. Therefore, we established an atherosclerotic rabbit model in order to investigate the potential effects of metformin on transcription factor nuclear factor κB (NF-κB) and serum high-sensitivity C-reactive protein (hs-CRP) level, which had been regarded as proatherogenic factors. New Zealand rabbits were randomly divided into three groups: a control group ( n = 8), an atherosclerotic group (AS group, n = 8), and a metformin treatment group (Met group, n = 8). The experimental atherosclerotic rabbit model was successfully established at the end of the 8th week. From the 9th week, rabbits in the Met group were administered with 150 mg/kg metformin daily by gavage. Blood samples were collected at days 0 and 8, and at 16 weeks to detect the level of blood lipid and serum glucose. At the end of the experiment, blood samples were withdrawn for determining serum hs-CRP. Aortic samples were harvested for histomorphometric analysis. Immunohistochemistry and Western blotting were used to detect the expression of NF-κB subunit p65 in nuclear extracts and phosphorylation of inhibitor of nuclear factor κB (IκB) in cytoplasmic extracts. An experimental atherosclerotic rabbit model was successfully established. The expression of nuclear NF-κB subunit p65 and cytoplasmic phosphorylation of IκB protein in the vessel wall was enhanced ( P < 0.01, respectively) in the AS group, and serum hs-CRP level was significantly increased in the AS group compared with the control group (3.90 ± 0.25 mg/l versus 1.36 ± 0.14 mg/l, P < 0.01). Treatment with metformin significantly attenuated the progression of aortic atherosclerosis. In the Met group, there was a marked reduction in nuclear NF-κB subunit p65 and cytoplasmic phosphorylation of IκB protein expression ( P < 0.01). Serum hs-CRP concentration was also significantly decreased (3.20 ± 0.20 mg/l versus 3.90 ± 0.25 mg/l, P < 0.05). Metformin inhibits the phosphorylation of IκB and the activation of NF-κB in the vessel wall of experimental atherogenesis of rabbits, as well as decreasing the serum level of hs-CRP, thus suggesting that metformin has vascular anti-inflammatory properties, which may be one of its antiatherogenic mechanisms. [ABSTRACT FROM AUTHOR]