The β-adrenoceptor antagonist Propranolol has been successfully used to treat infantile hemangioma. However, its mechanism of action is so far unknown. The hypothesis of this research was that β-adrenoceptor antagonists may interfere with endothelial cell differentiation of stem cells. Specifically, the effects of the non-specific β-adrenergic receptor (β-adrenoceptor) antagonist Propranolol, the β1-adrenoceptor-specific antagonist Atenolol and the β2-adrenoceptor-specific antagonist ICI118,551 on vasculogenesis of mouse embryonic stem (ES) cells were investigated. All three β-blockers dose-dependently downregulated formation of capillary structures in ES cell-derived embryoid bodies and decreased the expression of the vascular cell markers CD31 and VE-cadherin. Furthermore, β-blockers downregulated the expression of fibroblast growth factor-2 (FGF-2), hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor 165 (VEGF165), VEGF receptor 2 (VEGF-R2) and phospho VEGF-R2, as well as neuropilin 1 (NRP1) and plexin-B1 which are essential modulators of embryonic angiogenesis with additional roles in vessel remodelling and arteriogenesis. Under conditions of β-adrenoceptor inhibition, the endogenous generation of nitric oxide (NO) as well as the phosphorylation of endothelial nitric oxide synthase (eNOS) was decreased in embryoid bodies, whereas an increase in NO generation was observed with the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP). Consequently, vasculogenesis of ES cells was restored upon treatment of differentiating ES cells with β-adrenoceptor antagonists in the presence of NO donor. In summary, our data suggest that β-blockers impair vasculogenesis of ES cells by interfering with NO generation which could be the explanation for their anti-angiogenic effects in infantile hemangioma.

The optimal problem in the structural design is an important issue in the engineering design. Various authors have analyzed the optimization of steel structures using algorithmic approaches. These techniques are generally grouped in deterministic or meta-heuristic techniques. From the introduction of structural optimization in the 1960’ up to now, various methods have been proposed. A genetic algorithm, is built and applied in this study using MatLab soft R2017a to a crossed beams system. The structural analysis is done with the direct stiffness method with constraints verification based on EuroCode 3:2005 criteria. Results are reported in the study.

The structural engineering design problem consist in an iterative process of design. Various authors have analyzed the optimization of steel structures using different algorithmic approaches. These techniques are generally grouped in deterministic or meta-heuristics. From the introduction of structural optimization in the 1960' up to now, various methods have been proposed. A GA genetic algorithm, is built and applied in this study using MatLab soft R2017a to crossed beams systems. The structural analysis is done applying the direct stiffness method with constraints verification based on EuroCode 3:2005 criteria. Results are reported in the study.