Ultraviolet radiation is a potent inducer of apoptosis, whereas autocrine nerve growth factor protects human keratinocytes from programmed cell death. To evaluate the role of nerve growth factor in the mechanisms of ultraviolet B-induced apoptosis, cultured human keratinocytes were ultraviolet B irradiated following pretreatment with K252, a specific inhibitor of the tyrosine kinase high-affinity nerve growth factor receptor. Here we report that the addition of K252 significantly enhanced keratinocyte apoptosis. We then transfected normal human keratinocytes with pNUT-hNGF. Nerve growth factor overexpressing keratinocytes secreted the highest amounts of nerve growth factor in culture supernatants, were more viable, and had a higher rate of proliferation than mock-transfected cells. Whereas ultraviolet B radiation downregulated nerve growth factor mRNA and protein as well as the tyrosine kinase high-affinity nerve growth factor receptor in normal keratinocytes, it failed to do so in nerve growth factor-transfected cells. Moreover, nerve growth factor overexpressing keratinocytes were partially resistant to apoptosis induced by increasing doses of ultraviolet B at 24 and 48 h. These results indicate that downregulation of nerve growth factor function plays an important part in the mechanisms of ultraviolet B-induced apoptosis in human keratinocytes. In addition, ultraviolet B caused a decrease in BCL-2 and BCL-xL expression in mock-transfected keratinocytes, but not in nerve growth factor overexpressing cells. Finally, nerve growth factor prevented the cleavage of the enzyme poly(ADP-ribose) polymerase induced in human keratinocytes by ultraviolet B. These results are consistent with a model whereby the autocrine nerve growth factor protects human keratinocytes from ultraviolet B-induced apoptosis by maintaining constant levels of BCL-2 and BCL-xL, which in turn might block caspase activation.
The research reported in this paper proposes an Advanced Process Control system, denoted "i.Process | Steel -RHF", oriented to energy efficiency improvement in a pusher type billets reheating furnace located in an Italian steel plant. A tailored control method based on a two-layer Model Predictive Control strategy has been created that involves cooperating modules. Different types of linear models have been combined and an overall furnace global linear model has been developed and included in the controller formulation. The developed controller allows handling all furnace conditions, guaranteeing the fulfillment of the defined specifications. The reliability of the proposed approach has been tested through significant simulation scenarios. The controller has been installed on the considered real plant, replacing local standalone controllers manually conducted by plant operators. Very satisfactory field results have been achieved, both on process control and energy efficiency improvement. Optimized trade-offs between energy saving, environmental impact decreasing, product quality improvement and production maximization have been guaranteed. Consequently, Italian energy efficiency certificates have been obtained. The formulated steel industry reheating furnaces control method has been patented.
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