RORC antagonist(Boehringer Ingelheim Pharmaceuticals Inc /IDIBAPS)

Supercritical Brayton cycles have been considered as one of the technologies that present high thermal efficiencies in a wide range of energy conversion systems. Also, these systems can even increase their efficiency by incorporating a suitable bottoming cycle. In this article, a combined supercritical Brayton cycle with an Organic Rankine cycle (ORC) was analyzed. The influence of key system parameters such as the Brayton circuit high-pressure (Phigh), the turbine-1 inlet temperature (TIT), the turbine-1 efficiency ( __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ n t ), and the evaporation pressure ( __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ P e v a p ) on the economic indicators such as the Levelized Cost of Energy (LCOE), the Payback Period (PBP), the Specific Investment Cost (SIC), and net work ( __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ W ˙ n e t ) was studied. Besides, the effect of these parameters on the exergo-economic indicator __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ r k and the relative cost difference __-mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"-__ r k were studied. Finally, a thermo-economic optimization of the proposed configurations was carried out. The study revealed that the turbine-1 inlet temperature (TIT) was the variable with the most significant effect on the economic and energy indicators of the configurations analyzed. The increase in the turbine temperature up to 850 °C caused a rise of 63.8% for both configurations. Also, the results revealed that the Brayton/SORC configuration presented the best economic performance compared to the Brayton/RORC system. The thermo-economic optimization revealed that temperatures above 800 °C and pressures between 25-30 MPa increase system performance. In addition, the Brayton/SORC configuration has a comparative reduced levelized energy costs and low payback periods, which makes it more attractive.

Studies indicate that chronic vitamin D deficiency (VDD) may predispose to hypertension, yet, there is very little data characterizing its direct cardiac effects. Vitamin D modulates the function of transient receptor potential C cation channels (TRPC), which is a mechanosensitive cation channel that plays a role in cardiac slow-force responses to hemodynamic changes. The purpose of this study was to determine the cardiac effects of VDD and the potential role of TRPC.

Three-week old mice were placed on a VDD or normal diet (ND) for 19 weeks. Mice were then implanted with radiotelemeters for the measurement of heart rate (HR) and heart rate variability (HRV), while a separate group was anesthetized to measure blood pressure (BP) and left ventricular function using an intraventricular probe. Animals were treated with a TRPC antagonist or vehicle after which they were challenged with dobutamine to measure cardiac responses.

VDD mice had significantly increased BP (72 ± 3 mmHg vs. 62 ± 2 mmHg) and left ventricular pressure (LVP) (84.6 ± 0.8 mmHg vs. 78.2 ± 2.0 mmHg), and decreased cardiac contractility (-3 % vs. + 11 %) and HR response (+8 % vs. + 13 %) to dobutamine when compared to ND. These responses were blocked by the TRPC antagonist. HRV decreased with increasing dobutamine doses in ND but not VDD mice, however, the antagonist had no effect.

VDD increases BP and alters cardiac mechanical function in mice, the latter appears to be mediated by TRPC, in particular TRPC6. Although the cardiac effects might be due to increased BP, it is likely that VDD also affects the function of the heart directly. This is the first study to demonstrate the potentially deleterious effects of VDD on cardiac function and the role of TRPC6 in this response.