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Edited by Tamas DalmayKeywords: Hypoxia Hypoxia-inducible factor 1a (HIF-1a) MicroRNA miR-21 Cardiomyocytes a b s t r a c t Accumulating evidence suggests that hypoxia-inducible factor 1a (HIF-1a) regulates numerous miRNAs and is crucial for cellular response to hypoxia. However, the relationship between HIF-1a and miR-21 in hypoxic cardiomyocytes is little known. We found that hypoxia induced HIF-1a and miR-21 expression. HIF-1a knockdown increased cell apoptosis and reduced miR-21 expression. Furthermore, we found that HIF-1a transcriptionally enhanced miR-21 promoter activity by binding to its promoter, which required the recruitment of CBP/p300. In addition, we found that miR-21 inhibition increased cell apoptosis and reduced HIF-1a expression, and modulated the PTEN/Akt pathway. Our results indicate that HIF-1a-miR-21 feedback contributes to the adaptation of cardiomyocytes to hypoxia, and has potential as therapeutic target for myocardial ischemia.

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This paper investigates the physical and chemical ignition delay (ID) periods in the constant volume combustion cflamber of the Ignition Quality Tester (IQT). IQT was used to determine the derived cetane number (DCN) according to ASTM D6890-10a standards. The fuels tested were ultra low sulfur diesel (ULSD),, and two synthetic fuels ofSasol IPK and F-T SPK (S-8). A comparison was made between the DCN and cetane number (CN) determined according to ASTM-D613 standards. Tests were conducted under steady state conditions at a constant pressure of 21 bars and various air temperatures ranging from 778 K to 848 K. The rate of heat release (RHR) was calculated from the measured pressure trace, and a detailed analysis of the RHR trace was made particularly for the auto-ignition process. Tests were conducted to determine the physical and chemical delay periods by comparing results obtained from two tests. In the first test, the fuel was injected into air according to ASTM standards. In the second test, the fuel was injected into nitrogen. The point at which the two resultant pressure traces separated was considered to be the end of the physical delay period. The effects of the charge temperature on the total ID as defined in ASTM D6890-10a standards, as well as on the physical and chemical delays, were determined. It was noticed that the physical delay represented a significant part of the total ID over all the air temperatures covered in this investigation. Arrhenius plots were developed to determine the apparent activation energy for each fuel using dijferent IDs. The first was based on the total ID measured according to ASTM standards. The second was the chemical delay determined in this investigation. The activation energy calculated from the total ID showed higher values for lower CN fuels except Sasol IPK. The activation energy calculated from the chemical delay period showed consistency in the increase of the activation energy with the drop in CN including Sasol IPK. The difference between the two findings could be explained by examining the sensitivity of the physical delay period of different fuels to the change in air temperature.