Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lnc...Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts.展开更多
This paper discusses the uncertainty of ozone differential absorption lidar (DIAL) measurements due to the impact of background signal. The impact of background signal on ozone concentration profiles is proportional t...This paper discusses the uncertainty of ozone differential absorption lidar (DIAL) measurements due to the impact of background signal. The impact of background signal on ozone concentration profiles is proportional to the background intensity and the ratio of return signal intensities at “on” and “off” wavelength ( ) (hereinafter we call it the return signal intensity ratio). Analysis suggests that an appropriate return signal intensity ratio can make the impact of background signal very small, negligible. The simulations based on the analysis coincide with the experimental results. The experimental results show that the impact of background signal is negligible at an appropriate return signal intensity ratio of 0.96 at wavelength pair (280,285 nm). In case of unknown background intensity, we can adjust the laser pulse energy levels at the two wavelengths to obtain an appropriate return signal intensity ratio on the oscilloscope to suppress the impact of background signal and ensure the accuracy of night time ozone measurements.展开更多
In a context of increasing competition and sustainable development, service prices and unused capacity enhancement play a crucial role in freight or people transportation management. The focus of the paper is on a Dia...In a context of increasing competition and sustainable development, service prices and unused capacity enhancement play a crucial role in freight or people transportation management. The focus of the paper is on a Dial-a-ride Problem in the Saharan country context, for the particular of Taxi “woro-woro”1. More precisely, these taxis help to transport groups of people without any affinity, from point A to point B without stopping. Also, we propose for this problem an exact solution based on a mix integer program (MIP). A secondary study on a random instance generation algorithm is presented, which allows us to have a diversified and varied benchmark on which to apply our MIP program.展开更多
MOMENTS after Lei Jun finished his keynote address at the Global Mobile Internet Conference (GMIC) in Belling in May, the CEO of Chinese smart- phone maker Xiaomi was mobbed by young volun- teers working the event, ...MOMENTS after Lei Jun finished his keynote address at the Global Mobile Internet Conference (GMIC) in Belling in May, the CEO of Chinese smart- phone maker Xiaomi was mobbed by young volun- teers working the event, all eager to take pictures of the mop-haired 43-year-old and claim an autograph of their hero.展开更多
文摘Myocardial infarction (MI), the most serious of the ischemic heart diseases, is accompanied by myocardial metabolic disorders and the loss of cardiomyocytes. Increasing evidence has shown that long noncoding RNAs (lncRNAs) are involved in various pathological conditions such as cancer and cardiovascular diseases (CVDs), and are emerging as a novel biomarker for these disorders. This study aims to investigate the regulatory role and mechanisms of lncRNAs in myocardial remodeling in the setting of MI. We find that post-infarcted hearts exhibit a reduction of adenosine triphosphate (ATP) and an alteration of the glucose and lipid metabolism genes cluster of differentiation 36 (CD36), hexokinase 1 (HK1), and clucose transporter 4 (GLUT4), accompanied by cardiomyocyte pyroptosis. We then identify a previously unknown conserved lncRNA, AK009126 (cardiomyocyte pyroptosis-associated lncRNA, CPAL), which is remarkably upregulated in the myocardial border zone of MI mice. Importantly, the adeno-associated virus 9 (AAV9)-mediated silencing of endogenous CPAL by its short hairpin RNA (shRNA) partially abrogates myocardial metabolic alterations and cardiomyocyte pyroptosis during MI in mice. Mechanistically, CPAL is shown to bind directly to nuclear factor kappa B (NFκB) and to act as an activator of NFκB to induce NFκB phosphorylation in cardiomyocytes. We also find that CPAL upregulates caspase-1 expression at the transcriptional level and consequently promotes the release of interleukin (IL)-18 and IL-1β from cardiomyocytes. Collectively, our findings reveal the conserved lncRNA CPAL as a new regulator of cardiac metabolic abnormalities and cardiomyocyte pyroptosis in the setting of MI and suggest CPAL as a new therapeutic target to protect cardiomyocytes against ischemic injury in infarcted hearts.
文摘This paper discusses the uncertainty of ozone differential absorption lidar (DIAL) measurements due to the impact of background signal. The impact of background signal on ozone concentration profiles is proportional to the background intensity and the ratio of return signal intensities at “on” and “off” wavelength ( ) (hereinafter we call it the return signal intensity ratio). Analysis suggests that an appropriate return signal intensity ratio can make the impact of background signal very small, negligible. The simulations based on the analysis coincide with the experimental results. The experimental results show that the impact of background signal is negligible at an appropriate return signal intensity ratio of 0.96 at wavelength pair (280,285 nm). In case of unknown background intensity, we can adjust the laser pulse energy levels at the two wavelengths to obtain an appropriate return signal intensity ratio on the oscilloscope to suppress the impact of background signal and ensure the accuracy of night time ozone measurements.
文摘In a context of increasing competition and sustainable development, service prices and unused capacity enhancement play a crucial role in freight or people transportation management. The focus of the paper is on a Dial-a-ride Problem in the Saharan country context, for the particular of Taxi “woro-woro”1. More precisely, these taxis help to transport groups of people without any affinity, from point A to point B without stopping. Also, we propose for this problem an exact solution based on a mix integer program (MIP). A secondary study on a random instance generation algorithm is presented, which allows us to have a diversified and varied benchmark on which to apply our MIP program.
文摘MOMENTS after Lei Jun finished his keynote address at the Global Mobile Internet Conference (GMIC) in Belling in May, the CEO of Chinese smart- phone maker Xiaomi was mobbed by young volun- teers working the event, all eager to take pictures of the mop-haired 43-year-old and claim an autograph of their hero.