Innovation concentration in knowledge network.

This paper studies the increase in innovation concentration levels of U.S. industries over the last two decades. I present a model of imperfectly competitive patent market with heterogeneous firms that generate endogenous variable markups. Theoretically and empirically, the price of a firm's newly invented knowledge, the profit and survival rate of the innovating firm depends on the market share of this firm's knowledge stock and the position of industry in the knowledge network. In the process of innovating, firm pays a random fixed cost in each period which together with market share largely determines its decision on whether to innovate into different sectors. I find that firms with larger market share not only invest more in R&D but also enter into more sectors. Since innovating firms could create blueprints for new varieties and manufacture the products that have been invented, I bridge the gap between the product and the R&D markets to document the similar concentration trends between them. I prove that large firms in the product market would charge higher price on their product so that they can charge higher profit which is a part of the value of their knowledge. Lastly, the increasing trend of concentration could decrease consumers' welfare in the industries with high initial concentration levels.

Paeonol Pretreatment Attenuates Anoxia-Reoxygenation Induced Injury in Cardiac Myocytes via a BRCA1 Dependent Pathway.

Breast cancer type 1 sensitive protein (BRCA1) is a well-known tumor suppressor and its role in oxidative stress has been confirmed. The purpose of this study is to evaluate whether paeonol has a protective effect on myocardial hypoxia-reoxygenation (A/R) injury, and to explore H9C2 cells through a mechanism-dependent pathway mediated by BRCA1. H9C2 cells were pretreated with paeonol (10 µM) for 18 h before hypoxia was induced to establish a cell model of myocardial ischemia/reperfusion (I/R) injury. Use commercial kits to detect antioxidant indicators, including relative oxygen content (ROS) levels, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), lactate dehydrogenase (LDH) activity, and creatine kinase (CK-MB) and nuclear factor-kappaB (NF-κB) activity. The cell viability was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction method. Real-time fluorescent quantitative PCR was used to detect BRCA1 mRNA and protein levels. The expression levels of BRCA1, NLRP3 and ACS were determined by Western blotting. In addition, the release of interleukin (IL)-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α) was also evaluated by an enzyme-linked immunosorbent assay (ELISA) kit. The results showed that paeonol (10 µM) can significantly improve the hypoxic A/R damage of H9C2 cells, and the BRCA1 expression of H9C2 cells pretreated with paeonol was significantly increased before A/R damage was induced. BRCA1 is widely known in breast and ovarian cancer. Our data proves that the down-regulation of BRCA1 participates in the decrease of cell viability and the decrease of CK-MB and LDH activities, and protects cells by inhibiting the production of ROS and the activation of Nod-like receptor protein 3 (NLRP3) inflammasomes and NF-κB. In conclusion, paeonol significantly improved the A/R damage of H9C2 cells induced by hypoxia through the BRCA1/ROS-regulated NLRP3 inflammasome/IL-1ß and NF-κB/TNF-α/IL-6 pathways. It may be a potential drug against myocardial I/R injury.

Ileal perforation caused by a fish bone shortly after drug-eluting stent implantation for acute myocardial infarction.

During the past century, the incidence of myocardial infarction has markedly increased worldwide. Percutaneous coronary intervention with stent implantation is often considered as the first-choice treatment, especially in emergency cases. Current guidelines recommend delayed elective noncardiac surgery for such vulnerable patients. However, few suggestions are available regarding the exact treatment strategy for patients who have already undergone percutaneous coronary intervention but suddenly need emergent noncardiac surgery for an unrelated reason. We herein present a case involving a patient with acute myocardial infarction who had undergone implantation of a drug-eluting stent and developed an ileal perforation due to fish bone ingestion 3 days postoperatively. After carefully balancing the risks of stent thrombosis and uncontrollable bleeding, dual antiplatelet therapy and low-molecular-weight heparin were given with close monitoring. Emergency laparotomy and partial small bowel resection surgery were then performed, after which the patient eventually recovered. This case indicates a possible management strategy for patients with acute myocardial infarction complicated by emergency noncardiac surgery.

Interaction among hERG channel blockers is a potential mechanism of death in caffeine overdose.

Caffeine overdose death is due to cardiac arrest, but its mechanism has not been explored in detail. In this study, our data showed that caffeine significantly prolonged the heart rate-corrected QT interval (QTc) of rabbits in vivo (P<0.05; n=7). Caffeine was also found to be a hERG channel blocker with an IC50 of 5.04mM (n=5). Although these two findings likely link caffeine overdose death with hERG channel blockade, the amount of caffeine consumption needed to reach the IC50 is very high. Further study demonstrated that addition another hERG blocker could lower the consumption of caffeine significantly, no matter whether two hERG blockers share the same binding sites. Our data does not rule out other possibility, however, it suggests that there is a potential causal relationship between caffeine overdose death with hERG channel and the interaction among these hERG blockers.

J Wave Syndromes: History and Current Controversies.

The concept of J wave syndromes was first proposed in 2004 by Yan et al for a spectrum of electrocardiographic (ECG) manifestations of prominent J waves that are associated with a potential to predispose affected individuals to ventricular fibrillation (VF). Although the concept of J wave syndromes is widely used and accepted, there has been tremendous debate over the definition of J wave, its ionic and cellular basis and arrhythmogenic mechanism. In this review article, we attempted to discuss the history from which the concept of J wave syndromes (JWS) is evolved and current controversies in JWS.

Barium chloride impaired Kir2.1 inward rectification in its stably transfected HEK 293 cell lines.

Kir2.1 channel is a typical inward rectified channel with little outward currents when the membrane depolarized. Barium blocks the inward Kir2.1 currents in a voltage-dependent manner. However, in this study we found that barium would impair the rectification and open Kir2.1 outward currents at a depolarized voltage, causing increment of outward current amplitudes by 43±7% (n=5, P<0.01) after 200s barium application. In the meanwhile, a higher barium concentration did block the outward currents by 17.5±4.3% (n=4, P<0.01) and temporarily twisted current upward tendency. The increment was likely barium specific since both calcium and Kir2.1 specific blocker, Chloroethylclonidine (CEC), did not enhance the current amplitudes. The rectification of Kir2.1 was not recovered by washing barium off, which suggested a non-competitive mechanism. Since the currents occurred at phase 1, 2 of cardiac action potential, it would likely shorten the action potential plateau and it would decrease QT duration in electrocardiography (ECG).

Effects of mid-myocardial pacing on transmural dispersion of repolarization and arrhythmogenesis.

INTRODUCTION: Epicardial (Epi) activation of the left ventricular (LV) wall increases transmural dispersion of repolarization (TDR), which creates a substrate for the development of ventricular arrhythmia. We hypothesize that pacing from the LV mid-myocardium may decrease the TDR and occurrence of arrhythmias. METHODS AND RESULTS: A transmural electrocardiogram and transmembrane action potentials were simultaneously recorded from Epi, mid-myocardial (M), and endocardial (Endo) layers of the arterially perfused canine LV wedge preparations (n= 8). Transmural dispersion of repolarization varied when the preparations were paced at each layer, respectively (Endo pacing, 35.6 ± 6.6 ms; M pacing, 34.9 ± 7.3 ms; Epi pacing, 72.4 ± 4.9 ms; P< 0.001). A significant difference was noted in TDR between M pacing and Epi pacing (P< 0.001), but not between M pacing and Endo pacing (P= 0.831). This result was reproducible in the presence of ischaemia-reperfusion experiments (n= 8). Transmural dispersion of repolarization was amplified as compared with non-ischaemic experiments and differed when preparations were paced at each layer (Endo pacing, 62.8 ± 13.8 ms; M pacing, 63.3 ± 13.3 ms; Epi pacing, 111.1 ± 17.7 ms; P< 0.001). There was again no significant difference between Endo pacing and M pacing (P= 0.948). However, as pacing was shifted from M to Epi, there was a significant increase in TDR (P< 0.001). Ventricular arrhythmias were induced in two of eight ischaemic preparations during Epi pacing, but did not occur in either M or Endo pacing. CONCLUSION: Mid-myocardial pacing can significantly decrease the TDR and prevent the occurrence of ventricular arrhythmias as compared with Epi pacing.