Receptor Interacting Protein 3 is Required for Arsenite-mediated Necroptosis

Arsenic compounds such as sodium arsenite (SA) and arsenic trioxide (ATO) are toxic to human. Primarily, we pursued to outline the cell death modes caused by arsenic compounds and to address what proteins would be responsible for arsenite-induced cytotoxicity. Both SA and ATO substantially exhibited cytotoxic activity in L929 cells. Necrostatin-1 (Nec-1) treatment significantly protected cell death mediated by arsenic compounds, suggesting that cells are committed to die in a programmed necrotic way. A geldanamycin analog DMAG destabilized receptor interacting protein 3 (RIP3) and concomitantly protected cells from SA toxicity. Using interfering RNAs, we eventually found that RIP3 was responsible for its antagonizing effects on SA. Therefore, it is proposed that arsenic compounds execute necroptotic cell death of L929 via a RIP3 dependent pathway

The relationships between managerial metacognition, total quality management, and a firm\u27s sustainable competitive advantages: An empirical investigation based on structural equation modeling analysis

The purpose of this study is to explore how managerial metacognition has an influence on the effective implementation of total quality management (TQM) and the creation of a firm’s sustainable competitive advantages (P) by using the lens of Resource-Based View (RBV). In particular, this study conceptualized the existing TQM framework by two sub-constructs, technical quality management (TQ) and behavioral quality management (BQ) practices, and newly proposed the sequential relationship of \u27TQ→BQ→P\u27 based on the premise of the RBV. In addition, through post-hoc analysis, this study tested the mediation effect of a firm\u27s TQ practices on the relationship between managerial metacognition and their BQ implementation. An online survey method was adopted to collect a primary data for this study, and a total of 235 viable samples were obtained from quality managers working in the U.S.-based firms. Confirmatory factor analysis (CFA) was first conducted in order to examine the validation of the measurement models, and then structural equation modeling (SEM) analysis was performed to test the hypothesized research model by using AMOS 22. The test results show that a significant positive association between managerial metacognition and a firm\u27s quality practices, suggesting that a better effective TQM implementation could eventuate in a firm when they have a higher level of metacognitive ability. The study results also reveal that \u27TQ→BQ→P\u27 is a statistically more robust structure than \u27BQ→TQ→P\u27, implying that a firm\u27s BQ is a more critical strategic resource for generating a firm’s sustainable competitive advantages than is TQ. Furthermore, the test results of post hoc analysis demonstrate that a firm\u27s TQ-related tools and techniques have a role as an indispensable vehicle in materializing the positive influence of managerial metacognition on BQ implementation

Reversing the Weak Quantum Measurement for a Photonic Qubit

We demonstrate the conditional reversal of a weak (partial-collapse) quantum measurement on a photonic qubit. The weak quantum measurement causes a nonunitary transformation of a qubit which is subsequently reversed to the original state after a successful reversing operation. Both the weak measurement and the reversal operation are implemented linear optically. The state recovery fidelity, determined by quantum process tomography, is shown to be over 94% for partial-collapse strength up to 0.9. We also experimentally study information gain due to the weak measurement and discuss the role of the reversing operation as an information erasure

Discovery of Hits That Can Specifically Inhibit Necroptosis but Not Apoptosis

Necroptosis or programmed necrosis is a specialized and regulated necrosis, and is unmasked when apoptotic machinery for death stress is defective. Initially, it was proposed that necroptotic cell death was pathologically associated with ischemic brain injury and retinal disorders. In contrast, it plays a beneficial significance in innate immune response to viral infection that can evade host’s apoptotic surveillance. Also, it has been therapeutically emerging as the strategy to overcome the cancers with acquired anticancer drug resistance. Presently, a few small molecules to interfere with signaling pathways for necroptosis have been disclosed since necrostatin-1 (Nec-1) was for the first time identified as an inhibitor of receptor interacting protein 1 (RIP1), a key necroptosis regulator. In an effort to discover hits that can selectively inhibit necroptotic cell death, in this study, we screened in-house and in silico chemical libraries in a cell-based format. Eventually, 7 hits were identified from in-house chemical library while 2 hits were from computer modeling. Most hits less protected cells from tumor necrosis factor alpha (TNFα)- and zVAD-mediated necroptosis than a reference compound necrostatin-1, without affecting apoptotic cell death induced in HeLa. Interestingly, a few of hits had preferential protective effects on zVAD or TNFα while Nec-1 exhibited EC50 values at the similar concentrations against both necroptosis inducers, suggesting that chemicals deduced in our study can discriminate signaling pathways leading to receptor or nonreceptor-mediated necroptotic cell death.Therefore, some potent hits will be further improved to use for the treatment of necroptosis-associated disorders. &nbsp

Blue Ocean Strategy vs. Competitive Strategy: The Effect of Business Strategic Choices on Firm Performance, According to the Industry Life Cycle

The purpose of this study is to explore how blue ocean strategy and competitive strategy influence a firm\u27s business performance differently according to its stage in the industry life cycle (ILC). We developed a theoretical research model and the measure items to capture the different attributes of the blue ocean and competitive paradigms. We collected primary data from 309 business owners and senior managers working in the U.S. through a survey research. We tested the data by performing the exploratory factor analysis (EFA), the confirmatory factor analysis (CFA) and the structural equation modeling analysis (SEM) using SPSS and AMOS. The results from the statistical analysis demonstrate that the effects of blue ocean strategy on a firm\u27s business performance become increasingly weak as ILC stages pass, while the effects of competitive strategy gradually strengthen. However, our results show that, in general, blue ocean strategy has a more positive effect on a firm\u27s performance than competitive strategy. In addition, the study results suggest that blue ocean strategy fully mediates the relationship between a firm\u27s market orientation and its business performance, while competitive strategy only partially mediates the relationship. We discuss some theoretical implications and contributions of our research findings

The Relationship between Metacognition, Entrepreneurial Orientation, and Firm Performance: An Empirical Investigation

This study aims to examine the relationship between an entrepreneur’s metacognition, entrepreneurial orientation (EO), and firm performance. We collected primary data from 190 entrepreneurs (business owners or founders) working in the U.S. through a survey. By performing both the confirmatory factor analysis (CFA) and the structural equation modeling (SEM), we tested our hypothesized research model that represented the metacognition-EO-firm performance relationship. The results from the statistical analysis demonstrate that an entrepreneur\u27s metacognition has a significant positive impact on EO. Furthermore, the study result shows that EO has a full mediating effect on the relationship between entrepreneurial metacognition and firm performance. We, thus, anticipate that the findings of this study will help entrepreneurs to understand the mechanism on how their metacognitions impact their business outcomes as well as to recognize why they should consider their metacognitive abilities while executing entrepreneurial tasks

The QM evolution: Behavioral quality management as a firm’s strategic resource

Firms implement various quality management (QM) practices to improve process quality. Scholars recognize that QM practices consist of both technical and behavioral oriented practices. The relationship of technical and behavioral oriented practices on performance has led to paradoxical relationships. Improving quality performance necessitates understanding the relationship between technical and behavioral orientated practices. This study empirically examines the relationship between technical and behavioral quality practices by collecting survey data from both US-based (N = 152) and China-based (N = 222) firms. The analysis uses the structural equation modeling technique, and shows that behavioral QM practices fully mediate the relationship between technical QM practices and firm performance. This implies that behavioral QM practices act as a strategic resource which helps generate a competitive advantage. The results contribute to understanding how quality management practices can lead to a competitive advantage

The effect of phenylephrine on the onset time of rocuronium

BACKGROUND: Several studies have demonstrated that ephedrine shortens the onset time of muscle relaxants, and it does so probably by increasing the cardiac output. However, elevation of the systemic blood pressure through α adrenergic stimulation via ephedrine may affect the onset of muscle relaxants during the induction of anesthesia. We investigated the effect of phenylephrine, which is a selective α-1 agonist, on the onset time of rocuronium and the intubating conditions in adults after the administration of propofol. METHODS: Sixty-four patients were randomly assigned to two groups. Phenylephrine (0.9 µg/kg) (P group) or the same volume of saline (S group) was injected before rocuronium (0.6 mg/kg) administration. Anesthesia was induced with fentanyl 2 µg/kg and propofol 2 mg/kg. The onset time was defined as the time from the end of rocuronium injection to the time when a single twitch height gets to 0% or the minimum level. A well-trained anesthesiologist who was 'blinded' to the treatment groups evaluated the intubating conditions. The mean arterial pressure and heart rate were recorded before induction, before intubation, immediately after intubation and 1 minute and 2 minutes after intubation. RESULTS: The onset time was 84 ± 18 sec in the P-group and 72 ± 14 sec in the S-group. There was no difference of the intubating conditions, the mean arterial pressure and the heart rate between the two groups. CONCLUSIONS: A small dose of phenylephrine, which has a limited effect on blood pressure, delayed the onset time of rocuronium after the administration of propofol, and the vasoconstriction effect of phenylephrine may affect the prolongation of the rocuronium onset time at the induction of anesthesia with using propofol.ope

The HCV Core Protein Acts as a Positive Regulator of Fas-Mediated Apoptosis in a Human Lymphoblastoid T Cell Line

AbstractHepatitis C virus (HCV) is a major human pathogen causing mild to severe liver disease worldwide and is remarkably efficient at establishing persistent infections. Previously, we have shown that the core protein has an immunomodulatory function including the suppression of T lymphocyte responses to viral infection. To investigate the underlying mechanism for the role of core protein in immune modulation, we examined the effect of core on the sensitivity of the human T cell line, Jurkat, to Fas-mediated apoptosis. The transient and stable expression of core protein in Jurkat cells increased the sensitivity of cells to Fas-mediated apoptosis when compared to control cells expressing vector DNA alone. In addition, we demonstrated that the core protein binds to the cytoplasmic domain of Fas which may enhance the downstream signaling event of Fas-mediated apoptosis. The expression of core protein did not alter the cell surface expression of Fas, indicating that the increased sensitivity of core-expressing cells to Fas ligand was not due to upregulation of Fas. Furthermore, we observed the augmentation of caspase-3 activity in core-expressing cells. These results suggest that the core protein may promote the apoptosis of immune cells during HCV infection via the Fas signaling pathway, thus facilitating HCV persistence