Research summary: Researchers have increasingly emphasized the need to better understand how context affects the value of experiential learning. We address this gap by investigating when ...corporate-level experience ca be leveraged across borders and when experience needs to be country-specific to be valuable. We test our hypotheses using a unique multi-source panel dataset of 379 large MNCs from 29 home countries and their subsidiaries in 117 host countries over a 10-year period, 1999–2008. In contrast to prior research, we find that the ability of a firm to leverage its experience with political risk across borders is limited by the type of risk involved. Experience with nonstate violent conflicts may be transferrable, but only country-specific experience appears to yield measureable benefits for conflicts involving the host country government. Managerial summary: Violent conflicts not only increase social unrest but also impose added costs of doing business. For managers who find themselves in the midst of violent conflicts or who wish to survive and potentially gain a competitive advantage in operating in such challenging environments, is it possible to learn to manage such a seemingly "unmanageable" problem? In contrast to studies that have examined other types of political risk, we find that the ability of a firm to leverage its experience with violent conflict risk across borders is limited. Specifically, only country-specific experiential knowledge about how the host government prepares and manages such conflict risks yields measureable economic benefits for MNCs and their subsidiaries operating in countries during conflict.
Depression is a leading cause of disability. Current pharmacological treatment of depression is insufficient, and development of improved treatments especially for treatment-resistant depression is ...desired. Understanding the neurobiology of antidepressant actions may lead to development of improved therapeutic approaches. Here, we demonstrate that dopamine D1 receptors in the dentate gyrus act as a pivotal mediator of antidepressant actions in mice. Chronic administration of a selective serotonin reuptake inhibitor (SSRI), fluoxetine, increases D1 receptor expression in mature granule cells in the dentate gyrus. The increased D1 receptor signaling, in turn, contributes to the actions of chronic fluoxetine treatment, such as suppression of acute stress-evoked serotonin release, stimulation of adult neurogenesis and behavioral improvement. Importantly, under severely stressed conditions, chronic administration of a D1 receptor agonist in conjunction with fluoxetine restores the efficacy of fluoxetine actions on D1 receptor expression and behavioral responses. Thus, our results suggest that stimulation of D1 receptors in the dentate gyrus is a potential adjunctive approach to improve therapeutic efficacy of SSRI antidepressants.
We investigate the response of multinational corporations (MNCs) to major disasters at the subsidiary level. We examine the type and severity of the disaster and whether and how country governance ...moderates the relationship between exogenous disaster risk and subsidiary investment. We test our hypotheses with a panel dataset of 71 large European MNCs and their subsidiaries (2001–2006) with 31,285 total observations. Findings suggest that the number of a firm's foreign subsidiaries is likely to decrease in response to terrorist attacks or technological disasters but not natural disasters, regardless of the severity of the event. For terrorist activities, MNC subsidiary-level disinvestment is less likely when the quality of host country governance is higher.
Most antidepressants, including selective serotonin reuptake inhibitors (SSRIs), initiate their drug actions by rapid elevation of serotonin, but they take several weeks to achieve therapeutic onset. ...This therapeutic delay suggests slow adaptive changes in multiple neuronal subtypes and their neural circuits over prolonged periods of drug treatment. Mossy cells are excitatory neurons in the dentate hilus that regulate dentate gyrus activity and function. Here we show that neuronal activity of hippocampal mossy cells is enhanced by chronic, but not acute, SSRI administration. Behavioral and neurogenic effects of chronic treatment with the SSRI, fluoxetine, are abolished by mossy cell-specific knockout of p11 or Smarca3 or by an inhibition of the p11/AnxA2/SMARCA3 heterohexamer, an SSRI-inducible protein complex. Furthermore, simple chemogenetic activation of mossy cells using Gq-DREADD is sufficient to elevate the proliferation and survival of the neural stem cells. Conversely, acute chemogenetic inhibition of mossy cells using Gi-DREADD impairs behavioral and neurogenic responses to chronic administration of SSRI. The present data establish that mossy cells play a crucial role in mediating the effects of chronic antidepressant medication. Our results indicate that compounds that target mossy cell activity would be attractive candidates for the development of new antidepressant medications.
We investigate whether firm experience with discontinuous risks, particularly high-impact disasters that are episodic and difficult to anticipate, moderates the relationship between disasters, ...foreign entry, and expansion decisions. Using a panel data set with 57,500 observations from 106 large European multinational corporations and their subsidiaries operating across 109 countries from 2001 to 2007, we find that although discontinuous risk was negatively related to firm entry and expansion, firms that had experience with high-impact disasters were more likely to expand in countries experiencing disasters.
Ubiquitin-specific protease 7 inhibitors (USP7i) are considered a novel class of anticancer drugs. Cancer cells occasionally become insensitive to anticancer drugs, known as chemoresistance, by ...acquiring multidrug resistance, resulting in poor clinical outcomes in patients with cancer. However, the chemoresistance of cancer cells to USP7i (P22077 and P5091) and mechanisms to overcome it have not yet been investigated. In the present study, we generated human cancer cells with acquired resistance to USP7i-induced cell death. Gene expression profiling showed that heat stress response (HSR)- and unfolded protein response (UPR)-related genes were largely upregulated in USP7i-resistant cancer cells. Biochemical studies showed that USP7i induced the phosphorylation and activation of heat shock transcription factor 1 (HSF1), mediated by the endoplasmic reticulum (ER) stress protein kinase R-like ER kinase (PERK) signaling pathway. Inhibition of HSF1 and PERK significantly sensitized cancer cells to USP7i-induced cytotoxicity. Our study demonstrated that the ER stress-PERK axis is responsible for chemoresistance to USP7i, and inhibiting PERK is a potential strategy for improving the anticancer efficacy of USP7i.
This study presents the 2014 nationwide cancer statistics in Korea, including cancer incidence, survival, prevalence, and mortality.
Cancer incidence data from 1999 to 2014 was obtained from the ...Korea National Cancer Incidence Database and followed until December 31, 2015. Mortality data from 1983 to 2014 were obtained from Statistics Korea. The prevalence was defined as the number of cancer patients alive on January 1, 2015, among all cancer patients diagnosed since 1999. Crude and age-standardized rates (ASRs) for incidence, mortality, prevalence, and 5-year relative survivals were also calculated.
In 2014, 217,057 and 76,611 Koreans were newly diagnosed and died from cancer respectively. The ASRs for cancer incidence and mortality in 2014 were 270.7 and 85.1 per 100,000, respectively. The all-cancer incidence rate has increased significantly by 3.4% annually from 1999 to 2012, and started to decrease after 2012 (2012-2014; annual percent change, -6.6%). However, overall cancer mortality has decreased 2.7% annually since 2002. The 5-year relative survival rate for patients diagnosed with cancer between 2010 and 2014 was 70.3%, an improvement from the 41.2% for patients diagnosed between 1993 and 1995.
Age-standardized cancer incidence rates have decreased since 2012 and mortality rates have also declined since 2002, while 5-year survival rates have improved remarkably from 1993-1995 to 2010-2014 in Korea.
This study aimed to assess the effect of different calcium silicate-based root canal sealers (CSRS) on osteogenic effect in human periodontal ligament cells (hPDLCs). hPDLCs were cultured in a medium ...containing extract of 5 types of CSRS. The specimens were assessed by the cell cytotoxicity test, alkaline phosphatase staining, alizarin red S staining, quantitative real-time PCR, Western blot analysis, and enzyme-linked immunosorbent assay. The diluted concentrations of extracted solutions had no significant effect on the viability of hPDLCs. There was a statistically significant difference in the mRNA expression level of bone sialoprotein (BSP), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2) among some groups. The protein expressions of BSP, OCN, and RUNX2 were significantly higher in some groups compared to the control group. The CSRS did not interfere with the osteogenic differentiation of hPDLCs, compared to the control group. CSRS are shown to have biocompatibility and osteogenic differentiation effect on hPDLCs.
Research summary
Using collective action and social movement theory, we investigate the potential incentives and ability of stakeholders to engage in collective action that can increase firm‐specific ...nonmarket risk of mining companies. We argue that proximity to the nearest environmentally sensitive water source increases the probability that local stakeholders will take collective actions that impose material costs on the focal mine. We hypothesize that stock markets recognize this nonmarket risk and apply a discount on announcements related to mines located near such areas, and that these risks are moderated by the type of mineral, the nature of the water source, and the strength of host country institutions. Using a unique data set and an event study method, we find support for most of our arguments.
Managerial summary
We argue that mines located near environmentally sensitive water sources are subject to nonmarket risks arising from the potential collective actions of local stakeholders and their allies. Stakeholder mobilization can impose material costs on a mine in the form of delays, regulatory hurdles, and closure. We find that stock markets recognize these nonmarket risks and apply a discount on announcements by mining companies whose mines are located near environmentally sensitive water sources, particularly rivers. However, we also find that investor reaction is stronger in countries with strong institutions that support collective action. Thus, nonmarket risk management is important even in countries that are typically characterized by low political and institutional risks. We discuss the degree to which these results can be generalized beyond mining.
Much of the literature in international business analysing the multinational enterprise uses the country as the relevant environmental parameter. This paper presents both theoretical and empirical ...evidence to demonstrate that country‐level analysis now needs to be augmented by analysis at the ‘regional’ level of the broad triad markets of Europe, North America and the Asia Pacific. The great majority of the world's 500 largest firms concentrate their activities within their home region of the triad. This study uses variance component analysis and finds that this home region effect outperforms the country effect. Together, the regional and industry effects explain most of the geographic expansion of multinational enterprises (MNEs), whereas country, firm and year effects are very minor. The new data and variance component analysis on the activities of large MNEs reported here suggest that new thinking is required about the importance of large regions of the triad as the relevant unit of analysis for business strategy to supplement the conventional focus on the country.
PDF
