Modest levels of reactive oxygen species (ROS) are necessary for intracellular signaling, cell division, and enzyme activation. These ROS are later eliminated by the body’s antioxidant defense ...system. High amounts of ROS cause carcinogenesis by altering the signaling pathways associated with metabolism, proliferation, metastasis, and cell survival. Cancer cells exhibit enhanced ATP production and high ROS levels, which allow them to maintain elevated proliferation through metabolic reprograming. In order to prevent further ROS generation, cancer cells rely on more glycolysis to produce ATP and on the pentose phosphate pathway to provide NADPH. Pro-oxidant therapy can induce more ROS generation beyond the physiologic thresholds in cancer cells. Alternatively, antioxidant therapy can protect normal cells by activating cell survival signaling cascades, such as the nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway, in response to radio- and chemotherapeutic drugs. Nrf2 is a key regulator that protects cells from oxidative stress. Under normal conditions, Nrf2 is tightly bound to Keap1 and is ubiquitinated and degraded by the proteasome. However, under oxidative stress, or when treated with Nrf2 activators, Nrf2 is liberated from the Nrf2-Keap1 complex, translocated into the nucleus, and bound to the antioxidant response element in association with other factors. This cascade results in the expression of detoxifying enzymes, including NADH-quinone oxidoreductase 1 (NQO1) and heme oxygenase 1. NQO1 and cytochrome b5 reductase can neutralize ROS in the plasma membrane and induce a high NAD+/NADH ratio, which then activates SIRT1 and mitochondrial bioenergetics. NQO1 can also stabilize the tumor suppressor p53. Given their roles in cancer pathogenesis, redox homeostasis and the metabolic shift from glycolysis to oxidative phosphorylation (through activation of Nrf2 and NQO1) seem to be good targets for cancer therapy. Therefore, Nrf2 modulation and NQO1 stimulation could be important therapeutic targets for cancer prevention and treatment.
Iron is essential for life. Many enzymes require iron for appropriate function. However, dysregulation of intracellular iron homeostasis produces excessive reactive oxygen species (ROS) via the ...Fenton reaction and causes devastating effects on cells, leading to ferroptosis, an iron-dependent cell death. In order to protect against harmful effects, the intracellular system regulates cellular iron levels through iron regulatory mechanisms, including hepcidin-ferroportin, divalent metal transporter 1 (DMT1)-transferrin, and ferritin-nuclear receptor coactivator 4 (NCOA4). During iron deficiency, DMT1-transferrin and ferritin-NCOA4 systems increase intracellular iron levels via endosomes and ferritinophagy, respectively. In contrast, repleting extracellular iron promotes cellular iron absorption through the hepcidin-ferroportin axis. These processes are regulated by the iron-regulatory protein (IRP)/iron-responsive element (IRE) system and nuclear factor erythroid 2-related factor 2 (Nrf2). Meanwhile, excessive ROS also promotes neuroinflammation by activating the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). NF-κB forms inflammasomes, inhibits silent information regulator 2-related enzyme 1 (SIRT1), and induces pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). Furthermore, 4-hydroxy-2,3-
-nonenal (4-HNE), the end-product of ferroptosis, promotes the inflammatory response by producing amyloid-beta (Aβ) fibrils and neurofibrillary tangles in Alzheimer's disease, and alpha-synuclein aggregation in Parkinson's disease. This interplay shows that intracellular iron homeostasis is vital to maintain inflammatory homeostasis. Here, we review the role of iron homeostasis in inflammation based on recent findings.
Using a panel dataset of 105 developing countries for the period 2003–15, this paper assesses the effects of Aid for Trade (AfT) on greenfield FDI flows to the aid‐recipient countries. Particularly, ...this paper classifies the total dollar value of greenfield FDI flows to each recipient country in terms of four different layers: the extensive and intensive margins of projects as well as the extensive and intensive margins of source countries. Applying the system GMM estimator, this paper finds that AfT not only increases the dollar value of FDI flows to the recipient countries but also helps diversify the greenfield projects and source countries. In addition, this paper finds that AfT has a greater effect for greenfield FDI from donor (developed) countries than from non‐donor (developing) countries. Among the three components of AfT, aid for trade‐related infrastructure and aid for trade policy regulations are found to have positive links with greenfield FDI, irrespective of source‐country groups, yet their effects are larger for developed source countries. In contrast, aid for building productive capacity hinders greenfield FDI flows from non‐donor countries, while it promotes greenfield FDI from donor countries. We offer some explanations for this finding.
•Using panel data for 142 countries for the period from 1960 to 2014, we assess the effects of population aging on economic growth.•We find that population aging proxied by old-age population share ...(or old-age dependency ratio) negatively affects economic growth only when it reaches a certain high level and its negative effects grow stronger as population aging deepens.•We also find that population aging has hampered economic growth during more recent years, especially in more aged countries which are mostly developed countries.•This nonlinear effect of aging is mainly driven by the fact that we use old-age population share as a proxy for aging.•If we use lower working-age population share as a proxy for aging, the nonlinear relationship disappears: working-age population share is positively related to economic growth in a linear way.
Using panel data for 142 countries for the period from 1960 to 2014, we assess the effects of population aging on economic growth. We find that population aging proxied by old-age population share (or old-age dependency ratio) negatively affects economic growth only when it reaches a certain high level and its negative effects grow stronger as population aging deepens. The nonlinear relationship between population aging and economic growth is associated with the historical nonlinear relationship between the shares of old and working-age population. In the early stages of a demographic shift in most countries, as the old-age population share increases, the working-age population share also tends to increase. Only when the share of old-age population is sufficiently high, the increase in the share of old-age population has coincided with the decline in the share of working age population, thereby having a negative relationship with economic growth. These results can clarify why some previous papers failed to uncover a negative relationship between aging population and economic growth. We also find that population aging has hampered economic growth during more recent years, especially in more aged countries which are mostly developed countries.
ABSTRACT
Performance evaluations are typically based on a formula that specifies in advance all performance measures, their relative incentive weights, and targets to be met. However, ...beginning‐of‐year performance targets can become outdated due to unforeseen events that call for ex post adjustments to formula‐based incentive plans to restore incentives. We discuss three types of ex post incentive plan adjustments—end‐of‐year subjective performance evaluation, changes in next‐year relative incentive weights, and changes in next‐year performance targets—and empirically examine the extent to which they are used to discourage failure to meet a target by a wide margin. Specifically, we use 2004–2015 data on formula‐based bonus plans, subjective performance evaluations, and performance in Korean state‐owned enterprises. Consistent with our predictions, we find that very low performance relative to target is associated with (i) low subjective evaluations and (ii) an increase in next‐year incentive weights, conditions that render areas with poor performance more important in future evaluations. These findings are more pronounced on performance dimensions of high importance and less pronounced when very low performance is due to an adverse uncontrollable shock. Finally, we find evidence that ex post incentive plan adjustments are associated with future performance improvements. Combined, our findings suggest that ex post incentive plan adjustments can be used to strengthen incentives when performance targets get outdated.
RÉSUMÉ
Cibles de rendement et ajustements a posteriori aux programmes incitatifs
Les évaluations du rendement sont habituellement fondées sur une formule qui précise à l'avance toutes les mesures de rendement, leur poids incitatif relatif ainsi que les cibles à atteindre. Toutefois, les cibles de rendement de début d'exercice peuvent devenir obsolètes en raison d’événements imprévus, une situation qui requiert des ajustements a posteriori aux programmes incitatifs pour rétablir les incitatifs. Nous abordons trois types d'ajustements a posteriori—une évaluation subjective du rendement à la fin de l'exercice, des modifications au poids incitatif des mesures de rendement pour l'année suivante et des modifications aux cibles de rendement pour l'année suivante—, et nous examinons de façon empirique dans quelle mesure ils sont mis à profit pour éviter de rater une cible par une vaste marge. Plus précisément, nous recourons à des données de 2004 à 2015 portant sur des programmes de primes fondés sur une formule, des évaluations de rendement subjectives et le rendement des entreprises coréennes détenues par l’État. Conformément à nos prédictions, nous établissons qu'un rendement très faible par rapport à la cible établie est associé à i) de mauvais résultats lors des évaluations subjectives et à ii) une augmentation du poids incitatif des mesures de rendement de l'année suivante, ce qui renforce l'importance accordée aux domaines affichant un faible rendement lors des évaluations ultérieures. Ces résultats sont plus prononcés pour les aspects du rendement qui ont une grande importance, et moins marqués lorsque le très faible rendement est attribuable à un choc défavorable incontrôlable. Enfin, nous constatons que les ajustements a posteriori aux programmes incitatifs sont associés à des améliorations ultérieures sur le plan du rendement. Globalement, nos résultats donnent à penser que ce type d'ajustements peut servir à renforcer les incitatifs lorsque les cibles de rendement sont dépassées.
Many studies have found that Aid for Trade (AfT) is effective in promoting the exports and imports of recipient countries. Recently, Gnangnon (The World Economy, 42, 2019 and 396) and Kim (The World ...Economy, 42, 2019 and 2684) found that AfT also contributes to the export diversification of recipient countries. We extend previous studies by assessing the effects of AfT on import diversification of recipient countries by estimating a two‐step System GMM on a data set of 104 countries in 2003–2016. Our empirical results reveal that AfT contributes to the diversification of both import commodities and import partners. This effect is particularly strong when partner countries are Non‐DAC countries. Our empirical evidence further strengthens the case for AfT because previous literature indicates that both export and import diversification are beneficial.
Mitochondrial dysfunction caused by oxidative stress appears at early stages of aging and age-related diseases. Plasma membrane redox enzymes act in a compensatory manner to decrease oxidative stress ...and supply reductive capacity to ensure cell survival. Plasma membrane redox enzymes transfer electrons from NAD(P)H to oxidized ubiquinone and α-tocopherol, resulting in inhibition of further oxidative damage. Plasma membrane redox enzymes and their partners are affected by aging, leading to progression of neurodegenerative disease pathogenesis. Up-regulating plasma membrane redox enzymes via calorie restriction and phytochemicals make cells more resistant to oxidative damage under stress conditions by maintaining redox homeostasis and improving mitochondrial function. Investigation into plasma membrane redox enzymes can provide mechanistic details underlying the relationships between plasma membrane redox enzymes and mitochondrial complexes and provide a good therapeutic target for prevention and delay of neurodegenerative disorders.
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Designing air-stable perovskite solar cells (PSCs) is a recent trend in low-cost photovoltaic technology. Metal oxide-based electron transporting layers (ETLs) and hole transporting ...layers (HTLs) have attracted tremendous attention in PSCs, because of their excellent air stability, high electron mobility, and optical transparency. Herein, we report a co-precipitation method for the synthesis of p-type nanoporous nickel oxide (np-NiOx) thin films as the HTL for inverted (p-i-n) PSCs. The best-performing p-i-n PSC having np-NiOx HTL, (FAPbI3)0.85(MAPbBr3)0.15 (herein FAPbI3 stands for formamidinium lead iodide and MAPbBr3 stands for methylammonium lead bromide) perovskite and phenyl-C61-butyric acid methyl ester (PCBM)/ZnO ETL exhibited a 19.10% (±1%) power conversion efficiency (PCE) with a current density (JSC) of 22.76 mA cm−2, open circuit voltage (VOC) of 1.076 V and fill factor (FF) of 0.78 under 1 sun (100 mW cm−2). Interestingly, the developed p-i-n PSCs based on p-type NiOx and n-type ZnO could retain >80% efficiency after 160 days, which is much higher than conventional PEDOT:PSS HTL-based PSCs. Our findings provide air-stable perovskite solar cells with high efficiency.
Manuscript Type
Empirical
Research Question/Issue
While most prior studies on the value of political connections focus on the political connections of controlling shareholders and top management, we ...examine the performance impact of appointing politically connected outside directors (PCODs) in Korean chaebol firms.
Research Findings/Insights
Using a manually collected sample of PCODs in Korean chaebol firms, we find that larger, high‐performing, less volatile firms with a larger board and higher divergence between voting rights and cash flow rights are more likely to appoint PCODs in the next year. We also report that firms with a high number of PCODs exhibit better operating performance and enjoy lower risk. On the other hand, we find evidence of weak monitoring ability by PCODs. Overall, we suggest that the number of PCODs correlates positively with firm performance, and that the value effect of PCODs increases with the importance of internal trade among group affiliates, the existence of inside directorship by controlling shareholders, and potential settlements from pending litigation. We further differentiate between PCODs and find that former government officials as PCODs drive our findings.
Theoretical/Academic Implications
This study contributes to corporate governance knowledge by revealing the relationship between PCODs and firm performance via an empirical inquiry into the role of PCODs on the board. As the controlling shareholders of Korean chaebol firms obtain greater private benefits of control, and such firms may face active government involvement in curbing controlling shareholders’ rent extraction, we examine the role and effects of PCODs in these situations and find evidence of the PCOD's value‐enhancing effect. We also complement and extend prior studies by providing more direct mechanisms through which PCODs can add value above and beyond firms’ ownership structure. Additionally, we expand the concept of political connection by analyzing outside directors’ human and social capital from the resource dependence theory perspective. Our attempt complements prior research's exclusive focus on connections of large shareholders or top executives to political parties and is more comprehensive in illustrating the firm's dynamic business environment.
Practitioner/Policy Implications
The results of our study are potentially useful to regulators, who will benefit from an understanding of how the presence of PCODs on boards affects firm performance. In particular, our results suggest that in countries where recent reforms aim to improve minority investor protection and market confidence, regulators should consider the composition of outside directors as well as explicit board independence. The results of our study may also be useful to investors, financial analysts, and auditors, as they highlight the importance of considering specific features of board composition when assessing firms’ future operating performance and risk mechanisms.
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