•We consider innovation and subsidies, and different supply chain collaboration.•We find that the government may be indifferent as to how collaboration is formed.•We find that manufacturer may be ...worse off by initiating the collaboration.
Motivated by recently observed industry and government practices, in this paper we endogenize government subsidy in a research joint venture (RJV). In particular, we present a three-player game in which a government determines the amount of subsidy for a supply chain consisting of a manufacturer and a retailer conducting an RJV on a sustainable product. In addition to the retail and wholesale pricing decisions, the firms must determine the level of innovation effort as well as the division of innovation costs between the partners. In our analysis we consider two forms of RJV formation (retailer and manufacturer initiated) and two types of subsidy (per-unit production subsidy and innovation effort subsidy). We find that: (a) the government should never use both types of subsidies simultaneously for any cost-reduction research and development (R&D) effort, (b) whenever effort subsidy is present the government is indifferent as to how the RJV is formed, and (c) even though firms benefit most from initiating the RJV in many cases, the manufacturer is worse off by initiating the RJV if R&D effort increases per-unit production cost, innovation or production cost is high and only per-unit production subsidy is present.
This paper explores a buyer's tracing and its supplier's own sourcing decisions in a multi-tier supply chain. We explore what different stakeholders can do to achieve a more transparent and/or ...responsible supply chain. We establish that under rather general conditions, the two firms will adopt mixed strategies in equilibrium, a focal case of our analysis. The mixed-strategy results first explain at the micro level why many companies are not certain about whether their supply chains are ethical or not. At the more macro level, they also help explain why a significant proportion of the buyers did not trace or comply with transparency regulations. We then show that more responsible sourcing can be induced by lowering the buyer's tracing cost but not by reducing the supplier's own responsible sourcing cost. We also find that more transparency does not always imply more responsible sourcing. For the external stakeholders, more responsible sourcing may be obtained through lowering tracing costs, improving tracing or public discovery of violations, and imposing more significant reputational damage or penalties only on the buyer. For the internal stakeholders, a contract incorporating both responsible sourcing cost sharing and non-compliance penalty if found may be constructed for the first-best supply chain efficiency and likely social optimality under some simple sufficient conditions.
Atrial fibrillation (AF) is the most common cardiac arrhythmia. However, the development of preventative therapies for AF has been disappointing. The infiltration of immune cells and proteins that ...mediate the inflammatory response in cardiac tissue and circulatory processes is associated with AF. Furthermore, the presence of inflammation in the heart or systemic circulation can predict the onset of AF and recurrence in the general population, as well as in patients after cardiac surgery, cardioversion, and catheter ablation. Mediators of the inflammatory response can alter atrial electrophysiology and structural substrates, thereby leading to increased vulnerability to AF. Inflammation also modulates calcium homeostasis and connexins, which are associated with triggers of AF and heterogeneous atrial conduction. Myolysis, cardiomyocyte apoptosis, and the activation of fibrotic pathways via fibroblasts, transforming growth factor-β and matrix metalloproteases are also mediated by inflammatory pathways, which can all contribute to structural remodelling of the atria. The development of thromboembolism, a detrimental complication of AF, is also associated with inflammatory activity. Understanding the complex pathophysiological processes and dynamic changes of AF-associated inflammation might help to identify specific anti-inflammatory strategies for the prevention of AF.
Aging plays a critical role in the genesis of atrial fibrillation (AF) and also increases the risks of cardiac dysfunction and stroke in AF patients. AF is caused by increased AF triggering from ...abnormalities of the thoracic vein and/or modulated substrate (atrial) with enhancement of AF maintenance. Clinical and laboratory evidence indicates that aging is significant in the creation of atrial electrical and structural remodeling that leads to increased susceptibility to AF occurrence. Aging is commonly associated with cardiovascular comorbidities, oxidative stress, calcium dysregulation, atrial myopathy with apoptosis, and fibrosis, which all contribute to the genesis of AF. This review updates the current understanding of the effects of aging on the pathophysiology of AF.
Background
Atrial fibrillation (AF) is the most common sustained atrial arrhythmia. Accurate detection of the timing and possibility of AF termination is vital for optimizing rhythm and rate control ...strategies. The present study evaluated whether the ventricular response (VR) in AF offers a distinctive electrocardiographic indicator for predicting AF termination.
Methods
Patients experiencing sustained paroxysmal AF for more than 3 h were observed using 24‐h ambulatory Holter monitoring. VR within 5 min before AF termination (VR 0–5 min, BAFT) was compared with VR observed during the 60th to 65th min (VR 60–65 min, BAFT) and the 120th to 125th min (VR 120–125 min, BAFT) before AF termination. Maximum and minimum VRs were calculated on the basis of the average of the highest and lowest VRs across 10 consecutive heartbeats.
Results
Data from 37 episodes of paroxysmal AF revealed that the minimum VR0–5 min, BAFT (64 ± 20 bpm) was significantly faster than both the minimum VR120–125 min, BAFT (56 ± 15 bpm) and the minimum VR60–65 min, BAFT (57 ± 16 bpm, p < .05). Similarly, the maximum VR0–5 min, BAFT (158 ± 49 bpm) was significantly faster than the maximum VR120–125 min, BAFT (148 ± 45 bpm, p < .05). In the daytime, the minimum VR0–5 min, BAFT (66 ± 20 bpm) was significantly faster than both the minimum VR60–65 min, BAFT (58 ± 17 bpm) and minimum VR120–125 min, BAFT (57 ± 15 bpm, p < .05). However, the mean and maximum VR0–5 min, BAFT in the daytime were similar to the mean and maximum VR120–125 min in the daytime, respectively. At night, the minimum, mean, and maximum VR0–5 min, BAFT were similar to the minimum, mean, and maximum VR120–125 min, respectively.
Conclusions
Elevated VR rates during AF episodes may be predictors for the termination of AF, especially during the daytime and in patients with nondilated left atria. These findings may guide the development of clinical approaches to rhythm control in AF.
Growth arrest-specific protein 6 (Gas6) is a vitamin K-dependent protein expressed by endothelial cells and leukocytes that are involved in cell survival, migration, and proliferation in response to ...inflammatory processes. The aim of this study was to assess the implications of Gas6 in Sjögren syndrome (SS) and its expression in the labial salivary gland.
A total of 254 adults, including 159 with primary Sjögren syndrome (pSS), 34 with secondary Sjögren syndrome (sSS), and 61 normal controls, were recruited. Plasma Gas6 concentrations were determined, and Gas6 expressions in labial salivary gland (LSG) tissues from controls and pSS and sSS patients were also evaluated. Plasma Gas6 concentrations were significantly lower among patients with pSS than normal controls (13.5 ± 8.6 vs. 19.9 ± 13.4 ng/ml, p < 0.001). There were, however, no significant differences in plasma Gas6 levels between pSS and sSS patients (13.5 ± 8.6 vs. 16.9 ± 11.2 ng/ml, p = 0.068). In multivariate logistic regression analysis, after adjustment for white blood cell count, hemoglobin level, platelet count, lymphocyte count, and C3 and C4 levels, lower plasma Gas6 concentrations were significantly associated with an increased risk of SS. Moreover, by using a semi-quantitative scale to evaluate Gas6 expression in LSG tissues, Gas6 expression was found to be markedly lower in LSG tissues from pSS patients than in tissues from normal controls.
Decreased plasma Gas6 concentration and LSG expression were associated with pSS. As such, Gas6 may represent a novel independent risk factor for pSS, with a potential role in salivary gland inflammation and dysfunction.
Oxidative stress is an important pathomechanism found in numerous ocular degenerative diseases. To provide a better understanding of the mechanism and treatment of oxidant/antioxidant ...imbalance-induced ocular diseases, this article summarizes and provides updates on the relevant research. We review the oxidative damage (e.g., lipid peroxidation, DNA lesions, autophagy, and apoptosis) that occurs in different areas of the eye (e.g., cornea, anterior chamber, lens, retina, and optic nerve). We then introduce the antioxidant mechanisms present in the eye, as well as the ocular diseases that occur as a result of antioxidant imbalances (e.g., keratoconus, cataracts, age-related macular degeneration, and glaucoma), the relevant antioxidant biomarkers, and the potential of predictive diagnostics. Finally, we discuss natural antioxidant therapies for oxidative stress-related ocular diseases.
Macrophages form a major cell population in the tumor microenvironment. They can be activated and polarized into tumor-associated macrophages (TAM) by the tumor-derived soluble molecules to promote ...tumor progression and metastasis. Here, we used comparative metabolomics coupled with biochemical and animal studies to show that cancer cells release succinate into their microenvironment and activate succinate receptor (SUCNR1) signaling to polarize macrophages into TAM. Furthermore, the results from in vitro and in vivo studies revealed that succinate promotes not only cancer cell migration and invasion but also cancer metastasis. These effects are mediated by SUCNR1-triggered PI3K-hypoxia-inducible factor 1α (HIF-1α) axis. Compared with healthy subjects and tumor-free lung tissues, serum succinate levels and lung cancer SUCNR1 expression were elevated in lung cancer patients, suggesting an important clinical relevance. Collectively, our findings indicate that the secreted tumor-derived succinate belongs to a novel class of cancer progression factors, controlling TAM polarization and promoting tumorigenic signaling.
Display omitted
•Cancer cells secrete succinate to promote TAM polarization and cancer metastasis•Cancer-cell-derived secreted succinate is related to reduction of SDH activity•SUCNR1-triggered PI3K-HIF-1α axis mediates TAM polarization and cancer metastasis•Serum succinate is elevated in patients with lung cancer and serves as a biomarker
We have shown that cancer cells secrete succinate into extracellular milieu, which mediates TAM polarization and promotes cancer metastasis. Succinate exerts its effects on TAM polarization and cancer metastasis via a specific membrane receptor, SUCNR1, which transmits signaling through the PI3K/HIF-1α pathway.
Background
Ceramide is involved in regulating metabolism and energy expenditure, and its abnormal myocardial accumulation may contribute to heart injury or lipotoxic cardiomyopathy. Whether ceramide ...can modulate the electrophysiology of pulmonary veins (PVs) remains unknown.
Materials and methods
We used conventional microelectrodes to measure the electrical activity of isolated rabbit PV tissue preparations before and after treatment with various concentrations of ceramide with or without H2O2 (2 mM), MitoQ, wortmannin or 740 YP. A whole‐cell patch clamp and fluorescence imaging were used to record the ionic currents, calcium (Ca2+) transients, and intracellular reactive oxygen species (ROS) and sodium (Na+) in isolated single PV cardiomyocytes before and after ceramide (1 μM) treatment.
Results
Ceramide (0.1, 0.3, 1 and 3 μM) reduced the beating rate of PV tissues. Furthermore, ceramide (1 μM) suppressed the 2 mM H2O2‐induced faster PV beating rate, triggered activities and burst firings, which were further reduced by MitoQ. In the presence of wortmannin, ceramide did not change the PV beating rate. The H2O2‐induced faster PV beating rate could be counteracted by MitoQ or wortmannin with no additive effect from the ceramide. Ceramide inhibited pPI3K. Ceramide reduced Ca2+ transients, sarcoplasmic reticulum Ca2+ contents, L‐type Ca2+ currents, Na+ currents, late Na+ currents, Na+‐hydrogen exchange currents, and intracellular ROS and Na+ in PV cardiomyocytes, but did not change Na+‐Ca2+ exchange currents.
Conclusion
C2 ceramide may exert the distinctive electrophysiological effect of modulating PV activities, which may be affected by PI3K pathway–mediated oxidative stress, and might play a role in the pathogenesis of PV arrhythmogenesis.
Transfer‐induced wrinkles are universal issues when transferring transition metal dichalcogenide (TMDC) monolayer from an as‐grown substrate to a target substrate. The undesired transfer‐induced ...wrinkles can mainly be attributed to wettability, which refers to the ability of a liquid to come in contact with a solid surface. Herein, an adjustable wettability‐assisted transfer (AWAT) method with different mixtures of transfer media to reduce the density of wrinkles is developed. By manipulating the wettability of the transfer medium with different ratios of alcohol and de‐ionized (DI) water, the TMDC monolayer is smoothly attached to the target substrate, thus achieving a wrinkle‐less transferred TMDC monolayer. With this method, the density of wrinkles can be decreased by ≈15–20% compared with the conventional transfer method by pure DI water. The transferred MoS2 monolayer with the AWAT method can achieve enhanced carrier mobility from ≈20 to ≈35 cm2 V−1 s−1 in average, which is 30 times larger than that transferred by pure DI water. The AWAT method applied to a WS2 monolayer onto a SiO2/p+‐Si substrate and a MoS2 monolayer onto a HfO2/p+‐Si substrate are demonstrated, which is beneficial in research and applications involving the transfer of TMDC monolayer.
The rational design of wrinkle‐less transfer of transition metal dichalcogenide monolayer via an adjustable wettability‐assisted transfer (AWAT) method is demonstrated. With AWAT, the density of wrinkles can be decreased by ≈15–20% and carrier mobility can be enhanced 30 times compared with the conventional transfer method by the pure DI water.
PDF
