Delivery Service Optimization When the Information on the Consumers’ Time Values Is Asymmetric

When consumers’ time values are discrete and asymmetric, three delivery service schemes, which are single ordinary delivery, single expedited delivery, and a mixture of ordinary and expedited delivery, were analyzed and compared. From the perspective of the firm, the optimal lead time and price in each delivery service scheme were determined based on the principal-agent theory. The results show that when the proportion of higher time value consumers is not above a specific threshold, providing a mixture of delivery services outperforms providing single delivery services. Otherwise, providing a single expedited delivery service becomes the best choice. As the consumers’ time value increases, the optimal lead time of the delivery service that is targeted to them should be decreased and the optimal price should be increased. If the firm provides a mixture of delivery services, then the optimal lead time of expedited delivery should be equal to that of the single expedited delivery scheme, while the optimal lead time of ordinary delivery should be longer than that of the single ordinary delivery scheme. Moreover, the optimal lead time of ordinary delivery in the mixed case should be increased with the proportion of higher time value consumers until it reaches the maximum length of time that all consumers could bear

Determining the Operator for the Public Toll Road

After the BOT road operation contract expires, generally, the road will be transferred to the government, and then the government operates the road independently without charging costs from its users. Facing the huge amount of the operation cost, Chinese government tends to continue to charge the road users to guarantee the high quality of road operation. Then, the government will have to decide whether a private firm or government itself would be suitable to operate the road. A model is presented for decision-making through balancing interests between the government and the private firm with an introduction of an intermediate variable, i.e., bidding price. Three scenarios are investigated in the model, including the optimization of government operation, the optimization of private firm operation, and government operation with an improper decision of the intermediate variable. Improper intermediate variable will result in a higher toll charged by the government than by a private firm. The method of avoiding an improper decision is investigated. The result shows that the intermediate variable should be determined to be the government operation cost, based on which the private operator could be chosen, if available. With consideration of the private operator’s profit to be guaranteed by the government, the maximum subsidy should be equal to the minimum private operator’s profit to be disclosed when the contract is signed

IL‐19 induced by IL‐13/IL‐17A in the nasal epithelium of patients with chronic rhinosinusitis upregulates MMP‐9 expression via ERK/NF‐κB signaling pathway

Abstract Background Tissue remodeling is a crucial characteristic of chronic rhinosinusitis (CRS). Imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) is crucial for the pathologic tissue remodeling in CRS. Elevation of interleukin (IL)‐19 or MMP‐9 levels in patients with CRS had been proven in previous studies. Here, we aimed to investigate the role of IL‐19 in mediating MMP‐9 expression in CRS. Methods Nasal tissue samples were collected from 45 individuals having chronic rhinosinusitis with nasal polyps (CRSwNP), 24 CRS without nasal polyps (CRSsNP), and 17 controls. Expression of IL‐19, its receptors (IL‐20R1/IL‐20R2), and MMP‐9 were investigated using RT‐qPCR and Immunofluorescence (IF). Human nasal epithelial cells (HNECs) were stimulated by IL‐19; ERK phosphorylation, nuclear factor‐κB (NF‐κB) pathway activation, and MMP‐9 level were detected by RT‐qPCR, enzyme‐linked immunosorbent assay, western blot, and IF. We also explored the effect of type1/2/3 cytokines on IL‐19 production by RT‐qPCR, and western blot. Results Expression levels of IL‐19, its receptors (IL‐20R1/IL‐20R2), and MMP‐9 were increased in nasal tissues from individuals with CRSwNP compared to those with CRSsNP as well as the controls. IL‐19 significantly elevated the production of MMP‐9 in HNECs. Furthermore, IL‐19 could activate the ERK and NF‐κB pathways, accompanied by increased MMP‐9 production in HNECs. Conversely, both ERK and NF‐κB inhibitors significantly attenuated the role of IL‐19 in MMP‐9 production. siRNA knockdown of IL‐20R1 suppressed ERK and NF‐κB pathway activation, thereby decreasing MMP‐9 expression. IL‐13 and IL‐17A were found to stimulate IL‐19 production in HNECs. Conclusion IL‐19, promoted by IL‐13 and IL‐17A, contributes to the upregulation of secretion of the tissue remodeling factor MMP‐9 in patients with CRS

Tc17/IL-17A Up-Regulated the Expression of MMP-9 via NF-κB Pathway in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis

Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the upper airways involving nasal cavity and sinus. Deriving both from its clinical complexity with protean clinical manifestations as well its pathogenetic heterogeneity, the molecular mechanisms contributing to the pathogenesis of CRS remain unclear, and attract a wide interest in the field. Current evidences indicate that IL-17A is highly expressed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, its pathogenetic role in regulation of tissue remodeling of CRSwNP remains unknown. The present study aimed to investigate the cellular origins and functions of IL-17A cytokine in CRSwNP, and further determined whether IL-17A could affect the expression of metalloproteinases (MMPs), the remodeling factors of CRSwNP. The results showed that the expression of IL-17A was upregulated in nasal tissues of patients with CRSwNP compared to those with chronic rhinosinusitis without nasal polyps (CRSsNP) and controls. CD8+ cytotoxic T lymphocytes (Tc) were major IL-17A producers in nasal tissues of CRSwNP. Interleukin (IL)-17-producing CD8+ T cells (Tc17) was significantly higher in nasal tissues of CRSwNP than CRSsNP and controls. Nonetheless, no difference was observed among the IL-17A in peripheral blood lymphocytes of these three groups. Moreover, in the same patients, IL-17A expression was negligible in lymphocytes of peripheral blood when compared with nasal tissues. Increased gene and protein expression of MMP-7 and MMP-9 in patients with CRSwNP compared with controls were observed. In CRSwNP samples, IL-17A receptor (IL-17AR) co-localized with MMP-9 and they were mainly expressed in the epithelial cells. MMP-9 expression was up-regulated both in Primary human nasal epithelial cells (PHNECs) and a nasal epithelial cell line (RPMI 2650) by IL-17A treatment, and diminished by anti-IL-17AR treatment. Furthermore, IL-17A promoted the expression of MMP-9 by activating the NF-κB signal pathway. Thus, our results have revealed a crucial role of IL-17A and Tc cells on pathogenesis and tissue remodeling of CRSwNP

Influence of agri-environmental schemes on grey partridge

The final weights of mice with 6 different treatments. (TIF 537 kb

Additional file 2: Figure S2. of Targeting Rad50 sensitizes human nasopharyngeal carcinoma cells to radiotherapy

NPC xenografts of mice with 6 different treatments. (TIF 7044 kb