In this paper, we consider green product design in a supply chain consisting of one manufacturer and two retailers, where retailer 1 aims at monetary profit maximization, and retailer 2 has fairness concern. We consider two kinds of green products: a marginal-intensive green product (MIGP) and a development-intensive green product (DIGP). For the former, the green investment cost depends on the green level and the production quantity; while for the latter, the green investment cost depends on the green level solely. In each case, we investigate the impact of the retailer's fairness concern by comparing the optimal solutions and supply chain performance with those in the basic models in which all the supply chain members aim at profit maximization. We find that retailer 2 will set a higher retailing price and earn a smaller market share. Such inferiority increases as retailer 2's inequity aversion increases or as the substitutability degree of the products offered by the two retailers increases. We also find that retailer 2's fairness concern will always harm the manufacturer. If an equity outcome is achieved, the supply chain may achieve a better performance; however, if an inequity outcome is attained, the supply chain always performs worse.

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BackgroundAutoimmune hepatitis (AIH) is mediated by a cascade of T cell-mediated events directed at liver cells and persistent inflammation within the liver can eventually result in liver cirrhosis. Targeting glutamine metabolism has an impact on T cell activation and differentiation. However, the effect of glutamine metabolism blocking upon AIH remains unknown. We use glutaminase antagonist 6-diazo-5-oxo-L-norleucine (DON) for in vitro assays and its prodrug 2-(2-amino-4-methylpentanamido)-DON (JHU083) for in vivo assays to investigate the potential therapeutic effect and molecular mechanism of glutamine metabolism blocking in an AIH murine model.MethodsAIH mice were treated with JHU083 or vehicle before concanavalin A (ConA) administration, and disease severity was examined. Then activation and differentiation [including Th1/Th17 cells and cytotoxic T lymphocytes (CTL)] of T cells from Vehicle-WT, JHU083-AIH and Vehicle-AIH mice were tested. Furthermore, in vitro T cell activation and differentiation were measured using separated splenocytes stimulated with ConA with or without DON. The activation and differentiation of T cells were tested using flow cytometry, qRT-PCR and ELISA. Phosphorylation level of mammalian target of rapamycin (mTOR) and 70 kDa ribosomal protein S6 kinase (P70S6K) were examined by western blotting.ResultsJHU083 and DON significantly suppressed the activation of T cells and inhibited the differentiation of Th1/Th17 cells and CTL in vivo and in vitro. Besides, we demonstrated that glutamine metabolism blocking inhibited T cells activation and differentiation through decreasing the mRNA expression of amino acid transporter solute carrier family 7 member 5 (SLC7A5) and mitigating the activation of mTOR signaling.ConclusionsWe proved that targeting glutamine metabolism represents a potential new treatment strategy for patients with AIH and other T cell-mediated disease. Mechanistically, we demonstrated that glutamine metabolism blocking inhibits T cells activation and suppresses the differentiation of Th1/Th17 cells and CTL.

A proton therapy facility based on a linac injector and a slow-cycling synchrotron is proposed. To obtain good treatments for different cancer types, both the spot scanning method and the double-scattering method are adopted in the facility, whereas the nozzles include both gantry and fixed beam types. The proton accelerator chain includes a synchrotron of 250 MeV in maximum energy, an injector of 7 MeV consisting of an RFQ and a DTL linac, with a repetition rate of 0.5 Hz. The slow extraction using the third-order resonance and together with the RFKO method is considered to be a good method to obtain a stable and more-or-less homogenous beam spill. To benefit the spot scanning method, the extraction energy can be as many as about 200 between 60 MeV and 230 MeV. A new method - the emittance balancing technique of using a solenoid or a quadrupole rotator is proposed to solve the problem of unequal emittance in the two transverse planes with a beam slowly extracted from a synchrotron. The facility has been designed to keep the potential to be upgraded to include the carbon therapy in the future.