Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The cur...Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The current treatment methods for NKTCL are associated with several drawbacks.For example,chemotherapy can lead to drug resistance,while treatment with radiotherapy alone is inadequate and results in frequent relapses.Moreover,hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts.In recent years,immunotherapy has shown good clinical results and has become a hot spot in cancer research.Clinical activity of targeted antibodies,such as daratumumab(anti-CD38 antibody)and brentuximab vedotin(anti-CD30 antibody),have been reported in NKTCL.Additionally,dacetuzumab and Campath-1 H have demonstrated promising results.Further encouraging data have been obtained using checkpoint inhibitors.The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL.Furthermore,anti-CCR4 monoclonal antibodies(m Abs)exert cytotoxic actions on both CCR4+tumor cells and regulatory T cells.Depletion of these cells and the long half-life of anti-CCR4 m Abs result in enhanced induction of antitumor effector T cells.The role of IL10 in NKTCL has also been investigated.It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies.Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission.Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease.The present review outlines the known immunotherapy targets for the treatment of NKTCL.展开更多
In this paper, the optimal policy is considered when the buyer faces two supply sources： one is the contract supplier from which the buyer orders over a specific contract period （say, a year） at a pre-agreed price,...In this paper, the optimal policy is considered when the buyer faces two supply sources： one is the contract supplier from which the buyer orders over a specific contract period （say, a year） at a pre-agreed price, and the other is the spot market. However, when ordering from the contract supplier, the buyer must fulfill a pre-determined total order quantity, or the so-called definite total order quantity commitment, over the whole contract period. In other words, the commitment secures the buyer a fixed price but obliges him/her a total order quantity over the contract period. Although the spot market gives the buyer more flexibility in terms of order quantities, its prices are volatile. Such a combination of contract and spot procurements is often observed in practice. Within the contract period, there are multiple sub-periods, during each of which the buyer reviews the inventory, issues an individual order, and uses the on-hand inventory to meet the random demand. Thus, in each （ordering） period, the buyer will weigh between the current known spot price （by procuring from the spot market） and a lower future price （by waiting while consuming the remaining commitment）. An optimal dual ordering policy is characterized for each period, depending on the on-hand inventory level, the spot price, and the remaining commitment quantity. The optimal policy in each period is also shown to be independent of the contract price. Through a numerical study, the inventory cost is demonstrated to be （1） insensitive to the contract price when the total commitment quantity is lower than the total expected demand over the contract period and （2） non-increasing in the variability of spot prices.展开更多
In this paper we study the competitive order timing decisions of two manufacturers with demand forecasting updating and uncertain raw material price.Manufacturers can order the raw materials early when the market is h...In this paper we study the competitive order timing decisions of two manufacturers with demand forecasting updating and uncertain raw material price.Manufacturers can order the raw materials early when the market is highly uncertain with a fixed wholesale price(Contract procurement)or late when the market is less uncertain with an uncertain raw material price(Spot trading).Different from most existing literature,we assume the spot price and the market demand is correlated.We find that in the monopoly setting the manufacturer prefers the contract procurement to the spot trading when the unit wholesale price for the contract procurement is not greater than the expected unit spot price of the raw material.In the duopoly setting,we characterize the equilibria of a strategic order timing game in which manufacturers choose when to buy the raw materials.We find that when the demand during the contract procurement stage and the spot price uncertainty is small both manufacturers prefer the contract procurement strategy and when the demand during the contract procurement stage and the spot price uncertainty is large both manufacturers prefer the spot trading.When the demand during the contract procurement stage and the spot price uncertainty is high and purchase costs do not decline too severely over time,the unique equilibrium of this game is that one manufacturer chooses contract procurement to order early and the other chooses spot trading to order late.Further,we find that the correlation of spot purchasing price and the market demand signal during the contract procurement stage will weaken the advantages of spot trading strategy.When the spot purchasing price and the market demand signal during the contract procurement stage are not correlated,manufacturers prefer spot trading under the highly volatile spot trading price,fluctuating demand,and high information precision.展开更多
文摘Natural killer/T-cell lymphoma(NKTCL)is a highly invasive subtype of non-Hodgkin lymphoma,typically positive for cytoplasmic CD3,CD56,cytotoxic markers,including granzyme B and TIA1,and Epstein-Barr virus(EBV).The current treatment methods for NKTCL are associated with several drawbacks.For example,chemotherapy can lead to drug resistance,while treatment with radiotherapy alone is inadequate and results in frequent relapses.Moreover,hematopoietic stem cell transplantation exhibits limited efficacy and is not well recognized by domestic and foreign experts.In recent years,immunotherapy has shown good clinical results and has become a hot spot in cancer research.Clinical activity of targeted antibodies,such as daratumumab(anti-CD38 antibody)and brentuximab vedotin(anti-CD30 antibody),have been reported in NKTCL.Additionally,dacetuzumab and Campath-1 H have demonstrated promising results.Further encouraging data have been obtained using checkpoint inhibitors.The success of these immunotherapy agents is attributed to high expression levels of programmed death-ligand 1 in NKTCL.Furthermore,anti-CCR4 monoclonal antibodies(m Abs)exert cytotoxic actions on both CCR4+tumor cells and regulatory T cells.Depletion of these cells and the long half-life of anti-CCR4 m Abs result in enhanced induction of antitumor effector T cells.The role of IL10 in NKTCL has also been investigated.It has been proposed that exploitation of this cytokine might provide potential novel therapeutic strategies.Cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 has shown promising results and sustained remission.Cellular immunotherapy may be used either as maintenance therapy following initial induction chemotherapy or in cases of relapsed/refractory disease.The present review outlines the known immunotherapy targets for the treatment of NKTCL.
基金support from Hong Kong RGC Grant No: 2150518/410907support from NSFC projects under Grant Nos. 70725001,70821001 and 71090401/71090400
文摘In this paper, the optimal policy is considered when the buyer faces two supply sources： one is the contract supplier from which the buyer orders over a specific contract period （say, a year） at a pre-agreed price, and the other is the spot market. However, when ordering from the contract supplier, the buyer must fulfill a pre-determined total order quantity, or the so-called definite total order quantity commitment, over the whole contract period. In other words, the commitment secures the buyer a fixed price but obliges him/her a total order quantity over the contract period. Although the spot market gives the buyer more flexibility in terms of order quantities, its prices are volatile. Such a combination of contract and spot procurements is often observed in practice. Within the contract period, there are multiple sub-periods, during each of which the buyer reviews the inventory, issues an individual order, and uses the on-hand inventory to meet the random demand. Thus, in each （ordering） period, the buyer will weigh between the current known spot price （by procuring from the spot market） and a lower future price （by waiting while consuming the remaining commitment）. An optimal dual ordering policy is characterized for each period, depending on the on-hand inventory level, the spot price, and the remaining commitment quantity. The optimal policy in each period is also shown to be independent of the contract price. Through a numerical study, the inventory cost is demonstrated to be （1） insensitive to the contract price when the total commitment quantity is lower than the total expected demand over the contract period and （2） non-increasing in the variability of spot prices.
基金the National Natural Science Foundation of China under Grant Nos.71471118,71671040,71871145 and 71822103the Major Project of National Natural Science Foundation of China under Grant Nos.71790615,71991461 and 71991474。
文摘In this paper we study the competitive order timing decisions of two manufacturers with demand forecasting updating and uncertain raw material price.Manufacturers can order the raw materials early when the market is highly uncertain with a fixed wholesale price(Contract procurement)or late when the market is less uncertain with an uncertain raw material price(Spot trading).Different from most existing literature,we assume the spot price and the market demand is correlated.We find that in the monopoly setting the manufacturer prefers the contract procurement to the spot trading when the unit wholesale price for the contract procurement is not greater than the expected unit spot price of the raw material.In the duopoly setting,we characterize the equilibria of a strategic order timing game in which manufacturers choose when to buy the raw materials.We find that when the demand during the contract procurement stage and the spot price uncertainty is small both manufacturers prefer the contract procurement strategy and when the demand during the contract procurement stage and the spot price uncertainty is large both manufacturers prefer the spot trading.When the demand during the contract procurement stage and the spot price uncertainty is high and purchase costs do not decline too severely over time,the unique equilibrium of this game is that one manufacturer chooses contract procurement to order early and the other chooses spot trading to order late.Further,we find that the correlation of spot purchasing price and the market demand signal during the contract procurement stage will weaken the advantages of spot trading strategy.When the spot purchasing price and the market demand signal during the contract procurement stage are not correlated,manufacturers prefer spot trading under the highly volatile spot trading price,fluctuating demand,and high information precision.
