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On the Design of Sparse But Efficient Structures in Operations 操作中稀疏而高效的结构设计
Pub Date : 2016-11-08 DOI: 10.2139/ssrn.2899008
Zhenzhen Yan, S. Y. Gao, C. Teo
It is widely believed that a little flexibility added at the right place can reap significant benefits for operations. Unfortunately, despite the extensive literature on this topic, we are not aware of any general methodology that can be used to guide managers in designing sparse (i.e., slightly flexible) and yet efficient operations. We address this issue using a distributionally robust approach to model the performance of a stochastic system under different process structures. We use the dual prices obtained from a related conic program to guide managers in the design process. This leads to a general solution methodology for the construction of efficient sparse structures for several classes of operational problems. Our approach can be used to design simple yet efficient structures for workforce deployment and for any level of sparsity requirement, to respond to deviations and disruptions in the operational environment. Furthermore, in the case of the classical process flexibility problem, our methodolo...
人们普遍认为,在适当的地方增加一点灵活性可以为操作带来巨大的好处。不幸的是,尽管关于这个主题有大量的文献,但我们不知道任何通用的方法可以用来指导管理人员设计稀疏(即,稍微灵活)但高效的操作。我们使用分布鲁棒方法来解决这个问题,以模拟不同过程结构下随机系统的性能。我们使用从相关的二次曲线程序中得到的双重价格来指导管理者在设计过程中。这就产生了一种通用的解决方法,用于构造几种类型的操作问题的高效稀疏结构。我们的方法可用于为劳动力部署和任何级别的稀疏性要求设计简单而有效的结构,以响应操作环境中的偏差和中断。此外,在经典的过程灵活性问题的情况下,我们的方法…
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引用次数: 36
Designing Multi-Period Supply Contracts in a Two-Echelon Supply Chain Asymmetric Information 信息不对称下两梯队供应链的多期供给契约设计
Pub Date : 2016-11-01 DOI: 10.2139/ssrn.2862652
Z. Mobini, Wilco van den Heuvel, A. Wagelmans
We study a two-echelon supply chain consisting of a supplier and a retailer, where the supplier uses a simple and easily implementable incentive scheme - making a side payment - to influence the retailer’s ordering plan. The supplier makes a take-it-or-leave-it offer to the retailer in the form of a menu of contracts, each consisting of a procurement plan plus a side payment. The retailer, who possesses private information about customer demand and his cost parameters, either accepts one of the contracts or imposes his own optimal plan. We formulate the supplier’s problem of designing optimal contracts with the realistic assumption that the retailer’s outside option depends on his private information. Taking into account the retailer’s reaction to the proposed offer, the supplier faces a nested (bi-level) optimization problem, which we transform into a single-level mixed integer programming formulation. In our analysis, we use a network interpretation for the set of incentive constraints and show some properties of optimal contracts. This enables us to considerably reduce the number of incentive constraints and to find optimal values of the side payment quantities. Our findings regarding the possible behavior of the opportunistic retailer deviate from those of previous studies as a result of considering more realistic assumptions.
本文研究了一个由供应商和零售商组成的两级供应链,其中供应商使用一种简单且易于实施的激励方案——附带支付——来影响零售商的订购计划。供应商以一系列合同的形式向零售商提供“要么接受,要么放弃”的报价,每个合同都包括一个采购计划和一笔附加付款。零售商拥有关于顾客需求和成本参数的私人信息,要么接受其中一个合同,要么强加自己的最优计划。在现实假设零售商的外部选择取决于其私人信息的情况下,提出了供应商的最优契约设计问题。考虑到零售商对提议报价的反应,供应商面临嵌套(双级)优化问题,我们将其转化为单级混合整数规划公式。在我们的分析中,我们使用了激励约束集的网络解释,并给出了最优契约的一些性质。这使我们能够大大减少激励约束的数量,并找到最优的侧支付数量的值。由于考虑了更现实的假设,我们关于机会主义零售商可能的行为的发现偏离了以前的研究。
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引用次数: 0
Statistical Validity and Derivation of Balance Equations for the Two-Level Model of a Production Line 生产线两层模型平衡方程的统计有效性及推导
Pub Date : 2016-10-30 DOI: 10.15587/1729-4061.2016.81308
O. Pihnastyi
A method of constructing a system of multi-moment balance equations, based on the statistical description of a production system is proposed. The need for research is determined by current trends in the development of production systems. The system of equations, which simulates the behavior of the production line for the transient conditions is obtained. It is shown that the resulting balance equations are not closed. The methods of closure of the self-linking chain of balance equations: the small-parameter method and the method of setting the equations of states for higher-order moments are considered. The known models using various methods of closure of the system of equations are analyzed. The model of the production line for the assembly-line production method is considered. The limitations and constraint equations, which enable the transition to single-moment PDE model of description of the assembly line and two-moment PDE model of the production line using the Burgers' equation are shown. The model of the production line for the company with the flow production method is considered. One-, two- and three-moment systems of equations for the two-level model of the production line are obtained. A general system of balance equations for the flow parameters of the production line is constructed.
基于生产系统的统计描述,提出了一种构造多矩平衡方程组的方法。研究的需要是由生产系统发展的当前趋势决定的。得到了模拟生产线瞬态状态的方程组。结果表明,得到的平衡方程不是封闭的。考虑了自链平衡方程的闭合方法:小参数法和高阶矩状态方程的设置方法。分析了已知的各种方程组闭包方法的模型。考虑了装配线生产方法的生产线模型。给出了利用Burgers方程向装配线描述的单力矩PDE模型和生产线描述的双力矩PDE模型过渡的限制和约束方程。考虑了采用流程生产方法的公司生产线的模型。得到了生产线两层模型的一阶、二阶和三阶方程组。建立了生产线流动参数的一般平衡方程组。
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引用次数: 6
When Prospect Theory Meets Consumer Choice Models: Assortment and Pricing Management with Reference Prices 当前景理论遇到消费者选择模型:参考价格下的分类与定价管理
Pub Date : 2016-08-06 DOI: 10.2139/ssrn.2819600
Ruxian Wang
Problem definition: Reference prices arise as price expectations against which consumers evaluate products in their purchase scenarios. We investigate what will happen when prospect theory (e.g., reference prices) meets consumer choice models from the perspectives of both the consumers and the firm. Academic/practical relevance: Consumers see multiple relevant products on a particular purchase occasion and often compare their prices to form the willingness to pay when considering whether to purchase a particular product. Reference prices, which are not included in many choice models, may impact consumer choice behavior, so we incorporate reference prices into consumer choice models and investigate the operations management problems. Methodology: We take the widely used multinomial logit model as a showcase to examine the effects of reference prices through analytical and empirical study. We consider the optimization problems on assortment planning and pricing under consumer choice models with a variety of...
问题定义:参考价格是消费者在其购买场景中评估产品的价格预期。我们从消费者和企业的角度研究了当前景理论(如参考价格)与消费者选择模型相遇时会发生什么。学术/实践相关性:消费者在特定的购买场合看到多种相关的产品,在考虑是否购买某一特定产品时,经常会比较它们的价格,从而形成支付意愿。参考价格可能影响消费者的选择行为,而许多选择模型中没有包含参考价格,因此我们将参考价格纳入消费者选择模型,并研究运营管理问题。方法:采用广泛使用的多项logit模型,通过分析和实证研究来考察参考价格的影响。考虑了具有多种选择的消费者选择模型下的分类规划和定价优化问题。
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引用次数: 56
Contract Manufacturing and Quality Risk: Theory and Empirical Evidence 合同制造与质量风险:理论与实证
Pub Date : 2016-07-28 DOI: 10.2139/ssrn.2815520
John V. Gray, A. Roth, Brian Tomlin
This paper investigates the relationship between contract manufacturing and quality risk — a term defined as the propensity of a manufacturing plant to operate out of compliance with required procedures. Contract manufacturing plants (hereafter, CM) are increasingly being used in many industrial sectors. While CMs have been anecdotally blamed for many recalls and other outgoing product quality failures, there is a neither a strong coherent theory in operations and supply chain management nor empirical evidence that considers whether and when CMs pose a differential quality risk in contrast to internal plants (IPs). By definition, CMs produce products to another firm’s specifications, whereas IPs make products to their own firm’s specifications. This basic difference between CMs and IPs potentially leads to systemic dissimilarities in their operational contexts. Drawing upon these contextual dissimilarities, we posit that, on average, CMs will operate with higher quality risk than IPs. Subsequently, we develop contingencies related to key factors that moderate the relationship between plant type (CM vs. IP) and quality risk. We test our hypotheses using a plant-level measure of process compliance based on Food and Drug Administration (FDA) inspection data on a sample of 152 plants classified as drug manufacturers by the FDA. In addition to finding moderate evidence of a first-order difference, we do find evidence that production experience and the intensity of external regulation serve as important contingencies regarding quality risk. We find strong evidence that among plants with low production experience, CMs operate with higher quality risk than IPs, but this difference is mitigated as CMs gain production experience. We also find that increased regulatory intensity seems to influence CMs to reduce quality risk more than it does IPs.
本文研究了合同制造和质量风险之间的关系,质量风险是指制造工厂不遵守规定程序的倾向。合同制造工厂(以下简称CM)越来越多地应用于许多工业部门。虽然CMs因许多召回和其他外向产品质量失败而受到指责,但在运营和供应链管理方面既没有强有力的连贯理论,也没有经验证据来考虑CMs是否以及何时与内部工厂(ip)相比构成不同的质量风险。根据定义,CMs按照另一家公司的规格生产产品,而ip则按照自己公司的规格生产产品。CMs和ip之间的这种基本差异可能导致其操作环境的系统性差异。根据这些背景差异,我们假设,平均而言,CMs将比ip面临更高的质量风险。随后,我们开发了与调节植物类型(CM vs. IP)和质量风险之间关系的关键因素相关的突发事件。我们使用基于食品和药物管理局(FDA)对152家被FDA归类为药品制造商的工厂样本的检查数据的工厂级工艺合规性测量来检验我们的假设。除了发现一阶差异的适度证据外,我们还发现生产经验和外部监管强度是质量风险的重要偶然因素。我们发现强有力的证据表明,在生产经验较低的植物中,CMs的质量风险高于IPs,但随着CMs获得生产经验,这种差异会减轻。我们还发现,监管力度的增加似乎比ip更能影响CMs降低质量风险。
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引用次数: 5
Two-stage nanoparticle delivery of piperlongumine and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) anti-cancer therapy. 两阶段纳米递送胡椒曲明与肿瘤坏死因子相关凋亡诱导配体(TRAIL)抗癌治疗。
Pub Date : 2016-05-18 DOI: 10.1142/S2339547816500011
Charles C. Sharkey, Jiahe Li, S. Roy, Qianhui Wu, M. King
This study outlines a drug delivery mechanism that utilizes two independent vehicles, allowing for delivery of chemically and physically distinct agents. The mechanism was utilized to deliver a new anti-cancer combination therapy consisting of piperlongumine (PL) and TRAIL to treat PC3 prostate cancer and HCT116 colon cancer cells. PL, a small-molecule hydrophobic drug, was encapsulated in poly (lactic-co-glycolic acid) (PLGA) nanoparticles. TRAIL was chemically conjugated to the surface of liposomes. PL was first administered to sensitize cancer cells to the effects of TRAIL. PC3 and HCT116 cells had lower survival rates in vitro after receiving the dual nanoparticle therapy compared to each agent individually. In vivo testing involved a subcutaneous mouse xenograft model using NOD-SCID gamma mice and HCT116 cells. Two treatment cycles were administered over 48 hours. Higher apoptotic rates were observed for HCT116 tumor cells that received the dual nanoparticle therapy compared to individual stages of the nanoparticle therapy alone.
本研究概述了一种利用两种独立载体的药物递送机制,允许化学和物理上不同的药物递送。该机制被用于提供一种新的抗癌联合疗法,包括胡椒隆明(PL)和TRAIL,用于治疗PC3前列腺癌和HCT116结肠癌细胞。用聚乳酸-羟基乙酸(PLGA)纳米颗粒包封小分子疏水药物PL。TRAIL被化学偶联到脂质体表面。PL首先被用于使癌细胞对TRAIL的作用敏感。PC3和HCT116细胞在接受双纳米颗粒治疗后的体外存活率低于单独使用每种药物。体内试验采用NOD-SCID γ小鼠和HCT116细胞皮下小鼠异种移植模型。两个治疗周期超过48小时。与单独接受纳米颗粒治疗的单个阶段相比,接受双重纳米颗粒治疗的HCT116肿瘤细胞的凋亡率更高。
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引用次数: 16
Signal transduction of the physical environment in the neural differentiation of stem cells. 物理环境在干细胞神经分化中的信号转导。
Pub Date : 2016-05-18 DOI: 10.1142/S2339547816400070
Ryan Thompson, C. Chan
Neural differentiation is largely dependent on extracellular signals within the cell microenvironment. These extracellular signals are mainly in the form of soluble factors that activate intracellular signaling cascades that drive changes in the cell nucleus. However, it is becoming increasingly apparent that the physical microenvironment provides signals that can also influence lineage commitment and very low modulus surfaces has been repeatedly demonstrated to promote neurogenesis. The molecular mechanisms governing mechano-induced neural differentiation are still largely uncharacterized; however, a growing body of evidence indicates that physical stimuli can regulate known signaling cascades and transcription factors involved in neural differentiation. Understanding how the physical environment affects neural differentiation at the molecular level will enable research and design of materials that will eventually enhance neural stem cell (NSC) differentiation, homogeneity and specificity.
神经分化在很大程度上依赖于细胞微环境中的细胞外信号。这些细胞外信号主要以可溶性因子的形式激活细胞内信号级联反应,从而驱动细胞核的变化。然而,越来越明显的是,物理微环境提供的信号也可以影响谱系承诺,并且非常低模量的表面已被反复证明可以促进神经发生。控制机械诱导的神经分化的分子机制在很大程度上仍未确定;然而,越来越多的证据表明,物理刺激可以调节已知的信号级联反应和参与神经分化的转录因子。了解物理环境如何在分子水平上影响神经分化,将有助于研究和设计最终增强神经干细胞(NSC)分化、同质性和特异性的材料。
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引用次数: 14
Dextran functionalization enhances nanoparticle-mediated siRNA delivery and silencing. 右旋糖酐功能化增强纳米颗粒介导的siRNA传递和沉默。
Pub Date : 2016-05-18 DOI: 10.1142/S2339547816400100
D. Vocelle, Olivia M Chesniak, A. Malefyt, Georgina Comiskey, Kwasi Adu-Berchie, Milton R. Smith, C. Chan, S. Walton
Understanding the endocytosis and intracellular trafficking of short interfering RNA (siRNA) delivery vehicle complexes remains a critical bottleneck in designing siRNA delivery vehicles for highly active RNA interference (RNAi)-based therapeutics. In this study, we show that dextran functionalization of silica nanoparticles enhanced uptake and intracellular delivery of siRNAs in cultured cells. Using pharmacological inhibitors for endocytotic pathways, we determined that our complexes are endocytosed via a previously unreported mechanism for siRNA delivery in which dextran initiates scavenger receptor-mediated endocytosis through a clathrin/caveolin-independent process. Our findings suggest that siRNA delivery efficiency could be enhanced by incorporating dextran into existing delivery platforms to activate scavenger receptor activity across a variety of target cell types.
了解短干扰RNA (siRNA)递送载体复合物的内吞作用和细胞内运输仍然是设计用于高活性RNA干扰(RNAi)疗法的siRNA递送载体的关键瓶颈。在这项研究中,我们发现右旋糖酐功能化二氧化硅纳米颗粒增强了培养细胞中sirna的摄取和细胞内递送。使用药物抑制剂内吞途径,我们确定我们的复合物通过一种以前未报道的siRNA递送机制被内吞,其中葡聚糖通过网格蛋白/小泡蛋白独立的过程启动清除率受体介导的内吞作用。我们的研究结果表明,通过将葡聚糖结合到现有的递送平台中来激活各种靶细胞类型的清除率受体活性,可以提高siRNA的递送效率。
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引用次数: 9
Quantitative assessments of glycolysis from single cells. 单细胞糖酵解的定量评估。
Pub Date : 2015-12-23 DOI: 10.1142/S2339547815200058
Y. Shin, Jungwoo Kim, Dazy Johnson, A. Dooraghi, Wilson X. Mai, Lisa Ta, A. Chatziioannou, M. Phelps, D. Nathanson, J. Heath
The most common positron emission tomography (PET) radio-labeled probe for molecular diagnostics in patient care and research is the glucose analog, 2-deoxy-2-[F-18]fluoro-D-glucose (18F-FDG). We report on an integrated microfluidics-chip/beta particle imaging system for in vitro18F-FDG radioassays of glycolysis with single cell resolution. We investigated the kinetic responses of single glioblastoma cancer cells to targeted inhibitors of receptor tyrosine kinase signaling. Further, we find a weak positive correlation between cell size and rate of glycolysis.
在患者护理和研究中,用于分子诊断的最常见的正电子发射断层扫描(PET)放射性标记探针是葡萄糖类似物,2-脱氧-2-[F-18]氟-d -葡萄糖(18F-FDG)。我们报道了一种集成微流控芯片/ β粒子成像系统,用于糖酵解的体外18f - fdg放射分析,具有单细胞分辨率。我们研究了单个胶质母细胞瘤癌细胞对受体酪氨酸激酶信号传导靶向抑制剂的动力学反应。此外,我们发现细胞大小和糖酵解速率之间存在微弱的正相关关系。
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引用次数: 2
A microfluidic biochip for complete blood cell counts at the point-of-care. 一种微流控生物芯片,用于在护理点进行全血细胞计数。
Pub Date : 2015-12-23 DOI: 10.1142/S2339547815500090
U. Hassan, B. Reddy, G. Damhorst, O. Sonoiki, T. Ghonge, C. Yang, R. Bashir
Complete blood cell counts (CBCs) are one of the most commonly ordered and informative blood tests in hospitals. The results from a CBC, which typically include white blood cell (WBC) counts with differentials, red blood cell (RBC) counts, platelet counts and hemoglobin measurements, can have implications for the diagnosis and screening of hundreds of diseases and treatments. Bulky and expensive hematology analyzers are currently used as a gold standard for acquiring CBCs. For nearly all CBCs performed today, the patient must travel to either a hospital with a large laboratory or to a centralized lab testing facility. There is a tremendous need for an automated, portable point-of-care blood cell counter that could yield results in a matter of minutes from a drop of blood without any trained professionals to operate the instrument. We have developed microfluidic biochips capable of a partial CBC using only a drop of whole blood. Total leukocyte and their 3-part differential count are obtained from 10 μL of blood after on-chip lysing of the RBCs and counting of the leukocytes electrically using microfabricated platinum electrodes. For RBCs and platelets, 1 μL of whole blood is diluted with PBS on-chip and the cells are counted electrically. The total time for measurement is under 20 minutes. We demonstrate a high correlation of blood cell counts compared to results acquired with a commercial hematology analyzer. This technology could potentially have tremendous applications in hospitals at the bedside, private clinics, retail clinics and the developing world.
全血细胞计数(CBCs)是医院最常用和最具信息性的血液检查之一。CBC的结果通常包括白细胞(WBC)计数与差异,红细胞(RBC)计数,血小板计数和血红蛋白测量,可以对数百种疾病的诊断和筛选和治疗产生影响。目前,笨重且昂贵的血液学分析仪被用作获取全血细胞计数的金标准。目前,几乎所有进行全血细胞计数的患者都必须前往拥有大型实验室的医院或集中实验室检测设施。人们迫切需要一种自动化的便携式即时血液计数器,这种计数器可以在几分钟内从一滴血中得出结果,而无需任何训练有素的专业人员操作仪器。我们已经开发出了微流控生物芯片只需一滴全血就能检测出部分全血细胞计数。在片上裂解红细胞,用微加工铂电极电计数后,从10 μL血液中获得白细胞总数及其3部分差异计数。对于红细胞和血小板,用片上PBS稀释1 μL全血,电计数。测量总时间不超过20分钟。我们证明了与商业血液学分析仪获得的结果相比,血细胞计数具有很高的相关性。这项技术可能在医院、私人诊所、零售诊所和发展中国家有巨大的应用前景。
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引用次数: 36
期刊
Technology (Elmsford, N.Y.)
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