bluuebunny/crossref_metadata_2025 huggingface dataset:
The Combination of p53 Mutation and neu/erbB-2 Amplification Is Associated With Poor Survival in Node-Negative Breast Cancer
Authors: Bull Shelley B. , Ozcelik Hilmi , Pinnaduwage Dushanthi , Blackstein Martin E. , Sutherland Donald A.J. , Pritchard Kathleen I. , Tzontcheva Anjela T. , Sidlofsky Saul , Hanna Wedad M. , Qizilbash Ali H. , Tweeddale Mary E. , Fine Sheldon , McCready David R. , Andrulis Irene L.
Published: December 2003

Purpose

Increases in neu/erbB-2 have been implicated in breast cancer prognosis, but do not predict all recurrences. On the basis of evidence that p53 mutation is involved in the development of human neoplasia, we examined the prognostic value of p53 alterations in combination with neu/erbB-2 amplification.

Patients and Methods

A consecutive series of women were observed for recurrence and death (median follow-up of 85 months) and tumors from 543 individuals were analyzed for p53 mutation status and neu/erbB-2 amplification. Exons 4 through 10 of the p53 gene were analyzed by single-stranded conformational polymorphism and mutations were confirmed by DNA sequencing. The association of p53 mutation status and neu/erbB-2 amplification with risk of recurrence and death was examined in survival analyses with traditional and histologic markers as prognostic factors.

Results

p53 mutations occurred in 24.5% of the axillary node-negative breast carcinomas. Mutations were more frequent in carcinomas with neu/erbB-2 amplification: 38.9% compared with only 20.9% in those without neu/erbB-2 amplification. We found elevated risks of disease recurrence and overall mortality in patients with both p53 mutation and neu/erbB-2 amplification in their tumor compared with patients with neither or only one of the alterations. This increase persisted with adjustment for other prognostic factors (relative risk, 2.32; P = .002 for recurrence; relative risk, 2.22; P = .004 for death).

Conclusion

Evaluation of tumors for p53 mutations may be beneficial to identify women at higher risk of disease recurrence and death when the tumor has neu/erbB-2 amplification, but in the absence of neu/erbB-2 amplification, the presence of p53 mutation may not provide additional independent prognostic information.
Menopausal Status Dependence of Early Mortality Reduction Due to Diagnosis of Smaller Breast Cancers (T1 v T2-T3): Relevance to Screening
Authors: Demicheli Romano , Bonadonna Gianni , Hrushesky William J.M. , Retsky Michael W. , Valagussa Pinuccia
Published: December 2003

Purpose

To provide data relevant to the paradoxical mortality excess for women age 40 to 49 years observed during the first 6 to 8 years in the invited group in all mammography screening studies.

Patients and Methods

In 1,173 patients undergoing mastectomy alone as primary treatment, allocated to subsets according to menopausal status and tumor size, hazard rates for death were calculated. The ratios between the hazard rate for T2-T3 patients and the corresponding value for T1 patients were assessed over time.

Results

For postmenopausal patients, the ratio appeared to be time-dependent, dropping from the maximum value of approximately 5 at the first year after surgery to a near constant value of approximately 2 after 5 to 6 years. Premenopausal patients, on the contrary, showed a nearly constant ratio of approximately 3. Therefore, although in each T-category the 10-year survival of premenopausal and postmenopausal patients was similar, its time distribution was menopause-dependent. In particular, the difference between cumulative survival of premenopausal and postmenopausal T2-T3 patients attained statistical significance after 3 years.

Conclusion

The mortality reduction due to the diagnosis of smaller tumors is significantly higher for postmenopausal women than for premenopausal women during early postsurgery time. According to the hypothesis that primary tumor surgical removal, occurring sooner in the invited group than in the control arm of screening trials, results in some acceleration of metastasis development, a greater number of unfavorable events (recurrence and death) should occur in the invited group. We suggest that for younger women, the early balance between benefit from tumor downsizing and harm from surgery-induced metastasis acceleration results in harm. This disadvantage does not occur in postmenopausal women.
Sperm from β1,4-galactosyltransferase I-null mice exhibit precocious capacitation
Authors: Rodeheffer Carey , Shur Barry D.
Published: December 2003

Mammalian sperm must undergo a physiological maturation, termed capacitation, before they are able to fertilize eggs. Despite its importance,the molecular mechanisms underlying capacitation are poorly understood. In this paper, we describe the capacitation phenotype of sperm lacking the long isoform of β1,4-galactosyltransferase I (GalT I), a sperm surface protein that functions as a receptor for the zona pellucida glycoprotein, ZP3, and as an inducer of the acrosome reaction following ZP3-dependent aggregation. As expected, wild-type sperm must undergo capacitation in order to bind the zona pellucida and undergo a Ca2+ ionophore-induced acrosome reaction. By contrast, GalT I-null sperm behave as though they are precociously capacitated, in that they demonstrate maximal binding to the zona pellucida and greatly increased sensitivity to ionophore-induced acrosome reactions without undergoing capacitation in vitro. The loss of GalT I from sperm results in an inability to bind epididymal glycoconjugates that normally maintain sperm in an `uncapacitated' state; removing these decapacitating factors from wild-type sperm phenocopies the capacitation behavior of GalT I-null sperm. Interestingly, capacitation of GalT I-null sperm is independent of the presence of albumin, Ca2+ and HCO3–; three co-factors normally required by wild-type sperm to achieve capacitation. This implies that intracellular targets of albumin, Ca2+ and/or HCO3–may be constitutively active in GalT I-null sperm. Consistent with this, GalT I-null sperm have increased levels of cAMP that correlate closely with both the accelerated kinetics and co-factor-independence of GalT I-null sperm capacitation. By contrast, the kinetics of protein tyrosine phosphorylation and sperm motility are unaltered in mutant sperm relative to wild-type. These data suggest that GalT I may function as a negative regulator of capacitation in the sperm head by suppressing intracellular signaling pathways that promote this process.
Six1controls patterning of the mouse otic vesicle
Authors: Ozaki Hidenori , Nakamura Kazuaki , Funahashi Jun-ichi , Ikeda Keiko , Yamada Gen , Tokano Hisashi , Okamura Hiro-oki , Kitamura Ken , Muto Shigeaki , Kotaki Hayato , Sudo Katsuko , Horai Reiko , Iwakura Yoichiro , Kawakami Kiyoshi
Published: December 2003

Six1 is a member of the Six family homeobox genes, which function as components of the Pax-Six-Eya-Dach gene network to control organ development. Six1 is expressed in otic vesicles, nasal epithelia,branchial arches/pouches, nephrogenic cords, somites and a limited set of ganglia. In this study, we established Six1-deficient mice and found that development of the inner ear, nose, thymus, kidney and skeletal muscle was severely affected. Six1-deficient embryos were devoid of inner ear structures, including cochlea and vestibule, while their endolymphatic sac was enlarged. The inner ear anomaly began at around E10.5 and Six1was expressed in the ventral region of the otic vesicle in the wild-type embryos at this stage. In the otic vesicle of Six1-deficient embryos,expressions of Otx1, Otx2, Lfng and Fgf3,which were expressed ventrally in the wild-type otic vesicles, were abolished,while the expression domains of Dlx5, Hmx3, Dach1and Dach2, which were expressed dorsally in the wild-type otic vesicles, expanded ventrally. Our results indicate that Six1functions as a key regulator of otic vesicle patterning at early embryogenesis and controls the expression domains of downstream otic genes responsible for respective inner ear structures. In addition, cell proliferation was reduced and apoptotic cell death was enhanced in the ventral region of the otic vesicle, suggesting the involvement of Six1 in cell proliferation and survival. In spite of the similarity of otic phenotypes of Six1- and Shh-deficient mice, expressions of Six1 and Shhwere mutually independent.
Requirement ofLim1for female reproductive tract development
Authors: Kobayashi Akio , Shawlot William , Kania Artur , Behringer Richard R.
Published: December 2003

Lim1 encodes a LIM-class homeodomain transcription factor that is essential for head and kidney development. In the developing urogenital system, Lim1 expression has been documented in the Wolffian(mesonephric) duct, the mesonephros, metanephros and fetal gonads. Using, a Lim1 lacZ knock-in allele in mice, we identified a previously unreported urogenital tissue for Lim1 expression, the epithelium of the developing Müllerian duct that gives rise to the oviduct, uterus and upper region of the vagina of the female reproductive tract. Lim1expression in the Müllerian duct is dynamic, corresponding to its formation and differentiation in females and regression in males. Although female Lim1-null neonates had ovaries they lacked a uterus and oviducts. A novel female mouse chimera assay was developed and revealed that Lim1 is required cell autonomously for Müllerian duct epithelium formation. These studies demonstrate an essential role for Lim1 in female reproductive tract development.
Androgen receptor function is required in Sertoli cells for the terminal differentiation of haploid spermatids
Authors: Holdcraft Robert W. , Braun Robert E.
Published: December 2003

Androgen receptor function is required for male embryonic sexual differentiation, pubertal development and the regulation of spermatogenesis in mammals. During spermatogenesis, this requirement is thought to be mediated by Sertoli cells and its genetic and pharmacological disruption is manifested in spermatocytes as meiotic arrest. Through studies of a hypomorphic and conditional allele of the androgen receptor (Ar) gene, we have uncovered a dual post-meiotic requirement for androgen receptor activity during male germ cell differentiation. Observations in Ar hypomorphic animals demonstrate that terminal differentiation of spermatids and their release from the seminiferous epithelium is AR dependent and maximally sensitive to AR depletion within the testis. Cell-specific disruption of Ar in Sertoli cells of hypomorphic animals further shows that progression of late-round spermatids to elongating steps is sensitive to loss of Sertoli cell AR function, but that progression through meiosis and early-round spermatid differentiation are surprisingly unaffected.
An “Alternating Recognition” Model of English Auctions
Authors: Harstad Ronald M. , Rothkopf Michael H.
Published: December 2003

We present an alternative abstraction of an English (oral ascending) auction to the standard, in Milgrom and Weber (1982), that accords more closely with practices in some auction markets. In particular, the assumptions that exits are irrevocable and necessarily public are dropped, making endogenous the decision to compete silently and privately, or openly. In the model, the price rises in a stylization of an auctioneer alternately recognizing two bidders who affirm willingness to pay the current price. The auctioneer pays attention to other bidders only when a recognized bidder exits. Such exits may be temporary, although we construct an equilibrium in which there is no benefit to exit and reentry. The number of public exits is stochastic; frequently a losing “bidder” will remain silent, giving no indication of his willingness to pay, and hence yielding no useful inference about his private information. Thus, the source of the expected revenue advantage of English auctions over second-price auctions is only stochastically available. Moreover, when public exits are incomplete, the ordinal rank of the bidder whose private information can be inferred is unknown, making that information less valuable. Consequently, the simpler formula for expected revenue in second-price auctions may be the preferred approximation for English auctions.
Heuristic Computation of Periodic-Review Base Stock Inventory Policies
Authors: Roundy Robin O. , Muckstadt John A.
Published: December 2003

We study the problem of determining production quantities in each period of an infinite horizon for a single item produced in a capacity-limited facility. The demand for the product is random, and it is independent and identically distributed from period to period. The demand is observed at the beginning of a time period, but it need not be filled until the end of the period. Unfilled demand is backordered. A base stock or order-up-to policy is used. The shortfall is the order-up-to level minus the inventory position. The inventory system is easily understood and managed if we know the distribution of the shortfall. We develop a new approximation for this distribution, and perform extensive computational tests of existing approximations. Our new approximation works extremely well as long as the coefficient of variation of the demand is less than two. For practical applications this is by far the most interesting case. No known approximations work well consistently when the coefficient of variation of the demand is greater than two.
Processes and Their Frameworks
Authors: Mackenzie Kenneth D.
Published: December 2003

A process is a time-dependent sequence of events governed by a process framework. A group process has five components: the entities performing the process, the steps or elements of a process, the relationship between any pair of elements, the links to other processes, and the resources and their characteristics-in-use involved with the elements. A process framework is denoted by Y = F(C) where Y is the set of outcomes or consequences of a process, C is the set of considerations or elements in the process, and F is the network linking the considerations to each other and to the outcomes. The properties of the set of considerations, the linkages between pairs of consequences, the set of outcomes or consequences, the network, F, and the use of process frameworks are discussed in detail with examples. Process models are compared to variable models.
A Discrete-Time Approach to Arbitrage-Free Pricing of Credit Derivatives
Authors: Das Sanjiv Ranjan , Sundaram Rangarajan K.
Published: December 2003

This paper develops a framework for modelling risky debt and valuing credit derivatives that is flexible and simple to implement, and that is, to the maximum extent possible, based on observables. Our approach is based on expanding the Heath-Jarrow-Morton term-structure model to allow for defaultable debt. Rather than follow the procedure of implying out the behavior of spreads from assumptions concerning the default process, we work directly with the evolution of spreads. The risk-neutral drifts in the resulting model possess a recursive representation that facilitates implementation and makes it possible to handle path-dependence and early exercise features without difficulty. The framework permits embedding a variety of specifications for default; we present an empirical example of a default structure which provides promising calibration results.
Path Generation for Quasi-Monte Carlo Simulation of Mortgage-Backed Securities
Authors: Åkesson Fredrik , Lehoczky John P.
Published: December 2003

Monte Carlo simulation is playing an increasingly important role in the pricing and hedging of complex, path dependent financial instruments. Low discrepancy simulation methods offer the potential to provide faster rates of convergence than those of standard Monte Carlo methods; however, in high dimensional problems special methods are required to ensure that the faster convergence rates hold. Indeed, Ninomiya and Tezuka (1996) have shown highdimensional examples, in which low discrepancy methods perform worse than Monte Carlo methods. The principal component construction introduced by Acworth et al. (1998) provides one solution to this problem. However, the computational effort required to generate each path grows quadratically with the dimension of the problem. This article presents two new methods that offer accuracy equivalent, in terms of explained variability, to the principal components construction with computational requirements that are linearly related to the problem dimension. One method is to take into account knowledge about the payoff function, which makes it more flexible than the Brownian Bridge construction. Numerical results are presented that show the benefits of such adjustments. The different methods are compared for the case of pricing mortgage backed securities using the Hull-White term structure model.
Risk-Constrained Dynamic Active Portfolio Management
Authors: Browne Sid
Published: December 2003

Active portfolio management is concerned with objectives related to the outperformance of the return of a target benchmark portfolio. In this paper, we consider a dynamic active portfolio management problem where the objective is related to the tradeoff between the achievement of performance goals and the risk of a shortfall. Specifically, we consider an objective that relates the probability of achieving a given performance objective to the time it takes to achieve the objective. This allows a new direct quantitative analysis of the risk/return tradeoff, with risk defined directly in terms of probability of shortfall relative to the benchmark, and return defined in terms of the expected time to reach investment goals relative to the benchmark. The resulting optimal policy is a state-dependent policy that provides new insights. As a special case, our analysis includes the case where the investor wants to minimize the expected time until a given performance goal is reached subject to a constraint on the shortfall probability.
Price and Service Discrimination in Queuing Systems: Incentive Compatibility of Gcμ Scheduling
Authors: Van Mieghem Jan A.
Published: December 2003

This article studies the optimal prices and service quality grades that a queuing system—the “firm”—provides to heterogeneous, utility-maximizing customers who measure quality by their experienced delay distributions. Results are threefold: First, delay cost curves are introduced that allow for a flexible description of a customer's quality sensitivity. Second, a comprehensive executable approach is proposed that analytically specifies scheduling, delay distributions and prices for arbitrary delay sensitivity curves. The tractability of this approach derives from porting heavy-traffic Brownian results into the economic analysis. The generalized cμ (Gcμ) scheduling rule that emerges is dynamic so that, in general, service grades need not correspond to a static priority ranking. A benchmarking example investigates the value of differentiated service. Third, the notions of grade and rate incentive compatibility (IC) are introduced to study this system under asymmetric information and are established for Gcμ scheduling when service times are homogeneous and customers atomistic. Grade IC induces correct grade choice resulting in perfect service discrimination; rate IC additionally induces centralized-optimal rates. Dynamic Gcμ scheduling exhibits negative feedback that, together with time-dependent pricing, can also yield rate incentive compatibility with heterogeneous service times. Finally, multiplan pricing, which offers all customers a menu with a choice of multiple rate plans, is analyzed.
An Extreme-Value Model of Concept Testing
Authors: Dahan Ely , Mendelson Haim
Published: December 2003

We model concept testing in new product development as a search for the most profitable solution to a design problem. When allocating resources, developers must balance the cost of testing multiple designs against the potential profits that may result. We propose extreme-value theory as a mathematical abstraction of the concept-testing process. We investigate the trade-off between the benefits and costs of parallel concept testing and derive closed-form solutions for the case of profits that follow extreme-value distributions. We analyze the roles of the scale and tail-shape parameters of the profit distribution as well as the cost of testing in determining the optimal number of tests and total budget for the concept phase of NPD. Using an example, we illustrate how to estimate and interpret the scale and tail-shape parameters. We find that the impact of declining concept-testing costs on expected profits, the number of concepts tested, and total spending depend on the scale/cost ratio and tail-shape parameter of the profit distribution.
Developing Products on “Internet Time”: The Anatomy of a Flexible Development Process
Authors: MacCormack Alan , Verganti Roberto , Iansiti Marco
Published: December 2003

Uncertain and dynamic environments present fundamental challenges to managers of the new product development process. Between successive product generations, significant evolutions can occur in both the customer needs a product must address and the technologies it employs to satisfy these needs. Even within a single development project, firms must respond to new information, or risk developing a product that is obsolete the day it is launched. This paper examines the characteristics of an effective development process in one such environment—the Internet software industry. Using data on 29 completed development projects we show that in this industry, constructs that support a more flexible development process are associated with better-performing projects. This flexible process is characterized by the ability to generate and respond to new information for a longer proportion of a development cycle. The constructs that support such a process are greater investments in architectural design, earlier feedback on product performance from the market, and the use of a development team with greater amounts of “generational” experience. Our results suggest that investments in architectural design play a dual role in a flexible process: First, through the need to select an architecture that maximizes product performance and, second, through the need to select an architecture that facilitates development process flexibility. We provide examples from our fieldwork to support this view.
Integrating Operations and Marketing Perspectives of Product Innovation: The Influence of Organizational Process Factors and Capabilities on Development Performance
Authors: Tatikonda Mohan V. , Montoya-Weiss Mitzi M.
Published: December 2003

This paper adopts a multidisciplinary view of innovation by integrating operations and marketing perspectives of product development. The conceptual framework builds on the resource-based view of the firm and organizational information-processing theory to characterize relationships among organizational process factors, product development capabilities, critical uncertainties, and operational/market performance in product development projects. Data from a cross-sectional sample of 120 completed development projects for assembled goods is analyzed via a two-stage hierarchical moderated regression approach. The findings show that: (1) the organizational process factors studied are associated with achievement of operational outcome targets for product quality, unit cost, and time-to-market; (2) achievement of operational outcomes aids the achievement of market outcomes, in turn suggesting that development capabilities are indeed valuable firm resources; and (3) these relationships are robust under conditions of technological, market, and environmental uncertainty. This article provides practical insight into how product development projects can be better managed for operational and market success. Additionally, this article sets a theoretical and empirical basis for future research on the influence of organizational process factors and capabilities on diverse product-innovation outcomes.
Performance Measurement and Design in Supply Chains
Authors: Baiman Stanley , Fischer Paul E. , Rajan Madhav V.
Published: December 2003

This paper examines the relationship between product architecture, supply-chain performance metrics, and supply-chain efficiency. We model the contracting relationship between a supplier and a buyer. The supplier is privately informed about the outcome of his design/production investment. The buyer both appraises the supplier's component and does further processing/component production of his own. If the final product produced by the buyer exhibits decoupling and no function sharing with respect to the components (termed separable architecture), the first-best outcome is attained if both internal and external failures are contractible. When only one type of failure can be contracted on, we derive conditions under which contracting on internal failure is superior to contracting on external failure, and vice versa. If the buyer's final product has a nonseparable architecture with respect to the components, first-best cannot be achieved even if both internal and external failures are contractible. The value of contracting on internal failure alone is unaffected by the architecture design, while that of external failure declines relative to the separable setting; the net result is often to make the former the uniformly dominant performance metric. Our results highlight the interaction between the performance metrics used for contracting within the supply chain, the architecture of the product produced by the supply chain, and the incentive efficiency of the chain.
Sourcing By Design: Product Complexity and the Supply Chain
Authors: Novak Sharon , Eppinger Steven D.
Published: December 2003

This paper focuses on the connection between product complexity and vertical integration using original empirical evidence from the auto industry. A rich literature has addressed the choice between internal production and external sourcing of components in the auto industry. More recent literature has developed the concept of product architecture as another choice variable that may be one of the important contributors to product complexity. In this paper, we connect these two important decisions and study them jointly. We use the property rights approach to argue that complexity in product design and vertical integration of production are complements: that in-house production is more attractive when product complexity is high, as firms seek to capture the benefits of their investment in the skills needed to coordinate development of complex designs. We test this hypothesis with a simultaneous equations model applied to data from the luxury-performance segment of the auto industry. We find a significant and positive relationship between product complexity and vertical integration. This has implications for optimal incentive structures within firms, as well as for interpreting firm performance.
A Cross-Functional Approach to Evaluating Multiple Line Extensions for Assembled Products
Authors: Ramdas Kamalini , Sawhney Mohanbir S.
Published: December 2003

Assembled product manufacturers often introduce line extensions that share components with existing products, or among themselves, resulting in cost interactions among products because of shared costs, and revenue interactions because of cannibalization. We present a cross-functional approach to evaluating multiple line extensions that simultaneously considers revenue implications of component sharing at the product level and cost implications at the component level. We develop a source-of-volume model and a measurement procedure to decompose the life-cycle sales volume from a line extension into sales from cannibalization, competitive draw, and demand expansion. We develop an activity-based costing procedure for estimating the life-cycle costs of line extensions that share components. We develop an optimization model that uses these revenue and cost estimates to identify a subset of line extensions that maximizes incremental profits. We implement our approach at a quartz wristwatch manufacturer. Results suggest that our approach would have improved profits for the firm by over 5%, while actually launching fewer line extensions. We also find that the drivers of cannibalization are counterintuitive. In simulation studies, our approach outperforms three managerial heuristics. We demonstrate that this approach is most valuable when cannibalization dominates competitive draw as a source of volume, and discuss its relative merits under low and high parts-sharing.
Creating and Transferring Knowledge for Productivity Improvement in Factories
Authors: Lapré Michael A. , Van Wassenhove Luk N.
Published: December 2003

Can a firm accelerate its learning curve if knowledge about the production function is incomplete? This article identifies a production line specifically set up to create technological knowledge about its production function through scientific experimentation (formal learning) as opposed to learning by doing. The organizational structure of this line was very successful in creating technological knowledge. Formal learning resulted in huge productivity improvements. Replication of this organizational structure on three production lines in other plants within the same firm fell short of expectations. Formal learning did not result in similar productivity improvements. Our research suggests two factors that may facilitate creation and transfer of technological knowledge: management buy-in and knowledge diversity to solve interdepartmental problems.
Job Rotation as a Learning Mechanism
Authors: Ortega Jaime
Published: December 2003

This article analyzes the costs and benefits of job rotation as a mechanism with which the firm can learn about the employees' productivities and the profitability of different jobs or activities. I compare job rotation to an assignment policy where employees specialize in one job along their career. The gains from adopting a job rotation policy are larger when there is more prior uncertainty about employees and activities. I argue that this firm learning theory fits the existing evidence on rotation better than alternative explanations based on employee motivation and employee learning.
Stocking Decisions for Low-Usage Items in a Multilocation Inventory System
Authors: Kukreja Anil , Schmidt Charles P. , Miller David M.
Published: December 2003

This research shows that organizations with a number of “sister” plants, warehouses, or other stocking points can profit from the concept of proactive use of transshipments as an element of their inventory control policy. For certain types of parts, employing transshipments can significantly reduce the total inventory needed throughout the entire collection of stocking points. The study is motivated by a real-life situation involving a large utility company having 29 power-generating plants in five Southeastern states where there are thousands of parts that are commonly used at multiple plants.

At present, each plant operates independently and maintains enough stock to meet its own requirements. Transshipments take place between plants whenever there is an emergency requirement for a part, but no explicit consideration is given to this effect while deciding on stocking levels at different plants. In the case we examined, by setting stocking levels to explicitly take account of transshipments, total system cost could be reduced by about 70% over the company's decentralized policy.

In general, this work considers a single-echelon, N-location, continuous-review inventory system in which complete pooling of stock is permitted among the locations. A model is developed for slow-moving, expensive, and consumable parts that are common to two or more locations. A one-for-one ordering policy and queueing theory allow development and solution of a system of equations for the probability distribution of net inventory at each location. A heuristic procedure is also developed to determine cost-effective stocking levels. Actual data from the utility company are used to demonstrate the applicability of the model. Savings achieved as a result of pooling are reported.
The Latest Arrival Hub Location Problem
Authors: Kara Bahar Y. , Tansel Barbaros Ç.
Published: December 2003

The traditionally studied hub location problems in the literature pay attention to flight times but not to transient times spent at hubs for unloading, loading, and sorting operations. The transient times may constitute a significant portion of the total delivery time for cargo delivery systems. We focus on the minimization of the arrival time of the last arrived item in cargo delivery systems and develop a model that correctly computes the arrival times by taking into account both the flight times and the transient times. Nonlinear and linear integer formulations are given and computational results are provided. The effects of delays on the system performance are analyzed.
Leveraging the Customer Base: Creating Competitive Advantage Through Knowledge Management
Authors: Ofek Elie , Sarvary Miklos
Published: December 2003

Professional services firms (e.g., consultants, accounting firms, or advertising agencies) generate and sell business solutions to their customers. In doing so, they can leverage the cumulative experience gained from serving their customer base to either reduce their variable costs or increase the quality of their products/services. In other words, their “production technology” exhibits some form of increasing returns to scale. Growth and globalization, coupled with recent advances in information technology, have led many of these firms to introduce sophisticated knowledge management (KM) systems in order to create sustainable competitive advantage. In this paper, the authors analyze how KM is likely to affect competition among such professional services firms. In particular, they first explore what type (supply-side versus demand-side) of economies of scale are likely to be exploited in KM systems. In the former case, KM's role is to reduce the operating costs of the firm, while in the latter case, its role is to create added value to customers by significantly increasing product quality. Second, the authors analyze the competitive dynamics and market structure that emerge as a result of firms competing with KM systems. The results shed light on the current literature exploring the deployment of KM systems by suggesting that in a competitive setting, when firms' ability to leverage their customer base is high, KM should lead to quality improvement rather than cost reductions. In a dynamic setting, it is also shown that when firms use their KM system to improve product quality, higher ability to leverage the customer base may actually hurt profits and lead to industry shakeout. Beyond normative insights, the results also support a number of recent market trends in management consulting, including the increased emphasis on knowledge-creating activities in modern KM systems, the wave of mergers between consulting firms, and the recent emergence of “retail consulting” services.
On Continuous-Time Optimal Advertising Under S-Shaped Response
Authors: Feinberg Fred M.
Published: December 2003

Continuous-time monopolistic models of advertising expenditure that rely on strict response concavity have been shown to prescribe eventual spending at a constant rate. However, analyses of discrete analogs have suggested that S-shaped response (convexity for low expenditure levels) may allow for the periodic optima encountered in actual practice. Casting the dynamic between advertising and sales in a common format (an autonomous, first-order relationship), the present paper explores extensions along three dimensions: an S-shaped response function, the value of the discount rate, and the possibility of diffusion-like response. Supplementing the treatment by Mahajan and Muller (1986), a flexible class of S-shaped response models is formulated for which it is demonstrated that, in contrast to findings in the literature on discretized advertising models, continuous periodic optima cannot be supported. Further, a set of conditions on the advertising response function are derived, that contains and extends that suggested by Sasieni (1971). Collectively, these results both suggest a set of baseline properties that reasonable models should possess and cast doubt on the ability of first-order models to capture effects of known managerial relevance.
Validation of Trace-Driven Simulation Models: Bootstrap Tests
Authors: Kleijnen Jack P. C. , Cheng Russell C. H. , Bettonvil Bert
Published: December 2003

Trace-driven (or correlated inspection) simulation means that the simulated and the real systems have some common inputs (say, historical arrival times) so that the two systems' outputs are cross-correlated. To validate such a simulation, this paper focuses on the difference between the average simulated and real responses. To evaluate this validation statistic, the paper develops a novel bootstrap technique—based on replicated runs. This validation statistic and the bootstrap technique are evaluated in extensive Monte Carlo experiments with specific single-server queues. These experiments show acceptable Type-I and Type-II error probabilities.
Optimal Operating Policies for Multiplant Stochastic Manufacturing Systems in a Changing Environment
Authors: Li Lode , Porteus Evan L. , Zhang Hongtao
Published: December 2003

This paper addresses the horizontal coordination between production units located in different countries within a supply chain in a changing environment. The model incorporates (1) congestion and delay through uncertainties in demand and processing times, (2) a changing production cost environment through uncertainty in an environmental state (such as the exchange rate), and (3) allowing production to stock. The main contribution of the paper is to characterize the optimal production policy, assuming no switchover cost, as a barrier-type control policy for a series of models. For each plant, there is a barrier function defined on the environmental state that gives the total worldwide stock level barrier: This plant should be operated if and only if the stock level is below this barrier. The authors also show that, in a simple setting of two plants in different countries, the barrier functions are not always monotone in the exchange rate even when the production costs are. The authors present a condition under which the control barriers are shown to be monotone. Under this condition and with only two plants, it is optimal to follow a primary/secondary plant policy in which, given a fixed environmental state, it is optimal to operate both plants when stock is low, only the primary plant when stock is moderate, and neither when stock is high. Furthermore, the roles of the plants switch as the environmental state passes through the equal production cost state. In addition, the firm seeks to carry the most stock as a hedge against future environmental state moves, when one plant is significantly cheaper than the other. The firm seeks to carry the least stock when both plants are equally costly to operate.
A Coordinated Production Planning Model with Capacity Expansion and Inventory Management
Authors: Rajagopalan Sampath , Swaminathan Jayashankar M.
Published: December 2003

Motivated by a problem faced by a large manufacturer of a consumer product, we explore the interaction between production planning and capacity acquisition decisions in environments with demand growth. We study a firm producing multiple items in a multiperiod environment where demand for items is known but varies over time with a long-term growth and possible short-term fluctuations. The production equipment is characterized by significant changeover time between the production of different items. While demand growth is gradual, capacity additions are discrete. Therefore, periods immediately following a machine purchase are characterized by excess machine capacity. We develop a mathematical programming model and an effective solution approach to determine the optimal capacity acquisition, production and inventory decisions over time. Through a computational study, we show the effectiveness of the solution approach in terms of solution quality and investigate the impact of product variety, cost of capital, and other important parameters on the capacity and inventory decisions. The computational results bring out some key insights—increasing product variety may not result in excessive inventory and even a substantial increase in set-up times or holding costs may not increase the total cost over the horizon in a significant manner due to the ability to acquire additional capacity. We also provide solutions and insights to the real problem that motivated this work.
Information Technology and Trader Competition in Financial Markets: Endogenous Liquidity
Authors: Dewan Sanjeev , Mendelson Haim
Published: December 2003

This note integrates the models of Dewan and Mendelson (1998) (DM) and Kyle (1985), extending the DM analysis of time-based competition in financial markets to the case of endogenous liquidity. The results enable us to examine the link between information technology investments, trading strategies, and liquidity.
Product Variety, Supply Chain Structure, and Firm Performance: Analysis of the U.S. Bicycle Industry
Authors: Randall Taylor , Ulrich Karl
Published: December 2003

Using data from the U.S. bicycle industry, we examine the relation among product variety, supply chain structure, and firm performance. Variety imposes two types of costs on a supply chain: production costs and market mediation costs. Production costs include, among other costs, the incremental fixed investments associated with providing additional product variants. Market mediation costs arise because of uncertainty in product demand created by variety. In the presence of demand uncertainty, precisely matching supply with demand is difficult. Market mediation costs include the variety-related inventory holding costs, product mark-down costs occurring when supply exceeds demand, and the costs of lost sales occurring when demand exceeds supply. We analyze product variety at the product attribute level, noting that the relative impact of variety on production and market mediation costs depends to a large extent on the attribute underlying the variety. That is, some types of variety incur high production costs and some types of variety incur high market mediation costs. We characterize supply chain structure by the degree to which production facilities are scale-efficient and by the distance of the production facility from the target market. We hypothesize that firms with scale-efficient production (i.e., high-volume firms) will offer types of variety associated with high production costs, and firms with local production will offer types of variety associated with high market mediation costs. This hypothesis implies that there is a coherent way to match product variety with supply chain structure. Empirical results suggest that firms which match supply chain structure to the type of product variety they offer outperform firms which fail to match such choices.
Performance of Coupled Product Development Activities with a Deadline
Authors: Joglekar Nitindra R. , Yassine Ali A. , Eppinger Steven D. , Whitney Daniel E.
Published: December 2003

This paper explores the performance of coupled development activities by proposing a performance generation model (PGM). The goal of the PGM is to develop insights about optimal strategies (i.e., sequential, concurrent, or overlapped) to manage coupled design activities that share a fixed amount of engineering resources subject to performance and deadline constraints. Model analysis characterizes the solution space for the coupled development problem. The solution space is used to explore the generation of product performance and the associated dynamic forces affecting concurrent development practices. We use these forces to explain conditions under which concurrency is a desirable strategy.
The Effects of Worker Learning, Forgetting, and Heterogeneity on Assembly Line Productivity
Authors: Shafer Scott M. , Nembhard David A. , Uzumeri Mustafa V.
Published: December 2003

The authors investigate through several simulations how patterns of learning and forgetting affect the operating performance of an assembly line. A unique aspect of this study is that a distribution of learning/forgetting behavior based on an empirical population of workers is used rather than assuming the same learning pattern for all employees. The paper demonstrates that modeling only central tendency and not the variations across workers tends to systematically underestimate overall productivity. The data used to estimate the parameters for the distribution of learning curves were collected from an assembly line that produces car radios.

Analysis of the models fit to a population of workers reveals that higher levels of previous experience are positively correlated with higher steady-state productivity levels and negatively correlated with the learning rate. To further motivate the study, a conceptual model with several factors hypothesized to influence assembly line productivity is presented. Among key factors included in the model are the rate of worker learning, the size of the worker pool, task tenure, and the magnitude of worker forgetting. In controlled computer simulation experiments, each of these factors was found to be statistically significant, as were a number of the two-way interaction terms.
A Two-Location Inventory Model with Transshipment and Local Decision Making
Authors: Rudi Nils , Kapur Sandeep , Pyke David F.
Published: December 2003

In situations where a seller has surplus stock and another seller is stocked out, it may be desirable to transfer surplus stock from the former to the latter. We examine how the possibility of such transshipments between two independent locations affects the optimal inventory orders at each location. If each location aims to maximize its own profits—we call this local decision making—their inventory choices will not, in general, maximize joint profits. We find transshipment prices which induce the locations to choose inventory levels consistent with joint-profit maximization.
Pricing Claims Under GARCH-Level Dependent Interest Rate Processes
Authors: Cvsa V. , Ritchken P.
Published: December 2003

This article considers the pricing of interest-rate-sensitive claims when the underlying interest rate is driven by a two-state-variable GARCH process. Analytical solutions are established for the case when the innovations in the short rate are normal and/or chi-squared random variables and the volatility of rates take on a special GARCH form. GARCH models that nest level-dependent interest rate models, including the Cox, Ingersoll, and Ross model, are also considered. Algorithms are provided that permit the efficient pricing of American-style interest rate claims under a rather broad array of GARCH-Level dependent processes.
Technological Opportunities and New Firm Creation
Authors: Shane Scott
Published: December 2003

Research on the creation of new high-technology companies has typically focused either on industry-level factors such as market structure and technology regime or on individual-level factors such as the work experience of entrepreneurs. This study complements these approaches by examining the effect of technological opportunities on firm formation. In particular, the study shows that the probability that an invention will be commercialized through firm formation is influenced by its importance, radicalness, and patent scope.