bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism of nicotine in rat lung microvascular endothelial cells
Authors: Ochiai Yoshinori , Itoh Kunio , Tanaka Yorihisa , Sakurai Eiichi , Nomura Akio
Published: February 2006

The aim of this study was to examine whether cultured rat lung microvascular endothelial cells (LMECs), which constitute the gas-blood barrier, have the ability to metabolize nicotine. Nicotine was biotransformed to cotinine and nicotine N′-oxide by cytochrome 450 (CYP) and flavin-containing monooxyganase (FMO), respectively, in rat LMECs. The intrinsic clearance (Vmax1/Km1) for the cotinine formation was about 20 times as high as that for the trans-nicotine N′-oxide formation in the low-Km phase, indicating that oxidation by CYP was much higher than that by FMO. On the other hand, as shown in Eadie-Hofstee plots, the formation of cis-nicotine N′-oxide was monophasic, whereas the plot for the trans-nicotine N′-oxide formation was clearly biphasic. These results suggest that nicotine N′-oxide was stereoselectively metabolized to cis and trans forms. However, in the high-Km phase there was no significant difference in N′-oxidation between the cis and trans forms. Moreover, we suggest that CYP2C11 and CYP3A2 are key players in the metabolism to cotinine of nicotine in rat LMECs using the respective enzyme inhibitors (tranylcypromine and troleandomycine). On the other hand, methimazole (5 μm) caused 73 and 45% decreases in the formation of N′-oxides of cis- and trans- enantiomers, respectively, demonstrating the presence of FMO in rat LMECs. These results suggest that rat LMEC enzymes can convert substrates of exogenous origin such as nicotine for detoxication, indicating LMECs are an important barrier for metabolic products, besides hepatic cells.
The novel application of tertiary butyl alcohol in the preparation of hydrophobic drug-HPβCD complex
Authors: Wang Zhixuan , Deng Yingjie , Zhang Xiaopeng
Published: February 2006

This report describes a novel application of tertiary butyl alcohol (TBA) in the preparation of hydrophobic drug-hydroxypropyl β-cyclodextrin (HPβCD) complex. The straightforward, economic preparation procedure consists of dissolving both the hydrophobic drug and HPβCD in TBA, which is subsequently freeze-dried to give the hydrophobic drug-HPβCD complex in the form of a porous powder. TBA was selected as the medium due to it being a good solvent for hydrophobic drug and HPβCD; in addition, it is also a versatile lyophilization medium and is widely used in pharmaceutical processes. In this study, ketoprofen and nitrendipine were used as model drugs and their HPβCD complexes were prepared by lyophilization of the TBA system. Based on the data from differential scanning calorimetry (DSC) and X-ray diffractometry (XRD), the drugs were amorphous in freeze-dried samples. The infra-red (IR) spectrum indicated that a drug-HPβCD interaction took place in the freeze-dried complex. Dissolution experiments showed that the hydrophobic drug dissolved rapidly from the HPβCD complex in both simulated gastric juice and simulated intestinal fluid. These results confirmed that this technique produced a hydrophobic drug-HPβCD complex. TBA was found to be a suitable freeze-drying medium for the preparation of hydrophobic drug-HPβCD complex. This approach is versatile, energy-conserving and can easily be scaled up. It is expected to have further application in modifying the physicochemical characteristics of hydrophobic drugs and improving their absorption and pharmacodynamic properties.
Art Is Not for Fear Russia's New Directors in Conversation
Authors: Chernyakov Dmitrii , Chusova Nina , Gremina Yelena , Karbauskis Mindaugas , Ryzhakov Viktor , Serebrennikov Kirill
Published: February 2006

Interviewed by Tom Sellar and Yana Ross

Translated by Yana Ross
Oxygen
Authors: Vyrypaev Ivan
Published: February 2006

Translated by Sasha Dugdale
Notch ligands with contrasting functions: Jagged1 and Delta1 in the mouse inner ear
Authors: Brooker Rachael , Hozumi Katsuto , Lewis Julian
Published: February 2006

Each of the sensory patches in the epithelium of the inner ear is a mosaic of hair cells and supporting cells. Notch signalling is thought to govern this pattern of differentiation through lateral inhibition. Recent experiments in the chick suggest, however, that Notch signalling also has a prior function -inductive rather than inhibitory - in defining the prosensory patches from which the differentiated cells arise. Several Notch ligands are expressed in each patch, but their individual roles in relation to the two functions of Notch signalling are unclear. We have used a Cre-LoxP approach to knock out two of these ligands, Delta1 (Dll1) and Jagged1 (Jag1), in the mouse ear. In the absence of Dll1, auditory hair cells develop early and in excess,in agreement with the lateral inhibition hypothesis. In the absence of Jag1, by contrast, the total number of these cells is strongly reduced, with complete loss of cochlear outer hair cells and some groups of vestibular hair cells, indicating that Jag1 is required for the prosensory inductive function of Notch. The number of cochlear inner hair cells, however, is almost doubled. This correlates with loss of expression of the cell cycle inhibitor p27Kip1 (Cdkn1b), suggesting that signalling by Jag1 is also needed to limit proliferation of prosensory cells,and that there is a core part of this population whose prosensory character is established independently of Jag1-Notch signalling. Our findings confirm that Notch signalling in the ear has distinct prosensory and lateral-inhibitory functions, for which different ligands are primarily responsible.
A retinoblastoma ortholog controls stalk/spore preference inDictyostelium
Authors: MacWilliams Harry , Doquang Kimchi , Pedrola Roberto , Dollman Gytha , Grassi Daniela , Peis Thomas , Tsang Adrian , Ceccarelli Adriano
Published: February 2006

We describe rblA, the Dictyostelium ortholog of the retinoblastoma susceptibility gene Rb. In the growth phase, rblA expression is correlated with several factors that lead to`preference' for the spore pathway. During multicellular development,expression increases 200-fold in differentiating spores. rblA-null strains differentiate stalk cells and spores normally, but in chimeras with wild type, the mutant shows a strong preference for the stalk pathway. rblA-null cells are hypersensitive to the stalk morphogen DIF,suggesting that rblA normally suppresses the DIF response in cells destined for the spore pathway. rblA overexpression during growth leads to G1 arrest, but as growing Dictyostelium are overwhelmingly in G2 phase, rblA does not seem to be important in the normal cell cycle. rblA-null cells show reduced cell size and a premature growth-development transition; the latter appears anomalous but may reflect selection pressures acting on social ameba.
Krox20hindbrain cis-regulatory landscape: interplay between multiple long-range initiation and autoregulatory elements
Authors: Chomette Diane , Frain Monique , Cereghini Silvia , Charnay Patrick , Ghislain Julien
Published: February 2006

The vertebrate hindbrain is subject to a transient segmentation process leading to the formation of seven or eight metameric territories termed rhombomeres (r). This segmentation provides the basis for the subsequent establishment of hindbrain neuronal organization and participates in the patterning of the neural crest involved in craniofacial development. The zinc-finger gene Krox20 is expressed in r3 and r5, and encodes a transcription factor that plays a key role in hindbrain segmentation,coordinating segment formation, specification of odd- and even-numbered rhombomeres, and cell segregation between adjacent segments, through the regulation of numerous downstream genes. In order to further elucidate the genetic network underlying hindbrain segmentation, we have undertaken the analysis of the cis-regulatory sequences governing Krox20 expression. We have found that the control of Krox20 transcription relies on three very long-range (200 kb) enhancer elements (A, B and C) that are conserved between chick, mouse and human genomes. Elements B and C are activated at the earliest stage of Krox20 expression in r5 and r3-r5,respectively, and do not require the Krox20 protein. These elements are likely to function as initiators of Krox20 expression. Element B contains a binding site for the transcription factor vHNF1, the mutation of which abolishes its activity, suggesting that vHNF1 is a direct initiator of Krox20 expression in r5. Element A contains Krox20-binding sites,which are required, together with the Krox20 protein, for its activity. This element therefore allows the establishment of a direct positive autoregulatory loop, which takes the relay of the initiator elements and maintains Krox20 expression. Together, our studies provide a basis for a model of the molecular mechanisms controlling Krox20 expression in the developing hindbrain and neural crest.
Steroid hormone-dependent transformation ofpolyhomeoticmutant neurons in theDrosophilabrain
Authors: Wang Jian , Lee Ching-Hsien J. , Lin Suewei , Lee Tzumin
Published: February 2006

Polyhomeotic (Ph), which forms complexes with other Polycomb-group (PcG)proteins, is widely required for maintenance of cell identity by ensuring differential gene expression patterns in distinct types of cells. Genetic mosaic screens in adult fly brains allow for recovery of a mutation that simultaneously disrupts the tandemly duplicated Drosophila phtranscriptional units. Distinct clones of neurons normally acquire different characteristic projection patterns and can be differentially labeled using various subtype-specific drivers in mosaic brains. Such neuronal diversity is lost without Ph. In response to ecdysone, ph mutant neurons are transformed into cells with unidentifiable projection patterns and indistinguishable gene expression profiles during early metamorphosis. Some subtype-specific neuronal drivers become constitutively activated, while others are constantly suppressed. By contrast, loss of other PcG proteins,including Pc and E(z), causes different neuronal developmental defects; and,consistent with these phenomena, distinct Hox genes are differentially misexpressed in different PcG mutant clones. Taken together, Drosophila Ph is essential for governing neuronal diversity,especially during steroid hormone signaling.
FGF negatively regulates muscle membrane extension inCaenorhabditis elegans
Authors: Dixon Scott J. , Alexander Mariam , Fernandes Raynah , Ricker Nicole , Roy Peter J.
Published: February 2006

Striated muscles from Drosophila and several vertebrates extend plasma membrane to facilitate the formation of the neuromuscular junction(NMJ) during development. However, the regulation of these membrane extensions is poorly understood. In C. elegans, the body wall muscles (BWMs)also have plasma membrane extensions called muscle arms that are guided to the motor axons where they form the postsynaptic element of the NMJ. To investigate the regulation of muscle membrane extension, we screened 871 genes by RNAi for ectopic muscle membrane extensions (EMEs) in C. elegans. We discovered that an FGF pathway, including let-756(FGF), egl-15(FGF receptor), sem-5(GRB2) and other genes negatively regulates plasma membrane extension from muscles. Although compromised FGF pathway activity results in EMEs, hyperactivity of the pathway disrupts larval muscle arm extension, a phenotype we call muscle arm extension defective or MAD. We show that expression of egl-15 and sem-5 in the BWMs are each necessary and sufficient to prevent EMEs. Furthermore, we demonstrate that let-756 expression from any one of several tissues can rescue the EMEs of let-756 mutants, suggesting that LET-756 does not guide muscle membrane extensions. Our screen also revealed that loss-of-function in laminin and integrin components results in both MADs and EMEs, the latter of which are suppressed by hyperactive FGF signaling. Our data are consistent with a model in which integrins and laminins are needed for directed muscle arm extension to the nerve cords, while FGF signaling provides a general mechanism to regulate muscle membrane extension.
Using Extreme Value Theory to Model Electricity Price Risk with an Application to the Alberta Power Market
Authors: Walls W. D. , Zhang Wei.
Published: February 2006

Value-at-risk (VaR) is a measure of the maximum potential change in value of a portfolio of financial assets with a given probability over a given time horizon. VaR has become a standard measure of market risk and a common practice is to compute VaR by assuming that changes in value of the portfolio are conditionally normally distributed. However, assets returns usually come from heavy-tailed distributions, so computing VaR under the assumption of conditional normality can be an important source of error. We illustrate in our application to competitive electric power prices in Alberta, Canada, that VaR estimates based on extreme value theory models, in particular the generalized Pareto distribution are, more accurate than those produced by alternative models such as normality or historical simulation.
Deep Structure Model and Dynamics of Mud Volcanoes, Southwest Absheron Peninsula (Azerbaijan)
Authors: Kadirov F. A. , Lerche I. , Guliyev I. S. , Kadyrov A. G. , Feyzullayev A. A. , Mukhtarov A. Sh.
Published: February 2006

Measurements have been made of gravitational field, geodetic uplift, regional horizontal tectonic movement, thermal patterns, and radioactivity in the general area of the Lokbatan mud volcano after its explosion on October 25, 2001, as well as in the crater itself. In addition, geochemical measurements of vitrinite reflectance with depth have been done and isotopic variations of methane and ethane are also made available. This massive compendium of information represents the first time such a detailed investigation has been possible of the deep structural effects of a mud volcano and also of the sources of mud and gas at outflow time. The data are integrated into a combined picture that shows the roots of both the mud outflow and of the gas causing the flaming eruption are at several kilometres depth into the sedimentary pile. The overall behaviour is best served by a model in which a relatively thin jet of liquefied mud is extruded from depth due to action of the varying tectonic stresses in the region, as adduced from the global positioning system (GPS) tectonic movement data. The variation of Bouguer gravity across a profile including the Lokbatan mud volcano, and combined with the geodetic vertical motion immediately after and long after (10 months) the explosion, confirms this basic model. The focusing of heat flux around the volcano prior to the explosion, and the thermal measurements made with time after the explosion both in the crater and also in the immediate vicinity of the Lokbatan volcano, are in accord with a thin hot jet model in which liquefied mud, with entrained gas from deeper in the sediments, rises through a neck region and, due to the Rayleigh–Bernard convective instability, produces a high temperature region. The geochemical evidence, showing low vitrinite maturity (<0.6%) to a depth of around 6 km, also indicates production of oil and gas from greater depths, as do the isotopic carbon measurements of methane and ethane in the unburnt gases. In short, it would seem that tectonic “squeezing” of a low-strength plastic mud layer from depth through a narrow vent with entrained gas and mud is the primary driver for mud volcano explosions. In the general regional, approximately linearly arranged lines of mud volcanoes, with their apparent focus centred on Shemakha from where the lines fan out, is also a strong indication of the basic tectonic origin. The combination of a rapidly filled sedimentary region, with unconsolidated (or deconsolidated) muds occupying a domain at several kilometre depth, and bracketed above and below by more competent formations, together with the active horizontal stress variations as measured by the GPS network, together form the basis for the spectacular mud volcano effects in this part of Azerbaijan.
Hydrocarbon Flow-up Intersecting Faults: Economic Aspects of Production and Bypass Considerations
Authors: Lerche Ian
Published: February 2006

The economic aspects are addressed towards production from reservoirs supplied with hydrocarbons along a master fault. In particular, the costs of production, the onset and termination times of production in relation with the supply time of hydrocarbons, as well as the supply rate and the production rates, in addition to the selling price of product, are all involved in determining if a positive net present value can be realized during the production phase of the reservoir. Depending on the relative timing, it is possible that the reservoirs cannot be made profitable unless the selling price exceeds a critical minimum. These aspects, and several residual concerns related to the desired production rate vs that allowed by reservoir fill rates, are addressed in this article.
Diagnosis of the Doubly-Fed Induction Generator of a Wind Turbine
Authors: Bennouna O. , Héraud N. , Camblong H. , Rodriguez M.
Published: February 2006

This paper presents a method of identifying and estimating gross errors for linear dynamic systems. The method is applied to wind power, in particular the doubly-fed induction generator. Measurements have errors, but it is possible to reduce the effect of such errors on control by exploiting relationships between the different variables of the system. Such analysis is called ‘data validation’. Data validation uses a mathematical model, based on equations, to simulate the real dynamic system. An analysis of systematic errors is made using a measurement test. The method has the potential to support the on-line multiparameter data analysis, and hence maintenance, of complex systems, such as wind turbines.
Generator-Damped Torsional Vibrations of a Vertical Axis Wind Turbine
Authors: Eriksson Sandra , Bernhoff H.
Published: February 2006

Torsional vibrations may be a critical issue for those vertical axis wind turbines having long drive trains as compared with standard horizontal axis wind turbines. Such vibrations are studied by simulation for two different types of generators used with a vertical axis wind turbine, namely a conventional induction generator with a gearbox and a directly-driven multipole synchronous generator. The synchronous generator has been designed with FEM simulations. The didactic calculations show from first principles that a directly-driven generator is to be preferred when torsional vibrations are considered, since the eigenfrequency of the fundamental vibration is greater for a directly driven generator than otherwise. Thus, the risk of resonance is reduced in a stiff assembly. The generator damping of the vibrations for the simulated, directly-driven synchronous generator is also studied.
Comparative study of the effects of heptameric slippery site composition on −1 frameshifting among different eukaryotic systems
Authors: PLANT EWAN P. , DINMAN JONATHAN D.
Published: February 2006

Studies of programmed −1 ribosomal frameshifting (−1 PRF) have been approached over the past two decades by many different laboratories using a diverse array of virus-derived frameshift signals in translational assay systems derived from a variety of sources. Though it is generally acknowledged that both absolute and relative −1 PRF efficiency can vary in an assay system-dependent manner, no methodical study of this phenomenon has been undertaken. To address this issue, a series of slippery site mutants of the SARS-associated coronavirus frameshift signal were systematically assayed in four different eukaryotic translational systems. HIV-1 promoted frameshifting was also compared between Escherichia coli and a human T-cell line expression systems. The results of these analyses highlight different aspects of each system, suggesting in general that (1) differences can be due to the assay systems themselves; (2) phylogenetic differences in ribosome structure can affect frameshifting efficiency; and (3) care must be taken to employ the closest phylogenetic match between a specific −1 PRF signal and the choice of translational assay system.
Attribute Dominance Utility
Authors: Abbas Ali E. , Howard Ronald A.
Published: February 2006

We present an analogy between joint cumulative probability distributions and a class of multiattribute utility functions, which we call attribute dominance utility functions. Attribute dominance utility functions permit assessing multiattribute utility functions using common techniques of joint probability assessment such as marginal-conditional assessments and the method of copulas. By itself, this class of utility functions appears in many cases of decision analysis practice. Furthermore, we show that many functional forms of multiattribute utility function can be decomposed into attribute dominance utility functions that are easier to elicit. We introduce the notion of utility inference analogous to Bayes’ rule for probability inference and provide a graphic representation of attribute dominance utility functions, which we call utility diagrams.
Influence Diagrams for Team Decision Analysis
Authors: Detwarasiti Apiruk , Shachter Ross D.
Published: February 2006

We consider the representation and evaluation of team decision making under uncertainty using influence diagrams. We assume that all team members agree on common beliefs and preferences, but complete sharing of information is generally impossible. As a result, the team can be represented as a single rational individual with imperfect recall, and the optimal solution with perfect recall might not be achievable, except in special cases we can recognize. An alternative solution concept is a stable solution that integrates the notion of optimality with that of equilibrium from game theory. We extend this concept from individual decisions to sets of decisions, and introduce the Strategy Improvement and its variation, Uniform Strategy Improvement, as the corresponding solution methods. We also provide a variety of simplifying transformations to the influence diagram by exploiting its graphical structure. The result is a requisite influence diagram, one that requires minimum assessment and creates additional opportunities for optimality.
Influence Diagrams: A Practitioner's Perspective
Authors: Buede Dennis M.
Published: February 2006

I have found influence diagrams to be indispensable in building models with clients, keeping track of what probability distributions are needed, explaining the results of calculations to clients, explaining the analysis process to clients, and teaching decision analysis to undergraduate and graduate students. As a professional decision analyst and as a teacher I have found influence diagrams to be almost as critical as a laptop computer.
Less Likely to Fail: Low Performance, Firm Size, and Factory Expansion in the Shipbuilding Industry
Authors: Audia Pino G. , Greve Henrich R.
Published: February 2006

The behavioral theory of the firm and prospect theory predict that performance below an aspiration level increases risk taking, but researchers also propose that performance below an aspiration level decreases risk taking. These conflicting predictions primarily hinge on whether decision makers perceive negative performance as a repairable gap or as a threat to firm survival. This study examines a boundary condition of these conflicting predictions. We argue that a firm’s resource endowment affects decision makers’ risk tolerance: Managers in firms with large stocks of resources are buffered from the threat of failure and conform to the prediction of greater risk taking in response to performance decreases; managers in firms with limited resources view low performance as a step closer to failure and decrease risk taking in response to performance decreases. Using data on the risky decision of factory expansion in shipbuilding firms and firm size as an indicator of the stock of tangible resources, we find that performance below the aspiration level reduces risk taking in small firms, but either does not affect risk taking or increases risk taking in large firms. These findings are largely consistent with our predictions and also suggest that large firms are more inert than small firms.
Multiplicative Background Risk
Authors: Franke Günter , Schlesinger Harris , Stapleton Richard C.
Published: February 2006

Although there has been much attention in recent years on the effects of additive background risks, the same is not true for its multiplicative counterpart. We consider random wealth of the multiplicative form x̃ỹ, where x̃ and ỹ are statistically independent random variables. We assume that x̃ is endogenous to the economic agent but that ỹ is an exogenous and nontradable background risk that represents a type of market incompleteness. Our main focus is on how the presence of the multiplicative background risk ỹ affects risk-taking behavior for decisions on the choice of x̃. We extend the results of Gollier and Pratt (1996) to characterize conditions on preferences that lead to more cautious behavior.
Reverse Channel Design: The Case of Competing Retailers
Authors: Savaskan R. Canan , Van Wassenhove Luk N.
Published: February 2006

The economical and environmental benefits of product remanufacturing have been widely recognized in the literature and in practice. In this paper, we focus on the interaction between a manufacturer’s reverse channel choice to collect postconsumer goods and the strategic product pricing decisions in the forward channel when retailing is competitive. To this end, we model a direct product collection system, in which the manufacturer collects used products directly from the consumers (e.g., print and copy cartridges) and an indirect product collection system, in which the retailers act as product return points (e.g., single-use cameras, cellular phones). We first examine how the allocation of product collection to retailers impacts their strategic behavior in the product market, and we discuss the economic trade-offs the manufacturer faces while choosing an optimal reverse channel structure. When a direct collection system is used, channel profits are driven by the impact of scale of returns on collection effort, whereas in the indirect reverse channel, supply chain profits are driven by the competitive interaction between the retailers. Subsequently, we show that the buy-back payments transfered to the retailers for postconsumer goods provide a wholesale pricing flexibility that can be used to price discriminate between retailers of different profitability.
Intuitions About Combining Opinions: Misappreciation of the Averaging Principle
Authors: Larrick Richard P. , Soll Jack B.
Published: February 2006

Averaging estimates is an effective way to improve accuracy when combining expert judgments, integrating group members’ judgments, or using advice to modify personal judgments. If the estimates of two judges ever fall on different sides of the truth, which we term bracketing, averaging must outperform the average judge for convex loss functions, such as mean absolute deviation (MAD). We hypothesized that people often hold incorrect beliefs about averaging, falsely concluding that the average of two judges’ estimates would be no more accurate than the average judge. The experiments confirmed that this misconception was common across a range of tasks that involved reasoning from summary data (Experiment 1), from specific instances (Experiment 2), and conceptually (Experiment 3). However, this misconception decreased as observed or assumed bracketing rate increased (all three studies) and when bracketing was made more transparent (Experiment 2). Experiment 4 showed that flawed inferential rules and poor extensional reasoning abilities contributed to the misconception. We conclude by describing how people may face few opportunities to learn the benefits of averaging and how misappreciating averaging contributes to poor intuitive strategies for combining estimates.
Managing New and Remanufactured Products
Authors: Ferrer Geraldo , Swaminathan Jayashankar M.
Published: February 2006

We study a firm that makes new products in the first period and uses returned cores to offer remanufactured products, along with new products, in future periods. We introduce the monopoly environment in two-period and multiperiod scenarios to identify thresholds in remanufacturing operations. Next, we focus our attention on the duopoly environment where an independent operator (IO) may intercept cores of products made by the original equipment manufacturer (OEM) to sell remanufactured products in future periods. We characterize the production quantities associated with self-selection and explore the effect of various parameters in the Nash equilibrium. Among other results, we find that if remanufacturing is very profitable, the original-equipment manufacturer may forgo some of the first-period margin by lowering the price and selling additional units to increase the number of cores available for remanufacturing in future periods. Further, as the threat of competition increases, the OEM is more likely to completely utilize all available cores, offering the remanufactured products at a lower price.
Price Competition with Reduced Consumer Switching Costs: The Case of “Wireless Number Portability” in the Cellular Phone Industry
Authors: Shi Mengze , Chiang Jeongwen , Rhee Byong-Duk
Published: February 2006

Wireless number portability (WNP) is a telecommunication regulatory policy that requires cellular phone service providers to allow customers who switch service subscriptions to retain their original phone numbers. The right to retain the number lowers the switching cost for a consumer. Thus, the purpose of the policy is to induce more competition and facilitate the growth of new or small service providers. In this paper, we show that WNP drives market price downward as expected but with a surprising twist—rather than helping the smaller firms grow, the policy may accelerate the process of market concentration. We find that the main contributing factor to this peculiarity is the discriminatory pricing scheme prevalent in the industry—that is, a service provider charges a lower per-minute fee for the calls initiated and received within the same network than for the calls connected across two networks. Under this pricing scheme, a consumer who subscribes to a larger network would benefit more than if subscribing to a smaller network, despite the relatively higher fixed access fee that the former may charge. By lowering the barrier of switching, WNP creates a market condition conducive for a larger network to gain market share. We support our analysis with the empirical evidence gathered from Hong Kong where WNP was adopted in March 1999.
In Search of Complementarity in Innovation Strategy: Internal R&D and External Knowledge Acquisition
Authors: Cassiman Bruno , Veugelers Reinhilde
Published: February 2006

Empirical research on complementarity between organizational design decisions has traditionally focused on the question of existence of complementarity. In this paper, we take a broader approach to the issue, combining a “productivity” and an “adoption” approach, while including a search for contextual variables in the firm’s strategy that affects complementarity. Analysis of contextual variables is not only interesting per se, but also improves the productivity test for the existence of complementarity. We use our empirical methodology to analyze complementarity between innovation activities: internal research and development (R&D) and external knowledge acquisition. Our results suggest that internal R&D and external knowledge acquisition are complementary innovation activities, but that the degree of complementarity is sensitive to other elements of the firm’s strategic environment. We identify reliance on basic R&D—the importance of universities and research centers as an information source for the innovation process—as an important contextual variable affecting complementarity between internal and external innovation activities.
Increasing Risk and Increasing Informativeness: Equivalence Theorems
Authors: Baker Erin
Published: February 2006

When considering problems of sequential decision making under uncertainty, two of the most interesting questions are: How does the value of the optimal decision variable change with an increase in risk? How does the value of the optimal decision variable change with a more informative signal? In this paper, we show that if the payoff function is separable in the random variable, then one model can simultaneously answer both questions. This result holds for the reaction functions and equilibria of noncooperative games, as well as for single decision makers, with virtually no restrictions on the payoff functions. This is useful because otherwise it is very difficult to get at general results on the impact of learning. Furthermore, we clarify why the impacts of risk and a more informative signal are different when the payoff function is nonlinear in the random variable. It is because the directional impacts of informativeness are independent of risk attitude; the impacts of risk are not.
Fluid Models for Multiserver Queues with Abandonments
Authors: Whitt Ward
Published: February 2006

Deterministic fluid models are developed to provide simple first-order performance descriptions for multiserver queues with abandonment under heavy loads. Motivated by telephone call centers, the focus is on multiserver queues with a large number of servers and nonexponential service-time and time-to-abandon distributions. The first fluid model serves as an approximation for the G/GI/s+GI queueing model, which has a general stationary arrival process with arrival rate λ, independent and identically distributed (IID) service times with a general distribution, s servers and IID abandon times with a general distribution. The fluid model is useful in the overloaded regime, where λ > s, which is often realistic because only a small amount of abandonment can keep the system stable. Numerical experiments, using simulation for M/GI/s+GI models and exact numerical algorithms for M/M/s+M models, show that the fluid model provides useful approximations for steady-state performance measures when the system is heavily loaded. The fluid model accurately shows that steady-state performance depends strongly upon the time-to-abandon distribution beyond its mean, but not upon the service-time distribution beyond its mean. The second fluid model is a discrete-time fluid model, which serves as an approximation for the Gt (n)/GI/s+GI queueing model, having a state-dependent and time-dependent arrival process. The discrete-time framework is exploited to prove that properly scaled queueing processes in the queueing model converge to fluid functions as s → ∞. The discrete-time framework is also convenient for calculating the time-dependent fluid performance descriptions.
Approximation Algorithms for Problems Combining Facility Location and Network Design
Authors: Ravi R. , Sinha Amitabh
Published: February 2006

We present approximation algorithms for integrated logistics problems that combine elements of facility location and transport network design. We first study the problem where opening facilities incurs opening costs and transportation from the clients to the facilities incurs buy-at-bulk costs, and provide a combinatorial approximation algorithm. We also show that the integer-programming formulation of this problem has small integrality gap. We extend the model to the version when there is a bound on the number of facilities that may be opened.
Discrete Optimization via Simulation Using COMPASS
Authors: Hong L. Jeff , Nelson Barry L.
Published: February 2006

We propose an optimization-via-simulation algorithm, called COMPASS, for use when the performance measure is estimated via a stochastic, discrete-event simulation, and the decision variables are integer ordered. We prove that COMPASS converges to the set of local optimal solutions with probability 1 for both terminating and steady-state simulation, and for both fully constrained problems and partially constrained or unconstrained problems under mild conditions.
A Robust Optimization Approach to Inventory Theory
Authors: Bertsimas Dimitris , Thiele Aurélie
Published: February 2006

We propose a general methodology based on robust optimization to address the problem of optimally controlling a supply chain subject to stochastic demand in discrete time. This problem has been studied in the past using dynamic programming, which suffers from dimensionality problems and assumes full knowledge of the demand distribution. The proposed approach takes into account the uncertainty of the demand in the supply chain without assuming a specific distribution, while remaining highly tractable and providing insight into the corresponding optimal policy. It also allows adjustment of the level of robustness of the solution to trade off performance and protection against uncertainty. An attractive feature of the proposed approach is its numerical tractability, especially when compared to multidimensional dynamic programming problems in complex supply chains, as the robust problem is of the same difficulty as the nominal problem, that is, a linear programming problem when there are no fixed costs, and a mixed-integer programming problem when fixed costs are present. Furthermore, we show that the optimal policy obtained in the robust approach is identical to the optimal policy obtained in the nominal case for a modified and explicitly computable demand sequence. In this way, we show that the structure of the optimal robust policy is of the same base-stock character as the optimal stochastic policy for a wide range of inventory problems in single installations, series systems, and general supply chains. Preliminary computational results are very promising.
A Branch-and-Cut Algorithm for the Multiple Depot Vehicle Scheduling Problem
Authors: Hadjar Ahmed , Marcotte Odile , Soumis François
Published: February 2006

We consider the multiple depot vehicle scheduling problem (MDVSP) and propose a branch-and-bound algorithm for solving it that combines column generation, variable fixing, and cutting planes. We show that the solutions of the linear relaxation of the MDVSP contain many “odd cycles.” We derive a class of valid inequalities by extending the notion of odd cycle and describe a lifting procedure for these inequalities. We prove that the lifted inequalities represent, under certain conditions, facets of the underlying polytope. Finally, we present the results of a computational study comparing several strategies (variable fixing, cutting planes, mixed branching, and tree search) for solving the MDVSP.
Fine-Tuning of Algorithms Using Fractional Experimental Designs and Local Search
Authors: Adenso-Díaz Belarmino , Laguna Manuel
Published: February 2006

Researchers and practitioners frequently spend more time fine-tuning algorithms than designing and implementing them. This is particularly true when developing heuristics and metaheuristics, where the “right” choice of values for search parameters has a considerable effect on the performance of the procedure. When testing metaheuristics, performance typically is measured considering both the quality of the solutions obtained and the time needed to find them. In this paper, we describe the development of CALIBRA, a procedure that attempts to find the best values for up to five search parameters associated with a procedure under study. Because CALIBRA uses Taguchi’s fractional factorial experimental designs coupled with a local search procedure, the best values found are not guaranteed to be optimal. We test CALIBRA on six existing heuristic-based procedures. These experiments show that CALIBRA is able to find parameter values that either match or improve the performance of the procedures resulting from using the parameter values suggested by their developers. The latest version of CALIBRA can be downloaded for free from the website that appears in the online supplement of this paper at http://or.pubs.informs.org/Pages.collect.html.
A Nonparametric Approach to Multiproduct Pricing
Authors: Rusmevichientong Paat , Van Roy Benjamin , Glynn Peter W.
Published: February 2006

Developed by General Motors (GM), the Auto Choice Advisor website ( http://www.autochoiceadvisor.com ) recommends vehicles to consumers based on their requirements and budget constraints. Through the website, GM has access to large quantities of data that reflect consumer preferences. Motivated by the availability of such data, we formulate a nonparametric approach to multiproduct pricing.

We consider a class of models of consumer purchasing behavior, each of which relates observed data on a consumer’s requirements and budget constraint to subsequent purchasing tendencies. To price products, we aim at optimizing prices with respect to a sample of consumer data. We offer a bound on the sample size required for the resulting prices to be near-optimal with respect to the true distribution of consumers. The bound exhibits a dependence of O(n log n) on the number n of products being priced, showing that—in terms of sample complexity—the approach is scalable to large numbers of products.

With regards to computational complexity, we establish that computing optimal prices with respect to a sample of consumer data is NP-complete in the strong sense. However, when prices are constrained by a price ladder—an ordering of prices defined prior to price determination—the problem becomes one of maximizing a supermodular function with real-valued variables. It is not yet known whether this problem is NP-hard. We provide a heuristic for our price-ladder-constrained problem, together with encouraging computational results.

Finally, we apply our approach to a data set from the Auto Choice Advisor website. Our analysis provides insights into the current pricing policy at GM and suggests enhancements that may lead to a more effective pricing strategy.
Solving Large-Scale Linear Multicommodity Flow Problems with an Active Set Strategy and Proximal-ACCPM
Authors: Babonneau F. , du Merle O. , Vial J.-P.
Published: February 2006

In this paper, we propose to solve the linear multicommodity flow problem using a partial Lagrangian relaxation. The relaxation is restricted to the set of arcs that are likely to be saturated at the optimum. This set is itself approximated by an active set strategy. The partial Lagrangian dual is solved with Proximal-ACCPM, a variant of the analytic center cutting-plane method. The new approach makes it possible to solve huge problems when few arcs are saturated at the optimum, as appears to be the case in many practical problems.
A Stochastic Programming Approach to Power Portfolio Optimization
Authors: Sen Suvrajeet , Yu Lihua , Genc Talat
Published: February 2006

We consider a power portfolio optimization model that is intended as a decision aid for scheduling and hedging (DASH) in the wholesale power market. Our multiscale model integrates the unit commitment model with financial decision making by including the forwards and spot market activity within the scheduling decision model. The methodology is based on a multiscale stochastic programming model that selects portfolio positions that perform well on a variety of scenarios generated through statistical modeling and optimization. When compared with several commonly used fixed-mix policies, our experiments demonstrate that the DASH model provides significant advantages.
Managing Patient Service in a Diagnostic Medical Facility
Authors: Green Linda V. , Savin Sergei , Wang Ben
Published: February 2006

Hospital diagnostic facilities, such as magnetic resonance imaging centers, typically provide service to several diverse patient groups: outpatients, who are scheduled in advance; inpatients, whose demands are generated randomly during the day; and emergency patients, who must be served as soon as possible. Our analysis focuses on two interrelated tasks: designing the outpatient appointment schedule, and establishing dynamic priority rules for admitting patients into service.

We formulate the problem of managing patient demand for diagnostic service as a finite-horizon dynamic program and identify properties of the optimal policies. Using empirical data from a major urban hospital, we conduct numerical studies to develop insights into the sensitivity of the optimal policies to the various cost and probability parameters and to evaluate the performance of several heuristic rules for appointment acceptance and patient scheduling.
Why Do Users Contribute to Firm-Hosted User Communities? The Case of Computer-Controlled Music Instruments
Authors: Jeppesen Lars Bo , Frederiksen Lars
Published: February 2006

Studies of the sources of innovations have recognized that many innovations are developed by users. However, the fact that firms employ communities of users to strengthen their innovation process has not yet received much attention. In online firm-hosted user communities, users freely reveal innovations to a firm's product platform, which can put the firm in a favorable position (a) because these new product features become available to all users through sharing on a user-to-user basis, or (b) because it allows the firm to pick up the innovations and integrate them in future products and then benefit by selling them to all users. We study the key personal attributes of the individuals responsible for innovations, namely the innovative users, to explain creation of value in this organizational context. The main question is why such users contribute to firm-hosted user communities. Analyzing data derived from multiple sources (interviews, a Web-log, and questionnaires), we find that innovative users are likely to be (i) hobbyists, an attribute that can be assumed to (positively) affect innovators' willingness to share innovations, and (ii) responsive to “firm recognition” as a motivating factor for undertaking innovation, which explains their decision to join the firm's domain. In agreement with earlier studies, we also find that innovative users are likely to be “lead users,” an attribute that we assume to affect the quality of user innovation. Whether or not a firm-hosted user community can be turned into an asset for the firm is to a great extent conditional on the issues studied in this paper.
The Social Network Ties of Group Leaders: Implications for Group Performance and Leader Reputation
Authors: Mehra Ajay , Dixon Andrea L. , Brass Daniel J. , Robertson Bruce
Published: February 2006

This paper uses data from the sales division of a financial services firm to investigate how a leader's centrality in external and internal social networks is related to the objective performance of the leader's group, and to the leader's personal reputation for leadership among subordinates, peers, and supervisors. External social network ties were based on the friendship ties among all 88 of the division's sales group leaders and the 10 high-ranking supervisors to whom they reported. Internal social network ties consisted of 28 separate networks, each representing the set of friendship relations among all members of a given sales group. Objective group performance data came directly from company records. Data on each group leader's personal reputation for leadership was based on the perceptions of three different constituencies: subordinates, peers, and supervisors. Results revealed that leaders' centrality in external and internal friendship networks was related both to objective measures of group performance and to their reputation for leadership among different organizational constituencies.